RespiRatoRy failuRe

Respiratory failureNicholas Hart

AbstractRespiratory failure is the consequence of lung failure leading to hypox­

aemia or respiratory muscle pump failure resulting in alveolar hypoventi­

lation and hypercapnia. type 1 respiratory failure is defined as a partial

pressure of arterial oxygen (pao2) less than 8.0 kpa or hypoxaemic respira­

tory failure, and type 2 respiratory failure is defined as pao2 <8 kpa and a

partial pressure of arterial carbon dioxide (paCo2) >6 kpa or hypercapnic

respiratory failure. Diagnosis is made easier by understanding the patho­

physiological mechanisms that cause hypoxaemia and hypercapnia. fur­

thermore, a basic knowledge of acid–base balance allows distinction

between acute, acute­on­chronic and chronic type 2 respiratory failure.

in addition to the standard assessment, careful consideration must be

given to neurological conditions as well as obstructive sleep apnoeas

as these are frequently overlooked causes of respiratory failure. imaging

and pulmonary function tests provide useful information to ascertain the

diagnosis. Management of these patients will depend on the underlying

cause, but the objective of treatment must be to improve oxygenation

and/or ventilation to resolve hypoxaemia and hypercapnia.

Keywords hypoxaemia; hypercapnia; lung failure; oxygen therapy;

respiratory muscle pump failure; ventilation

The two principal components of the respiratory system are the lungs and the respiratory muscle pump. Both are essential for sustaining life and work in a complementary fashion to ensure that adequate gas exchange and ventilation occurs. Respiratory failure results from the inability of the respiratory system to carry out one or both of its gas exchange functions: oxygenation of, and/or elimination of carbon dioxide from, mixed venous blood. The definition of respiratory failure is derived from the arterial blood gas measurements and defined as an arterial oxygen ten-sion (PaO2) less than 8.0 kPa and arterial carbon dioxide tension (PaCO2) greater than 6.0 kPa. This is further subdivided into type 1 hypoxaemic respiratory failure (PaO2 <8 kPa) and type 2 hyper-capnic respiratory failure (PaO2 <8 kPa with PaCO2 >6 kPa).

Incidence

Despite this clear definition of respiratory failure, the incidence of respiratory failure is difficult to determine. However, using

Nicholas Hart MRCP PhD is Consultant Physician and Honorary

Senior Lecturer at St Thomas’ Hospital, Guy’s and St Thomas’ NHS

Foundation Trust, London, UK. Competing interests: none declared.

MeDiCiNe 36:5 24

European data from patients admitted to intensive care requiring invasive mechanical ventilation for more than 24 hours, the esti-mate of acute life-threatening respiratory failure is between 77.6 and 88.6 cases per 100,000 population per year.1 In the UK, 2.9%, 1.7% and 5.9% of admissions to intensive care are the result of respiratory failure due to chronic obstructive airways disease (COPD), asthma and pneumonia respectively, and this accounts for around 24,000 admissions per year. The in-hospital mortalities of these conditions are 38.3%, 9.8% and 49.4%, respectively.2–4 The number of patients admitted with less severe respiratory fail-ure is probably greater, but there are limited data available.

Pathophysiology

It is easier to consider hypoxaemic respiratory failure as lung failure, such as occurs with pneumonia, interstitial lung disease and acute cardiac pulmonary oedema, and hypercapnic respira-tory failure as respiratory muscle pump failure in which alveo-lar hypoventilation predominates (Figure 1). Obviously, both respiratory muscle pump and lung failure can occur in the same patient, as in chronic obstructive pulmonary disease (COPD) or in an asthmatic crisis in which hypercapnia develops only if the hypoxaemic process progresses or persists. In order to generate a clinical conditions list, it is useful to consider the five patho-physiological mechanisms of hypoxaemia: • ventilation/perfusion (V/Q) mismatch • impaired diffusion • right-to-left intracardiac • intrapulmonary shunts or alveolar hypoventilation • reduced inspired oxygen concentration (Figure 2).It is necessary to highlight that V/Q mismatch is the commonest cause of hypoxaemia.

As with hypoxaemic respiratory failure, it is useful to con-sider the pathophysiological mechanisms of hypercapnic type 2 respiratory failure and then to generate a conditions list based on these mechanisms. First, we must consider that hypercapnia is a result of the respiratory muscle pump failure caused by an imbal-ance between neural respiratory drive, the load on the respiratory system and respiratory muscle capacity (Figure 3). Drive failure,

Types of respiratory failure

Respiratory failure

Lung failure Pump failure

Type 1 hypoxaemicrespiratory failure

Type 2 hypercapnicrespiratory failure

Figure 1

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RespiRatoRy failuRe

high respiratory muscle load and neuromuscular transmis-sion and respiratory muscle action failure are all important and impairment at one or more levels can result in hypercapnic respi-ratory failure. By considering these pathophysiological causes, even without an in depth knowledge of respiratory physiology, a clinically relevant list of conditions can be devised (Figure 4).

Acute, chronic and acute-on-chronic respiratory failure

This is an important distinction to be aware of as the clinical presentation and the arterial blood gas measurements are very different. In this section, we will focus on hypercapnic type 2 respiratory failure. Acute hypercapnic respiratory failure is defined by an acute rise in PaCO2 with accompanying respira-tory acidosis (pH <7.35). As PaCO2 is directly proportional to the rate of production of CO2 and inversely proportional to the rate of removal of CO2,(PaCO2 α VCO2/VA: VCO2 is the rate of pro-duction of CO2 and VA is the alveolar ventilation), the approach of considering the respiratory muscle load, capacity and neural respiratory drive to form a diagnostic list is still valid for acute, chronic and acute-on-chronic respiratory failure. In contrast to acute respiratory failure, patients with chronic respiratory fail-ure have a pH within the normal range (7.35–7.45), but with an elevated bicarbonate level (>26 mmol.L−1) as renal reten-tion of bicarbonate is promoted. The bicarbonate concentration (HCO3

−) acts to buffer the hydrogen ions (H+) that are increased as a consequence of an elevated PaCO2 combining with water and dissociating to produce increased quantities of H+. The term acute-on-chronic respiratory failure is a clinical description of an acute deterioration in a patient with chronic respiratory fail-ure. Although the bicarbonate level will be elevated, the patient will have an acidosis and the pH level will be less than 7.35.

Type 1 hypoxaemic respiratory failure

*Ventilation–perfusionmismatch

HypoxaemiaAnatomicalR-L shunt

Impaireddiffusion

Low partial pressureof imspired oxygen

Alveolarhypoventilation

e.g. chronic obstructive pulmonary disease, asthma, pulmonary embolus, pulmonary oedema, cystic fibrosis,bronchiectasis

Using the five pathophysiological mechanisms of hypoxaemia, a comprehensive list of conditions that cause hypoxaemia can be generated

e.g. diffuseparenchymallung disease

e.g. pulmonary arteriovenousmalformation, pneumonia

e.g. flying e.g. opiate overdose

*V/Q mismatch is the most important cause of hypoxaemia.

Figure 2

MeDiCiNe 36:5 24

However, with the increased HCO3− the PaCO2 level will be sig-

nificantly higher than seen in patients with acute hypercapnic respiratory failure.

History and examination

In general, type 1 hypoxaemic respiratory failure will be a rela-tively straightforward diagnosis based on a standard assessment including a history, examination and chest X-ray. However, the most important exception to this rule is obstructive sleep apnoea (OSA), which is commonly overlooked and requires both a sleep and respiratory history to be taken. Although type 2 hypercapnic respiratory failure is a less common clinical problem it is more difficult and requires a more careful and considered approach and often includes a thorough neurological examination to observe for signs such as tongue and peripheral muscle fascicu-lation, muscle wasting and weakness and sensory loss. The clini-cal presentation can be fairly insidious (see conditions listed in Figure 4) and despite breathlessness being a feature in patients with severe neuromuscular disease and skeletal deformity, mod-erate respiratory muscle pump failure may cause few problems unless an addition load is placed on the system, such as pneu-monia. Furthermore, a number of these conditions, such as Guillain–Barré syndrome, botulism, and motor neurone disease can present as an acute deterioration with hypercapnic encepha-lopathy requiring immediate intubation and ventilation. Those conditions with a slower presentation with a predicted decline, including Duchenne muscular dystrophy, myotonic dystrophy and scoliosis require close observation. COPD is another, not insignificant, cause of respiratory failure presenting both in the acute and chronic state. However, as a result of V/Q mismatch, hypoxaemia rather than hypercapnic respiratory failure is a more common presentation. In contrast to the conditions with respira-tory muscle weakness, with COPD patients there will be greater focus during the consultation on features such as cough, wheeze

Type 2 hypercapnic respiratory failure is an imbalancebetween neural respiratory drive, the load on therespiratory muscles and capacity of the respiratorymuscles

DRIVE FAILURECortex brainstem

TRANSMISSION &ACTION FAILURE

Spinal cordPeripheral nerves

Neuromuscular junctionRespiratory muscles

HIGH LOADResistive elastic

threshold

RESPIRATORY MUSCLEPUMP FAILURE

Type 2 hypercapnicrespiratory failure

Figure 3

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RespiRatoRy failuRe

MeDiCiNe 36:5

Type 2 hypercapnic respiratory failure

Using the model of imbalance between neural respiratory drive, respiratory muscle load, transmission and respiratory muscle action a comprehensive list of conditions causing hypercapnia can be generated

COPD, chronic obstructive pulmonary disease; NMD, neuromuscular disease; OHS, occipital horn syndrome;PEEP, positive end-expiratory pressure; CF, cystic fibrosis; OSA, obstructive sleep apnoea; ALI/ARDS, acutelung injury/acute respiratory distress syndrome; DPLD, diffuse parenchymal lung disease; CINMA, criticalillness neuromuscular abnormalities.

Cortex and brainstem

DR

IVE

FA

ILU

RE

GENERALTrauma, encephalitis, ischaemia, haemorrhage, Cheyne–Stokes respirationCENTRALLY ACTING DRUGSSedatives, opiates, anti-epilepticsMETABOLIC COMPENSATIONCOPD, NMD, OHS, skeletal deformity

Threshold load (Intrinsic PEEP)

HIG

H L

OA

D

COPD, asthma, bronchiectasis, CF

Bronchospasm, upper airways obstruction,bronchiectasis, COPD, CF, OSA

Respiratory muscles

AC

TIO

N F

AIL

UR

EMuscular dystrophiesInflammatory myopathiesMalnutrition myopathyAcid maltase deficiencyThyroid myopathyBiochemical anomalies

HypokalaemiaHypophosphataemia

Nerves and neuromuscular junction

TRA

NS

MIS

SIO

N F

AIL

UR

E

Spinal cord lesion (above C3)Polio

´

Motor neurone diseasePhrenic nerve injuryGuillain–Barre syndromeCINMANeruomuscular blocking agentsAminoglycosidesMyasthenia gravisBotulism

Resistive load

LUNG – pneumonia, alveolar oedema, atelectasis, ALI/ARDS, DPLD, COPD, CFCHEST WALL – kyphoscoliosis, obesity, OHS, abdominal distenstion, ascites

Elastic load

Figure 4

and sputum production, as well as activity and nutritional status (BMI; body mass index) as these have prognostic implications.

There are a number of clinical symptoms and signs that should alert the physician to the development of hypercapnic respiratory failure, and specific features to focus on with progressive neuro-logical conditions include the following: • sleep-disordered breathing – morning headache, daytime

sleepiness, disrupted sleep pattern, impaired intellectual func-tion, generalized fatigue, loss of appetite and weight

• respiratory muscle weakness – orthopnoea, breathlessness on immersion in water, breathlessness on leaning forward, breathlessness on exertion, poor cough, poor chest expansion, paradoxical abdominal motion during inspiration (inward motion of the anterior abdominal wall due to diaphragm weakness), abdominal muscle recruitment in expiration

• bulbar dysfunction – low-volume voice, difficulty swallowing, drooling, difficulty clearing secretions, poor cough, staccato/slurred speech, coughing on swallowing.

Investigations

Pulmonary function testsThe diagnosis of respiratory failure is made by obtaining PaCO2 and PaO2 on arterial blood gas measurements. As described above, the HCO3

− will provide evidence for duration of CO2 retention. However, respiratory assessment using some simple

24

bedside tests is useful. Basic spirometry will measure the forced expiratory volume in 1 second (FEV1) and the forced vital capac-ity (FVC). This will not only identify airways obstruction (mild FEV1/FVC 50–70%; moderate FEV1/FVC 30–50% and severe FEV1/FVC <30%), as in COPD, but also demonstrate a restrictive ventilatory defect (FEV1/FVC >75%) in the presence of respira-tory muscle weakness and interstitial lung disease. In addition to the restrictive ventilatory defect, the finding in patients with respiratory muscle weakness is a reduced VC with a fall in supine VC of >20%. The other classical findings with respiratory mus-cle weakness are a reduction in total lung capacity (TLC), with a reduction in overall gas transfer (TLCO) but with a ‘supranor-mal’ gas transfer corrected for alveolar volume (KCO).5 A VC less than 1 litre has a high predictive value to identify patients with significant respiratory muscle weakness and respiratory failure but due to the curvilinear nature of the relationship between VC and inspiratory muscle strength, maximal inspiratory pressure at the mouth (MIP) and sniff inspiratory pressure (SNIP) are better predictors of respiratory decline. However, both tests should be used in combination with the VC measurement.6

Nocturnal studiesPatients with hypoxaemic respiratory failure and/or a history suggestive of OSA should undergo an overnight oximetry, which can identify the frequency and severity of overnight desatura-tions. Respiratory muscle weakness initially leads to daytime

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RespiRatoRy failuRe

hypoxaemia, as a result of V/Q mismatch, and hypercapnic respi-ratory failure does not occur until there is profound weakness. Any cause of nocturnal hypoventilation, such as skeletal deformity, neuromuscular disease or COPD, predominates during rapid eye movement (REM) sleep as there is a reduction in the respiratory drive and a decrease in ventilation with a resultant rise in PaCO2. This can be measured by combined overnight capnography and oximetry, which is performed in the sleep laboratory or ward. It is important to identify nocturnal hypoxaemic hypercapnia as this develops prior to established daytime respiratory failure and can act as a signal that a patient is developing respiratory failure and will be at risk of developing acute respiratory failure at times of crisis. In patients with COPD, the monitoring of oximetry and capnography overnight, whilst using nocturnal oxygen therapy, is useful for identifying those COPD patients who are at risk of retaining CO2 and developing respiratory acidosis during oxy-gen administration. As well as abnormal overnight oximetry and capnography, elevated morning bicarbonate, chloride and base excess indicate nocturnal hypercapnia.

ImagingA plain chest radiograph is useful in all patients with type 1 and type 2 respiratory failure. In addition to any acute changes, such as pneumonia or acute cardiac pulmonary oedema, the chest X-ray is useful for demonstrating hyperinflation and prominent pulmonary vessels as observed in COPD and pulmonary hyper-tension, as well as the reticular and nodular shadowing seen in diffuse parenchymal lung disease (DPLD). However, it must be remembered that the chest X-ray can be misleading in patients with diaphragm weakness as diaphragm elevation is of little value in the diagnosis of diaphragm weakness. For a detailed evalua-tion of diaphragm function it is best to refer to a specialist centre that can measure the transdiaphragmatic pressure using a non- volitional technique involving stimulation of the phrenic nerves.

Special investigationsIn patients with suspected neurological disease, one must con-sider measuring the level of muscle creatinine kinase, an elec-tromyogram (EMG), nerve conduction studies (NCS), magnetic resonance imaging scanning as well as a muscle biopsy. Patients with suspected DPLD will require a high-resolution chest CT scan to further define the abnormality and determine the diagnosis.

Management

Hypoxaemic type 1 respiratory failure is treated with supple-mental oxygen. The diagnosis will determine the definitive man-agement strategy, but the aim must be to ensure the patient is adequately oxygenated and ventilating sufficiently. Supplemen-tal oxygen can be given in a controlled manner, such as using the Venturi system of face-masks (fraction of inspired oxygen (FiO2) from 24% to 60%), or in an uncontrolled manner, such as nasal cannulae, where the FiO2 is variable and must be used with caution. In general, targeted oxygen delivery must be adhered to and in the acute setting all patients should be prescribed oxygen therapy to target and maintain the saturations between 94 and 98% (<70 years age) and 92–98% (>70 years age). However, for those patients at risk of developing hypercapnic respiratory failure, such as those with COPD, neuromuscular disease and

MeDiCiNe 36:5 24

skeletal deformity, oxygen should be prescribed to maintain the saturations at 88–92%. This approach not only reduces the risk of hyperoxia-induced hypercapnia, but also ensures the effects of oxygen toxicity, such as myocardial ischaemia and depression, are minimized. Further information can be found in the Guide-lines for Emergency Oxygen Therapy on the British Thoracic Soci-ety website (http://www.brit-thoracic.org.uk/). In the chronic setting, the use of longterm oxygen therapy (LTOT), minimum use 15 hours per day, is reserved for those patients with a PaO2 less than 7.3 kPa or those patients with a PaO2 <8 kPa but with evidence of cor pulmonale and/or polycythaemia.

There have been major advances in invasive ventilation and the use of lung protective strategies for patients with life- threatening respiratory failure who require invasive ventilation.7,8 Furthermore, there has been a revolution in the management of patients with acute and chronic respiratory failure with the wide-spread use of non-invasive ventilation (NIV) in the hospital and home setting. In particular, for patients with acute exacerbations of COPD with type 2 respiratory failure that fail to respond to medical therapy, the first-line treatment is NIV, which has been shown to reduce mortality compared with conventional therapy, including invasive ventilation.9–11 ◆

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