“intelligence is the ability to adapt to change…” “if there´s a will, … › bitstream ›...

“Intelligence is the ability to adapt to change…”

“If there´s a will, there´s a way…”

Stephen Hawking

Patient with Amyotrophic Lateral Sclerosis and a ventilator user. English theoretical physicist and cosmologist, was the Lucasian Professor of Mathematics at the University of Cambridge for thirty years, taking up the post in 1979 and retiring on 1 October 2009, year he was awarded the Presidential Medal of Freedom, the highest civilian award in the United States.

Research work and line of investigation developed as

part of a PhD Thesis in Biomedicine presented at the

Faculty of Medicine of the University of Porto

PhD Tutors:

• Professor João Carlos Winck Fernandes Cruz

Faculty of Medicine, University of Porto

• Professor John Robert Bach

University of Medicine and Dentistry of New Jersey Medical School

Official Jury:

• President –Professor José Agostinho Marques

Director of the Faculty of Medicine, University of Porto

• Professor Dominique Robert

Faculty of Medicine, University of Lyon, France

• Professor Massimo Antonelli

Faculty of Medicine, Policlinico Universitario A. Gemelli, Universitá Cattolica del Sacro Cuore, Rome Italy

• Professor João Carlos Winck Fernandes Cruz


• Professor Maria Isabel Amorim de Azevedo


• Professor Henrique José Correia Queiroga


• Professor Marta Susana Monteiro Drummond de Freitas


CONTENTS

Introduction ___________________________________________________________________ 1

Historical perspective of mechanical ventilation and respiratory muscle aids _____________ 5

Equipments and techniques for noninvasive positive pressure ventilation _______________ 21

Characteristics of different modes of ventilation _____________________________ 21

Pressure cycled ventilation __________________________________________ 22

Volume cycled ventilation ___________________________________________ 25

Ventilators with mixed pressure and volume target modes __________________ 27

Interfaces for the delivery of NPPV ________________________________________ 28

Humidification during NPPV _____________________________________________ 31

Noninvasive ventilation in the acute care setting ____________________________________ 32

Rationale ______________________________________________________________ 32

Chronic obstructive pulmonary disease with acute exacerbation ________________ 35

Acute Cardiogenic Pulmonary Edema ______________________________________ 37

Hypoxemic Respiratory Failure ___________________________________________ 38

Imunocompromised patients ______________________________________________ 39

Weaning from Invasive ventilation and post extubation failure _________________ 40

Acute Respiratory Failure in Restrictive Disorders ___________________________ 41

Chest wall disorders _______________________________________________ 42

Neuromuscular Disorders ___________________________________________ 43

Amyotrophic Lateral Sclerosis _______________________________________ 44

Gullian-Barré syndrome and Myastenia Gravis __________________________ 49

Spinal Cord Injury _________________________________________________ 49

Critical- illness myoneuropathy _______________________________________ 51

Contraindications to NPPV in acute care ___________________________________ 51

Noninvasive ventilation in the chronic care setting __________________________________ 53

Rationale ______________________________________________________________ 53

Indications of Noninvasive ventilatory support _______________________________ 54

Disease categories _________________________________________________ 54

Patient selection ___________________________________________________ 55

Physiologic evaluations _____________________________________________ 56

Muscle strength ___________________________________________________ 57

Blood Gases ______________________________________________________ 58

Noninvasive ventilation in stable COPD ____________________________________ 59

Noninvasive ventilation in Restrictive Disorders ______________________________ 62

Chest wall disorders _______________________________________________ 62

Amyotrophic Lateral Sclerosis _______________________________________ 63

Duchenne muscular dystrophy _______________________________________ 65

Manual and Mechanical techniques for secretion management ________________________ 68

Rationale ______________________________________________________________ 68

Patient evaluation and monitoring _________________________________________ 71

Pulmonary function and cough tests ________________________________________ 72

Control of Mucus and Airway Clearance Techniques _________________________ 74

Chest physical therapy techniques _____________________________________ 75

Manual Assisted Cough techniques ____________________________________ 76

Mechanical Respiratory Muscle Aids for Secretion Management _______________ 78

Intrapulmonary Percussive Ventilation (IPV) ____________________________ 79

High Frequency Chest Wall Oscillation (HFCWO) _______________________ 80

Mechanical Insufflation-Exsufflation __________________________________ 82

Purpose of the Thesis __________________________________________________________ 86

Acute Respiratory Failure ________________________________________________________ 87

Chronic Respiratory Failure ______________________________________________________ 93

Home mechanical ventilation ____________________________________________________ 101

Studies and Publications _______________________________________________________ 109

Study 1- Extubation of Patients with Neuromuscular Weakness: A New

Management Paradigm _________________________________________________________ 109

Study 2- Noninvasive ventilation associated with mechanical assisted cough for

extubation and decannulation in high spinal cord injury patients ________________________ 121

Study 3- Effects of mechanical insuffaltion-exsufflation in preventing respiratory failure after

extubation: a randomized controlled trial __________________________________________ 147

Study 4- A Ventilator Requirement Index ___________________________________________ 169

Study 5- Expiratory Flow Maneuvers of Patients with Neuromuscular Disease _____________ 179

Study 6- Lung Insufflation Capacity in Neuromuscular Disease. ________________________ 189

Study 7- Indications and Compliance of Home Mechanical Insufflation-Exsufflation in Patients

with Neuromuscular Diseases ____________________________________________________ 197

Study 8- At Home and On Demand Mechanical Cough Assistance Program for Patients with

Amyotrophic Lateral Sclerosis ___________________________________________________ 205

Study 9- Home mechanical cough assistance for acute exacerbations in neuromuscular

disease ______________________________________________________________________ 213

Study 10- Evolution of Noninvasive Management of End-Stage Respiratory Muscle Failure in

Neuromuscular disease. ________________________________________________________ 231

General Discussion ___________________________________________________________ 265

Acute Respiratory Failure ________________________________________________ 265

Chronic Respiratory Failure _______________________________________________ 277

Home mechanical ventilation ______________________________________________ 285

Conclusions _________________________________________________________________ 299

Resumo _____________________________________________________________________ 301

Objectivos _____________________________________________________________ 302

Resultados ____________________________________________________________ 303

Conclusões ____________________________________________________________ 306

Summary (Abstract) __________________________________________________________ 308

Purpose _______________________________________________________________ 309

Results _______________________________________________________________ 310

Conclusions ___________________________________________________________ 313

References __________________________________________________________________ 314

Acknowledgments

� To Professor John Bach for all the guidance, mentorship and lessons throughout my clinical and academic career. It has been my greatest honor to be taught and trained by who i consider to be the most brilliant mind in the field of noninvasive ventilation. It is a privilege to be his friend and his personal and professional influence will be eternal in my life.

� To Professor João Carlos Winck for always believing in my work and always being there as a mentor and a very special friend. His teachings and advices were the support of this thesis and made me a better academic and clinical professional. It has been a great privilege to share with him the “challenge” of changing the paradigms and improving respiratory care in our country.

� To Professor Agostinho Marques for always making me believe in my potential to achieve this PhD degree. I will always be thankful to him for this opportunity and for his contribution to make this dream possible.

� To all the staff of the Pulmonology Department, Hospital S. João for the motivation and support throughout this thesis. It is a privilege for me to work in this department where a fantastic multidisciplinary “team work” spirit was crucial to perform this line of research. A special thanks to my colleague Tiago Pinto, Professor Marta Drummond, Dr João Almeida, Dr João Bento and Dr Anabela Marinho that gave me great support and actively contributed to this thesis line of research.

� To all the medical and nursing staff of the Intensive Care and Emergency Department, Hospital S. João for the motivation and both clinical and technical support in the critical care studies of this thesis. It has been an overwhelming experience to share knowledge and learn new concepts in this department. A special thanks to Dr Teresa Honrado, Dr Teresa Oliveira, Dr Celeste Dias, Dr Ana Maria Mota and Professor José Artur Paiva for trusting and believing in my research as well as in my daily clinical work.

� To all the private home care professionals that take good care of our home mechanical ventilated patients. Their dedication and competence in this field have improved significantly the quality of life of these patients and their availability and “team work” were crucial to achieve the results of the home care studies of this thesis. A special thanks to Nuno Silva (clinical Nurse) and all the Linde

home care team that gave me great support and actively contributed to this thesis line of research.

� To Dr. Michele Vitacca and his Respiratory Rehabilitation multidisciplinary team of Fondazione Salvatore Maugeri IRCCS,

Lumezzane (BS) Italy, for his kind friendship and for sharing with us all his knowledge and experience in home mechancial ventilation and telemedicine. It has been a great honor to perform a line of research together with this reference center.

� To Hugo Casais, long time and forever best friend, for his professional competence and outstanding creativity in developing all the thesis and presentation template design.

� To Paulo Abreu, Luísa Morais and Ana Menezes, my main influences in Respiratory Physiotherapy. Their teachings motivated me, still as a student, to dedicate my professional life to this field. Their words and advices still and always motivate me to continue my path.

� To all my old friends (that the number does not permit me to individualize) and all the new friends that i had the opportunity to meet during my journeys throughout the world teaching and learning about Noninvasive ventilation and Respiratory Care. I have had the privilege to meet fantastic people from USA, South America (Brazil, Argentina, Ecuador, Cuba, Mexico, Columbia, Chile), Europe (Spain, Italy, France, Belgium, United Kingdom, Germany, Switzerland, Greece, Sweden, Norway, Denmark), Japan, Middle East, Australia etc.. Each one of these international friends represent special moments that i will never forget

� To my Family, especially to my Mother, the main responsible for my educational and ethical principles. She is always an example for me and was a “solid anchor” that allowed me to grow as a professional as well as a human being. A special dedication to my grandfather Antonio Ramalho, that since i was a child always believed in my dreams but let his own dreams be prematurely ended by cancer. I know he would be proud of this “dream” thesis.

� To Luana, for all the Love and Support that where important to maintain the necessary emotional balance to finish this work. I thank her for all her patience, understanding and for always being there with a “kiss” when I needed.

� Last, but not the least, TO ALL THE VENTILATOR DEPENDENT PATIENTS that trusted me and gave me the responsibility to help them breathe better. They are, and always will be, my greatest source of inspiration and the main responsables for all this work.

With them i learned the most important lessons and to them I DEDICATE THIS THESIS.

INTRODUCTION

Most patients with impairment of pulmonary function can be differentiated into those

who have primarily oxygenation impairment due to predominantly intrinsic lung

disease, and those with lung ventilation impairment on the basis of respiratory muscle

weakness (1). This distinction is important because, although many patients in the

former category have been described to benefit from noninvasive ventilation in the

acute care setting (2-3), long term use is more controversial (4-8). Patients with

primarily ventilatory impairment, on the other hand, can benefit from the use of both

inspiratory and expiratory muscle aids and have excellent prognoses with long term

home mechanical ventilation (9-17).

One of the most important developments in the field of mechanical ventilation over the

past 15 years has been the emergence of noninvasive ventilation (NIV) as an increasing

part of the critical care armamentarium (18). Noninvasive positive-pressure ventilation

(NPPV) is the delivery of mechanical ventilation to patients with respiratory failure

without the requirement of an artificial airway. Although NPPV is often used for long-

term nocturnal or continuous support of patients with forms of chronic respiratory

failure (19), its use is increasingly popular in varied clinical situations in the intensive

care unit (ICU) setting as high level evidence supporting its use continues to accumulate

(2, 20-21).

The attraction for NPPV relates primarily to its advantages over invasive mechanical

ventilation. It has been shown to comparatively decrease resource utilization and

circumvents the myriad of complications associated with invasive mechanical

Noninvasive ventilation and mechanical assisted cough: efficacy from acute to chronic care

Miguel Ramalho do Souto Gonçalves 1

ventilation such as upper airway trauma, ventilator associated pneumonia, and

compromise of speech and swallowing (22-23). NPPV should, however, be considered

in some cases an alternative to invasive mechanical ventilation rather than its

replacement (24-28). Keys to the success of NPPV and to improving clinical outcomes

of patients with acute respiratory failure are careful patient selection and a well

designed clinical protocol because failure of NPPV only delays potentially more

definitive therapy with invasive ventilation (29). For patients with secretion

accumulation or a weak cough reflex, adequate secretion management with manual or

mechanical techniques might be advisable before non-invasive ventilation is declared

failed or contraindicated (2, 30).

Noninvasive ventilation has been proposed for several other applications, including

facilitation of weaning and extubation. One major determinant of weaning failure is an

excessive load on the respiratory muscles after disconnection from the ventilator (31-

32). In patients who fail a T-piece trial, invasive and noninvasive ventilation are equally

effective in reducing inspiratory effort and improving gas exchange, although

noninvasive ventilation results in better patient comfort (33). By allowing effective

ventilator assistance, while eliminating the risks associated with endotracheal

intubation, noninvasive ventilation may be a valuable alternative to the conventional

weaning techniques (20). Considering that difficult to wean patients have higher

morbidity and mortality and consume a substantial amount of health care resources(34),

these results could lead many of those who have so far considered noninvasive

ventilation ineffective or unsafe (35) to change their mind and reevaluate its potential.

Although a relatively straightforward technique, noninvasive ventilation has several

specific features that must be taken into account to avoid negative and disappointing

results (36).


2 Miguel Ramalho do Souto Gonçalves

In the intensive care setting very often patients have impaired airway clearance.

Endotracheal intubation prevents the patient from closing the glottis, which is necessary

for effective coughing (37). Care of the intubated patient includes direct suction applied

to the endotracheal tube which clears a small portion of the airway, is ineffective for

clearing secretions in the peripheral airways, and the patient is left dependent upon

mucociliary clearance rather than cough clearance (38). Conventional techniques for

augmenting the normal mucociliary clearance and cough efficacy have been used for

many years to treat patients with respiratory disorders from different etiologies. In

recent years, new technologies and more advanced techniques have been developed to

be more effective in acute respiratory failure These techniques involve mechanical

application of forces to the chest wall (39) or intermittent pressure changes to the airway

to assist airway mucus clearance (40-41).

Mechanical insufflation-exsufflation (MI-E) acts directly on the airway to assist or

substitute for expiratory muscle function in the elimination of airway secretions. The

effective elimination of airway mucus and other debris is one of the most important

factor that permits successful use of chronic and acute ventilation support (noninvasive

and invasive) for patients with either ventilatory or oxygenation impairment.

Decades of experience during the polio epidemics (42-43) and subsequently (13, 44-45)

established that long-term nocturnal noninvasive ventilation stabilizes gas exchange and

improves symptoms in patients with chronic respiratory failure. For home mechanical

ventilation, noninvasive ventilation has a number of advantages over invasive

mechanical ventilation, including greater ease of administration, reduced need for

skilled caregivers, elimination of tracheostomy-related complications, enhanced patient

comfort, and lower cost (46-47). However, as is the case in the acute setting, not all

patients with chronic respiratory failure are good candidates for noninvasive ventilation.



Long term mechanical ventilation at home now incorporate both ventilator dependent

(>16 h per day ventilatory support) and ventilator assisted (primarily nocturnal only)

individuals, using a variety of devices and interfaces including invasive ventilation and

NIV techniques(48). The diversity of conditions and variability in level of care needed

by these individuals means that introducing and maintaining long-term ventilation in the

home requires skill and experience on the part of the prescribing centre, particularly if

the patient is using ventilatory support on a near continuous basis or has a tracheostomy

in place for the delivery of ventilation (49-51). Additionally, introducing medical

technology into the home raises a number of issues for the patient and caregivers, as

well as local health services, which need to be identified on an individual basis (52-53).

Although no controlled trials have evaluated the efficacy of MI-E, significant amount of

evidence suggests that it enhances removal of secretions in patients with impaired

cough (54-62). It has been particularly useful in patients’ homes to treat episodes of

acute bronchitis, permitting avoidance of hospitalization (63). Clinicians caring for

patients with severe cough impairment should be familiar with the various techniques

available to assist expectoration. These are particularly important with noninvasive

ventilation, because there is no direct access to the airway, and secretion retention is a

frequent complication and common cause for failure. Although controlled data are

lacking, these techniques appear to be helpful in maintaining airway patency in patients

with cough impairment during use of noninvasive ventilation in both acute and chronic

settings.

Research on a continuum strategy of care, that include NIV therapy coupled with MI-E

from acute care to chronic settings in patients with muscle weakness is warranted to

support the application of specific protocols that may improve survival in this patient

population.



HISTORICAL PERSPECTIVE OF MECHANCIAL

VENTILATION AND RESPIRATORY MUSCLE AIDS

NIV was first described in Genesis Chapter 2 when the Lord God “breathed into his

(Adam’s) nostrils a breath of life”(64). Around 800 BC, mouth to mouth NIV was

provided by Elisha to resuscitate a child as he "...went up, and lay upon the child, and

put his mouth upon his mouth, and his eyes upon his eyes, and his hands upon his

hands; and he stretched himself upon the child; and the flesh of the child waxed warm.

Mechanical ventilatory assistance may have first been attempted by Theophrastus

Paracelsus in1530. Paracelsus used his chimney bellows to ventilate patients' lungs via

the mouth (Figure 1). This technique of respiratory resuscitation continued to be used

in Europe through the 1830s (65).

Figure 1- Description of mouth ventilation through a chimney bellows as described by Paracelsus in

1530



Thereafter, John Fathergill, and others used pumps and bellows to insufflate patients via

upper airway canulas (66). Successful mouth-to-mouth resuscitation was reported in

1744 (67). In 1767, the Dutch Humane Society published guidelines resuscitating

drowning victims. A memo from Louis D’Etiolles to the French Academy of Sciences

reported that death from drowning was markedly decreased from 1774 to 1829 by

mouth-to-mouth and orolaryngeal intubation resuscitation methods (68).

Orolaryngeal intubation actually dates to Hippocrates in the 4th century BC but was

apparently dropped until 1800 (69). For the next 30 years 10 to 20 others in France,

Germany, England, and Italy developed manual pumps to ventilate via translaryngeal

tubes as well as via noninvasive oral and nasal interfaces, and were “strong advocates of

insufflation of the lungs for asphyxia, believing this the best method to restore the

victims of asphyxia, no matter what the cause (69).

Then in 1893 Dr. George H. Fell of Buffalo, New York presented a hand-operated

bellows to deliver air via translarngeal or tracheotomy tubes at an International

Congress in Washington in 1893. He then substituted an oronasal interface for the

invasive tubes to ventilate CO2 narcosis patients(not surgical), using a finger as an

“exhalation valve (69). Ignez von Hauke of Austria was probably the first person to use

NIV via an oronasal interface in the 1870s (70). In 1896 the Fell-O’Dwyer foot operated

manual resuscitator bellows made at Columbia Presbyterian Hospital in New York

provide ventilation via orolaryngeal tubes to treat CO2 narcosis due to opium (71). In

1898 Matas used these ideas to provide both anesthesia and ventilatory support via an

orolaryngeal tube for thoracic surgery. However, the idea of supporting ventilation

rather than just providing anesthesia via airway tubes during surgery did not catch on.



Until around 1830, mouth-to-mouth and tranlaryngeal positive pressure methods were

used for resuscitation but gradually the paradigm shifted from applying pressures via

airways to pressures to the body. In the “Inversion Method” of the 1770s the body was

turned upside down and the chest intermittently compressed. In the “Barrel Method,”

(1773) the victim was hoisted onto a wine barrel and rolled back and forth to compress

the chest. In 1812 Lifeguards hoisted drowning victims onto horses that trotted to

bounce the chest. This was banned in 1815 by "Citizens for Clean Beaches". In 1856,

Marshall Hall rolled drowning victims 16 times a minute and applied pressure to the

back during exhalation when prone and achieved tidal volumes of 300 ml to 500 ml

(72).

The first tank ventilator was described by the Scottish physician, John Dalziel, in 1838.

The negative pressure was created in the tank by a pair of bellows worked from outside

the tank by manually operating a piston rod (73).

In 1931 John Emerson of Cambridge, Massachusetts built a simplified, inexpensive, and

more convenient iron lung that operated quietly, permitted speed changes, and could be

operated by hand if electricity failed (Figure 2)(74). Then, in 1936 Fred Snite Jr., age

25, son of Colonel Frederick Snite, a prominent Chicago financier, was stricken with

poliomyelitis while traveling with his family in Beijing. The Drinker iron lung, one of

only 222 iron lungs in the world in 1936, was used by Mr. Snite for 1 year. He then

returned to the United States via truck, ocean liner, and train along with a physician, 7

Chinese nurses, a Chinese physiotherapist, two American nurses, and his family(75).

The fanfare, including the fact that he married and fathered 3 daughters, stimulated

public awareness and resulted in mass production of Emerson iron lungs in time for the

poliomyelitis epidemics that were to come (Figure 3) (76). Mr. Snite lived using the

iron lung continuously until 1954 when he died from cor pulmonale.



Figure 2- Emerson™ Iron Lung opened for nursing care, while the patient was ventilated through a

dome that covered their heads.

Figure 3- Iron lung wards that managed hundreds of patients during the poliomyelitis epidemics

In 1947 Emerson placed transparent glass domes that enclosed the users' heads and

sealed at the iron lung's neck collar. The iron lung bellows could create both negative

and positive pressure in the cylinder, and after 1947, the bellows could create positive

pressure under the dome. Just as the negative tank pressure insufflated the lungs, the



subsequent positive pressure forcibly exsufflated the patient, increasing tidal volumes.

When iron lungs had to be opened to permit nurses access to the body, patients with no

breathing tolerance received IPPV via the dome (Figure 2) (43, 76).

The Fairchild-Huxley chest respirator (77) and Monaghan Portable (chest shell)

Respirator(78) were introduced in 1949 and became the first mass produced chest

shells. Emerson came out with a negative pressure cycling generator for chest shells in

1950. Although the shells were portable, the negative pressure generators used for them

were not. These devices were built by hand and so were very expensive. There were no

filters so that patients inhaled a great deal of dust and particles from the ventilator itself.

Figure 4- Chest shells for daytime ventilatory support

Chest shells were used long-term for daytime ventilatory support with the user sitting

(Figure 4) as well as for nocturnal support with the user supine. Similar chest shells are

manufactured today and are used predominately for nocturnal ventilatory assistance(68).

After successfully resuscitating drowned cats with a negative pressure body jacket,

Alexander Graham Bell developed a similar negative pressure jacket to assist

ventilation in premature infants in 1881. However, Bell's invention was not picked up

by the medical community until the British Tunnicliffe breathing jacket was described



in 1955 and Jack Emerson put the Poncho "wrap" style ventilator on the market in 1957

(79). These ventilators, and the wrap ventilators that followed them, consist of a firm

grid covering at least the thorax and upper abdomen. The grid and the body under it are

covered by a wind-proof jacket that is sealed around the neck and extremities. As

negative pressure is cycled under the wrap and grid, air enters the upper airway to

ventilate the lungs. The only significant changes in modern wrap ventilators from the

original designs are the plastics used to fabricate the jacket and grid, and the length and

form of the extremity sleeves (Figure 5).

Figure 5- The pneumowrap ventilator used by a patient with late-onset chronic ventilatory failure.

Figure 6- The rocking bed ventilator (J. H. Emerson Company, Cambridge, MA)



The Rocking Bed Ventilator (J. H. Emerson Company, Cambridge, MA) has been used

for ventilatory assistance since 1932 (Figure 6). It rocks the patient 15o to 30o, thereby

using gravity to cyclically displace abdominal contents for diaphragmatic

excursion(80). It was used until the late 1950s by predominantly poliomyelitis and

muscular dystrophy patients and is still occasionally used today. This device is

generally less effective than other body ventilators but can be adequate for some

patients.

The intermittent abdominal pressure ventilator (IAPV) was developed by Alvin Barach

in the United States in 1955 where he used a pump made by the Gast Rotary Pump

Company to pump air from an air reservoir into the sac inside the belt that was attached

to the abdomen (68).

In 1946, after anesthesiologist James Elam had read about mouth-to-mouth NIV in a

historical article on resuscitation, a child became apneic on his ward and he “went into

total reflex behavior.”.. .I stepped out in the middle of the corridor, stopped the gurney,

grabbed the sheet, wiped the copious mucous off his mouth and face, sealed my lips

around his nose and inflated his lungs. In four breaths he was pink..." In 1951, Elam

demonstrated that his expired air blown into an endotracheal tube maintained normal

oxygen saturation on postoperative patients before ether anesthesia wore off. This was

exactly what Elsberg had done in 1910, Paracelsus in 1530, and even Hippocrates.

Elam then recruited 31 physicians and medical students, and one nurse to observe

ventilation in anaesthetised and curarized patients most of them for several hours each.

Blood O2 and CO2 were analyzed. He demonstrated the method to over 100 lay persons

who were then asked to perform the method. These dramatic demonstrations along with

the lack of iron lungs during a polio epidemic in Denmark in 1952 resulted in a

paradigm shift from body ventilator to tracheostomy tubes for ventilatory support (81)



Galen reported using tracheostomies to ventilate animals in the 2nd century.

Trendelenburg was the first to describe the use of a tracheostomy tube with an inflated

cuff for manual application of positive pressure ventilatory assistance during anesthesia

of a human in 1869(43).Tracheostomy was also used for drowning victims from the 17th

century through the mid-19th century and tubes were placed into polio iron lung users

with severe bulbar-innervated muscle impairment to suction out airway secretions.

Noninvasive IPPV had not yet been reported and mechanical forced exsufflation

devices to assist cough were not widely available until after 1953(82-84).

Furthermore, during the Danish epidemic the mortality rate was 94% for patients with

respiratory paralysis and concomitant bulbar muscle involvement and 28% for those

without bulbar involvement. Lassen reported that mortality figures for ventilator

supported patients decreased from 80% to 41%, or to about 7% for the entire Danish

acute paralytic poliomyelitis population overall(85). This was in part due to more

frequent use of tracheostomy, particularly for those with severe bulbar involvement.

In the meantime, specialized centers in the United States were also reporting equally

impressive decreases in mortality by "individualizing" patient care. From 1948 to 1952,

3500 patients were treated at Los Angeles General Hospital. Fifteen to 20% required

ventilatory support. Acute poliomyelitis mortality decreased from about 15% in 1948 to

2% in 1952 without the use of tracheostomy for ventilatory support(86). Better nursing

care and attention to managing airway secretions including the use of devices to help

eliminate them were factors in decreasing mortality rates.

A long debate ensued as to whether tracheostomy IPPV or body ventilators were

preferable for ventilatory support. In 1955, an International Consensus Symposium

defined the indications for tracheostomy as the combination of respiratory insufficiency



with swallowing insufficiency and disturbance in consciousness or vascular

disturbances (86).

Tracheostomy ventilation facilitated mobility by permitting patients to leave iron lungs

for wheelchairs with positive pressure ventilators rolled behind them, an obvious

advantage considering that the iron lungs were very heavy to transport. The switching to

tracheostomy spread across the United States where, in 1956, the small, portable,

pressure-limited Bantam ventilator came onto the market for positive pressure through

the tube. Tracheostomy also provided for a closed system of ventilatory support that

was amenable to precise monitoring of ventilatory volumes and pressures, oxygen

delivery, and the use of the high technology respirators and alarm systems that were to

come (68).

As the use of endotracheal methods became widespread, manually assisted coughing

was no longer taught in medical, nursing, and respiratory therapy curricula and

clinicians lost familiarity with body ventilators. Noninvasive IPPV methods were not to

be described until 1969 and 1973 (43) and their 24 hour use was not reported for a large

population until 1993 (87). Further, the only studies of the use of MI-E devices had

been for acute poliomyelitis patients and patients with severe intrinsic pulmonary

disease (84). The former was felt to be a transient population, and the latter a population

for which the use of noninvasive respiratory muscle aids was not ideal. Although MI-E

devices went off the market in the 1950s or early 1960s they continued to be used by

patients who had access to them. Meanwhile, with widespread use of translaryngeal

intubation and tracheostomy, numerous reports of complications appeared.

Ironically, what may now seem like the simplest solution to the problem of providing

ventilatory support, that of delivering positive pressure ventilation via a simple mouth



piece, continues to be the last to be considered. In 1953, Dr. John E. Affeldt of Rancho

Los Amigos Hospital in Los Angeles reported in a post-poliomyelitis respiratory

equipment conference that the positive pressure attachment used to deliver the IPPV

was the simple mouth piece used for pulmonary function testing. Patients would

intermittently block the mouth piece to cycle adequate tidal volumes into their lungs

(42).

The ventilator unit of Goldwater Memorial Hospital in New York City was opened in

1955. In a short period of time the 80 bed unit was filled with mostly post-poliomyelitis

body ventilator users. Most of the patients had been recumbent in iron lungs in their

local hospitals since having poliomyelitis. At Goldwater Hospital these patients, often

with no breathing tolerance, were encouraged to leave their iron lungs during daytime

hours and use the chest shell ventilator or IAPV when sitting. These patients could now

be placed in wheelchairs using chest shells, IAPVs, or IPPV via mouth pieces and the

"portable" negative-positive pressure ventilators were rolled behind them until the

smaller portable machines like the Bantam became available in 1957(68).

Because mouth piece IPPV can provide much greater air volumes directly to the lungs

than can IAPV or chest shell use, it became the mode of ventilatory support that the

patients used during intercurrent chest infections and other times of stress. Although in

centers other than Goldwater Hospital the great majority of ventilator users were

switched to tracheostomy IPPV, isolated patients around the country refused

tracheotomy and some reported that they themselves had the idea to ventilate their lungs

via mouthpieces.

Dr. Augusta Alba took charge of the Goldwater Memorial Hospital ventilator unit in

1956. She encouraged patients to use mouthpiece IPPV for daytime ventilatory support.



Like Dr. Affeldt before her, she soon discovered that mouthpiece IPPV users would nap

during the daytime without the mouthpieces falling out of their mouths. This was

remarkable because many of these patients had little or no autonomous breathing

ability; their ventilators did not have alarms; there was nothing to hold the mouthpiece

in the mouth other than the patient's own oropharyngeal muscles and these muscles are

not thought to function during REM sleep; and they had little or no extremity function

so they could not have put the mouthpieces back into their mouths if they had fallen out.

In 1964 she permitted a number of patients to use mouthpiece IPPV overnight rather

than return to body ventilators (88). It is remarkable that few if any patients died by

losing their mouthpieces during sleep.

No patients were admitted to or managed with tracheostomy tubes on the Goldwater

Memorial Hospital ventilator unit until 1968. From the mid-1960s until nocturnal nasal

IPPV was described in 1987 (89), simple mouthpiece IPPV was the only method of

daytime or nocturnal noninvasive IPPV. It was not until oximeters became widely

available in the early 1980s that it was discovered that these patients experienced

frequent, and at times, severe SpO2 desaturation associated with periods of leakage of

ventilator delivered air (insufflation leakage) during sleep (90).

The Bennett mouth piece with lipseal retention (Mallincrodt, Pleasanton, CA) came

onto the market in 1968. It was designed to be used for pulmonary function testing. To

prevent the mouthpieces from falling out of the mouths of her IPPV users during sleep,

Dr. Alba convinced many of her patients to use mouthpiece IPPV with lipseal retention.

Besides mouthpiece retention, by sealing the lips it greatly reduced insufflation leakage

out of the mouth (90).



In 1981, as a technical advisor to Professor Yves Rideau of the University of Poitiers,

France, Dr. John R. Bach introduced mouthpiece and lipseal IPPV into France. It was

in the Winter of 1981-82 that Dr. Rideau suggested to Drs. Delaubier and Bach that

ventilation should be tried via nasal access (13). He felt that humidification would be

facilitated and the nasal route would prove more physiologic for IPPV. Drs. Bach and

Delaubier first used urinary drainage catheters with the cuffs inflated in each nostril to

deliver nasal IPPV to themselves and then to French muscular dystrophy patients for

daytime and nocturnal ventilatory assistance (91). Nasal IPPV was first used as an

alternative to airway intubation for 24 hour ventilatory support in 1984 and it was first

reported in 1987 (92).It was in 1984 that nasal CPAP masks became commercially

available and could be used as IPPV interfaces (93). This permitted rapidly expanding

application of nasal ventilation.

Excessive nasal bridge pressure and insufflation leakage into the eyes were common

complaints when using nasal IPPV with the first commercial CPAP "masks". Attempts

at customizing nasal interfaces for IPPV were first described in 1987 (92). Custom

molded nasal interfaces eventually became available both commercially and

individually (94).

In the late 1980s Dr. Adolphe Ratza, a Swedish postpoliomyelitis survivor,

experimented with the construction of strap-retained custom nasal and oral-nasal

interfaces. His oral-nasal interfaces, with strap retention systems much like those used

for lipseal and nasal IPPV, were described for long-term supported ventilation in 1989.

Over the last 15 years, strap-retained oral-nasal interfaces have been marketed by

several ventilatory companies both for chronic and acute care (68).



By 1949 there were over 400 respiratory polio survivors using ventilators in the United

States in custodial care at over a hundred hospitals scattered around the country. They

were funded by the National Foundation for Infantile Paralysis (March of Dimes) which

President Franklin Roosevelt had founded. The hospital charges were so high that the

March of Dimes funded a study to find ways to reduce the cost. The study showed that

it would be far more economical to move the patients to regional centers with

multidisciplinary professional teams. Thus, 16 polio respiratory and rehabilitation

centers with 15 to 160 patients were created at the teaching hospitals of 16 medical

schools. The March of Dimes paid for the centers' professional staff, patient care,

equipment, research, and ultimately for home care, home modifications, and personal

care attendants (95). Interestingly, there were no pulmonologists and respiratory therapy

did not exist at that time. The patients' and their families were taught how to ventilate

lungs and to facilitate airway secretion elimination and were made key participants in

the rehabilitation team.

In 1953 a home care plan was developed at Rancho Los Amigos Hospital in California

to save money when it was shown that de-institutionalization with home care by

attendants could result in 75% cost savings. The first attendants were trained by the

centers but ultimately attendants were hired and trained by the patients and families

themselves. In 1953 it was estimated that 1800 post-poliomyelitis patients had been

respirator (iron lung) supported for one month or more and that 20% of these patients

had already been discharged home. Forty-four percent of the home mechanical

ventilation users were cared for solely by their families, and 15% of these patients were

under 9 years of age. Over 50% of the patients required ventilatory support over 16

hours per day. By 1956, 92% of permanently ventilator dependent individuals had been

discharged to their homes (68).



In 1952, Barach and Beck, began applying negative pressure to patient airways via a

face mask(84). In May of 1953 Dr. John Affeldt of Rancho Los Amigos noted that he

had had his patients try many methods of assisted coughing including Barach's

mechanical cough chamber, the suction of vacuum cleaners, manual chest and

abdominal compression, and providing maximal insufflation in an iron lung then

closing the glottis until positive pressure peaks in the tank to maximize cough flows.

He reported being disappointed that he was unable to clear atelectasis in a number of

patients with these methods. Mr. Emerson, however, noted that it made much more

sense to apply positive and then negative pressure to a face mask to increase cough

flows than it did to place patients into the mechanical cough chamber(42). Five months

later, Fagin and Barach's brother Edward's company OEM put the

Exsufflation-with-Negative Pressure device called a "Cof-flator" (Figure 8) on the

market.

Figure 7 - The OEM™ Exsufflation-with-Negative Pressure device called the "Cof-flator®"

In 1954 Beck and Alvin Barach wrote of the Cof-flator, "The life-saving value of

exsufflation with negative pressure was made clear through the relief of obstructive



dyspnea as a result of immediate elimination of large amounts of purulent sputum, and,

in a second episode, by the substantial clearing of pulmonary atelectasis after 12 hours'

treatment” (83). Although many studies demonstrated its efficacy and no major

untoward effects were described with its use, the Cof-flator was abandoned with the

increasing resort to tracheostomy. However, patients who had access to the original

Cof-flators kept them and used them effectively as needed. Occasional medical

publications continued to refer to its effective use even though it was no longer on the

market (81, 88, 96-98).

In February of 1993, a new mechanical insufflator-exsufflator (In-Exsufflator, J. H.

Emerson Co., Cambridge, MA) was released onto the market. The In-exsufflator

operated like the Cof-flator except that cycling between positive and negative pressure

had to be done manually. The manual cycling feature facilitated care giver-patient

coordination of inspiration and expiration with insufflation and exsufflation but it

required that an additional hand be available to deliver an abdominal thrust (99). Then,

in 1995, an automatically cycling device became available. In 2001 it was renamed the

"Cough-AssistTM".

The creation of the medical specialty of respiratory therapy in 1961 and the training of

respiratory therapists has become of paramount importance for the noninvasive

management of patients with ventilatory impairment(94). Respiratory therapists have

been and continue to be essential for evaluating and training patients in the use of

noninvasive ventilation and expiratory muscle aids.

Although NPPV first made its mark in the home environment, as confidence grew,

criticall ill patients with acute ventilatory failure were ventilated in hospital, and now

the noninvasive approach is considered by some to be the treatment of choice for acute



ventilatory failure of whatever etiology (2). Because ventilation can be assisted without

the need for paralysing and sedating drugs, patients do not need continuous one-to-one

nursing care and assisted ventilation for acute ventilatory failure outside the intensive

care unit (ICU) has become a feasible option (19). There is now an ever-growing body

of prospective randomized control data to inform medical practice, and it is likely that,

just as NPPV has been described as "a new standard of care" in patients admitted to

hospital with an acute exacerbation of COPD (18, 100-101), it will assume a still greater

role in the management of acutely ill patients with respiratory disease from other

etiologies (102-106).



EQUIPMENT AND TECHNIQUES FOR NON INVASIVE

POSITIVE PRESSURE VENTILATION

Successful assisted ventilation depends critically upon adapting mechanical ventilation

to the patient needs. This is particularly true when the noninvasive mode is used

because the patient is conscious and if ventilation is ineffective or uncomfortable the

patient may reject it. An understanding of the technical equipment, in particular the

modes of ventilation and the potential problems with each, is crucial, as is the selection

of an appropriate interface(101)

Characteristics of different modes of ventilation

During noninvasive positive pressure ventilation (NPPV) positive- end expiratory

pressure (PEEP) is combined with positive inspiratory pressure. The delivery of positive

inspiratory pressure is triggered by the patient’s inspiratory effort, and usually titrated to

produce either constant volume (assist volume control; AVC) or constant pressure

(pressure-support ventilation; PSV)(107).

Pressure-cycled machines deliver a predetermined pressure and the volume delivered

will depend upon the impedance to inflation. If there is a leak in the circuit, flow will

increase to compensate, but if there is airway obstruction, tidal volume will be

reduced(108). Volume cycled machines deliver a fixed tidal or minute volume and will

generate a pressure sufficient to achieve this. If the impedance to inflation is high,

pressure will be increased and the targeted tidal volume will be delivered. However, if

there is a leak, there will be no increase in flow rate to compensate, a lower pressure

will be generated, and the delivered tidal volume will fall(107). Triggering into

inspiration and cycling into expiration can be timed by the machine or on the basis of

detection of patient initiated changes in flow or pressure(109). Mechanical ventilation



can be "controlled" (i.e. the machine determines respiratory frequency), "assisted" (i.e.

the machine augments the patient´s spontaneous breaths), or a combination of the two,

"assist/control" (A/C) mode, which is called "spontaneous-timed" (S/T) mode in

pressure targeted ventilators. The backup rate is usually set at slightly below the

spontaneous breathing rate (110).

In chronic respiratory failure (CRF), timed modes alone may be used in patients with

unreliable respiratory effort, unstable ventilatory drive or mechanics, apnoea or

hypopneas, massively overloaded respiratory muscles or in patients where the assist

mode fails to augment spontaneous breathing. In practice, however, the A/C or S/T has

the advantages of the timed mode but allows augmentation of extra spontaneous efforts

that may occur with irregular breathing patterns that may be seen at sleep onset or

during rapid eye movement (REM) sleep. The proportion of breaths which are assisted

and those which are controlled will depend upon the backup rate that is set (111).

Pressure cycled ventilation.

In this mode, inspiratory pressure delivered by the ventilator is constant to the preset

pressure level, regardless of the magnitude of the patient’s inspiratory effort. It also

unloads the fatigued inspiratory muscles by decreasing their inspiratory work of

breathing and oxygen consumption(112). For these reasons, it has gained widespread

acceptance as a mode of delivering NPPV in both the acute and chronic setting(113).

Pressure cycled modes are available on most ventilators designed for use on intubated

patients in critical care units. Most such “critical care ventilators” provide pressure

support ventilation (PSV) that delivers a preset inspiratory pressure to assist

spontaneous breathing efforts and has attained popularity in recent years as a weaning



mode(114). Most such modes also permit patient-triggering with selection of a backup

rate. Nomenclature for these modes varies between manufacturers, causing confusion.

For the pressure support mode, some ventilators require selection of a pressure support

level that is the amount of inspiratory assistance added to the preset expiratory pressure

and is not affected by adjustments in PEEP. Bi-level pressure ventilation requires the

selection of inspiratory and expiratory positive airway pressures (IPAP and EPAP) and

the difference between the two determines the level of pressure support. It is important

to recall that with the latter configuration, alterations in EPAP without parallel changes

in IPAP will alter the pressure support level(115).

What distinguishes PSV from other currently available ventilator modes is the ability to

vary inspiratory time breath by breath, permitting close matching with the patient’s

spontaneous breathing pattern. A sensitive patient-initiated trigger signals the delivery

of inspiratory pressure support, and a reduction in inspiratory flow causes the ventilator

to cycle into expiration. In this way, PSV allows the patient to control not only

breathing rate but also inspiratory duration(116). As shown in patients undergoing

weaning from invasive mechanical ventilation, PSV offers the potential of excellent

patient-ventilator synchrony, reduced diaphragmatic work, and improved patient

comfort. However, PSV may also contribute to patient- ventilator asynchrony,

particularly in patients with COPD as brief rapid inhalations that may be seen in these

patients with may not permit adequate time for the PSV mode to cycle into expiration,

so that the patient’s expiratory effort begins while the ventilator is still delivering

inspiratory pressure(117). During NPPV these forms of asynchrony are exacerbated in

the presence of air leaks.

Although noninvasive PSV is often administered using standard critical care ventilators,

portable devices that deliver pressure- limited ventilation (Figure 8) have also seen



increasing use for both acute and chronic applications. These devices, sometimes

referred to as “bi-level” devices because they cycle between two different positive

pressures, are lighter and more compact than critical care ventilators, offering greater

portability at lower expense.

Figure 8 – Bi-level portable devices

Some offer not only a spontaneously triggered pressure support mode but also pressure-

limited, time-cycled, and assist modes. Some also offer adjustable trigger sensitivities,

“rise time” (the time required to reach peak pressure), and inspiratory duration, all

features that may enhance patient-ventilator synchrony and comfort(118). Further, the

performance characteristics of these ventilators compare favorably with those of critical

care ventilators (119). On the other hand, unlike the critical care ventilators, the bi-level

are not currently recommended for patients who require high oxygen concentrations or

inflation pressures, or are dependent on continuous mechanical ventilation unless

appropriate alarm and monitoring systems can be added. Recently, however, new

versions of bi-level ventilators (Figure 9) have been introduced that have more

sophisticated alarm and monitoring capabilities, graphic displays, and oxygen blenders

and are quite suitable for use in the acute care and ICU setting.

Because of their portability, convenience, and low cost, the bi-level devices have proven

ideal for home use in patients with chronic respiratory failure requiring only nocturnal



ventilatory assistance. In addition, unlike volume-limited ventilators, they are able to

vary and sustain inspiratory airflow to compensate for air leaks, thereby potentially

providing better support of gas exchange during leaking(120)

Figure 9 – V60 acute care bi-level ventilator (Philips Respironics, Inc)

Volume cycled ventilation

In this mode, inspiratory pressure delivered by the ventilator is titrated in order to

achieve a preset constant volume target. Most critical care ventilators offer both

pressure- and volume-limited modes, either of which can be used for administration of

noninvasive ventilation. However, the expiratory volume alarm of intensive care

volume ventilators makes them almost impractical to use to deliver NPPV and they are

usually not sufficiently portable for home use(121). Portable volume-cycled ventilators,

however, are most often conventionally used for providing long-term tracheostomy

rather than NPPV, using standard tubing with exhalation valves and humidification as

necessary(122). Compared with the portable pressure-limited ventilators described

above, the volume-limited portable ventilators are more expensive and heavier.

However, they also have more sophisticated alarm systems, the capability to generate

higher positive pressures, and built-in backup batteries that power the ventilator for at



least a few hours in the event of power failure(123). These ventilators are usually set in

the assist/control mode to allow for spontaneous patient triggering, and backup rate is

usually set at slightly below the spontaneous patient breathing rate. The only important

difference relative to invasive ventilation is that tidal volume is usually set higher (10 to

15 ml/kg) to compensate for air leaking. Volume cycled ventilators can generally

deliver up to 2500 ml volumes and are well suited for patients in need of continuous

ventilatory support or those with severe chest wall deformity or obesity who need high

inflation pressures(124-125).

The minimum inspiratory effort required by the patient is to trigger the ventilator. The

volumes delivered to the lungs correlate with ventilator gauge pressures. Thus, the

pressures indicated on the volume ventilator pressure gauge vary depending on

ventilator delivered volumes, insufflation leakage, and lung impedance. There are also

low and high pressure alarms, sensitivity controls that permit the patient to trigger

ventilator delivered breaths, and flow rate adjustments. Alternatively, when the patient

increases their inspiratory effort, due to increased ventilatory needs, the inspiratory

pressure delivered by the ventilator will decrease in order to keep the constant volume

target(126). The greater the patient’s inspiratory effort, the lesser the ventilator’s

assistance. The ventilator might even deliver negative inspiratory pressure (i.e. pull air

back), when the patient makes an adequately strong inspiratory effort, in order not to

exceed the preset volume target(125). Additionally, it has been shown that some home

ventilators are inaccurate in delivering the preset VT, especially when faced with

deteriorating structural properties of the lung(107). For this reason, this mode has been

disfavored for use as NPPV in the acute setting(18) and, currently, is used merely for

home NIMV for patients with chronic respiratory failure due to neuromuscular

disease(1, 127).



Ventilators with mixed pressure and volume -targeted modes.

In order to make the most of the advantages of pressure and volume ventilators, new

machines which combine the two modes have recently been released (Figure 10). These

respirators are similar to critical care ventilators and may be useful for difficult-to-adapt

patients and those with rapidly changing breathing patterns and mechanics(119). The

clinical impact of these "dual mode ventilators" has not been well evaluated and

therefore it is not known if they offer important advantages to other respirators in

routine practice. In an effort to combine the advantages of pressure- and volume-

targeted modes into one ventilation mode, new hybrid modes such as average volume-

assured pressure support(128) and adaptive servo ventilation(129-130) have recently

been introduced in the NPPV setting.

Figure 10 – Elysée 150 for both pressure and volume targeted ventilation (ResMed, Inc)



Interfaces for the delivery of NPPV

The major difference between invasive and NPPV is that with the latter, gas is delivered

to the airway via a mask or “interface” rather than via an invasive conduit. The open

breathing circuit of NPPV permits air leaks around the mask or through the mouth,

rendering the success of NPPV critically dependent on ventilator systems designed to

deal effectively with air leaks and to optimize patient comfort and acceptance.

Apart from the choice of ventilator type, mode and setting, another crucial issue when

starting NIV is to find an optimal interface(131). However, despite a broad variety, until

now only little attention has been focused on the choice of interface and no generally

accepted consensus has been reached concerning the management of interfaces(21). In

general, six different types of interface exist: total face masks, oronasal masks, nasal

masks, nasal pillows or plugs, mouthpieces and helmets. Advantages and disadvantages

of each interface is listed in figure 11.

Early studies dealing with NIV in ARF used nasal masks(132). The nasal mask adds

less dead space, causes less claustrophobia and allows expectoration and oral intake. In

order to reduce mouth leaks while wearing a nose mask a chin strap is sometimes

required but is rarely effective (119). The improvement in arterial blood gas tensions

appear to be slower in some studies using nasal masks compared to face masks (133).

Compared to nasal masks, the more common application of full face masks in ARF is

also a reflection of better quality of ventilation (at least during the initial phase of the

intervention) in terms of minute ventilation and improved blood gases (134). Compared

to nasal masks, face masks are generally more claustrophobic, impede communication,

limit oral intake and increase the dead space which may cause CO2 rebreathing (135).

However, based on practical experience, dead space does not seem to reduce the

effectiveness of NIV in ARF. In addition, further types of full face masks both for open



and closed circuits are available. Some of these masks have addressed the issue of dead

space and have increased leak rates, which may improve the quality of NIV(136-137).

Reducing the risk of skin damage is one of the major goals. The most common sites of

friction and skin damage are the bridge of the nose, the upper lip, the nasal mucosa, and

the axillae (with the helmet) (136). The most important strategy to prevent skin damage

is to avoid an excessively tight fit. Masks that have angle adjustments between the

forehead support and the interface can help prevent pressure and friction against the

bridge of the nose (119). Rotating interfaces might reduce the risk of skin damage, by

changing the distribution of pressure and friction, especially on the bridge of the nose

(138-139).

Air leaks may reduce the efficiency of NIV, reduce patient tolerance, increase patient-

ventilator asynchrony (through loss of triggering sensitivity), and cause awakenings and

sleep fragmentation (140). During pressure-support ventilation (PSV) leaks can hinder

achievement of the inspiration- termination criterion (136). In patients with

neuromuscular disorders receiving nocturnal NIV, leaks are associated with daytime

hypercapnia (141). In order to compensate for a significant leak a ventilator needs high

flows. Pressure-targeted ventilators have leak compensating abilities with peak

inspiratory flow rates of 120–180 L/min (142). Modern pressure ventilators can

compensate for very large leaks, but if they are allowed, sleep quality may be sacrificed.

Recently, respiratory system model studies have been published which investigated

mask mechanics and leak dynamics during simulated NIV (143). Leak compensation is

much more limited in volume-targeted ventilators; adding a leak to the circuit of these

ventilators caused a fall in tidal volume of 50% (125). However, moderate leaks can be

compensated for by increasing the tidal volume (124).



Figure 11 – Advantages and disadvantages of different types of interfaces (Adapted from

Nava and Hill (2)



Humidification during NPPV

Humidification and warming of the inspired gas may be needed to prevent the adverse

effects of cool, dry gases on the airway epithelium. Unidirectional inspiratory nasal

airflow, which can worsened by mouth air-leak, can dry the nasal mucosa, because the

nasal mucosa receives little or none of the moisture it would receive from the exhaled

gas(136).

If the gas delivered from the ventilator is not humidified, it will have lower than the

ambient air, and this is particularly true as the level of inspiratory support

increases(140) Humidification can prevent these adverse effects. The 2 types of

humidification device, heated humidifier, and heat-and-moisture exchanger (HME), are

used both for both short-term and long-term NIV(144). Heat and moisture exchangers

(HMEs) are widely used in intubated patients, because HMEs are easy to use and may

be less expensive than heated humidifiers(136). However, an HME, which is usually

placed between the Y-piece and the interface, can add an important amount of dead-

space, compared to a heated humidifier, which is placed in the inspiratory limb(145).



NON INVASIVE VENTILATION IN THE ACUTE CARE

SETTING

Rationale

Non-invasive ventilation refers to the delivery of mechanical ventilation with techniques

that do not need an invasive endotracheal airway(146). It should not, therefore, be used

when patients cannot protect their airway. It is not appropriate for all, and the selection

of candidates is important Compared with invasive mechanical ventilation, this type of

ventilation achieves the same physiological benefits of reduced work of breathing and

improved gas exchange(22, 33). Furthermore, it avoids the complications of intubation

and the increased risks of ventilator-associated pneumonia and sinusitis(103), especially

in patients who are immunosuppressed or with co-morbidities(147).

Studies published in the 1990s (132, 148) that evaluated the efficacy of noninvasive

positive-pressure ventilation for treatment of diseases such as chronic obstructive

pulmonary disease, congestive heart failure and acute respiratory failure have

generalized its use in recent years and made a major advance in the management of

acute respiratory failure(21). Over the past decade alone, it has been the subject of over

1,500 scientific papers, including 14 meta-analyses(2).

The use of non-invasive ventilation varies greatly between hospitals and geographical

regions, and has changed over time. Investigators of a worldwide prospective survey of

mechanical ventilation noted that use rose from 4% of all ventilators started in 2001, to

11% in 2004(149).It is increasingly being used in many countries, but frequency of use

is highly variable(2)



In 1996, Meduri et al(150). reported their experience with NPPV in 158 patients with

various diagnoses, of whom 65% avoided intubation with NPPV. They suggested that

NPPV be first-line therapy for patients with acute hypercapnic and hypoxemic

respiratory failure. In parallel with the evolving evidence supporting the use of NPPV

for acute respiratory failure, technical advances have increased the variety of interfaces

and ventilators for NPPV and facilitated wider application. Surveys have reported the

utilization of NPPV in several settings. Carlucci et al.(151) conducted a 3-week

observational survey in 42 French intensive care units (ICUs) to evaluate the use of

NPPV and to assess its efficacy in everyday practice. NPPV was used in 35% of the

patients who were not intubated on admission. This included 14% of patients with

hypoxemic respiratory failure, 27% with pulmonary edema, and half of those with

hypercapnic respiratory failure, but never in patients with coma.

In a follow-up survey, Demoule et al.(152) reported that NPPV use significantly

increased in French ICUs from 1997 to 2002 (up to 24% overall and 52% of patients

admitted without prior intubation), and the success rate remained unchanged (47% vs

48%, respectively).

Non-invasive ventilation in acute setting is used mainly for exacerbations of chronic

obstructive pulmonary disease (COPD) and for cardiogenic pulmonary oedema(18).

Use for hypoxic respiratory failure and facilitation of weaning is still infrequent and is

mainly done in specialised centres (153-156).

In patients with ARF due to restrictive disorders the evidence is lower, although

published studies demonstrate positive results (157). In fact, randomized clinical trials

(RCT) of NIV in ARF tend to exclude patients with restrictive disorders (153-155, 158-

161).



Despite these limitations, this technique is increasingly being used outside the

traditional and respiratory intensive care units(19), including in emergency

departments(29); postsurgical recovery rooms(104); cardiology(162), neurology(163),

oncology(164-165) wards; and palliative care units(166-167) Noninvasive ventilation

for acute respiratory failure has the potential of reducing hospital morbidity, facilitating

the weaning process from mechanical ventilation, shortening length of hospitalization

and thereby costs, and improving patient comfort(2). However, patients must be

selected carefully (Panel 1) because the risk of complications could be increased if

noninvasive ventilation is used inappropriately(156).

Panel 1: Recommendations for NIV to treat acute respiratory failure Recommendations based on levels of evidence

Level 1 Systematic reviews (with homogeneity) of RCTs

Evidence of use (favourable)

• COPD exacerbations • Facilitation of weaning/extubation in patients with COPD • Cardiogenic pulmonary oedema • Immunosuppressed patients Evidence of use (caution)

• None Level 2 Systematic reviews (with homogeneity) of cohort studies (including low quality RCTs; eg, <80% follow-up) Evidence of use (favourable)

• Do-not-intubate status • End-stage patients as palliative measure • Extubation failure (COPD or congestive heart failure) (prevention) • Community-acquired pneumonia in COPD • Postoperative respiratory failure (prevention and treatment) • Prevention of acute respiratory failure in asthma Evidence of use (caution)

• Severe community acquired pneumonia • Extubation failure (prevention)



Level 3 Systematic reviews (with homogeneity) of case–control studies, individual case-control study Evidence of use (favourable) • Neuromuscular disease/kyphoscoliosis • Upper airway obstruction (partial) • Thoracic trauma • Treatment of acute respiratory failure in asthma Evidence of use (caution)

• Severe acute respiratory syndrome Level 4 Case series (and poor quality cohort and case-control studies) Evidence of use (favourable) • Very old age, older than age 75 years • Cystic fibrosis • Obesity hypoventilation Evidence of use (caution) • Idiopathic pulmonary fibrosis

Chronic Obstructive Pulmonary Disease with acute exacerbation

Patients with acute respiratory acidosis caused by an exacerbation of COPD are the

group that benefits most from non-invasive ventilation(21). These benefits are because

NIPPV is able to decrease work of breathing (WOB) and eliminate diaphragmatic work

by unloading the respiratory muscles, lessening diaphragmatic pressure swings,

decreasing respiratory rate and counteracting the threshold loading effects of auto-

PEEP(168).

In an early study using historically matched control subjects, Brochard and colleagues

reported that only 1 of 13 patients with acute exacerbations of COPD treated with face

mask NPPV required endotracheal intubation, compared with 11 of 13 control subjects.

In addition, patients treated with NPPV were weaned from the ventilator faster and

spent less time in the intensive care unit than did the control subjects(169). Individual



trials and meta analyses have confirmed the benefit of NPPV for patients with COPD

exacerbation.

Lightowler et al.(170) conducted a meta-analysis of 8 studies restricted to the use of

NPPV for COPD exacerbation. NPPV significantly lowered the risk of treatment failure

risk of mortality, the risk of endotracheal intubation, complications of treatment, and

hospital stay. NPPV significantly improved pH, PaCO2 and respiratory rate within 1

hour of initiation. Keenan et al.(171) also conducted an updated systematic review and

meta-analysis of 15 randomized trials limited to COPD exacerbation. NPPV was

associated with significantly lower in-hospital mortality and a significantly lower rate of

endotracheal intubation.

Early use in patients with COPD who have with mild respiratory acidosis (as low as pH

7·30) and mild-to-moderate respiratory distress prevents further deterioration, and thus

avoids endotracheal intubation and improves survival compared with standard medical

therapy. In a large multicentre trial in patients with mild-to-moderate acidotic COPD

who were admitted to a respiratory ward, Plant and colleagues noted that intubation and

mortality rates were lower with non-invasive ventilation than with standard therapy

alone, but subgroup analysis showed that these rates did not differ when pH at

enrolment was less than 7.30(172). The investigators surmised that these patients with

low pHs might have fared better in an intensive care unit than in the respiratory ward.

Strong evidence of efficacy (from randomised controlled trials and meta-analyses) and

low risk of failure (10–20%) means that use of noninvasive ventilation to avoid

intubation in patients with mild-to-moderate COPD and acute respiratory failure (pH

7·30–7·34) is regarded as the ventilatory therapy of first choice and can be safely

administered in appropriately monitored and staffed areas outside intensive care(173).



Patients with a low pH are still candidates for this technique but transfer to a closely

monitored location is strongly advisable(174).

Acute Cardiogenic Pulmonary Edema

Non-invasive ventilation has been used to treat acute respiratory failure in patients with

cardiogenic pulmonary edema, mainly in emergency departments(175). Investigators of

several meta-analyses concluded that this technique, including CPAP, is better than is

standard medical therapy for reduction of intubation rate(176-177). This conclusion was

not supported in a multicentre trial that compared oxygen therapy alone, CPAP, and

non-invasive pressure support ventilation. The physiological improvements were faster

with non-invasive ventilation than with oxygen alone but without a statistically

significant effect on intubation or mortality rates(178). However, the very low

intubation rate (<3%) raises questions as to whether the patients’ population was similar

to that of other studies. Studies that compared non-invasive ventilation with CPAP alone

in patients with Cardiogenic pulmonary edema showed that intubation and mortality

rates did not differ, although investigators of some studies noted more rapid

improvements in dyspnea scores, oxygenation, and arterial partial pressure of carbon

dioxide (PaCO2) with non-invasive ventilation than with CPAP (179-181). Nonetheless,

because of ease of use, some clinicians regard CPAP as first-line treatment for

cardiogenic pulmonary oedema. In another meta-analysis, Winck et al.(177) also

concluded that robust evidence supports the use of CPAP and NPPV in acute

cardiogenic pulmonary edema, and that both techniques decrease the need for

endotracheal intubation but only CPAP decreases mortality, compared to standard

medical therapy.



Hypoxemic Respiratory Failure

Studies have investigated the use of NPPV in patients with acute hypoxemic respiratory

failure (defined as those with a PaO2/FIO2 ratio of < 200, respiratory rate> 35/min from

more generalized causes). Antonelli et al.(182) conducted a randomized controlled trial

of NPPV in patients with a variety of diagnoses associated with acute hypoxemic

respiratory failure. Patients received NPPV or immediate intubation and invasive

ventilation. Only 31% of the patients who received NPPV required endotracheal

intubation, and more patients in the conventional ventilation group had serious

complications (66% vs 38%) and had pneumonia or sinusitis (31% vs 3%,). Among the

survivors, patients in the NPPV group had shorter periods of ventilation and shorter

ICU stays.

Ferrer et al.(154) conducted a randomized controlled trial of NPPV with patients with

acute hypoxemic respiratory failure from a variety of diagnoses. NPPV was associated

with less need for intubation, lower incidence of septic shock, and lower ICU mortality.

The improvement in hypoxemia and tachypnea was more rapid in the NPPV group.

Moreover, NPPV was associated with better cumulative 90-day survival.

Keenan et al(183). conducted a meta-analysis of randomized controlled trials of patients

who had acute hypoxemic respiratory failure not due to cardiogenic pulmonary edema.

The trials compared NPPV plus standard therapy to standard therapy alone, and

outcomes included need for endotracheal intubation, ICU and hospital stay, and ICU

and hospital survival. They concluded that patients with acute hypoxemic respiratory

failure are less likely to require endotracheal intubation when NPPV is added to

standard therapy. However, the effect on mortality is less clear, and the heterogeneity

found among studies suggests that the effectiveness differs among different settings,

patient populations, and diagnostic groups.



Thus, although some studies suggest benefit of NPPV in hypoxemic respiratory failure,

its use in acute respiratory distress syndrome or severe community-acquired pneumonia

is controversial and not recommended routinely(156). Results of a survey in three

intensive care units(184), with staff highly skilled in this technique, showed that only

30% of patients with a diagnosis of acute respiratory distress syndrome met criteria for

a trial of this type of ventilation. Of these patients, intubation was avoided in 54%,

which was associated with much lowered morbidity (by about 40%) and mortality rates

(roughly 30%). This finding suggests that in real-life situations and in expert hands only

about 15% of such patients can be treated successfully with this technique; mainly those

with a low severity of illness, not in shock, and rapid improvement in oxygenation after

therapy is started.

Immunocompromised Patients

Acute respiratory failure in patients who are immunocompromised often signals a

terminal phase of the underlying disease, with short survival time and high costs of

admission to intensive care(105). Early use of non-invasive ventilation could be very

helpful, as shown by randomised studies in intensive care units that compared this

technique with standard treatment. In patients receiving a solid-organ transplant and

who had hypoxaemic acute respiratory failure, such ventilation reduced intubation rate,

complications, mortality, and duration of stay in intensive care(185).

In a second study this technique lowered intubation, complication, and mortality rates

compared with standard therapy in patients with hypoxaemia and bilateral pulmonary

infiltrates and immunosuppression secondary to hematological malignancies(24).

Hilbert et al. (186)conducted a randomized controlled study to compare NPPV with

standard medical treatment in 52 patients with immunosuppression from various causes



and acute hypoxemic respiratory failure. In the NPPV group, periods of NPPV of at

least 45 min delivered via face mask were alternated with 3-hour periods of spontaneous

breathing with supplemental oxygen. Fewer patients in the NPPV group than in the

standard treatment group required endotracheal intubation, had serious complications or

died in the ICU.

These results support use of NPPV in immunocompromised patients who develop acute

hypoxemic respiratory failure. One reason for the better survival in immunosuppressed

patients treated with NPPV is their lower likelihood of developing ventilator- associated

pneumonia(103, 187)

Weaning From Invasive Ventilation and Post Extubation Failure

NPPV may allow earlier extubation and thereby reduce the duration of mechanical

ventilation. Several randomized trials showed that non-invasive ventilation can be

safely and successfully used to enable weaning from mechanical ventilation in stable

patients recovering from an episode of hypercapnic acute respiratory failure (ie, COPD

exacerbations)(114, 161) and even in those who previously had an unsuccessful

spontaneous breathing trials(153, 188).

This application has been investigated in a meta-analysis. that compared traditional

weaning to early extubation with immediate application of NPPV, Burns et al found that

extubation to NPPV resulted in favorable outcomes, including lower mortality, lower

rate of ventilator-associated pneumonia, and shorter total mechanical ventilation. Burns

et al concluded that early extubation to NPPV decreased mortality, and that the use of

NPPV to facilitate early extubation is promising(20).

Another related potential application of NPPV in the weaning process is to avoid

reintubation in patients who fail extubation. Epstein and colleagues(189) have observed



that such patients have much higher morbidity and mortality rates than do those who are

extubated successfully.

Although controversial, accumulating evidence suggests that NIV may have a role in

treatment of extubation failure, but mainly in patients with hypercapnic and congestive

heart failure who are at high risk for extubation failure(155, 190). Furthermore, patients

should be monitored closely to avoid delays in intubation.

Acute Respiratory Failure in Restrictive Disorders

International surveys performed in ICU’s around the world in 1996 and 1998, showed

that neuromuscular patients correspond to 1.8-10% of patients receiving mechanical

ventilation (191-192). An Italian survey of Respiratory Intensive Care Units during

1997-1998 showed that chest wall and neuromuscular disorders accounted for 9% of

patients admitted (193).

Restrictive disorders are the most frequent indication for Long-term Home Mechanical

Ventilation, with thoracic cage and neuromuscular patients accounting for 65% of

patients ventilated at home in Europe (194).

NIV has been shown to be the first line intervention for ARF due to COPD (195). In

patients with ARF due to restrictive disorders the evidence is lower, although published

studies demonstrate positive results (157). In fact, randomized clinical trials (RCT) of

NIV in ARF tend to exclude patients with restrictive disorders. In the only RCT of NIV

in ARF that included patients with NMD (n=6) the authors did not discuss those

patients because the group was too small for analysis (196).

While Portier et al (197) in a prospective multicentre study of patients with acute-on-

chronic respiratory failure (including 16.7% with restrictive disorders) suggested that



the underlying disorder did not influence prognosis, Robino et al (198) in a

retrospective study with the larger sample of restrictive patients published to date

(mainly with CWD), suggested that effectiveness of NIV was less in this group of

patients.

Recently Banfi et al (199) successfully managed at home 7 Kyphoscoliotic patients with

infection-related respiratory failure. In fact by increasing daily duration of mechanical

ventilation to > 20h, they corrected respiratory acidosis and returned the patients to their

baseline condition in 4 weeks.

It seems that Respiratory Failure due to these disorders needs a different approach from

the more common obstructive pulmonary diseases (198, 200).

Acute Respiratory Failure in Chest Wall Disorders

Patients with severe Kyphoscoliosis (KS) and acute decompensation of respiratory

failure, exhibit marked decrease of pulmonary compliance but, contrary to COPD,

increase in airway resistance and intrinsic PEEP seem to play only a secondary role

(201). Because cough is not impaired like in NMD, secretion management is not so

critical in this context, and management of ARF may be easier.

Some case series have shown that ARF occurring in KS can be managed non-

invasively, either through negative (202) or positive pressure ventilation (157, 203).

Recently Banfi et al (199) have shown reversal of respiratory acidosis in KS patients

with ARF, by increasing duration of home mechanical ventilation up to > 20h, both

with volume and pressure-cycled ventilators.



Acute Respiratory Failure in Neuromuscular Disorders

In neuromuscular disorders, the normality of the respiratory function requires the

integrity of three main respiratory muscles: 1) inspiratory muscles, responsible for

ventilation; 2) expiratory muscles, involved in the ability to cough and 3) Bulbar

muscles, that protect against the risk of aspiration (204). Laryngeal weakness and

swallowing dysfunction can lead to aspiration which is the main reason for failure of

non-invasive respiratory aids during ARF in NMD (27).

In patients with previous NMD, respiratory failure is commonly triggered by upper

respiratory tract infections (205). These can impair the three muscle components (200,

205). Those patients normally present with rapid shallow breathing, tachycardia,

accessory-muscle use, thoraco-abdominal asynchrony, and orthopnea. Blood gases, vital

capacity, maximum inspiratory and expiratory pressures and peak cough flow should be

evaluated and give useful information about the integrity of the respiratory muscle

system. According with the disease and objective parameters need for mechanical

ventilation can be predicted. Hypercapnia is a late finding of impending ventilatory

failure whereas hypoxemia may suggest atelectasis and secretion encumbrance or

pneumonia.

To avoid NMD to be admitted to hospital with ARF, a regular follow-up of all chronic

NMD patients with lung function evaluation in order to establish domiciliary non-

invasive respiratory aids is fundamental (206). Moreover a pro-active intervention with

intensification of home mechanical assisted cough and NIV guided by oxygen

saturation has been proposed by some authors (207). In fact this protocol reduces

hospitalization in NMD followed in specific outpatient clinics.

However there will always be cases where ARF will be the presentation for NMD,

especially those with a rapid evolution like ALS (208-209); apart from those patients,



acute neuromuscular disorders (like Guillain-Barré Syndrome) together with the ICU-

acquired neuromuscular disorders are the most frequent NMD associated with ARF (see

Table I).

Table I- Major NMD Diseases associated with ARF

Motor Nerves Neuromuscular

Junction

Myopathies Spinal Cord Acquired NMD

Amyotrophic

Lateral Sclerosis

Myasthenia

Gravis

Myotonic

dystrophy

Trauma Criticall ill

myoneuropathy

Guillain-Barré

syndrome

Duchennne

Muscular

Dystrophy

Transverse

myelitis

Acute Respiratory Failure in Amyotrophic Lateral Sclerosis

Analysing a large US database, Lechtzin N et al (210), report that in hospitalized ALS

patients mortality is 15%. According with conventional protocols, patients with ALS

who present acutely in respiratory failure and require endotracheal intubation and

invasive ventilation are rarely weaned and rarely return home (211).

If the cause of ARF is secretions encumbrance, and assisted mucus clearance techniques

were unavailable at home, a strict protocol of mechanical in-exsufflation (MI-E) should

be implemented (sometimes with a 5 min frequency) together with continuous NIV

until blood gases are normalized (212). It should be noted that patients with NMD and

excessive secretions/atelectasis may need very frequent assisted cough techniques



requiring time-consuming care from the nursing and respiratory therapists staffs,

making the help of family caregivers essential (213). This will reverse the majority of

cases (214); however some patients can be intubated for 24/48 hours to rest and

optimize secretion clearance with MI-E through the endotracheal tube (212).

Subsequently it might be possible to extubate them directly continuous NIV.

There are not so many studies analysing the role of NIV in ARF due to ALS. In 2000

Vianello et al (215) published the first paper, prospectively comparing the efficacy of

NIV combined with cricothyroid «mini-tracheostomy» and conventional mechanical

ventilation via endotracheal tube in 14 patients with ARF and NMD (including 3 ALS).

Mean pH was 7.29 in both groups, mortality was lower and ICU stay was shorter in the

NIV group compared with controls suggesting their «non-invasive ventilatory

approach» could be a first line intervention in this setting.

Five years later Vianello et al. (216) evaluated the short-term outcomes of 11 NMD

patients (including 2 ALS), not so severely acidotic (mean pH 7.36), with acute upper

respiratory tract infections and tracheobronchial mucous encumbrance. Apart from NIV,

they were submitted to MI-E treatment in addition to standard physical therapy. The

outcomes were compared with 16 historical matched controls who had received chest

physical therapy alone. The treatment failure (defined as the need for cricothiroid

“minitracheostomy” or endotracheal intubation, despite treatment) was significantly

lower in the MI-E group that in the conventional chest physical treatments group (2/11

vs 10/16 cases). No side effects were related to the use of MI-E alone, while the need of

bronchoscopy assisted suctioning was similar in the two groups (5/11 vs 6/16).

As noted by Gonçalves and Bach in the commentary accompanying the paper (213),

some mistakes concerning the use of the MI-E probably compromised the final results.

Setting the machine at a very low insufflation and exsufflation pressures (less than 30



cmH20), and forgetting the abdominal thrust during the exsufflation phase were reasons

for sub-optimal results. These low pressures have been shown not to be effective in lung

models (217) as well as in clinical studies (218-219) and accordingly did not effectively

avert bronchoscopy-assisted aspiration. Moreover, using the MI-E 2.7 times a day as

described in this paper may be insufficient. In fact as mentioned before, during an acute

episode of respiratory tract infection, MI-E may have to be applied very frequently and

the only way to solve this problem is allowing the primary care providers or relatives to

stay at the bedside to use it anytime is required (220).

Servera et al (27) in a non-intensive care setting prospectively evaluated the efficacy of

continuous NIV together with coughing aids (including MI-E) to avoid endotracheal

intubation for 17 patients with NMD during ARF. The studied group had a mean pH of

7.38 and included 11 patients with ALS (5 of which with Bulbar dysfunction). There

was treatment failure in 20.8% and mortality in 8.3% cases, significantly related with

patients with severe bulbar impairment. Those patients (in which NIV and assisted

coughing may be unsuccessful) and those who cannot cooperate, may have a more

invasive approach: endotracheal intubation and mechanical ventilation followed by

tracheostomy (221) or as Vianello (222) proposes minitracheostomy.

However, even in Bulbar ALS patients, MI-E should be tried, since Hanayama et al

(223) described an ALS woman with immeasurable CPF, already with a gastrostomy, in

which MI-E was able to clear bronchial secretions and reverse ARF.

In our experience with 11 consecutive non bulbar ALS with ARF, non invasive

respiratory aids (continuous NIV and high-intensity mechanical assisted cough) had a

success rate of 100%, with resolution of respiratory failure and discharge after 8 days

(214) (Figure12). With this protocol, MI-E resolved atelectasis and none of those



patients needed endotracheal intubation or fiberoptic bronchoscopy-assisted aspiration

(Figure 13).

Figure 12-Outcomes of 11 patients with non-bulbar ALS and ARF

LOS 7.9 ± 8.9 days

pH 7.37 ± 1.3

PaO2 57.8 ± 8.4 mmHg

PaCO2 64.7 ± 26.1 mmHg

Tt Failure 0

Legend: LOS-Length of stay; Tt Failure-Treatment Failure; CPF-Peak Cough Flow (L/min)

Figure 13-Resolution of Left lower lobe atelectasis in one patient ALS with MI-E (Left before;

right After MI-E)

33

57,8 64,7

242

76,7

40,6

0

50

100

150

200

250

Baseline Discharge

PCF

PaO2

PaCO2



Concerning the mode of non-invasive ventilation, it is preferable to use volume-cycled

ventilators in assist control with high tidal volumes, for sufficient lung expansion and to

allow air-stacking for coughing (27, 214). This can be done during the day through

mouthpiece and at night with a nasal or oral interface. As soon as the patient learns to

air-stack and can autonomously produce CPF above 160L/min, assisted coughing can

be reduced in frequency, provided that oxygen saturation levels on the ventilator are

above 95% (224). In the beginning the patient will need continuous NIV but at

discharge will return to the previous duration of home NIV (27, 214).

When patients with ALS under home mechanical ventilation need to be hospitalized due

to ARF there are some technical as well some ethical aspects that need to be considered.

We need to confirm if all non-invasive respiratory aids were optimized at home, if the

patient has refused tracheostomy, if bulbar impairment is severe and the risk of

aspiration is high. Lung function status previous to the decompensation can help in the

decision making. Discussions about aggressiveness of resuscitation should have been

carried out with the family and patient in a stable state (225).

Another different issue is when patients with non-bulbar NMD are intubated because of

failure of NIV or due to a more conventional approach. In this context, it is a common

attitude to gradually reduce the support of the ventilator until the patient is weaned.

Unfortunately NMD patients with a pre-existing respiratory dysfunction often fail to

wean from invasive ventilation and almost invariably are tracheostomized. MI-E in

these cases can be really successful to help clearing secretions first via the tube, and

then, after the tube is removed, via an oronasal mask while the ventilation in delivered

through non-invasive interfaces. MI-E, applied in this circumstance, avoid mucus

encumbrance, the need of blind suctioning through the nose and definitely

tracheostomy, also for patients 24 hours ventilator dependent.



Acute Respiratory Failure in Guillain-Barré Syndrome and in Myasthenia Gravis

In the developed world Guillain-Barré Syndrome (GBS) and Myasthenia Gravis (MG)

account for the majority of cases of respiratory failure associated with NMD.

Although the use of NIV in this setting has not been extensively evaluated (226-228), it

should be always tried unless there is significant bulbar dysfunction. In fact, GBS and

MG are not so different diseases from other NMD where a non-invasive respiratory aids

protocol has avoided endotracheal intubation (27, 214, 216). The only difference is that

contrary to the majority of ALS and DMD patients with ARF, those patients are naïve

to NIV.

According with the literature, between 25-50% of GBS patients and 15-27% MG gravis

patients require mechanical ventilation (229-230). A practical rule (the «20/30/40 rule»)

proposed by Lawn et al (231) in which a VC<20ml/kg, Pimax<-30cmH20,

Pemax<40cmH20 were associated with progression to respiratory failure, may be useful

in deciding to initiate ventilatory support. These simple bed-side tests of respiratory

function may be clinically generalizable to other neuromuscular conditions.

Acute Respiratory Failure in Spinal Cord Injury

Demographic data form the US Spinal Cord Injury (SCI) data base between 1973 and

2003 show a significant increase in the percentage of cervical injuries and of ventilator-

dependent cases, with 6.8% of SCI patients requiring ventilation on discharge between

2000 and 2003 (232). Most SCI patients who require ventilatory support undergo

tracheostomy during their acute hospitalization (233). Despite improvements in SCI

medical management, re-hospitalization rates remain high, associated with respiratory

complications (234). Cervical spine injuries can be separated into higher cervical cord



injuries (levels C1 and C2) and mid and lower cervical cord injuries (C3 to C8). The

former produce almost total respiratory muscle paralysis, while the latter have limited

expiratory function. Lesions from C3-C5 cause also significant compromise of

inspiration (233).

During the 80’s, survival for ventilatory dependent tetraplegic patients ranged from

63% at 3 years (235) to 33% at 5 years (236). In those times, only 51% of SCI patients

with C3 injury levels were able to be weaned (236). Life expectancy was considerably

improved in those successfully weaned (237).

Because of their youth, intact mental status and bulbar musculature, high level

tetraplegic patients are perfect candidates for non invasive ventilatory assistance (238).

In fact, Bach et al suggest that patients with lesions under C1 level, can be managed by

using noninvasive respiratory aids (up to continuous noninvasive IPPV and manually

and mechanically assisted coughing) provided that they are able to generate assisted

peak cough flow >160 L/min (239).

It is recommended that all patients with acute SCI have their Vital Capacity measured

every 6h during the first few days of admission. If symptoms or signs of impending

ventilatory failure develop or VC decreases < 1500ml, the patient should be placed on

continuous oximetry monitoring and trained in using MIV and Manually and

mechanically assisted coughing (240).

When patients with SCI are tracheostomized, there will always be the potential for

decannulation. Although this topic his beyond the scope of this chapter, it must be

emphasized that even in patients with little ventilator-free breathing ability, switch to

NIV and «aggressive» mechanical insufflation-exsufflation can lead to successful

decannulation (241).



Critical-illness myoneuropathy

ICU-acquired NMD is reported in 25% of patients who have been ventilated for ≥ 7

days (242). This figure increases in patients with sepsis and severe acute asthma (243).

Normally patients present with diffuse skeletal-muscle weakness and difficult weaning.

ICU-acquired NMD is associated with longer duration of mechanical ventilation, longer

ICU stay and increased mortality (243). Cough inefficacy and reduction in maximal

respiratory pressures have been reported in these patients (244), suggesting the

implementation of secretion clearance techniques together with non invasive ventilatory

support can have a role (200). Although studies reporting application of Non-invasive

Respiratory aids in this context are lacking, in the authors’ experience, application of

this protocol in ICU-acquired NMD has allowed decannulation and weaning in a

significant number of patients (data not published).

Critical-illness myoneuropathy have been also implicated in respiratory failure that

develops after discharge from the ICU (244). Recovery of peripheral and respiratory

muscle function is highly variable, with some patients having persisting weakness at 2

years of follow-up.

Contraindications to Noninvasive Positive Pressure Ventilation in

acute care

There are few absolute contraindications to NPPV, the majority of which assume that

endotracheal intubation (ETI) is an immediate option(174). The need for a secure

airway contraindicates use of NPPV, as do severe facial trauma or burns and an ongoing

need to clear airway secretions that cannot be cleared by noninvasive means (including

mechanical assisted cough)(245-246). Altered mental status not due to CO2 retention is

a commonly cited contraindication, as are nausea and vomiting,Most studies have



excluded patients with significant hypotension and/or recent gastric surgery (within one

week). An uncooperative or combative patient is unlikely to benefit from NPPV(36).

Light sedation or analgesia may aid in the control of the latter type of patient. The

exclusion of patients with acute apnea, active cardiac ischemia, or ongoing arrhythmia

seems reasonable.

Panel II: Contraindications for NPPV in ARF:

The contraindications to NIPPV include (18, 21):

• severe hypoxemia (PaO2/FiO2 < 75mmHg)

• severe acidemia

• multi-organ failure or slowly reversible disease

• upper airway obstruction

• anatomic abnormalities that interfere with gas delivery (i.e., facial burns,

trauma)

• respiratory arrest/apnea

• cardiac arrest and hemodynamic or cardiac instability

• unconscious / uncooperative patient

• encephalopathy with the inability to protect the airway

• increased risk of aspiration (copious secretions, vomiting)

• severe Gastro-intestinal(GI) bleeding

• recent airway or GI surgery



NON INVASIVE VENTILATION IN THE CHRONIC

CARE SETTING

Rationale

Noninvasive ventilation (NIV) constitutes one of the major advances in pulmonary

medicine in recent times, having assumed an important role in the therapy of respiratory

failure in chronic settings(46). Long term NIV in the chronic setting refers to the

provision of NIV mainly at night during sleep, usually for 12 to 24 h, although some

NMD patients gradually extend hours of use to continuous as their disease

progresses(1).

From the 1950s through to the early 1990s, home mechanical ventilation (HMV) was

limited to a relatively small number of individuals using negative pressure devices or

receiving positive pressure ventilation through a tracheostomy(247). More recently,

noninvasive ventilation (NIV) has emerged as an effective and acceptable approach to

managing chronic respiratory failure (CRF) patients outside of the hospital setting(48).

The significant benefits of this therapy have been widely documented, and include relief

of symptoms, improved quality of life, reduced need for unplanned hospitalisation and

improved survival. Consequently, over the past 20 years a dramatic increase in the

number of individuals using HMV has occurred(248).

Before starting respiratory support, it is essential to ask three main questions: 1) Does

the patient have a disease known to cause ventilatory failure? 2) Does the patient have

symptoms suggesting hypoventilation? 3) Does the patient have physiological

abnormalities confirming hypoventilation? Sometimes, due to disease progression,



ventilatory dependency can increase and ventilatory support must be adapted

accordingly(249).

Indications of Noninvasive ventilatory support

Disease categories (table 1)

A large number of conditions can result in chronic ventilatory failure and benefit from

home ventilation. Typically, patients with restrictive disorders have decreased

compliance of the chest wall, resulting from thoracic cage deformity or respiratory

muscles involvement (250). In patients with severe Obstructive Pulmonary Disorders,

respiratory muscle fatigue and sleep hypoventilation are thought to contribute to

respiratory failure (251-252).

It is useful to define disease category in order to predict natural history and specific

intervention. It is well known that patients with primarily restrictive disorders can have

both inspiratory and expiratory muscle weakness and so apart from non-invasive

ventilatory support they also need cough assistance (207, 219). On the other hand,

patients with obstructive disorders rarely need mechanical expiratory aids except for

severe acute infectious exacerbations when difficulties in clearing copious secretions

can ensure (219, 253-254).

Some neuromuscular diseases, for example Guillain-Barre syndrome, may only require

temporary ventilatory support(255) while other, such as post-polio syndrome requires

lifelong noninvasive ventilatory support (45). Amyotrophic lateral sclerosis, an example

of a rapidly evolving disease, needs a specific approach particularly for the bulbar

involvement which may render noninvasive ventilatory support less effective (221).



Table II- Indications for Non-invasive ventilatory support

Restrictive disorders

Chest wall disorders

Kyphoscoliosis

Thoracoplasty

Fibrothorax

Obesity-hypoventilation syndrome

Stable Neuromuscular Disorders

Old polyomyelitis

Myopathies

Progressive Neuromuscular Disorders

Amyotrophic Lateral Sclerosis

Duchenne Muscular Dystrophy

Other Neurological Disorders

Cervical Spinal Cord Injury

Phrenic nerve lesions

Obstructive disorders

Chronic Obstructive Pulmonary Disease

Bronchiectasis and Cystic Fibrosis

Patient selection

Symptoms of nocturnal hypoventilation

Every consensus statement reinforces the importance of detecting symptoms of

nocturnal hypoventilation(252, 256-259). However, symptoms may be subtle due to the

variability of patient sensitivity and sometimes it is difficult for the patient to establish



differences between fatigue, dyspnea, and sleepiness. So, carefully designed

questionnaires that assess symptoms systematically may be very useful. Jackson et al

(260) have described a pulmonary symptom scale consisting of 14 questions, answered

on a scale from 1-7. Others evaluated by simple questionnaires the positive and negative

effects of ventilation(261). Although symptom questionnaire are insensitive in

identifying patients with SDB and nocturnal hypercapnic hypoventilation (260, 262)

their systematic evaluation is useful in evaluating response to NIV, as compliance to it

is strongly correlated with patients symptoms (263).

Using rating scales for different symptoms has been also recommended. Dougan et al

(264) developed a useful tool (the MND dyspnoea rating scale) consisting of 16

questions each rated on a five-point likert scale that allows the patients with ALS to

quantify how dyspnea affects their daily life. This specific questionnaire may be more

appropriate to quantify dyspnea in neuromuscular patients compared with other existing

measures such as the Medical Research Council (MRC) dyspnea scale (265).

Moreover, one of the most common used sleepiness scales, the Epworth Sleepiness

scale, may not be as reliable in NMD like Myotonic Dystrophy (266).

Physiologic evaluations

Together with the careful evaluation of symptoms, monitoring of respiratory function

should be evaluated routinely. Vital Capacity (VC) is one of the most reproducible tests

of lung function. Although it may not fall below normal limits until there is a 50%

reduction in muscle strength (267), its rate of decline has been shown to predict survival

(268). Although no consensus exist as to how often pulmonary function should be



evaluated, some authors propose that if VC is > 60% predicted it should be performed

every 6 months while if under 60% every 3-4 months (269)

Measurement of the VC in the supine position gives and index of weakness of the

diaphragm. A fall of more than 15% indicates diaphragmatic dysfunction and correlates

with complaints of orthopnea (270) and a supine FVC under 75% was highly sensitive

and specific of low transdiaphragmatic pressure (271).

Muscle strength

Like VC, testing for respiratory muscle strength should be obtained periodically.

Maximal inspiratory mouth pressure (MIP) values > 80cmH20 exclude clinically

relevant respiratory muscle weakness(267). A low MIP with a normal MEP suggests

isolated diaphragmatic weakness. Sniff nasal inspiratory pressure (SNIP) is a more

natural and easier to perform manoeuvre than MIP (272). Values greater than -

70cmH20 (for males) and -60cmH2O (for females) exclude significant inspiratory

muscle weakness(273). Moreover a SNIP < 40cmH20 was associated with nocturnal

hypoxemia and predicted median survival at 6 months(273). Chaudri et al (274) also

recommend that patients with SNIP<30 % of predicted are at risk of developing

hypercapnia and should have their ABG measured. Some authors advise that in patients

with moderate to severe restrictive defect MIP is higher than SNIP so suggesting that

the latter may overestimate the level of inspiratory weakness in this context(275).

Transdiaphragmatic pressures and nonvolitional tests of respiratory muscle strength are

more accurate and may be indicated when others tests are difficult to interpret or in the

context of clinical trials (268).



Blood Gases

Once the VC drops below 50% of predicted or MIP (or SNIP) below 30% predicted,

daytime arterial blood gases (ABG) should be checked (276). However, performance of

ABG analysis at every clinic attendance is uncomfortable for patients. Accurate devices

for measuring PaO2/PaCO2 non-invasively are becoming available and will become

standard practice in the future.

Daytime oxygen saturation (SpO2) measurement by pulse oximetry can be routinely

used as screening tool. If SpO2 is under 95% it can either be caused by inspiratory,

expiratory of bulbar dysfunction (221). In ALS, when SpO2 can not be normalized by

NIV and mechanical assisted cough tracheostomy needs to be considered due to severe

bulbar dysfunction (221).

Capnography as been recommended as ideal for measuring carbon dioxide

tensions(277). It measures end-tidal CO2 and can be performed during daytime

evaluations and continuously during sleep (278-279). According to recent data,

measuring ETCO2 by a VC maneuver provides a more accurate estimate of PaCO2 and

can be very useful for check-point determinations in hospital or at home (278).

Transcutaneous CO2 (TcCO2) has been widely used for long-term measurement during

sleep and after NIV (280-282). TcCO2 measurements require more time and its levels

are normally 3-12 mmHg higher and more accurate than ETCO2 (283-284). However

some authors advise that the accuracy of TcCO2 seems to be restricted to patients with

PaCO2 values <56mmHg (285).



Noninvasive methods of CO2 monitoring normally tend to give a slightly higher PaCO2

level, so a normal reading can exclude hypercapnia (267).

More recently combined TcCO2-SpO2 single sensors have been investigated, and seem

valid in various settings (286-288).

Noninvasive ventilation support in stable COPD

Long term NIV in COPD remains an area of controversy. The central conundrum is that

while there are have been no randomised trials which demonstrate a major impact on

survival or quality of life, the use of home NIV in COPD is a major growth area. A

European survey (194) has shown that in some countries far more obstructive lung

disease patients then restrictive patients are long term NIV recipients, even adjusted for

prevalence.

It is interesting to observe that early studies showed very mixed results. Case series (8,

289) from the early 1990s indicated that a possible target group for home NIV might be

those COPD patients that developed hypercapnia on long term oxygen therapy (LTOT).

Several uncontrolled (290) or retrospective studies (291) suggested significant

improvement in arterial blood gas tensions, and a possible reduction in hospital

admissions and General Practitioner consultation rates (292). In a cross over study of

LTOT v. NIV plus LTOT Meecham Jones and colleagues (293) demonstrated

improvements in nocturnal and arterial blood gas tensions on NIV and enhanced sleep

quality and improvement in quality of life. These results are offset by another

crossover study (294) that showed worse sleep quality using NIV v.LTOT, and two



small randomised trials (295-296) which showed no significant improvement in

physiological measures. In the RCT by Gay et al (296) bilevel pressure support was

compared to sham NIV. Poor tolerance of NIV was noted in both RCTs. A number of

messages emerge from this early work – firstly a suggestion that more hypercapnic

subgroups of patients may be more likely to benefit, and secondly in some studies

relatively low level of inspiratory positive pressure support were applied which may not

have been effective.

Finally is seems that acclimatisation to NIV may be slower in some COPD patients than

in those with restrictive disorders, therefore trials lasting only a few weeks may be

insufficient to gauge the impact of the intervention, even on physiological endpoints.

Clearly, longer trials are also required to investigate effects on the key outcomes of

frequency of exacerbations, quality of life and survival. More recently there have been

two longer term randomised controlled trials. Casanova et al in a one year study (297)

randomised 52 COPD patients to standard care or standard care plus NIV. Outcomes

included rate of acute exacerbations, hospital admissions, need for intubation and

mortality at 3, 6 and 12 months. For the NIV group, ventilation was initiated as an

inpatient using a bilevel positive pressure system in spontaneous mode. The authors

targeted an expiratory positive airway pressure (EPAP) level of 4 cmH2O and an

inspiratory positive airway pressure (IPAP) level of at least 12 cmH2O. Pressures were

adjusted to decrease perception of dyspnoea and accessory muscle use, and oxygen

delivered to the mask to achieve a SaO2 > 90%. Five of the NIV group (total n=26) did

not tolerate NIV. Average ventilation in the remainder was 6.2 hours per 24 hours and

marginally decreased to 5.9 hours/24 hours at 9 months. Eleven percent used NIV for

less than 3 hrs/day.



One year survival was similar in both groups. The number of acute exacerbations did

not differ between standard and NIV groups at all time points. However, the frequency

of admissions was decreased at 3 months in the NIV group (5% versus 15%, p<0.05),

although this difference was not sustained at 6 months. Borg breathlessness scores

decreased in the NIV group, but only one psychomotor test improved. The authors

carried out a subgroup analysis to see if any clinical or functional variables were

predictive of benefit, but in this study there was no evidence that more hypercapnic

patients (PaCO2 >7.3 kPa versus PaCO2< 7.3Kpa), or those that used NIV for >5 hours

per 24 hours did better than standard group.

In an Italian multicentre trial (298) which has furthered the debate, 122 stable

hypercapnic COPD patients on LTOT for > 6 months were randomised to continue

LTOT alone, or LTOT plus NIV using a bilevel positive pressure device over a 2 year

period. The study was powered to assess reduction in daytime PaCO2 rather than

mortality. Drop out rates were similar in both groups, and compliance with NIV was

impressive at 9 hours/24 hours.

The authors showed no significant difference in hospital or ICU admissions, although

there was a trend to fewer admissions in the NIV group (compared to the previous year

admissions decreased by 45% in NIV group and increased by 27% in LTOT group).

Mortality did not differ. PaCO2 was slightly reduced in NIV patients using LTOT and

there was also a reduction in dyspnoea and increase in heath related quality of life

scores in NIV group. Potential criticisms of the study are that the IPAP levels used

were low, it is difficult to know whether nocturnal hypoventilation was corrected by

nighttime NIV, and it is possible that some quality of life and symptomatic

improvements might be related to a placebo effect. A reasonable riposte to this last

point is that although short term trials using sham CPAP and sham NIV have been



perfomed, it would be difficult practically and ethically to carry out a randomised trial

of NV over several years with a sham NIV limb.

It is evident therefore that widespread use of longterm NIV across the board in COPD

patient cannot be justified on the evidence presented above. The studies do however

suggest that primary end points of number of acute exacerbations and hospital

admissions may be a more sensitive measure than mortality. The frequency of acute

exacerbations of course has economic implications. On that point Tuggey et al (299)

examined the economic impact of home NIV in a selected group of COPD with

recurrent exacerbations who had responded well to NIV during these acute episodes. In

this group, preselected because of good tolerance, provision of home NIV resulted in a

mean cost saving of 11720 euros (5698-17,743 euros) per patient year. The number of

hospital admissions in the year on NIV compared to the year pre NIV was reduced from

5 to 3, mean hospital days decreased from a mean (SD) of 78 (51) to 25 (25) p=0.004,

and ICU days fell from 25 to 4 (p=0.24). Outpatient visits also decreased.

Noninvasive ventilation support in restrictive disorders

Chest wall disorders

Patients with untreated scoliosis have an increased risk of developing respiratory failure

(300) . The larger the scoliotic angle, the lower the vital capacity and the younger the

age of scoliosis onset, the greater is the risk (301). Patients who have reached skeletal

maturity and have a vital capacity below 45% of predicted value the risk of developing

respiratory failure increases with age (301). Symptoms of cardio-respiratory failure



generally appear between the fourth and sixth decade of life, however some patients

survive into the seventh decade without experiencing cardio-respiratory problems (302).

It is well known that severe kyphoscoliosis may induce sleep-related respiratory

abnormalities (303) and retrospective long-term studies of nocturnal NIV have shown a

better prognosis of those patients compared with neuromuscular and obstructive

disorders (8, 289). In fact, in prospective studies, NIV improves hypoventilation-based

symptoms, muscle function and nocturnal oxygenation in patients with daytime

hypercapnia and FVC< 50% (304-305). In patients with less severe respiratory

impairment, nocturnal NIV improves significantly exercise capacity and there is a trend

for an increase in daytime PaO2 (306). Data from a large French observatory (307) and

a recent prospective study (308) clearly show that kyphoscoliotic patients treated by

home mechanical ventilation experience a better survival than those treated by oxygen

therapy alone. Moreover, Masa et al have shown that NIV but not oxygen improved

nocturnal hypoventilation in 7 patients with Kyphoscoliosis and normal daytime ABG

(309). So, in symptomatic patients with daytime normocapnia but significant nocturnal

desaturation (according with Masa (309) > 10% of Total sleep time with <90% SpO2 or

mean REM SpO2 <90% and minimum SpO2<90% and according with the consensus

conference (252) SpO2≤ 88% for 5 consecutive minutes) NIV is warranted (252).

Amyotrophic Lateral Sclerosis

Although initially regarded as controversial because of fear that it would simply delay

death without improving quality of life, NIV has become the standard of care for

patients with symptoms and evidence of respiratory involvement (310). In fact, NIV

improves symptoms, quality of life (260, 311) and survival (312).



Because ALS patients eventually become quadriplegic, they require a high level of

assistance from caregivers (313). In one study, one of the best predictors of success of

NIV was a good caregiver support (314).

Although there is no clear evidence regarding timing for NIV, it seems reasonable to

start in symptomatic patients (table II) with signs of respiratory muscle weakness

(FVC<80% or SNIP<40cmH20) and evidence of significant nocturnal desaturation or

PaCO2> 49mmHg (310). Bourke et al suggest that ortopnea was the most useful

criterion for benefit and compliance with NIV (311) , and Sivak (315) that there was a

lack of correlation between VC at the institution of NIV and the duration of its

successful use.

In a small prospective study Jackson et al (260) suggest that early intervention, based on

nocturnal oximetry criteria (SpO2<90% form 1 cumulative minute), may result in

improved quality of life with NIV.

For most patients, NIV begins at night but may rapidly develop 24h ventilator

dependence (316). If bulbar function is well preserved, continuous NIV (daytime

mouth-piece and nocturnal oro-nasal NIV) may manage up to 20% of ALS patients

safely for long years (221, 239, 316), avoiding tracheostomy.

Unlike patients with Duchenne Muscle Dystrophy, Post-Poliomyelitis Syndrome, and

most other NMD, ALS may have bulbar muscle dysfunction, carrying a high risk of

aspirating saliva and not being able to clear airways secretions (316).

Bulbar muscles involvement carries a worse prognosis (317) and in those patients, NIV

may be less tolerated (318-319). However the recent RCT found that patients with

moderate to severe bulbar impairment gained a smaller, although clinically significant

quality of life benefit from NIV (312).



Bulbar muscle dysfunction should be evaluated in patients with ALS. Apart from rating

scales like the ALSFRS (320) one of the best ways to measure it objectively is by

comparing the MIC with the VC and the PEF with the CPF. The wider the gradient, the

better the bulbar function (321-322). Bach has shown that in ALS, that the ability to

generate assisted CPF>180L/min and to have an high MIC VC difference is associated

with the capacity to use continuous NIV (224). However, when strictly tailored NIV

and Mechanical Assisted Cough does not prevent oxygen desaturation below 95%,

saliva aspiration is likely and tracheostomy should be offered (221).

Care should also be put into secretion management since Mechanical Assisted Cough to

prevent airway encumbrance is an essential complement to NIV and a key to successful

full-time NIV (316)

Duchenne muscular dystrophy

Duchenne Muscular dystrophy (DMD) has an X-linked recessive pattern of inheritance

and affects up to 1 in 3300 live male births. (323) Affected patients typically become

wheel chair dependent by the age 10-12 years at which VC plateaus. With the

development of respiratory muscle weakness and skeletal deformity, VC starts to fall

(324). The patients usually remain asymptomatic until VC decreases below 450ml and

begin daytime hypercapnia (212). Hukins et al suggest that once FEV1 falls below 40%

predicted, arterial blood gases should be performed (325) and Hahn et al report that

hypercapnia appears in patients with MIP lower than 30cmH2O or 30% of predicted

normal (326).

The first signs of respiratory involvement occur during sleep. Obstructive sleep apnea is

very frequent in DMD, with some authors reporting a prevalence of 57% (327), and



occurring more commonly in younger children (328). Hypoventilation was the major

abnormality in older children (early second decade) (328).

By the time patients become hypercapnic, nocturnal NIV is clearly indicated. Vianello

et al (329) have shown that life expectancy is <1 year once diurnal hypercapnia

develops and compared with a non-ventilated control group, NIV significantly

prolonged survival in DMD patients with symptomatic daytime hypercapnia. In fact the

majority of published studies using NIV in DMD included patients with symptoms and

diurnal hypercapnia (17, 324, 330). In a UK study that followed a cohort of 23 severely

hypercapnic patients with DMD, the use of NIV has increased median survival, with a 5

year survival of 73% (17).

In a randomised controlled trial, including normocapnic, essentially asymptomatic

patients with VC between 20-50%, Raphael et al did not show any improvement in

survival (331). However this study should not be viewed as definitive as their findings

may have been caused by a lack of standardized ventilator and mask use between

investigators (332). In addition it may be argued that for NIV to be effective longterm,

the implementation of assisted cough techniques are critical a intervention that was not

considered in this trial, in which the main causes of death in the NIV group were due to

infection with retention of tracheobronchial secretions.

Although some authors suggest that once the VC is <1L the 5 year survival rate is 8%

(333) with inspiratory and expiratory non-invasive respiratory aids, 10 year survival can

be up to 93.3% (212). In fact, compared with a conventional approach before 1993, with

a proactive protocol that included NIV (up to full time) together with Mechanical In-

Exsufflation guided by home oximetry, the New Jersey University Hospital has



managed to significantly extend survival and avoid respiratory mortality in patients with

DMD(63).

More recently several groups in Europe have shown that once nocturnal hypercapnia

(measured by transcutaneous CO2) is present treatment with NIV should be

implemented (334-336). Others, in the absence of nocturnal CO2 measurements,

suggest that symptomatic patients with mean nocturnal SpO2 below 94% should be

encouraged to use NIV, especially if they had symptomatic relieve or correction of

nocturnal desaturation (207).

According with the ATS consensus statement daytime ventilation should be considered

when measured waking PaCO2 exceeds 50mmHg or when haemoglobin saturation

remains <92% while awake (277). The most commonly used noinvasive technique is

mouth-piece intermittent positive pressure ventilation (M-IPPV), which was first

reported in 1969 (337). Since then the New Jersey University Hospital has extensively

reported their experience with M-IPPV for continuous NIV as an alternative to

tracheostomy (338-340). Others centers from the US have also described their

successful experience (330, 341-344). In Europe, although an expert group report

recommended its use in 1993 (345), it was not until very recently that diurnal

ventilation via mouthpiece was described in end-stage DMD patients (335). In this

prospective study, Toussaint et al have shown that a simple angled mouthpiece held

stable near the mouth could confortably deliver volume cycled ventilation during the

daytime, stabilising VC, decreasing symptoms, daytime hypercapnia and extending

survival up to 7 years in 51% of 42 M-IPPV users(335).

Death from cardiomyopathy is significant in patients with DMD, so regular cardiac

assessment and adequate medication should be implemented (346)



A recent study has shown that although patients with DMD are severely disabled they

still perceive a high quality of life, not correlated with physical impairment nor the need

of NIV (347).

MANUAL AND MECHANICAL TECHNIQUES FOR

SECRETION MANAGEMENT

Rational

In healthy individuals, mucociliary clearance and cough mechanisms are normally

effective and efficient for defence on secretion encumbrance, but may become

ineffective if these systems malfunction and in the presence of excessive bronchial

secretions. Mucus secretion and clearance are extremely important for airway integrity

and pulmonary defence. It has been estimated that mucus secretion volume is between

10 and 100ml per day in healthy subjects (348).

Mucus is transported from the lower respiratory tract into the pharynx by airflow and

mucociliary clearance. Overload of normal secretion or mucociliary clearance impairs

pulmonary function and increases risk of infection. When there is extensive ciliary

damage and secretion encumbrance, coughing becomes critically important for airway

hygiene (349). Airflow dependent clearance can also be increased by moving secretions

from the periphery of the lung to the more proximal airways, were greater secretion

depth and higher expiratory air flow can improve expectoration. This is why cough is

generally incorporated into most chest physical therapy techniques (350).



Cough and expectoration of mucus are the best-known symptoms in patients with

pulmonary impairment disorders. Airway clearance may be impaired in disorders

associated with abnormal cough mechanics, altered mucus rheology, altered

mucociliary clearance, or structural airway defects. A variety of interventions are used

to enhance airway clearance with the goal of improving lung mechanics and gas

exchange, and preventing atelectasis and infection (351).

Techniques for augmenting the normal mucociliary clearance and cough efficacy have

been used for many years to treat patients with respiratory disorders from different

etiologies. In recent years, new technologies and more advanced techniques have been

developed to be more comfortable and effective for the majority of patients. Postural

drainage with manual chest percussion and shaking has, in most parts of the world, been

replaced by more independent and effective techniques such as the active cycle of

breathing, autogenic drainage, R-C Cornet®, Flutter®, positive expiratory pressure

mask, high frequency chest wall oscillation, intrapulmonary percussive ventilation and

mechanical insufflation-exsufflation (349). The evidence in support of these techniques

is variable and the literature is confusing and sometimes conflicting, regarding the

clinical indication for each technique. This fact may be related to the intensity, duration

and frequency being different between physiotherapists in different parts of the world,

and have changed over the years (352). Moreover, it can be confusing for health care

professionals, patients and their caregivers when it comes to choosing and utilizing the

most appropriate airway clearance techniques and products.

Patients who require mechanical breathing assistance or pharmaceutical intervention,

often also need assistance to mobilize and clear secretions from their airways and lungs.

It is critically important for these patients to keep their airways clear of secretions to

avoid the risk of atelectasis caused by mucus plugs and infections, including



pneumonia, which can often lead to numerous hospitalizations and even premature

death. Patients with chronic lung disease, such as chronic obstructive pulmonary disease

(COPD) and Cystic Fibrosis (CF), those that have neuromuscular disorders such as

muscular dystrophy (MD), amyotrophic lateral sclerosis (ALS), spinal muscular atrophy

(SMA), post-polio syndrome, and those paralyzed due to Spinal Cord Injury (SCI), are

at the greatest risk of developing such infections.

The effective elimination of airway mucus and other debris is one of the most important

factor that permits successful use of chronic and acute ventilation support (noninvasive

and invasive) for patients with either ventilatory or oxygenation impairment. In

ventilatory dependent patients, the goals of intervention are to maintain lung

compliance and normal alveolar ventilation at all times and to maximize cough flows

for adequate bronchopulmonary secretion clearance (353).

In patients with primarily ventilatory impairment, such us neuromuscular disease, 90%

of episodes of respiratory failure are a result of inability to effectively clear airway

mucus during intercurrent chest colds (354). Although the use of respiratory muscle

aids is the single most important intervention for eliminating airway secretions for

patients with inspiratory and expiratory muscle weakness, as for normal coughing these

aids may not adequately expulse secretions from the very small peripheral airways more

than 6 divisions from the trachea, the flows they create may not be sufficient to

eliminate secretions that are obstructing the smaller airways (355). In these situations, it

is important to consider secretion mobilization techniques to gradually loosen and

mobilize secretions to assist mucociliary clearance from the lower airway into the upper

airway where they then need to be cleared by either assisted coughing techniques or the

patient’s natural cough.



A great majority of episodes of secretion encumbrance develop in acute respiratory

failure and it has been demonstrated that in even in acute episodes of respiratory failure

morbidity and mortality can be avoided without hospitalisations with a correct and

effective secretion management protocol (356). Moreover, it has been reported that

conventional chest physical therapy for secretion management does not increase the

chances of weaning and extubation success in critical ill patients (357). However, some

of these patients may have normal mucociliary clearance but ineffective peak cough

flows (CPF) which itself has been associated with extubation failure (37, 358). A

protocol that includes assisting coughing techniques as adjunct to a efficient NIV

application may increase the success rates of extubation in difficult to wean patients.

Patient evaluation and monitoring

The respiratory patient evaluation includes a survey for symptoms of chronic and /or

acute alveolar hypoventilation, medical history, physical examination, cough evaluation

and simple pulmonary function tests. Measurement of mucous transport through the

bronchial tree by radiolabeled tracers is a technique that has been used above all to

study mucociliary clearance, as well as the measurement of the volume of expectorated

mucous (359).

Respiratory physiotherapy interventions can be evaluated using different outcome

variables, such as bronchial mucus transport measurement, measurement of the amount

of expectorated mucus, pulmonary function, medication use, frequency of acute

exacerbations and quality of life(349, 352, 360).



Pulmonary function and cough tests

Evaluation of respiratory physiotherapy interventions only with pulmonary function

tests appears to be inadequate for significant conclusions. However it is knowned that

mucus retention has a strong impact on pulmonary function and gas exchange. Severe

mucus retention can cause an acute decrease in vital capacity (VC), forced VC, flow

rates, as well as SpO2. Patients with severe airway obstruction have more difficulties

expectorating mucus. Patients with ineffective cough and low VC´s are in extreme

respiratory distress in the presence of secretion accumulation. A correct evaluation of

pulmonary function and cough parameters may predict a successful respiratory

physiotherapy treatment.

Poponick et al.(361) demonstrated that acute viral illness was associated with a

reduction in vital capacity (VC) due to a reduction in inspiratory and expiratory

respiratory muscle strength (by 10–15% of baseline values), which causes a decline in

CPF to the critical level of 160 L·min-1.

A spirometer is used to measure VC in sitting, recumbent, and sidelying positions. The

spirometer is also used to measure the maximal insufflation capacity (MIC) for patients

with VCs at least 30% less than predicted normal levels who are trained in air stacking

(362). Usually a manual resuscitator is used for the patient to air stack via a mouthpiece

for the MIC measurements (Figure 14).



Figure 14: Air stacking with manual resuscitator via a mouthpiece in a DMD patient with low

vital capacity and suboptimal peak cough flow.

An effective CPF requires a pulmonary inspiration or insufflations until 85-90% of the

vital capacity, and the generation of high intratoracic pressure so as to expel 2,3-2,5 L of

air at a CPF of 6-20 L/sec. In order for an effective cough to occur, the Peak Cough

Flow (CPF) must be higher than 270 L/min (363)

Unassisted cough peak flows (CPF) are measured by having the patient cough as hard

as possible through a peak flow meter to get a baseline value. Kang and Bach (364)

proved that the CPF value could be even higher if it is performed through the Maximum

Insufflation Capacity (MIC). The MIC is related to the pulmonary compliance and with

the pharyngeal and oropharingeal muscles function. After a deep inspiration the subject

makes an apnoea and receives an extra air volume of air (through a manual resuscitator

or volume ventilator) via a mouthpiece, nasal interface. This extra air volume will

produce the lung distension, allowing a cough at a higher volume, and therefore more

effective. The patient coughs via an oronasal interface if there is a tendency for

insufflated air to leak out of the nose.



Finally, (fully) assisted CPF are measured from the MIC with an abdominal

thrust timed to glottic opening. The most important CPF measurement is usually the

latter because it is the manually assisted cough from the MIC that the patient must often

use to clear airway secretions to avoid respiratory failure. The inability to generate a

CPF greater than 2.7 L/s even when MIC exceeds 1 L, generally indicates the existence

of fixed upper airway obstruction or significant bulbar impairment, with

hypopharyngeal collapse during mechanical assistance to aid cough (60, 365-366).

Control of Mucus and Airway Clearance Techniques

Airway clearance refers to two separate, but connected, mechanisms: mucociliary

clearance and cough clearance. Techniques for controlling and assisting the

mobilization of secretions from the airways have long been advocated for use in the

patient with impairment in mucociliary clearance or an ineffective cough mechanism.

The goals of this therapy are to reduce airway obstruction, improve mucociliary

clearance and ventilation and optimise gas exchange.

Approaches to preventing airway secretion retention include pharmacotherapy to

reduce mucus hypersecretion or to liquefy secretions, and the application of chest

physiotherapy techniques. Chest physiotherapy (CPT) can be defined as the external

application of a combination of forces to increase mucus transport that include postural

drainage positions, special breathing exercises, manual chest vibration and percussion,

autonomous instrumental techniques and manual assisted coughing.

Research studding the results of airway clearance are often difficult to evaluate because

the components of a given treatment have not been standardized. Availability of

equipment or education about a technique as well cultural differences in its application

confounds the results. CPT does not appear to benefit patients during recovery from



acute exacerbations of COPD or pneumonia. These conditions are characterized by

interstitial pathology, which cannot be influenced by physical interventions in the

airways (367-369). Further studies are needed to identify the patients and more

circumstances, which are at risk from complications or adverse effects of chest

physiotherapy.

Chest physical therapy techniques

Approaches to preventing retention of airway secretions include the use of medication

to reduce mucus hypersecretion or to liquefy secretions and the facilitation of mucus

mobilization. To complement this objective, chest physiotherapy techniques (CPT) are

shown to be very effective in preventing pulmonary complications in infant and adult

patients with bronchopulmonary secretion accumulation. The principles of manual chest

physiotherapy techniques consists in the application of external forces in the thoracic

cage that have direct effect on mucus mobilization.

Manual chest percussion, sometimes referred to as chest clapping, is very well knowed

in the respiratory physiotherapy community. Some authors demonstrated an increase in

airflow obstruction when chest clapping was included in an airway clearance regimen

(370). Chest clapping has also been shown to cause an increase in hypoxemia, but when

short periods of chest clapping have been combined with three or four thoracic

expansion exercises, no fall in oxygen saturation has been seen(349). Some patients

with severe lung disease demonstrate oxygen desaturation with self-chest clapping. This

may be due to the work of the additional upper limb activity. On the basis of three

randomised, controlled trials of chest physiotherapy and one observational study,

manual chest percussion as applied by physical or respiratory therapists is ineffective



and perhaps even detrimental in the treatment of patients with acute exacerbations of

COPD(371).

Another manual chest physical therapy technique is vibration applied throughout

exhalation concurrently with mild compression of the patient’s chest wall. Vibration is

proposed to enhance mucociliary transport from the peripheral of the lungs fields to the

larger airways.

Manual thoracic techniques are effective in removing pulmonary secretions, facilitating

inspiration and improving alveolar ventilation. Guidebooks have been published that

demonstrates the hand placements and thrusting techniques in children and adults (372).

Manual assisted coughing techniques

Cough is the primary defense mechanism against foreign bodies in the lower airways.

Any stimulation of the pharyngeal, laryngeal, tracheal or bronchial receptors can create

a cough. When this mechanism is not functioning correctly mucus restrain will occur, as

bronchial obstruction. This problem may be due to the fact that the subject cannot make

a deep inspiration, or incapable of glottis closure, or incapable of rising intra abdominal

and intra thoracic pressure.

An effective cough is based of expiratory muscles force, capable of producing effective

CPF´s. The CPF is a routine measure in the evaluation of neuromuscular patients (373)

and clinical investigations such suggest that it should be used in spinal cord patients as

well (88, 97).

The patient with partial or complete abdominal muscle paralysis is unable to produce an

effective cough. Manually assisted cough is the external application of pressure to the



thoracic cage or epigastric area, coordinated with a forced exhalation. This action serves

to simulate the normal cough mechanism by generating an increase in the velocity of the

expired air and may be helpful in moving secretions toward the trachea, where they can

be removed by nasotracheal suctioning.

The abdominal thrust is an assisted coughing technique which consists of the

association of two techniques: the costo-phrenic compression and the Heimlich

manoeuvre. The combination of deep lung insufflations to the MIC followed by manual

assisted cough with abdominal thrust (Figure 15) has been shown to increase

significantly CPF´s values in restrictive patients (366, 374).

Although an optimal insufflation followed by an abdominal thrust provides the greatest

increase in CPF, it can also be significantly increased by providing only a maximal

insufflation or providing only an abdominal thrust without a preceding maximal

insufflation. Interestingly, CPF are increased significantly more by the maximal

insufflation than by the abdominal thrust (375-376).

Manually assisted coughing and MIC maneuver requires a cooperative patient, good

coordination between the patient and care giver), and adequate physical effort and often

frequent application by the family care giver (Figure 2). It is usually ineffective in the

presence of severe scoliosis because of a combination of restricted lung capacity and the

inability to effect diaphragm movement by abdominal thrusting because of severe rib

cage and diaphragm deformity.



Figure 15: Air stacking and manual assisted cough in a patient with neuromuscular disease, performed by

the family care giver

Abdominal compressions should not be used for 1 to 1.5 hours following a meal,

however, chest compressions can be used to augment CPF. Chest thrusting techniques

must be performed with caution in the presence of an osteoporotic rib cage.

Unfortunately, since it is not widely taught to health care professionals manually

assisted coughing is under utilized (377).

Mechanical Respiratory Muscle Aids for Secretion Management

Respiratory muscle aids for secretion management are devices and techniques that

involve mechanical application of forces to the body or intermittent pressure changes to

the airway to assist expiratory muscle function and airway mucus clearance. The

devices that act on the body include high frequency chest wall oscillators that create

atmospheric pressure changes with oscillations around the thorax and abdomen,

intrapulmonary percussive ventilators that create a rapid frequency adjusted for internal

percussion for mucus progression to the large airways, and insufflation- exsufflation

devices that apply force and pressure changes directly to the airway to assist the



expiratory muscles for cough augmentation and the inspiratory muscles for lung

expansion.

Intrapulmonary Percussive Ventilation (IPV)

The intrapulmonary percussive ventilator is an airway clearance device that

simultaneously delivers aerosolized solution and intrathoracic percussion. This modified

method of intermittent positive-pressure breathing imposes high-frequency minibursts

of gas (at 50–550 cycles/min) on the patient’s own respiration. This creates a global

effect of internal percussion of the lungs, which could promote clearance of the

peripheral bronchial tree.

IPV devices include: Im®-F00012, IPV1C®-F00001-C, IPV2C®-F00002-C

(Percussionaire® Corporation, ID, USA); and IMP II (Breas Medical, Sweden). The

percussions (sub-tidal-volume) are delivered continuously through a sliding air-

entrainment device (called Phasitron) powered by compressed gas at 20–40 psi. The

high frequency gas pulses expand the lungs, vibrate and enlarge the airways, and deliver

gas into distal lung units, beyond accumulated mucus (378-380) . Treatment with IPV is

titrated for patient comfort and visible thoracic movement. The patient initiates the flow

of gas and during inspiration the pulsatile flow results in an internal percussion.

Interruption of the inspiratory flow allows for passive expiration.

This technique has been shown to be as effective as a standard chest physiotherapy and

to assist mucus clearance in patients with secretion encumbrance from different

etiologies, such as cystic fibrosis (381), acute exacerbations of COPD (41) and

Duchenne muscle dystrophy (378). In cystic fibrosis IPV was shown to be as effective



as the other methods of airway clearance in sputum mobilization, when the amount of

sputum produced was assessed by dry weight(382).

IPV can be delivered through a mouthpiece, a facial mask and also through a

endotraqueal and tracheostomy tube (383). The primary aims of this technique are to

reduce secretion viscosity, promote deep lung recruitment, improve gas exchange,

deliver a vascular “massage”, and protect the airway against barotrauma. The main

contraindication is the presence of diffuse alveolar haemorrhage with homodynamic

instability. Relative contraindications include active or recent gross hemoptysis,

pulmonary embolism, subcutaneous emphysema, bronchopleural fistula, esophageal

surgery, recent spinal infusion, spinal anesthesia or acute spinal injury, presence of a

transvenous or subcutaneous pacemaker, increased intracranial pressures, uncontrolled

hypertension, suspected or confirmed pulmonary tuberculosis, bronchospasm, empyema

or large pleural effusion and acute cardiogenic pulmonary edema(384).

High-frequency chest wall oscillation (HFCWO)

In 1939 it was recognized that alveolar ventilation and blood circulation could be

assisted by rapidly alternating negative and positive pressure under a chest shell. J. H.

Emerson developed the first high frequency chest wall oscillation jacket, the Ucyclist-B

Vest, to facilitate bronchial secretion clearance in the early 1950s but he provided

oscillation only during part of the breathing cycle. Barach described use of a similar unit

by patients with chronic bronchial asthma and emphysema in 1966 (385).

During HFCWO, positive pressure air pulses are applied to the chest wall. Oscillation

and vibration can be applied externally to the chest wall or abdomen by rapidly

oscillating pressure changes in a vest that include the SmartVest® (Electromed Inc,



MN, USA), The Vest® (Hill-Rom, MN, USA) and the ThAIRapy Vest™, (American

Biosystems, Inc., St. Paul, MN), or by cycling oscillating pressures under a chest shell

(Hayek™ oscillator, Breasy Medical Equipment Inc., Stanford, CN).

This technique provides oscillation at 5 to 25 Hz. Mechanical vibration is performed at

frequencies up to 40 Hz. Vibration is applied during the entire breathing cycle or during

expiration only. The adjustable I/E ratio permits asymmetric inspiratory and expiratory

pressure changes (for example +3 to -6 cm H20), which favor higher exsufflation flow

velocities to mobilize secretions. Baseline pressures can be set at negative,

atmospheric, or positive values thus commencing oscillation above, at, or below the

functional residual capacity (FRC) (39, 353). The average length of time spent in each

treatment session will vary according to patient tolerance, amount and consistency of

secretions, and the phase of the patient´s illness (acute or chronic)(380). Simultaneous

use of an aerosolized medication or saline is recommended throughout the treatment.

This humidifies the air to counteract the drying effect of the increased airflow (41).

HFCWO may act like a physical mucolytic, reducing both the spinability and

viscoelasticity of mucus and enhancing clearance by coughing (353, 379, 386). High

frequency chest wall oscillation (HFCWO) has demonstrated efficacy in assisting

mucus clearance in patients with disorders associated with mucus hyper-secretion but

preserved muscle function such as cystic fibrosis (CF) (386). HFCWO is an external

non-invasive respiratory modality proven effective in mobilizing airway secretions from

the small peripheral airways and improving mucus rheology in patients with CF and has

become an important modality in the airway clearance techniques of this group of

patients (387-389). High frequency oscillation to the airways has also been reported to

increase mucus transport in healthy subjects (390).



These beneficial effects upon both mucus clearance and clinical parameters are are not

so evident in other groups of patients such as COPD. Moreover, side effects of

percussion and vibration include increasing obstruction to airflow for patients with

COPD. (369, 391-392). The proven value of HFCWO in patients with relatively normal

mucus composition and characteristics but neuromuscular weakness is still under

investigation, especially as a long-term treatment modality. In one study, the addition of

HFCWO to randomly selected patients with ALS failed to achieve any significant

clinical benefits in relation to the time of death (survival days). In addition, HFCWO

failed to modify the rate of decline in FVC given the progressive nature of this chronic

neurodegenerative disease process. There were no significant differences concerning the

frequency of atelectasis, pneumonia and number of hospitalisations for a respiratory

related abnormality, or requirement for tracheostomy and mechanical ventilation (39).

On another hand, Lange et al (393) also compared lung function parameters in ALS

patients who were randomized to 12 weeks of HFCWO or no treatment. Results showed

maintenance of FVC and decreased fatigue and dyspnoea in HFCWO group compared

to the untreated group.

Contraindications for HFCWO are mostly the same as for IPV, plus head or neck injury

not yet stabilized, burns, open wounds, infection or recent thoracic skin grafts,

osteoporosis, osteomyelitis, coagulopathy, rib fracture, lung contusion, distended

abdomen, and chest wall pain (353, 388).

Mechanical Insufflation-Exsufflation (MI-E).

Mechanical insufflator-exsufflators (Cough Assisttm, Philips Respironics, Inc) deliver

deep insufflations (at positive pressures of 30 to 60cmH2O) followed immediately by

deep exsufflations (at negative pressures of -30 to -60cmH2O). The insufflation and



exsufflation pressures and delivery times are independently adjustable(55). With an

inspiratory time of 2 seconds and an expiratory time of 3 seconds, there exists a very

good correlation between the pressures used and the flows obtained(56) (394).

Except after a meal, an abdominal thrust is applied in conjunction with the exsufflation

(MAC) (376). Mechanical in-exsufflation can be provided via an oral-nasal mask a

simple mouthpiece, or via a translaryngeal or tracheostomy tube. When delivered via

the latter, the cuff, when present, should be inflated (395).

MI-E applied with an oronasal mask can generate CPFs greater than 2.7 L/s in motor

neuron disease patients, with the exception of those with very acute bulbar dysfunction

(396), in whom there exists great instability of the upper airways (60). If, in normal

subjects, the sudden application of negative pressure at this level produces reflex

activation of the genioglossus to maintain permeability, in those patients with

diminished strength and speed of the pharyngeal muscles there will be obstruction

during the expiratory phase (363).

The Cough AssistTM can be manually or automatically cycled. Manual cycling

facilitates care giver-patient coordination of inspiration and expiration with insufflation

and exsufflation, but it requires hands to deliver an abdominal thrust, to hold the mask

on the patient, and to cycle the machine. One treatment consists of about five cycles of

MI-E or MAC followed by a short period of normal breathing or ventilator use to avoid

hyperventilation(62). Insufflation and exsufflation pressures are almost always from

+35 to +60 cm H2O to -35 to -60 cm H2O. Most patients use 35 to 45 cm H2O

pressures for insufflations and exsufflations. In experimental models, +40 to -40 cm

H2O pressures have been shown to provide maximum forced deflation VCs and flows

(365, 375, 394). Multiple treatments are given in one sitting until no further secretions



are expulsed and any secretion or mucus induced dessaturations are reversed. Use can

be required as frequently as every few minutes around the clock during chest

infections(58). Although no medications are usually required for effective MI-E in

neuromuscular ventilator users, liquefaction of sputum using heated aerosol treatments

may facilitate exsufflation when secretions are inspissated.

The use of MI-E via the upper airway can be effective for children as young as 11

months of age. Patients this young can become accustomed to MI-E and permit its

effective use by not crying or closing their glottises. Between 2 1/2 and 5 years of age

most children become able to cooperate and cough on queue with MI-E. Exsufflation

timed abdominal thrusts are also used for infants (397-398).

Whether via the upper airway or via indwelling airway tubes, routine airway suctioning

misses the left main stem bronchus about 90% of the time. MI-E, on the other hand,

provides the same exsufflation flows in both left and right airways without the

discomfort or airway trauma of tracheal suctioning and it can be effective when

suctioning isn't. Patients almost invariably prefer MI-E to suctioning for comfort and

effectiveness and they find it less tiring (399-400).

When mucous plugs are eliminated in acute episodes in ventilated neuromuscular

patients, MI-E may attain 300% improvement in VC as well as normalization of oxygen

saturation (401). Contraindications of the technique include previous barotrauma, the

existence of bullae, emphysema, or bronchial hyperreactivity (402). There continue to

be no publications contradicting the reports of effectiveness or describing significant

complications of MI-E. Even when used following abdominal surgery and following

extensive chest wall surgery no disruption of recently sutured wounds was noted (403-

404). Secondary effects, such as pneumothorax, aspiration, or coughing up blood are



reduced considerably by treating the mentioned contraindications. On the other hand,

gurgling noises and abdominal distension are rare and can be eliminated by lowering the

insufflation pressure. The significant increase of forced expiratory flows in periods

immediately following post-exsufflation indicates that MI-E does not provoke

obstruction of the airways. As patients with spinal shock can present bradycardias, MIE

should be carried out with cautious in them, with gradual increase in pressures or

premedication with anticholinergics (405). In patients with very low VC who have not

previously received maximum insufflations, the use of high pressures may cause

thoracic muscle discomfort; thus, progressive increase is also indicated.

The use of MI-E has been demonstrated to be very important in extubating NMD

patients following general anesthesia despite their lack of any breathing tolerance, and

to manage them with noninvasive ventilation (355-356, 373). It has also permitted to

avoid intubation or to quickly extubate NMD patients in acute ventilatory failure with

no breathing tolerance and profuse airway secretions due to intercurrent chest infections

(27, 406-407). MI-E in a protocol with manually assisted coughing, oximetry feedback,

and home use of noninvasive IPPV was shown to effectively decrease hospitalizations

and respiratory complications and mortality for patients with NMD (354, 408).



PURPOSE OF THE THESIS

Inspiratory and expiratory muscle aids are devices and techniques that involve the

manual or mechanical application of forces to the body or intermittent pressure changes

to the airway to assist inspiratory or expiratory muscle function. Noninvasive

ventilation (NIV) and mechanical assisted cough (MAC) are techniques that may have a

role in different phases of both acute and chronic respiratory failure. In fact, there is

sufficient evidence that support the physiological benefits of these techniques in aiding

both inspiratory (NIV) and expiratory muscle function (MAC) in different patient

populations.

Patients with impaired respiratory muscle function from different etiologies may be at

risk of developing ventilatory failure during an acute exacerbation or during the primary

disease progression in a chronic setting. Protocols and timing of NIV and MAC

application have to be adjusted according to the different clinical scenarios and

treatment goals should be based on a continuous level of care from acute to long term

management. In this patient population, primary treatment goals in acute care are

reversion of the episode of acute respiratory failure (ARF), avoid (when possible) or

minimize the time on invasive ventilation, prevent and reduce complications of

treatment and promote a safe hospital discharge to the community. In the chronic care

setting, the main treatment goals are to prevent complications with close follow up,

reduce hospitalizations due to ARF, prolong survival and enhance quality of life.

The main purpose of this thesis is to describe the efficacy of NIV and MAC in the

different “windows of opportunity” set to achieve specific goals from acute to chronic



care, and present new management and evaluation paradigms in patients with muscle

weakness from different etiologies. Methodological design of the thesis goals is

presented in Figure 16.

Figure 16: Methodological design of the thesis studies (1 to 10) according to the

different settings.

Acute Respiratory Failure

Mechanical ventilation using an artificial airway is probably the most frequently life-

saving procedure used in the management of critically ill patients with severe

respiratory failure(35). However, it is associated with multiple complications, primarily

increased risk of pneumonia(409) with a high mortality rate, but also generalized

myopathy, possibly related to the sedation or curarization necessary for invasive

mechanical ventilation(410). In the majority of cases, mechanical ventilation can be

withdrawn after resolution or significant improvement of the underlying indication for

mechanical ventilation. However, it is estimated that 20 to 30% of patients require

gradual withdrawal of ventilatory support, namely weaning(411).

4 5

10

3 2

1 6 7 8

9



A distinction must be made between dependence on the ventilator and an ongoing need

for endotracheal intubation. When there is no need for an artificial airway ,conventional

extubation attempts follow successful “spontaneous breathing trials (SBTs) and the

passing of ventilator weaning parameters that include respiratory rate less than 38 per

minute and a rapid shallow breathing index below 100 breaths/min/L (412). This

presupposes that ventilator weaning is mandatory before a patient can be safely

extubated, otherwise patients are extubated only after tracheotomy. However, even for

patients who satisfy weaning criteria and pass ventilator weaning trials, there is an

extubation failure rate of 10 to 20% (413). The reasons given for extubation failure

include lack of improvement in work of breathing, hypoxemia, respiratory acidosis,

retained secretions, and decreased consciousness (414).

The process of discontinuing mechanical ventilation may be a major challenge,

especially in patients with chronic respiratory disorders, in whom weaning is

particularly difficult (415). Patients that develop acute respiratory failure that could

result in prolonged invasive ventilation include COPD, spinal cord injury,

neuromuscular disease (NMD), chest wall disease, and primary central nervous system

disease.

The process of weaning from mechanical ventilation must balance the risk of

complications due to unnecessary delays in extubation with the risk of complications

due to early discontinuation and the need of reintubation(411). Patients who require

reintubation have been noted to have a significantly higher mortality rate than those

who are successfully extubated on the first attempt(416).

While studies have reported that NIV has been used in the emergency setting to avert

intubation (21, 29, 417), and to facilitate extubation and weaning in the critical care



setting (114, 153, 158) in patients with lung/airways diseases (primarily oxygenation

impairment) (155, 161, 418), the studies either report very few patients with primarily

ventilatory impairment (unable to sustain spontaneous breathing) due to neuromuscular

weakness i.e. 18 of 162 (155), 17 of 900 (413)) or they completely exclude these

patients when weaning is considered unlikely (357) or the risk of post-extubation failure

is considered high (160). This is true despite the fact that neither adequate ventilator

settings for full continuous noninvasive ventilatory support nor mechanically assisted

coughing (MAC) were used in any of the studies on adult patients (419). Some studies

do not even report the NIV settings (413).

Patients with pre-existing NMD are relatively infrequently in critical care (420), about 4

to 12.5% of cases (34, 156) (up to 25% in weaning centers) (421), and are seldom

included in randomized critical care controlled trials of NIV (422). On the other hand,

acquired critical care NMD is common yet often unrecognized (410, 423). Controlled

invasive mechanical ventilation can induce diaphragmatic dysfunction (424) and

becomes part of a positive feedback loop leading to respiratory muscle failure (425). In

multicenter prospective studies 25.3% of patients who underwent invasive mechanical

ventilation for more than 7 days developed acquired NMD (410). Risk factors include

malnutrition (423), corticosteroids (424), neuromuscular blocking agents (426),

aminoglycosides, hyperglycemia, sepsis (425, 427), and “prolonged” invasive

mechanical ventilation (428-429). These patients commonly fail extubation by

conventional approaches and are considered “unweanable” (188, 430-431).

Ventilatory insufficiency and impaired airway secretion clearance are common acute

care complications of NMDs and high level spinal cord injury patients (SCI) and can

lead to prolonged ventilation(415) with very difficult weaning (429, 432). Since the

extubation failure risk is very high in this patient population, they are also considered



“unweanable”(411, 431, 433). Standard invasive ventilatory management options such

as early intubation and tracheostomy for long term care have been described as

alternatives to minimize respiratory complications in these patients (434-437).

Although it might be presumed that self-directed adult unweanable muscle weakness

patients who have failed multiple ventilator weaning trials can cooperate with the use of

NIV and MAC, there are no critical care publications that have reported the use of

those methods to extubate them. We hypothesized that, since there is no chronic lung

disease in these totally ventilator dependent patients, and if at extubation the lungs are

healthy with SpO2>95% in ambient air, ventilation could be fully maintained

noninvasively even with no ventilatory autonomy (Study nr 1).

It has also been described that decannulation and conversion to NIV can facilitate

weaning in patients with no ventilator-free breathing ability(438), and that MAC can be

used for effective secretion clearance as an alternative to bronchoscopy to relieve

atelectasis and normalize Spo2.(358) Further, patients almost invariably prefer

noninvasive aids over tracheostomy for safety, convenience, appearance, comfort,

facilitating effect on speech, sleep, and swallowing, and general acceptability (439).

However, respiratory complications are highly prevalent in ASIA A SCI patients with

84% of patients with C1-C4 and 60% of those with C5-C7 injury levels present severe

ventilatory failure(440). Such patients are conventionally managed by translaryngeal

intubation and mechanical ventilatory support(441) and the overall incidence of

tracheostomy in these cases was between 81 and 83% (442-443). The number of

respiratory complications during this acute phase contributes significantly to both

hospital length of stay and costs(444).



Following the line of research of this thesis, we hypothesized that noninvasive methods

of assisted ventilation and coughing may facilitate both extubation and decannulation

with significant improvement on ventilatory dependence and pulmonary function in

totally ventilator dependent patients with high level SCI. We also questioned if early

intervention in extubation can produce better outcomes than late decannulation (study

nr 2)

It has been reported that conventional chest physical therapy for secretion management

does not increase the chances of weaning and extubation success (357). However,

critically ill patients may have normal mucociliary clearance but ineffective cough peak

flows (CPF) which itself has been associated with extubation failure (37, 358) due to

airway secretion accumulation (37, 358) but very few studies reported CPF at

extubation. (37, 445)

Early extubation, coupled with the use of noninvasive ventilatory support has been used

effectively in several critical ill populations to facilitate weaning(20, 114, 155), improve

survival(161), decrease the incidence of ventilator-associated pneumonia(103, 153) and

reduce ICU length of stay(153, 161). However there is a higher risk of NIV failure

when applied in patients that develop ARF after extubation and the evidence that

supports its application is controversial (159-160, 446).

Despite a great interest in this field, it is still not clear the role of impaired airway

secretion clearance on the outcome of post-extubation respiratory failure in critical ill

ventilator dependent patient treated with non-invasive ventilation. Airway clearance

may be impaired in disorders associated with abnormal cough mechanics, altered mucus

rheology, altered mucociliary clearance, or structural airway defects. A variety of

interventions are used to enhance airway clearance with the goal of improving lung



mechanics and gas exchange, and preventing atelectasis and infection (351). We

hypothesized that the inclusion in a weaning protocol of mechanical insufflation-

exsufflation (MI-E) device for mechanical cough assistance may prevent the

development of respiratory failure after extubation in patients that successfully pass the

SBT and may reduce the incidence of NIV failure in those who develop ARF after

extubation. We also questioned if this technique has a role in reducing both re-

intubation rates and ICU length of stay (study nr 3).

Considering the incidence of mortality and respiratory morbidity in “high risk” critical

ill patients with severe inspiratory and expiratory muscle weakness managed by

standard ventilatory invasive techniques, we question if NIV coupled with MAC is

efficient in treating post-extubation respiratory failure and can facilitate both extubation

and decannulation in “unweanable” patients with significant improvement on

ventilatory dependence and pulmonary function

Questions:

- Question 1 – Is it possible to extubate and prevent post-extubation failure in

cooperative, totally ventilator dependent (unweanable) neuromuscular weakness

patients without tracheotomy using a protocol that include full, continuous NIV and

MAC? Answer described in study nr 1.

- Question 2 – Can totally ventilator dependent neuromuscular weakness patients

wean from ventilatory support, with significant improvement in Vital Capacity



(VC) and CPF after being submitted to an extubation protocol that include full,

continuous NIV and MAC. Answer described in study nr 1

- Question 3 – Is it possible to extubate and decanulate totally ventilator dependent

ASIA A SCI patients with a protocol that include full and continuous NIV and

MAC? Answer described in study nr 2

- Question 4- Does a protocol that include full and continuous NIV and MAC

produce better outcomes when applied during extubation rather than in

decannulation of ASIA A SCI patients ? Answer described in study nr 2

- Question 5 – Can totally ventilator dependent ASIA A SCI patients wean from

ventilatory support, with significant improvement in Vital Capacity (VC) and CPF

after being submitted to an extubation or a decannulation protocol that include full,

continuous NIV and MAC. Answer described in study nr 2

- Question 6 - Is the inclusion of MI-E in weaning protocol effective in reducing

NIV failure and re-intubation rates in patients that successfully pass SBT´s, but

develop respiratory failure after extubation? Does it have any impact on ICU length

of stay? Answer described in study nr 3

Chronic Respiratory Failure

Chronic respiratory patients with primarily ventilatory impairment such as NMD and

other restrictive syndromes benefit significantly with the use of long term noninvasive

ventilation (8, 15, 447-449). In this line of research, noninvasive ventilation (NIV)

refers only to devices aimed to assist inspiratory muscles (CPAP excluded) through bi-



level positive airway pressure ventilation or volume cycled intermittent positive

pressure ventilation.

Standardized protocols for managing and monitoring NIV at home are lacking, and

depend on organizational, administrative and funding structures not only between

countries but often within different regions of the same country (248). Before starting a

patient on long term NIV(450), it is essential to ask three main questions: 1) Does the

patient have a disease known to cause ventilatory failure? 2) Does the patient have

symptoms suggesting hypoventilation? 3) Does the patient have physiological

abnormalities confirming hypoventilation? (249).

Ventilatory insufficiency progresses insidiously in most of restrictive muscle weakness

patients and NIV typically relieves fatigue and other daytime symptoms of which

patients may have been unaware (309, 451-453). Every consensus statement reinforces

the importance of detecting symptoms of nocturnal hypoventilation (252, 256-259).

However, symptoms may be subtle due to the variability of patient sensitivity and

sometimes it is difficult for the patient to establish differences between fatigue,

dyspnea, and sleepiness. So, carefully designed questionnaires that assess symptoms

systematically may be very useful. Jackson et al (260) have described a pulmonary

symptom scale consisting of 14 questions, answered on a scale from 1-7. Others

evaluated by simple questionnaires the positive and negative effects of ventilation(261).

Although symptom questionnaire are insensitive in identifying patients with nocturnal

hypercapnic hypoventilation (260, 262) their systematic evaluation is useful in

evaluating response to NIV, as compliance to it is strongly correlated with patients

symptoms (263).



Since 1993, different consensus conferences and guidelines have proposed indications

for initiating ventilatory support in patients with chronic respiratory failure (252, 256-

259, 277, 345, 454). Initially, criteria for beginning ventilatory support have relied on

abnormal awake blood gases (PaO2< 60mmHg and PaCO2 ≥ 45mmHg) or significant

nocturnal desaturation (SpO2 below 90% for ≥ 20% recorded time) (345), then on

Forced Vital Capacity (FVC) impairment (under 50% of predicted (256) or under

1L(258)) or mouth pressures (maximum inspiratory pressure under 60cmH20(252)).

More recently more sensitive parameters have also being included and nocturnal

hypercapnia (transcutaneous CO2 of 50 mmHg for more than 50% of sleep time(258))

and Sniff nasal pressure (SNP under 40cmH20(259, 310)) may be better in assessing the

need for ventilatory support.

Vital Capacity (VC) is one of the most reproducible tests of lung function in restrictive

patients. Although it may not fall below normal limits until there is a 50% reduction in

muscle strength (267), its rate of decline has been shown to predict survival (268).

Although no consensus exist as to how often pulmonary function should be evaluated,

some authors propose that if VC is > 60% predicted it should be performed every 6

months while if under 60% every 3-4 months (269). Measurement of the VC in the

supine position gives and index of weakness of the diaphragm. A fall of more than 15%

indicates diaphragmatic dysfunction and correlates with complaints of orthopnea (270)

and a supine FVC under 75% was highly sensitive and specific of low

transdiaphragmatic pressure (271).

Bellemare and Grassino demonstrated a relationship between tension time index of the

diaphragm (TTIdi) and diaphragm endurance or limitation time (Tlim)(455). TTIdi

signals the extent to which diaphragm action can continue unabated or fail due to

muscular fatigue. However, because of its invasive nature and the difficulties in its



interpretation in seriously compromised patients, TTIdi is neither practical for the acute

care nor for outpatient settings.

The TTIdi is the product of the fraction of time that the diaphragm spends in contraction

(Ti/Ttot) and the ratio of the tension generated at each contraction (Pdi) to the maximal

Pdi that can be achieved voluntarily during a near isometric contraction (PdiMax).

Bellemare and Grassino reported that this index correlates significantly with extent of

respiratory impairment in lung disease patients(456).

We hypothesized that the ratio of tidal volume to vital capacity (Vt/VC) could substitute

for the Pdi/PdiMax in the Bellemare and Grassino equation. A validated noninvasive

measurement of TTIdi (457) in NMD patients could play a role in the decision to

initiate ventilator use (458). We realized if this index would probably better correlate

with symptomatic inspiratory muscle dysfunction if it reflects ongoing inspiratory

muscle action rather than effort over only one breath cycle. Thus we proposed a

Ventilator Requirment Index (VRI) were we multiplied the Ti/Ttot x Vt/VC x

respiratory rate (RR), to determine whether this index could distinguish patients with

NMDs with various levels of inspiratory muscle dysfunction and need for ventilator use

and if such an index could add to the diagnostic efficiency of simple VC measurement

in determining need for ventilator use (study nr 4).

The main cause of morbidity and mortality in patients with NMD is respiratory failure

and, in particular, cough dysfunction (447, 459-460). Inspiratory, expiratory, and bulbar

innervated musculature are required for effective coughing (461-462). Normal pre-

cough inspiration is to 85-90% of total lung capacity(463). Thus, cough flows are

diminished for patients who have VCs less than 1500 ml (460).



Both, peak expiratory flows (PEF) and cough peak flows (CPF) have been described as

useful clinical parameters of respiratory muscle function (364).“Dart flows” (DF) are

generated by creating pressure behind the lips and tongue with the mouth closed. As

the lips open in a maneuver like spitting or projecting a dart through a narrow tube, the

flows can also be measured by peak flow meter. These flows can be confused with PEF

and CPF and cause the latter to be overestimated. They are largely a function of the

ability to seal the lips and control the tongue and buccal muscles.

To optimize CPF for patients with low VCs, particularly for those with VCs below 1000

ml, coughing needs to be preceded by the delivery of maximal insufflations or

maximum air stacking(462). The delivered air should be to the maximum insufflation

capacity (MIC)(362) which, even when not greater than 1500 ml, can greatly increase

the pressure of the lung's recoil once the glottis is opened during the cough(364). This

can dramatically increase CPF even without applying an abdominal thrust to manually

augment the flows(464).

Expiratory muscles can be manually assisted by providing thoracoabdominal

thrusts(465). The combination of applying an abdominal thrust to a maximally inflated

lung is an assisted cough (54, 464, 466). While unassisted cough flows depend on

inspiratory, expiratory, and bulbar-innervated musculature, air stacking ability and,

therefore, assisted cough flows depend only on glottic control or on bulbar-innervated

muscle function alone. Thus, the greater the difference between the MIC and the VC

and the difference between assisted and unassisted cough peak flows (CPF), the greater

is bulbar-innervated muscle function by comparison to inspiratory muscle function(10,

396, 460). Patients who cannot close the glottis cannot air stack. They may “huff” but

cannot cough. CPF better reflect the capacity to expulse debris from the airways than do

peak expiratory flows (PEF) which occur without glottic closure (461).



There are no standard normal values for CPF or DF but PEF range from 500 to 700

L/min for men and from 380 to 500 L/min for women, and from 150 to 840 L/sec for

children and adolescents with variations due to age, race, gender, and height(467).

We proposed to describe and compare the CPF, PEF, and DF in NMD patients, whose

VCs were less than normal, and question if they correlate with VC or MIC, to consider

their use in the evaluation of the respiratory muscles and to justify the indication of

inspiratory and expiratory muscle aids (study nr 5).

As VC decreases markedly, the largest breath that one can take can only expand a small

portion of the lungs. Use of incentive spirometry or deep breathing can expand the

lungs no greater than the VC. Although possibly useful, manual chest wall stretching

and rocking the pelvis onto the chest to decrease costovertebral tightness has not been

shown to increase lung volumes. As has been recognized since at least 1952, this can

only be achieved by air stacking, by providing deep insufflations (via the upper airway

or by "sighs" for patients using invasive mechanical ventilation), or by nocturnal

noninvasive ventilation for patients who can not cooperate with air stacking or

insufflation therapy(468).

A patient's maximum insufflation capacity (MIC) is determined by measuring

spirometrically the largest volume of air that a patient can hold with a closed

glottis(362). The patient air stacks via a mouth piece consecutively delivered volumes

from a volume-cycled ventilator or a manual resuscitator. This is performed multiple

times three times daily. The patient stacks the consecutively delivered volumes with a

closed glottis until the lungs are maximally expanded(469). If the lips or cheeks are too

weak to permit air stacking, stacking is done via a nasal interface or lipseal.



The extent to which the MIC is greater than the VC predicts the capacity of the patient

to be maintained by noninvasive rather than tracheostomy ventilatory support. This is

because the MIC /VC difference, like the extent of assisted CPF, is a function of bulbar

muscle integrity (470-471).

With complete loss of glottic closure, MIC no longer exceeds VC; the NMD patient can

no longer air stack or cough, and both the glottis, and many bulbar-innervated muscles,

are extremely impaired. In this case, lung insufflation can only be provided by

bypassing glottic function. This can be done by using a manual resuscitator with a

closed expiratory valve mimicking glottic closure and insufflate to the approached

predicted maximum insufflation.

We proposed that the maximum passive lung insufflation volume achieved in this

manner is defined as the lung insufflation capacity (LIC). We questioned if passively

insufflating the patient to the maximum LIC could be efficient for chest wall ROM

when bulbar muscle impairment is present We hypothesized that LIC could be

compared with MIC (lung inflation by air stacking) and with vital capacity (VC) and

that relationships between these variables could correlate with glottic function and CPF

(study nr 6).

Questions:

- Question 7 – Can the measurement of a new proposed ventilator requirement index

(VRI) distinguish patients with NMDs according to various levels of inspiratory

muscle dysfunction and need for ventilator use? Answer described in study nr 4



- Question 8 – Does the VRI add new findings to the diagnostic efficiency of simple

VC measurement for determining the need and the extent for ventilator use?

Answer described in study nr 4.

- Question 8 – Can a simulation expiratory flow maneuver like the DF overestimate

PEF and CPF in NMD patients? Answer described in study nr 5.

- Question 9 – Is there any correlation between CPF and PEF with VC or MIC, for

evaluation of bulbar muscle function and how can it influence the efficacy of

inspiratory and expiratory muscle aids? Answer described in study nr 5.

- Question 10 – Will lung volumes be significantly greater by passive insufflation

than by air stacking, especially in patients with severe bulbar innervated muscle

dysfunction, and will both LIC and MIC significantly exceed VC and increase

CPF? Answer described in study nr 6.

- Question 11 – Will LIC-MIC correlate inversely with MIC-VC and, therefore,

correlate inversely with glottic integrity? Answer described in study nr 6.

- Question 12 – Can LIC and MIC increase with practice were the greatest increases

will be for the most severely affected patients, that is, with the lowest VC? Answer

described in study nr 6.



Home mechanical ventilation

Preparing the patient for discharge on home mechanical ventilation requires planning.

Most respiratory patients are discharged home with a simple bi-level device for

nocturnal use only. Those patients have normally sleep disorder breathing defined as

nocturnal hypoventilation during sleep due to several causes that include either

obstructive lung/airways disease or mild to moderate restrictive syndromes(472).

However there are an increasing number of individuals on HMV that are continuous

ventilator dependent through either noninvasive interfaces or tracheostomy. Those

patients normally have severe muscle weakness associated in the majority of cases to

NMD that may include patients with severe bulbar muscle dysfunction, such as ALS.

Training, organizing and funding appropriate equipment and resources for such

individuals is more complex and time consuming(49, 473-476).

In patients with neuromuscular disorders with severe ventilatory impairment, instigating

a secretion-management protocol is an essential component of any home management

programme(46), and this needs to be carried out on a regular basis. Approaches to

preventing peripheral airway secretion retention at home for patients with NMD include

the use of medications to liquefy secretions and manual techniques of mucus

mobilization to transport mucus from the peripheral to the central airways from where it

can more easily be eliminated. As already described in the line of research of this thesis,

an optimal insufflation to the MIC followed by an abdominal thrust provides the

greatest increase in CPF in NMD patients with intact bulbar function. When these

techniques alone are no longer effective, MAC defined as the use of mechanical

insufflation-exsufflation (MI-E) (62) with an exsufflation-timed abdominal thrust can be



applied at home both through a oronasal interface or through a tracheostomy tube with

cuff inflated(61).

An optimal home management of both ventilatory failure and profuse secretion

retention should be guided by an oximetry feedback protocol. Since supplemental

oxygen is avoided for NMD patients, once artifact is ruled out, SpO2 below 95% is due

to one of three causes: hypercapnia (hypoventilation), airway encumberment

(secretions), and if these are not managed properly, intrinsic lung disease, usually gross

atelectasis or pneumonia(127). This protocol consists of using an oximeter for feedback

to maintain SpO2 greater than 94% by maintaining effective alveolar ventilation and

airway secretion elimination. However, application of these techniques and protocols at

home require skill and coordination if they are to be performed effectively(63).

Therefore, not only do the techniques need to be taught initially, periodic assessment of

the caregivers skills in performing the technique is required.

Despite increasing experience and published results concerning this technique as a first-

line intervention for hospitalized patients with ALS and others with neuromuscular

diseases (58-59, 61, 127, 246, 401, 477-478), there are limited data related to its

indications for home care use. We aimed at describing the indications of home MAC

use with oximetry feedback and questioned its safety and compliance in NMD patients,

under continuous mechanical ventilation either through noninvasive or tracheostomy

ventilation, when centred in non-professional caregivers, with the support of a trained

health care professional in a home on-call regime (study nr 7).

Particularly in patients with Amyotrophic Lateral Sclerosis (ALS), secretion

encumbrance episodes often result in acute respiratory failure especially during acute

chest infections(401, 460, 479). Moreover, in case of severe bulbar-innervated muscle



dysfunction with inability to protect the airways both manual assisted coughing with

lung insufflation and MAC may be ineffective(10, 60, 480) and result in hospitalization

and need for tracheotomy(481).

Organization of home care programs that include the use of MAC in this population

with severe ventilatory impairment requires more study. While effective when

continuously available at home(63, 127), expense can be mitigated by on-demand rather

than continuous access of MAC if on-demand use can be demonstrated to be effective.

In Europe, home respiratory care is often inadequate because home care companies

provide only equipment, not assistance, instruction, or expertise for which the patient

must depend on emergency services(476), and there is great burden on caregivers(482).

Thus, hospitalization rates and lengths of stay in this patient population are high,

especially when ARF and intubation result in tracheotomy. It has been reported that the

mean acute hospitalization for patients undergoing tracheotomy is 72 days, mostly in

intensive care(483) at a very high cost per day.

To help reduce hospitalizations costs and establish an optimal MI-E provision regimen

at home, we studied a telephone accessed integrated care (TAIC)(53) program with

oximetry feedback, that provided equipment and professional home care services on an

“as needed basis” to treat clinical exacerbations due to secretion encumbrance and

related respiratory problems in ALS patients (study nr 8).

For the great majority of NMD patients, up to continuous use of noninvasive ventilation

(NIV) can maintain quality of life,(484) and markedly prolong a survival(10) that is,

nevertheless, punctuated by respiratory tract infections (RTIs). Intercurrent RTIs are the

main cause of morbidity, prolonged hospitalizations, acute respiratory failure (ARF),

intensive care admissions, and mortality (47, 63, 127, 460). When MAC is used for



airway secretion clearance, multiple treatments are given until no further secretions are

expulsed and any secretion or mucus induced O2 desaturations are reversed. Use can be

required as frequently as every few minutes around-the-clock during intercurrent

RTIs(58, 127, 485). Because respiratory muscles are weakened and bronchial secretions

are profuse during RTI´s patients often need to NIV continuously at these times both to

maintain alveolar ventilation and for air stacking to increase CPF (246, 363). If, when

using NIV at adequate delivered volumes the SpO2 is not above 94%, the desaturation is

not due to hypoventilation but to mucus accumulation especially during chest infections

and ARF(27, 47).

In hospital application, MAC has been described an effective first-line intervention for

NMD patients with ARF,(61, 246, 401, 478, 486-487). However, similar immediate

effects of this technique when applied at home during ARF have not been widely

explored. We hypothesized that MAC when applied at home, according to previous

protocols included in this thesis, can be efficient in treating NMD patients with acute

exacerbations due to secretion encumbrance. We questioned if MAC could normalize

SpO2 in time to avoid hospitalizations and reduce the number of deep airway suctions

in patients under continuous ventilatory support either by NIV or tracheostomy (study

nr 9).

Respiratory insufficiency appears in the course of NMD patients first during sleep and

then at a later stage during the day. Nocturnal only NIV produces 24-h effective blood-

gas improvement and symptom control for several years(15). However, in end-stage

respiratory muscle failure patients such as Duchenne muscular dystrophy (DMD),

amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy type 1 (SMA 1),

nocturnal NIV needs to be progressively extended during the day as increasing

ventilatory dependency develops(11, 16, 447, 488-489). Mouthpiece intermittent



positive pressure ventilation (IPPV) is the most important method of daytime

ventilatory support for patients who need ventilatory support continuously since

continuous NIV with a nasal or oronasal mask may create skin breakdown or may even

interfere with the patient’s social activity (87, 490-491).

Although mouthpiece IPPV is being used for ventilatory support since 1953 (42) very

few studies reported its use for long-term management(1, 87, 90, 491-492). Since

ventilatory support delivered noninvasively is the single most import inspiratory muscle

aid in patients with NMD routine evaluations are recommended to predict its

application and monitor its efficacy both for nocturnal only and continuous use(9).

Although nocturnal only NIV can benefit mildly affected patients, instead of increasing

the spans or switching to the use of volume-cycled ventilators for daytime mouthpiece

IPPV, when low span pressure assistance is no longer adequate and ventilator

dependence progresses to daytime use, clinicians conventionally recommend

tracheotomy(15, 493-496).

For the final work of this thesis and to conclude this line of research, we proposed to

analyse the historical evolution of practice regarding the use of noninvasive mechanical

ventilation (NIV) and complementary interventions for long-term full-time noninvasive

ventilatory support of patients with neuromuscular diseases (NMDs) with primary focus

on the three most common and severe disorders, that is, Duchenne muscular dystrophy

(DMD), amyotrophic lateral sclerosis (ALS), and spinal muscular atrophy type 1 (SMA

1). To reinforce the argument that noninvasive alternatives for ventilatory support and

secretion management are feasible and efficient, we aimed to analyze data from

different international centers that provide continuous NIV for this patient population as

an alternative to tracheostomy to prolong survival and develop conclusions and

recommendations that may permit its widespread use (study nr 10).



.

Questions

- Question 13 – Is home based MAC with oximetry feedback effective and can it be

safely applied by trained non professional caregivers in continuous ventilator

dependent NMD patients, according to specific indications? Answer described in

study nr 7

- Question 14 – What is the frequency use of home MAC in NMD patients? Do

patients under tracheostomy ventilation used it more than patients under NIV?

Answer described in study nr 7

- Question 15 – Is a telephone accessed integrated care, that include on-demand

consult and MI-E device rapid access, efficient and feasible for ALS patients?

Answer described in study nr 8

- Question 16 – Is a home on-demand MAC program cost effective and can it

produce significant cost savings when compared to continuous home MAC

prescription in ALS patients? Answer described in study nr 8.

- Question 17 – Can home MAC with oximetry feed-back be efficient in reverting

O2 desaturations related to secretion encumbrance during an acute exacerbation in

NMD patients under continuous ventilatory support either by NIV or tracheostomy?

Answer described in study nr 9.

- Question 18 – Are the effects of home MAC sufficient to avoid hospitalizations for

ARF episodes related to secretion encumbrance in NMD patients under continuous

ventilatory support either by NIV or tracheostomy? Answer described in study nr

9.



- Question 19 – During the last two decades, has there been an evolution of practice,

regarding the recommendations of continuous full time NIV and MAC for patients

with NMD? Answer described in study nr 10.

- Question 20 – What are the outcomes from international centers that provide

continuous full time NIV and MAC for patients with NMD? Answer described in

study nr 10.

Analyzing the body of works that support the line of research of this thesis, our main

goal was to achieve a continuum of care for patients with respiratory muscle weakness,

that, due to their severe ventilatory impairment, can benefit either in acute or chronic

settings, from specific evaluation protocols and management paradigms that include

NIV for ventilatory assistance and MAC for secretion management.



Study 1

Extubation of Patients with Neuromuscular Weakness:

A New Management Paradigm

John R. Bach, Miguel R. Gonçalves, Irram Hamandi, João Carlos Winck



DOI 10.1378/chest.09-2144 2010;137;1033-1039; Prepublished online December 29, 2009;Chest

Carlos WinckJohn Robert Bach, Miguel R. Gonçalves, Irram Hamdani and Joao Weakness : A New Management ParadigmExtubation of Patients With Neuromuscular

http://chestjournal.chestpubs.org/content/137/5/1033.full.htmlservices can be found online on the World Wide Web at: The online version of this article, along with updated information and

ISSN:0012-3692)http://chestjournal.chestpubs.org/site/misc/reprints.xhtml(

of the copyright holder.may be reproduced or distributed without the prior written permission Northbrook, IL 60062. All rights reserved. No part of this article or PDFby the American College of Chest Physicians, 3300 Dundee Road,

2010Physicians. It has been published monthly since 1935. Copyright is the official journal of the American College of ChestCHEST



CHEST Original ResearchCRITICAL CARE MEDICINE

www.chestpubs.org CHEST / 137 / 5 / MAY, 2010 1033

Conventional extubation attempts follow successful “spontaneous breathing trials” (SBTs) and the

passing of ventilator weaning parameters, 1 otherwise patients undergo tracheotomy. Patients are often extubated to supplemental oxygen and bilevel positive airway pressure (PAP), but settings are infrequently reported,2 and extubation studies report very few if any patients with neuromuscular disease (NMD) (eg, 18 of 162, 3 17 of 900 4 ) and completely exclude unweanable patients. 5-7

Patients with preexisting NMD make up only 4% to 12.5% of cases in critical care, 8-10 but about 25%

in weaning centers. 11 While acquired critical care myopathy (CCM) is common, it is an often unrecog-nized12,13 cause of extubation failure by conventional approaches.14-16

There are no guidelines for extubating unweanable patients with NMD and CCM. Many are dependent on noninvasive mechanical ventilation (NIV) with no autonomous breathing ability for years before being intubated, and they refuse tracheotomy. 17-20 Further, these patients can have ineffective cough peak fl ows (CPFs), which can result in extubation failure due to airway secretion accumulation, 21-24 but very few studies

Background: Successful extubation conventionally necessitates the passing of spontaneous breath-ing trials (SBTs) and ventilator weaning parameters. We report successful extubation of patients with neuromuscular disease (NMD) and weakness who could not pass them . Methods: NMD-specifi c extubation criteria and a new extubation protocol were developed. Data were collected on 157 consecutive “unweanable” patients, including 83 transferred from other hospitals who refused tracheostomies. They could not pass the SBTs before or after extubation. Once the pulse oxyhemoglobin saturation (Sp o 2) was maintained at � 95% in ambient air, patients were extubated to full noninvasive mechanical ventilation (NIV) support and aggressive mechani-cally assisted coughing (MAC). Rather than oxygen, NIV and MAC were used to maintain or return the Sp o 2 to � 95%. Extubation success was defi ned as not requiring reintubation during the hospitalization and was considered as a function of diagnosis, preintubation NIV experience, and vital capacity and assisted cough peak fl ows (CPF) at extubation. Results: Before hospitalization 96 (61%) patients had no experience with NIV, 41 (26%) used it , 24 h per day, and 20 (13%) were continuously NIV dependent. The fi rst-attempt protocol extubation success rate was 95% (149 patients). All 98 extubation attempts on patients with assisted CPF� 160 L/m were successful. The dependence on continuous NIV and the duration of depen-dence prior to intubation correlated with extubation success ( P , .005). Six of eight patients who initially failed extubation succeeded on subsequent attempts, so only two with no measurable assisted CPF underwent tracheotomy. Conclusions: Continuous volume-cycled NIV via oral interfaces and masks and MAC with oxime-try feedback in ambient air can permit safe extubation of unweanable patients with NMD. CHEST 2010; 137(5):1033–1039

Abbreviations: ALS 5 amyotrophic lateral sclerosis; CCM 5 critical care myopathy; CPF 5 cough peak fl ows; IPPV 5

intermittent positive pressure ventilation; MAC 5 mechanically assisted coughing; NIV 5 noninvasive mechanical ventila-tion; NMD 5 neuromuscular disease; PAP 5 positive airway pressure; SBT 5 spontaneous breathing trial; SMA 1 5 spinal muscular atrophy type 1; S p o 2 5 pulse oxyhemoglobin saturation; VC 5 vital capacity

Extubation of Patients With Neuromuscular Weakness

A New Management Paradigm

John Robert Bach , MD ; Miguel R. Gonçalves , PT ; Irram Hamdani , MD ; and Joao Carlos Winck , MD , PhD



1034 Original Research

a CPF , 160 L/m were offered extubation if acknowledging that three extubation failures would necessitate tracheotomy. Other, at least temporary, exclusion criteria were medical instability, inadequate cooperation, and imminent surgery. 20,35

Protocol

While intubated, sufficient ventilatory support was used to maintain normocapnia and normal respiratory rates. MAC (CoughAssist; Respironics, Inc.; Murrysville, PA) was used at 40 to 2 40 cm H 2 O or greater to rapidly achieve clinically full chest expansion to clinically complete emptying of the lungs, with exsuffl ation-timed abdominal thrusts. The MAC sessions were up to every 20 min to maintain or return the pulse oxyhemoglobin saturation ( S p o

2 ) to � 95% in ambient air. Tracheotomy would

have been recommended if the Table 1 criteria could not be met within 2 weeks of transfer.

Once the Table 1 criteria were met, the orogastric or nasogas-tric tube was removed to facilitate postextubation nasal NIV. The patient was then extubated directly to NIV on assist/control of 800 to 1,500 mL, at a rate of 10 to 14 min in ambient air. Pressure control of at least 18 cm H 2 O was used if abdominal distension developed. The NIV was provided via a combination of nasal, oro-nasal, and mouthpiece interfaces. 36 Assisted CPF and CPF obtained by abdominal thrust following “air stacking” were measured within 3 h as the patient received full volume-cycled NIV support. Patients kept 15-mm angled mouthpieces accessible ( Fig 1 ), and weaned themselves, when possible, by taking fewer and fewer IPPVs as tolerated. Diurnal nasal IPPV was used for those who could not secure the mouthpiece. Patients took as much of the delivered vol-umes as desired. They used nasal or oronasal interfaces ( Figs 2, 3 ) for nighttime ventilation. For episodes of Sp o 2 , 95%, ventilator positive inspiratory pressure, interface or tubing air leakage, CO 2retention, ventilator settings, and MAC were considered.

Patients were taught to maximally expand their lungs by air stacking (retaining consecutive) ventilator delivered volumes to the largest volume the glottis could hold. 37 Once the lunges were air stacked, an abdominal thrust was provided to manually assist the cough, 29,37 and these assisted CPFs were measured. For patients using pressure-cycling, air stacking volumes were provided by manual resuscitator. The therapists, nurses, and in particular, the family and personal care attendants provided MAC via oro-nasal interfaces up to every 20 min until the Sp o 2 no longer dipped below 95% and the patients felt clear of secretions. In seven cases, the postextubation oral intake was considered unsafe, so open

have reported CPF 2,21 and none systematically used mechanically assisted coughing (mechanical insuffl ation-exsuffl ation with exsuffl ation-timed abdominal thrust) (MAC).4,24 There are no “ventilator weaning parameters” that address the ability to expel secretions. With success in decannulating unweanable patients with traumatic tetraplegia and others to continuous MAC and NIV, which includes noninvasive intermittent positive pressure ventilation (IPPV) and high-span bilevel PAP, 20,25-27 we used similar criteria to extubate unweanable patients with NMD and CCM and report the success rates.

Materials and Methods

The data were gathered in two centers, with 113 patients in New Jersey and 44 in Portugal, using the inclusion criteria described in Table 1 . The study was approved by the institutions’ review boards. All intubated patients were treated conventionally except for the use of MAC via the tube. Although virtually unknown in critical care, MAC has been instrumental in avoiding pneumonia, respiratory failure, and hospitalizations for NIV-dependent patients with NMD. 28-30 Vital capacities (VCs) (Wright Mark 3 spirometer; Ferraris Ltd; London, England) and unas-sisted and assisted CPFs (Access Peak Flowmeter; Health Scan Products Inc.; Cedar Grove, NJ) were measured within 12 months before intubation for the local patients (group 1). The other 83 intubated patients were transferred intubated from other hospitals after one to four failed extubation attempts (group 2) or after failing multiple SBTs (group 3).

VC was measured via the tube with the cuff infl ated following clearing of the airways by MAC just prior to extubation. Patients were ready for extubation and inclusion in this study only when all Table 1 criteria were satisfi ed and SBTs failed, as described. 31-33

Patients had to experience immediate distress, precipitous oxyhe-moglobin desaturation, and hypercapnia without stabilization before return to full ventilatory support both before and immediately postextubation. Local patients were considered to be group 1 because their greater experience with NIV and MAC could have affected outcomes. All transferred patients had been told that extubation and survival were not possible without tracheotomy.

We reported that the risk for extubation failure is high when assisted CPF cannot attain 160 L/m. 22 Considering that patients with advanced averbal bulbar amyotrophic lateral sclerosis (ALS) can rarely attain a CPF of 160 L/m 34,35 we generally did not accept such patients for transfer (exclusion criteria). Local patients with

Manuscript received September 11, 2009; revision accepted November 29, 2009. Affiliations: From the Department of Physical Medicine and Rehabilitation (Dr Bach ) and the Department of Medicine (Dr Hamdani), University of Medicine and Dentistry of New Jersey–the New Jersey Medical School, Newark, NJ; and the Lung Function and Ventilation Unit, Pulmonary Medicine Department, Intensive Care and Emergency Department (Mr Gonçalves ), and the Pulmonary Medicine Department (Dr Winck), Faculty of Medicine University, Hospital of S. João, Porto, Portugal. Correspondence to: John R. Bach, MD, Department of Physical Medicine and Rehabilitation, University Hospital B-403, 150 Bergen St, Newark, NJ 07103; e-mail: [email protected] © 2010 American College of Chest Physicians. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians ( www.chestpubs.org/site/misc/reprints.xhtml ). DOI: 10.1378/chest.09-2144

Table 1— Extubation Criteria for Unweanable Ventilator-Dependent Patients

Afebrile and normal WBC countAged 4 y and olderNo ventilator-free breathing tolerance with 7-cm pressure support in ambient air on the basis of NMD or CCMVC, 20% of normalPaco2 � 40 mm Hg at peak inspiratory pressures , 35 cm H 2 O on full-setting assist/control mode at a rate of 10-13/minSpo2 � 95% for 12 h or more in ambient airAll oxyhemoglobin desaturations , 95% reversed by MAC and suctioning via translaryngeal tubeFully alert and cooperative, receiving no sedative medicationsChest radiograph abnormalities cleared or clearingAir leakage via upper airway suffi cient for vocalization upon cuff defl ation

CCM5 critical care myopathy; MAC 5 mechanically assisted coughing; NMD5 neuromuscular disease; S p o

25 pulse oxyhemoglobin saturation;

VC5 vital capacity.




in means were compared using the Wilcoxon rank test. A P value � .05 was considered signifi cant. Univariate comparisons of potential predictive factors for failure or success were run with the Fisher exact test for categorical variables and the Wilcoxon rank-sums test for continuous variables.

Results

The 157 patients, mean age 37 6 21 years, included 139 (89%) with NMD who were intubated for acute respiratory failure and compromise due to pneumo-nia and/or surgery and 18 patients with CCM (11%). The 74 local patients (group 1) were intubated at our institutions, and 83 others were intubated elsewhere. Demographic data are in Table 2 . VC and CPF data are in Table 3 . Twenty (13%) of the 157 patients had been continuously NIV dependent for 12.2 years (range5 1-47) before being intubated. Forty-one (26%) used NIV part-time ( , 24 h/d), and 96 (61%) used no NIV before intubation. All patients satisfi ed the Table 1 criteria in , 2 weeks.

Univariate comparisons of potential predictive fac-tors for extubation success yielded signifi cant differ-ences for continuous NIV use ( P , .0001) and for the duration of continuous NIV use and MAC use prior to intubation ( P5 .0038), indicating that experience with NIV and MAC was signifi cant in predicting suc-cess. Given only 15 failures in eight patients, it was not possible to run multivariable logistic regression models considering diagnosis, patient group, VC, and CPF.

Of 172 extubations on 157 patients, all 98 on patients with assisted CPF � 160 L/m were successful. Fifty-nine of 74 attempts (80%) on patients with CPF, 160 L/m were successful, including 52 of 60 (87%) at fi rst extubation. Six patients who initially failed, succeeded on second (four patients) and third (three patients) attempts. One with advanced bulbar ALS and one with facioscapulohumeral muscular dys-trophy, both with no measurable assisted CPF, failed a total of fi ve extubations and underwent tracheotomy. Only one of the eight who failed any extubation attempt had preintubation experience with NIV and MAC, but she and several others had suboptimal postextubation care provider support for aggressive MAC. She and eight patients with bulbar ALS with little residual bulbar-innervated muscle function required oro-nasal interfaces for a closed system of postextuba-tion NIV (Hybrid NE; Telefl ex Medical; Research Triangle Park, NC) ( Fig 2 ). All nine had gastrostomy tubes for total enteral nutrition. One lip-seal nocturnal NIV user for 28 years prior to intubation was extubated back to lip-seal NIV ( Fig 3 ). 36

Data on VC, CPF, and duration of NIV use as a function of postextubation weaning capacity are included in Table 4 . Weaning from full-time to part-time

modifi ed Stamm gastrostomies were performed under local anes-thesia using NIV, as in Figure 2, without complication. 38

Extubation was considered successful if the patient was dis-charged without reintubation. When reintubation was necessary, the patient was again extubated after achieving the Table 1 criteria. Multiple failures necessitated tracheotomy. Extubation success was considered as a function of diagnosis, patient group, VC, CPF, and preintubation NIV experience. VC was measured 3 to 6 months after extubation. The total days intubated were compared pre-transfer and posttransfer.

Statistical Analysis

Results are expressed as mean 6 SD. Statistical analyses were carried out using SPSS 12.0 (SPSS, Inc.; Chicago, IL). Differences

Figure 1. A 10-year-old girl with neurofi bromatosis status post-spinal cord tumor resection, extubated with a vital capacity (VC) of 180 mL and no ventilator-free breathing ability, using a 15-mm angled mouthpiece (Malincrodt-Puritan-Bennett; Pleasanton, CA) for ventilatory support. Current VC 380 mL and minimal ventilator-free breathing ability. The patient provided written consent for the use of this photograph.

Figure 2. A 20-year-old man with Duchenne muscular dystrophy transferred for extubation after failing three extubations over a 26-day period. He used a 15-mm angled mouthpiece, as in Figure 1 , for daytime ventilatory support and a lip-seal phalange with nasal prongs for nocturnal ventilatory support. His VC was 260 mL at extubation in October 2007 and 720 mL in July 2009. See Figure 1 legend for expansion of the abbreviation. The patient provided written consent for the use of this photograph.




and 97 6 39 L/m (range 0-150), respectively. No clin-ically or radiographically apparent barotrauma was noted for any patients.

The 83 patients in groups 2 and 3 had been intu-bated for 11 6 9.1 days (range 5 1-80) before transfer and 2 6 1 days (range 5 1-11) on our units before extu-bation ( P , .005). Upon admission, on 21% fraction of inspired O 2 , 71 (85%) of the patients’ Sp o2 levels set-tled below 95%. Increased NIV support to normalize CO2 and especially MAC normalized Sp o2 generally within 24 to 48 h to satisfy a criterion for extubation.

The intensivists and respiratory therapists esti-mated that noninvasive treatment necessitated more time than invasive respiratory treatment. The extuba-tion itself required about 1.5 h for a specifi cally trained respiratory therapist to train the patients and care providers in NIV and MAC. In part because only one local nursing/rehabilitation facility would accept NIV users, all except one patient who had a tracheo-stomy were discharged home. One hundred thirty-one patients are alive using NIV ( Table 4 ). Nine patients (6%) died of cardiac failure, six (4%) from lung disease/respiratory failure, two (2%) with bulbar ALS died after tracheotomy from sepsis and decubiti, and nine (6%) died of unknown causes. Although offered, no patients accepted tracheotomy following successfulextubation.

Discussion

There are no extubation studies on continuously NIV-dependent patients with NMD. 6 A recent controlled

NIV took 3 to 21 days and was usually accomplished at home. As supine VC increased to approach 1,000 mL, we encouraged patients to sleep without NIV but with Sp o2 and end-tidal CO 2 monitoring, and when these remained stable for 2 weeks to discontinue NIV. The mean extubation VCs and assisted CPFs for the 29 patients � 18 years of age who were suc-cessfully extubated at fi rst attempt despite assisted CPF, 160 L/m were 245 6 114 mL (range 120-620)

Figure 3. A 59-year-old woman with spinal cord injury at birth and 31 years of dependence on a daytime mouthpiece and noctur-nal lip-seal (seen here) ventilation. She was extubated back to noninvasive mechanical ventilation despite a VC of 130 mL and no autonomous breathing ability and continued to use simple 15-mm angled-mouthpiece ventilation for daytime ventilatory support and lip-seal ventilation overnight with the nose clipped to prevent air leakage. Current VC is 340 mL. She is employed full-time as a psychologist. See Figure 1 legend for expansion of the abbreviation. The patient provided written consent for the use of this photograph.

Table 2— Demographic Data

Characteristics Group 1 a Group 2 b Group 3 c Total

Subjects, No. (%) 74 (47) 45 (29) 38 (24) 157 (100)Sex, No. (%) 52 male (70) 28 male (62) 17 male (45) 97 male (62)

22 female (30) 17 female (38) 21 female (55) 60 female (38)Diagnoses, No. (%) ICUMy, 15 (20) SMA, 10 (22) SMA, 10 (26) SMA, 25 (16)

SCI, 13 (18) MD, 9 (20) DMD, 9 (24) MD, 22 (14)ALS, 11 (15) DMD, 8 (18) MD, 5 (13) DMD, 20 (13)MG, 9 (12) MG, 6 (13) PPS, 5 (13) SCI, 17 (11)MD, 8 (11) PPS, 4 (9) oNMD, 4 (11) ALS, 16(10)

oNMD, 8 (11) oNMD, 4 (9) SCI, 3 (8) oNMD, 16 (10)SMA, 5 (7) ALS, 3 (7) ALS, 2 (5) ICUMy, 15 (10)DMD, 3 (4) SCI, 1 (2) . . . MG, 15 (10)PPS, 2 (3) . . . . . . PPS. 11 (7)

Use of NIV preintubation, No. (%) No NIV, 51 (69) No NIV, 24 (53) No NIV, 21 (55) No NIV, 96 (61)Cont, 10 (14) Cont, 7 (16) Cont, 3 (8) Cont, 20 (13)Noct, 13 (17) Noct, 14 (31) Noct, 14 (37) Noct, 41 (26)

ALS5 amyotrophic lateral sclerosis; Cont 5 continuous noninvasive ventilation; DMD 5 Duchenne muscular dystrophy; ICUMy 5 ICU-acquired neuromuscular disease; MD 5 muscular dystrophy; MG 5 myasthenia gravis; NIV 5 noninvasive ventilation; Noct 5 nocturnal noninvasive ventilation;oNMD5 other neuromuscular disease; PPS 5 postpolio syndrome; SCI 5 spinal cord injury; SMA 5 spinal muscular atrophy, including types 1, 2, and 3, and other neuromuscular disease.a Local patients.b Patients transferred after failing extubations in other institutions.c Patients transferred after failing multiple spontaneous breathing trials in other institutions.




acutely increase VC and Sp o2 .30,40,41 Our success stemmed not only from providing continuous full-setting NIV via a variety of interfaces but also from frequent and aggressive MAC to expel secretions and maintain or return Sp o2 . 95%.

In our earlier study of extubation/decannulation to NIV, considering the extent of need for NIV, age, VC, and maximum assisted CPF, only assisted CPF � 160 L/m predicted success in 62 extubation/decannulation attempts on 49 consecutive patients, including 34 with no ventilator-free breathing ability. 22 None of the 15 attempts on those with maximum CPF , 160 L/m succeeded, as opposed to an 87% fi rst-attempt extu-bation success rate in this study. The most likely rea-sons for the difference between then and now are: baseline Sp o2 criterion for extubation of 92% vs 95%, and thus the earlier patients had more residual airway secretions or lung disease at extubation; 5% vs 39% of patients with pre-extubation experience with NIV and MAC; less hospital staff experience with NIV and MAC; 50 of 62 patients were decanulated, not extu-bated; the patients were in various hospital locations; and MAC was used less often and without family involvement.22

The 87% fi rst-attempt extubation success rate on patients with maximum CPF , 160 L/m in this study is greater than the 82.4% (61 of 74) success rate reported for extubating NIV-dependent infants with spinal muscular atrophy type 1 (SMA 1), according to an almost identical protocol. 42 The difference may be the result of the ability of these patients, as opposed to babies, to cooperate with NIV and MAC. The SMA 1 infants may have also had more severe bulbar-innervatedmuscle dysfunction. Thus, while higher than those

postextubation respiratory failure study of 106 patients included only two with restrictive syndromes, but none with NMD, and all had passed SBTs. They were extubated to supplemental O 2 alone or in con-junction with bilevel PAP at spans up to 14 cm H 2 O, pressures inadequate for normal alveolar ventilation for our patients. 39 A metaanalysis of 12 extubation studies to bilevel PAP demonstrated decreased mortality, ventilator-associated pneumonia, length of stay, and resort to tracheotomy, but unweanable patients with NMD were uniformly excluded. 6 Eligi-bility for extubation was based on “readiness for weaning” and failure of SBTs after 30 min or more. 6

While this justifies extubation to NIV for patients who primarily have lung/airways disease with some autonomous breathing ability and for whom Spo2 . 90% may be acceptable with or without sup-plemental O 2 , our patients had no ability to sustain breathing before or after extubation with VCs as low as 0 mL. Thus, no control group extubation to O 2 or less than full NIV would be possible, ethical, or per-missible by any review board. While there are always limitations of uncontrolled studies when comparing two approaches, this was a study of only one approach to extubate patients not previously considered extu-batable. For our long-term NIV users, aspiration causing persistent Sp o2 , 95% despite continuous NIV and MAC in ambient air is the indication for tracheotomy.35

Besides hypoventilation, ineffective CPF have been associated with extubation failure. 21,22 MAC is essentially noninvasive suctioning via noninvasive or invasive interfaces. It can clear the left airways that are often not cleared by invasive suctioning and can

Table 3— Pulmonary Function

Characteristics Group 1 a Group 2 b Group 3 c Total

Subjects, n (%) 74 (47%) 45 (29) 37 (24%) 157Assisted CPF at extubation, L/min 1876 85 1626 86 1786 62 1776 77VC at extubation, mL 3556 171 2736 189 2956 155 3156 173VC 3-6 mo postextubation, mL 1,1216 748 7096 679 6176 412 8776 698

Intergroup differences were not statistically signifi cantly different except for postextubation VC, with that of group 1 being greater than for groups 2 and 3 ( P , .05). CPF 5 cough peak fl ows. See Table 1 for expansion of the other abbreviation.a Local patients.b Patients transferred after failing extubations in other institutions.c Patients transferred after failing multiple spontaneous breathing trials in other institutions.

Table 4— Postextubation Long-Term Noninvasive Ventilation Use for 155 Patients

Characteristics Weaned in 1 wk Weaned to Part-Time NIV Unweanable

Subjects, n 23 62 72VC at extubation, mL 4236 157 3446 152 2596 179CPF at extubation, L/min 2046 58 1796 73 1586 85VC 6 mo postextubation, mL 17976 683 8966 649 5026 353Duration ventilator use, mo (range) . . . 486 55 (1-204) 716 62 (1-228)

See Tables 1 and 3 for expansion of abbreviations.




Dr Winck: oversaw the extubations on all of the Portuguese patients and added material to the introductory and “Discussion” sections of the manuscript. Financial /nonfi nancial disclosures: The authors have reported to CHEST the following confl icts of interest: Respironics, Inc, is the manufacturer of the CoughAssist, a device mentioned in this article. Dr Winck has been reimbursed by Respironics, Inc, for attending a sleep conference, received 4,500€ for organizing two postgraduate courses on noninvasive ventilation for Respironics, Inc, and received 500€ for lectures in a conference sponsored by Respironics, Inc. Mr Gonçalves received lecture honoraria of 4,000€ from Respironics, Inc, for two postgraduate courses on noninvasive ventilation. Drs Bach and Hamdani have reported no confl icts of interest exist with any companies/organizations whose products or services may be discussed in this article. Other contributions: We wish to thank Teresa Honrado, MD; Teresa Oliveira, MD; and Celeste Dias, MD, as well as the ICU medical, respiratory therapy, and nursing staffs of both institutions for their assistance and support in treating the patients.

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for a comparable infant population, the success rate was signifi cantly less (87% vs 100%) ( P , .05) than for patients with assisted CPF � 160 L/m. Unmeasur-able assisted CPFs indicate an inability to close the glottis and are associated with stridor, saliva aspira-tion, and less effective NIV and MAC.

An NIV/MAC protocol has been used to avoid over 100 hospitalizations for continuously ventilator-dependent (NIV) patients with NMD. 20,35 Here we considered unweanable patients with NMD for whom intubation could not be avoided. Upon extubation, most patients with a VC of 200 mL or more eventually were weaned from continuous to part-time NIV by taking fewer and fewer mouthpiece IPPVs. Thus, the paradigm of weaning then extubation can be changed to extubation to permit self-weaning for patients with NMD. The notion that early tracheotomy after intu-bation somehow facilitates ventilator weaning 43 should be reassessed for patients with NMD. NIV is also associated with over 75% fewer ventilator-associated pneumonias.6,44 Use of mouthpieces rather than “masks” interfaced in acute-care facilitated speech, oral intake, comfort, and glossopharyngeal breathing 45 ; elimi-nated the risk of skin pressure sores; and permitted air stacking to maintain pulmonary compliance, 37,45

diminish atelectasis, and facilitate manually assisted coughing.

The purpose here was not to facilitate ventilator weaning or to consider long-term outcomes, but to extubate unweanable patients. Benefi ts included no mortality, fewer days intubated, no tracheostomies, and return home. Decannulation, too, can facilitate ventilator weaning. 46 Avoidance of tracheostomy for continuous ventilator (NIV) users can also better maintain quality of life, 47-49 significantly diminish long-term pneumonia and respiratory hospitalization rates,50 maximize ventilator-free breathing, 46 and facilitate return home. 49

In conclusion, unweanable intubated patients with NMD who satisfy specifi c criteria can be successfully extubated to full NIV and MAC. Patients with mea-surable assisted cough fl ows should no longer be advised to refuse intubation for fear of extubation failure and tracheotomy. We no longer consider tracheotomy for any ventilator-dependent patients with NMD who satisfy Table 1 criteria, and now offer extubation to most with CPF , 160 L/m.

Acknowledgments

Author contributions: Dr Bach: wrote all drafts of the paper and, with Dr Hamdani, extubated all the patients in New Jersey. Mr Gonçalves: performed the extubations on all of the patients in Portugal, gathered data on the Portuguese patients, and added material to the text of the manuscript. Dr Hamdani: performed the extubations on some of the patients in New Jersey, gathered data on the New Jersey patients, and added material to the text of the manuscript.




14 . Simonds AK . Streamlining weaning: protocols and weaning units . Thorax . 2005 ; 60 ( 3 ): 175 - 182 .

15 . Winck JC , Gonçalves M . Muscles and lungs: fatal attrac-tion, but time for intervention . Monaldi Arch Chest Dis . 2005 ; 63 ( 3 ): 121 - 123 .

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17 . Benditt JO , Boitano L . Respiratory treatment of amyotrophic lateral sclerosis . Phys Med Rehabil Clin N Am . 2008 ; 19 ( 3 ): 559 - 572 .

18 . Benditt JO . Full-time noninvasive ventilation: possible and desirable . Respir Care . 2006 ; 52 ( 9 ): 1012 - 1015 .

19 . Soudon P , Steens M , Toussaint M . A comparison of invasive ver-sus noninvasive full-time mechanical ventilation in Duchenne muscular dystrophy . Chron Respir Dis . 2008 ; 5 ( 2 ): 87 - 93 .

20 . Gomez-Merino E , Bach JR . Duchenne muscular dystrophy: prolongation of life by noninvasive ventilation and mechani-cally assisted coughing . Am J Phys Med Rehabil . 2002 ; 81 ( 6 ): 411 - 415 .

21 . Smina M , Salam A , Khamiees M , Gada P , Amoateng-Adjepong Y , Manthous CA . Cough peak fl ows and extubation outcomes . Chest . 2003 ; 124 ( 1 ): 262 - 268 .

22 . Bach JR , Saporito LR . Criteria for extubation and tracheos-tomy tube removal for patients with ventilatory failure. A dif-ferent approach to weaning . Chest . 1996 ; 110 ( 6 ): 1566 - 1571 .

23 . Salam A , Tilluckdharry L , Amoateng-Adjepong Y , Manthous CA . Neurologic status, cough, secretions and extubation out-comes . Intensive Care Med . 2004 ; 30 ( 7 ): 1334 - 1339 .

24 . Ferrer M , Esquinas A , Arancibia F , et al . Noninvasive venti-lation during persistent weaning failure: a randomized con-trolled trial . Am J Respir Crit Care Med . 2003 ; 168 ( 1 ): 70 - 76 .

25 . Bach JR , Alba AS . Noninvasive options for ventilatory sup-port of the traumatic high level quadriplegic patient . Chest . 1990 ; 98 ( 3 ): 613 - 619 .

26 . Bach JR . New approaches in the rehabilitation of the traumatic high level quadriplegic . Am J Phys Med Rehabil . 1991 ; 70 ( 1 ): 13 - 19 .

27 . Bach JR . Amyotrophic lateral sclerosis: prolongation of life by noninvasive respiratory AIDS . Chest . 2002 ; 122 ( 1 ): 92 - 98 .

28 . Tzeng AC , Bach JR . Prevention of pulmonary morbidity for patients with neuromuscular disease . Chest . 2000 ; 118 ( 5 ): 1390 - 1396 .

29 . Bach JR . Mechanical insuffl ation-exsuffl ation. Comparison of peak expiratory fl ows with manually assisted and unassisted coughing techniques . Chest . 1993 ; 104 ( 5 ): 1553 - 1562 .

30 . Winck JC , Gonçalves MR , Lourenço C , Viana P , Almeida J , Bach JR . Effects of mechanical insuffl ation-exsuffl ation on respiratory parameters for patients with chronic airway secre-tion encumbrance . Chest . 2004 ; 126 ( 3 ): 774 - 780 .

31 . Ely EW , Baker AM , Dunagan DP , et al . Effect on the dura-tion of mechanical ventilation of identifying patients capable of breathing spontaneously . N Engl J Med . 1996 ; 335 ( 25 ): 1864 - 1869 .

32 . Meade M , Guyatt G , Sinuff T , et al . Trials comparing alterna-tive weaning modes and discontinuation assessments . Chest . 2001 ; 120 ( 6 Suppl ): 425S - 437S .

33 . MacIntyre NR , Cook DJ , Ely EW Jr , et al ; American College of Chest Physicians ; American Association for Respiratory Care ; American College of Critical Care Medicine . Evidence-

based guidelines for weaning and discontinuing ventilatory support: a collective task force facilitated by the AmericanCollege of Chest Physicians; the American Association for Respiratory Care; and the American College of Critical Care Medicine . Chest . 2001 ; 120 ( 6 Suppl ): 375S - 395S .

34 . Sancho J , Servera E , Díaz J , Marín J . Predictors of ineffec-tive cough during a chest infection in patients with stable amyotrophic lateral sclerosis . Am J Respir Crit Care Med . 2007 ; 175 ( 12 ): 1266 - 1271 .

35 . Bach JR , Bianchi C , Aufi ero E . Oximetry and indications for tra-cheotomy for amyotrophic lateral sclerosis . Chest . 2004 ; 126 ( 5 ): 1502 - 1507 .

36 . Bach JR , Alba AS , Saporito LR . Intermittent positive pressure ventilation via the mouth as an alternative to tracheostomy for 257 ventilator users . Chest . 1993 ; 103 ( 1 ): 174 - 182 .

37 . Bach JR , Kang SW . Disorders of ventilation: weakness, stiff-ness, and mobilization . Chest . 2000 ; 117 ( 2 ): 301 - 303 .

38 . Bach JR , Gonzalez M , Sharma A , Swan K , Patel A . Open gas-trostomy for noninvasive ventilation users with neuromuscular disease . Am J Phys Med Rehabil . 2010 ; 87 ( 1 ): 1 - 6 .

39 . Ferrer M , Sellares J , Valencia M , et al. Non-invasive venti-lation after extubation in hypercapnic patients with chronic respiratory disorders: randomised controlled trial. Lancet. 2009 ; 374 (9695): 1044 - 1045 .

40 . Bach JR , Ishikawa Y , Kim H . Prevention of pulmonary mor-bidity for patients with Duchenne muscular dystrophy . Chest . 1997 ; 112 ( 4 ): 1024 - 1028 .

41 . Servera E , Sancho J , Zafra MJ , Catalá A , Vergara P , Marín J . Alternatives to endotracheal intubation for patients with neu-romuscular diseases . Am J Phys Med Rehabil . 2005 ; 84 ( 11 ): 851 - 857 .

42 . Bach JR , Niranjan V , Weaver B . Spinal muscular atrophy type 1: a noninvasive respiratory management approach . Chest . 2000 ; 117 ( 4 ): 1100 - 1105 .

43 . Blot F , Melot C ; Commission d’Epidémiologie et de Recherche Clinique . Indications, timing, and techniques of tracheostomy in 152 French ICUs . Chest . 2005 ; 127 ( 4 ): 1347 - 1352 .

44 . Kollef MH . Avoidance of tracheal intubation as a strategy to prevent ventilator-associated pneumonia . Intensive Care Med . 1999 ; 25 ( 6 ): 553 - 555 .

45 . Bach JR , Bianchi C , Vidigal-Lopes M , Turi S , Felisari G . Lung infl ation by glossopharyngeal breathing and “air stacking” in Duchenne muscular dystrophy . Am J Phys Med Rehabil . 2007 ; 86 ( 4 ): 295 - 300 .

46 . Bach JR , Goncalves M . Ventilator weaning by lung expan-sion and decannulation . Am J Phys Med Rehabil . 2004 ; 83 ( 7 ): 560 - 568 .

47 . Bourke SC , Bullock RE , Williams TL , Shaw PJ , Gibson GJ . Noninvasive ventilation in ALS: indications and effect on quality of life . Neurology . 2003 ; 61 ( 2 ): 171 - 177 .

48 . Viroslav J , Rosenblatt R , Tomazevic SM . Respiratory man-agement, survival, and quality of life for high-level traumatic tetraplegics . Respir Care Clin N Am . 1996 ; 2 ( 2 ): 313 - 322 .

49 . Bach JR , Intintola P , Alba AS , Holland IE . The ventilator-assisted individual. Cost analysis of institutionalization vs rehabil-itation and in-home management . Chest . 1992 ; 101 ( 1 ): 26 - 30 .

50 . Bach JR , Rajaraman R , Ballanger F , et al . Neuromuscular ventilatory insuffi ciency: effect of home mechanical ventilator use v oxygen therapy on pneumonia and hospitalization rates . Am J Phys Med Rehabil . 1998 ; 77 ( 1 ): 8 - 19 .



DOI 10.1378/chest.09-2144; Prepublished online December 29, 2009; 2010;137; 1033-1039Chest

WinckJohn Robert Bach, Miguel R. Gonçalves, Irram Hamdani and Joao Carlos

Management ParadigmExtubation of Patients With Neuromuscular Weakness : A New

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Study 2

Noninvasive ventilation associated with mechanical

assisted cough for extubation and decannulation in high

spinal cord injury patients

Miguel R. Gonçalves, Tiago Pinto, Teresa Honrado, Teresa Oliveira,

Celeste Dias, Ana Maria Mota and João Carlos Winck

(Critical Care Medicine, submitted)



1

Noninvasive ventilation associated with mechanical

assisted cough for extubation and decannulation in

high spinal cord injury patients

Concise title: Extubation and decannulation in spinal cord injury

Authors: Miguel R. Gonçalves, Tiago Pinto, Teresa Honrado, Teresa Oliveira, Celeste

Dias, Ana Maria Mota and João Carlos Winck

Affiliation: Lung Function and Ventilation Unit, Pulmonology Department; Intensive

Care and Emergency Department;, Faculty of Medicine, University Hospital of S. João

Corresponding author:

Miguel R. Gonçalves Lung Function and Ventilation Unit – Pulmonary Medicine Department Intensive Care Unit – Emergency Department University Hospital of S. João Address: Av. Prof. Hernani Monteiro, Porto, Portugal Phone: 00351 225512100 (extension 1042); [email protected] [email protected]



2

Abstract

Purpose: to compare extubation vs. decannulation outcomes of continuously ventilator dependent (CVD) high level spinal cord injured (SCI) patients. Methods: 20 (3 females) CVD high level SCI patients with 44±16.3 years of age, were either extubated (n=13) or decannulated (n=7) to continuous noninvasive ventilation (NIV) and mechanically assisted coughing (MAC). Successful extubation/decannulation was defined by not requiring re-intubation/tracheotomy during hospitalization. Vital capacity (VC) and cough peak flows (CPF) were measured immediately (T1), at 48 hours (T2), and at 6 months (T3) after tube removal. Days using invasive ventilation, extubation/decannulation success rates, Intensive Care Unit (ICU) lengths of stay, days required for protocols and extent of ventilator dependence at discharge and after 6 months were analyzed. Readmissions and survival were evaluated at 1 year. Results: All extubations and decannulations were successful. Extubation required significantly fewer ICU days than decannulation. The VC, unassisted and assisted CPF at T1, T2 and T3 improved significantly more for the extubation than for the decannulation. Patients had comparable ASIA levels and VCs at T1 but the extubation group had significantly higher VC at T2 and unassisted and assisted CPF at T2 and T3. All patients were discharged home using either NIV or breathing autonomously. During the year follow-up, 1 extubated patient was hospitalized due to a respiratory tract infection (RTI) and 1 died. Two decanulated patients were hospitalized for a RTI and a stroke. None required critical care. Conclusions: Decannulation or avoidance of tracheostomy by extubation of CVD SCI patients can result in better respiratory outcomes.

Key-words: Noninvasive ventilation, Mechanical Insufflation-Exsufflation, Extubation,

Decannulation, Spinal Cord Injury.



3

Introduction

Ventilatory insufficiency and impaired airway secretion clearance are common

complications of high level spinal cord injury (SCI) and can lead to respiratory failure

in both the acute and chronic stages. Standard invasive ventilatory management options

include early intubation and tracheostomy for long term care [1].

High level SCI, ascending cord edema, spinal shock, and perhaps other factors

can result in progressive ventilatory insufficiency usually shortly after hospital

admission for SCI. Following intubation, failure to pass “spontaneous breathing trials

(SBTs)” and ventilator weaning parameters [2] is common and often results in

intubation and tracheostomy [1]. It is presumed that ventilator weaning is necessary

before patients can be safely extubated/decanulated [3]. However, more recently, a

successful extubation protocol was described for 157 continuously ventilator dependent

(CVD) patients who could not pass SBTs before or after extubation [4]. Further, in 1990

Bach et al. reported the decannulation of “unweanable” CVD high level spinal cord

injured (SCI) patients and their transition to non-invasive mechanical ventilation (NIV)

and mechanically assisted coughing (MAC) [5].

Mechanical assisted cough is the use of mechanical insufflation-exsufflation

(CoughAssistTM, Phillips Respironics International Inc., Murrysville, Pa) via invasive

tube or oronasal interface to fully expand and then fully empty the lungs, thereby

expelling airway secretions. An abdominal thrust is applied simultaneously with

exsufflation. By expelling secretions MAC can return SpO2 to normal, avoiding

respiratory failure [6-7], and solving atelectasis [8-9].

Other than for occasional use of bi-level positive airway pressure at less than

ventilatory support levels [10], there has been no further research in this domain.

Despite the fact that cough impairment is one of the most common reasons for



4

extubation failure and respiratory complications long-term, there have been few studies

that considered its evaluation[11-12] and the use of assisted coughing to facilitate

extubation/decannulation of CVD SCI patients[4,13]

The role of NIV in the ICU continues to increase as evidence accumulates

regarding the prevention of post-extubation respiratory failure [14-15]. However, few

studies focus on the role of NIV in extubation and decannulation of high level SCI

patients [16-17]. Since the patients in our study were CVD, total ventilatory support was

necessary following tube removal. Our purpose is to report and compare extubation and

decannulation success rates and outcomes of self-directed, CVD SCI patients using a

management protocol that included continuous full setting NIV and MAC to maintain

SpO2≥95% in ambient air [4,16].

Patients and Methods

This study received approval from the department and institutional review

boards. Twenty (3 females) consecutively admitted, CVD high level SCI patients with

44±16.3 years of age, who failed multiple SBTs were studied between 2004 to 2009.

There were 13 intubated patients (Group 1 –G1) and seven with tracheostomies (Group

2- G2). Besides CVD and failing multiple SBTs, inclusion criteria included the ability

to cooperate, medical stability, and the resolution of surgical issues. Exclusion criteria

were age less than 18 years, lung disease, lack of cooperation, traumatic head injury or

otherwise impaired cognition, and chest trauma. Patients’ SCI levels were established

according to American Spinal Injury Association (ASIA) criteria[18].

Vital capacity (VC) (Wright Mark 8 spirometer, Ferraris Ltd., London),

unassisted and assisted CPF (Access Peak Flow Meter, Health Scan Products Inc.,

Cedar Grove, New Jersey) were measured immediately (T1), at 48 hours (T2), and 6



5

months after tube removal (T3) for both groups. Assisted CPF were measured by having

the patient air stack to the maximum lung volumes[19] that could be held by the glottis

then have an abdominal thrust applied as they cough into a peak flow meter[20].

Extubation and decannulation success was defined by not requiring re-intubation

or re-cannulation during the same hospitalisation. The days using invasive mechanical

ventilation (MV), VC and (unassisted and assisted) CPF at T1, T2, and T3, ICU lengths

of stay, days required for extubation/decannulation, and extent of ventilator dependence

at discharge and 6 months later were compared for the two groups. One year incidence

of readmissions and survival is reported.

Extubation protocol:

Criteria for extubation were: normal white blood cell count, chest radiograph

abnormalities cleared or clearing, oxyhemoglobin saturation greater than or equal to

95% in ambient air, and afebrile[4].Once these criteria were met the nasogastric tube

was removed if present to facilitate immediate post-extubation nasal NIV, and

measurement of CPF and VC.

The extubation protocol included maintaining normal alveolar ventilation by full

ventilator support settings and using MAC (pressures 40 to 60 cm H2O to -40 to -60 cm

H2O with exsufflation-timed abdominal thrust) via the translaryngeal tube every 30 to

120 minutes as needed until SpO2 remained ≥95% in ambient air.

Patients were then extubated directly to mouth piece or nasal NIV with a

portable ventilator on pressure control with 18-20 cm H2O or assist/control mode with

800 to 1500 ml delivered volumes and a back up rate of 10 to 12 per minute[21]. For

mouth piece NIV patients kept 15mm or 22mm angled mouth pieces accessible to their

mouths (Figure 1). Patients weaned themselves, when possible, by taking fewer and



6

fewer mouth piece intermittent positive pressure ventilations (IPPVs) as needed. For

night-time ventilation patients used nasal, oral or oronasal interfaces. No supplemental

oxygen was used.

Patients were taught how to maximally expand their lungs by “air stacking”

(retaining consecutive) ventilator delivered volumes to the largest volume the glottis

could hold[19].Once the patient maximally air stacked, an abdominal thrust was timed

to glottic opening to manually assist the cough[20,22]. The respiratory therapy and

nursing staff were trained in and provided MAC via oro-nasal interfaces (Figure 2) post-

extubation until airway secretion elimination was no longer a problem and the SpO2 no

longer dipped below 95%. Generally, pressures of 40 to -40 cm H2O were used with an

exsufflation-timed abdominal thrust. All clinical staff used this strategy with oximetry

as feedback to maintain SpO2≥ 95%. Re-intubation was indicated for acute distress and

irreversible oxyhemoglobin desaturation.

Decannulation protocol:

Our protocol is similar to one previously described[16,23]. Besides having to

satisfy the same criteria as for extubation, all patients from G2 had to be able to

verbalize when the tube cuff was deflated, have effective swallow and be medically

stable. Normal alveolar ventilation was maintained by adequate ventilator settings.

Supplemental oxygen therapy was discontinued and MAC used via tube (with

cuff inflated) until SpO2 remained ≥95% in ambient. Through the tube MAC was used

at gauge pressures of 50 to 60 cm H2O to -50 to -60 cm H2O. All of the patients were

placed on portable volume-cycled ventilators or, when preferred by the patient, portable

pressure-cycled ventilators. The cuffs were completely deflated for increasing periods,

hourly, until cuff deflation could be tolerated both throughout daytime hours and



7

overnight. When necessary, the patient's tracheostomy tube diameter was changed to

permit sufficient leakage for speech while maintaining adequate fit to permit effective

assisted ventilation with delivered ventilator volumes generally of 1 to 2 liters to

compensate leaks through the upper airway. Ventilator parameters were set on

assist/control mode, rate 10 to 12, and were titrated to maintain paCO2 levels between

35 to 40 mm Hg. Tracheal integrity, tracheostomy tube width, volitional glottic and

vocal cord movements were evaluated through upper airway fiberoptic examination.

Patients were advanced to the use of 24 hour tracheostomy ventilation with a

fenestrated tracheostomy tube with a deflated cuff, and after that period they were

trained in the use of mouthpiece IPPV for daytime ventilatory support with the

tracheostomy tube capped and ventilator settings adjusted. Each patient learned to close

off the nasopharynx with the soft palate to prevent nasal leakage. Once daytime

mouthpiece IPPV was mastered, effective NIV during sleep through a nasal or oronasal

mask was also implemented. When the efficacy of continuous NIV had been observed

and before definitive decannulation, the tracheostomy tube was replaced by a

tracheostomy button that allowed more accurate measurement of VC and CPF.

After 48 hours, patients maintained NIV, the tracheostomy button was removed

and a compressive silicon material was placed over an occlusive tracheostomy site

dressing that was fit to avoid leaks. Although the tracheostomy site usually closed in 24

to 72 hours, if not closed after 2 weeks it was usually sutured closed.


Results are expressed as mean and standard deviation. Statistical analysis was

carried out using SPSS version 15.0 (SPSS, Inc, Chicago, IL). Differences between VC,

unassisted and assisted CPF, as well as ICU length of stay, days on invasive MV, days



8

on protocol and ventilatory dependence at discharge were compared using the Wilcoxon

rank test. A p value ≤ 0.05 was considered significant.

Results

Demographic data are in Table 1. There were no significant differences on age

and level of injury severity between groups and none of the patients had lung disease.

All patients failed multiple SBTs before the application of the protocols. Other than for

3 local patients, the tracheostomy patients were transferred to our ICU for

decannulation.

The patients required NIV for 43±8 and 45±7 of the first post-

extubation/decannulation 48 hours, respectively. Outcomes data are noted in Table 2.

Vital capacity, unassisted and assisted CPF over time are shown in Figures 3 and

4 respectively. Both patient groups had significant improvements in VC and unassisted

and assisted CPF from T1 to T2 and T2 to T3 (p<0,05). In addition, the extubated

patients had significantly higher VC at T2 (1.5±0.50L or 40±15% of predicted normal

vs. 0.9±0.4L or 24±8% of predicted normal, p<0.05), unassisted CPF (170±58L/min vs.

84±25L/min at T2, p<0.05; 247±60 L/min vs. 114±46 L/min at T3, p<0.05) and assisted

CPF (263±78L/min vs. 198±41L/min at T2, p<0.05; and 359±98 L/min vs. 226±74

L/min at T3, p<0.05) than the decanulated patients.

All patients were successfully extubated/decanulated with no respiratory

complications. Two decanulated patients’ stomas were sutured for final closure. All

were discharged home with caregivers proficient in providing NIV, manually assisted

cough and air-stacking, During the first post-discharge year, one extubated patient was

hospitalized for a RTI and 2 decanulated patients (one on nocturnal-only NIV) were

hospitalized, one for a RTI and the other for a stroke. None of the hospitalizations



9

resulted in intubation or critical care. One year post discharge, 1 extubated patient died

from non-respiratory causes and 2 were lost to follow up. All others were alive and

well.

Discussion

Seventy-four percent of ASIA A acute SCI patients above the C5 level have

been reported to require intubation[24]and the overall incidence of tracheostomy in

these cases was between 81 and 83%[3,25]. The number of respiratory complications in

SCI including ventilator associated pneumonia (VAP) during the acute phase

contributes significantly to both hospital length of stay and cost[26]. However, it is not

ventilator use that causes VAP but the invasive interface [27]. After the conversion to

NIV and MAC, none of the patients in this study developed pneumonia or other

respiratory complications during the hospitalization.

Guidelines for respiratory management after SCI were published in 2005[28].

However, the guidelines assumed the need for tracheostomy for unweanable CMV

patients. In 2006, Bach challenged the medical community to decanulate high level SCI

patients to NIV to avoid the complications of tracheostomy, to facilitate training in

glossopharyngeal breathing to increase autonomous breathing ability and security in the

event of ventilator failure, and to return home [13]This work is the first to accept this

challenge.

In this study, besides successful extubation and decannulation of CVD patients,

after the protocol, only 9 (45%) of the total population used NIV at discharge and all

others weaned to autonomous breathing. The use of high delivered NIV volumes has

been reported to facilitate the weaning process and lessen risk of respiratory

complications[29] as well as result in increased VC and CPF for patients who are



10

extubated[4] or decanulated[16,17,30] and our results are consistent with those studies.

Moreover, it is not expected that continuous NIV can be a successful alternative to

invasive ventilation, if patients use only mask ventilation[31]. Further, for both groups,

mouthpiece ventilation normalized speech, provided normal daytime ventilation,

permitted "air stacking" for lung expansion and assisted coughing, and

weaning[4,21,30].

Aggressive use of MAC via translaryngeal and tracheostomy tubes was the main

intervention that may have improved pulmonary function (VC and CPF) and normalized

SpO2 in ambient air to satisfy the most important criterion for

extubation/decannulation. Our findings are consistent with those of Bach et al.[16,32],

however our patients were all successfully extubated despite some having assisted CPF

below 160l/min at T1. This was possibly due to the more aggressive use of MAC up to

every 15 min to maintain normal SpO2. Pillastrini et al.[33], too reported that

mechanical in-exsufflation aided in clearance of bronchial secretions and increased

forced VC, forced expiratory volume in 1 second, and peak expiratory flows for

tracheostomized SCI subjects. Vital Capacity and CPF also improved in our patients

because of lung expansion and secretions removal.

Transition from tracheostomy to continuous NIV was progressive and implied a

specific protocol that included ventilation with a deflated cuff for increasing periods

until it could be tolerated throughout daytime hours and overnight.

This “open system” ventilation[34] permitted the patients to improve their vocal

cord function that was essential for successful NIV training with a capped cuffless

fenestrated tube. In 2004 we reported that decannulation and conversion to NIV and

MAC can facilitate ventilator weaning of CMV dependent patients[30]. It has also been

reported that decanulated patients invariably prefer NIV over return to tracheostomy



11

ventilation for safety, convenience, appearance, comfort, facilitating effect on speech,

sleep, and swallowing, and overall[35]. Despite this, until this study, no other has

described the systematic extubation/decannulation of CVD SCI patients to noninvasive

alternatives or the avoidance of tracheotomy for unweanable intubated patients.

In this study, both short –term and long term outcomes for the extubated patients

were better than for the decanulated patients. Thus, it appears preferable, in this patient

population, to prevent tracheotomy in the first place, whenever possible, rather than

decanulate later on. Certainly, patients with severe bulbar-innervated muscle

involvement, head injury, chest trauma, medical fragility, complicated courses including

the need for surgical procedures over a greater than 3 or 4 week period are best

managed by tracheotomy.

Our data show that the extubated SCI patients had significantly shorter ICU

stays, were more quickly extubated than the decanulated patients decanulated, had

higher VC at 48 hours after tube removal, higher unassisted and assisted CPF at 48

hours and at 6 months after tube removal than those decannulated. This can be due to

the fact that extubated patients had significant less time on invasive ventilation with

consequent less respiratory muscle deconditioning, were somehow less severely

affected despite comparable VCs and ASIA levels at T1, or had less risk of upper

airway instability and less secretion encumbrance or segmental atelectasis despite the

same CPF and normal SpO2. Moreover, the decanulated patients needed MAC to clear

airway secretions for longer periods of time as well as more time for NIV training and

tracheostomy site closure.

The higher values of VC at 48 hours after extubation explains the greater

number of extubated patients discharged to the community with no ventilatory support.



12

Although tracheostomy may have physiologic benefits over endotracheal tubes

in terms of reduced work of breathing[36]and permitting more efficient suctioning, over

90% of the time suction catheters enter only the right mainstem bronchus resulting in

80% of pneumonias occurring on the left lungs of these patients[37] and work of

breathing is readily compensated by providing pressure support during SBTs. There are

no reports of better outcomes with tracheostomy ventilation when compared to the

NIV/MAC protocols.

This study has the limitations by its retrospective nature and small number of

participants suggesting caution when generalizing the importance of its outcomes.

Considering the incidence of mortality and respiratory morbidity in this

population of SCI patients managed by standard ventilatory invasive techniques, the

results of this study suggest that noninvasive methods of assisted ventilation and

coughing can facilitate both extubation and decannulation with significant improvement

on ventilatory dependence and pulmonary function and may facilitate return home

rather than prolonged institutionalization for weaning attempts. Randomized controlled

trials to evaluate these precepts may be unethical since noninvasive management is

clearly effective.



13

Acknowledgments:

The authors wish to thank the medical, respiratory therapy and nursing staffs of

both ICU and Pulmonology departments for their assistance and support in managing

the patients.



14

Figure 1- Forty nine year old man with C4 ASIA A spinal cord injury extubated with

no ventilator-free breathing ability, using volume cycled ventilation through a 15 mm

angled mouth piece for ventilatory support.

Figure 2- Twenty- one year old man with a C3 ASIA A spinal cord injury, using post-

extubation mechanically assisted coughing (MAC) with the CoughAssistTM (Philips

Respironics International Inc.) via an oronasal interface at pressures of 40 to -40

cmH2O.



15

Figure 3 – Vital capacity at extubation (T1), after 48 hours (T2) and at 6months follow up (T3)

Legend: VC – Vital Capacity (Liters).

# - p<0,05; &- p<0,05; ¶ -p < 0.05

#

&

#

#

&

&

¶

¶



16

Figure 4- Unassisted and Assisted CPF data at extubation (T1), after 48 hours (T2) and at 6months follow up (T3)

Legend: CPF – Unassisted cough peak flow (L/min); AsCPF – Assisted cough peak flow (L/min). #1,#2,#3 – p <0,05; &1,&2,&3 – p <0,05 #2 and &2 – p <0,05; #3 and &3 – p <0,05

#1

#1

&1

#2

#2

#3

#3

&1

&2

&3

&2 &3



17

Table 1 – Demographic data

G1

G2

N 13 7

Age (years)

42±19

48±11

Sex, n (%)

FVC, Liters (%) *

male – 10 (77%)

female – 3 (23%)

0,5±0,6 (16±24)

male – 7 (100%)

0,2±0,3 (8±10)

FEV1/FVC (%) *

CPF (L/min) *

Level SCI, n (/%)

ASIA scale, n (/%)

88±5

64±64

C2-C3 – 4 (31%)

C4-C5 –8 (62%)

C6 -1 (7%)

A – 11 (85%)

B – 2 (15%)

78±5

23±29

C2-C3 – 2 (29%)

C4-C5 –5 (71%)

A- 6 (86%)

B- 1 (14%)

Legend: G1 – Extubated patients; G2 – Decannulated patients; N – number of patients; FVC –Forced Vital Capacity; FEV1 – Forced expiratory volume at 1

st second; CPF- (Unassited) Cough Peak Flow; SCI –

Spinal cord injury; ASIA – American Spinal Injury Association

* - measured at T1 (immediately after tube removal) Note – p value is non- significant in all items between the 2 groups



18

Table 2 – ICU and discharge outcomes:

G1

G2

Days on invasive mechanical

Ventilation

ICU length of stay (days)

15±12 &

22±16*

61±34 &

97±93*

Duration of protocol (days)

8±6 #

14±3 #

Ventilatory

dependence

at discharge, n (%)

Ventilatory

dependence

at 6 months, n (%)

SB – 8 (61%)

nNIV - 5 (39%)

SB – 11 (85%)

nNIV – 2 (15%)

SB – 3 (43%)

nNIV - 3 (43%)

cNIV – 1 (14%)

SB - 4 (57%)

nNIV - 2 (29%)

cNIV – 1 (14%)

Data presented as mean ± standard deviation Legend: : G1 – Extubated patients; G2 – Decannulated patients; ICU – Intensive Care Unit; Duration of

protocol - days required to finish the protocol; SB – Spontaneous breathing; nNIV – nocturnal noninvasive

ventilation; cNIV – continuous noninvasive ventilation

& - p<0,05

* - p < 0,05

# - p < 0,05



19

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14. Ferrer M, Valencia M, Nicolas JM, Bernadich O, Badia JR, Torres A (2006) Early

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Am J Respir Crit Care Med 173 (2):164-170

15. Burns KE, Adhikari NK, Meade MO (2003) Noninvasive positive pressure

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23

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Study 3

Effects of mechanical insufflation-exsufflation in

preventing respiratory failure after extubation:

A randomized controlled trial.

Miguel R. Gonçalves, Teresa Honrado, João Carlos Winck, José Artur Paiva

(Critical Care, submitted)



Effects of mechanical insufflation-exsufflation in preventing

respiratory failure after extubation.

A randomized controlled trial.

Authors: Miguel R. Gonçalves, Teresa Honrado, João Carlos Winck, José Artur Paiva

Affiliation: Lung Function and Ventilation Unit, Pulmonology Department; Intensive

Care and Emergency Department;, Faculty of Medicine, University Hospital of S. João,

Porto, Portugal


Miguel R. Gonçalves Lung Function and Ventilation Unit – Pulmonary Medicine Department Intensive Care Unit – Emergency Department University Hospital of S. João Address: Av. Prof. Hernani Monteiro, Porto, Portugal Phone: 00351 225512100 (extension 1042); [email protected] [email protected]



Abstract:

(Word count 341)

Background: Weaning protocols that include the use of noninvasive ventilation (NIV),

decreases the incidence of re-intubation and ICU length of stay. However, the role of

NIV in post-extubation failure is still not clear. Impaired airway clearance is associated

with NIV failure. Mechanical Insufflation-Exsufflation (MI-E) is an assisted coughing

technique that has been proven to be very effective in patients under NIV.

Aims: To assess the efficacy of MI-E as part of a protocol for patients that develop

respiratory failure after extubation.

Methods: Patients under mechanical ventilation (MV) for more than 48 hours with

specific inclusion criteria, who successfully tolerated an spontaneous breathing trial

(SBT) were randomly allocated before extubation, either for (A) conventional

extubation protocol (control group) or (B) MI-E extubation protocol (study group). Re-

intubation rates, ICU length of stay and NIV failure rates were analyzed.

Results: Seventy five patients (26 females) with a mean age of 61.8±17.3 years old

were randomized to control group (n=40, mean SAPS II) and to study group (n=35,

mean SAPS II 45.0±15.0). MV time before enrollment for was 9.4 ±4.8 and

10.5±4.1days for control and study group respectively. In the 48 hours post extubation,

20 control patients (50%) and 14 study patients (40%) used NIV. Study group patients

had a significant lower re-intubation rate than controls; 6 patients (17%) vs 19 patients

(48%), p<0.05 respectively and a significant lower time under MV; 17.8±6.4 vs

11.7±3.5 days, p<0.05, respectively. Considering only the sub-group of patients that

used NIV, the re-intubation rates related to NIV failure were significantly lower in the

study group when compared to controls; 2 patients (6%) vs 13(33%), p<0.05,

respectively. Mean ICU length of stay pós - extubation was significantly lower in the

study group when compared to controls (3.1± 2.5 vs 9.8± 6.7 days, p<0.05). There were

no differences in the total ICU length of stay

Conclusions: Inclusion of MI-E in post-extubation failure may reduce re-intubation

rates with consequent reduction in post-extubation ICU length of stay. This technique

seems to b efficient in improving the efficacy of NIV in this patient population.



(Word count 2977)

Introduction

The process of weaning from mechanical ventilation must balance the risk of

complications due to unnecessary delays in extubation with the risk of complications

due to early discontinuation and the need of reintubation[1]. Patients who require

reintubation have been noted to have a significantly higher mortality rate than those

who are successfully extubated on the first attempt[2].

Patients in the intensive care setting very often have impaired airway clearance.

Endotracheal intubation prevents the patient from closing the glottis, which is necessary

for effective coughing[3]. Care of the intubated patient includes direct suction applied

through the endotracheal tube which clears a small portion of the airway, is ineffective

for clearing secretions in the peripheral airways, and leaves the patient dependent upon

mucociliary clearance rather than cough clearance[4]. Deep insufflation with a self-

inflating ventilation bag can help, especially if accompanied by chest physiotherapy, but

it does not recreate a cough[5].

Ventilator-associated pneumonia is an exceedingly common problem in

intensive care units (ICUs), occurring in as many as 27% of patients [6]. The reasons for

this are complex, but a significant role is played by the aspiration of upper-airway

secretions and gastric contents[7]. In reality, “ventilator-associated” pneumonia is more

“interface-associated” pneumonia as pathogenic mechanisms are related to the

(invasive) interface used for mechanical ventilation rather than the ventilator itself [8],

Despite the many reports and reviews on ventilator-associated pneumonia, little

emphasis is placed on airway clearance[9].

Predictors for successful weaning include respiratory rate less than 38 per

minute and a rapid shallow breathing index below 100 breaths/min/L [10]. However,



even in patients who satisfy weaning criteria and pass ventilator weaning trials, there is

an extubation failure rate of 10 to 20% [11].

Post –extubation respiratory failure is defined as the presence of signs and

symptoms of respiratory distress in the first 48 hours after extubation. The reasons

given for extubation failure include lack of improvement in work of breathing,

hypoxemia, respiratory acidosis, retained secretions, and decreased consciousness [12].

However, if at extubation the lungs are healthy and ventilation can be fully maintained

noninvasively[13], then the only remaining concern is the effective expulsion of airway

secretions[14]. Despite the importance of this factor, no ventilator weaning parameter

addresses the ability to cough.

Early extubation, coupled with the use of noninvasive ventilatory support has

been used effectively to facilitate weaning[15-17], improve survival[18], decrease the

incidence of ventilator-associated pneumonia[8, 19] and reduce ICU length of stay[18-

19]. However there is a higher risk of NIV failure when applied in patients that develop

ARF after extubation and the evidence that supports its application is controversial [20-

22].

Despite a great interest in this field, the role of impaired airway secretion

clearance on the outcome of post-extubation respiratory failure in critically ill ventilator

dependent patient treated with non-invasive ventilation is still not clear. Airway

clearance may be impaired in disorders associated with abnormal cough mechanics,

altered mucus rheology, altered mucociliary clearance, or structural airway defects. A

variety of interventions are used to enhance airway clearance with the goal of improving

lung mechanics and gas exchange, and preventing atelectasis and infection [23].

Conventional techniques for augmenting the normal mucociliary clearance and

cough efficacy have been used for many years to treat patients with respiratory



disorders from different etiologies. In recent years, new technologies and more

advanced techniques have been developed to be more effective in acute respiratory

failure These techniques involve mechanical application of forces to the chest wall[24]

or intermittent pressure changes to the airway to assist airway mucus clearance[25-26].

Mechanical insufflation-exsufflation (MI-E) applies positive pressure followed

by negative pressure across the entire airway (both central and peripheral), in contrast to

direct tracheal suction, which applies negative pressure to a small, localized area[27].

This therapy is perhaps the most physiologic recreation of a natural cough.

The purpose of this study is to assess the efficacy of MI-E as part of a weaning

protocol for patients that develop acute respiratory failure after extubation.

Methods:

The data of this randomized control trial was gathered in a 12 bed general ICU

between 2007 and 2009. The study was approved by the ethical institutional committee

and review board.

Patients:

Patients older than 18 years and under mechanical ventilation, for more than 48

hours, for acute hypoxemic and/or hypercapnic respiratory failure from a specific

etiology were considered potentially eligible for the study. Exclusion criteria included

facial or cranial trauma, tracheostomy, active upper gastrointestinal bleeding, neurologic

instability (inability to respond to direct simple orders), hemodynamic instability, lack

of cooperation and confirmed diagnosis of neuromuscular disease.



All patients included were evaluated for discontinuation of mechanical

ventilation through the application of a spontaneous breathing trial (SBT). The

application of a SBT trial was considered appropriate when all of the following criteria

were met : improvement of the condition that caused acute respiratory failure,

respiratory rate less than 38 per minute, rapid shallow breathing index below 100

breaths/min/L [10] suspension of sedative medications, ability to stay alert and

communicate, core temperature less than 38ºC throughout the last 24h, suspension of

vasoactive drugs, with the exception of dopamine at doses lower than 5ug per kilogram

of body weight per minute and partial pressure of oxygen greater than 60mmHg on an

inspired fraction of oxygen(FiO2) of 0.40 (PaO2/FiO2 >200) or less, with a positive

end-expiratory pressure (PEEP) of 5cmH2O

Discontinuation of mechanical ventilation was assessed by a trial of spontaneous

breathing with a T tube on a FiO2 of 50% for up to 60 to 120 minutes. The SBT was

considered successful when during the trial time none of the following symptoms were

found: Respiratory Rate > 35bpm, SpO2 < 90 %, 20% variation of Heart rate or Blood

pressure, respiratory distress, agitation and loss of conscience[28].

Patients who successfully tolerated the SBT were randomly allocated before

extubation, using a computer-generated table either for (A) conventional extubation

protocol (control group) or (B) MI-E extubation protocol (study group). During the first

48 hours after extubation, patients were observed for symptoms of acute respiratory

distress/insufficiency as defined by dyspnea and the presence of at least two of the

following: respiratory acidosis (pH < 7.35 with a PaCO2 >45mmHg), increased use of

accessory respiratory muscles, increased respiratory rate (>35 bpm), and decreasing

oxyhemoglobin saturation, i.e. Spo2 < 90% and PaO2 <80 mmHg with fiO2 > 50%.



Group A patients received (post-extubation) standard medical treatment (SMT),

including NIV in case of specific indications, whereas Group B received the same post-

extubation approach plus mechanical in-exsufflation (MI-E).

Patients with persistent weaning failure who failed 3 or more SBTs in one week

were excluded.

Standard medical therapy:

All patients received post extubation standard medical therapy including

supplemental oxygen as needed, respiratory chest physiotherapy, bronchodilators,

antibiotics and any other therapies as directed by the attending physician.

Criteria for NIV were the same in the two groups. Patients were submitted to

NIV, if they met at least one of the following criteria, as judged after they had

undergone the assigned treatment: Respiratory Rate > 35bpm, SpO2 < 90 %, 20%

variation of Heart rate or Blood pressure, dyspnoea with respiratory distress, PaO2<

60mmHg, PaCO2 > 45mmHg, pH < 7,35.

Noninvasive ventilation was provided via an ICU ventilator with noninvasive

mode or via a portable pressure cycled ventilator through a oronasal mask as first

choice. Other interfaces such as nasal, total face, helmet and mouthpieces were used in

case of patient´s intolerance to the oronasal mask.

The fraction of inspired oxygen and the positive end-expiratory pressure were

titrated to maintain the arterial oxygen saturation above 90 percent ( or PaO2 >

60mmHg). The ventilator settings were subsequently adjusted as needed for the

patient’s comfort The facial skin was assessed every four hours to prevent damage from

the tightly fitting mask.



The decision regarding when to discontinue noninvasive ventilation was left to

the attending physician.

Mechanical Insufflation-Exsufflation Protocol (study group):

After passing the SBT and randomized to the study group, before extubation, all

patients were submitted to a treatment of MI-E (3 sessions) with the Cough Assist™

(Philips Respironics, Inc) through the endotracheal tube with pressures set at 40 cm

H2O for insufflation and -40 cm H2O for exsufflation pressure. An

insufflation/exsufflation time ratio of 3secs/2 secs and a pause of 3 sec between each

cycle was used. Eight cycles were applied in every session with an abdominal thrust

timed to the exsufflation cycle.

On top of the standard medical therapy, during the first 48 hours post extubation,

each patient received 3 daily treatments by means of a light-weight, elastic oronasal

mask. Treatments (3 sessions each) were divided between morning, afternoon and night,

making a total of 9 daily sessions.

The daily treatment frequency and its outcomes were recorded in a diary by the

nursing staff. All MI-E treatments were administered by a trained respiratory therapist,

ICU physician or nurse.

Criteria for reintubation:

In both patient groups, the final decision to reintubate was left to and made by

the attending physician, who recorded the single most relevant reason for reintubation.

Reason to reintubate was the existence of at least one of the following, as judged after

they had undergone the assigned treatment: (a) respiratory or cardiac arrest, (b)

respiratory pauses with loss of consciousness, (c) respiratory distress despite 2 hour



treatment with SMT and NIV, (d) decreasing level of consciousness, (c) intolerance to

NIV; (f) hypotension, with a systolic blood pressure below 90 mm Hg for more than 30

minutes despite adequate volume challenge, the use of vasopressors, or both and (g)

copious secretions that could not be adequately cleared or that were associated with

severe hypoxemia. The final decision to reintubate was made by the attending

physician, who recorded the single most relevant reason for reintubation. Only re-

intubations required in the first 48 hours post-extubation was considered for this study.

Outcomes:

Reintubation rate was considered as primary endpoint. Total ICU length of stay,

post-extubation ICU length of stay and reasons for reintubation and NIV failure were

also analysed and compared between groups as secondary endpoints. A sub-group

analysis, both for primary and secondary outcomes, was performed in patients that were

submitted to post-extubation NIV

Statistical analysis:

Descriptive data are reported as mean± standard deviation (SD). Statistical analysis was

performed by SPSS software (Release 15.0 SPSS, Chicago, I1, USA).

Sample size calculation: The primary end-point variable was to decrease reintubation

rates defined by the necessity of mechanical positive pressure ventilation through

orotracheal intubation in the first 48 hours post-extubation in the treatment group.

Initial calculations revealed a required sample size of 33 subjects in each group

with reintubation rates to be reduced by 30%. One interim analysis was performed after

inclusion of 50% of the estimated patients using an α curtailment (p< 0.005) to correct

the analysis.



Comparisons between groups: For all endpoints, differences between groups were

analyzed by using a paired Student’s t-test for the parametric variables and unpaired

Mann-Whitney for the non parametric ones, respectively. P-values were considered

significant if <0.05.

Results:

A total of 92 patients were considered for the study period, 17 of which did not

meet the inclusion criteria. Seventy five patients (26 females) with a mean age of

61,8±17,3 years old were randomized, 40 to control group and 35 to the study group.

Baseline characteristics at baseline were similar in both groups, as well as the reasons

for MV. Demographic data and patients characteristics at the entry of the study are

listed in Table 1.

In the 48 hours post- extubation, 20 controls (50%) and 14 study patients (40%)

used NIV. Considering this sub-group of patients, the re-intubation rates related to NIV

failure were significantly lower in the study group when compared to controls; 2

patients (6%) vs 13(33%), p<0.05, respectively.

Outcomes of both patients groups in the first 48 hours post-extubation and ICU

length of stay data are listed in Table 2. When compared to controls, both duration of

invasive mechanical ventilation and post – extubation ICU length of stay were shorter

by 6 days (p<0,05), and reintubation rate was lower (17% vs 48%) in the study group.

There were no significant differences in total ICU length of stay



Discussion:

The results found in this trial suggest that secretion management with MI-E may

work as a useful complement technique to treat patients who develop ARF in the first

48 hours post-extubation. The use of MI-E had a stronger impact in preventing re-

intubation in the group of patients that required NIV, as shown by the lower NIV failure

rates in the patients that were submitted to MI-E.

Significant debate still exists concerning the precise indications and efficacy of

NIV in this patient population[29] without any mention to the problem of impaired

airway secretion.

The randomized controlled studies performed by Esteban et al [21]. and Keenan

et al[20]. concluded that NIV is not efficient in reducing re-intubation rates, duration of

invasive mechanical ventilation and ICU and hospital length of stay. None of these

studies showed improvement in survival in patients that used NIV in addition to SMT.

On the contrary, the trials conducted by Nava et al.[30] and Ferrer et al.[15] showed that

NIV could prevent ARF after extubation. Several reasons may explain these differences.

First, whereas the studies by Keenan et al[20] and Esteban et al[21] applied NIV after

patients had developed symptoms of respiratory failure, the studies by Nava et al[30]

and Ferrer et al[15] previously identified the high-risk patients and applied NIV

immediately after extubation. As longer time from extubation to re-intubation is

associated with worse outcome[31], delay in re-intubation correlates with worse

survival rates in patients who received NIV for established post-extubation respiratory

failure[20-21]. Thus, the early application of NIV seems crucial to avoid respiratory

failure after extubation, and consequently re-intubation. Second, a significantly higher

proportion of patients with chronic respiratory disorders were included in the studies



that used early NIV in high risk patients, whereas the NIV post-extubation respiratory

failure trials enrolled only 10–11% of patients with chronic pulmonary disease and used

different definitions for post-extubation respiratory failure.

In our study, both study and control groups included 20% of patients with

chronic respiratory disorders, and all patients were closely monitored during the first 48

hours for early detection of signs and symptoms that indicated post-extubation

respiratory failure. Similarly Esteban et al.[21] and Keenan et al.[20] NIV was only

applied after the development of those symptoms according to specific criteria.

However, in our study NIV was applied in both study group patients and controls and

only MI-E application was considered an independent variable.

Secretion encumbrance with impaired airway clearance has been considered an

independent factor for extubation failure[32], and associated to NIV failure both in

persistent weaning[19] and in post-extubation failure[21] patients. While it is relatively

easy managing secretions through an endotracheal tube, it can be a serious problem

after extubation and specially during NIV. Deep airway suction suctioning through the

tube is a strategy most commonly used by nursing staff to manage secretions while

patients are on invasive MV, however it can be traumatic, difficult to perform and often

ineffective in the extubated patients since it must be performed blindly through the nose

or the mouth.

This study randomly used MI-E (CoughAssistTM, Phillips Respironics

International Inc., Murrysville, Pa) pre- extubation via invasive tube and post-

extubation through oronasal interface at sufficient inspiratory and expiratory pressures

(minimum of 40 to -40 cm H2O) to fully expand and then fully empty the adult lungs in

6-8 seconds, thereby expelling airway secretions while avoiding both hyper and

hypoventilation. The ability to use MI-E through the endotracheal tube immediately



before extubation was the main intervention that permitted the study group patients to

minimize the risk of post-extubation secretion encumbrance and, together with its 3

time daily noninvasively application, may have had influence on the reduction of re-

intubation and NIV failure rates.

Although MI-E has been described as a very efficient technique in the acute

setting for patients with neuromuscular disease (NMD), in the treatment of respiratory

failure due to upper respiratory tract infections[27], to avoid intubation[33] and to

facilitate extubation, decannulation and prevent post-extubation failure[34-36], the

evidence supporting the role of this technique in this other critical ill patient population

is lacking. Indeed, this study is the first randomized controlled trial focused on MI-E in

critical care.

The fact that there is strong evidence on the efficacy of MI-E in critically ill

patients with NMD, and the authors´ positive experience with this technique in this

patient population, was the ethical reasons to exclude them from the study. In fact, our

group recently reported a 97% extubation success to full-setting noninvasive ventilation

(NIV) and MI-E in 157 NMD patients who had previously failed extubations and/or

SBTs [37].

Potential limitations have to be taken into account when analyzing the

differences between the two groups. First, although there were no significant differences

in baseline characteristics at the entry of the study between the two groups hypoxemic

respiratory failure was slightly more frequent in group A and this may had impact on

the NIV failure rate in this patient group, since NIV is more likely to fail when severe

hypoxia is present[38]. Second, 6 controls and 4 study group patients were re-intubated

immediately with no indication for NIV. This fact was associated with causes that could



not be solved by MI-E, since cooperation with the technique is crucial in extubated

patients.

Another potential limitation of this type of open clinical trials is the difficulty for

a correct blinding of the investigators that might lead to possible bias. Despite the fact

that we predefined the criteria for all relevant interventions and clinical decisions to be

made by the attending physicians, as well as the outcome variables, this bias could not

be entirely controlled.

Thus, our results recommend that MI-E for secretion clearance should be

included in an extubation protocol in specific subgroups of patients that may require

post-extubation NIV. However, because of the paucity of data, and the fact that this is a

pilot study performed in a center highly experienced with MI-E, more studies are

required to settle the issue.

Acknowledgments:

The authors wish to thank all medical and nursing staffs of the emergency

department ICU of our institution, for their motivation, assistance and support in

managing the patients according to the trial.



Table 1 – Baseline characteristics of patients at entry into the study Group A

(n = 40)

Group B (MI-E) (n=35)

p

Age (years) 62±19,2 61,4±15,1 NS

Sex (M/F) 21/19 28/7 NS

SAPS II 47,8±17,7 45±15 NS

Duration of MV (days) 9,4±4,8 10,5±4,1 NS

Patients with chronic pulmonary disorders (n,%)

9(23%) 7 (20%) NS

Patients with hypoxemic respiratory failure (n,%) Reasons of MV (n)

24 (60%) 18(52%) NS

COPD exacerbations 6 4

Congestive heart failure 5 4

Community – acquired pneumonia 11 6

Hospital – acquired pneumonia Postoperative respiratory failure Acute lung injury Thoracic trauma Sepsis Cardiac arrest

-- 5 --

6 7 --

2 8 1

3 4 3

Data is Data presented as mean ± standard deviation Legend- SAPS II - New Simplified Acute Physiology Score; MV – mechanical ventilation; COPD –chronic obstructive pulmonary disease; NS – Non significant



Table 2 – Post-extubation outcomes data Group A

(n = 40)

Group B (MI-E) (n=35)

NIV application, n (%) Reasons for NIV (n)

20 (50%) 14 (40%)

Respiratory Rate > 35bpm 5 (25%) 9 (64%)

SpO2 < 90% 4(20%) 1(7%)

20% variation of HR or BP 1(5%) -----

PaO2<60; PaCO2>45

10(50%) 4 (29%)

Total period of MV (days)

17,8±6,4* 11,7±3,5*

Patients re-intubated (n,%)

Causes of re-intubation (n)

19 (48%) * 6 (17%) *

Respiratory pauses with loss of consciousness --- 1

Respiratory distress after 2h NIV 6 2

Decreasing level of consciousness 2 --

Intolerance to NIV Hypotension (systolic BP< 90 mm Hg for more than 30 minutes) Secretion encumbrance associated with severe hypoxemia.. NIV failure rate, n (%) Total ICU length of stay Post-extubation ICU length of stay

2

---

9

13 (65%) *

19,3±8,1

9,8±6,7*

--

1

2

2 (14%) *

16,9±11,1

3,1±2,5*

Data is Data presented as mean ± standard deviation Legend- NIV – Noninvasive ventilation; APS II - New Simplified Acute Physiology Score; MV – mechanical ventilation; COPD –chronic obstructive pulmonary disease; NS – Non significant

*- p<0,05



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Study 4

A Ventilator Requirement Index

John R. Bach, Miguel R. Gonçalves, Yuka Ishikawa, Michal Eisenberg, João Carlos Winck , Eric Altschuler



Authors:

John R. Bach, MDMiguel Goncalves, RTMichal Eisenberg, MDYuka Ishikawa, MDEric Altschuler, MDJoao Carlos Winck, MD, PhDEugene Komaroff, PhD

Affiliations:

From the Department of PhysicalMedicine and Rehabilitation,UMDNJ–New Jersey Medical School,Newark, New Jersey (JRB, ME, EA,EK); Hospital Universitario de SanJoao, Porto, Portugal (MG, JCW); andDepartment of Pediatrics, YakumoByoin National Sanatorium,Hokkaido, Japan (YI).

Correspondence:

All correspondence and requests forreprints should be addressed to JohnR. Bach, MD, Department of PhysicalMedicine and Rehabilitation,University Hospital B-403, 150Bergen St., Newark, NJ 07103.

0894-9115/08/8703-0001/0

American Journal of Physical

Medicine & Rehabilitation

Copyright © 2008 by Lippincott

Williams & Wilkins

DOI: 10.1097/PHM.0b013e318164a96e

A Ventilator Requirement Index

ABSTRACT

Bach JR, Goncalves M, Eisenberg M, Ishikawa Y, Altschuler E, Winck JC,Komaroff E: A ventilator requirement index. Am J Phys Med Rehabil 2008;87:000–000.

Objective: To determine the efficacy of vital capacity (VC) and aproposed ventilator requirement index (VRI) for justifying ventilator pre-scription and use for patients with neuromuscular/chest wall diseases(NMD).

Design: Prospective observational study in which 319 patients withNMD, including 187 ventilator users, were separated into four groups:(1) asymptomatic, (2) abnormal specific screening factors and/or symp-tomatic, (3) ventilator use 8–20 hrs/day, and (4) �20 hrs/day ofventilator use. The VRI was defined as 60 � Ti/(Ttot)2

� (Vt/VC) � RR,where Ti � inspiratory time of one breath (secs), Ttot � total time of onebreath (secs), Vt � tidal volume (ml) at rest, VC � vital capacity (ml), andRR � respiratory rate.

Results: The overall analysis of variance F-tests and post hoc pairwisecontrasts were significant (P � 0.001) for differences in the VC and VRIacross groups. Thus, VC and VRI are independent predictors of groupmembership. Satisfying VC or VRI criteria signaled the highest number ofpatients benefiting from ventilator use.

Conclusions: The prescription of one or two ventilators can be justifiedby both VC and VRI, with the combination being most sensitive.

Key Words: Ventilator Requirement Index, Noninvasive Mechanical Ventilation, Respi-

ratory Insufficiency, Home Mechanical Ventilation, Neuromuscular Disease

When a patient is not able to fully sustain the muscular work of breathingto maintain normal alveolar ventilation in the presence of increasing ventilatoryload or decreasing work capacity, muscle fatigue can only be averted by symp-tomatic hypoventilation or by ventilatory assistance. Bellemare and Grassino1

examined the effects of the tension time index of the diaphragm (TTIdi) oninspiratory muscle endurance and fatigue. They define the point at which atarget tension could no longer be sustained as the Tlim. In the case of thediaphragm, there are two main factors influencing Tlim or muscle fatigue. They

March 2008 Ventilator Requirement Index 1

ORIGINAL RESEARCH ARTICLE

Pulmonary



are the product of the TTIdi or the product of thefraction of time that the inspiratory muscles spendin contraction (Ti/Ttot) (the duty cycle of the in-spiratory muscles), and the ratio of the tensiongenerated at each contraction (Pdi) to the maxi-mum Pdi that can be achieved during a near iso-metric contraction (PdiMax). Thus, TTIdi � (Ti/Ttot) � (Pdi/PdiMax). Tlim is the percentage ofTTIdi such that effective diaphragm contraction isnot sustainable. Because the diaphragm contractsmainly during inspiration, it should fatigue morerapidly at any given tension if Ti/Ttot is abnormallyincreased. It should also fatigue more rapidly at anygiven Ti/Ttot if the Pdi/PdiMax ratio increases withadvancing inspiratory muscle weakness/dysfunc-tion. Bellemare and Grassino1 report that the Tlimfor patients with chronic obstructive pulmonarydisease is (TTIdi equal to) 0.12. That is, with TTIdigreater than this, chronic obstructive pulmonarydisease patients’ respiratory muscles fatigue. TTIdi �

0.15–0.2 was reported as “the critical zone forfatigue” in that fatigue could occur in less than 1hr at this TTIdi level. Thus, diaphragm (inspiratorymuscle) endurance could be predicted by the TTIdi.However, determining TTIdi requires placement ofan esophageal balloon to measure Pdi and PdiMax.This makes it impractical for general use.

We have already demonstrated that tidal vol-ume (Vt)/vital capacity (VC) can substitute for Pdi/PdiMax, because the more Vt approaches VC, theless ability the inspiratory muscles have to sustainalveolar ventilation.1 Our previous data, on pre-dominantly chronic obstructive pulmonary diseasepatients, suggest that a breathing intolerance indexusing Vt/VC can supplement VC criteria to helpgauge the need for ventilator use by reflectingventilatory reserve.1 Subsequently, we hypothe-sized that the index might better correlate withsymptomatic inspiratory muscle dysfunction if itreflected ongoing inspiratory muscle action ratherthan effort over only one breath cycle. Thus, wemultiplied the index (Ti/Ttot � Vt/VC) by respira-tory rate, or 60 � Ti/(Ttot)2

� Vt/VC (an equivalentequation), to define a new ventilator requirementindex (VRI). The purpose of this study was to de-termine whether this VRI could distinguish pa-tients with neuromuscular diseases (NMD) withvarious levels of inspiratory muscle dysfunctionand need for ventilator use, and whether such anindex could add to the efficacy of simple VC mea-surement in indicating the extent of the need forventilator use.

MATERIALS AND METHODS

This was a prospective analysis of data gath-ered on 332 consecutively referred patients withNMDs. It was approved by our institutional reviewboards. Three hundred nineteen of the 332 could

achieve steady-state breathing sufficiently for sixbreaths to be averaged for data analysis, and 13 couldnot (were continuously ventilator dependent). Of the319, there were 187 males and 132 females, 36.8 �

19.1 yrs of age. They had the following diagnoses:Duchenne muscular dystrophy, 90 (mean age 22.7range 9–45); non-Duchenne myopathy, 83 (meanage 28.8, range 13–78); amyotrophic lateral sclerosis,64 (mean age 56.3, range 19–84); spinal muscularatrophy, 25 (mean age 25.3, range 16–53); postpolio-myelitis, 18 (mean age 60.9, range 44–77); myotonicdystrophy, 13 (mean age 38.3, range 29–48); spinalcord injury, 11 (mean age 28.8, range 18–52); myas-thenia gravis, 6 (mean age 42.8, range 31–58); mul-tiple sclerosis, 5 (mean age 48.1, range 34–59); Char-cot–Marie–Tooth disease, 2 (ages 57 and 42); andmiscellaneous, 15 (mean age 37, range 18–85).

All of the patients underwent evaluation forspecific ventilator need–screening factors, whichincluded symptoms of inspiratory muscle dysfunc-tion (chronic alveolar hypoventilation) as previ-ously published,2 recent or increasing fatigue, dys-pnea at rest (especially on waking), morningheadaches, nocturnal arousals associated with dys-pnea/tachycardia or urination, difficulty arousingin the morning, difficulty in getting to sleep, hy-persomnolence or need for multiple naps, impair-ment of concentration, nightmares, signs of right-heart failure, anxiety, depression, and weightchange. Dyspnea caused by walking or stair climb-ing was excluded because most patients werewheelchair dependent, because ambulation re-quires much greater minute ventilation than mostactivities from a wheelchair, and because nocturnalnoninvasive mechanical ventilation (NIV) has notbeen reported to relieve exertional dyspnea.

Other abnormal screening factors were derivedfrom spirometry (Wright spirometer, Mark 14, Fer-raris Development and Engineering Co., Ltd, Lon-don), end-tidal CO2 levels (Microspan 8090 capno-graph, Biochem International, Waukesha, WI), andpulse oximetry (SpO2) (Ohmeda Model #3760oximeter, Louisville, CO). They were VC measuredin a sitting position less than 50% of predictednormal (Medicare standard), VC sitting/VC supineratio greater than 1.2 (normal ratio �1.07), diur-nal end-tidal carbon dioxide (CO2) greater than 44mm Hg, diurnal pulse oxyhemoglobin saturation(SpO2) decreasing to less than 95%, and ventilator-free breathing ability �10 mins in any position.The VC was recorded as the maximum observed infive or more attempts. The American Academy ofRespiratory Care Clinical Practice Guidelines werefollowed.3 The VC percentage of predicted normalwas calculated as 100 times the VC (ml) divided bythe predicted normal VC (ml), using the Baldwinformula: males’ predicted VC (liters) � [27.63 �

0.112 � age] � height (cm)/1000; females’ pre-

2 Bach et al. Am. J. Phys. Med. Rehabil. ● Vol. 87, No. 3



dicted VC (liters) � [21.78 � 0.101 � age] �

height (cm)/1000.4 For patients with scoliosis, armspan was used rather than height.5 Some question-ably symptomatic patients, especially those using ac-cessory breathing muscles and not having clearsymptoms or other abnormal screening factors, un-derwent polysomnography (13%) or nocturnal oxim-etry and end-tidal CO2 monitoring (33%). Sleep end-tidal CO2 maximum �50 mm Hg, nocturnal SpO2

decreases � 95% at least four times per hour or 10mins or more total during the night, and apnea/hypopnea index �10/hr on polysomnography wereconsidered abnormal screening factors.

The VRI was determined by Meteor digitalspirometer with a liquid crystal diode monitor(Cardio-Pulmonary Technologies Inc.), usingcustom-prepared software to analyze flow andvolume signals on a Windows-based personalcomputer (FMV-660MC/W, A Fujitsu Corp., To-kyo, Japan). The computer selected the six mostconsistent consecutive Vt waveforms with thepatient sitting at rest, and it averaged them forthe Ti, Ttot, and Vt data.

Group 1 patients were asymptomatic and hadno abnormal specific screening factors. Group 2patients had one or more abnormal screening fac-tors. Forty-two of 97 patients were clearly and 55were questionably symptomatic for hypoventila-tion. Group 3 patients depended on ventilator use8–20 hrs/day for symptomatic relief (Fig. 1). Group4 patients required ventilatory assistance aroundthe clock (Fig. 2).

The four respiratory impairment categorieswere correlated with VRI and VC in the sittingposition, using Spearman correlation coefficients.The VC was transformed into natural logarithmbecause the standard deviations seemed to corre-late with means, and residuals from the analysis ofvariance model were obviously skewed. The Tukey–Kramer post hoc adjustment for multiple compar-isons was used to protect �. � 0.05 for statisticalsignificance. Data on 25 historical normals from a

previous study, age 33.9 � 8.5 yrs, were also mul-tiplied by their respiratory rates and were consid-ered for comparison.6

RESULTS

The VRI and VC of 25 historical normals(group 0) and our group 1–4 subjects are shown inTable 1 and 2. The overall analysis of varianceF-tests and post hoc pairwise contrasts were signif-icant (P � 0.001) for all intergroup pairwise com-parisons for both VC and VRI. Thus, VC and VRIwere both independent, significant predictors ofgroup membership (P � 0.001, P � 0.0016, respec-tively). On the basis of Spearman correlation coef-ficients, the four respiratory impairment categoriescorrelated significantly with VRI (rS � 0.05, P �

0.001) and VC (rS � �0.55, P � 0.001) in thesitting position.

The Medicare ventilator prescription criterionof VC �50% captured 82 of 97 (85%) group 2patients but also 12 of 35 (35%) group 1 members.Having a VRI index �1.2 captured 89 of 97 (92%)of group 2 and 16 of 35 (46%) group 1 members. AtVRI �1.3, these figures were 87/97 (90%) and11/35 (31%), respectively; at VRI �1.1, 91/97(94%) and 17/35 (49%), respectively; and at 0.9,93/97 (96%) and 23/35 (66%), respectively. Sensi-tivity is more important than specificity becauseventilator prescription indication parameters needto support ventilator use for patients who can ben-efit from it, whereas patients who do not benefitsufficiently to offset the inconvenience and dis-comfort of ventilator use are unlikely to useventilators, irrespective of parameter values.Thus, a VRI of 1–1.2 or greater may be useful tojustify initial ventilator prescription, whether byvolume-limited or pressure-limited ventilatorssuch as bilevel positive airway pressure devices.

FIGURE 1 Patient with Duchenne muscular dystro-

phy using nasal ventilation.

FIGURE 2 Patient with amyotrophic lateral sclerosis

dependent on continuous noninvasive

mechanical ventilation support uses a

15-mm angled mouthpiece for diurnal

ventilatory support (shown here) and a

nasal interface for nocturnal support.




VRI �1.2 or VC �50% of predicted normal cap-tured 92 of 97 (95%) of group 2 members. Thisincluded 18 patients with initially questionablesymptoms who, after a trial of NIV, appreciatedsufficient benefit on fatigue and other mildsymptoms to go on using it.

Of the group 3 ventilator users, 91 were usingsleep-only NIV, and 54 were using NIV into daytimehours up to 20 hrs/day. Twenty-one patients hadVC greater than 50% in the sitting position but stillrequired nocturnal NIV. For all group 3 patients,except the 13 with myotonic dystrophy, symptomswere relieved, and normal daytime end-tidal CO2

and SpO2 were maintained early on with nocturnalventilator use. The myotonic dystrophy patientstended to use nocturnal NIV sporadically and rarelythroughout sleep. The NMD patients who eventu-ally required more than nocturnal-only NIV oftenspontaneously used it into daytime hours, usuallyvia 15-mm angled mouth pieces (Fig. 2), until theyrequired it around the clock (group 4). They oftenused oximetry as feedback to use diurnal NIV suf-ficiently to maintain sufficient alveolar ventilationto maintain SpO2 �95%.

Whereas all of the group 4 patients were es-sentially continuous NIV users, they had sufficientbreathing autonomy to establish six consistent Vtfor a 2-min period of ventilator-free breathing.Considering Figure 3 for group 4, for whom itcould be argued that a back-up (daytime use)ventilator is warranted, 37 of the 42 were cap-tured by the criterion of VC �1100 ml (88%),with 109 of 277 also meeting this criterion ingroups 1 through 3 (39%) (specificity 100 � 39,or 61%). At VC �1000, these figures were 34/42and 99/277 (39%), respectively; at VC �800 ml,they were 33/42 and 76/277 (27%), respectively;and at 1200 ml, they were 38/42 and 120/277(43%), respectively. Considering that sensitivityis more important than specificity when consid-ering the safety afforded by having a back-upventilator for around-the-clock users, and thatless severely affected (with higher VC and lowerVRI) continuous ventilator users can survivelonger breathing autonomously or using a manualresuscitator or glossopharyngeal breathing in the

event of ventilator failure than the more severelyaffected (lower VC and higher VRI) patients, itseems that a VC of 1100 ml (capturing 88% ofgroup 4 membership) as opposed to a VC of 1000(capturing 81% with slightly higher specificity)might be the more appropriate threshold to sup-port prescription of a second ventilator. Similarly,a VC of 700 ml (point at which the sensitivity andspecificity lines cross on Fig. 3) strongly supportsprescription of a second ventilator. Likewise, bysimilar analysis of Figure 4, a VRI of 2.4 captures34 of 42 (81%) group 4 members and 125 of 277(45%) group 1–3 patients. At a VRI of 2.2, sensi-tivity is unchanged (36/42) and specificity de-creases, with 145/277 meeting the criterion (57%).At VRI � 3.3, the point at which sensitivitytransects specificity in Figure 4, 31/42 (74%) group4 and only 63/277 (23%) group 1–3 patients meetthe criterion. This level might be considered tostrongly support prescription of a second ventila-tor. Having a VRI �2.4 or VC �1100 captured 39 ofthe 42 (93%) group 4 patients.

In addition to the group 4 patients, 13 othersrequired continuous ventilatory support but couldnot breathe long enough for the computer to es-tablish a VRI by analyzing six consistent breaths.These patients either could not complete the studyor, in three cases, had VRI �2.0 because Vt valueswere unsustainably low for steady-state analysis.

DISCUSSION

Third-party payors demand justification forthe prescription of both initial and secondary ven-tilators. Decisions about ventilator use have beenlargely based on the results of polysomnograms,pulmonary function testing, and arterial bloodgases. However, daytime arterial blood gases maybe normal despite symptomatic nocturnal hy-poventilation, and 30% of patients hyperventilatefrom the pain of arterial puncture, so normalPaCO2 may need to be corrected for pH for evi-dence of hypercapnia.7 Further, conventionalpulmonary function testing, including forced expi-ratory flows and volumes, is designed for patientswith lung and airway diseases, rather than muscleweakness and hypoventilation. The VC measured

TABLE 1 Spirometric and ventilator use data

Group n Age Mean vital capacity, ml Percent vital capacity Hvuse per day, hrs

0* 25 33.9 � 8.5 3680.4 � 860.5 106.6 � 13.7 01 35 37.7 � 17.5 2735.7 � 1174.5 79.3 � 17.9 02 97 31.5 � 20.0 1499.3 � 697.2 43.2 � 12.1 03 145 40.6 � 19.2 1184.1 � 799.7 38.1 � 13.0 9.65 � 4.34 42 35.2 � 15.1 550.3 � 547.8 15.8 � 9.1 23.3 � 1.1

Hvuse, home ventilator use in hours per day. * Historical controls.14




with the patient supine is not part of routine pul-monary function testing, but it reflects diaphragmweakness better than the VC measured in the sit-ting position. In a recent study, supine VC �75% ofpredicted normal was 100% sensitive and specificfor predicting an abnormally low Pdi.8 Patients canhave VC levels that approach normal when sittingbut that are less than 50% of normal, and thesepatients might have no ability to breathe whensupine. The inaccuracy of considering VC alone,especially in the sitting position, to indicate venti-lator use has already been reported.4 Accessorymuscle use and abdominal paradox were also bothsignificantly negatively associated with Pdi, and thepresence of accessory muscle use had a sensitivityof 84% and a specificity of 100% for detecting alow Pdi,8 but these signs are not quantitative indi-cations for ventilatory assistance. Numeric param-eters such as respiratory rate, rapid shallow breath-ing index, maximal inspiratory pressure, andPaCO2 have been offered as indicators for noctur-nal NIV, but they have been unreliable.9 CurrentMedicare guidelines for ventilator use mandate aVC �50% of predicted normal, yet there are pa-tients with NMDs who have 10% or less of pre-dicted normal VC who are eucapnic and whobreathe asymptomatically unaided, and there areothers with �70% of predicted normal VC whorequired continuous ventilatory support.10–12

Although polysomnography has become popu-lar in the assessment of NMD patients for sleep-disordered breathing,13 polysomnnograms are pro-grammed to interpret all hypopneas and apneas ascentral or obstructive in nature rather than frominspiratory muscle impairment. This often resultsin inappropriate treatment with continuous posi-tive airway pressure or low-span bilevel positiveairway pressure, methods that maintain airway pa-tency but give little or no assistance to inspiratorymuscles. Further, many asymptomatic NMD pa-tients fail to appreciate benefit and do not tolerateNIV despite polysomnographic abnormalities. Poly-somnography is also expensive and inconvenient.

Meeting VRI or VC criteria better indicatesextent of ventilator need by comparison with VC orVRI alone or with other measures. This requiresonly simple spirometry with specific software.Anyone with neuromuscular weakness and symp-toms of alveolar hypoventilation should be offereda trial of NIV. However, a VC �50% or a VRI �1.2supports the justification of a ventilator for noc-turnal use. Patients whose benefit from nocturnalNIV more than offsets the inconvenience of using itare likely to continue use, regardless of whetherthe ventilator is pressure cycled (bilevel positiveairway pressure) or volume cycled. Nasal or oralinterfaces can be used.14 –17 Once a patient re-quires ventilator use �20 hrs/day, a second ven-

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tilator should be prescribed and might be justi-fied by having a VC �1100 ml or VRI �2.5.

A limitation of interpreting these outcomes isthe large number of diagnoses and age rangesstudied. It has been noted that with age, largerabsolute values and percentages of predicted nor-mal VC are needed for one to maintain normalPaCO2 levels.18 Thus, young patients with diag-noses like spinal muscular atrophy type 2 or Duch-enne muscular dystrophy might be expected tomaintain more normal alveolar ventilation at lowerVC levels than older patients with amyotrophiclateral sclerosis or spinal cord injury, for example.Nevertheless, satisfying VC or VRI criteria mayfacilitate ventilator prescription justification tothird-party payors.

REFERENCES

1. Bellemare F, Grassino A: Force reserve of the diaphragm inpatients with chronic obstructive pulmonary disease. J ApplPhysiol 1983;55:8–15

2. Bach JR, Alba AS: Management of chronic alveolar hypoven-tilation by nasal ventilation. Chest 1990;97:52–7

3. American Association for Respirtory Care: Clinical practiceguidelines: static lung volumes: 2001 revision & update.Respir Care 2001;46:531–9

4. Gelinas D: Nocturnal oximetry as an early indicator ofrespiratory involvement in ALS—correlation with FVC plussymptoms and response to NIPPV therapy. Amyotroph Lat-eral Scler Other Motor Neuron Disord 2000;1:38–9

5. Johnson BE, Westgate HD: Methods of predicting vitalcapacity in patients with thoracic scoliosis. J Bone JointSurg (Am) 1970;52A:1433–9

6. Koga T, Watanabe K, Sano M, Ishikawa Y, Bach JR: Thebreathing intolerance index for ventilator use. Am J PhysMed Rehabil 2006;85:24–30

FIGURE 3 The percentage of members of group 4 (sensitivity) vs. group 1, minus the percentage of members of

groups 1–3 (specificity) having vital capacities less than that indicated on the x-axis.

FIGURE 4 The percentage of members of group 4 (sensitivity) vs. 100%, minus the percentage of members of

groups 1–3 (specificity) having ventilator requirement index values (VRI) greater than that indicated

on the x-axis.




7. Cinel D, Markwell K, Lee R, Szidon P: Variability of therespiratory gas exchange ratio during arterial puncture. AmRev Respir Dis 1991;143:217–8

8. Lechtzin N, Wiener CM, Shade DM, Clawson L, Diette GB:Spirometry in the supine position improves the detection ofdiaphragmatic weakness in patients with amyotrophic lat-eral sclerosis. Chest 2002;121:436–42

9. Pierson DJ: Indication for mechanical ventilation in adultswith acute respiratory failure. Respir Care 2002;47:249–65

10. Wedzicha JA, Muir JF: Noninvasive ventilation in chronicobstructive pulmonary disease, bronchiectasis and cysticfibrosis. Eur Respir J 2002;20:777–84

11. AARC: Consensus statement. Noninvasive positive pressureventilation. Respir Care 1997;42:365–9

12. International Consensus Conferences in Intensive CareMedicine: Noninvasive positive pressure ventilation in acuterespiratory failure. Am J Respir Crit Care Med 2001;163:283–91

13. Chaudhry SS, Bach JR: Management approaches in muscu-lar dystrophy association clinics. Am J Phys Med Rehabil2000;79:193–6

14. Bach JR, Alba AS, Mosher R, Delaubier A: Intermittentpositive pressure ventilation via nasal access in the man-agement of respiratory insufficiency. Chest 1987;92:168–70

15. Ellis ER, Bye PTP, Bruderer JW, Sullivan CE: Treatment ofrespiratory failure during sleep in patients with neuromus-cular disease, positive-pressure ventilation through a nosemask. Am Rev Respir Dis 1987;135:148–52

16. Kerby GR, Mayer LS, Pingleton SK: Nocturnal positivepressure ventilation via nasal mask. Am Rev Respir Dis1987;135:738–40

17. Kirshblum SC, Bach JR: Walker modification for ventilatorassisted individuals. Am J Phys Med Rehabil 1992;71:304–6

18. Bach JR: Noninvasive ventilation: mechanisms for inspira-tory muscle substitution, in Bach JR (ed): NoninvasiveMechanical Ventilation. Philadelphia, Hanley & Belfus,2002, pp 83–102




Study 5

Expiratory Flow Maneuvers of Patients with

Neuromuscular Diseases

John R. Bach, Miguel R. Gonçalves, Sylvia Páez, João Carlos Winck, Sandra Leitão, Paulo Abreu



Authors:

John R. Bach, MDMiguel R. Goncalves, BS, PTSylvia Paez, MDJoao Carlos Winck, MD, PhDSandra Leitao, BS, PTPaulo Abreu, BS, PT

Affiliations:

From the Department of PhysicalMedicine and Rehabilitation, UMDNJ–New Jersey Medical School, Newark,New Jersey (JRB); Pulmonology,Fundacion Neumologica Colombiana,Bogota, Colombia (SP); theDepartment of Pulmonary Medicine,Sao Joao University Hospital, Porto,Portugal (MRG, JCW); and thePhysiotherapy Department, Universityof Alcoitao, Estoril, Portugal (SL, PA).

Disclosures:

This work was performed atUniversity Hospital, Newark, NewJersey; Sao Joao University Hospital,Porto, Portugal; and AlcoitaoUniversity, Estoril, Portugal.

Correspondence:

All correspondence and requests forreprints should be addressed to JohnR. Bach, MD, Department of PhysicalMedicine and Rehabilitation,University Hospital B-403, 150Bergen Street, Newark, NJ 07871.

0894-9115/06/8502-0105/0




Williams & Wilkins

DOI: 10.1097/01.phm.0000197307.32537.40

Expiratory Flow Maneuvers inPatients with NeuromuscularDiseases

ABSTRACT

Bach JR, Goncalves MR, Paez S, Winck JC, Leitao S, Abreu P: Expiratory flowmaneuvers in patients with neuromuscular diseases. Am J Phys Med Rehabil2006;85:105–111.

Objectives: To compare cough peak flows (CPF), peak expiratoryflows (PEF), and potentially confounding flows obtained by lip and tonguepropulsion (dart flows, DF) for normal subjects and for patients withneuromuscular disease/restrictive pulmonary syndrome and to correlatethem with vital capacity and maximum insufflation capacity.

Design: A cross-sectional analytic study of 125 stable patients and 52normal subjects in which CPF, PEF, and DF were measured by peak flowmeter and vital capacity and maximum insufflation capacity by spirometer.

Results: In normal subjects and in patients, the DF significantly exceededPEF and CPF (P � 0.001). For normal subjects, PEF and CPF were notsignificantly different. For patients with neuromuscular disease/restrictive pul-monary syndrome, the CPF significantly exceeded PEF (P � 0.05). Nonormal subjects but 14 patients had DF lower than CPF. Thirteen of these14 had the ability to air stack (maximum insufflation capacity greater than vitalcapacity), indicating greater compromise of mouth and lip than of glotticmuscles. For 14 of 88 patients, maximum insufflation capacity values did notexceed vital capacity, mostly because of inability to close the glottis (inabilityto air stack). Nonetheless, for 11 of these 14 patients, the DF were withina standard deviation of the whole patient group; thus, bulbar-innervatedmuscle dysfunction was not uniform. CPF and PEF correlated with vitalcapacity (r � 0.85 and 0.86, respectively), and with maximum insufflationcapacity (r � 0.76 and 0.72, respectively).

Conclusions: Measurements of CPF, PEF, and DF are useful forassessing bulbar-innervated, inspiratory, and expiratory muscle function.Care must be taken to not confuse them.

Key Words: Amyotrophic Lateral Sclerosis, Duchenne Muscular Dystrophy, Neuro-

muscular Disease, Cough Peak Flows, Peak Expiratory Flows, Dart Flows, Vital Capacity,

Maximum Insufflation Capacity, Respiratory Muscles, Glottic Muscles

February 2006 Expiratory Flow Maneuvers 105

RESEARCH ARTICLE

Neuromuscular Disease



Both peak expiratory flows (PEF) and cough

peak flows (CPF) have been described as useful

clinical variables of respiratory muscle function.1

“Dart flows” (DF) are generated by creating pres-

sure behind the lips and tongue with the mouth

closed. As the lips open and tongue releases the air,

in a maneuver like spitting or projecting a dart

through a narrow tube, these flows can also be

measured by peak flow meter. These flows can be

confused with PEF and CPF and cause the latter to

be overestimated. They are largely a function of the

ability to seal the lips and control the tongue and

buccal muscles.

The main cause of morbidity and mortality in

patients with neuromuscular disease/restrictive

pulmonary syndrome (NMD) is respiratory muscle

dysfunction and, in particular, cough dysfunc-

tion.2–4 Inspiratory, expiratory, and bulbar-inner-

vated musculature are required for effective cough-

ing.5,6

Normal precough inspiration is to 85–90% of

total lung capacity.7 Thus, cough flows are dimin-

ished for patients who have decreased ability to

inflate the lungs, especially when vital capacity

(VC) is �1500 ml.8 After a deep breath, the glottis

is closed by intrinsic laryngeal (bulbar-innervated)

muscles. The expiratory muscles (abdominal and

intercostals) then contract, resulting in intrapleu-

ral pressures of 200 cm H2O.9 On full glottic open-

ing with hypopharyngeal patency maintained by

other bulbar-innervated musculature, there is an

explosive decompression that normally generates

flows of 300–1200 liters/min to expulse airway

secretions.

In patients with NMD, weak inspiratory mus-

cles can be assisted by providing deep lung insuf-

flations or by the stacking of consecutively deliv-

ered volumes of air held with a closed glottis to

approach a maximum insufflation capacity

(MIC).10–12 Expiratory muscles can be manually

assisted by providing thoracoabdominal thrusts.

The combination of applying an abdominal thrust

to a maximally inflated lung is an assisted

cough.1,10 Unassisted cough flows depend on in-

spiratory, expiratory, and bulbar-innervated mus-

culature. However, air stacking ability and, there-

fore, assisted cough flows depend only on glottic

control or on bulbar-innervated muscle function

alone. Thus, the greater the difference between the

MIC and the VC and between assisted and unas-

sisted CPF, the greater is bulbar-innervated muscle

function by comparison with inspiratory muscle

function. Patients who cannot close the glottis

cannot air stack. They may “huff” but cannot

cough. CPF better reflect the capacity to expulse

debris from the airways (cough efficacy) than do

PEFs. CPF not exceeding 160 liters/min are asso-ciated with extubation failure.13

There are no standard normal values for CPFor DF, but PEF range from 500 to 700 liters/minfor men and from 380 to 500 liters/min for women,and from 150 to 840 liters/min for children andadolescents, with variations due to age, race, sex,and height.14,15 For patients with asthma, theirdiminution generally indicates bronchospasm.16

The purpose of this study was to compare the CPF,PEF, and DF, to see if they correlate with VC orMIC, and to consider their use in the evaluation ofthe respiratory muscles.

METHODS

A cross-sectional study was conducted on allNMD patients entering an outpatient clinic be-tween August 2003 and May 2004. The charts of thepatients were reviewed for anthropometric data(age, sex) and for diagnosis. All cooperative NMDpatients whose VCs were �80% of predicted nor-mal were studied. No one meeting these criteriawas excluded. Normal subjects were recruited, in-formed about the purpose of the study, and signedconsent forms that were approved by the hospitals’ethics committee. The patients and controls re-ceived a written description of the maneuvers andhad a 3-min training period before the measure-ments were taken.

The following variables were measured: PEFaccording to the recommendations of the Ameri-can Thoracic Society,17 CPF, and DF, all via anAccess Peak Flow Meter (model 710, Health ScanProducts, Cedar Grove, NJ), and VC (sitting andsupine) and MIC via a spirometer (Mark 14, Fer-raris Development and Engineering, London, UK).All of these measurements were done by a specifi-cally trained respiratory therapist who was un-aware of the study and recorded the highest valueof four or more correctly performed efforts. Thepeak flow meter measured flows from 60 to 880liters/min. Flows of �60 liters/min were recordedas 0 and flows of �880 liters/min were recorded as881 liters/min. No patients had been hospitalizedduring the previous 30 days.


Data for the categorical variables are expressedas number and percentage of patients. Data for thecontinuous variables are reported as median withdispersion of minimum, maximum, and interquar-tile range and range. The use of median valuesrather than mean values eliminated the effect ofimprecisely measured ceiling and floor data.

Normally distributed continuous variableswere compared using the unpaired and paired Stu-dent’s t test, as appropriate, and nonparametriccontinuous variables using Wilcoxon’s signed-




ranks test and Mann–Whitney U test, as appropri-ate. The statistical analyses were repeated assum-ing that all flows of �60 liters/sec were 59 liters/min, except for CPF, which occur without glotticclosure and which, by definition, could only be 0liters/min. PEF of �880 liters/min were estimatedas 881 and then re-estimated as 1008 liters/min,which is 20% greater than 840 liters/min or 2 SDgreater than maximum normal PEF. In addition, aunivariable linear regression analysis was con-ducted to compare expiratory flows with pulmo-nary capacities. All statistical tests were two tailed.A P value of �0.05 was considered to indicatestatistical significance. Statistical analysis was con-ducted with the use of Stata, version 7.0, and SPSS,version 12.0.

RESULTS

There were 125 patients with a mean age of 41� 21 (range, 7–82) yrs; 64% were men (n � 80)and 100 were �18 yrs old (80%). The patients’diagnoses are listed in Table 1. The 52 normalsubjects were 28.6 � 9.8 (range, 19–58) yrs of age,65.4 � 11.4 (range, 49–100) kg, and 165.8 � 8.4(range, 152–183) cm tall. CPF, PEF, and DF dataare presented in Table 2. Two patients were unableto attain any measurable flows, two had measur-able PEF and CPF but not DF, nine had measurableCPF and DF but no measurable PEF, six had mea-surable DF but not CPF or PEF, and one patienthad measurable PEF and DF but not CPF.

The DF were significantly greater than CPFand PEF (P � 0.001) for both the normal subjectsand the patient group. The CPF and PEF were notsignificantly different for the normal subjects. Forthe patient group, assuming unmeasurable flows tobe 0 liters/min, the CPF were significantly greaterthan PEF (P � 0.01) (Table 2). The differencesremained significant (P � 0.01) when considering

adults only but not children only. The patients’CPF remained significantly greater than PEF (P �

0.05) when the eight patients with unmeasurableCPF and PEF were eliminated and when PEF wereestimated to be 59 liters/min for the nine patientswith measurable CPF but not measurable PEF.

The flow data for the six patients (5.5%) withunmeasurable PEF and CPF but measurable DF arein Table 3. Thus, these patients had relatively well-preserved bulbar-innervated musculature, despitesevere inspiratory and expiratory muscle weakness.This was consistent with their diagnoses of post-poliomyelitis1 and congenital muscular dystrophy,5

conditions that, relatively speaking, spare bulbarmusculature.

There were two patients with unmeasurableDF who had severe bulbar amyotrophic lateral scle-rosis yet had mean CPF of 205 liters/min. In fact,the CPF exceeded the DF for 12 patients: two chil-dren with non-Duchenne muscular dystrophy andten adults, of whom seven had amyotrophic lateralsclerosis, two had fascioscapulohumeral dystrophy,and one had myotonic dystrophy. Only one wasunable to air stack. These 12 patients had a greatercapacity to air stack, as seen by a greater MIC–VCdifference, than in the general group (Table 4),suggesting less compromise of glottic musclesthan of the cheeks, lips, and tongue. The 16 pa-tients whose PEF exceeded CPF and, thus, whoseexpiratory muscles were relatively preserved bycomparison with bulbar-innervated muscles areconsidered in Table 5. The PEF of 11 normal sub-jects (21.1%) also exceeded their CPF.

The MIC was measured for 88 patients. For 14of the 88, the MIC did not exceed the VC because ofinability to firmly close the glottis or prevent airleakage out of the nose or mouth during the air-stacking process; their mean VC was 1518.6 �

764.8 ml, significantly lower than the mean VC ofthe whole population (2000 ml, P � 0.03), suggest-ing more advanced disease. Eight of these 14 hadCPF equal to or lower than PEF, confirming moresevere compromise of facial and glottic muscula-ture. In only three of these 14 cases were the DFlower than or equal to CPF, indicating that bulbarmusculature was variably involved with relativesparing of the tongue and lips.

Good correlation was found between CPF andMIC (r � 0.76) (Fig. 1) and between PEF and MIC(r � 0.72) (Fig. 2). Correlation was also foundbetween MIC and DF (r � 0.73). For the remaining37 patients, MIC was not measured because the VCwas too close to the normal range (3155 � 1091.7ml in 27 adults and 2861 � 997.9 ml for the tenchildren) and bulbar musculature was clinicallyintact. There was also a direct correlation betweenCPF and PEF with VC (r � 0.85 and 0.86, respec-tively) and with MIC (r � 0.76 and 0.72, respec-

TABLE 1 Diagnosis of neuromuscular patients

Diagnosis n %

Amyotrophic lateral sclerosis 41 32.8Duchenne–Becker muscular

dystrophy27 21.6

Other muscular dystrophies 18 14.4Postpoliomyelitis 12 9.6Myopathies (nonmuscular

dystrophy)8 6.4

Myasthenia gravis 6 4.8Spinal muscular atrophy 5 4.0Myotonic dystrophy 4 3.2Neuropathies 2 1.6Spinal cord injury 1 0.8Obesity hypoventilation syndrome 1 0.8Total 125 100




tively) for the entire patient group (Fig. 3). This isnot surprising because CPF and PEF are dependenton the ability to take a deep breath. DF also cor-related with VC (r � 0.79), indicating relative pres-ervation of tongue and lips in early disease.

DISCUSSION

Unlike in a previous report by Suarez et al.18,although CPF were greater than PEF for normalsubjects, we did not find the difference to be sta-tistically significant. However, our patient popula-tion may have been too small to observe a signifi-cant difference.18 As Suarez et al.18 reported for

patients with Duchenne muscular dystrophy, wedid observe significantly greater CPF than PEF forpatients with NMD.

The three flow maneuvers we studied are sim-ilar in that they are expiratory flows measured atthe mouth using a peak flow meter. However, eachmethod requires different respiratory musclegroup combinations. With glottic closure, thegreater transpulmonary pressures created bycoughing rather than by PEF maneuvers resultedin greater flows measured at the mouth for 88.2%of patients and 78.9% of normal subjects. However,cough efficacy is dependent on the peak flow ve-locity, which is greater as airways narrow during

TABLE 2 Expiratory maneuvers for normal subjects and patients with neuromuscular diseases

Measurement Variable

Group Statistics CPF PEF DF

Normal patients(n � 52)

Median, liters/min 455 445 881Minimum, liters/min 290 320 370Maximum, liters/min 880 720 881Interquartile range, liters/min 225 160 148Range, liters/min 590 400 510Measurement above reference

range of �880 liters/min, n (%)a0 0 34 (65.4)

Measurement below referencerange of �60 liters/min, n (%)b

0 0 0

Patients(n � 125)

Median, liters/min 250 220 335Minimum, liters/min 0 0 0Maximum, liters/min 710 635 881Interquartile range, liters/min 210 188 270Range, liters/min 650 575 820Measurement above reference

range of �880 liters/min, n (%)a0 0 5 (4.0)

Measurement below referencerange of �60 liters/min, n (%)b

9 (7.3) 17 (13.5) 5 (4.0)

�18 yrs of age (n � 100),mean � SD

280.1 � 167.6 225.6 � 159.9 395 � 260.3

�18 yrs of age (n � 25),mean � SD

248.4 � 108 234.6 � 98.5 332.8 � 158.7

CPF, cough peak flows; PEF, peak expiratory flows; DF, dart flows.a Flows of �880 liters/min were recorded as 881 liters/min.b Flows of �60 liters/min were recorded as 0 liters/min.

TABLE 3 Patients with unmeasurable cough and expiratory flows vs. group as a whole

Patients with Unmeasurable CPF and PEF (n � 6) All 125 Patients P

Age, yrs 29.5 � 14.6 41 � 21 0.06DF, liters/min 128.3 � 50.9 382.6 � 244.1 �0.01VC, ml 358.3 � 115.5 2000.0 � 1245.6 �0.01

CPF, cough peak flow; PEF, peak expiratory flow; DF, dart flows; VC, vital capacity. Data (except for significance) providedas mean � standard deviation.




coughing, making coughing more effective at ex-pulsing airway secretions than huffing, eventhough PEF and CPF may be comparable whenmeasured at the mouth.8 The reduction of thecross-sectional area of the airways during coughingis due to smooth muscle constriction mediated bya vagal reflex (presumably preserved in these dis-eases) and due to dynamic compression of theairways generated by the expiratory (transpulmo-nary) pressure.19,20 The reduction in the cross-sectional area of the airways increases five-fold thevelocity of gas and 25-fold the kinetic energy of theairstream. This explains why the subgroup of 16patients (12.8%) with CPF lower than PEF never-theless coughed rather than huffed to expel secre-

tions. Effective CPF and PEF share the need fordeep lung volumes, explaining their good correla-tion with VC and MIC.

The correlation of CPF with MIC or MIC–VCdifference is explained by their dependence on bul-bar-innervated muscle (glottic) function. CPF arealso dependent on hypopharyngeal patency beingmaintained by bulbar-innervated hypopharyngealmusculature. DF, on the other hand, are indepen-dent of laryngeal and hypopharyngeal dysfunctionand usually exceed CPF and PEF. However, DF donot emanate from the airways and require little orno inspiratory or expiratory muscle effort. We haveseveral patients who operate sip-and-puff motor-ized wheelchairs and generate high DF, despite

TABLE 4 Patients with cough peak flows (CPF) greater than dart flows (DF)

CPF > DF (n �12) All Group (n � 125) P

VC 1220.8 � 611.9 2000.0 � 1245.6 �0.01MIC 1974.0 � 643.3 2179.8 � 1097.9 NSMIC – VC 822.0 � 580.3 632.1 � 474.7 NSCPF 179.2 � 49 273.8 � 157.6 �0.01PEF 113.8 � 55.8 227.4 � 149.4 �0.01DF 107.9 � 75.1 382.6 � 244.1 �0.01

VC, vital capacity; MIC, maximum insufflation capacity; NS, not significant; PEF, peak expiratory flows. Data (except forsignificance) provided as mean � standard deviation.

TABLE 5 Patients with peak expiratory flows (PEF) greater than cough peak flows (CPF)

PEF > CPF (n �16) Entire Group (n � 125) P

VC 2042.3 � 899.8 2000 � 1245.6 NSMIC 2324.2 � 943.1 2179.8 � 1097.9 NSMIC – VC 588.5 � 580.5 632.1 � 474.7 NSCPF 213.4 � 103.2 273.8 � 157.6 0.04PEF 257.8 � 92.0 227.4 � 149.4 NSDF 387.8 � 168.4 382.6 � 244.1 NS

VC, vital capacity; NS, not significant; MIC, maximum insufflation capacity; DF, dart flow. Values (except for significance)provided as mean � standard deviation.

FIGURE 1 Correlation between cough peak flows

(CPF) and maximum insufflation capac-

ity (MIC).

FIGURE 2 Correlation between peak expiratory

flows (PEF) and maximum insufflation

capacity (MIC).




having no measurable VC. DF, although also de-pendent on bulbar-innervated muscles but notglottic function, do not seem to reflect risk ofrespiratory complications. Inability to create mea-surable DF, however, is associated with ineffectivesaliva control and drooling. Thus, different pat-terns of bulbar-innervated muscle dysfunction oc-cur. Figures 1 and 2 demonstrate that DF tend tocorrelate linearly with height and weight. In thisway, DF are similar to PEF because these have alsobeen reported to correlate with height andweight.21,22 Wohlgemuth et al.21 and Holcroft etal.22 also pointed out the need to caution theirsubjects from spitting during PEF measurements.

Although all of the flow maneuvers are depen-dent on effort and motivation, we do not think thiswas a confounding factor in our study because thethree measures were obtained in the same visit, invarying order, by the same examiner, and only themaximum value of many attempts was recorded.

Measurement “ceiling” and “floor” artifacts arecommon in empirical studies. There are elaboratestatistical procedures that can be employed to es-timate the range of plausible effects of the mea-surement limitation on actual P values. However,in this study, simpler and more direct logic suf-fices. This is because DF values exceeded 880 liters/min for 65% of normal subjects but for only 4% ofpatients and because DF values were significantlygreater for normal subjects than for patients evenwhen analyzing the data using ceiling DF of 881

liters/min when the actual values had to be greaterthan this figure. Likewise, for both patients andnormal subjects, DF were significantly greater thanPEF and CPF even when a ceiling value of 881liters/min was used. The P values, already �0.001,were even more significant when the analyses wererepeated using greater values for DF. Thus, therestriction of measurement range produced a con-servative bias in the test of significance of DF groupdifferences.

In summary, assisted and unassisted CPF,PEF, and DF are useful measures of bulbar-inner-vated and respiratory muscle function for patientswith NMD,1 permitting greater knowledge of thepattern of respiratory muscle compromise. DF,CPF, and MIC correlate with bulbar-innervatedmuscle function. It is important to pay specialattention to the technique of each flow measure-ment because DF can be mistaken for CPF or PEFand respiratory risk can be underestimated. Thetechniques are simple, and the peak flow meter isinexpensive and widely available. Further study iswarranted to determine standard values of PCF andDF by age, height, and weight. Peak flow meterswith greater range need to be developed to moreaccurately measure high flows. Effective interven-tions to assist inspiratory and expiratory musclefunction and the accurate characterization of riskof respiratory complications depend on accurateassessment of expiratory flow maneuvers.23–25

ACKNOWLEDGMENT

We thank Dr. Luis Filipe Azevedo of the De-partment of Biostatistics and Medical Informatics,Oporto Medical School, University of Porto, forassistance in the data analyses.

REFERENCES

1. Kang SW, Bach JR: Maximum insufflation capacity: Therelationships with vital capacity and cough flows for pa-tients with neuromuscular disease. Am J Phys Med Rehabil2000;79:222–7

2. Fanburg BL, Sicilian L: Respiratory dysfunction in neuro-muscular disease. Clin Chest Med 1994;15:607–15

3. Baydur A: Respiratory muscle strength and control of ven-tilation in patients with neuromuscular disease. Chest1991;99:330–8

4. Braun NMT, Arora MS, Rochester DF: Respiratory muscleand pulmonary function in polymyositis and other proximalmyopathies. Thorax 1983;38:616–23

5. Bach JR: Update and perspectives on noninvasive respira-tory muscle aids: part 1–the inspiratory muscle aids. Chest1994;105:1230–40

6. Bach JR: Update and perspectives on noninvasive respira-tory muscle aids: Part 2. The expiratory muscle aids. Chest1994;105:1538–44

7. Leith DE: Lung biology in health and disease: Respiratorydefense mechanisms. Part 2, in Brain JD, Proctor D, Reid L(eds): Cough New York, Marcel Dekker, 1977, pp. 545–92

8. Bach JR: Mechanical insufflation-exsufflation: Comparisonof peak expiratory flows with manually assisted and unas-sisted coughing techniques. Chest 1993;104:1553–62

FIGURE 3 Correlation between cough peak flows

(CPF) and peak expiratory flows (PEF)

with vital capacity (VC).




9. Evans JN, Jaeger MJ: Mechanical aspects of coughing. Pneu-monologie 1975;152:253–7

10. Chaudhry SS, Bach JR: Management approaches in muscu-lar dystrophy association clinics. Am J Phys Med Rehabil2002;79:193–6

11. Giggs RG, Donohoe KM, Utell MJ, et al: Evaluation ofpulmonary function in neuromuscular disease. Arch Neurol1981;38:9–12

12. Ishikawa Y, Minami R: The effect of nasal IPPV of patientswith respiratory failure during sleep due to Duchenne mus-cular dystrophy. Clin Neurol 1993;33:856–61

13. Bach JR, Saporito LR: Criteria for extubation and tracheos-tomy tube removal for patients with ventilatory failure: Adifferent approach to weaning. Chest 1996;110:1566–71

14. Nunn AJ, Gregg I: New regression equations for predictingpeak expiratory flow in adults. BMJ 1989;298:1068–70

15. Polgar G, Promadhat V: Pulmonary Function Testing inChildren: Techniques and Standards. Philadelphia, WBSaunders, 1971

16. Jain P, Kavuru MN, Emerman CL, et al: Utility of peakexpiratory flow monitoring. Chest 1998;114:861–76

17. Standardization of spirometry, 1994 Update: American Tho-racic Society. Am J Respir Crit Care Med 1995;152:1107–36

18. Suarez AA, Pessolano F, Monteiro SG, et al: Peak flow andpeak cough flow in the evaluation of expiratory muscleweakness and bulbar impairment of neuromuscular pa-tients. Am J Phys Med Rehabil 2002;81:506–11

19. Irwin RS, Boulet LP, Cloutier MM, et al: Managing cough asa defense mechanism and as a symptom: A consensus panelreport of the American College of Chest Physicians. Chest1998;114:133S–81S

20. McCool FD, Leith DE: Pathophysiology of cough. Clin ChestMed 1987;2:189–95

21. Wohlgemuth M, Van Der Kooi EL, Hendriks JC, et al: Facemask spirometry and respiratory pressures in normal sub-jects. Eur Respir J 2003;22:1001–6

22. Holcroft C, Eisen E, Sama S, et al: Measurement charac-teristics of peak expiratory flow. Chest 2003;124:501–509

23. Gomez-Merino E, Bach JR: Duchenne muscular dystrophy:Prolongation of life by noninvasive respiratory muscle aids.Am J Phys Med Rehabil 2002;81:411–5

24. Bach JR, Baird JS, Plosky D, et al: Spinal muscular atrophytype 1: Management and outcomes. Pediatr Pulmonol 2002;34:16–22

25. Bach JR: Amyotrophic lateral sclerosis: Prolongation of lifeby noninvasive respiratory aids. Chest 2002;122:92–8




Study 6

Lung Insufflation Capacity in Neuromuscular Diseases

John R. Bach Kedar Mahajan Bethany Lipa, Lou Saporito, Miguel Goncalves, Eugene Komaroff,



Authors:

John Robert Bach, MDKedar Mahajan, BSBethany Lipa, BSLou Saporito, BSMiguel Goncalves, BSEugene Komaroff, PhD

Affiliations:

From the Department of PhysicalMedicine and Rehabilitation,University of Medicine and Dentistryof New Jersey (UMDNJ)–New JerseyMedical School, Newark, New Jersey(JRB, KM, BL, LS, EK); andDepartment of Pulmonary Medicine,Sao Joao University Hospital, Porto,Portugal (MG).

Correspondence:

All correspondence and requests forreprints should be addressed to JohnR. Bach, MD, Professor of PhysicalMedicine and Rehabilitation,Professor of Neurosciences,Department of Physical Medicine andRehabilitation, University HospitalB-403, 150 Bergen Street, Newark, NJ07103.

Disclosures:

The authors have received nofinancial support from any companymentioned in this manuscript.

0894-9115/08/8709-0720/0




Williams & Wilkins

DOI: 10.1097/PHM.0b013e31817fb26f

Lung Insufflation Capacity inNeuromuscular Disease

ABSTRACT

Bach JR, Mahajan K, Lipa B, Saporito L, Goncalves M, Komaroff E: Lunginsufflation capacity in neuromuscular disease. Am J Phys Med Rehabil 2008;87:720–725.

Objective: To compare maximal passive lung insufflation capacity (LIC)with lung inflation by air stacking (to maximum insufflation capacity [MIC]) andwith vital capacity (VC); to explore relationships between these variables thatcorrelate with glottic function and cough peak flows (CPF); to demonstratethe effect of routine inflation therapy on LIC and MIC; and to determine therelative importance of lung inflation therapy as a function of disease severity.

Design: Case series of 282 consecutive neuromuscular disease(NMD) clinic patients 7 yrs and older with VC �70% of the predictednormal value. All cooperative patients meeting these criteria were pre-scribed thrice-daily air stacking and/or maximal passive lung insufflation topressures of 40–80 cm H2O, and they underwent measurements of VC,MIC, LIC, and unassisted and assisted CPF on every visit.

Results: Means � standard deviations for VC, MIC, and LIC were1131 � 744, 1712 � 926, and 2069 � 867 ml, respectively, and, forunassisted and assisted CPF, they were 2.5 � 2.0 and 4.3 � 2.2liters/sec, respectively, with all differences statistically significant (P �

0.001). MIC minus VC correlated inversely with LIC minus MIC (P �

0.01) and, therefore, with glottic function. Both MIC and LIC increasedwith practice (P � 0.001). Increases in LIC but not MIC over VC weregreatest for patients with the lowest VC (P � 0.05). There were nocomplications of lung mobilization therapy.

Conclusions: Passive lung insufflation can distend the lungs of pa-tients with NMD significantly greater than air stacking, particularly whenglottic and bulbar-innervated muscle dysfunction is severe. LIC, MIC, andVC measurements permit quantifiable assessment of glottic integrity and,therefore, bulbar-innervated muscle function for patients with NMD. Thepatients who benefit the most from insufflation therapy are those who havethe lowest VC.

Key Words: Neuromuscular Disease, Lung Insufflation Capacity, Pulmonary Compli-

ance, Cough Flows, Air Stacking

720 Am. J. Phys. Med. Rehabil. ● Vol. 87, No. 9


Pulmonary



Respiratory failure for patients with pediatricneuromuscular disease (NMD) is often caused byineffective coughing during otherwise benign chestinfections.1–3 Whereas a normal tidal volume canbe 500 ml, a normal cough volume is 2.3 � 0.5liters.4 Indeed, the lower the VC, the poorer arecough peak flows (CPF) independently of expira-tory (thoracoabdominal) muscle strength.5

Lung expansion to optimize lung recoil pres-sure and increase CPF can be achieved by maxi-mally “air stacking” consecutively delivered vol-umes of air held with a closed glottis. Themaximum volume that can be held in this manneris defined as the maximum insufflation capacity(MIC).6 The MIC can exceed predicted inspiratorycapacity (IC) in people with intact glottic func-tion,7–9 but it only approaches predicted IC in pa-tients with moderate to severe glottic dysfunction.6

With complete loss of glottic closure, MIC nolonger exceeds VC; the NMD patient can no longerair stack or cough, and the glottis, and many, if notall, bulbar-innervated muscles, are extremely im-paired. In this case, lung insufflation can only beprovided by bypassing glottic function. This can bedone by using a manual resuscitator with a closedexpiratory port mimicking glottic closure, or byusing a CoughAssist or volume-cycled ventilator atdelivered volumes/pressures that approach pre-dicted IC.6 The maximum passive lung insufflationvolume achieved in this manner is defined as thelung insufflation capacity (LIC).

The goal of conventional prescriptions for“range-of-motion” mobilization of extremity artic-ulations is to slow the development of musculo-skeletal contractures for patients with limb muscleweakness. However, the prevention of chest wallcontractures and lung restriction has only recentlybeen addressed. In 2006, Lechtzin et al.10 reportedthe use of short-term noninvasive intermittentpositive pressure ventilation (IPPV) to increase pul-monary compliance for patients with amyotrophiclateral sclerosis (ALS). In 2000, we demonstratedthat lung volumes could be increased significantlyover VC by air stacking to approach MIC for pa-tients with NMD.6 This resulted in significantlyincreased (assisted) CPF that can decrease the riskof pneumonia.11,12 For patients such as those withadvanced bulbar ALS whose MIC equals VC, as-sisted CPF cannot be increased by air stacking, andprognosis is poor.13

The purpose of this work was to explore thefollowing hypotheses: (1) lung volumes will be sig-nificantly greater by passive insufflation than by airstacking, especially in patients with severe bulbar-innervated muscle dysfunction, and both LIC andMIC will significantly exceed VC and increase CPF;(2) LIC-MIC will correlate inversely with MIC-VC

and, therefore, correlate inversely with glottic in-tegrity; (3) LIC and MIC can increase with practice;and (4) the greatest increases in MIC and LIC willbe for the most severely affected patients, that is,with the lowest VC.

METHODS

The institutional review board approved thisstudy. In 1979, we began to routinely prescribe airstacking and/or maximal (passive) lung insufflationat pressures of 40 cm H2O or more, three timesdaily, for all patients with VC less than 70–80% ofnormal. Beginning in 2005, we routinely measuredVC, MIC, and LIC in all 290 consecutive patients 7yrs and older whose VC were less than 70%. Ex-clusion criteria were inability to cooperate attrib-utable to severe cognitive impairment, medical in-stability, and primarily lung/airways rather thanventilatory pump insufficiency. Two with DMD,one with congenital myotonic dystrophy, and twoothers with poorly characterized NMD could notcooperate. Three patients were acutely ill and hos-pitalized. No NMD patients had signs of lung/air-ways disease sufficient to warrant evaluation forconcomitant chronic obstructive pulmonary dis-ease or reversible bronchospasm.

All lung volumes were measured by Wrightspirometer model Mark 14 (Ferraris Ltd., London,England) and recorded as the greatest observedvalue in five or more attempts. The MIC was ob-tained by the patient air stacking volumes deliveredvia an oronasal interface from a manual resuscita-tor with a directed expiratory port and with eitherno pressure-limitation device or with the pressurerelease value deactivated, or obtained by air stack-ing via a volume-cycled mechanical ventilator forpatients using daytime noninvasive ventilation.Once no more air could be held with a closedglottis, the patient exhaled into the spirometer toresidual volume (MIC).7

Cough peak flows, both unassisted and as-sisted, were measured by Access Peak Flow Meter(Health Scan Products Inc., Cedar Grove, NJ). Thelargest value of five or more attempts was recorded.Cough flows were assisted by air stacking to ap-proach MIC and an expiratory-timed abdominalthrust.

The LIC was obtained by using the same man-ual resuscitator connected to a spirometer. Thespirometer’s reset button was held and the expira-tory port of the spirometer was occluded duringinsufflation. After insufflation to maximal observedlung (chest wall) expansion with maximum toler-able resistance to further insufflation, the spirom-eter’s reset button and the expiratory port of thespirometer were simultaneously released, and thepatient exhaled to residual volume into the spirom-eter via a tightly held anesthesia (oronasal) inter-

September 2008 Lung Insufflation Capacity 721



face (Fig. 1). The maximum insufflation pressuretolerated by the patient, and the correspondingresistance felt by the therapist, were then repro-duced by insufflating the patient, using theCoughAssist. This was done to observe the pres-sures required for full insufflations to prescribeinsufflation therapy three times daily at home.Thus, glottic closure was unnecessary for the mea-surement of LIC.

Correlation analysis was done between LIC-MIC and MIC-VC using Spearman correlation co-efficients (rS) with P � 0.05 as the level of statis-tical significance (alpha). The same Spearmancorrelation analyses were done for ALS and DMDpatient subgroups. A categorical variable from VCwas based on quartiles, and the correlations wererun within each quartile. Wilcoxon signed rankstests were used to determine possible significance inthe differences between the means of the lung vol-ume variables and also the CPF variables. The differ-ences in the means of the lung volume variables(MIC � MIC, LIC � VC, and MIC � VC) by VC(sitting) levels were evaluated by analysis of variance.

RESULTS

The 290 patients had the following diagnoses:ALS/motor neuron disease 81, DMD 54, non-DMDmuscular dystrophy 38, other myopathies 23, post-

poliomyelitis 26, spinal muscular atrophy 32, and

other conditions 36. Two hundred eighty-two NMD

patients met the criteria. Seventy-eight of these

had had multiple visits and had been prescribed

maximal lung expansion therapy three times daily,

with 10–15 cycles of air stacking/passive insufflations

for a 6-mo to 24-yr period, before the most recent

clinic visit, during which data points were taken for

this study. Among the patients, 103, 116, and 69 were

using continuous NIV, nocturnal-only NIV, or no aid,

respectively.

The patient population had mean � standard

deviation values of 1131 � 744 ml for VC, 1712 �

926 ml for MIC (significantly greater than VC, P �

0.001), and 2069 � 867 ml for (passive) LIC (sig-

nificantly greater than MIC and VC at P � 0.001) at

the most recent evaluation. For 46 of the 78 pa-

tients with two or more measurements who were

prescribed daily air stacking/lung insufflation, the

MIC and LIC increased 462 � 260 and 365 � 289

ml, respectively, despite a decrease in VC of 209 �

97 ml. The increase in lung volumes by air stacking

to approach MIC combined with abdominal thrust

resulted in CPF of 4.3 � 1.7 liters/sec by compar-

ison with unassisted CPF of 2.5 � 2.0 liters/sec

(P � 0.001). Patients’ diagnoses, VC, MIC, LIC, CPF,

and extent of ventilator use are noted in Table 1.

Although they could not be measured, “cough” flows

FIGURE 1 Air is delivered via the manual resuscitator (bottom) to full lung expansion, with the exhalation port

of the spirometer manually covered so that the insufflated air does not exit the patient (or enter the

spirometer) until its exhalation port is uncovered at maximally tolerated lung inflation (top).




from the greater lung volumes at LIC can only exceedflows obtained from the necessarily smaller MIC.

For 15 patients, the LIC did not exceed theMIC; any insufflation beyond VC triggered cough-ing that was most likely attributable to airwayirritation or atelectasis from saliva aspiration be-cause no patients had lung/airways disease or highpressure resistance to insufflation. Deep breathsalso caused these patients to cough. These patientshad little or no ability to air stack, because of severebulbar-innervated muscle dysfunction. Eleven ofthe 15 patients had gastrostomy tubes, and 13 whohad had modified Barium swallow examinationshad faucial pooling of secretions with glottic pen-etration.

For the 282 patients, the Spearman correlationcoefficient revealed a negative association betweenLIC � MIC and MIC � VC (rS � �0.23, P � 0.01)(Fig. 2). Even stronger negative associations werefound for the ALS (rS � �0.30, P � 0.0085) andDMD (rS � �0.38, P � 0.0051) subpopulations.The LIC � MIC trended inversely with VC (sitting)(P � 0.001). The MIC � VC did not vary signifi-cantly as a function of VC (sitting). The LIC � VCtrended inversely with VC (sitting), with marginalstatistical significance (P � 0.048).

DISCUSSION

This work describes a simple technique forproviding deep lung insufflations and for quanti-tating them. Patients with NMD often lose VC tothe extent that they can expand their lungs to onlya small fraction of predicted volumes. For example,DMD patients’ VC decrease to approximately 10%of predicted normal by age 20,14 and typical SMAtype 1 patients’ VC have been reported to neverexceed 250 ml, which, by age 10, amounts to lessthan 10% of the predicted normal value.2 Incentivespirometry is, therefore, useless because such pa-tients’ tidal volumes approach their deepestbreaths, and these cannot exceed a small percent-age of their IC. Likewise, in reviews of studies inwhich inspiratory resistive exercise was performedby NMD patients, no effect on VC, lung volumes, ormaximum inspiratory or expiratory pressures wasreported.15,16 On the other hand, expanding thelungs well beyond IC by air stacking or by single,deep insufflations permits greater lung distension,voice volume, and CPF6 and can decrease atelecta-sis and loss of pulmonary compliance.10 Our re-sults show that the benefits can be greatest for themost advanced patients with the lowest VC. Thefact that lung expansion to LIC � VC trends in-versely with VC, whereas MIC � VC does not,indicates that, for the most advanced patients, it isincreasingly important to expand the lungs by pas-sive insufflation rather than by air stacking. Inaddition, MIC and LIC can increase with practice.

Tab

le1

Pat

ient

diag

nose

s

Maj

or

Dia

gn

ose

sN

o.

of

Pat

ien

tsM

ean

Age

Mea

nV

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tM

ean

MIC

Mea

nL

ICM

ean

CP

FM

ean

AC

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>8

hrs

NIV

8h

rsN

on

e

DM

D53

26

(14–44)

�7

62

2(1

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71

0)

�5

95

12

52

(22

0–

32

80

)�

67

01

69

6(8

40

–3

40

0)

�5

48

1.5

8(0

.1–

5.7

)�

1.7

3.7

6(0

–6

.2)

�1

.43

31

65

Myo

ton

ic6

47

(36–53)

�7

20

38

(11

90

–3

58

0)

�8

64

22

80

(11

90

–3

72

0)

�8

74

24

47

(13

80

–3

85

0)

�8

51

4.0

3(2

.7–

4.7

)�

0.8

5.1

0(4

.4–

5.9

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0.6

02

4O

ther

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s55

39

(11–85)

�18

11

95

(27

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27

70

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64

21

74

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36

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20

26

(50

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31

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19

(7–56)

�14

86

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81

54

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1.7

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1.5

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AL

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57

(27–82)

�13

13

71

(20

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�7

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19

39

(15

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24

09

(78

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98

92

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Post

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66

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41

87

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�6

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21

68

(12

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96

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.51

01

05

Mis

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36

44

(16–58)

�14

13

54

(35

0–

17

60

)�

70

01

98

4(3

80

–3

80

0)

�9

84

22

29

(45

0–

38

50

)�

98

53

.05

(0.1

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�2

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(0–

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Tota

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42

(7–85)

�20

11

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71

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9

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ity;

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Inability to air stack no longer means that patientscannot simply and inexpensively expand theirlungs beyond IC.

This study demonstrates that like MIC minusVC17 and assisted minus unassisted CPF,12 LIC �

MIC, too, is an objective, quantifiable, reproduciblemeasure that (inversely) correlates with glottic in-tegrity. Glottic function is the most important as-pect of bulbar-innervated muscle function for NMDpatients6,12 because it is most important for airwayprotection and cough effectiveness and, therefore,permits the use of NIV to avoid otherwise inevitablerespiratory failure leading to death or tracheos-tomy with decreased quality of life.11 In fact, in arecent study, all decanulated/extubated patientswith sufficient glottic function for (assisted) CPFgreater than or equal to 160 liters/min were suc-cessfully extubated, whereas those with less than160 liters/min failed extubation within 48 hrs.18

Previously reported correlates of bulbar-innervatedmuscle function have been based on subjective-only assessments of speech and swallowing.19,20

Some patients were hypercapnic on presenta-tion and had lungs stiff to the extent that using amanual resuscitator to increase tidal volumes tonormalize CO2 failed to do so and resulted in highairway pressures and chest discomfort. With regu-lar lung mobilization therapy and nocturnal NIV,however, five such patients became able to renor-malize CO2 when breathing autonomously withoutchest discomfort. This is consistent with previousstudies in which passive lung insufflation volumeswere greatly diminished for patients who were ven-tilated at constant pressures/volumes without reg-ular deep insufflations.10,21 Patients supported byNIV at large delivered volumes (1100–1500 ml)11

physiologically vary tidal volumes, can air stack todeep lung volumes as a function of their bulbar-innervated muscle integrity, and can better retainlung distensibility. Thus, if pressure-cycled venti-

lators such as “BiPAP” units (with which air stack-ing is impossible) are used for nocturnal NIV, pa-tients with diminished VC should be equipped forair stacking/maximal insufflations. One DMD pa-tient who had been using continuous tracheostomyventilation at 250 ml delivered volumes for 9 yrs,had PaCO2 76 cm H2O, and could not tolerate a100-ml volume increase without chest pain. Bycontrast, our 53 DMD patients who practice dailyinsufflation, mean age 26 � 7 yrs, tolerated deliv-ered volumes that exceeded VC by 1074 � 406 ml.Eight of these patients with VC less than 200 ml(mean 101 ml) have MIC values of 874 � 548 mland LIC values of 1414 � 764 ml.

In conclusion, regular lung insufflation, eitherby air stacking (to approach MIC) or by passivelung insufflation (to approach LIC), is indicated forall NMD patients with diminishing VC. Because thegoal is to approach the predicted IC, passive insuf-flation is used when the patient obtains a deepervolume in this manner than by air stacking (i.e.,when bulbar musculature is very weak). It is oftenbeneficial to prescribe both methods.

REFERENCES

1. Bach JR, Rajaraman R, Ballanger F, et al: Neuromus-

cular ventilatory insufficiency: the effect of home

mechanical ventilator use vs. oxygen therapy on

pneumonia and hospitalization rates. Am J Phys Med

Rehabil 1998;77:8–19

2. Bach JR, Saltstein K, Sinquee D, Weaver B, Komaroff

E: Long term survival in Werdnig-Hoffmann disease.

Am J Phys Med Rehabil 2007;86:339–48

3. Finder JD, Birnkrant D, Carl J, et al: Respiratory care

of the patient with Duchenne muscular dystrophy:

American Thoracic Society consensus statement.

Am J Respir Crit Care Med 2004;170:456–65

4. Leith DE: Lung biology in health and desease: respi-

ratory defense mechanisms, part 2, in Brain JD,

Proctor D, Reid L (eds): Cough. New York, Marcel

Dekker, 1977, pp 545–92

FIGURE 2 Plot of LIC � MIC vs. MIC � VC in milliliters, where LIC is lung insufflation capacity, MIC is

maximum insufflation capacity, and VC is vital capacity.




5. Gauld LM, Boynton A: Relationship between peak

cough flow and spirometry in Duchenne muscular

dystrophy. Pediatr Pulmonol 2005;39:457–60

6. Kang SW, Bach JR: Maximum insufflation capacity:

vital capacity and cough flows in neuromuscular

disease. Am J Phys Med Rehabil 2000;79:222–7

7. Seccombe LM, Rogers PG, Mai N, et al: Features of

glossopharyngeal breathing in breath-hold divers.

J Appl Physiol 2006;101:799–801

8. Bach JR, Tewfik G: “Air doping”: an expose on “frog”

insufflation in competitive sports. Am J Phys Med

Rehabil 2007;86:301–3

9. Mygren-Bonnier M, Lindholm P, Markstrom A,

Skedinger M, Mattsson E, Klefbeck B: Effects of

glossopharyngeal pistoning for lung insufflation on

vital capacity in healthy women. Am J Phys Med

Rehabil 2007;86:290–4

10. Lechtzin N, Shade D, Clawson L, Wiener CM: Supra-

maximal inflation improves lung compliance in sub-

jects with amyotrophic lateral sclerosis. Chest 2006;

129:1322–9

11. Gomez-Merino E, Bach JR: Duchenne muscular

dystrophy: prolongation of life by noninvasive respi-

ratory muscle aids. Am J Phys Med Rehabil 2002;81:

411–5

12. Bach JR, Gonzalves M, Paez S: Expiratory flow ma-

neuvers of patients with neuromuscular diseases.

Am J Phys Med Rehabil 2006;85:105–11

13. Bach JR, Bianchi C, Aufiero E: Oximetry and indica-

tions for tracheotomy in amyotrophic lateral sclero-

sis. Chest 2004;126:1502–7

14. Bach J, Alba A, Pilkington LA, Lee M: Long-term

rehabilitation in advanced stage of childhood onset,

rapidly progressive muscular dystrophy. Arch Phys

Med Rehabil 1981;62:328–31

15. DiMarco AF, Kelling JS, DiMarco MS, Jacobs I,

Shields R, Altose MD: The effects of inspiratory re-

sistive training on respiratory muscle function in

patients with muscular dystrophy. Muscle Nerve

1985;8:284–90

16. Martin AJ, Stern L, Yeates J, Lepp D, Little J: Respi-

ratory muscle training in Duchenne muscular dys-

trophy. Dev Med Child Neurol 1986;28:314–8

17. Kang SW, Bach JR: Maximum insufflation capacity.

Chest 2000;118:61–5

18. Bach JR, Saporito LR: Criteria for extubation and

tracheostomy tube removal for patients with venti-

latory failure: a different approach to weaning. Chest

1996;110:1566–71

19. Gilardeau C: Troubles de la deglutition dans la dys-

trophie musculaire de Duchenne de Boulogne, in:

Gastro-Enterologie et Maladies Neuromusculaires.

Evry, Association Francaise Contre les Myopathies,

1991, pp 79–87

20. Norris FH, Calanchini PR, Fallat RJ, et al: The ad-

ministration of guanidine in amyotrophic lateral

sclerosis. Neurology 1974;24:721–8

21. Bach JR, Kang SW: Disorders of ventilation: weak-

ness, stiffness, and mobilization. Chest 2000;117:

301–3




Study 7

Indications and Compliance of Home Mechanical

Insufflation-Exsufflation in Patients with

Neuromuscular Diseases

João Bento, Miguel Gonçalves, Nuno Silva, Tiago Pinto Anabela Marinho João Carlos Winck



Órgano Oficial de la Sociedad Española de Neumología y Cirugía Torácica (SEPAR),la Asociación Latinoamericana del Tórax (ALAT) y la Asociación Iberoamericana de Cirugía Torácica (AIACT)

Volumen 46, Número 7, Julio 2010

www.archbronconeumol.org

Originales

Auditoria clínica de los pacientes hospitalizados por

exacerbación de EPOC en España (estudio AUDIPOC):

método y organización del trabajo

Factores asociados con el control del asma en

pacientes de atención primaria en España:

el estudio CHAS

Valores pretratamiento e inducidos por el tratamiento

de enolasa específica de neurona en pacientes con

cáncer de pulmón microcítico: estudio prospectivo,

abierto

Relación del test de control del asma (ACT) con la

función pulmonar, niveles de óxido nítrico exhalado

y grados de control según la Iniciativa Global para

el Asma (GINA)

Revisión

Hipercapnia permisiva o no permisiva: mecanismos

de acción y consecuencias de altos niveles de

dióxido de carbono

Artículo especial

Archivo de Archivos: 2009

Archivos deBronconeumolog ía

ISSN: 0300-2896

www.archbronconeumol.org

0300-2896/$ - see front matter © 2009 SEPAR. Published by Elsevier España, S.L. All rights reserved.

Arch Bronconeumol. 2010;46(8):420-425

Original Article

Indications and Compliance of Home Mechanical Insufflation-Exsufflation in Patients with Neuromuscular Diseases

João Bento,a,* Miguel Gonçalves,a,b Nuno Silva,c Tiago Pinto,a Anabela Marinho,a and João Carlos Winck,a,b

a Pulmonology Department, HS João, Oporto, Portugalb Faculty of Medicine, University of Porto, Oporto, Portugalc Linde homecare, Oporto, Portugal

*Corresponding author.

E-mail address: [email protected] (J. Bento).

A R T I C L E I N F O

Article info:

Received October 20, 2009

Accepted April 22, 2010

Keywords:

Mechanical insufflation-exsufflation

Home

Safety

Efficacy

Neuromuscular disease

Palabras clave:

Insuflación-exuflación mecánica

Domicilio

Seguridad

Eficacia

Enfermedad neuromuscular

A B S T R A C T

Introduction: Neuromuscular disease (NMD) patients frequently have impaired cough. Mechanical

insufflation-exsufflation (MI-E) has proven efficacy in improving airway clearance, however data related to

its long-term home use is lacking. The purpose of this study was to describe indications, safety and

compliance of home MI-E in NMD patients.

Methods: Four years observational analysis of 21 NMD patients on home MI-E. Diagnosis included bulbar

and non-bulbar Amyotrophic Lateral Sclerosis (ALS) and other NMD. Median age was 58 years. Only

cooperative patients with unassisted baseline Peak Cough Flow (PCF) < 270 L/min were included. All

patients were under continuous mechanical ventilation (6 by tracheostomy). Pulmonary function before

initiation of MI-E (median): FVC = 0.81 L, MIP = 28 cmH2O, MEP = 22 cmH2O and PCF = 60 L/min. MI-E was

performed by previously trained non-professional caregivers, with an on-call support of a trained health

care professional. Patients had pulse oximetry monitorization and applied MI-E whenever SpO2 < 95 %.

Median follow-up was 12 months (3-41 months).

Results: Ten patients (9 ALS) used MI-E daily. Eleven patients used MI-E intermittently, during exacerbations,

and in 8 patients early application of MI-E (guided by oximetry feed-back) avoided hospitalization. All

tracheostomized patients used MI-E daily and more times a day than patients under NIV. Four patients

(3 bulbar ALS), were hospitalized due to secretion encumbrance. MI-E was well-tolerated and there were

no complications. In general, caregivers considered MI-E effective. During this period, 4 patients died,

related to disease progression.

Conclusions: Home MI-E is well tolerated, effective and safe if used by well trained caregivers. MI-E should

be considered as a complement to mechanical ventilation.

© 2009 SEPAR. Published by Elsevier España, S.L. All rights reserved.

Indicaciones y cumplimiento con la insuflación-exuflación mecánica domiciliaria en pacientes con enfermedades neuromusculares

R E S U M E N

Introducción: Con frecuencia, los pacientes con enfermedades neuromusculares (ENM) presentan un dete-

rioro del mecanismo de la tos. Se ha demostrado la eficacia de la insuflación-exuflación mecánica (IEM) en

la mejora del aclaramiento de las vías respiratorias aunque no se dispone de datos relacionados con su uti-

lización domiciliaria a largo plazo. El objetivo del presente estudio fue describir las indicaciones, tolerabili-

dad y cumplimiento con la IEM domiciliaria en pacientes con ENM.



J. Bento et al / Arch Bronconeumol. 2010;46(8):420-425 421

Métodos: Análisis observacional de 4 años de duración de 21 pacientes ENM tratados con IEM domiciliaria.

El diagnóstico incluyó esclerosis lateral amiotrófica (ELA) bulbar y no bulbar y otras ENM. La edad mediana

fue de 58 años. Sólo se incluyeron pacientes cooperadores con valores de flujo pico de tos basal (FTM) no

asistido < 270 l/min. Todos los pacientes estaban sometidos a ventilación mecánica continua (seis mediante

traqueostomía). La función pulmonar previa al inicio de la IEM (mediana) era: FVC, 0,81 l, MIP, 28 cmH2O,

MEP = 22 cmH2O y PCF = 60 l/min. Cuidadores no profesionales adiestrados previamente con el apoyo per-

manente de un profesional sanitario experto efectuaron la IEM. En los pacientes se monitorizó la pulsioxi-

metría y se aplicó IEM siempre que la SpO2 fue < 95 %. El seguimiento mediano fue de 12 meses (3-41 me-

ses).

Resultados: Utilizaron diariamente IEM 10 pacientes (nueve con ELA). La utilizaron de forma intermitente

11 pacientes durante las exacerbaciones y en 8 la aplicación precoz de IEM (guiada por la información de la

oximetría) evitó la hospitalización. Todos los pacientes traqueostomizados utilizaron la IEM a diario y un

mayor número de veces al día que los pacientes sometidos a ventilación mecánica no invasiva (VNI). Requi-

rieron ingreso hospitalario 4 pacientes (3 ELA bulbar) debido a la acumulación de secreciones. La IEM fue

bien tolerada y no se asoció a complicaciones. En general, los cuidadores la consideraron eficaz. Durante

este período, 4 pacientes fallecieron, en relación con la progresión de la enfermedad.

Conclusiones: La IEM domiciliaria es bien tolerada, eficaz y segura cuando la utilizan cuidadores adiestrados

apropiadamente. Debe considerarse un complemento de la ventilación mecánica.

© 2009 SEPAR. Publicado por Elsevier España, S.L. Todos los derechos reservados.

Introduction

Patients with neuromuscular diseases (NMD) frequently have weak respiratory muscles and a deteriorated cough mechanism. Effective coughing depends on the capacity of the inspiratory muscles to achieve an inspiration of about 80 % of total pulmonary capacity, followed by closure of the glottis and a pause with an increase in pulmonary volume. 1 After the contraction of the expiratory muscles, intrathoracic pressure increases and, when the glottis opens, air is expelled and secretions are propelled to the central airways. 1 Therefore, deterioration of the cough reflex in patients with NMD is related to weakness of the respiratory muscles, bulbar dysfunction that causes disability to control the glottis or even a deformity of the chest wall due to scoliosis. 1-5 Deterioration of the cough reflex causes insufficient airway clearance, pneumonia, athelectasia, and respiratory failure related to the accumulation of secretions. 2,5 Based on basal function, a peak cough flow (PCF) < 160 l/min has been proposed as an indication of an ineffectual cough. 2,5-8 However, Even a basal PCF < 270 l/min has been associated with pulmonary complications, since, during acute disease, there are additional reductions of the force of the respiratory muscles with an even greater reduction of PCF. 2,9-11 As a result, management of airway secretions, especially during intercurrent airway infections, is a significant problem in patients with NMD and is the main cause of morbidity, prolonged hospitalisation, intensive care admissions and mortality. 2,5,9,12-15 The techniques to improve airway clearance can reduce complications related to the accumulation of secretions and hospitalisation rates to a minimum. 3,15,16 However, in patients with chest wall deformity, physiotherapy and manually assisted expectoration techniques can be ineffectual. 17 These techniques are also time-consuming and require an appropriately trained carer.

Mechanical Insufflation-exsufflation (MIE) is a mechanically assisted cough technique. It gradually applies positive pressure to the airways, followed by a rapid change due to negative pressure. It can be applied using a face mask or a tracheotomy tube. 2,5 In 1953, the first device for mechanical assistance of coughing was marketed. Since then, various studies have confirmed its efficacy. MIE is considered more effective than other reference techniques to increase the coughing mechanism. 4,5,7 In spite of ever greater experience and published results on this technique, only limited data is available on its indications for home use, as also on compliance and safety.

The aim of this study is to describe the indications for home treatment using MIE, as also to determine its safety and compliance in patients with NMD.

Material and Methods

Since 1989, the Pneumology Service of the Sant João Hospital has an ambulatory clinic for NMD in collaboration with the Neurology Service. This clinic offers respiratory care to many patients suffering from NMD.

IEM devices have been used for home care since February 2005. The device was prescribed for continuous daily rent. These devices are included in the respiratory material offered to patients according to specific clinical indications. This material includes instruments for ventilation, monitoring, and control of secretions and is hired by a home care private company that also provides regular home visits by health professionals. The MIE device and a portable oximeter have a daily rental cost of 10 Euros. All the expenses caused by this home treatment are the responsibility of the Hospital. All the strategies related to clinical assessment of patients, adaptation of devices and programs for carer training are carried out by professionals from the Pneumology Service of the NMD ambulatory clinic.

All the patients prescribed home MIE were included in this study. An observational analysis was carried out with a 4 year follow-up. The patients were recruited in the Pneumology Service from those on the multidisciplinary NMD clinic. The protocol was approved by the Investigation Committee of the Hospital and the study was carried out according to the ethical directives for investigation in humans and the principles of the Helsinki Declaration (1975, revised in 1983).

Patients

Patients were studied from February 2005 to February 2009. Home MIE was prescribed for 21 NMD patients (15 men) of a median age of 58 years (27-72 years). The diagnosis included bulbar and non-bulbar amyotrophic lateral sclerosis (ALS), Duchenne muscular dystrophy (DMD) and other NMD. The demographic data of the population studied are described at table 1. Inclusion criteria were as follows: diagnosis of NMD, basal assisted < 270 l/min and continuous dependence on mechanical ventilation (24 hours a day). For the prescription of home MIE the decisive criteria was insufficient assisted PCF, after a technique of air entrapment (in patients with non-bulbar ALS) in combination with abdominal thrust. All patients with NMD receiving mechanical ventilation through a tracheotomy were also included.

Patients who could not cooperate or did not receive dedicated care were excluded. All patients depended on continuous home



422 J. Bento et al / Arch Bronconeumol. 2010;46(8):420-425

mechanical ventilation through a volume limited time-cycled ventilator (mean current volume 1,000 ml). At the beginning of the study, 6 patients had tracheotomy tubes and 15 patients used continues VNI combining ventilation through a mouthpiece during the day and ventilation with a face-mask during the night.

Before entering the ambulatory MIE protocol, 20 patients had come to the emergency service due to respiratory complications related to the accumulation of secretions (median 3 hospitalisations per patient) and 12 patients had required hospitalisation due to respiratory infections (median 2 hospitalisations per patient).

Determinations

All patients underwent pulmonary function, respiratory muscle force and PCF screening. Pulmonary function was determined by spirometry (Vmax 229, Autobox, Sensormedics), registering the maximum expiratory volume during the first second of forced expiration (FEV1) and forced vital capacity (FVC). All lung function tests were carried out in a sitting position according to reference procedures defined by the ATS-ERS 2005work group. 18

Maximum inspiratory pressure (MIP) and maximum expiratory pressure (MEP) were determined with a portable pressure manometer with an occludable mouthpiece (Micro RPM, Micromedical Limited) during maximum inspiratory and expiratory manoeuvres through the mouthpiece starting with the residual volume (MIP) and from total lung capacity (MEP). These determinations were performed according to reference procedures defined by the ATS-ERS 2002 work group. 19 The manoeuvres were repeated until three determinations with a variability < 5 % were obtained.

The PCF was only determined in non-tracheotomised patients by requesting the patient in a sitting position to carry out a cough manoeuvre beginning by total lung capacity (TLC) by means of a standard (Assess Healthscan products, Inc.) flow-meter connected to a face-mask.

Maximum insufflation capacity (MIC) was assessed by spirometry requesting the patient to retain 2 consecutive air volumes supplied by a manual resuscitator bag (air entrapment technique). 20 Bulbar deterioration and glottic dysfunction were evaluated in non-tracheotomised patients by assessing the MIC/FVC ratio. It was considered that patients with a ratio # < 1 presented bulbar dysfunction. For patients with appropriate bulbar function assisted PCF is determined after the air entrapment test with synchronised manual abdominal compression synchronised with the cough effort.

Since the patients with bulbar dysfunction could not carry out the air entrapment test, assisted PCF was only determined by application of manual abdominal compression.

Protocol for Home MIE

Home MIE was carried out using the Cough-Assist® (Philips, Respironics, Inc) device using an oronasal mask or a non-fenestrated tracheotomy tube with an inflated cuff. Both patients and carers were trained in the use of a portable pulse-oximeter (Nonin 9500

oximeter Minneapolis Plymouth USA) and given information on the use of MIE in their homes, in which a MIE session was applied in each episode of SpO2 < 95 %, until a value > 95 % was obtained. 23 For better tolerance periods of rest with ventilation between sessions were applied. Before the prescription of home MIE, all the patients and carers in our service were convened to receive specific training on the technique with a specialized respiratory physiotherapist. Training included device management (adjustments and circuit connections) and a practical seminar with clinical simulations, and also detection of clinical signs necessary to determine efficacy. Each session consisted of 6-8 cycles of insufflation-exsufflation with mean pressures of 40 to -40 cmH2O. The duration of each cycle was 3 seconds for insufflation, 2 seconds for exsufflation and 4 seconds for the post-exsufflation pause. During the exsufflation phase, patients were trained to cough, at the same time a carer applied abdominal compression. The adaptation of the technique was gradual, pressure was increased progressively to obtain an adequate chest expansion at a comfortable level to eliminate secretions.

Home MIE was always administered y non-professional trained carers (family members or private assistants) with the support of a health care professional with experience from a home care private company (nurse or respiratory physiotherapist). In case of doubt, the carer called the health professional to resolve the problem or to help carry out the technique in difficult situations. Both patients and carers were trained to detect early signs of respiratory failure or respiratory infections and were instructed to contact service staff (pneumologist or respiratory physiotherapist) on appearance of the first sign. Whenever dyspnoea increased, secretions accumulated or a value of SpO2 < 95 % persisted, in spite of continuous use of the ventilator and an aggressive home technique (with the support of expert health carers), the patients were instructed to come in to the emergency service (ES) of the local hospital. The aim of the treatment

Diagnosis Amyotrophic lateral

sclerosis

Duchenne muscular

dystrophy

Other neuromuscular

diseases

Multiple sclerosis All

Patients, number 15 2 3 1 21

Age (onset of respiratory deterioration) 62 (46-72) 32 (30-34) 35 (27-36) 68 58 (27-72)

Duration of symptoms, months 26 (9-90) 83 (27-139) 38 (8-271) 7 29 (7-271)

FVC (l and predictable %) 0.99 (0.4-1.93) 0.4 (0.26-0.54) 0.6 (0.26-0.84) 0.7 0.81 (0.26-1.93)

32.5 % (15-48 %) 9.5 % (7-12 %) 14 % (7-20 %) 29 % 27.5 % (7-48 %)

FEV1 (l and predictable %) 0.95 (0.3-1.76) 0.37 (0.24-0.49) 0.57 (0.24-0.84) 0.67 0.72 (0.24-1.76)

34 % (7-56 %) 10 % (7-13 %) 16.5 % (7-23 %) 33 % 28 % (7-56 %)

MIP (cmH2O) 31 (0-45) 14 (0-28) 16 (0-28) ND 28 (0-45)

MEP (cmH2O) 27 (0-56) 15 (3-27) 21 (3-27) ND 22 (0-56)

Spontaneous PCF (l/min) 60 (0-250) 90 (80-100) 115 (80-150) 40 60 (0-250)

Assisted PCF (l/min) 160 (0-260) 170 (160-180) 192.5 (130-250) 80 160 (0-260)

NIV, No. of patients 10 2 2 1 15

Tracheotomy, No. of patients 5 0 1 0 6

Time undergoing continuous ventilation

support, months.

24.5 (9-51) 81.5 (24-139) 37 (7-271) 6 29 (7-271)

Table 1

Characteristics and prior lung function in patients before applying mechanical insufflation-exsufflation protocol

FEV1 indicates forced expiratory volume in first second; MEP, maximum expiratory pressure; MIP, maximum inspiratory pressure; NIV, non invasive ventilation; PCF, peak cough

flow.




was defined as satisfactory control of acute dyspnoea or secretion accumulation, confirmed by pulse-oximetry data (SpO2 > 95 %).

Variables Analysed

A descriptive statistical analysis was performed using the SPSS 14.0 database for Windows. Data presented are function on diagnosis, symptom duration, time on mechanical ventilation, spirometry, force of respiratory muscles and assisted and non-assisted PCF. Compliance, tolerance and efficacy were assessed based on daily frequency of MIE use, number of complications, number of visits to the ES due to episodes of secretion accumulation and number of hospitalisations related to airway infections. Clinical files were analysed to assess the number of visits to the ES and the number of hospitalizations prior to the MIE protocol.

Intolerance and adverse effects of the technique were also examined.

Results

A total of 21 patients with NMD undergoing continuous mechanical ventilation (6 with tracheotomies) and home MIE treatment were studied. The diagnoses were the following: Amyotrophic lateral sclerosis (ASL) (n = 5), Duchenne muscular dystrophy (DMD) (n = 2), other NMDs (n = 3) and multiple sclerosis (EM) (n = 1) (table 1). Other NMDs included a heterogeneous group of diseases: Myopathy due to cytoplasmic inclusion bodies, type 2 spinal muscular atrophy and non-classified myopathies. Lung function prior to MIE can be seen at table 1.

Median time of onset of respiratory deterioration of the patients were 29 months (7-271 months) and had been using home ventilation support treatment for a median of 29 months (7-271 months) before their inclusion in the protocol (table 1). As to the ALS patients, at the beginning of the program, there were 6 patients with severe bulbar dysfunction. During follow-up, there was disease progression, so that, at the end of treatment, 10 patients presented severe bulbar dysfunction, 5 of them had undergone tracheotomy (5 rejected it). There was also a patient with non-classified myopathy, ventilated through a tracheotomy, without bulbar dysfunction, that rejected decannulation to VNI.

Compliance with MIE is shown in table 2. This technique was used daily by 10 patients (7 with bulbar ALS and 1 with non-classified myopathy) (table 2). The 6 patients with tracheotomy (5 with bulbar ALS and 1 with non-classified myopathy) and 4 patients undergoing VNI (2 with bulbar ALS that rejected tracheotomy and 2 with non-bulbar ALS) used the technique daily. The data related to daily frequency of sessions in the groups of daily users are shown in table 3. In this group, the patients with tracheotomies used MIE more times a day than those with VNI (table 3).

The technique was used intermittently by 11 patients (table 2). These patients only used the device during acute exacerbations, such as infection of the airways or during individual episodes of secretion accumulation. When the exacerbation was resolved of the secretions reduced to the point of maintaining a SpO2 > 95 %, its use was interrupted.

In general, the carers considered the device was effective.In 8 patients the early application of MIE (guided by oximetry

data) prevented visits to the ES due to an accumulation of secretions

and the device inverted the episode of desaturations and normalized SpO2 without the need to administer supplementary oxygen. The 8 patients and their respective carers reported that, if they had not had access to the device, they would have had to come in to the emergency service.

In 4 patients (3 bulbar ALS and 1 non-bulbar ALS), home MIE was not sufficient to normalise oxygen saturation and required hospitalisations to treat accumulated secretions during acute respiratory airway infections (table 4). Of the 3 bulbar ALS patients, one of them had undergone a tracheotomy and the other 2 had constantly rejected it.

Home MIE was well tolerated and there were no complications related to treatment (table 4).

During the study period, 4 patients with bulbar ALS died due to disease progression (table 4).

Discussion

The efficacy of MIE to increase PCF and improve the efficacy of cough manoeuvre has already been demonstrated. 1-4,7,13,14,21,22 Chatwin et al compared different interventions (cough assisted by physiotherapy, cough assisted by VNI, cough assisted by exsufflation and MIE) with non-assisted cough and showed that MIE was the technique associated with the greatest increase in PCF. 4 Oximetry data has shown the usefulness of this technique since it makes it possible to detect a sudden decrease of oxygen saturation as a consequence of a mucous plug. 2,3,15,21 The patients described in this study suffered from severe ventilation failure and continuously depended on mechanical ventilation (24 hours a day). They had all used volume limited time-cycled ventilation for many years before inclusion in the study.

This study was based on the protocol proposed by Bach et al, that consists in home treatment with a VNI support, oximetry monitoring during 24 hours and the use of MIE guided by the data from this (SpO2 < 95 %). 3,7,15,23,24

In this study home MIE was carried out by non-professional carers of the patients with the support of health professionals trained in home care.

Few studies have described home respiratory treatment with MIE in patients with NMD, although many studies describe the efficacy of the combination of cough assistance techniques, manual and mechanical, in acute in-hospital situations. 8,9,21 Although MIE carried out by non-professional carers has been considered effective and well tolerated, it causes certain controversy and we still require more data on its home use in the long term. 15,21,23,24

In our strategy, the main condition for effective home care after hospital discharge was the presence of appropriately trained and

Diagnosis Bulbar amyotrophic

lateral sclerosis

Non-bulbar amyotrophic

lateral sclerosis

Duchenne muscular

dystrophy

Other myopathies Multiple sclerosis All

Daily users 7 2 0 1 0 10

Intermittent users 3 3 2 2 1 11

Table 2

Compliance with mechanical insufflation-exsufflation

Patients with ventilator support Median (min-max) No. of patients

Users of ventilations that

underwent tracheotomy

6 (3-6) times a day 6 (100 %)

Users of non-invasive ventilation 3 (1-4) times a day 4 (26.7 %)

All 4.5 (1-6) times a day 10 (47.6 %)

Table 3

Daily users of mechanical insufflation-exsufflation



424 J. Bento et al / Arch Bronconeumol. 2010;46(8):420-425

motivated carers. This study supports the importance of an appropriate early training phase, administered to both patients and carers in the hospital, as has also been proposed by Tzeng et al. 15 Furthermore, This study confirmed that carers with appropriate training and motivation can detect respiratory worsening and effectively use a home MIE protocol. Patients with neuromuscular diseases, especially ALS, can suffer progressive disease with early decrease of respiratory muscle force and cough deterioration, both associated with premature death. 3,9,14,25,26 The natural course of NMD does not make it possible to clarify the influence of home MIE on visits to the ES/hospitalizations. The number of episodes before and after the home MIE protocol is not comparable. Indeed, before beginning home treatment, the patients’ cough reflex was more powerful and therefore, they suffered fewer episodes of secretion accumulation. In contrast to other NMD, ALS also includes glottic muscle control. In general, in patients with non-bulbar NMD non-invasive support treatment may be used and they have a higher survival rate. 3,5,16 However, the almost inevitable progression to bulbar dysfunction is one of the more negative characteristics of this disease and the main reason due to which, in contrast to other NMDs, tracheotomy becomes necessary to prolong survival. 1,3,6-9,12,13,16,23,24,26,27 The MIC/FVC ratio has been widely used to assess bulbar function, due to the fact that appropriate glottic function is necessary to accumulate consecutive volumes of air to achieve MIC. 20 Furthermore, a severe bulbar dysfunction is also responsible for dysfunction of the higher respiratory airway muscles in this group of patients. 2,4,13,23,25 Sancho et al have identified 2 types of bulbar ALS patients: those that only suffer from failure of glottis closure that cannot entrap air but in which MIE can be effective and those that present a dynamic collapse of the upper respiratory airways in which MIE is not effective and can even cause risk. 25 In this study, ALS, the most usual diagnosis, is seen in a heterogeneous group: from a non-bulbar disease with inadequate PCF to a severe bulbar disease that requires tracheotomy. This in itself represents an additional problem concerning patient acceptance or associated problems (local inflammation, increase of secretions and infections). 2,3,12,15,26,28 Indeed, although it was offered to all patients with severe bulbar dysfunction, some continued to reject it and preferred to continue with VNI and the MIE protocol. Bach et al have also described the fact that patients with severe bulbar ALS can receive support treatment with the combined use of VNI and MIE, which delays tracheotomy, as long as they can maintain an oxygen saturation > 95 % with ambient air. 23 However, these patients required careful regular supervision to anticipate the failure of a non-invasive strategy, so that therapeutic options can be examined and analysed with patients and their families, so that decisions can be made beforehand and not at the time of a respiratory crisis. Farrero et al have suggested that a follow-up every 3 months or on patient demand makes it possible to opportunely recognise disease progression. 16

In this study, each MIE session consisted of 6-8 cycles of insufflations-exsufflations with mean pressures of 40 to –40 cm H2O, titrated according to patient tolerance. Chatwin and Sivasothy have considered that lower pressures are more comfortable and involve fewer risks. 4,17 However, the adjustments used in this study are widely preferred due to their effects on patient welfare and their efficacy and are also suggested by the manufacturers. 1,3,8,24,29 In general, they are well tolerated and have been considered the most effective means of obtaining higher values of PCF with practically no complications. 1,3,5,7,8,21,24 In spite of this, we paid special attention to careful individual titration of the MIE pressure, to obtain maximum chest expansion, respecting welfare, which can justify the tolerance and absence of complications seen in this study. The application of MIE was adjusted to the needs of each patient in as far as frequency of use, considering daily and intermittent users. With intermittent users it was not possible to register the number of MIE sessions per month or week because compliance was not regular and depended on the number and severity of respiratory exacerbations. In contrast, daily users reported that they used the device every day, independently of exacerbations, both for secretion control and for lung insufflation and to revert episodes of SpO2 < 95 %. This study also shows that patients that had undergone tracheotomy used MIE daily and more times a day than patients with VNI. This fact may be due to local inflammation and the increase of secretions related to tracheotomy. We also found that some patients with bulbar ALS, incapable of air entrapment, did not only use MIE as a technique for cough assistance, but also for lung insufflation.

According to this study, both patients and carers described greater efficacy in clearance of airway secretions with this home protocol. Its early application, guided by oximetry data with normalisation of oxygen saturation with ambient air, prevented visits to the Emergency Service due to secretion accumulation. Patients stated that, during these episodes, without MIE, they would have had to go to hospital due to their acute respiratory problems. Furthermore, there were very few episodes in which home MIE was not sufficient to resolve the problem of secretion accumulation and made it unnecessary to visit the ES or to require hospitalisation. None of these patients required intubation. Indeed, it would seem that the protocol reduces the risk of airway infection and prevents both visits to the ES and hospitalizations. Bach et al have reported that patients with NMD dependent on VNI that used MIE guided by oximetry data can be treated at home without risk or need of hospitalisation. 3,6,7,13,14,15

This study did not show any complications related to use of the device. Potential complications are very infrequent and include abdominal distension, increase of gastroesophageal reflux, haemoptysis, chest and abdominal discomfort, acute cardiovascular events, barotraumas and pneumothorax. 5 Bach et al have not described any complications in more than 500 batches of MIE. 7 Some simple but prudent measures to prevent complications are: brief

Diagnosis Bulbar amyotrophic

lateral sclerosis

Non-bulbar amyotrophic

lateral sclerosis

Duchenne muscular

dystrophy

Other

myopathies

Multiple

sclerosis

All

Patients, No. 10 5 2 3 1 21

Time undergoing MIE, months 6.5 (3-41) 19 (12-38) 7.5 (3-12) 16 (6-16) 4 12 (3-41)

Intolerance MIE 0 0 0 0 0 0

Complications due to MIE 0 0 0 0 0 0

Visits to the emergency service

(No. of patients/No. of events)

3/5 1/1 0/0 0/0 0/0 4/6

Hospitalisations

(No. of patients/No. of events)

3/3 1/1 0/0 0/0 0/0 4/4

Deaths, No. of patients 4 0 0 0 0 4

Table 4

Follow-up and results of mechanical insufflations-exsufflation

MIE indicates mechanical Insufflation-exsufflation.




pauses between applications (to avoid hyperventilation), avoiding applications after meals, appropriate treatment of gastroesophageal reflux and reduction of insufflation pressure according to tolerance. 5

During the study period, 4 patients with bulbar ALS died. The main cause of death was rapid progressive disease with severe bulbar dysfunction. These 4 patients had constantly rejected tracheotomy.

The main limitations of this study are the fact that it is observational, the reduced number of patients including the absence of a control group. However, shortly after beginning this protocol, the benefits of the treatment as far as efficacy in management of accumulated secretions, preventing visits to the Emergency Service and improvement of quality of life in these patients became evident As a result, we consider that it would not be ethical to deprive the patients of a treatment that has been shown to be effective.

Conclusion

The most important conclusion of this study is that it is possible to treat patients with severe NMD with sufficient clearance of the secretions of their respiratory airways with home MIE based on careful training of non-professional carers. This is valid for patients with VNI and those with tracheotomies. According to the patients, greater use of MIE during respiratory infections can prevent visiting the emergency service.

This technique can be considered a useful complement to ventilation support in these patients.

References

1. Gomez-Merino E, Sancho J, Martin J. Mechanical insufflaton-exsufflation: pressure, volume and flow relationships and the adequacy of manufacturer’s guidelines. Am J Phys Med Rehabil. 2002;81:579-83.

2. Servera E, Sancho J, Zafra MJ. Cough and neuromuscular diseases. Noninvasive airway secretion management. Arch Bronconeumol. 2003;39:418-27.

3. Bach JR. Amyotrophic lateral sclerosis: prolongation of life by non-invasive respiratory aids. Chest. 2002;122:92-8.

4. Chatwin M, Ross E, Hart N, Nickol AH, Polkey MI, Simonds AK. Cough augmentation with mechanical insufflation/exsufflation in patients with neuromuscular weakness. Eur Respir J. 2003;21:502-8.

5. Homnick DN. Mechanical insufflation-exsufflation for airways mucus clearance. Respir Care. 2007;52(10):1296-305.

6. Bach JR. Amyotrophic lateral sclerosis: predictors for prolongation of life by non-invasive respiratory aids. Arch Phys Med Rehabil. 1995;76:828-32.

7. Bach JR. Mechanical insufflation-exsufflation. Comparison of peak expiratory flows with manually assisted and unassisted coughing techniques. Chest. 1993;104:1553-62.

8. Bach JR, Saporito LR. Criteria for extubation and tracheostomy tube removal for patients with ventilatory failure: a different approach to weaning. Chest. 1996;110:1566-71.

9. Sancho J, Servera E, Diaz J, Marin J. Predictors of ineffective cough during a chest infection in patients with stable amyotrophic lateral sclerosis. Am J Respir Crit Care Med. 2007;175:1266-71.

10. Mier-Jedrezejowicz A, Brophy C, Green M. Respiratory muscle weakness during upper respiratory tract infections. Am Rev Respir Dis. 1988;138:5-7.

11. Poponick JM, Jacobs I, Supinski G, DiMarco AF. Effect of upper respiratory tract infection in patients with neuromuscular disease. Am J Respir Crit Care Med. 1997;156:659-64.

12. Bach JR, Rajaraman R, Ballanger F, Tzeng AC, Ishikawa Y, Kulessa R, et al. Neuromuscular ventilatory insufficiency: the effect of home mechanical ventilator use vs oxygen therapy on pneumonia and hospitalization rates. Am J Phys Med Rehabil. 1998;77:8-19.

13. Bach JR. Mechanical insufflation/exsufflation: has it come of age? A commentary. Eur Respir J. 2003;21:385-6.

14. Gomez-Merino E, Bach JR. Duchenne muscular dystrophy: prolongation of life by noninvasive ventilation and mechanically assisted coughing. Am J Phys Med Rehabil. 2002;81:411-5.

15. Tzeng AC, Bach JR. Prevention of pulmonary morbidity for patients with neuromuscular disease. Chest. 2000;118:1390-6.

16. Farrero E, Prats E, Povedano M, Martinez-Matos JA, Manresa F, Escarrabill J. Survival in amyotrophic lateral sclerosis with home mechanical ventilation: the impact of systematic respiratory assessment and bulbar involvement. Chest. 2005;127:2132-8.

17. Sivasothy P, Brown L, Smith IE. Effect of manually assisted cough and mechanical insufflation on cough flows of normal subjects, patients with chronic obstructive pulmonary disease (COPD) and patients with respiratory muscle weakness. Thorax. 2001;56:438-44.

18. Pellegrino R, Viegi G, Brusasco V, Crapo RO, Burgos F, Casaburi R, et al. Series “ATS/ERS task force: standardisation of lung function testing”. Eur Respir J. 2005;26:948-68.

19. American Thoracic Society/European Respiratory Society. ATS/ERS Statement on Respiratory Muscle Testing. Am J Respir Crit Care Med. 2002;166:518-624.

20. Bach JR, Kang SW. Disorders of ventilation. Chest. 2000;117:301-3.21. Vianello A, Corrado A, Arcaro G, Gallan F, Ori C, Minuzzo M, et al. Mechanical

insufflation-exsufflation improves outcomes for neuromuscular disease patients with respiratory tract infections. Am J Phys Med Rehabil. 2005;84:83-8.

22. Winck JC, Gonçalves MR, Lourenço C, Viana P, Almeida J, Bach JR. Effects of Mechanical Insufflation-Exsufflation on Respiratory Parameters for patients with chronic airway secretion encumbrance. Chest. 2004;126:774-80.

23. Bach JR, Bianchi C, Aufiero E. Oximetry and indications for tracheotomy for amyotrophic lateral sclerosis. Chest. 2004;126:1502-7.

24. Gonçalves MR, Bach JR. Mechanical insufflation-exsufflation improves outcomes for neuromuscular disease patients with respiratory tract infections. A step in the right direction. Am J Phys Med Rehabil. 2005;84:89-91.

25. Sancho J, Servera E, Díaz J, Marín J. Efficacy of Mechanical Insufflation-Exsufflation in Medically Stable Patients with Amyotrophic Lateral Sclerosis. Chest. 2004;125:1400-5.

26. Simonds AK. Recent advances in respiratory care for neuromuscular disease. Chest. 2006;130:1879-86.

27. Magnus T, Beck M, Giess R. Disease progression in amyotrophic lateral sclerosis: predictors of survival. Muscle Nerve. 2002;25:709-14.

28. Bach JR. A comparison of long-term ventilatory support alternatives from the perspective of the patient and the care giver. Chest. 1993;104:1702-6.

29. Bach JR. Noninvasive respiratory muscle aids: intervention goals and mechanism of action. In Management of patients with neuromuscular disease. Philadelphia, PA: Hanley & Belfus; 2004. p. 211-69.



Study 8

At Home and on Demand Mechanical Cough Assistance

Program for Patients With Amyotrophic Lateral

Sclerosis

Michele Vitacca, Mara Paneroni, Debora Trainini, Luca Bianchi, Giuliano Assoni ND, Manuela Saleri RTD, Sonia Gilè PHD, João C. Winck and

Miguel R. Gonçalves



Authors:

Michele Vitacca, PhDMara Paneroni, RTDDebora Trainini, RTDLuca Bianchi, PhDGiuliano Assoni, NDManuela Saleri, RTDSonia Gile, PhDJoao C. Winck, PhDMiguel R. Goncalves, RTD

Affiliations:

From the UO di PneumologiaRiabilitativa e Terapia IntensivaRespiratoria (MV, MP, DT, LB, MS,SG), Fondazione Salvatore MaugeriIRCCS, Lumezzane, Brescia, Italy;Servizio di Telemedicina FondazioneSalvatore Maugeri IRCCS (GA),Lumezzane, Brescia, Italy; and LungFunction and Ventilation Unit (JCW,MRG), Pulmonology Department andFaculty of Medicine, UniversityHospital S. Joao Porto, Portugal.

Correspondence:

All correspondence and requests forreprints should be addressed to:Michele Vitacca, PhD, FondazioneSalvatore Maugeri, IRCCS, Division ofPneumology, Via Giuseppe Mazzini,129, 25066 Lumezzane, Brescia, Italy.

Disclosures:

This study was supported, in part, bythe Associazione Italiana SclerosiLaterale Amiotrofica, grant no.060765. Financial disclosurestatements have been obtained, andno conflicts of interest have beenreported by the authors or by anyindividuals in control of the contentof this article.

0894-9115/10/8905-0401/0




Williams & Wilkins

DOI: 10.1097/PHM.0b013e3181d89760

At Home and on DemandMechanical Cough AssistanceProgram for Patients WithAmyotrophic Lateral Sclerosis

ABSTRACT

Vitacca M, Paneroni M, Trainini D, Bianchi L, Assoni G, Saleri M, Gile S, WinckJC, Goncalves MR: At Home and on Demand Mechanical Cough AssistanceProgram for Patients With Amyotrophic Lateral Sclerosis. Am J Phys MedRehabil 2010;89:401–406.

Objective: To establish a cost-effective telephone-accessed consultationand mechanical in-exsufflation (MI-E) and manually assisted coughing, oxim-etry feedback program for 39 patients with amyotrophic lateral sclerosis.

Design: Rapid access to healthcare consultation and to MI-E wasprovided to treat episodes of distress as a result of secretion encum-brance not reversed by suctioning and associated with a decrease inoxyhemoglobin saturation (SpO2) baseline. Avoided hospitalizations, de-fined by relief of respiratory distress and return of SpO2 baseline to�95% by continuous ventilator use and assisted coughing, were re-corded. Patient satisfaction was queried at 6 mos, and a cost analysis wasperformed of continuous vs. on demand MI-E use.

Results: Thirty-nine patients made a total of 1661 calls in 7.46 � 5.8mos of follow-up. Twenty-seven patients had 66 home care visits by arespiratory therapist for a total time commitment of 89.7 � 99.3 min/patient/mo. Twelve patients, all ventilator users, were also brought me-chanical in-exsufflators for mechanically assisted coughing for 47 respi-ratory episodes. Thirty hospitalizations were avoided. Seventy-five percentof the patients were extremely satisfied. Mean monthly cost per patient foron-demand telephone consultation, professional home healthcare visits,and MI-E as deemed necessary was €403 � €420 or 59% less than forcontinuous MI-E rental. Hospitalization costs were also spared.

Conclusions: An on-demand consult and MI-E access program canavoid hospitalizations for patients with amyotrophic lateral sclerosis withsignificant cost savings.

Key Words: Amyotrophic Lateral Sclerosis, Home Care, Acute Respiratory Failure,

Mechanically Assisted Coughing

www.ajpmr.com Cough Assistance in ALS 401


ALS



For patients with neuromuscular diseases, in-cluding amyotrophic lateral sclerosis (ALS), con-tinuous dependence on noninvasive intermittentpositive pressure ventilation (NIV) can markedlyprolong survival,1 maintain optimal quality-of-life,2 and along with mechanically assisted cough-ing (MAC)3–5 can be used in the home to avoidhospitalizations, acute respiratory failure with en-dotracheal intubation, and tracheotomy.4,6,7 MACis the use of mechanical in-exsufflation (MI-E)8

with an exsufflation-timed abdominal thrust. Al-though effective when continuously available, ex-pense can be mitigated by on-demand rather thancontinuous access if on-demand use can be dem-onstrated to be effective.

Severe bulbar-innervated muscle dysfunctionwith inability to protect the airways can renderMI-E ineffective, and even when effective, patientscan require considerable assistance and train-ing.1,7,9 In Europe, home respiratory care is ofteninadequate because home care companies provideonly equipment, not assistance, instruction, or ex-pertise for which the patient must depend on emer-gency services,10 and there is great burden oncaregivers.11 Thus, hospitalization rates andlengths of stay are high, especially when acuterespiratory failure and intubation result in trache-otomy. Even in the United States, it has beenreported that the mean hospitalization duration forpatients with neuromuscular disease undergoingtracheotomy is 72 days, most of which is spent inintensive care12,13 at great expense, and long andexpensive ventilator weaning unit stays often fol-low this.

To help reduce costs, avoid hospitalizations,and establish an optimal MI-E provision regimen athome, we studied a telephone-accessed integratedcare14 program with oximetry feedback that pro-vided equipment and professional home care ser-vices on an “as needed basis” to treat clinical exac-erbations and related respiratory problems.

METHODS

All 47 patients with a diagnosis of ALS accord-ing to El Escorial criteria15 referred to our reha-bilitation department for adaptation and trainingin some combination of cough assistance, mechan-ical ventilation, and tracheostomy managementwere analyzed. Our center has 145 beds for multi-disciplinary intermediate care. Reimbursement de-pended on diagnosis and comorbidities. Exclusioncriteria were death before enrollment, location�80 km from the center, and inadequate careproviders or cooperation. The protocol was ap-proved by the ethics committee, and the study wasconducted in accordance with the ethical standardsof the Declaration of Helsinki (1975, revised in

1983, clinical trials identifier #NCT00613899). Allpatients gave informed consent.

Hospital Phase: Training

All patients were offered the telephone-ac-cessed integrated care program that included tele-phone access to a triage nurse who directed thecalls to a pulmonologist, neurologist, psychologist,or physio-respiratory therapist (RT) for consulta-tion14 and possibly home visit. The patients wereeducated and trained in oximetry feedback (9500 byNonin, Minneapolis Plymouth) to maintain or re-turn SpO2 to �95% by manually assisted coughingor MAC or both as needed4,16,17 and in mechanicalventilation, including interface use, cleaning, hu-midification, safety, and tracheostomy care, as ap-propriate. Manually assisted coughing involved theapplication of deep lung insufflation followed byabdominal thrust. For MAC, the maximum toler-ated MI-E pressures (range, 35–60 cmH2O) wereused. The tube cuff was inflated for MI-E use viatracheostomy tubes.18

The patients were told to contact the call cen-ter for: dyspnea, 3% reduction in baseline SpO2,20% increase in need for deep airway suctioning,18

increased airway mucus congestion or changes insecretion properties,19 fever, headache, asthenia,sleepiness, or confusion, and consideration for an-tibiotic therapy.16

Before discharge, the patients underwent pul-monary function testing, including spirometry(VMAX 20, Sensor Medics, Yorba Linda, CA) andpeak cough flow measurement via a standard peakflow meter (MiniRight Peak Flow Meter, ClementClarke International, England, UK) connected to afacial interface.20

Home Phase

An RT called each patient every 7 days. Thecalls and home visits reinforced the oximetry/as-sisted coughing protocol. MI-E was brought topatients for whom, despite NIV or tracheostomyintermittent positive pressure ventilation (TIV) andmanually assisted coughing, the SpO2 would notremain �94%.3,4,16 All patients were instructed tocall the emergency service for hospitalization if theSpO2 remained �95% despite continuous ventila-tory support and assisted coughing, includingMAC.

Outcome Measurements

Mortality and the number of telephone callsfor assistance, respiratory exacerbations with SpO2

baseline �95%, RT home visits, home MAC rent-als, days of home MAC requirement, the percentageof SpO2 improvement with intervention, side ef-fects of MAC, avoided hospitalizations defined byrelief of dyspnea and return of SpO2 baseline to

402 Vitacca et al. Am. J. Phys. Med. Rehabil. ● Vol. 89, No. 5, May 2010



�95% by assisted coughing and continuous venti-latory support without hospitalization, and hospi-talizations were recorded. At 6 mos, patients werealso telephoned to question their satisfaction andestimate the efficacy of the program.

Costs

On-call telephone access costs have been al-ready reported by our group.14 The RT home visitsand rental costs for suction machine, manualresuscitator, and ventilator were additional. Perdiem MI-E rental costs were compared with con-tinuous rental costs in Italy and in the UnitedStates. The latter information was provided by anaccredited respiratory home care company (Mil-lennium Respiratory Services, Whippany, NJ) atMedicare reimbursement rates. Inpatient respi-ratory rehabilitation admission costs were €289per day, and critical care costs were €1600 perday. When applicable, costs were converted fromdollars to euros.


Descriptive data are reported as mean � SD.Statistical analysis was performed by using SPSSsoftware (Release 12.0 SPSS, Chicago, IL). For allparameters, the differences between treatmenttimes were analyzed using a paired Student’s t testfor the parametric variables and an unpaired Wil-coxon-test for the nonparametric ones. P values�0.05 were considered significant.

RESULTS

Between October 2006 and September 2008,47 consecutive patients with ALS were screened.Eight were excluded: three died before enrollment,two refused to participate, one lived �80 km from

the referring center, one showed poor compliance,

and one had no caregiver. The remaining 39 re-

ceived riluzole and were followed up for 7.46 � 5.8

mos. Twenty-seven of the 39 were ventilator users.

Their baseline anthropometric, clinical, and func-

tional characteristics are shown in Table 1. All

tracheotomized patients (n � 12) required contin-

uous TIV, whereas the NIV patients (n � 15) used

NIV 8–16 hr/d.

Telephone-Accessed Integrated Care

Program

The total nurse/RT time commitment was

1.49 � 1.65 hr/patient/mo or the equivalent of a 0.4

full-time RT. During the 7.46 � 5.8-mo follow-up,

there were 1661 calls with a high interindividual

variability (6.65 � 6.45, range 1–138). All except

one call to a physician was triaged to an RT. Seven

and one-half percent of the calls triggered a home

RT visit. Sixty-seven home visits were required and

38 had MI-E delivered.

Outcomes and hospitalization data are listed in

Table 2. Overall, 10 NIV users (26%) died: two

suddenly and eight from respiratory causes and

refusing intubation. Only 1 of the 10 called the

center. No TIV user died.

All MAC deliveries were for TIV and NIV users

who were also followed up for a longer than aver-

age period of time. Table 3 shows outcomes of MAC

intervention performed during a 12.6 � 3.3-mo

period. The latency period for initiating home MAC

use was 3 � 3 mos for the tracheotomy patients

and 10 � 3 mos for the NIV users. The TIV users

required MI-E twice as many days per month as the

NIV users.

TABLE 1 Patient characteristics

Patients (n) 39Age, years � SD (range) 62 � 11 (39–83)Gender (M/F) 21/18Years of diseasea 3.47 � 3.21Distance from the referring center, Km (range) 34 � 18 (1–80)Bulbar/nonbulbar involvementb 23/16No ventilator use (n) 12NIV users (n) 15TIV users (n) 12VC, % predicted (n) Total population (24) 66 � 29

Tracheotomized patients (6) 50 � 20Nontracheotomized patients (30) 71 � 29

PCF, cmH2O (n � 27) no-T patients 186 � 113PEF, cmH2O (n � 12) 88 � 51

aFrom diagnosis.bFrom time of respiratory therapist evaluation.TIV, tracheostomy mechanical ventilation; NIV, noninvasive mechanical ventilation; VC, vital capacity; PCF, peak cough

flow; PEF, peak expiratory flow.




Costs

Table 4 shows costs. One NIV and two nonven-tilator users underwent tracheotomy during thestudy. Comparing the costs of “on-demand” MI-Ewith standard continuous use for the 6660 days ofventilator use for the 27 patients, the cost savingswas €108,758.

The daily rental of MI-E in the United States is$10 per day for a monthly rental and Medicarereimbursement of $424 (€301). Rental for mechan-ical ventilation, MI-E, and supplies and on-call RTservices is about $1000 per month or about 30%greater than the cost of this rental program. Theavoidance of 34 hospitalizations added to the costsavings.

All 39 patients were satisfied with the project,and 86% of the MAC users considered it effective,whereas 14% considered it somewhat effective.There were no significant side effects of assistedcoughing, including MAC.

DISCUSSION

For patients with ALS, a program of tele-phone access and as needed home intervention,including manually assisted coughing and MAC,was shown to be feasible, well tolerated, and costeffective. A previous ALS study used continuousvideoconferencing and telephone consultationfor four patients with ALS, although it was lim-ited by the small number of subjects and by their

TABLE 3 Outcomes of the 12 users of mechanically assisted coughing

Patients Having RTVisits and Provision

of MI-E (n � 12)

TIV Users Having RTVisits and Provision

of MI-E (n � 9)

NIV Users Having RTVisits and Provision

of MI-E (n � 3)

Total home MI-E rentals,a n 30 27 3Mean change in SpO2 (%) with

intervention, all baselines werecorrected

�3.2 � 0.8 3.5 � 0.9 2.2 � 0.0

Total MI-E rental days, n 46.7 � 27.4 56.7 � 24 16.7 � 5.8Time to normalization of baseline SpO2

�20 days 33% 0 34%20 and 40 days 17% 34% 66%�40 days 50% 66% 0

Days of home MI-E rental, n 54.2 � 30.0 50 � 28.2 23.3 � 11.5

aHome respiratory therapist (RT) visit for reinforcement of instruction in manually assisted coughing and provision of amechanical insufflator-exsufflator for mechanically assisted coughing (MAC).

TIV, tracheostomy intermittent positive pressure ventilation; NIV, noninvasive intermittent positive pressure ventilation;MI-E, mechanical insufflation-exsufflation; SpO2, pulse oxyhemoglobin saturation.

TABLE 2 Outcomes of home care visits

Total PatientsHaving Home

Visits (n � 27)

Patients WithHome Visits

Only(n � 15)

Patients WithHome VisitsPlus MI-Ea

(n � 12)

TIV Users HavingHome Visits and

Provision of MI-E(n � 9)

NIV Users HavingHome Visits and

MIE (n � 3)

Total respiratoryexacerbations, n

67 20 47 40 7

Home visits withoutMI-E delivery, n

13 4 9 9 0

Home visits plusprovision of MI-E, n

21 0 21 18 3

Patients hospitalized, n 18 8 10 7 3Total hospitalizations, n 33 16 17 13 4Avoided

hospitalizations, n34/67 (51%) 4/20 (22%) 30/47 (64%) 27/40 (67%) 3/7 (42%)

Avoided hospitalizations are defined by the domiciliary need for continuous ventilatory support and correction of a persistentdecrease in baseline oxyhemoglobin saturation by assisted coughing.

aOnly the TIV and NIV users required home visits plus MI-E, all of which resulted in correction of SpO2 baseline by somecombination of adjusting ventilator use and assisted coughing.

TIV, tracheostomy intermittent positive pressure ventilation; NIV, noninvasive intermittent positive pressure ventilation;MI-E, mechanical insufflation-exsufflation.




inability to master the use of the Internet and

Webcams.21

Patients with severe bulbar-innervated muscle

dysfunction and those with only moderate dysfunc-

tion but without tracheostomy tubes are consid-

ered to have a poor prognosis.9 However, our re-

sults indicate that the severity of clinical

exacerbations as a result of airway secretion en-

cumbrance in such patients can be monitored and

secretion expulsion guided by oximetry. Normal-

ization of SpO2 baseline by aggressive assisted

coughing and MAC can avert hospitalization de-

spite continuous ventilatory support. This can only

be effective with trained care provider assistance.16

This is consistent with the findings of Bach et

al.12,22,23 who in one study demonstrated that an

uncorrected decrease in baseline SpO2 �95% re-

sulted in 33 of 35 patients with ALS dying or

requiring tracheotomy within 2 mos, but that

about one-half of such patients’ baseline SpO2s can

be temporarily normalized by MAC for about 11

mos.4 Thus, a motivated caregiver can often use

NIV and cough assistance to prevent acute respira-

tory failure for ALS as has also been described for

patients with Duchenne muscular dystrophy3,24

and other patient populations.16

Oximetry monitoring with on-demand medical

attention and MAC is a cost-saving alternative to

institutionalization and to continuous access to

MI-E. In one study in which the indication for

continuous home MI-E prescription was assisted,

peak cough flow �300 L/m as opposed to the mean

of 186 L/m (unassisted) peak cough flow in our

patients, the average period of time before MI-E

was needed to avert a hospitalization with contin-

uous rental was 11 mos.3 In our study, 56% of the

patients did not obtain MI-E at all, and those who

used it, did so for �20% of the total follow-up

period.

In conclusion, the telephone access and on-

demand MAC program increased both the patients’

and clinicians’ feelings of security for home man-

agement and was effective in averting hospitaliza-

tions for patients with ALS. Limitations of the

study are (1) lack of controls; (2) lack of quality-

of-life assessment; and (3) lack of outcomes com-

parisons with programs in which MI-E access is

continuous.

ACKNOWLEDGMENTS

We thank Mario Melazzini, who is a doctor,

patient, and profound human being, for his joy of

being alive. We also thank Millennium Respiratory

Services, Whippany, NJ, for their support in pro-

viding data.

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in chronic respiratory failure patients: A randomised

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15. Brooks BR, Miller RG, Swash M, et al: El Escorial

revisited: Revised criteria for the diagnosis of amyo-

trophic lateral sclerosis. Amyotroph Lateral Scler

Other Motor Neuron Disord 2000;1:293–9

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bidity for patients with neuromuscular disease.

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parison of peak expiratory flows with manually as-

sisted and unassisted coughing techniques. Chest

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18. Sancho J, Servera E, Vergara P, et al: Mechanical

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habil 2003;82:750–3

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Rehabil 2004;83:608–12

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RM, et al: Tele-treatment of patients with amyotro-

phic lateral sclerosis (ALS). J Telemed Telecare

2006;12(suppl 1):31–4

22. Bach JR: A comparison of long-term ventilatory sup-

port alternatives from the perspective of the patient

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23. Bach JR, Barnett V: Ethical considerations in the man-

agement of individuals with severe neuromuscular dis-

orders. Am J Phys Med Rehabil 1994;73:134–40

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Parekh R. Cough augmentation in Duchenne mus-

cular dystrophy. Am J Phys Med Rehabil 2008;87:

726–30




Study 9

Home mechanical cough assistance for acute

exacerbations in neuromuscular disease

Miguel R. Gonçalves, Mara Paneroni, João Bento, Debora Trainini, Luca Bianchi, João C. Winck and Michele Vitacca

(Respiratory Medicine, submitted)



Home mechanical cough assistance for acute exacerbations in neuromuscular diseases. Miguel R. Gonçalves *, Mara Paneroni**, João Bento*, Debora Trainini**, Luca Bianchi **, João Carlos Winck* and Michele Vitacca**

* Lung Function and Ventilation Unit, Neuromuscular clinic, Pneumology Department, Faculty of

Medicine, S. João Hospital Porto, Portugal

** UO di Pneumologia Riabilitativa e Terapia Intensiva Respiratoria, Fondazione Salvatore

Maugeri IRCCS, Lumezzane (BS) Italy


Miguel R. Gonçalves Lung Function and Ventilation Unit – Pulmonary Medicine Department University Hospital of S. João Faculty of Medicine, University of Porto Address: Av. Prof. Hernani Monteiro, Porto, Portugal Phone: 00351 225512100 (extension 1042); [email protected] [email protected]



Abstract

Background: Mechanically assisted coughing (MAC) has been used successfully in hospital for

patients with neuromuscular disease (NMD), however, limited data exist on long-term home use.

Objective: To determine outcomes of home MAC for NMD patients using tracheostomy

mechanical ventilation (TMV) or noninvasive ventilation (NIV) during acute episodes.

Material and methods: The study was performed in two centers with NMD clinics. Forty six

NMD patients (14 females) continuously ventilator dependent (28 using NIV and 18 TMV) with a

mean age 51.3±22.3 years, were analyzed. Pulmonary function and cough efficacy were assessed

during routine evaluations. Hospitalization rates, avoided hospitalizations defined by normalization

of SpO2 within 24 hours by continuous ventilatory support and MAC, and resort to deep airway

suctioning were recorded. Treatment tolerance and side effects were also assessed.

Results: During 42±57 months of follow up, for 180 acute episodes, 146 hospitalizations were

avoided. Hospitalization rates for NIV users were significantly lower than for TMV users. Home

MAC during acute episodes normalized baseline SpO2 and decreased resort to deep airway

suctioning via tracheostomy tube per day. In all MAC sessions there were no complications.

Conclusion: Home MAC with oximetry feedback is effective and can avoid hospitalizations for

both NIV and TMV users.

Key words: Home mechanical ventilation, Mechanical assisted cough, Neuromuscular

disorders,



Introduction

Mechanical assisted cough (MAC) is the use of mechanical insufflation-exsufflation (MI-E)

(1) with an exsufflation-timed abdominal thrust. It can be applied via oral, oronasal interfaces or via

invasive airway tubes preferably with inflated cuffs (2). The physiological effects and efficacy of

MAC have been described for adults (1, 3-6) and children (7-8).

Patients with neuromuscular diseases (NMD) have respiratory muscle weakness and

impaired cough (9-10). For these patients, up to continuous use of noninvasive ventilation (NIV)

can maintain quality of life,(11) and markedly prolong survival (12) that is, nevertheless, punctuated

by respiratory tract infections (RTIs). Intercurrent RTIs are the main cause of morbidity, prolonged

hospitalizations, acute respiratory failure (ARF), intensive care admissions, and mortality (13-16).

The use of mechanically assisted coughing (MAC) has been reported to be effective in preventing

ARF and for avoiding hospitalizations in patients with Duchenne Muscular Dystrophy (DMD) (16).

In hospital application, MAC has been described as a first-line intervention for NMD

patients with ARF (2, 7, 17-20), however, its efficacy and optimal application in the home has not

been widely explored. The purpose of this study was to describe the outcomes of home MAC for

avoiding hospitalizations in NMD patients.

Material and Methods

The data were retrospectively gathered in two centers with NMD clinics and extending

home care organizations that include the provision of MAC. The study was approved by the

institutions’ review boards.



Patients

A 4 year follow up observational analysis was performed for 46 totally ventilator dependent

patients (14 females) that included 33 with ALS and 13 with other NMDs (5 Duchenne muscular

dystrophy (DMD), 3 spinal muscular atrophy (SMA) type 1, 3 SMA type 2, 1 multiple sclerosis and

1 congenital muscular dystrophy) with mean age 51.3±22.3 years. Inclusion criteria were: NMD

diagnosis, baseline assisted cough peak flow (CPF) <270 L/min and continuous ventilator

dependence (> 20h per day) and decrease in SpO2 baseline below 95% during intercurrent episodes

of respiratory distress. Patients with lung disease, inability to cooperate and without dedicated

caregivers were excluded.

Measurements

Unassisted and assisted CPF were noted for NIV users and peak expiratory flow (PEF) noted

for TMV users. Spirometric (Vmax 229, Autobox, Sensormedics) recording of forced expiratory

volume in one second (FEV1) and forced VC (FVC) was noted. In TMV users, tracheotomy

pulmonary function tests were performed through the non-fenestrated tracheotomy tube with an

inflated cuff. All pulmonary function testing was done in sitting position according to standard

procedures(21).

Unassisted CPF was measured by having the patient cough forcefully through a standard

peak flow meter (miniRight, standard range Peak Flow Meter Clement Clarke International

England) connected to a facial mask. Assisted CPF involved the patient “air stacking” to approach

maximum insufflation capacity (22) using their volume-cycling ventilator or a manual resuscitator

and coughing into the peak flow meter as the abdominal thrust was applied at glottic opening (3).

Bulbar impairment and glottic dysfunction correlated with unassisted/assisted CPF ratio for NIV

users. Patients with a ratio =1 could not close the glottis and were considered to have severe

“bulbar” impairment (10, 13, 23).



Home oximetry feedback/MAC protocol

All patients and their caregivers attended a hospital-based educational program on lung

expansion techniques (air stacking), manual assisted coughing, and MAC with oximetry feedback.

MAC training included adjustment of settings on the Cough-Assist (Philips, Respironics, Inc,

Murrysville, PA) and use during practical clinical simulations, as well as training in awareness of

symptoms and signs of airway congestion that indicate need for MAC via oronasal mask or via

tracheostomy tube that had to be with an inflated cuff (2). The Cough-Assist and an oximeter

(Nonin 9500 oximeter Minneapolis Plymouth USA) was then provided for home use.

Secretion encumbrance that caused SpO2 to decrease to less than 95% despite continuous

full-setting ventilatory support in ambient air with dyspnea, that did not revert after manually

assisted coughing techniques, or, for patients with tracheotomy tubes, after several secretion

mobilization and suctioning sessions, indicated an acute episode and resort to MAC with settings

suggested by medical literature.(1, 3, 24) A effective MAC application by trained non-professional

caregivers (family members, private attendant) was the expulsion of airway secretions by MAC that

resulted in return of SpO2 to≥95%. A trained health care professional (respiratory therapist or

nurse) was always available 24h/day on free on-call to answer questions as well as to go to the

home to supervise MAC in difficult situations (25). Patients and caregivers were also instructed to

detect early signs of respiratory tract infections and instructed to contact our staff for medical

therapy.

Hospitalization avoidance was defined as MAC-engendered expulsion of mucus with

resulting normalization of SpO2 to values equal to baseline within 24 hours. Whenever dyspnea and

secretion encumbrance or SpO2 <95% persisted despite continuous ventilator use and aggressive

MAC (more than 4 sessions per hour), patients were instructed to go to Emergency Departments of

local hospitals. In addition, the TMV users were instructed to seek attention if requiring an increase

in the need for airway suctioning. These were the criteria established for hospital admission.



Outcome Monitors

Numbers of: acute episodes of secretion encumbrance with desaturation indicating need for MAC,

hospitalizations, and avoided hospitalizations were analyzed and compared between NIV and TMV patient

groups. SpO2 baseline values during acute episodes were compared with pre-morbid baseline values and

values at recovery (after a 24h MAC application). For TMV patients, the number of deep airway suctionings

were also recorded both during the acute episode and at recovery. Tolerance and side effects were

monitored.


Statistical analysis was performed by SPSS 15.0 software (SPSS, Chicago, I1, USA). Descriptive

data are reported as mean±SD. Comparisons between groups were done using the Mann-Whitney U-

test and differences between baseline, acute episode and recovery were compared using the

Wilcoxon rank test. A p value ≤ 0.05 was considered significant.

Results

During a follow up of 42±57 months, 46 subjects, that included, 28 (61%) NIV users and 18

(39%) TMV users, were studied. All had CPFs that satisfied the inclusion criteria. Demographic

data and clinical and functional characteristics are listed in table 1.

The home oximetry feedback/MAC protocol was used for a total of 180 (mean 3.9±2.9 per

patient) acute episodes of respiratory insufficiency due to secretion encumbrance during the follow

up of the study. During these episodes SpO2 significantly decreased in all patients in comparison

with baseline and significantly reverted in 24 hours after MAC (Figure 1). In TMV patients, during

the acute episodes, the number of deep airway suctionings significantly increased in comparison

with baseline and after MAC significantly decreased again in 24 hours to values similar to baseline

(Figure 2). Hospitalization data and outcomes are listed in table 2.



During the follow up period 10 patients died (8 NMV and 2 TMV users), 4 suddenly and

presumably from cardiac arrhythmia (3 ALS and 1 SMA type 1), 3 with ALS from pneumonia, and 2 ALS

patients from stroke. All MAC sessions were well-tolerated and there were no complications related

to the treatment.

Discussion

The organization of home MAC access and patient compliance with it has already been

reported by our group for ALS patients (25). We have now reported data that focused on the clinical

effects of home MAC during acute episodes of secretion encumbrance in ALS and other NMD

patients. The results confirm that hospitalizations for ARF can be avoided for NMD patients by a

protocol of oximetry feedback for using ventilatory support and MAC in the home (12, 15-16, 26).

Moreover our findings support the clinical justification for availability and prescription of cough

assist devices and portable oximeters at home for this patient population, specially during

intercurrent RTI´s.

Provided that supplemental oxygen therapy be avoided, oximetry was critical since, once

artefact is ruled out, all desaturations indicated less than full ventilatory support (airflow leak or

inadequate ventilator settings), airway secretion congestion, and if the latter was not resolved by

MAC, persistent SpO2 decrease was caused by pneumonia or other persistent complications of

congestion(5, 15, 17, 27) Since all patients were continuously ventilator dependent during the

episodes, had the oxyhemoglobin desaturations and dyspnea not been reversed by MAC, they

would have had to have been hospitalized for problems related to upper respiratory tract infections

and inability to clear secretions. However, in our study, as a result of the protocol, 81% of the acute

episodes resolved without hospitalization.

These results are consistent with those reported by Gomes-Merino et al (16) that, with a similar

approach, described hospitalization avoidance and survival increase in a population with Duchenne muscular

dystrophy under NIV. Our study focused on other NMD diagnoses including having 71% ALS patients.



Moreover, we found that, while the incidence of acute episodes was the same, the TMV users had

significantly more hospitalizations per desaturation episode than NIV users. This may be due specifically to

complications caused by the invasive tubes (28-30) and unrelated to MAC or by poorer bulbar-innervated

muscle function and airway protection mechanisms in the ALS population despite TMV with cuff

inflation(31-32)

Indeed, it is well known that the severely impaired bulbar-innervated muscle function in ALS

can render MAC ineffective (5, 12) via the upper airway and necessitate tracheostomy to be

effective (13, 32). Bach et al. described that persistent SpO2 < 95% in room air despite optimal use of NIV

and MAC, indicates need for tracheostomy in ALS patients (26) and presumably in patients with other NMDs

as well. In our study, MAC not only significantly improved SpO2 in all patients, it also significantly

decreased the number of airway suctionings in TMV patients. All TMV patients in this study had bulbar

muscle impairment and the fact that only 3 NIV users had bulbar impairment, may justify the good results of

MAC on reversion of desaturations at home.

The main requisite for home MAC prescription was the presence of adequate and motivated

patients and caregivers to learn the protocol from trained health care professionals. Our results

imply that the training and equipping be done early, before ARF occurs, and in the outpatient

setting as reported by Tzeng et al (15). Our results confirm that the caregiver can successfully use MAC

at home cough with oximetry feedback and can early detect possible acute episodes of secretion

encumbrance. However, according to our experience, to guarantee an optimal continuous support to the

caregiver, an easy access by phone to a heath care professional 2nd opinion, 24 h/day is strongly advised.

Limitations of the study include its retrospective nature with no control group, the small

number of patients and multiple diagnoses. Thus, we advise caution in the generalization of the

results.

In conclusion, it is possible and effective to manage episodes of acute respiratory

decompensation, related to secretion encumbrance, in continuously ventilator dependent NMD

patients in the home with patient and care provider training and equipping in a protocol of MAC

with oximetry feedback. This is true for patients dependent on either NIV or TMV.



Table 1: Patient baseline characteristics

Patients, (n) 46

Age, years ± SD (range) 51±22 (1-83)

Gender M/F 32/14

Years of Onset* 5.7±5.6

Follow up after mechanical ventilation, months ± SD (range) 42±57 (6-300)

Bulbar/Non bulbar Involvement** 21/25

NIV users (n, %)

TMV users (n, %)

28 (61%)

18 (39 %)

VC, Liters (%) Tot – 1.0 ±0.5 (31±13%)

TMV users – 1.1 ±0.51 (34±10%)

NIV users – 0.97 ±0.52 (30±14%)

FVC/FEV1 (%) Tot - 88±12

TMV users - 86±12

NIV users - 88±13

Unassisted PCF, L/min (NIV users)

Assisted PCF, L/min (NIV users)

92±86

198±65

PEF, cmH20 (TMV users) 40±28

Legend: TMV – tracheostomy mechanical ventilation; NIV- noninvasive mechanical ventilation; Tot- Total

population;;VC - vital capacity; PCF – Peak Cough Flow; PEF . Peak Expiratory Flow; *from diagnosis; **from time

of entry in the study



Table 2 – Outcomes of Home MAC and hospitalization data

Patients under tracheostomy mechanical ventilation

(n=18)

Patients under noninvasive mechanical ventilation

(n = 28)

Total patients

(n=46)

Total home acute episodes of secretion encumbrance with MAC activation, nr

78 102 180

Home acute episodes of secretion encumbrance with MAC activation (per patient), mean±SD

4.3±3.7 3.6±2.3 3.9±2.9

Total Hospitalizations, nr 21 13 34 Hospitalizations (per patient), mean±SD 1.2±1.3 * 0.5±0.7 * 0.7±1.0 Avoided Hospitalizations, nr 57/78

(73%) 89/102 (87%)

146/180 (81%)

Legend: MAC – mechanical assisted cough; nr - number

* p < 0,05



Figure 1 – Oxygen saturation (SpO2) monitoring during baseline, acute epiosde and at recovery

(after MAC)

Legend: MAC – mechanical assisted cough

* p < 0,05- when comparing baseline to acute episode and acute episode to after MAC

*

*

*



Figure 2 – Number of deep airway suctionings in TMV patients during baseline, acute epiosde

and at recovery (after MAC)

Legend: MAC – mechanical assisted cough

* p < 0,05- when comparing baseline to acute episode and acute episode to after MAC

*

*

*



References

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mechanical insufflation-exsufflation on respiratory parameters for patients with chronic

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vs. tracheal suctioning via tracheostomy tubes for patients with amyotrophic lateral

sclerosis: a pilot study. Am J Phys Med Rehabil. 2003 Oct;82(10):750-3.

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flows with manually assisted and unassisted coughing techniques. Chest. 1993

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4. Mustfa N, Aiello M, Lyall RA, Nikoletou D, Olivieri D, Leigh PN, et al. Cough

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5. Sancho J, Servera E, Diaz J, Marin J. Efficacy of mechanical insufflation-

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6. Chatwin M, Ross E, Hart N, Nickol AH, Polkey MI, Simonds AK. Cough

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9. Perrin C, Unterborn JN, Ambrosio CD, Hill NS. Pulmonary complications of

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maneuvers in patients with neuromuscular diseases. Am J Phys Med Rehabil. 2006

Feb;85(2):105-11.

11. Mustfa N, Walsh E, Bryant V, Lyall RA, Addington-Hall J, Goldstein LH, et al.

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respiratory aids, Chest. 2002 Jul;122(1):92-8.

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chest infection in patients with stable amyotrophic lateral sclerosis. Am J Respir Crit

Care Med. 2007 Jun 15;175(12):1266-71.

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Neuromuscular ventilatory insufficiency: effect of home mechanical ventilator use v

oxygen therapy on pneumonia and hospitalization rates. Am J Phys Med Rehabil. 1998

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16. Gomez-Merino E, Bach JR. Duchenne muscular dystrophy: prolongation of life

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9.

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5.

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2002 Jul;81(7):506-11.

24. Sancho J, Servera E, Marin J, Vergara P, Belda FJ, Bach JR. Effect of lung

mechanics on mechanically assisted flows and volumes. Am J Phys Med Rehabil. 2004

Sep;83(9):698-703.



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home and on demand mechanical cough assistance program for patients with

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26. Bach JR, Bianchi C, Aufiero E. Oximetry and indications for tracheotomy for

amyotrophic lateral sclerosis. Chest. 2004 Nov;126(5):1502-7.

27. Bach JR, Ishikawa Y, Kim H. Prevention of pulmonary morbidity for patients

with Duchenne muscular dystrophy. Chest. 1997 Oct;112(4):1024-8.

28. Baydur A, Kanel G. Tracheobronchomalacia and tracheal hemorrhage in patients

with Duchenne muscular dystrophy receiving long-term ventilation with uncuffed

tracheostomies. Chest. 2003 Apr;123(4):1307-11.

29. Pignatti P, Balestrino A, Herr C, Bals R, Moretto D, Corradi M, et al.

Tracheostomy and related host-pathogen interaction are associated with airway

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Feb;103(2):201-8.

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Quality-of-life evaluation of patients with neuromuscular and skeletal diseases treated

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Nov;122(5):1695-700.

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lateral sclerosis: efficacy of noninvasive ventilation and uncuffed tracheostomy tubes.

Am J Phys Med Rehabil. 2010 May;89(5):407-11.

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Survival in amyotrophic lateral sclerosis with home mechanical ventilation: the impact

of systematic respiratory assessment and bulbar involvement. Chest. 2005

Jun;127(6):2132-8.



Study 10

Evolution of Noninvasive Management of End-Stage

Respiratory Muscle Failure in Neuromuscular Disease

Miguel R. Gonçalves, John R. Bach, Yuka Ishikawa, Eduardo Luis DeVito,

Francisco Prado, Pamela Salinas, Marie Eugenia Dominguez, Emilia Luna

Padrone, Mauro Vidigal-Lopes, Rita Guedes, Douglas McKim, Marcello

Villanova, Seong-Woong Kang, Emilio Servera, Jesús Sancho, Michel

Toussaint, Philippe Soudon, Michelle Chatwin, Anita K. Simonds, Martin

Bachmann, Michael Baumberger, Tsz-Kin Kwok, Konrad Bloch, David

Birnkrant, Juan Isquierdo, Ditza Gross, Louis Saporito, Brian Weaver,

Alice Hon, Bilal Saulat and João Carlos Winck,

(CHEST, in preparation for submission November 2010)



Evolution of Noninvasive Management of End-Stage Respiratory

Muscle Failure in Neuromuscular Disease

Centers involved:

1- Miguel R. Gonçalves, João Carlos Winck, Department of Pulmonology,

University Hospital of S. João, Faculty of Medicine, University of Porto,

Portugal.

2- John R. Bach., Louis Saporito, Brian Weaver, Alice Hon, Bilal Saulat,

Department of Physical Medicine and Rehabilitation, UMDNJ-New Jersey

Medical School, University Hospital, Newark, N.J. USA

3- Yuka Ishikawa, National Organization Yakumo Hospital, Yakumo, Japan

4- Eduardo Luis DeVito, Instituto de Investigaciones Médicas Alfredo Lanari,

Facultad de Medicina, Universidad de Buenos Aires, Argentina.

5- Francisco Prado, Pamela Salinas, Universidad de Chile, Health Chilean

Ministry, Santiago, Chile.

6- Marie Eugenia Dominguez, Emilia Luna Padrone, Instituto National de

Enfermidades Respiratorias, Universidad National Autonoma de Mexico,

Mexico, D.F., Mexico.

7- Mauro Vidigal-Lopes, Rita Guedes, VentLar Home Care Program, FHEMIG,

Belo Horizonte, Brasil.

8- Douglas McKim, Respiratory Rehabilitation unit, Ottawa University Hospital,

Canada.



9- Marcello Villanova, Neuromuscular Unit, Nigrisoli Hospital, Bologna, Italy

10- Seong-Woong Kang, Department of Rehabilitation Medicine, Gangnam

Severance Hospital, Seoul, South Korea.

11- Emilio Servera, Jesus Sancho Department of Pulmonology, Hospital Clínico

Valência, Spain

12- Michel Toussaint, Philippe Soudon, Center for home mechanical ventilation,

Indekaal Rehabilitation Hospital, Brussels, Belgium.

13- Michelle Chatwin, Anita K. Simonds, Sleep and Ventilation Unit, Royal

Brompton Hospital, London, UK.

14- Martin Bachmann, Asklepios Klinik Hamburg-Harburg, Germany

15- Michael Baumberger, Franz Michel, Centre Suisse des Paraplégiques,

Nottwil, Switzerland

16- Tsz-Kin Kwok, Tung Wah Hospital, Hong Kong, China

17- Konrad E.Bloch, Zurich, Switzerland.

18- David Birnkrant, Metro-Health Medical center, Case Western Reserve

University, USA

19- Juan Isquierdo, MedicalDiagnostic Inc., St. Petersburg, Florida, USA.

20- Ditza Gross, Telavive University Hospital, Israel



Abstract

From 20 centers in 18 countries, data are presented on 1623 nocturnal only

ventilated neuromuscular disease patients (NMD) that include amyotrophic lateral

sclerosis, Duchenne muscular dystrophy and spinal muscular atrophy type 1, in which

760 (47%) progressed to continuous full-setting noninvasive ventilation (NIV) over a

follow up of 15 years. A protocol of oximetry feedback using mechanically assisted

coughing and full-setting NIV permitted safe 229 safe extubations and 35 decanulations

of patients who could not pass spontaneous breathing trials (SBTs) before or after

extubation/decanulation. After the follow up period, 522 (69%) patients are still alive on

continuous full-setting NIV and tracheostomy was placed in a total of 140 (9%). An

expert panel reviewed recommendations of previous consensus and reviews on NIV use,

respiratory evaluations and assisted coughing in NMD to consider changes and updated

recommendations based on the evolution in practice patterns.

Introduction and Historical Perspective

Before 1953 noninvasive ventilation referred to the use of body ventilators like

the iron lung1. Despite their success for continuous ventilatory support, tracheostomy

positive pressure ventilation (TMV) became the standard for ventilatory support after a

1952 Danish polio epidemic for which there were few iron lungs2. Since TMV facilitated

mobilizing patients from iron lungs because positive pressure ventilators could be rolled

behind wheelchairs this invasive approach spread to the United States.



Then in 1953 Dr. John Affeldt wrote, “…some of our physical therapists, in

struggling with (iron lung) patients, noticed that they could simply take the positive

pressure attachment, apply a small plastic mouthpiece..., and allow that to hang in the

patient's mouth….We even had one patient who has no breathing ability who has fallen

asleep and been adequately ventilated by this procedure, so that it appears to work very

well, and I think does away with a lot of complications of difficulty of using (invasive)

positive pressure. You just hang it by the patients and they grip it with their lips, when

they want it, and when they don't want it, they let go of it. It is just too simple."3.

Patients who were using body ventilators around the clock began using mouth

piece noninvasive intermittent positive pressure ventilation (NIV) during daytime hours.

Many then refused to go back to body ventilator use and used mouth piece NIV around-

the-clock. Losing the mouth piece during sleep could have meant death but there is no

indication that that ever happened4.

In 1956 Harris Thompson released a portable 28 lb. Bantam ventilator. The next

year it was noted, “If a patient is going to be left a respirator cripple with a very low VC,

a tracheotomy may be a great disadvantage. It is very difficult to get rid of a tracheotomy

tube when the VC is only 500 or 600 cc and there is no power of coughing, whereas, as

we all know, a patient who has been treated in a respirator (body ventilator) from the first

can survive and get out of all mechanical devices with a VC of that figure."5 Thus, it was

recognized that TMV could result in greater ventilator dependence because of

deconditioning, tube induced secretions, hyperventilation, bypassing upper airway

afferents, and possibly other factors6.



In 1968 the lipseal interface came onto the market. Lipseals prevented loss of the

mouth piece during sleep and diminished air leakage, normalizing alveolar ventilation

during sleep even for patients with little or no measurable vital capacity (VC)4. Mouth

piece/lipseals were used up to continuously for long-term ventilatory support for 257

patients managed by Goldwater Memorial Hospital and by others scattered around the

country7 from 1968 through the advent of nasal NIV in 1987 when it was first recognized

that nasal NIV could provide full ventilatory support for a multiple sclerosis patient with

100 ml of VC8. Despite this no other centers reported using mouthpiece NIV for diurnal

ventilatory support in NMD until Servera et al. did so to avert intubations in 20059 and

Toussaint et al. for continuous support in 200610.

Once articles on nasal NIV proved its efficacy in long term ventilated patients

nasal and oro-nasal NIV were used in critical care11-12. Interfaces designed for treatment

with CPAP were modified for use with ventilator circuits. Nevertheless, most long-term

use of these interfaces was for “sleep disordered breathing” whereas inspiratory muscle

failure was not specifically addressed13-14. This was in part due to the fact that PaCO2

monitoring and assessment of inspiratory muscle failure were not included in

polysomnography that is programmed to interpret paradoxical chest wall motions as

obstructive and/or central apneas rather than from respiratory muscle dysfunction. This

may justify that neuromuscular disease (NMD) patients have been treated by nocturnal

continuous positive airway pressure (PAP) or low span (spans less than 10 cm H2O) bi-

level PAP, often referred to as “noninvasive ventilation” rather than by up to continuous

full setting NIV as they would eventually require with end-stage respiratory muscle

failure15.



The use of CPAP and bi-level PAP has been reported in over 100 NMD papers

including in the 50 reviewed in this work, and in many it resulted in statistical

prolongation of life before continuous support became necessary and patients either

developed ARF and underwent tracheotomy or died16-17. Bi-level PAP at low spans were

considered inadequate for patients with little or no VC18-19. Bi-level PAP devices also do

not permit air stacking6, have low autonomy internal batteries20, and not always make

possible for infants to trigger21. Meanwhile, portable ventilators, rather than bi-level

devices, have been used by continuously NIV dependent patients for up to 56 years.

Airway secretion congestion, especially during intercurrent respiratory tract

infections (RTIs) can result in acute respiratory failure (ARF)22 and intubation, and with

failure to pass spontaneous breathing trials (SBTs), tracheotomy or death23. The ability

to increase cough flows by mechanically assisted coughing (MAC), available since 1993

facilitated long-term use of NIV by permitting patients to avert pneumonia and ARF22, 24-

25as well as for “unweanable” patients to be extubated without resort to tracheotomy26-27

Methodology

At the 69th Congress of the Mexican Society of Pulmonologists and Thoracic

Surgeons in April 2010, clinicians from centers who use NIV for full, long-term

ventilatory support submit their data for three diagnoses: Duchenne muscular dystrophy

(DMD), amyotrophic lateral sclerosis (ALS), and spinal muscular atrophy type 1 (SMA

1). Other centers were invited to send their data soon after. An expert panel considered

the evolution NIV reviews and consensus statements since 1993 and the importance of

complimentary interventions that permit long-term NIV as an alternative to TIV.



Results

The data from 20 NMD centers in 18 countries on prolongation of life for NMD

patients as defined by continuous NIV dependence with little or no autonomous breathing

ability are in Tables 1-3. Data is presented as mean±SD for each center and the total data

display (all centers together) was performed using a mean correction factor for all the

items analyzed.

The centers with experience in extubation/decannulation of unweanable NMD

patients to NIV/MAC despite failing all SBTs, reported 229 safe extubations in DMD,

ALS and SMA1 patients and had 5 of 222 DMD, 52 of 139 ALS and 7 of 33 SMA 1

continuous NIV users undergo tracheotomy. Centers reported that 47% of ALS, 54% of

DMD and 39% of SMA 1 patients progressed to become continuously ventilator

dependent without being hospitalized or developing ARF.

Review of Evolution of NIV Reviews/Consensuses and Recommendations

Three members of the panel (MRG, JRB, AH) reviewed 50 consensuses and

Medline reviews from 1993-2010 with keywords for: NMD, DMD, ALS, SMA type 1,

NIV, respiratory management, respiratory care, long term ventilation, and ARF. The 50

NMD NIV references included 34 on various NMDs, 5 only on DMD, 5 on SMA 1, and

6 on ALS.

The literature was analyzed for the use over time of the following: oxygen

therapy, peak cough flow evaluation and augmentation, air stacking, low pressure (≤30



cmH2O) and high pressure (≥ 40 cm H2O) MAC, bi-level PAP used at both low and high

spans, NIV that includes nasal and mouthpiece NIV, part-time (<23 hours/day) and full-

time (>23 hours/day), oximetry feedback for NIV and MAC, elective tracheotomy

without meeting reported criteria for tracheotomy28, and extubation/decanulation of

unweanable patients to NIV. The importance of each was considered by the panel. Table

4 lists the reference papers and the evolution of intervention utilization over time.

Oxygen therapy

Avoidance of supplemental oxygen was recommended by 24 of the 50 papers and

its use ignored by the rest. Home oxygen therapy was strongly discouraged by

consensuses of 200429 and 201030. This panel concurred, recommending that

supplemental oxygen be used only for hospitalized patients when full-setting NIV and

MAC can not normalize (≥95%) oxyhemoglobin saturation (SpO2) and then only when

the patient can be readily intubated. Low flow oxygen has been reported to exacerbate

hypercapnia in NMD31. Most such patients who become CO2 narcotic do so receiving

oxygen rather than assisted ventilation. Besides decreasing ventilatory drive it appears to

exacerbate mouth leak of nasal NIV during sleep thereby exacerbating nocturnal

hypercapnia and renders oximetry less useful as a gauge of hypoventilation, airway

mucus congestion, atelectasis and pneumonia6, 22, 32. Oxygen supplementation, instead of

no treatment or assisted ventilation was reported to result in significantly more

pneumonias, hospitalizations, and hospitalization days31. Supplemental oxygen and

morphine are indicated for euthanasia such as in advanced bulbar-ALS patients who

satisfy criteria for but refuse tracheotomy33.



Lung insufflation techniques: “air stacking”

Air stacking was cited in 21 of the 50 consensuses, in only 2 papers before 2002

but in 6 of 12 since 2009. Deep passive or active (air stacking) lung insufflation is

required to prevent chest wall contractures and lung restriction, to maximize cough peak

flows (CPF)34 and voice volume, promote lung growth, and prevent chest deformity in

children with NMD6. Air stacking involves the glottis holding consecutively delivered

air volumes (from a volume- cycled ventilator or a manual resuscitator) until maximum

possible lung inflation, the “maximum insufflation capacity” (MIC)35. The panel

unanimously recommended that NMD patients with VCs less than 80% of normal

practice daily air stacking and, if unable, passive maximal lung expansion. The MIC-VC

is also recommended as an objective, reproducible, quantitative measure of glottic

integrity36. For small children with paradoxical breathing who can not air stack,

nocturnal NIV can prevent pectus excavatum and promote lung growth and chest wall

development37-38

Evaluation and augmentation of cough peak flows (CPF)

Evaluation of CPF was cited in 25 of 50 papers, only one before 2000 but all but 5

since 2009. Measurement of unassisted and assisted CPF is useful to indicate introduction

of manually assisted coughing and MAC39. Manually assisted coughing consists of

maximal air stacking followed by a cough-timed abdominal thrust. These “assisted CPF”

are measured by peak flow meter and, when less than 270 to 300 L/m, indicate need for

access to MAC especially during intercurrent respiratory tract infections (RTI)40.The



panel unanimously recommended routine measurement of CPF and augmenting them

when they are less than 270 L/m.

Noninvasive Ventilation (NIV)

Three reviews and consensuses of respiratory management of NMD did not

mention NIV. Of the remaining 47, 11 recommended high span (IPAP, EPAP spans>10

cm H2O) bi-level PAP and 29 only low span PAP. Ten of 50 papers recognized the use

of NIV for full ventilatory support but none noted that tracheostomy could be avoided by

this when the patients are critically ill. In 1993 indication for tracheotomy was described

as need for NIV over 15 hours a day41. In that report, there was only one dissenting voice

who argued for continuous NIV use both in acute and chronic settings(the second author).

The use of some daytime mouth piece NIV was recommended in 16 of 47 papers

but despite this, its use has been reported in only four centers7, 9-10, 19. This panel

unanimously felt that low bi-level spans suboptimally rest inspiratory muscles and

insufficiently support patients with little or no VC. Further, since most of currently

available pressure- cycled units are limited to less than 40 cm H2O, they can be

inadequate for patients with poor pulmonary compliance. However, the panel

unanimously recommended that bi-level PAP be introduced to all patients symptomatic

for hypoventilation who can not air stack because of bulbar-innervated muscle

impairment of glottic closure as in bulbar ALS42. The panel also unanimously

recommended that volume cycling be used for all patients capable of air stacking unless it

caused excessive abdominal distension43-44. Nocturnal NIV can then be easily extended

through daytime hours as needed by switching from nocturnal nasal to diurnal mouth



piece NIV. When less than full support settings is used, tracheostomy or death becomes

inevitable.

Mechanically Assisted Cough

Mechanically assisted coughing (MAC) is defined as mechanical insufflation-

exsufflation (Cough Assisttm, Phillips Respironics, Inc.) (MI-E) with an exsufflation-

timed abdominal thrust. The MI-E delivers positive then negative pressures via an oro-

nasal interface or invasive airway tube to full clinical expansion then emptying of the

lungs45. Only 12 papers mentioned MI-E at what this panel considers effective absolute

pressures of >35 cm H2O46-48, 19 recommended low pressures, 3 noted no MI-E settings,

and 15 did not even mention MI-E. Only 3 papers29, 49-50 cited the importance of MAC,

that is, MI-E with an abdominal thrust. None cited the use of MAC via invasive airway

tubes, found to be so critical for extubation/decanulation of patients failing SBTs27.

MAC can also significantly decrease hospitalization rates24, 51. The panel unanimously

recommended that MAC be used, whether noninvasively or via invasive airway tube, for

all NMD patients with airway secretion congestion to prevent pneumonia and to facilitate

extubation/decanulation.

Extubation and Decannulation

Despite NIV and MAC, aspiration and intercurrent RTIs can result in pneumonia

and ARF and early tracheotomy has been proposed to “minimize respiratory

complications”52-54. Before 2010, no papers described the extubation or decanulation of

continuously ventilator dependent patients who could not pass SBTs before or after



extubation/decanulation. The conventional approach presupposes that ventilator weaning

is necessary for safe extubation. A 2010 publication reported successful extubation of

155 of 157 unweanable NMD patients in 2 centers using a protocol including extubation

to full setting NIV with the patients subsequently “weaning” themselves by taking fewer

and fewer mouth piece NIVs as needed, and using MAC to clear secretions27. Protocols

for decanulation of unweanable patients to NIV/MAC have also been described26, 55, with

advantages noted by patients for safety, convenience, appearance, comfort, speech, sleep,

swallowing, and general acceptability56. The panel unanimously recommended that all

NMD patients with some bulbar-innervated muscle function be extubated or offered

decanulation to full setting NIV and MAC with oximetry feedback. It appears that the

great majority of NMD patients for whom post-extubation assisted CPF attain 160 L/m

can be successfully extubated to full-setting NIV and MAC.

Tracheostomy

Tracheostomy for end-stage respiratory management was cited in 46 of 50 of the

papers. Conventional strategies recommend tracheotomy when continuous NIV is

required57, when intubated patients are unable to pass SBTs58, and electively, for

example, for impending surgery59. Even without ventilator use tracheostomies are often

retained because of lack of familiarity with MAC for clearing airway secretions60-61. This

is true despite long-term complications of tracheostomy mechanical ventilation (TMV)62.

In addition, patients using TMV tend to become and remain continuously ventilator

dependent whereas when extubated/decanulated to continuous NIV and having VCs of

250 ml or more, wean to nocturnal only NIV55; tracheostomy renders cough impossible



because glottic closure does not maintain thoraco-abdominal pressure and it results in air

leaks around the walls of the tube63. This panel unanimously recommended that

tracheotomy be indicated for all patients who aspirate so much saliva that SpO2 baseline

decreases and remains below 95% despite optimal NIV and MAC and that can not be

reversed by translaryngeal intubation over a 1 month period as has only been reported for

patients with ALS28.

Oximetry Feed-back Protocol

An oximetry, NIV/MAC protocol consists of using an oximeter for feedback to

maintain SpO2≥95% by full-setting NIV and aggressive MAC as needed22. The protocol

was recommended in 8 of 50 papers and in only 1 before 2003. Since supplemental

oxygen is avoided, patients and care providers are instructed that, once artifact is ruled

out, SpO2 below 95% is due to: hypoventilation with hypercapnia, airway secretion

congestion, and if not expeditiously managed, gross atelectasis or pneumonia28, 64. The

protocol is most important during RTIs and for extubation/decanulation27. If the baseline

SpO2 during RTIs decreases below 95% despite the protocol, the patient presents for a

formal evaluation. The panel unanimously agreed that, since it is impossible to develop

ARF with SpO2≥95% in ambient air, patients should be taught the protocol once CPF

can not exceed 270 to 300 L/m to prevent pneumonia and ARF, particularly during

intercurrent RTIs that can be managed at home24-25.



Discussion

Mechanisms by which nasal or mouthpiece/lipseal NIV can improve the clinical

picture include: resting respiratory muscles and decreasing metabolic demand, increasing

tidal volumes and relieving hypercapnia, resetting chemoreceptors, opening atelectatic

areas, maintaining airway patency, improving ventilation/perfusion matching,

maintaining lung and chest wall range-of-motion and possibly compliance, improving

mucociliary clearance, and most importantly, by assisting, supporting, and substituting

for inspiratory muscle function6, 32.

This work keyed on three NMD diagnoses, however, continuous full-setting NIV

via mouth pieces had already been reported for 257 mainly post-polio survivors in 19937,

59 high level traumatic tetraplegics decanulated to full-setting NIV65-67 and patients with

non-Duchenne muscular dystrophies and other myopathies18, 68 All of the centers

reporting data in this study had long-term full-time NIV users with other diagnoses but it

was felt that limiting the data to these common and severe conditions would be more

practical and establish the point.

Nocturnal- only nasal NIV or bi-level PAP can at best marginally prolong life and

delay ARF. It can possibly do so by providing moderately deeper lung volumes to assist

in coughing. With advancing weakness, full-setting NIV can eventually be needed

continuously without requiring intubation and hospitalization, thereby avoiding ARF and

ultimately pressure by physicians to recommend tracheotomy.

Most conventionally managed patients develop ARF and die or undergo

intubation and tracheotomy due to airway congestion during RTIs22, the cause of 90% of

episodes of ARF for DMD patients without access to NIV and MAC24, 69. Suctioning



patients' airways via the nose or mouth is rarely effective and impairs breathing.

Whereas with “invasive suctioning” there is little chance of a suction catheter entering

the left mainstem bronchus, “noninvasive suctioning” using MI-E would not favor right

over left airway clearance63, 70.

Since MAC can only replace inspiratory and expiratory muscle function, it can

not be used to avert tracheotomy indefinitely if glottic dysfunction prevents air stacking

and airway protection to maintain baseline SpO2 (≥95%) as eventually occurs in

advanced bulbar ALS28, 42, 71. The patients who benefit most from MAC are those whose

bulbar muscle function is impaired but can maintain adequate airway patency but is

insufficient to permit optimal air stacking for assisted CPF over 250 to 300 L/m71.

The data presented suggest that reported “NIV failure” can result from inadequate

NIV interfaces, from inadequate ventilator settings, when MAC is not used, and when

mouth piece NIV is not used for air stacking or daytime support.

Whereas some recent consensuses recommend most of the interventions that this

panel considers important, all gave sufficient rationales to resort to tracheotomy for

advanced patients, largely because none reported extubating or decanulating unweanable

patients. Indeed, the 2010 DMD consensus30 was the first to make all of the

recommendations that this panel considered important, however, they concluded that

tracheostomy was appropriate when: preferred by the patient and clinician; NIV could not

successfully be used by the patient; when there was inability of “the local medical

infrastructure to support NIV”; for three extubation failures despite optimal use of NIV

and MAC; for aspiration of airway secretion to the extent that SpO2 remains below 95%

despite optimal use of NIV and MAC. However, this panel of 11 experts had only 4 with



any experience in continuous NIV including via mouthpiece and only one from a center

where NMD patients who failed SBTs are extubated without tracheotomy.

This is markedly different from this panel in which every member has continuous

long-term NIV users and at least 5 are from centers that routinely extubate and decanulate

“unweanable” NMD patients including 155 consecutive successful extubations of

unweanable NMD and SCI patients27. In addition, no one on this panel has ever noted

any patient who: “preferred” to undergo tracheotomy when they could be managed by

NIV and MAC. We suggest that only the patients not offered expert NIV/MAC “prefer”

tracheostomy. Other than for severely mentally retarded patients no one on this panel has

encountered a DMD patient who could “not successfully use NIV.” We are also unaware

of “inability of local medical infrastructure to support NIV” except in countries where

ventilator use is not funded. The centers that extubate unweanable DMD patients have

not yet had a DMD patient fail 3 extubations and, thereby, require tracheotomy. None on

this panel has witnessed a DMD patient aspirate so much saliva that the SpO2 remained

below 95% (or normal SpO2 for altitude) and thereby require a tracheostomy as per

tracheotomy indications for ALS28. Thus, while the 2010 panel’s NIV use

recommendations are comprehensive up to the point of requiring intubation30, this panel

suggests that with the ability to consistently extubate continuously ventilator dependent

DMD patients and others, resort to tracheotomy should be much less common. A basic

problem with the tracheotomy recommendations of the 2010 consensus is that they can

be interpreted by any clinician to justify tracheostomy rather than organizing a support

system of comprehensive instruction and training in NIV and MAC. Such a premise

perpetuates invasive care whereas noninvasive management is less costly, requires less



technology and skilled nursing, facilitates community care and quality of life, and is

invariably preferred by patients51.

For SMA 1 it is as yet unclear whether all will some day require tracheostomy

tubes for survival. Thus far, survival has been extended to up to age 17 using full-time

NIV for 16 years or more for children continuously NIV dependent since as young as 4

months of age72-73. There are now 5 such severely affected SMA 1 patients over age 15,

all with VCs less than 20 ml, and none with baseline SpO2 less than 95% because of

saliva aspiration. Thus, it is likely that at least some of these typically severe SMA1

patients will survive into adulthood without tracheostomy tubes despite continuous

ventilatory support since infancy. Despite these outcomes, consensuses of experts as

recently as 2009 report that 95% of SMA 1 children die before 18 months of age with a

mean age of death at 25 weeks74-75. Although acknowledging that NIV treated SMA 1

children can live much longer, in disbelief and without justification they dismissed this as

reflecting “less severely affected children”.

End of life and palliative care issues

Over a 6-year period, many journals published numerous papers on the futility of

managing ALS with palliative care without once referring to prolonging life by

NIV/MAC33, 76-80. The data from our 1623 NIV supported patients (that include 822 ALS)

suggest the inappropriateness of using palliative care precepts for properly equipped and

trained patients with adequate personal care support. A number of our DMD patients, for

example, are over age 40 and/or have depended on continuous NIV for over 20 years.

Unlike patients deciding about tracheotomy, few patients refuse NIV or MAC when



dyspneic from inspiratory or expiratory muscle insufficiency. Our panel unanimously

agreed that no properly trained and equipped patients that do not meet our criteria for

tracheotomy have ever chosen elective tracheotomy or to cease NIV/MAC and die.

Thus, it was unanimously felt that the use of the term “palliative respiratory care” for

NMD patients perpetrates the misconception that “NIV” is only for symptom relief rather

than to prolong life.

Conclusion

In conclusion, up to total failure of inspiratory and expiratory musculature without

severe bulbar-innervated muscle dysfunction is not indication for tracheotomy.

Tracheostomy ventilation has neither been demonstrated to be associated with better

survival nor better quality of life than full-setting NIV, and all patients having used both

TMV and NIV and who are decanulated prefer NIV overall as well as for speech,

swallowing, sleep, appearance, and security.303 The panel recommends against elective

tracheotomy for any NMD patient not meeting our criteria.116



Tab

le 1

– D

ata

on

Am

yo

tro

ph

ic L

ate

ral

Scl

erosi

s

Cen

ter

Nu

mb

er

PtN

IV

Ag

e p

tNIV

D

ura

tio

n

ptN

IV

Nu

mb

er

FtN

IV

Ag

e F

tNIV

D

ura

tio

n

FtN

IV

Cu

rren

t A

ge

Nu

mb

er

FtN

IV

no

Ho

sp

Sti

ll

Ali

ve

Ex

tub

ati

on

D

eca

nu

lati

on

D

eath

s T

MV

1

64

58.5

±12.

0 0.

9±1.

4 30

60

.9±1

0.4

2.3±

2.1

63±1

2.7

25

15

7 3

15

8

2

176

52.5

±5.6

0.

9±1.

1 10

9 53

.3±5

.3

0.8±

2.2

54.6

±5.7

34

67

15

6

42

44

4

62

58.0

±13.

4 1.

9±1.

9 20

57

.1±1

2.6

0.7±

0.6

61.4

±12.

2 4

35

0 0

27

7

7

23

55±1

4 1.

3±1.

6 11

55

±15

1±0.

9 60

±2

NK

2

4 1

9 5

8

83

56.1

±9.0

0.

9±0.

9 19

55

.5±9

.0

1.1±

2.1

NK

N

K

6 0

0 7

6

10

4 67

.8±6

.9

1.3±

0.8

4 69

.3±6

.6

2.0±

1.9

70.5

±8.4

N

K

1 0

0 3

1

11

78

59.5

±9.4

0.

9±1.

1 27

60

.3±1

.3

0.6 ±0.5

62

.2±9

.1

NK

14

0

0 13

6

13

120

64±2

4.2

NK

47

N

K

1,84

±0.8

N

K

NK

34

N

K

NK

86

7

16

13

59.3

±10.

4 1.

3±0.

8 13

59

.3±1

0.4

2.1±

2.5

NK

N

K

NK

0

0 N

K

NK

19

49

61.9

±13.

4 0.

9±1.

0 22

N

K

0.3±

0.7

70.4

±7.6

22

12

0

0 10

6

20

150

58.6

±24.

5 N

K

33

NK

23

.8

NK

N

K

29

0 0

4 6

Leg

end

– N

ptN

IV –

num

ber

of p

atie

nts

begi

nnin

g no

ctur

nal n

onin

vasi

ve v

enti

lati

on (

NIV

); A

ge p

tNIV

- ag

e w

hen

begi

nnin

g pa

rt-t

ime

(noc

turn

al)

NIV

; Dur

atio

n pt

NIV

-tim

e of

use

of

NIV

<20

ho

urs

per

day;

N f

tNIV

- n

umbe

r of

pat

ient

s pr

ogre

ssin

g to

>20

hr/

d ve

ntil

ator

dep

ende

nce;

Dur

atio

n ft

NIV

-dur

atio

n of

con

tinu

ous

NIV

sup

port

; Cur

rent

Age

-ag

e cu

rren

tly

or a

t tim

e of

dea

th;

Sti

ll A

live

-num

ber

of c

onti

nuou

sly

NIV

dep

ende

nt p

atie

nts

stil

l usi

ng c

onti

nuou

s N

IV; E

xt-N

umbe

r of

ext

ubat

ions

of

“unw

eana

ble”

pat

ient

s to

ful

l-se

ttin

g N

IV s

uppo

rt; D

ecan

-Num

ber

of

cont

inuo

usly

ven

tila

tor

depe

nden

t pat

ient

s de

canu

late

d to

NIV

; Dea

ths-

res

pira

tory

/tot

al; T

MV

– n

umbe

r of

pat

ient

s un

der

trac

heos

tom

y ve

ntil

atio

n; N

K –

not

kno

wne

d

Tota

l p

tNIV

– 8

22

pa

tien

ts

To

tal

ftN

IV –

335 p

ati

ents

Tota

l E

xtu

bati

on

s – 2

6

T

ota

l D

ecan

ula

tion

s – 1

0

Tota

l D

eath

s –

21

6 p

ati

ents

T

ota

l T

rach

eost

om

y –

96

Med

ian

Age

ptN

IV –

58,1

±12,6

yea

rs

Med

ian

Du

rati

on

ptN

IV -

1,0

±0

,8 y

ears

Med

ian

Age

ftN

IV -

56,2

±4,9

yea

rs

Nu

mb

erF

tNIV

noH

osp

- 8

5

Med

ian

Du

rati

on

ftN

IV -

3,4

±1

,3 y

ears

Cu

rren

t A

ge

– 5

9,3

±7,6

yea

rs

S

till

Ali

ve

– 1

86 f

tNIV

pati

ents



Tab

le 2

– D

ata

on

Du

chen

ne

Mu

scu

lar

Dyst

rop

hy

Cen

ter

Nu

mb

er

PtN

IV

Ag

e p

tNIV

D

ura

tio

n

ptN

IV

Nu

mb

er

FtN

IV

Ag

e F

tNIV

D

ura

tio

n

FtN

IV

Cu

rren

t A

ge

Sti

ll

Ali

ve

Nu

mb

er

FtN

IV

no

Ho

sp

Ex

tub

ati

on

D

eca

nu

lati

on

D

eath

s T

IPP

V

1

18

16.3

±4.6

3.

4±1.

8 14

20

.4±6

.3

5.4±

4.4

20.1

±9.2

11

12

7

2 3

0 2

12

0 20

.3±2

.8

2±2.

1 10

1 22

.3±5

.9

7±5.

9 30

.3±6

.1

87

23

29

9 14

0

3

88

18.9

±3.3

5.

4±3.

3 56

24

.7±4

.6

5.8±

3.4

31±5

.2

46

NK

8

2 10

0

4

28

20.5

±4.1

4.

7±3.

4 4

27.2

±6.2

2±

0.8

25.3

±4.5

1

0 0

1 4

1 5

38

12

.8±2

,9

25±1

4,6

2 12

±0,3

17

±22

14.9

±3

32

1 1

0 7

1

7

16

21±4

2±

1.6

9 25

±2

1.8±

1.3

25±1

5

NK

1

2 4

0 8

25

18

.3±4

3.

5±2.

4 11

21

.9±2

.4

5±4.

4 26

.9±4

.3

8 9

2 1

3 0

9

24

18±1

.6

9.9±

4.5

24

28.1

±4.6

4.

2±2.

8 32

.3±2

.8

24

24

0 0

0 0

10

10

22

.7±3

.2

1.7±

1.9

10

24.3

±4.1

4.

6±1.

6 28

.4±4

.6

10

10

0 4

0 0

11

9

18.7

±5.2

4.

6±2.

2 4

23.3

±6.5

4±

2.8

27±5

3

NK

0

0 1

1 1

2

100

18.9

±3.2

8.

3±4.

3 56

23

.6±3

.5

5.7±

3 28

.7±4

.2

23

38

1 0

33

12

13

16

2 17

±12.

9 N

K

51

NK

N

K

27.5

30

N

K

12

4 21

5

14

4

21.3

±3

5±3

4 25

±4

3.8±

1.4

28

2 N

K

0 0

2 0

15

6

22±2

.8

3±1.

1 6

25±2

.4

4.9±

3.2

29.9

±3.6

4

NK

0

0 2

0 1

6

3 20

±3.9

10

.0±5

.6

3 30

±4

2.4±

1.4

32.4

±3.9

3

3 0

0 0

0 1

7

36

20.8

±4.6

3.

3±1.

8 17

24

.5±4

.5

4.0±

2.6

28.2

±4.9

8

NK

0

0 4

7 1

8

13

19.8

±2.8

5.

7±2.

2 13

25

.5±4

.2

4.8±

3.6

30.8

±4.2

11

N

K

0 0

2 2

Leg

end

– N

ptN

IV –

num

ber

of p

atie

nts

begi

nnin

g no

ctur

nal n

onin

vasi

ve v

enti

lati

on (

NIV

); A

ge p

tNIV

- ag

e w

hen

begi

nnin

g pa

rt-t

ime

(noc

turn

al)

NIV

; Dur

atio

n pt

NIV

-tim

e of

use

of

NIV

<20

ho

urs

per

day;

N f

tNIV

- n

umbe

r of

pat

ient

s pr

ogre

ssin

g to

>20

hr/

d ve

ntil

ator

dep

ende

nce;

Dur

atio

n ft

NIV

-dur

atio

n of

con

tinu

ous

NIV

sup

port

; Cur

rent

Age

-ag

e cu

rren

tly

or a

t tim

e of

dea

th;

Sti

ll A

live

-num

ber

of c

onti

nuou

sly

NIV

dep

ende

nt p

atie

nts

stil

l usi

ng c

onti

nuou

s N

IV; E

xt-N

umbe

r of

ext

ubat

ions

of

“unw

eana

ble”

pat

ient

s to

ful

l-se

ttin

g N

IV s

uppo

rt; D

ecan

-Num

ber

of

cont

inuo

usly

ven

tila

tor

depe

nden

t pat

ient

s de

canu

late

d to

NIV

; Dea

ths-

res

pira

tory

/tot

al; T

MV

– n

umbe

r of

pat

ient

s un

der

trac

heos

tom

y ve

ntil

atio

n ; N

K –

not

kno

wne

d T

ota

l p

tNIV

– 7

00

pati

ents

To

tal

ftN

IV –

385

pati

ents

To

tal

Extu

ba

tio

ns

– 6

1

To

tal

Dec

an

ula

tio

ns

– 2

5

To

tal

Dea

ths

- 110

To

tal

Tra

cheo

stom

y –

29

M

edia

n A

ge

ptN

IV –

18.9

±4

.91

yea

rs

Med

ian

Du

rati

on

ptN

IV –

3.6

3±

2.7

yea

rs

Med

ian

Age

ftN

IV –

23

.8±

6.6

yea

rs

Nu

mb

er F

tNIV

no

Ho

sp –

120

M

edia

n D

ura

tion

ftN

IV –

5.5

6±

1.6

yea

rs

Sti

ll A

live

– 3

08

ftN

IV p

ati

ents

Cu

rren

t A

ge

- 28

,5±

4,2

yea

rs



Tab

le 3

– D

ata

on

Sp

ina

l M

usc

ula

r A

trop

hy t

yp

e 1

Cen

ter

Nu

mb

er

PtN

IV

Ag

e p

tNIV

D

ura

tio

n

ptN

IV

Nu

mb

er

FtN

IV

Ag

e F

tNIV

D

ura

tio

n

FtN

IV

Cu

rren

t A

ge

Nu

mb

er

FtN

IV

no

Ho

sp

Sti

ll

Ali

ve

Ex

tub

ati

on

D

eca

nu

lati

on

D

eath

s T

IPP

V

1

11

0.3±

0.3

0.2±

0.4

10

0,4±

0,2

2,4±

1.7

5.3±

3.1

7 6

8 0

4 3

2

76

0.4±

0.3

0.6±

0.1

22

0.9±

2.7

9.4±

3.5

10.3

±3.4

5

19

121

0 3

4

5

3 0.

5±0.

45

3.7±

4 4

0.6±

0.65

1.

8±0.

8 1.

2±0.

04

2 0

0 0

4 6

7

3 0.

7±0.

8 1.

4±2.

2 2

0,3±

0,1

0,1±

0 5±

5 N

K

2 0

0 1

2

13

7 0,

9 N

K

1 0,

1 0,

3 4.

8 N

K

0 13

0

7 0

16

1 0.

5 0.

4 1

0,5

4.5

5 N

K

1 0

0 0

0 L

egen

d –

N p

tNIV

– n

umbe

r of

pat

ient

s be

ginn

ing

noct

urna

l non

inva

sive

ven

tila

tion

(N

IV);

Age

ptN

IV-

age

whe

n be

ginn

ing

part

-tim

e (n

octu

rnal

) N

IV; D

urat

ion

ptN

IV-t

ime

of u

se o

f N

IV<

20

hour

s pe

r da

y; N

ftN

IV -

num

ber

of p

atie

nts

prog

ress

ing

to >

20 h

r/d

vent

ilat

or d

epen

denc

e; D

urat

ion

ftN

IV-d

urat

ion

of c

onti

nuou

s N

IV s

uppo

rt; C

urre

nt A

ge -

age

curr

entl

y or

at t

ime

of d

eath

; S

till

Ali

ve-n

umbe

r of

con

tinu

ousl

y N

IV d

epen

dent

pat

ient

s st

ill u

sing

con

tinu

ous

NIV

; Ext

-Num

ber

of e

xtub

atio

ns o

f “u

nwea

nabl

e” p

atie

nts

to f

ull-

sett

ing

NIV

sup

port

; Dec

an-N

umbe

r of

co

ntin

uous

ly v

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TABLE 4 - The Evolution of Consensus and Review Articles on Noninvasive Ventilation and Neuromuscular Disease.

Legend: Year - year of publication, O2 - oxygen avoidance, CPF – cough peak flow; AS- air stacking; MAC – mechanical assisted cough; lpMAC - mechanically assisted coughing with low pressure (<35); hpMAC – mechanical assisted coughing, high pressure (>35); lsp- low span BiPAP; hsp - high span BiPAP; MP – mouthpiece NIV, ptNIV - part-time NIV (up to 16 hours/day); ftNIV - full-time NIV (>20hours/day); TMV – tracheostomy mechanical ventilation;SpO2 feedback – protocol with oximetry feedback

Reference Year O2 avoidance

CPF AS MAC lpMAC hpMAC lsP HsP MP ptNIV ftNIV Extubation/Dednulation TMV SpO2 feedback

81 1993 X 41 1993 X X X X X X 17 1994 X X X 82 1995 X X X X X 50 1996 X X X X X X X X X X X 83 1997 X X X X 84 1997 X 85 1997 X X X 23 1998 X X X X X X X X 86 1998 X X X X X 87 2000 X X X X X 88 2002 X X X X X X X 57 2002 X X X X X X 89 2003 X X X X X 90 2003 X X X X X X X X 29 2004 X X X X X X X X X X X 91 2004 X X X X X X 92 2004 X X X X X X X X 93 2005 X X X X X 94 2005 X X X X X X X 95 2005 X X X X X 96 2006 X X X X X X X X X X 19 2006 X X X X X X X X 97 2006 X X X X X X X 98 2006 X X X X X X X X 99 2006 X X X X X X 100 2006 X X X X 58 2006 X X X 101 2006 X X X X X X X X 102 2007 X X X X X X 103 2007 X X X X X X X X X X 104 2007 X X X X X X X X X(Extubation) 105 2007 X X X 75 2007 X X X X X X X X 106 2008 X X X X X 107 2008 X X 108 2008 X X 109 2008 X X X 110 2009 X X X X X X X X 74 2009 X X X X X 111 2009 X X X X X X 112 2009 X X X 113 2009 X X X X X X X X 49 2009 X X X X X X X X X X 114 2009 X X X X X X 115 2009 X X X X X X 116 2009 X X X X 117 2009 X X X X X X X 118 2009 X X X X X X X X X

30 2010 X X X X X X X X X X X X



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GENERAL DISCUSSION

All 10 studies that were part of this thesis were clinical and had direct positive impact

on the patients studied in which NIV was insufficient due to secretion encumbrance.

The addition of new measurements (VRI, MI-LIC, DF, PCF-PEF) in the chronic setting

permitted the correct indication for lung expansion and air stacking techniques. MAC

was able to achieve adequate CPF to clear secretions and was crucial to invert the ARF

episode and avoid hospitalizations. Failure to provide adequate settings for effective

nocturnal ventilatory support, mouthpiece IPPV, and manually and mechanical assisted

coughing continue to make respiratory failure inevitable for the great majority this

patient population.

Acute Respiratory Failure

During acute critical care, in most patients, mechanical ventilation is a short-term

treatment used for up to 7 days to support or replace spontaneous breathing until the

cause of respiratory failure resolves or results in death. Patients who receive mechanical

ventilation for more than 7 days, when remain unweanable after 4 weeks of resolution

of the acute respiratory failure (ARF) episode, have been classified as chronic

ventilator-dependent patients(19). Intubated ventilator supported patients can develop

hypo- or hypercapnia, decreases in pulmonary function because of airway mucus, and

inspiratory muscle deconditioning.

When there is no need for an artificial airway, conventional extubation attempts follow

successful “spontaneous breathing trials (SBTs) and the passing of ventilator weaning

parameters(411). This may either cause anxiety because the patient is not ready to



breathe autonomously, or the schedule is too conservative, delaying respiratory muscle

reconditioning. Further, the use of pulse oximetry, which can signal the presence of

airway mucus encumberment as well as their elimination with treatment, is lost with

oxygen administration that is typically arbitrarily used in this setting. Some patients

with muscle weakness are unable to sustain spontaneous breathing effort and are

dependent on mechanical ventilation for life support. Some of them may be successfully

treated with partial time NIV (nocturnal and for daytime periods), but patients who

require continuous mechanical ventilation usually require more attention and support

that is most cases end in tracheostomy ventilation(415).

Until our study nr 1, there have been no studies that focused on extubation of adult

complete ventilator dependent NMD patients. (155, 190). A recent controlled post-

extubation respiratory failure study of 106 patients included 2 with pure restrictive

syndromes but none with NMD and all had passed SBTs despite hypercapnia. They

were extubated to either supplemental O2 alone or in conjunction with bi-level PAP at

spans of up to 14 cm H2O, pressures inadequate to sustain our patients(497). A meta-

analysis of 12 extubation studies to bi-level PAP demonstrated decreased mortality,

ventilator associated pneumonia, length of stay, and resort to tracheotomy, however

unweanable NMD patients were uniformly excluded in all papers(20). Eligibility for

extubation was based on “readiness for weaning” and failure of SBTs in 30 minutes or

more. The outcomes of these studies were important to justify extubation to NIV for

primarily lung/airways diseases patients with some autonomous breathing ability. For

such patients SpO2>90% is usually acceptable with or without supplemental oxygen.

Unlike all previous studies, patients included in study nr 1 had no ability to

autonomously sustain breathing before or after extubation with VCs as low as 0 ml, so

no control group extubation to O2 would be possible, ethical, or permissible by any



review board. For our patients long-term inability to maintain SpO2≥95% despite

continuous NIV and MAC in ambient air is the indication for tracheotomy(481).

The success of our protocol was not only from providing continuous full-setting NIV

via a variety of interfaces, but from frequent and aggressive MAC (up to every 30 min)

both pre- and post-extubation to expel secretions and maintain or return SpO2 over

95%. Such a regimen simulates the normal need to cough during episodes of

bronchitis/pneumonia. The aggressive use of MAC via the endotracheal tube was the

main intervention that resulted in normalization of SpO2 in ambient air, the most

important criterion for extubation.

In an earlier study of extubation to NIV, of possible independent variables including

extent of need for ventilatory support, age, VC, and maximum CPF measured at

extubation, only maximum CPF predicted extubation success or failure for 62

consecutive extubation/decannulation attempts on 49 consecutive self-directed NMD

patients (358). Thirty-four of the patients were continuously ventilator dependent both

pre- and post-extubation/decannulation. In that study none of the 15

extubation/decannulation attempts on those with maximum CPF below 160 L/m

succeeded as opposed to an 89% success rate in this study. The most likely reasons for

the difference between then and now are: baseline SpO2 criterion for extubation 92%

vs. 95% and thus the earlier patients had more residual airway secretions or lung disease

at extubation; 5% vs. 39% of patients with pre-extubation experience with NIV and

MAC; less hospital staff experience with NIV and MAC; 50 of 62 were decanulated

(not extubated); the patients were in various hospital locations; and MAC was used less

often and without family involvement (9, 462).



The 87% first attempt extubation success rate on patients with maximum CPF<160 L/m

study nr 1 is greater than the 82.4% (61 of 74) success rate reported for extubating

ventilator dependent infants with SMA type 1 according to an almost identical

protocol(498). The difference is most likely due to the ability of these patients, as

opposed to babies, to fully cooperate with NIV and MAC. The SMA 1 patients may

have also had more severe bulbar-innervated muscle dysfunction. Thus, while the

extubation success rates for our patients with CPF<160 L/m were higher than those for

a comparable infant population they were significantly less (89% vs. 100%) (p<0.05)

than for patients with assisted CPF≥160 L/m. Unmeasurable assisted CPF indicate

inability to close the glottis and are often associated with airway collapse (stridor) and

saliva aspiration that render MAC less effective.

An NIV/MAC protocol has already been demonstrated to have avoided over 100

hospitalizations for continuously NIV dependent NMD patients (63, 127, 481). Study

nr 1 considered unweanable NMD patients for whom an acute hospitalization and

intubation could not be or were not avoided.

In this study, patients were extubated when the following criteria were satisfied: no

supplemental oxygen requirement to maintain SpO2 greater than 94%, chest radiograph

abnormalities cleared or clearing, respiratory depressants discontinued, airway

secretions less than on admission, and any nasal congestion cleared. Thus, once the

patient is afebrile with a normal white blood cell count and the SpO2 is normal on room

air, the nasogastric tube is first removed to facilitate immediate post-extubation nasal

IPPV. MAC is then provided via the upper airway via an oral-nasal interface and the

oximetry feedback protocol is followed.



The general notion that early tracheotomy after intubation somehow facilitates

ventilator weaning (436) should be reassessed for patients with NMD. In most

instances, upon extubation, patients with VC of 250 ml or more eventually weaned from

continuous to nocturnal-only aid by taking fewer and fewer mouth piece IPPVs. Thus,

the paradigm of weaning then extubation can be changed to extubation then weaning.

Employing noninvasive rather than invasive mechanical ventilation has also been

reported to decrease risk of ventilator associated pneumonia by 75% or greater(103,

499) and other subsequent complications associated with invasive airway tubes. Use of

mouth pieces rather than other interfaces for daytime ventilatory support also facilitated

speech, oral intake, comfort, and air stacking to deep lung insufflations to maintain

pulmonary compliance, (127, 362, 500) diminished atelectasis, and augmented

CPF(362). Nasal interface skin pressure was also avoided with mouthpiece use.

The main purpose of study nr 1 was not to facilitate ventilator weaning or to consider

long-term outcomes but simply to extubate unweanable NMD patients without

tracheotomy. It has already been suggested that extubation and decannulation can

facilitate ventilator weaning and quality of life(438). Likewise, over 10,000 patient-

years of continuous noninvasive ventilatory support has already been reported(9) and no

one has demonstrated greater outcomes or survival by invasive rather than by

noninvasive means for this patient population.

In study nr 2 we report 13 intubated and 7 tracheostomized SCI patients (above C5-C6,

ASIA A and B) completely ventilatory dependent that were all successfully extubated

and decanulated with specific protocols. It is has been described that 74% of ASIA A

SCI patients above the level of C5 required intubation(441) and the overall incidence of

tracheostomy in these cases was between 81 and 83%(442-443). The number of



respiratory complications during this phase contributes significantly to both hospital

length of stay and costs(444).

Guidelines for respiratory management after SCI were published in 2005 (501),

however these recommendations relied on evidence that did not pertain to the acute

ventilatory impairment of the SCI population. In 2006, Bach challenged the medical

community to decanulate high level SCI patients to NIV to avoid the complications of

tracheostomy, to facilitate training in glossopharyngeal breathing to increase

autonomous breathing ability and security in the event of ventilator failure, and to return

home (502) Study nr 2 is the first to accept this challenge.

In this study, besides successful extubation and decannulation of totally ventilator

dependent patients, after the protocol, only 9 (45%) of the total population used NIV at

discharge and all others weaned to autonomous breathing. The use of high delivered

NIV volumes has been reported to facilitate the weaning process and lessen risk of

respiratory complications(503) as well as result in increased VC and CPF for patients

who are extubated(487) or decanulated(358, 438, 504) and our results are consistent

with those studies. Moreover, it is not expected that continuous NIV can be a successful

alternative to invasive ventilation, if patients use only mask ventilation(492). Further,

for both groups, mouthpiece ventilation normalized speech, provided normal daytime

ventilation, permitted "air stacking" for lung expansion and assisted coughing, and

weaning(87, 438, 487).

Patients with high SCI are expected to be ventilator weaned with supplemental oxygen,

despite some combination of hypercapnia and airway mucus encumbrance. This effec-

tively is the main reason for patients to require reintubation(445) and tracheostomy(442)

that did not occur in any patient extubated in study nr 2. As in study nr 1, aggressive



use of MAC via translaryngeal and tracheostomy tubes was the main intervention that

may have improved pulmonary function (VC and CPF) and normalized SpO2 in

ambient air to satisfy the most important criterion for extubation/decannulation. Our

findings are consistent with those of Bach et al.(358, 505), however our patients were

all successfully extubated despite some having assisted CPF below 160l/min (at

extubation). This was possibly due to the more aggressive use of MAC up to every 15

min to maintain normal SpO2. Pillastrini et al.(506), too reported that mechanical in-

exsufflation aided in clearance of bronchial secretions and increased forced VC, forced

expiratory volume in 1 second, and peak expiratory flows for tracheostomized SCI

subjects. Vital Capacity and CPF also improved in our patients because of lung

expansion and secretions removal.

Decannulation protocols in long term mechanical ventilated patients have been

described in other studies (507-508), however these reports only consider decannulation

when ventilatory weaning was achieved and considered as failures the patients who

could not be weaned from the ventilator, without considering the use of NIV. Therefore

patients from study nr 2 would have been considered “unweanable” under current

recommendations (415, 431).Transition from tracheostomy to continuous NIV was

progressive and implied a specific protocol that included ventilation with a deflated cuff

for increasing periods until it could be tolerated throughout daytime hours and

overnight.

This “open system” ventilation(509) permitted the patients to improve their vocal cord

function that was essential for successful NIV training with a capped cuffless

fenestrated tube. In 2004 we reported that decannulation and conversion to NIV and

MAC can facilitate ventilator weaning of CMV dependent patients(438). It has also



been reported that decanulated patients invariably prefer NIV over return to

tracheostomy ventilation for safety, convenience, appearance, comfort, facilitating

effect on speech, sleep, and swallowing, and overall(439). Although there are studies

that report successful extubation and decannulation rates with the use of NIV and MAC

in high SCI patients (97, 358), study nr 2 is the first to compare the extubation with the

decannulation outcomes using the same protocol in this patient population.

In this study, both short –term and long term outcomes for the extubated patients were

better than for the decanulated patients. Thus, it appears preferable, in this patient

population, to prevent tracheotomy in the first place, whenever possible, rather than

decanulate later on. Certainly, patients with severe bulbar-innervated muscle

involvement, head injury, chest trauma, medical fragility, complicated courses including

the need for surgical procedures over a greater than 3 or 4 week period are best

managed by tracheotomy.

Data from study nr 2 also show that the extubated SCI patients had significantly shorter

ICU stays, were more quickly extubated than the decanulated patients decanulated, had

higher VC at 48 hours after tube removal, higher unassisted and assisted CPF at 48

hours and at 6 months after tube removal than those decannulated. This can be due to

the fact that extubated patients had significant less time on invasive ventilation with

consequent less respiratory muscle deconditioning, were somehow less severely

affected despite comparable VCs and ASIA levels at extubation, or had less risk of

upper airway instability and less secretion encumbrance or segmental atelectasis despite

the same CPF and normal SpO2. Moreover, the decanulated patients needed MAC to

clear airway secretions for longer periods of time as well as more time for NIV training

and tracheostomy site closure. The higher values of VC at 48 hours after extubation



explains the greater number of extubated patients discharged to the community with no

ventilatory support.

Although tracheostomy may have physiologic benefits over endotracheal tubes in terms

of reduced work of breathing(510)and permitting more efficient suctioning, over 90% of

the time suction catheters enter only the right mainstem bronchus resulting in 80% of

pneumonias occurring on the left lungs of these patients(511) and work of breathing is

readily compensated by providing pressure support during SBTs. There are no reports

of better outcomes with tracheostomy ventilation when compared to the NIV/MAC

protocols.

Improvement in VC, CPF and SpO2 following MAC has been reported (54, 60, 62, 84).

Studies 1 and 2 are consistent with those reports in acute setting with direct impact on

extubation and decannulation outcomes. A controlled study with a crossover design

controlled study would be needed to compare the effectiveness of noninvasive secretion

management (MAC) to invasive airway suctioning, however, due to the significant

efficacy of MAC in severe totally ventilator dependent patients with muscle weakness,

it would not be ethical to include this patient population in such trials.

In critical care, patients' mucociliary elevators are impaired by intubation. Thus, mucus

accumulation can greatly hamper ventilator weaning and the ability to remain extubated

and is one of the main reasons for patients to require reintubation. These effects are

exacerbated by the tendency of intubated patients to develop malnutrition often in part

due to the presence of the tube. Thus, it is not surprising that conventional extubation is

very significantly less often successful by comparison to extubation using respiratory

muscle aids. Early extubation, coupled with the use of noninvasive ventilatory support

has been used effectively in several critical ill populations to facilitate weaning(20, 114,



155), improve survival(161), decrease the incidence of ventilator-associated

pneumonia(103, 153) and reduce ICU length of stay(153, 161). However there is a

higher risk of NIV failure when applied in patients that develop ARF after extubation

and the evidence that supports its application is conflicting (159-160, 446).

The results found in the trial included in study nr 3 suggest that secretion management

with MI-E may work as an useful complement technique to treat patients who develop

ARF in the first 48 hours post-extubation. The efficacy of MI-E had a stronger impact

in preventing re-intubation in the group of patients that required NIV, justified by the

lower NIV failure rates in the patients that were submitted to MI-E. By contrast,

significant debate still exists concerning the precise indications and efficacy of NIV in

this patient population(512) without any mention to the problem of impaired airway

secretion.

The randomized controlled studies performed by Esteban et al (159). and Keenan et

al(160). concluded that NIV is not efficient in reducing re-intubation rates, duration of

invasive mechanical ventilation and ICU and hospital length of stay. None of these

studies showed improvement in survival in patients that used NIV other than SMT. In

contrary, the trials conducted by Nava et al.(190) and Ferrer et al.(155) found positive

outcomes with NIV in preventing ARF after extubation. Several reasons may explain

these differences. First, whereas the studies by Keenan et al(160) and Esteban et al(159)

applied NIV after patients had developed symptoms of respiratory failure, the studies by

Nava et al(190) and Ferrer et al(155) previously identified the high-risk patients and

applied NIV immediately after extubation. Because longer time from extubation to re-

intubation is associated with worse outcome(32), the delay in re-intubation correlates

with worse survival rates in patients who received NIV for established post-extubation

respiratory failure(159-160). Thus, the early application of NIV seems crucial to avoid



respiratory failure after extubation, and consequently re-intubation. Second, a

significantly higher proportion of patients with chronic respiratory disorders were

included in the studies that used early NIV in high risk patients, whereas the NIV post-

extubation respiratory failure trials enrolled only 10–11% of patients with chronic

pulmonary disease and used different definitions for post-extubation respiratory failure.

In our study, both experimental and control groups included 20% of patients with

chronic respiratory disorders, and all patients were closely monitored during the first 48

hours for early detection of signs and symptoms that indicated post-extubation

respiratory failure. As in the trials by Esteban et al.(159) and Keenan et al.(160) NIV

was only applied after the development of those symptoms according to specific

criteria. However, in our study NIV was applied in both study group patients and

controls and only MI-E application was considered an independent variable.

Secretion encumbrance and impaired airway clearance have been considered an

independent factor for extubation failure(513), and associated to NIV failure both in

persistent weaning(153) and in post-extubation failure(159) patients. While it is

relatively easy managing secretions through an endotracheal tube, it can be a serious

problem after extubation and specially during NIV. Deep airway suction suctioning

through the tube is a strategy most commonly used by nursing staff to manage

secretions while patients are on invasive MV, however it can more traumatic, difficult

to perform and often ineffective in extubated patients since it must be performed blindly

through the nose or the mouth.

It has been reported that conventional chest physical therapy for secretion management

does not increase the chances of weaning and extubation success (357). However,



critically ill patients may have normal mucociliary clearance but ineffective CPF which

itself has been associated with extubation failure (37, 358).

Study nr 3 randomly used MI-E (CoughAssistTM, Phillips Respironics International

Inc., Murrysville, Pa) pre- extubation via invasive tube and post-extubation through

oronasal interface at sufficient inspiratory and expiratory pressures (minimum of 40 to -

40 cm H2O) to fully expand and then fully empty the adult lungs in 6-8 seconds,

thereby expelling airway secretions while avoiding both hyper and hypoventilation.

The ability to use MI-E through the endotracheal tube immediately before extubation

was the main intervention that permitted the patients from the study group to minimize

the risk of post-extubation secretion encumbrance and, together with its 3 time daily

noninvasively application, may have had influence on the reduction of re-intubation and

NIV failure rates.

Although MI-E has been described as a very efficient technique in the acute setting for

patients with neuromuscular disease (NMD), in the treatment of respiratory failure due

to upper respiratory tract infections(246), to avoid intubation(27) and to facilitate

extubation, decannulation and prevent post-extubation failure(358, 438, 505), the

evidence supporting the role of this technique in this other critical ill patient population

is lacking. Indeed, study nr 3 is the first randomized controlled trial focused on MI-E

in critical care.

The fact that there is strong evidence on the efficacy of MI-E in critical ill patients with

NMD, and the authors´ positive experience with this technique in this patient population

(study nr 3), was the ethical reasons to exclude them from the study nr 3.

Potential limitations have to be taken into account when analyzing the differences

between the two groups. First, although there were no significant differences in baseline



characteristics at the entry of the study between the 2 groups patients from the

conventional extubation group had slightly more hypoxemic respiratory failure which

may have had impact on the NIV failure rate in this patient group, since NIV is more

likely to fail when severe hypoxia is present(156). Second, 6 controls and 4 study group

patients were re-intubated immediately with no indication for NIV. This fact was

associated with causes that could not be solved by MI-E, since cooperation with the

technique is crucial in extubated patients, fact that justified the best outcomes in patients

that required NIV.

Chronic Respiratory Failure

Numerical parameters such as respiratory rate (RR), Rapid Shallow Breathing Index,

maximal inspiratory pressure, and PaCO2 have been offered as indicators for nocturnal

NIV but have been unreliable(514). Although numerous unsubstantiated opinions have

also been given on indications for initiating nocturnal NIV, and current Medicare

guidelines for ventilator use mandate VC less than 50% of predicted normal, no

universally accepted objective parameters have yet been defined(18, 101, 515).

Decisions about ventilator use are largely based on the results of polysomnograms,

pulmonary function testing, and arterial blood gas samples. However, daytime arterial

blood gases may be normal despite symptomatic nocturnal hypoventilation. Indeed,

30% of patients hyperventilate from the pain of arterial puncture(516).

Polysomnograms do not distinguish apneas/hypopneas due to central and obstructive

events from those due to inspiratory muscle weakness(517). Further, conventional

pulmonary function testing is designed for patients with lung and airways diseases

rather than muscle weakness.



Forced VC, flow and diffusion studies evaluated with the patient in the sitting position

reflect lung/airways disease. The VC measured with the patient supine is not part of

routine pulmonary function testing but better reflects diaphragm weakness. In a recent

study, supine VC less than 75% of predicted normal was 100% sensitive and specific

for predicting an abnormally low transdiaphragmatic pressure (Pdi)(518). Indeed,

patients can have VCs approaching normal when sitting but be less than 50% of normal

and have no ability to breathe when supine. The inaccuracy of considering VC alone,

especially in the sitting position, to indicate ventilator use has also been reported by

others(519).

Most often, asymptomatic patients with NMD are offered nocturnal continuous PAP or

low-span bi-level PAP on the basis of routine polysomnograms. This approach is valid

for treating central or obstructive apneas but not severe inspiratory muscle weakness

and hypoventilation for which high ventilator volumes and pressures are needed for

ventilatory support and muscle rest(10). The failure of skeletal muscle to continue to

generate a given tension is defined as muscle fatigue. When a patient is not able to

sustain the muscular work of breathing in the presence of increasing ventilatory load or

decreasing work capacity, muscle fatigue can occur and ventilatory assistance become

necessary. Bellemare and Grassino quantitated inspiratory muscle fatigue by measuring

the time elapsed between the onset of diaphragm contraction and the point at which a

target tension can no longer be sustained (Tlim)(456). In the case of the diaphragm,

there are two main factors influencing muscle fatigue or Tlim. The first is the Ti/Ttot or

duty cycle of the diaphragm. Since the diaphragm contracts mainly during inspiration,

it should fatigue more rapidly at any given tension if Ti/Ttot is abnormally increased.

The second is Pdi/PdiMax or the mean trans-diaphragmatic pressure swing developed

with each inspiration. The diaphragm should fatigue more rapidly at any given Ti/Ttot,



if the Pdi/PdiMax is greater than normal. They reported the relationship between Tlim

and TTIdi, that is, (Ti/Ttot) x (Pdi/PdiMax), and determined that Tlim = 0.1(TTIdi).

Thus, diaphragm endurance time could be predicted by the TTIdi. Determining TTIdi

requires placement of an esophageal balloon to measure Pdi and PdiMax. This makes it

impractical for general use. It has already demonstrated that Vt/VC can substitute for

Pdi/PdiMax because the more Vt approaches VC, the less the ability of inspiratory

muscles to sustain alveolar ventilation(520). Our data suggest that the VRI using

Vt/VC can supplement VC to help gauge the need for ventilator use by reflecting

ventilatory reserve.

In a previous study, Koga et al. described a breathing intolerance index (Ti/Ttot x

Vt/VC) in patients with lung/chest wall disease including 11 who were nocturnal-only

ventilator users, and in healthy subjects, and observed that it could be useful for

justifying ventilator use (520). In study nr 4 we proposed a Ventilator Requirment

Index (VRI) were we multiplied the Ti/Ttot x Vt/VC x respiratory rate (RR), to

determine whether this index could distinguish patients with NMDs with various levels

of inspiratory muscle dysfunction and need for ventilator use

An accurate index of extent of ventilator need can be important to justify the

prescription of one, two, or no ventilators. Patients with symptomatic hypoventilation

on the basis of inspiratory muscle dysfunction benefit from ventilator use at least during

sleep(89). These patients can use either pressure-cycled (BiPAPTM) or volume-cycled

machines. Likewise, two ventilators are required when a patient is continuously

ventilator dependent. Considering our data, anyone with NMD who appears to be

symptomatic for alveolar hypoventilation or who has a VC less than 50% or VRI

greater than 1.2 should have a trial of nocturnal NIV for symptomatic relief. Even 8 of

18 patients without obvious symptoms but with VC less than 50% or VRI greater than



1.2 felt sufficient benefit to go on using nocturnal NIV once introduced to it. Thus,

documentation of a VRI greater than 1.2 or a VC less than 50% is justification for the

prescription of a trial of part-time ventilator use. Once a patient requires ventilator use

greater than 20 hours day, a second ventilator should be prescribed provided that the VC

is less than 1000 ml or the VRI is greater than 2.5.

Maximum inspiratory pressures and maximum expiratory pressures are direct measures

of inspiratory and expiratory muscle strength. For patients with primarily ventilatory

impairment expiratory muscles are usually weaker than inspiratory muscles(521).

Expiratory muscle weakness not only decreases peak expiratory flows but it decreases

CPF(461). Routine pulmonary function testing includes the measurement of maximum

expiratory pressures and peak expiratory flow rates but not CPF(495, 522).

Cough peak flows are generally between 40 and 50% greater than peak expiratory flows

in normals as well as in patients with DMD(464). In severe bulbar ALS patients,

however, they may not be measurable because of inability to close the glottis(461).

Despite their importance, CPF have not yet been standardized.

Besides inspiratory and expiratory muscle weakness, CPF are also decreased by bulbar

muscle dysfunction that impairs glottic retention of an optimal breath, that impairs

glottic patency, vocal cord movement, and pharyngeal dilator function, and that leads to

aspiration of food or saliva. CPF are the best indication of the functional integrity of

bulbar musculature. They are also decreased by upper or lower airway obstruction,

anatomical or functional.

In study nr 5 we found that “dart flows” (DF) are significantly greater than CPF which

are, in turn, significantly greater than PEF for normals as well as for this group of



patients with NMD. The fact that CPF are normally greater than PEF in healthy people

as well as for patients with Duchenne muscular dystrophy has already been

reported(464). These three flow maneuvers are similar in that they are expiratory flows

measured at the mouth using a peak flow meter. However, each method of flow

generation requires different respiratory muscle groups.

With glottic closure, the greater transpulmonary pressures created by coughing

rather than by PEF maneuvers resulted in flows measured at the mouth being greater for

the former except for 12.8% of patients. However, cough efficacy is dependent on the

peak flow velocity which is greater as airways narrow during coughing, making

coughing more effective at expulsing airway secretions than huffing even though PEF

and CPF may be comparable when measured at the mouth(54). The reduction of the

cross sectional area of the airways during coughing is due to smooth muscle constriction

mediated by a vagal reflex (presumably preserved in these diseases), and due to

dynamic compression of the airways generated by the expiratory (transpulmonary)

pressure(523).The reduction in the cross sectional area of the airways increases fivefold

the velocity of gas and 25 fold the kinetic energy of the airstream. This explains why

the subgroup of 16 patients (12.8%) with CPF lower than PEF coughed rather than

huffed to expel secretions. Effective CPF and PEF share the need for deep lung

volumes, explaining their good correlation with VC and MIC.

The correlation of CPF with MIC or MIC, VC difference is explained by their

dependence on bulbar-innervated muscle (glottic) function. Whereas diminished CPF

and MIC-VC difference can be due to laryngeal dysfunction and are associated with

elevated risk of respiratory complications, DF usually exceed CPF and PEF. However,

DF are measured at the mouth but do not emanate from the airways and require little or

no inspiratory or expiratory muscle effort. DF, while also dependent on bulbar-



innervated muscles but not glottic function, do not appear to reflect risk of respiratory

complications. Inability to create measurable DF, however, is associated with

ineffective saliva control and drooling. These flows can also be confused with CPF if

the clinician is not careful to listen for glottic closure during CPF measurements. For

nine patients, seven with motor neuron disease, maximum DF were less than CPF.

Thus, different patterns of bulbar-innervated muscle dysfunction occur. In this way, DF

are similar to PEF since Wohlgemuth et al.(524) and Holcroft et al.(525) have pointed

out the need to caution their subjects from spitting during the measurement of PEF.

Although all of the flow maneuvers are dependent on effort and motivation, we

don’t think this was a confounding factor in our study since the three measures were

obtained in the same visit, in varying order, by the same examiner, and only the

maximum value of many attempts was recorded.

The techniques are simple and the peak flow meter required for measuring CPF and

PEF is very inexpensive and more widely available than spirometers required for

measuring VC and MIC. Assessment of both assisted and unassisted CPF is a

convenient method to objectify bulbar-innervated muscle function and respiratory

risk(364). A larger study is warranted to determine standard values of CPF and DF by

age, height, and weight. Peak flow meters with greater range should be developed to

more accurately measure the high range flows(526).

Like limb articulations and other soft tissues, the lungs and chest wall, too, require

regular motion to prevent chest wall contractures and lung restriction. As has been

recognized since at least 1952, this can only be achieved by air stacking, by providing

deep insufflations (via the upper airway or by "sighs" for patients using invasive



mechanical ventilation), or by nocturnal noninvasive ventilation for patients who cannot

cooperate with air stacking or insufflation therapy (83).

Kang and Bach also proved that the CPF value could be even higher if it is performed

through the Maximum Insufflation Capacity (MIC). The MIC is related to the

pulmonary compliance and with the pharyngeal and oropharingeal muscles function

(362). For most patients with NMD, while the VC decreases with time the MIC

increases for years before, however in ALS patients with bulbar impairment the

decrease of VC is proportional to the decrease of MIC (527)

The goal of conventional prescriptions for “range-of-motion” mobilization of extremity

articulations is to slow the development of musculoskeletal contractures for patients

with limb muscle weakness. However, the prevention of chest wall contractures and

lung restriction has only recently been addressed. In 2006, Lechtzin et al.(528) reported

the use of short-term noninvasive intermittent positive pressure ventilation (IPPV) to

increase pulmonary compliance for patients with amyotrophic lateral sclerosis (ALS).

Kang et al. demonstrated that lung volumes could be increased significantly over VC by

air stacking to approach MIC for patients with NMD. This resulted in significantly

increased (assisted) CPF that can decrease the risk of pneumonia. For patients such as

those with advanced bulbar ALS whose MIC equals VC, assisted CPF cannot be

increased by air stacking, and prognosis is poor(10).

Study nr 6 describes a simple technique that bypasses glottic function for providing

deep lung insufflations and for quantitating them as Lung Insufflation Capacity (LIC).

Patients with NMD often lose VC to the extent that they can expand their lungs to only

a small fraction of predicted volumes. For example, DMD patients’ VC decrease to

approximately 10% of predicted normal by age 20(529) and typical SMA type 1



patients’ VC have been reported to never exceed 250 ml(530), which, by age 10,

amounts to less than 10% of the predicted normal value(531). Incentive spirometry is,

therefore, useless because such patients’ tidal volumes approach their deepest breaths,

and these cannot exceed a small percentage of their insufflation capacity (IC). Likewise,

in reviews of studies in which inspiratory resistive exercise was performed by NMD

patients, no effect on VC, lung volumes, or maximum inspiratory or expiratory

pressures was reported(532). On the other hand, expanding the lungs well beyond IC by

air stacking or by single, deep insufflations permits greater lung distension, voice

volume, and CPF and can decrease atelectasis and loss of pulmonary compliance(364).

Our results show that the benefits can be greatest for the most advanced patients with

the lowest VC. The fact that lung expansion to LIC -VC trends inversely with VC,

whereas MIC -VC does not, indicates that, for the most advanced patients, it is

increasingly important to expand the lungs by passive insufflation rather than by air

stacking. In addition, MIC and LIC can increase with practice.

Inability to air stack no longer means that patients cannot simply and inexpensively

expand their lungs beyond IC. Study nr 6 demonstrates that like LIC-MIC, too, is an

objective, quantifiable, reproducible measure that (inversely) correlates with glottic

integrity. Glottic function is the most important aspect of bulbar-innervated muscle

function for NMD patients (364, 461)because it is most important for airway protection

and cough effectiveness and, therefore, permits the use of NIV to avoid otherwise

inevitable respiratory failure leading to death or tracheostomy with decreased quality of

life(63).

In this study, some patients were hypercapnic on presentation and had lungs stiff to the

extent that using a manual resuscitator to increase tidal volumes to normalize CO2

failed to do so and resulted in high airway pressures and chest discomfort. With regular



lung mobilization therapy and nocturnal NIV, however, five such patients became able

to renormalize CO2 when breathing autonomously without chest discomfort. This is

consistent with previous studies in which passive lung insufflation volumes were greatly

diminished for patients who were ventilated at constant pressures/volumes without

regular deep insufflations (468, 528). Patients supported by NIV at large delivered

volumes (1100–1500 ml) physiologically vary tidal volumes, can air stack to deep lung

volumes as a function of their bulbar innervated muscle integrity, and can better retain

lung distensibility(9). Thus, if pressure-cycled ventilators such as bi-level units (with

which air stacking is impossible) are used for nocturnal NIV, patients with diminished

VC should be equipped with a manual resuscitator or a volume cycled ventilator for air

stacking/maximal insufflations.

Home mechanical ventilation

Although only about 31% of ventilator users in acute hospitals have neuromuscular

ventilatory failure by comparison to 60% with cardiopulmonary disorders, because

neuromuscular ventilator users have a better prognosis and tend to use ventilators much

longer, they constitute over 50% of home mechanical ventilator users in the United

States(474)The population of home mechanical ventilator users has, in fact, more than

doubled since 1987(248) in Europe.

The vital use of manually assisted coughing was reported in only 18%, and MI-E in

only 5% of the clinics that prescribe respiratory care for patients with NMD(377).

Thus, failure to provide effective nocturnal ventilatory support, mouthpiece IPPV, and



assisted coughing continue to make respiratory failure inevitable for the great majority

of people with NMD.

Approaches to preventing peripheral airway secretion retention at home for patients

with NMD include the use of medications to reduce mucus hypersecretion or to liquefy

secretions, and facilitation of mucus mobilization. The latter can include manual or

mechanical chest percussion or vibration, direct oscillation of the air column, and

postural drainage. The goal is to transport mucus from the peripheral to the central

airways from where it can more easily be eliminated by manual assisted coughing and

mechanical assisted cough (MAC).

Home ventilated patients with NMD, however, do not have adequate inspiratory

and expiratory strength for sufficient cough flows. Thus, instead of overemphasizing

the effort-intensive use of secretion drainage techniques, these patients mostly need to

learn how to normalize their cough flows by using inspiratory and expiratory muscle

aids. Moreover, chest clapping also causes hypoxia so at times supplemental oxygen

needs to be administered(533).

Study nr 7 describes the indications of home MAC and its safety and compliance in

NMD patients. Oximetry feedback has proven usefulness by allowing to detect a sudden

decrease in SpO2 resulting from mucus plug (127, 481) Patients referred in this study

presented severe ventilatory failure and were on continuous mechanical ventilation

through noninvasive interfaces or tracheostomy.

The main condition for an efficacious home care after hospital discharge was the

presence of an adequate and motivated caregiver. In this study home basis MI-E was

centred in non-professional caregivers, with the support of a trained health care

professional in a home on-call regime. Moreover, it describes the importance of an



educational phase, introduced early to both patients and caregivers in the hospital, as

also proposed by Tzeng et al(127). Therefore, study nr 7 confirms that the caregiver,

when trained and motivated, can successfully use MI-E at home, and detect early signs

and symptoms of possible clinical respiratory worsening.

According to the methods applied in studies 5 and 6 of this thesis, bulbar muscle

function was evaluated, because severe bulbar dysfunction is responsible for

malfunction of the upper airway muscles, creating a dynamic collapse during the

exsufflation phase of MI-E, making this technique ineffective in this group of

patients(10, 60, 396). In this study ALS, which is the most common diagnosis,

represents a heterogeneous group: from non-bulbar with inadequate CPF to severe

bulbar requiring tracheostomy. The need of tracheostomy represents itself an extra

problem either concerning to its acceptance by the patients or associated to

tracheostomy related problems (local inflammation, increased secretions and

infections)(534-537).

Moreover, even though tracheostomy was proposed to all our severe bulbar patients,

some still rejected tracheostomy and preferred to continue with NIV and MAC protocol

at home. Bach et al have also reported that even severe bulbar ALS patients, can be

supported by combined used of VNI and MAC, delaying tracheostomy as long as the

SpO2 can be maintained above 95% in room air(481). However, these patients require a

close periodic monitoring in order to anticipate failure of non-invasive approach, so that

therapeutic options can be explored and discussed with patients and family, with the

intention that decisions can be made in advance rather than at the time of a respiratory

crisis(538).



In this study nr 7 each home MAC session consisted on 6 to 8 MI-E cycles at mean

pressures of 40 to -40 cmH2O, titrated according to patients’ tolerance. Chatwin et

al.(56) and Sivasothy et al.(539) have considered lower pressures to be more

comfortable and safe. However our settings are widely preferred for both comfort and

effectiveness and were also similar to those suggested by physiological studies.(57, 62,

365). Moreover, we had special attention on a careful individualized MI-E pressure

titration, trying to achieve maximal chest expansion, respecting comfort, which may

justify the tolerance and absence of complications.

According to patients and their caregivers there were few episodes in which home MAC

was not sufficient to deal with secretions encumbrance and emergency department visits

or hospitalizations were necessary. Other studies have already reported that NMD

patients dependent on NIV and using MAC guided by oximetry feed-back may be

safely managed at home without hospitalizations (10, 63, 127, 470).

We observed in study nr 7 that patients use home MAC according to their needs and

following oximetry feedback that consisted on using an oximeter for to maintain SpO2

greater than 94% by maintaining effective alveolar ventilation and airway secretion

elimination. Some patients used it daily and others intermittently during RTIs. This

study also showed that all patients with tracheostomy used MAC daily and more times a

day than patients under NIV, which used it more intermittently during RTIs. This fact

may be justified to local inflammation and increased secretions related to tracheostomy.

Study nr 7 showed that compliance of home MAC is different among NMD patients

and the organization of home care MAC programs in this population with severe

ventilatory impairment requires more study. Study nr 8 questioned that, although MAC

can be effective when continuously available at home (63, 127), expense can be



mitigated by on-demand rather than continuous access if on-demand MAC use can be

demonstrated to be effective. This study demonstrated that, for patients with ALS, a

program of telephone access, educational intervention, and on-demand home assisted

coughing interventions was shown to be feasible, very well accepted and resulted in

significant cost savings.

Although there are a number of studies that describe the efficacy of manual and

mechanical cough assistance techniques in hospital acute situations, until now there have

been no studies that focus directly on the feasibility and management of cough

assistance techniques at home for ALS patients. Only one previous ALS study used

continuous videoconferencing and telephone consultation for only four ALS patients. It

was also limited by the patients’ inability to master the use of the Internet and

Webcams(540).

Severe bulbar patients and moderate bulbar patients without tracheotomy had a poor

prognosis and high risk of death as previously noted(396). As in study nr 7, these

results also confirm that clinical worsening related to secretion encumbrance can be

detected by oximetry and SpO2 baseline normalized by MAC in the home setting for

ALS patients(481).

Study nr 8 also confirmed that respiratory care of advanced ALS is only effective if

families and care providers assist with oximetry and assisted coughing. Thus, a

motivated caregiver can successfully use at home cough assistance to prevent lung

pathology and hospitalizations. The higher number of avoided hospitalizations in the

patients with clinical worsening, that activated home MAC may suggest that this

approach can reduce and/or prevent respiratory infections with consequent reduction in

number of hospitalizations in ALS patients.



When home visits are performed by a health care professional, the “on request” use and

rental of MI-E devices prescribed by a multidisciplinary team of experts, can offer a

clinical service together with a significant financial saving compared with continuous

care strategy prescription (to all ALS patients for all the days) of home cough assist

devices. This choice, up to now, is particularly costly and has not been demonstrated to

be the best approach to achieve a good cost/benefit. Oximetry monitoring with on-

demand professional attention and MAC is a cost-saving alternative that is not only

relevant for the European health care system but also for the American system where the

continuous prescription of MI-E is widely used even though most patients do not need

assisted coughing every day. Indeed, study nr 8 showed that 56% of the patients did

not need to use MAC and those who used it, did so for <20% of the total follow-up

period. Moreover we also confirmed in study nr 8, that ALS patients under

tracheostomy have more necessity to use MAC, justified by the higher number of

episodes of clinical worsening compared to the patients under NIV. We found also in

study nr 8, that this on-demand program adds considerably to the patients’ and

clinicians’ feelings of security in managing such patients at home with concomitant

positive outcomes and reduced costs.

After confirming in studies 7 and 8, the feasibility, patients´ compliance and better

organization of efficient home MAC access, in study nr 9, we reported data that

focused on the clinical effects of home MAC during acute episodes of secretion

encumbrance in ALS and other NMD patients, all totally ventilator dependent either

through NIV or by tracheostomy.

The results of study nr 8 confirm that hospitalizations for ARF can be avoided for

NMD patients by a protocol of oximetry feedback for using ventilatory support and

MAC in the home (10, 63, 127, 481). Moreover these findings support again the clinical



justification for availability and prescription of cough assist devices and portable

oximeters at home for this patient population, especially during intercurrent RTI´s.

Since all patients were continuously ventilator dependent during the episodes, had the

oxyhemoglobin desaturations and dyspnea not been reversed by MAC, they would have

had to have been hospitalized for problems related to upper respiratory tract infections

and inability to clear secretions. However, in study nr 9, as a result of the protocol,

81% of the acute episodes resolved without hospitalization.

These results are consistent with those reported by Gomes-Merino et al (63) that, with a

similar approach, described hospitalization avoidance and survival increase in a

population with Duchenne muscular dystrophy under NIV. Study nr 9 focused on other

NMD diagnoses including having 71% ALS patients. Moreover, we found that, while

the incidence of acute episodes was the same, the tracheostomy users had significantly

more hospitalizations per desaturation episode than NIV users. This may be due

specifically to complications caused by the invasive tubes (534, 537, 541) and unrelated

to MAC or by poorer bulbar-innervated muscle function and airway protection

mechanisms in the ALS population despite tracheostomy with cuff inflation(396, 542)

In our study, MAC not only significantly improved SpO2 in all patients, it also

significantly decreased the number of airway suctionings in the tracheostomy patients.

All tracheostomy patients in this study had severe bulbar muscle impairment and the fact

that only 3 NIV users had bulbar impairment, may justify the good results of MAC on

reversion of desaturations at home.

Our results in study nr 9 implied that the patient and caregiver training and home

equipping be done early, before acute respiratory failure (ARF) occurs, and in the

outpatient setting as reported by Tzeng et al (127). Our results confirm that the



caregiver can successfully use MAC at home cough with oximetry feedback and can

early detect possible acute episodes of secretion encumbrance.

According to the results of studies 7, 8 and 9, nasotracheal deep airway suctioning

should be the last resort considered for both NIV and tracheostomized NMD patients

with upper or lower airway secretion encumbrance. Even though indications for airway

suctioning have not been determined, patients with tracheostomy tubes are routinely

suctioned an average of 8 times a day and 30 or more times per day when they have

chest infections(47). At best, suctioning can clear only superficial airway secretions.

Suctioning misses mucus adherent between the tube and the tracheal wall and the left

main stem bronchus 54 to 92% of the time that can lead to a high incidence of left lung

pneumonias, potentially fatal mucus plugging, and perceived need for

bronchoscopies(511). Results from a survey indicate that 42% of institutions prescribed

cough assistance devices for outpatient use(543) in tracheostomized patients. Moreover

Garstang et al(399) reported that patients have a significant preference of mechanical

insufflation-exsufflation (MI-E) through the tube over deep suctioning as a mean of

removing secretions.

As a conclusion, to support the evidence of this line of research in the clinical practice,

study nr 10 analysed the historical evolution of practice regarding the use of

noninvasive mechanical ventilation (NIV) and complementary interventions for long-

term full-time noninvasive ventilatory support of patients with NMD and reported data

from different international centers that provide continuous NIV for this patient

population as an alternative to tracheostomy.

It has already been described that 55 to 90% of conventionally managed DMD patients

die from pulmonary cardio-complications between 16.2 and 19 years of age and



uncommonly after age 25(544). Studies have reported outcomes of tracheostomy IPPV

for patients who undergo prophylactic tracheostomy or who survive an initial episode of

respiratory failure and who subsequently undergo tracheostomy. Baydur et al.(545)

reported 7 DMD patients who received full-time tracheostomy, from the mean age of

22.3 to 28.5 years. Two of the 7 died from pneumonia and 5 of the 7 patients were

reported as having had pneumonia or recurrent pneumonias. Soudon et al.(546) reported

a 3.6 year mean survival for 23 tracheostomy IPPV users, most of whom had DMD.

Eagle et al. reported survival of 200 DMD patients as 19.5 years for those untreated and

24.8 years for those receiving tracheostomy IPPV(544).

In 80% of the NMD clinics in the U.S, patients are being offered nocturnal-only “low

span” NIV on the basis of polysomnograms(377). Many of these patients are found to

have nocturnal desaturations and frequent hypopneas. The hypopneas tend to be

associated with reduced chest wall movement or with chest wall paradox suggesting

non-central origin, that is, inspiratory muscle weakness(547-548). In DMD patients, the

use of “low span” NIV has been shown to prolong tracheostomy-free survival by a

matter of months-only with respiratory failure ultimately inevitable(549-551). Simonds

et al.(17) began it for 23 DMD patients with a one year survival of 85%, 2 year survival

of 73%; and a 5 year survival was less than 40% with at least 5 deaths due to respiratory

failure. As the VC decreases below 800 ml DMD patients often begin to rock back and

forth in their wheelchair to compress their abdomens during exhalation to increase their

tidal volumes. They also tend to develop hypercapnia during sleep at this point. They

eventually begin to use accessory breathing muscles and usually remain grossly

asymptomatic, though, until their VCs decrease below 450 ml and hypercapnia extends

into daytime hours. (552). This first occurs during sleep and eventually with the patient

awake. It is usually around this time that nocturnal NIV is indicated (553).



SMA type I is typically characterized by profound global weakness were early

respiratory failure is the major cause of morbidity and mortality and most children do

not survive beyond 2 years of age without specialised treatment(530). Oskoui et al.(554)

showed that survival of children with SMA type I from the international SMA register

born in 1995–2006 has increased compared with those born in 1980 –1994. They

concluded that this was due to more patients receiving ventilation (82% vs. 31%), MI-E

(63% vs. 8%) and supplementary feeding (78% vs. 40%).

There has been consensus and international statement on the standards of care in SMA

with specific reference to the management of infants in the with SMA type I(555-556).

These documents do not address care of infants with non severe SMA type 1. These

statements tend to ignore that clearly, as for patients with other NMDs, the survival of

many SMA type 1 patients with or without severe bulbar muscle involvement can be

prolonged by ventilatory support both by NIV or via indwelling tracheostomy tubes, as

long as respiratory muscle aids are provided.

Pulmonary complications and respiratory failure account for at least 84% of ALS

mortality(557). and death can occasionally occur in as little as 2 months from onset of

symptoms and can occur at the time of initial presentation to a physician(396).

In the U.S. less than 10% of ALS patients undergo tracheotomy(558). However, 80 to

97% of ALS tracheostomy continuous ventilator users are glad to have chosen

mechanical ventilation, are satisfied with their lives, and would use mechanical

ventilation over again if they had to(10, 559). Thus, tracheostomy can at times prolong

survival by 10 years or more. However, deterioration in physical functioning and in the

ability to communicate, limited family resources, and most importantly, lack of a

national personal attendant care policy, often make it difficult for ALS patients to be



managed in the community(538). In addition, as well as from airway mucus plugging,

much of the sudden death post-tracheotomy may be due to autonomic dysfunction(560).

From 20 centers in 17 countries, study nr 10 keyed on analyzing 1623 nocturnal only

ventilated NMD patients in which 760 (48%) progressed to continuous full-setting NIV

over a follow up of 15 years. A protocol of oximetry feedback using mechanically

assisted coughing (MAC) and full-setting NIV permitted 228 safe extubations and 35

decannulations of patients who could not pass spontaneous breathing trials (SBTs)

before or after extubation/decannulation. After the follow up period, 522 (69%) patients

are still alive on continuous full-setting NIV and tracheostomy was placed in a total of

140 (8%). This study focused only in patients with DMD, ALS and SMA type 1,

however, all of the centers reporting data in this study had long-term full-time NIV

users with other diagnoses but it was felt that limiting the data to these common and

severe conditions would be more practical and establish the point.

Mechanisms by which nasal or mouthpiece IPPV can improve the clinical picture

include: resting respiratory muscles and decreasing metabolic demand, increasing tidal

volumes and relieving hypercapnia, resetting chemoreceptors, opening atelectatic areas,

maintaining airway patency, improving ventilation/perfusion matching, maintaining

lung and chest wall range-of-motion and possibly compliance, improving mucociliary

clearance, and most importantly, by assisting, supporting, and substituting for

inspiratory muscle function. Although mouthpiece IPPV is being used for ventilatory

support since 1953 (42) very few studies reported its use for long-term management(1,

87, 90, 491-492).

Nocturnal-only nasal NIV or bi-level PAP can at best marginally prolong life and delay

ARF. It can possibly do so by providing moderately deeper lung volumes to assist in



coughing. With advancing weakness, full-setting NIV can eventually be needed

continuously without requiring intubation and hospitalization, thereby avoiding ARF

and ultimately pressure by physicians to recommend tracheotomy.

The data presented suggest that reported “NIV failure”(15, 561-562) in cooperative

NMD patients can result from inadequate NIV interfaces, from inadequate ventilator

settings, when MAC is not used, and when mouth piece IPPV is not used for air

stacking or daytime support.

Patients usually require daytime mouthpiece IPPV with the ventilator on the back of the

wheelchair and the mouth piece adjacent to the mouth once the VC is less than 350

ml(491). About 15% of patients eventually lose the ability to use mouthpiece IPPV

because of oro-motor weakness(44, 87). These patients typically prefer to use nasal

IPPV around-the-clock rather than undergo tracheotomy(563).

Other than for severely mentally retarded patients no center included in study nr has

encountered a DMD patient who could “not successfully use NIV.” Thus, while the

NIV recommendations from a recent consensus panel(529) are comprehensive up to the

point of requiring intubation, we suggest that with the ability to consistently extubate

continuously ventilator dependent DMD patients and others, resort to tracheotomy

should be much less common.

For SMA 1 it is as yet unclear whether all will some day require tracheostomy tubes for

survival. Thus far, survival has been extended to up to age 17 using full-time NIV for

16 years or more for children continuously NIV dependent since as young as 4 months

of age. According to study nr 10, one center reported 5 of such severely affected SMA

1 patients over age 15, all with VCs less than 20 ml, and none with baseline SpO2 less

than 95% because of saliva aspiration. Thus, it is likely that at least some of these



typically severe SMA1 patients will survive into adulthood without tracheostomy tubes

despite continuous ventilatory support since infancy.

Over a 6-year period, numerous papers published on the futility of managing ALS and

other NMD patients with palliative care without once referring to prolonging life by

NIV/MAC(166, 564-570). Palliative care can be defined as interventions for easing

pain, dyspnea, and other symptoms that accompany the dying process of patients with

terminal illnesses. However, publications fail to distinguish between “palliative care”

for terminal cancer and organ supporting interventions for neuromuscular diseases,

many of which cause end-organ failure of only one system, the neuromuscular system

and in particular, end-stage respiratory muscle failure(571).

The data from this thesis suggest the inappropriateness of using palliative care precepts

for properly equipped and trained patients with adequate personal care support. Some of

our NMD patients, for example, are over age 40 and/or have depended on continuous

NIV for over 20 years and numerous patients becoming continuously ventilator

dependent without hospitalization or intubation, demonstrates that death from end-organ

respiratory muscle failure is often avoidable without resort to invasive measures.

The pervading NMD respiratory paradigm is that diminishing VC bodes poorly for

prognosis. The use of NIV and MAC as described in this thesis, to prolong life by

continuous ventilatory support is contrary to current emphasis on invasive interventions

and high technology. Thus it is considered that tracheotomy is the only option for

prolonging survival and a crisis decision must eventually be made to "go on a respirator

(undergo tracheostomy) for the rest of your life" or die(572). This often leaves patients

and families feeling hopeless and depressed. Thus, conventional management strategies

are invasive and reactive rather than noninvasive and proactive, ignoring the problem



until ARF results in intubation or death. Since NMDs are considered to be terminal,

clinicians tend to do not prevent ARF or need for invasive airway tubes(166)

It was unanimously agreed upon by the centers involved in study nr 10 that no properly

equipped and trained NIV patients that do not meet our reported criteria for tracheotomy

has ever chosen to electively undergo tracheotomy or stop NIV/MAC and die. Thus, it

was unanimously felt that the use of the term “palliative respiratory care” for NMD

patients perpetrates the misconception that “noninvasive ventilation” is only useful for

symptom relief rather than to prolong life by continuous ventlatory support.



CONCLUSIONS

- Intubated patients with NMD unable to pass spontaneous breathing trials achieve

successful extubation by using full NIV and MAC. Our extubation success rates

for these patients, suggest the avoidance of tracheotomy for ventilator dependent

NMD disease patients who have some residual bulbar-innervated muscle

function and who satisfy our extubation criteria. This ca now be offered even to

those with CPF less than 160 L/m.

- Considering the incidence of mortality and respiratory morbidity in the

population of high SCI patients managed by standard ventilatory invasive

techniques, we suggest that noninvasive methods of assisted ventilation and

coughing may facilitate both extubation and decannulation with significant

improvement on ventilatory dependence and pulmonary function and may

facilitate return home rather than prolonged institutionalization for weaning

attempts. Although some authors suggest a benefit on performing early

tracheostomy, we would like to suggest that for cooperative high level SCI

patients, an extubation protocol including full time NIV and MAC, can produce

better outcomes and avoid the necessity of tracheostomy.

- Our results recommend that MI-E devices for secretion clearance should be

included in an extubation protocol in specific subgroups of patients that may

require post-extubation NIV.

- The VRI as a simple, noninvasive index can be used as a complement and/or

alternative to VC in the evaluation of ventilatory impairment requiring

ventilatory assistance in NMD patients. Further validation of this index in other

populations and in the acute care setting as a weaning parameter is warranted.

- Cough Peak flows, PEF, and DF are useful measures of bulbar-innervated and

respiratory muscle function for patients with NMD, permitting greater

knowledge of the pattern of respiratory muscle compromise. It is important to

pay special attention to the technique of each flow measurement since DF can be



mistaken for CPF or PEF and respiratory risk can be underestimated. Effective

interventions to assist inspiratory and expiratory muscle function and the

accurate characterization of risk of respiratory complications depend on accurate

assessment of expiratory flow maneuvers.

- Regular lung insufflation, either by air stacking (to approach MIC) or by passive

lung insufflation (to approach LIC), is indicated for all NMD patients with

diminishing VC. Because the goal is to approach the predicted IC, passive

insufflation is used when the patient obtains a deeper volume in this manner than

by air stacking (i.e.when bulbar musculature is very weak).

- It is possible to manage severe NMD patients with inadequate airway clearance

on a home-based MAC regimen centred on trained non-professional caregivers.

This is valid for patients under NIV and for those requiring tracheostomy. MAC

should be considered as a useful complement to ventilatory support in these

patients at home.

- A telephone access and on-demand MAC program offers a technologic update to

increase both the patients’ and clinicians’ feelings of security for home

management and was effective in averting hospitalizations for patients with

ALS, with concomitant positive results in reducing home care costs.

- Home MAC use with oximetry feedback during respiratory infections can avoid

hospitalizations and effectively manage episodes of acute respiratory

decompensation, related to secretion encumbrance, in continuously ventilator

dependent NMD patients dependent on either NIV or tracheostomy.

- Since neither DMD, SMA, nor essentially any other NMD full time NIV users

appear to meet the same criteria established to indicate tracheotomy for patients

with advanced bulbar-ALS, these patients can be safely maintained using up to

continuous NIV with good survival outcomes. Assisted lung ventilation and

normal SpO2 can be maintained indefinitely during sleep as well as during

daytime hours for patients with little or no VC by using NIV at full ventilatory

support.



RESUMO

Introdução

Um dos desenvolvimentos mais importantes na área da ventilação mecânica ao longo

dos últimos 15 anos foi o surgimento da ventilação não-invasiva (VNI) como uma

técnica crescente do arsenal terapêutico em cuidados intensivos. Além disso, tem sido

utilizada como terapêutica domiciliária em pacientes com insuficiência respiratória

crónica, de diferentes etiologias. De facto, a população sob ventilação mais do que

duplicou desde 1987.

Os argumentos para o uso da VNI dizem respeito principalmente às suas vantagens

sobre a ventilação mecânica invasiva, com redução significativa das complicações

relacionadas com cuidados intensivos, tais como trauma da via aérea superior,

pneumonia associada a ventilação mecânica e elevado nível de sedação. Para os

pacientes sob ventilação mecânica domiciliária a VNI tem vantagens sobre a ventilação

por traqueostomia, nomeadamente uma maior facilidade de adaptação do paciente e

cuidadores maior conforto menor com redução de custos.

Para pacientes totalmente dependentes do ventilador, com fraqueza muscular, a eficácia

da tosse está normalmente comprometida e a acumulação de secreções é frequente. O

manejo adequado de secreções com técnicas manuais ou mecânicas de tosse assistida

deve ser considerado antes do falhanço da VNI ser declarado.

São necessárias mais linhas de investigação com foco numa estratégia continuada de

cuidados respiratórios que incluem VNI optimizada e continua associada a tosse

assistida mecanicamente (TAM) em pacientes com fraqueza muscular e grave limitação

ventilatória, para justificar a aplicação de protocolos específicos que poderão melhorar a

sobrevida desta população



Objectivos

� Descrever as taxas de sucesso/falhanço na extubação de pacientes colaborantes

com fraqueza muscular, totalmente dependentes do ventilador, incapazes de

tolerar uma prova de ventilação espontânea, com um protocolo que inclui VNI

optimizada e continua e TAM numa unidade de cuidados intensivos (UCI)

� Descrever e comparar as taxas de sucesso na extubação e descanulação e seus

resultados em pacientes com lesão vértebro medular alta, orientados e totalmente

dependentes do ventilador com um protocolo que inclui VNI optimizada e

continua e TAM para manter SpO2 > 95% em ar ambiente

� Avaliar a eficácia da TAM como parte integrante de um protocolo de desmame

em pacientes que toleram a prova de ventilação espontânea, mas desenvolvem

falência respiratória pós extubação

� Determinar se um novo índex de requerimento ventilatório (IRV) poderá

contribuir para a distinção de pacientes com doença neuromuscular (DNM) com

vários níveis de disfunção dos músculos inspiratórios e dependência ventilatória

e verificar se este índex poderá acrescentar algo á eficácia da medida da

capacidade vital (CV) para indicar o suporte ventilatório

� Comparar os valores de pico fluxo da tosse (PFT), pico de fluxo expiratório

(PFE) e de um fluxo potencialmente simulador obtido através de uma propulsão

da língua e lábios (“dart flow”,DF) em indivíduos saudáveis e em pacientes com

DNM/patologia restritiva e correlacionar estes valores com a CV e a máxima

capacidade de insuflação ( CMI)

� Comparar a capacidade máxima de insuflação passiva (LIC) com a capacidade

de insuflação por “armazenamento de ar” (CMI) e com a CV, no sentido de

explorar relações entre estes valores e correlacioná-los com a função glótica e

PFT. Demonstrar os efeitos de insuflações diárias na LIC em MIC, bem como a

sua a importância na caracterização da severidade da doença.

� Descrever as indicações de TAM domiciliária e explorar a segurança, frequência

e eficácia em pacientes com DNM, totalmente ventilados por VNI ou por

traqueostomia



� Optimizar o protocolo de TAM domiciliário com monitorização de oximetria,

com a inclusão de uma consulta telefónica, no sentido de reduzir os custos e

evitar internamentos hospitalares em pacientes com DNM, totalmente ventilados

por VNI ou por traqueostomia

� Reportar dados de vários centros acerca da eficácia e resultados de uso continuo

de VNI em pacientes com distrofia muscular de Duchenne, esclerose lateral

amiotrófica e atrofia muscular tipo 1 ventilados cronicamente no seu domicilio e

avaliar a evolução das recomendações sobres esta matéria publicados nas

recentemente publicadas revisões e conferências de consenso.

Resultados

Taxa de sucesso na extubação á primeira tentativa com VNI e TAM foi de 95% (149

pacientes). Todas as tentativas de extubação em 98 pacientes com PFT assistidos ≥ 160

L / m foram bem sucedidas. A dependência de VNI contínua e autonomia ventilatória

prévia à intubação correlaciona-se com o sucesso da extubação (p <0,005). Seis dos oito

pacientes que inicialmente falharam a extubação foram bem sucedidos na tentativa

subsequente. Apenas dois pacientes com PFT assistidos imensuráveis foram submetidos

a traqueotomia.

Quando comparados com os pacientes com lesão vértebro-medular alta que foram

decanulados, os pacientes extubados apresentaram menor tempo de internamento em

UCI com menor tempo de duração do protocolo de VNI e TAM. Após o protocolo, CV,

PFT voluntário e assistido melhorou significativamente em todos os pacientes. Os

pacientes extubados apresentaram melhores valores de CV e PFT às 48h pós-extubação

e melhores valores de PFT aos 6 meses de follow up.

Setenta e cinco pacientes críticos (26 mulheres) com idades e índices de gravidade

similares, que toleraram com sucesso o desmame foram randomizados pré extubação

para receber tratamento convencional (grupo controlo) e para receber o mesmo

tratamento com a inclusão de TAM (grupo estudo) Nas 48 horas pós extubação, 20

pacientes do grupo controle (50%) e 14 pacientes do estudo (40%) utilizaram VNI.



Pacientes do grupo de estudo tiveram uma significativa taxa mais baixa de re-intubação

em relação ao grupo de controlo, 6 (17%) vs 19 (48%), pacientes respectivamente.

Considerando apenas o subgrupo de pacientes que usaram VNI, as taxas de re-intubação

relacionados ao falhanço da VNI foram significativamente menores no grupo de estudo,

quando comparado ao grupo controle, 2 (6%) vs (33%) pacientes, respectivamente. O

tempo de internamento em UCI pós – extubação foi significativamente menor no grupo

de estudo (3,1 ± 2,5 vs 9,8 ± 6,7 dias).

O IRV superior a 1,2 foi atingido por 82 dos 91 pacientes que beneficiaram de

assistência ventilatória parcial. A CV inferior a 50% do normal previsto foi atingido por

82 dos 91 pacientes que beneficiaram de assistência ventilatória parcial. Tendo em

conjunto, um IRV superior a 1,2, e um VC inferior a 50% do normal previsto foi

atingido por 87 dos 91 pacientes. Da mesma forma, o IRV superior a 2,5 foi atingido

por 35 dos 42 pacientes que necessitaram de assistência ventilatória superior a 20

horas/dia em que se exigia um ventilador suplente. Uma CV inferior a 1000 ml foi

atingida por 36 de 42 pacientes. Tendo em conjunto um índice superior a 2,5 ou inferior

a 1000 VC ml foi atingido por 38 dos 42 pacientes que necessitaram de assistência

ventilatória superior a 20 horas/dia em que se exigia um ventilador suplente.

Para os pacientes com DNM, o DF foi significativamente maior do que PFT (p <0,01)

que, por sua vez, excedeu significativamente o PEF (p <0,05). 14 pacientes tiveram DF

inferior PFT. Treze desses 14 tinham a capacidade de armazenamento de ar (CMI>

CV), indicando maior comprometimento da boca e dos lábios do que dos músculos da

glote. Para 14 dos 88 pacientes com DNM, os valores de CMI não excederam a CV,

principalmente devido á incapacidade de encerrar a glote. PFT e PEF correlacionam-se

com a CV (r = 0,85 e 0,86, respectivamente), e com a CMI (r = 0,76 e 0,72,

respectivamente).

Em pacientes com DNM, os valores de CV, CMI e LIC foram de 1131 ± 744, 1712 ±

926 e 2069 ± 867 ml, respectivamente, e os valor por PFT voluntário e assistido foram

de 2,5 ± 2,0 e 4,3 ± 2,2 litros / seg, respectivamente, com todas as diferenças



estatisticamente significativas (P <0,001). CMI menos a CV correlacionou inversamente

com a LIC menos CMI (p <0,01) e, portanto, com a função glótica. Ambos os valores

de CMI e LIC aumentaram com a prática (p <0,001). Aumentos na LIC, foram maiores

para os pacientes com menor CV (p <0,05).

Pacientes com DNM usam TAM em casa diariamente ou de forma intermitente durante

as exacerbações agudas Todos os pacientes traqueostomizados usaram TAM

diariamente e mais vezes por dia do que pacientes sob VNI. Os cuidadores foram

considerados competentes e eficazes na aplicação de TAM em casa, com boa tolerância

e sem complicações.

Durante 42 ± 57 meses de seguimento, por 180 episódios agudos, 146 internamentos

foram evitados. As taxas de hospitalização para os pacientes sob VNI foram

significativamente inferiores do que para os traqueostomizados. TAM domiciliário,

durante os episódios agudos normalizou a SpO2 e diminuiu o nº diário de aspirações

profundas através do tubo de traqueostomia. O custo médio mensal por paciente para a

TAM domiciliário por demanda com consulta telefónica profissional, foi de € 403, que

representaram 420 € ou 59% menos do que o preço de uma prescrição contínua TAM

domiciliário.

Vinte centros de 17 países apresentaram 1492 pacientes com DNM ventilados

parcialmente durante a noite em que 713 (48%) evoluíram para suporte ventilatório não

invasivo contínuo durante um seguimento de 15 anos. Um protocolo de monitorização

por oximetria para a aplicação de TAM e VNI continua em ar ambiente permitiu 228

extubações bem sucedidas e 35 descanulações seguras de pacientes incapazes de passar

por provas de respiração espontânea. Após o período de seguimento, 493 (69%)

pacientes estão ainda vivos e em pleno uso contínuo de VNI. A traqueostomia foi

colocada em um total de 125 (8%) pacientes.



Conclusões

� Um protocolo que inclui VNI continua e optimizada com TAM permite a

extubação segura de pacientes com fraqueza muscular devido a DNM e com

lesão vértebro-medular alta, que são incapazes de tolerar provas de ventilação

espontânea Embora alguns autores sugerem benefícios na realização da

traqueostomia precoce, resultados sugerem que, para pacientes com lesão

vértebro-medular com bom nível de cooperação, a extubação com a aplicação de

um protocolo que inclui VNI e MAC, pode produzir melhores resultados e evitar

a necessidade de traqueostomia.

� A aplicação de TAM para manejo de secreções aplicado em subgrupos

específicos de pacientes pode produzir melhores resultados da VNI para o

tratamento da insuficiência respiratória. pós-extubação

� A IRV pode ser usado como um complemento e / ou alternativas para a CV na

avaliação do comprometimento ventilatório e necessidade de assistência

ventilatória em pacientes com DNM.

� Picos de fluxo da tosse, PFE e DF são medidas úteis para avaliar a função da

musculatura bulbar em pacientes com DNM, permitindo um maior

conhecimento do padrão de comprometimento dos músculos respiratórios.

� Insuflação pulmonar regular seja por armazenamento de ar seja por insuflações

passivas são indicadas para todos os pacientes com DNM e CV

significativamente reduzido. Insuflação passiva é utilizada quando o paciente

apresenta comprometimento grave da musculatura bulbar.

� É possível manejar no domicílio a acumulação de secreções e exacerbações

agudas relacionadas, em pacientes com DNM, com um regime á demanda de

TAM centrado na formação e treino de cuidadores não- profissionais e com

acesso a consulta telefónica profissional. Este protocolo foi eficaz na prevenção

de hospitalizações em pacientes com esclerose lateral amiotrófica e outras DNM

totalmente ventilados seja por VNI contínua ou traqueostomia



� A ventilação pulmonar assistida e SpO2 normal pode ser mantida durante o sono, bem

como durante o dia em pacientes com DNM com pouca ou nenhuma CV usando VNI

em suporte ventilatório contínuo. A eficácia da VNI continua Resultados depende mais

da função da musculatura bulbar do que a capacidade vital.



SUMMARY (Abstract)

Introduction

One of the most important developments in the field of mechanical ventilation over the

past 15 years has been the emergence of noninvasive positive pressure ventilation

(NPPV) as an increasing part of the critical care armamentarium. Moreover, it has been

effectively used for long term management in patients with chronic respiratory failure,

from different etiologies. Indeed, the population of home mechanical ventilator users

has, in fact, more than doubled since 1987.

The attraction for NPPV relates primarily to its advantages over invasive mechanical

ventilation with significant reduction of related critical care complications such as upper

airway trauma, ventilator associated pneumonia and high level of sedation. For patients

with long-term home mechanical ventilation, NPPV has advantages over tracheostomy

mechanical ventilation, including greater ease of administration, reduced need for

skilled caregivers, enhanced patient comfort, and lower costs.

For totally ventilator dependent patients with muscle weakness, cough is normally

impaired and secretion accumulation is frequent. Adequate secretion management with

manual or mechanical cough augmentation techniques might be advisable before NPPV

is declared failed or contraindicated in this population, both in acute and chronic

settings.

Research on a continuum strategy of care, from acute to chronic settings that include

NPPV coupled with mechanical assisted cough (MAC) in severely ventilatory impaired

patients with muscle weakness is warranted to support the application of specific

protocols that may improve survival in this patient population.



Purpose

� Report extubation success/failure rates in cooperative, totally ventilator

dependent muscle weakness patients, unable to pass weaning trials, using a

protocol that include full, continuous NPPV and MAC in the intensive care unit.

� Report and compare extubation and decannulation success rates and outcomes of

self-directed, totally ventilator dependent patients with high spinal cord injury

using a management protocol that include full, continuous NPPV and MAC to

maintain SpO2≥95% in ambient air.

� Assess the efficacy of MAC as part of a weaning protocol for patients that pass

specific weaning trials but develop acute respiratory failure after extubation.

� Determine whether a new designed ventilator requirement index (VRI) could

distinguish patients with neuromuscular disease (NMD) with various levels of

inspiratory muscle dysfunction and ventilator dependence and if such an index

could add to the diagnostic efficiency of simple vital capacity (VC)

measurement in determining need for ventilator use.

� Compare cough peak flows (CPF), peak expiratory flows (PEF), and potentially

confounding flows obtained by lip and tongue propulsion (“dart flows”, DF) for

normals and for patients with neuromuscular disease/restrictive pulmonary

syndrome (NMD) and correlate them with vital capacity (VC) and maximum

insufflation capacity (MIC).

� Compare maximal passive lung insufflation capacity (LIC) with lung inflation

by air stacking MIC and with vital capacity (VC); to explore relationships

between these variables that correlate with glottic function and cough peak flows

(CPF); to demonstrate the effect of routine inflation therapy on LIC and MIC;

and to determine the relative importance of lung inflation therapy as a function

of disease severity.



� Describe the indications of MAC treatment at home as well as, determine its

safety, compliance and efficacy within NMD patients under continuous NPPV

and tracheostomy.

� Establish an optimal MAC with oximetry feedback provision regimen at home,

with a telephone consultation to help reduce costs and avoid hospitalizations in

NMD patients under continuous NPPV and tracheostomy.

� Report multicentric data and outcomes of the use of NPPV for full, long-term

ventilatory support in Duchenne muscular dystrophy (DMD), amyotrophic

lateral sclerosis (ALS), and spinal muscular atrophy type 1 (SMA 1) and

consider the evolution of practice recommendations reported in reviews and

consensus statements

Results

First attempt extubation success rate with NPPV and MAC in was 95% (149 patients).

All 98 extubation attempts on patients with assisted cough CPF ≥ 160 L/m were

successful. Dependence on continuous NPPV and duration of dependence prior to

intubation correlated with extubation success (p<0.005). Six of 8 patients who initially

failed extubation succeeded on subsequent attempts and only two patients with no

measurable assisted CPF underwent tracheotomy.

When compared to high SCI patients that were decannulated, extubated patients had a

lower ICU length of stay with less time on NPPV and MAC protocol. After the

protocol, VC, unassisted and assisted CPF significantly improved in all patients.

Extubated patients had higher values of VC and CPF at 48h post-extubation and higher

values of CPF at a 6 month follow up.

Seventy five critical ill patients (26 females) with similar age and gravity successfully

weaned were randomized pre extubation to receive conventional post-extubation



treatment (control group) and to the same treatment with MAC (study group) In the 48

hours post extubation, 20 control patients (50%) and 14 study patients (40%) used

NPPV. Study group patients had a significant lower re-intubation rate than controls; 6

(17%) vs 19 (48%), patients respectively. Considering only the sub-group of patients

that used NIV, the re-intubation rates related to NIV failure were significantly lower in

the study group when compared to controls; 2(6%) vs (33%) patients respectively. Post

– extubation ICU length of stay was significantly lower in the study group (3.1± 2.5 vs

9.8± 6.7 days).

A VRI greater than 1.2 captured 82 of 91 patients who benefited from part-time

ventilatory assistance. A VC less than 50% of predicted normal captured 82 of 91

patients who benefited from part-time NPPV. Having an index greater than 1.2 or a VC

less than 50% of predicted normal captured 87 of 91 such patients. Likewise, a VRI

greater than 2.5 captured 35 of 42 patients who required ventilatory support greater than

20 hours per day and required a back-up ventilator. Having a VC less than 1000 ml

captured 36 of 42 such patients. Having an index greater than 2.5 or a VC less than

1000 ml captured 38 of 42 patients who required a back-up ventilator for full-time

ventilatory support.

For NMD patients, the DF were significantly greater than CPF (p<0.01) which, in turn,

significantly exceeded PEF (p<0.05). 14 patients had DF lower than CPF. Thirteen of

these 14 had the ability to air stack (MIC>VC) indicating greater compromise of mouth

and lip than of glottic muscles. For 14 of 88 NMD patients MIC values did not exceed

VC, mostly because of inability to close the glottis (inability to air stack). Nonetheless,

in 11 of these 14 patients the DF were within the standard deviation of the whole group,

thus, bulbar-innervated muscle dysfunction was not uniform. CPF and PEF correlated

with VC (r= 0.85 and 0.86, respectively), and with MIC (r=0.76 and 0.72, respectively).



In NMD patients, VC, MIC, and LIC were 1131 ±744, 1712±926, and 2069± 867 ml,

respectively, and, for unassisted and assisted CPF, they were 2.5±2.0 and 4.3±2.2

liters/sec, respectively, with all differences statistically significant (P<0.001). MIC

minus VC correlated inversely with LIC minus MIC (P <0.01) and, therefore, with

glottic function. Both MIC and LIC increased with practice (P <0.001). Increases in LIC

but not MIC over VC were greatest for patients with the lowest VC (P <0.05).

Patients with NMD used MAC at home either daily or intermittently during acute

exacerbations All tracheostomized patients used MI-E daily and more times a day than

patients under NPPV. Caregivers were competent and considered MAC effective at

home with good tolerance and no complications.

During 42±57 months of follow up, for 180 acute episodes, 146 hospitalizations were

avoided. Hospitalization rates for NPPV users were significantly lower than for

tracheostomy users. Home MAC during acute episodes normalized baseline SpO2 and

decreased resort to deep airway suctioning via tracheostomy tube per day. Mean

monthly cost per patient for on-demand home MAC with professional telephone

consultation, was €403, that represented 420€ or 59% less than the rental for continuous

home MAC prescription.

Twenty centers from 17 countries presented 1492 nocturnal only ventilated

neuromuscular disease (NMD) patients in which 713 (48%) progressed to continuous

full-setting noninvasive ventilation (NIV) over a follow up of 15 years. A protocol of

oximetry feedback using mechanically assisted coughing (MAC) and full-setting NIV

permitted safe 228 safe extubations and 35 decannulations of patients who could not

pass spontaneous breathing trials (SBTs) before or after extubation/decannulation. After

the follow up period, 493 (69%) patients are still alive on continuous full-setting NIV

and tracheostomy was placed in a total of 125 (8%).



Conclusions

� Continuous full setting NPPV and MAC permits safe extubation of NMD and

high SCI patients that are unable to pass spontaneous breathing trials Although

some authors suggest a benefit on performing early tracheostomy, we would like

to suggest that for cooperative high level SCI patients, an extubation protocol

including NPPV and MAC, can produce better outcomes and avoid the necessity

of tracheostomy.

� Secretion clearance with MI-E, applied in specific subgroups of patients may

produce better outcomes of NPPV to treat post-extubation respiratory failure.

� The VRI can be used as a complement and/or alternative to VC in the evaluation

of ventilatory impairment requiring ventilatory assistance in NMD patients.

� Cough Peak flows, PEF, and DF are useful measures of bulbar-innervated and

respiratory muscle function for patients with NMD, permitting greater

knowledge of the pattern of respiratory muscle compromise.

� Regular lung insufflation, either by air stacking (to approach MIC) or by passive

lung insufflation (to approach LIC), is indicated for all NMD patients with

diminishing VC. Passive insufflation is used when the patient has severe

impairment of the bulbar musculature.

� It is possible to manage secretion encumbrance and acute exacerbations at home

in NMD patients, with an on demand MAC regimen centred on trained non-

professional caregivers and telephone consultation. This was effective in

averting hospitalizations for patients with ALS and other NMD patients either

on continuous NPPV or tracheostomy

� Assisted lung ventilation and normal SpO2 can be maintained during sleep as

well as during daytime hours for patients with little or no VC by using NPPV at

full ventilatory support. Successful outcomes of continuous NPPV in NMD

patients depends more on the bulbar muscle function than on the vital capacity.



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