202 ANESTHESIA AND ANALGESIA . . . Current Researches VOL. 53, NO. 2, MARCH-APRIL, 1974

The Complications of Tracheal Intubation: A New Clxsi f icat ion With a Review of the Literatwe

VICTOR FARIA BLANC, M.D., F.R.C.P.(C) NORMAND A. G. TREMBLAY, M.D.

Montreal, Quebec, Canada*

The literature on complications of tracheal intubation is reviewed and a new classification is proposed for these complications. Incidents and accidents (early or immediate complications) are arranged in three etiopathogenic classes and in topographic subclasses, the status of endo- tracheal intubation being divided into three distinct periods: I: the act of intubation; 11: the tube in place; 111: extubation. Sequelae (late complications) are classified according to clinico- pathologic criteria. The etiologic factors of sequelae are divided into three groups: predisposing factors, adjuvant factors, and decisive or determinant factors.

Possible prevention or remedy of many complications is presented.

HE complications of tracheal intubation T were reviewed by Wyliel in 1950, by Fields’ in 1959, and by Lewis and Swerdlows in 1964. Why another review? What is new?

The widespread use of tracheal intubation in patients of all ages and of almost any medicosurgical status, the massive use of new synthetic disposable materials, the pro- cedure of prolonged translaryngeal intuba- tion, are hut some of the factors which prompted us to review and to reclassify this fundamental subject. In short, we felt that the accelerated change we have witnessed in this field was reason enough to reassess the complications of this common technic.

Such revisions must be done as prophy- laxis against the malady of “future shock in academic medicine.”

CLASSIFICATION At least seven different criteria have been

used to classify the complications of tracheal intubation:

1. Chronologic:385 whether occurring dur- ing laryngoscopy, when the tube is in place, or following extubation.

2. Topographic: whether lesions occur in eyes, lips, teeth, pharynx, larynx, and so on.

3. Etiopathogenic: grouped as traumatic, as neurogenic or reflex, as chemical, allergic, etc.

4. Pathologic: as defined by pathologists and by otolaryngologists.

5. Statistical: divided as common or rare. 6. Severity:4 according to the gravity of

the complication, the degree of airway ob- struction, whether the cause is remediable or not, etc.

7. Mixed: using two or more of the above criteria.

Since all these classifications are of some practical value, the choice among them re- mains arbitrary. From a didactic point of view, we propose the following classification:

‘*Department of Anesthesiology-Reanimation, University of Montreal and HBpital Sainte-Justine pour les Enfants, Montreal, Quebec, Canada.

A bibliography of 198 additional citations is available from the authors on request.

Paper received: 5/22/73 Accepted for publication: 7/31/73

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204 ANESTHESIA AND ANALGESIA . . . Current Researches VOL. 53, No. 2, MARCH-APRIL, 1974

TABLE 2 Sequelae are disorders or lesions that manifest themselves within minutes to months after extubation.

The Sequelae of Tracheal lntubation

1. 2. 3.

4.

5. 6.

7.

8. 9.

10. 11. 12. 13. 14. 15. 16.

Sore jaw Sore throat, dysphagia Intermittent aphonia and recurrent sore throat Paresis of the hypoglossal and/or lingual nerves Ulceration of the lips, mouth, pharynx Traumatic laryngitis (dysphonia or apho- nia) Infections (laryngitis, sinusitis, abscess, respiratory t ract infection) Stricture of the nostril Glottic e d e m a (supraglottic, subglottic, retroarytenoidal) Vocal cord paralysis Laryngeal ulcers Laryngeal granulomas and polyps Synechia of the vocal cords Laryngotracheal membranes and webs Laryngeal fibrosis Tracheal stenosis

Prolonged tracheal intubation is that oral or nasal translaryngeal intubation whose duration is equal to or longer than 24 hours.G.7

We further divide the status of endotra- cheal intubation into three distinct chrono- logic periods:

1. First period (the act of intubation) : starts with preparatory maneuvers (hyper- extension of the head, laryngoscopy, etc. ) and is finished when the tube is fixed, with the cuff inflated.

3. Second period (tube in place) : the time during which the patient breathes through the tracheal tube.

3. Third period (extubation): from the deflation of the cuff to the time when the patient resumes normal breathing through his upper airways.

I. Incidents and accidents (early or im- mediate complications) : arranged in 3 etio- pathogenic classes and in topographic sub- classes (table 1).

11. Sequelae (late complications) : clas- sified according to the clinicopathologic cri- teria (table 2).

Zncidents are transient disorders, usually spontaneously reversible. They are often po- tential accidents and most frequently occur in the first period of intubation.

1. INCIDENTS AND ACCIDENTS (EARLY OR IMMEDIATE

COMPLICATIONS ) (table 1 ) The history of accidents from tracheal

intubation is almost as old as that of intuba- tion itself. Although MacEwen, who first introduced tracheal intubation for anesthe- sia in 1868, does not mention complications, ODwyer, in 1887, described seven types of accidents with his technic of translaryngeal intubation in cases of croup, with explana- tions as to their prevention.

Accidents are grave physiologic disturb- The most frequent and common incidents ances or lesions that can occur a t any in- and accidents of tracheal intubation are stant of intubation. more-or-less well described in anesthesiology

* VICTOR F. BLANC, M.D., F.R.C.P. (C), is an Assistant Professor at the University of Montreal, and a Staff Anesthesiologist at the HBpital Sainte-Justine pour les Enfants, Montreal, QuBbec, Canada. Dr. Blanc graduated in medicine from Oporto University Faculty of Medi- cine (Portugal), and started his training in Anesthesi- ology at the Hospital Geral de Santo Antonio, Oporto, Portugal. After four years as Anesthesiologist a t the H6pital Avicenne of Rabat (Morocco), Dr. Blanc held a 4-year Residency in Internal Medicine and in Anesthesiology at the HBpital Notre-Dame and at the Royal Victoria Hospital in Montreal.

Complications . . . Blanc and Tremblay 205

textbooks. We cite the rarer ones and de- scribe in some detail those that appear to us to merit particular attention.

1. First Period of Zntubation (the act of intubation).

a. Traumatic or Mechanical Complica- tions.-Reckless mobilization maneuvers of the head can produce serious lesions (frac- ture-luxation of the cervical column with spinal compression or section), especially when muscle tone is abolished by curariz- ing agents. Such lesions are most easily made in patients with congenital weak- nesses or malformations of the cervical col- umn (Morquio’s syndrome), in patients with fractures or dislocations of the cervical col- umn, in the elderly as in patients with path- ologic fragility of the cervical spine (osteo- porosis, lytic bone tumors, connective tissue diseases).

Laryngoscopy can damage teeth, with the possibility of legal repercussions. Hoydo and associates report tooth damage in 37 patients out of 5387 tracheal intubations, the incidence being maximal between 30 and 40 years of age and decreasing with the ex- perience of the performer. Aspiration of a dislodged tooth can lead to the need of thoramtomy and bronchotomy. Tooth and gingival protectors for endotracheal intuba- tion have been described. A careful case his- tory, an equally pertinent examination, a perfect intubation technic, as the use of tooth guards, render the anesthesiologist less likely to suffer from “legal complications.”

The value of the preanesthetic history and examination in the prevention of rare acci- dents is well illustrated by Scott and Brech- ner, who report an extensive retrobulbar hemorrhage secondary to nasotracheal intu- bation in a woman with a maxillary tumor.

Perforation of the pyriform fossa in at- tempted blind nasotracheal intubation can cause subcutaneous and/or mediastinal em- physema. The esophagus can also be per- forated.

Tracheal tubes can be swallowed and lead to major surgery, a very disagreeable occur- rence in small babies.

b. Neurogenic or Reflexly Caused Corn- plications. - Laryngotracheal stimulation during laryngoscopy and tracheal intubation can give rise to three different types of reflexes:

Laryngovagal reflexes, which give rise to spasm of the glottis, bronchospasm, apnea,

bradycardia, cardiac arrhythmias, arterial hypotension. The mere presence of the tra- cheal tube seems to be the most common precipitating cause of bronchospasm in an- esthetized asthmatic patients. Laryngospasm can be produced by laryngotracheal intuba- tion in goats as well as in humans.

Bradycardia, bradyarrhythmia, and arte- rial hypotension are reportedly rarer than their opposites of sympathetic stimulation.

Laryngosympathetic reflexes, which in- clude tachycardia, tachyarrhythmias, acute arterial hypertension as frequent complica- tions. The hypertensive-hyperdynamic state during laryngoscopy may be related in some cases to an increased noradrenaline fraction of the total plasma catecholamines.

Atropinization can prevent bradycardia, as phentolamine can prevent hypertension, during tracheal intubation.

Laryngospinal reflexes, which include coughing, vomiting, bucking.

All such reflexes are most readily precipi- tated in the presence of hypoxemia, hyper- capnia, or too light a plane of general anes- thesia. Protection is given by deeper gen- eral anesthesia (stage 111, plane 2) as well as by topical anesthesia or bilateral superior laryngeal nerve block.

Hyperoxemia with normocapnia or hypo- capnia provides some protection, under light general anesthesia, against such reflexes. Nevertheless, Noble and Derrick noted that 60 percent of the arrhythmias in their study occurred before laryngoscopy and intuba- tion.

Acute sialadenopathy during induction of anesthesia has been reported.

2. The Secondperiod of Zntubation (tube in place).

a. Traumatic or Mechanical Cornplica- tions.-The patient is still threatened by cervical column injuries due to positional changes. Yet the dominant feature of the second period of tracheal intubation is the possibility of respiratory obstruction due to: kinking of the tube (by the surgeon or his assistant, by changing the position of the patient’s head) ; overinflated cuff (protrud- ing, herniating, against the tracheal orifice of the tube; collapse of a weak, overused tube) ; tube bevel lying against either the tracheal or the bronchial wall; excessive dried secretions, dried lubricant, blood clots; free piece of ruptured cuff lodging in a bronchus; accidental extubation.

206 ANESTHESIA AND ANALGESIA. . . Current Researches VOL. 53, No. 2, MARCH-APRIL, 1974

Rupture of the inflatable cuff followed by fatal tracheal bleeding and tracheal dilation have been reported.

The posterior, membranous part of the trachea is very friable and susceptible to tearing in the elderly. Perforation or rup- ture of the trachea is most apt to occur when these intubated patients are recklessly moved. Such a grave accident leads to hem- orrhage and hypoventilation associated with emphysema and/or pneumothorax. Obvious- ly, one should not extubate until after sur- gical repair of the trachea. Boyd tells of an antistatic endotracheal tube which burned in the patient’s mouth in the absence of an explosive agent-at clinical concentrations.

Mehta; makes a beautiful demonstration of the possibility of tracheobronchial aspi- ration even in the presence of an inflated cuffed tube: contrast media slipped past the inflated cuff in 18 out of 90 intubated pa- tients.

Armored tubes do not always prevent re- spiratory obstruction and/or other severe complications.

b. Neurogenic or Reflexly Caused Com- p1ications.--The same problems as described for the first period of tracheal intubation can occur here.

c. Pharmacochemically Caused Compli- cations-Bronchospasm may be due to for- maldehyde having been incompletely re- moved from the tracheal tube or to phenol mistakenly used to clean the tube. Such accidents are obviously preventable.

3. The Third Period of Zntubation (ex-

a. Traumatic or Mechanical Complica- cations.-Difficult or impossible extubation may be attributed to three different mecha- nisms:

-Undeflated cuff, because the connector compresses the cuff tube, preventing defla- tion; because a constrictive band of the in- ternal wall of the cuff isolates a herniated portion of it. Entrapped air may have to be released by puncture through the cricothy- roid membrane.

-Excessively large cuff hooking on the vocal cords.

-Adhesion of the tube to the tracheal wall due to absence of lubricant.G Respira- tory obstruction may be due to:

tubation).

-Biting on the tube.

-Pharyngeal pack forgotten after extu- bation.

--Inflated cuff separated from the endo-

-Flaccidity of the larynx-the most fre- quent cause of congenital respiratory dis- tress in the newborn.

-Tracheomalacia can be congenital or secondary (to tumors of the neck, or of the thyroid, or Pott’s disease of the cervical column) and can produce respiratory ob- struction at extubation only. One of us wit- nessed this situation in a 14-year-old boy with cervical Pott’s disease. Obstruction manifested itself on extraction of the tube 4 to 5 cm. from the carina, with correction of the problem by pushing the tube to within 1 to 2 cm. from the carina. In these cir- cumstances, extubation must be slow and careful, cuff inflation is better avoided; should obstruction occur, the tube should be left in place, in good position, until the tra- cheal lesion is surgically corrected. An iden- tical situation is possible in Morquio’s dis- ease with malformation of the tracheal car- tilages. Patients with this genetic mucopoly- saccharidose should not be intubated before having a good radiologic investigation of the trachea to exclude tracheal malforma- tion.

tracheal tube and left in the trachea.

Lindholm? reports that 6 patients out of 225 under prolonged tracheal intubation had respiratory obstruction on extubation, 4 of them requiring tracheostomy.

We agree with those who say that laryng- oscopy on extubation is mandatory in cases of prolonged tracheal intubation.?

b. Neurogenic or Reflexly Caused Com- plications.-These are essentially identical to those of the first period of intubation. Laryngospasm after extubation may disap- pear on removal of a nasogastric tube. Car- diac arrhythmias seem to be as frequent during extubation as during intubation.

Reilly reports two cases of acute swelling of the parotid gland on extubation.

c. Pharmacochemically Induced Compli- cations.-Some local anesthetics, as some lubricants, tend to cause glottic edema, pre- sumably due to hypersensitivity or allergy. Glottic edema is discussed in more detail as a sequela of tracheal intubation.

Complications . . . Blanc and Tremblay 207

TABLE 3 The Frequency of Postintubation Sore Throat

Frequency in Number of Authors Year percent cases

Wolfson’” 1958 22.1 521 Brunelle e t al’ 1961 29 863 Jones et all’ 1968 6 190 Borchet” 1969 43 5 00 Conway e t als 1969 38.2 642 Paykoc et all’ 1971 24.4 45

11. SEQUELAE ( LATE COMPLICATIONS )

We divide this class of complications of tracheal intubation according to clinicopath- ologic criteria (table 2 ) . These include:

Sore Throat.-The most benign and the most frequent of the sequelae of tracheal in- tubation (table 3 ) . Conway and coworkers* found that sore throat occurred in 10.2 per- cent of 617 patients who had not been in- tubated! Since the 1951 report of Baron and Kahlmoos,s authors generally agree that this is a fleeting sequela that disappears within 48 to 72 hours without any specific therapy. Humidity seems to benefit patients suffering from postintubation sore throat. Cinchocaine jelly-covered tubes cause a sig- nificant lowering in the incidence of sore throat.

Intermittent Aphonia and Recurrent Sore Throat.-Harrison and Tonkin bring out these poorly defined “functional” entities which have no visible macroscopic lesion. These conditions can persist for many years after extubation and may be due to minor alterations in the laryngeal articulations or in the tonicity of the vocal cords.

Paresis of the Hypoglossal andlor Lin- gual Nerues.-These are sequelae possibly due to pressure of a MacIntosh laryngoscope blade in the retrolingual region.

Traumatic Laryngitis (Dysphonia or Aphonia) . - According to Kanis, this se- quela is found in 50 percent of intubated patients. Arner and Diamant reported ap- proximately one-third of 77 patients fol- lowed to have sustained this complication. Macroscopically, there is discreet epiglottic and/or arytenoidal edema, the vocal cords moving freely. There can be transient supra- glottic edema, at most accompanied by con- gestion or submucosal hemorrhages. In the Baron and Kahlmoos study: some 42 per- cent of the patients intubated presented dys-

phonia with congestion and edema of the posterior third of the vocal cords. This lar- yngitis disappeared without treatment in 2 to 3 days.

Debain and associates6 state that aphonia without evident lesions could be of psycho- genic origin.

Infections.-It is known that nasotracheal intubation can be followed by sinusitis. Albeit rare in this era of antibiotics and sterilized tracheal tubes, postintubation in- fections can still occur if a terrain exists for their development: retropharyngeal abscess after a difficult intubation for thyroid sur- gery; difficult intubation in an obese, bull- necked patient.

Airway infection is less common from pro- longed intubation than in tracheostomy, yet there remains the risk of pulmonary infec- tion due to atelectasis caused by retained secretions.

Gross and Gros report a chondritis of the cricoid cartilage with abscess formation in a patient who had been intubated for 34 days.

Glottis Edema.-Shaw, in 1946, was the first to point to tracheal intubation as a cause of laryngeal edema. Iglauer and Molt, in 1939, had already reported 10 cases of glottic edema due to a gastroduodenal tube, with 8 cases going on to laryngeal stenosis. Kauffman and colleagues, in 1942, further documented this sequela.

Stoelting and Proctor discuss 4 cases of postextubation respiratory obstruction and provide a classification of the causes of post- intubation laryngeal edema.

Children are the most frequently afflicted by this complication, whose localizations can be:

Supraglottic Edema-hose areolar con- nective tissue is found, in the larynx, on the anterior surface of the epiglottis and on the arytenoepiglottic folds. These areas are therefore prone to develop edema. The epi- glottis may be pushed backwards by ede- matous swelling, blocking the glottic aper- ture on inspiration and causing severe re- spiratory obstruction.

Retrowytemidal Edema.-While the sub- mucous connective tissue is dense on the vocal cords, it is loose just below the cords and behind the arytenoid cartilages. A sig- nificant edema behind these cartilages can

208 ANESTHESIA AND ANALGESIA . . . Current Researches VOL. 53, NO. 2, MARCH-APRIL, 1974

limit their movement and so limits the ab- duction of the vocal cords on inspiration. In these conditions, a more-or-less pronounced respiratory obstruction may be established.

Subglottic Edema.-This is the gravest of the glottic edemas and the most susceptible to be the cause of urgent reintubation or tracheostorny, especially in infants and chil- dren.'-' The internal cross-section area of the larynx of a newborn is no greater than 14 sq.mm. An edema 1 mm. thick on the inter- nal subglottic perimeter is sufficient to re- duce the mentioned area to 5 sq.mm. (35.7 percent of normal). The cricoid cartilage surrounding completely the subglottic re- gion forestalls any external expansion of the swollen surfaces, which can expand only in- ternally, giving rise to a very dangerous air- way obstruction. Moreover, the subglottic region has a fragile respiratory epithelium with loose submucosal connective tissue that is easily traumatized and is edema prone.

Glottic edema persisting beyond 24 hours after extubation is often associated with more serious lesions.

Laryngeal Ulcers.--This subject was mas- terfully reviewed in 1953 by Chevalier Jackson,1z who had first coined the term in 1928.

Dwyer and associates describe the macro- scopic laryngeal lesions from tracheal intu- bation in the following sequence of events: Within 2 to 4 hours of endotracheal intuba- tion, there is laryngeal irritation with muco- sal congestion; within 6 hours, laryngeal erosions are invariably present.

Lu and coworkers describe the microscop- ic pathology, chronologically, as follows: inflammatory reaction with small hemor- rhages; epithelial degeneration with ulcer formation covered by a pseudomembrane of fibrin and necrotic epithelial debris; separa- tion of the pseudomembrane by edema for- mation.

Donnelly and colleagues,lc in a prospec- tive study of 99 necropsies, found that after 48 hours there is also bacterial infection of the perichondral vocal processes and of the cricoid lamina, and that within 96 hours all cases had pronounced ulcerations.

Hilding, using methylene blue staining in necropsies, showed convincingly that the maximal damage occurs on the arytenoid vocal processes, on the cricoid plates, and on the anterior wall of the trachea. The cuff area was always affected to some degree.

Since the report of Bergstrom's group in 1962, it has been recognized that mucosal necrosis can easily reach the adjacent car- tilage.

Way and Sooy, in 1965, demonstrated identical lesions in 14 cynamolgus monkeys, whose larynges resemble quite closely those of humans, and stated that dexamethasone decreases the intensity of the inflammation; that the ulcers are more likely to be found on the same horizontal plane as the cricoid cartilage; and that re-epitheliazation begins within 48 hours after extubation to end about 100 hours later.

Debain and associates6 found that the most common localizations of laryngeal ul- cers are the free edges of the posterior halves Gf the vocal cords (along with a reduction in the arytenoidal mobility) ; the posterior halves of the cords and the posterior com- missure of the larynx; the posterior subglot- tic region, just below the arytenoid vocal processes.

LindholmT describes laryngeal ulcers at the interarytenoid area, the medial sides of the arytenoids, and at the inner posterola- teral area of the cricoid region.

Hilding and Hilding'? stated that laryn- geal ulcers heal by epithelial regeneration from the basilar layer of the remaining epi- thelium.

Of important moment is that laryngeal ulcers are most probably the lesions on which more serious lesions may develop.

Laryngeal Granulomas and Polyps.--In 1932, Clausen'8 and Griffith19 reported the first cases of laryngeal granuloma attributed to endotracheal intubation. An important bibliography has accumulated since then. Several cases were published all around the world.20.21 Many good reviews exist on this

Howland and LewiG3 fix the incidence of laryngeal granuloma at 1:800 to 1000 intu- bations. With prolonged intubation, Tonkin and Harrison" report 4 cases in 166 patients and Lindholm? gives 4 cases out of 267 patients.

There are some reports on polyps coughed out spontaneouslyla and on granulomas healed without treatment, but usually these sequelae require surgical excision. Zinc sul- phate treatment has also been reported.

Laryngeal granuloma locations correspond approximately to those of laryngeal ulcers,

s~b,ject .~2,~3

Complications . . . Blanc and Tremblay 209

from which they appear to emerge. They are usually unilateral but many reports of bi- lateral granulomata have been published.Z1

Laryngeal granuloma affects adults more than children and women more than men (see etiology of sequelae, below).

Acute granuloma existsG but is rare. Usually, these lesions manifest themselves

from a few weeks to a few months after tra- cheal intubation.9 Clinical manifestations are hoarseness, sore throat, dysphagia. Gran- uloma can be very large and present as respiratory obstruction, especially if the le- sion is subglottic, an eventuality that is for- tunately rare.

Synechia of the Vocal Cords.-Necrosis of the free edges of the vocal cords can set the conditions for sticking and welding of their posterior third. The same can occur with the arytenoid vocal processes, thereby leaving only a small anterior aperture and a retro- arytenoidal slit for the airway.' There is aphonia and respiratory obstruction. With early diagnosis, surgical correction is satis- factory."

Luryngotracheal Membranes and Webs.- Laryngeal and subglottic membranes can be congenital or acquired from tracheal intuba- tion.

Stein and coworkers found 3 cases of laryngotracheal membrane formation in a series of 42 autopsies performed on previous- ly intubated patients.

Membrane formation between the vocal cords can occupy some 213 of the glottic opening.

Warner reports a case of subglottic fibrous cord developing in a 25-year-old woman, probably secondary to 5 days of nasotra- cheal intubation 2 years before, whereas Kenntnis describes a subglottic web in a 64-year-old woman 4 days after tracheal in- tubation.

These sequelae are particularly dangerous since a portion of the membrane can free itself, leading to sudden respiratory obstruc- tion.

Surgical removal of membranes and webs can be difficult, as they epithelialize in con- tinuance with the laryngotracheal mucosa.

Laryngeal Fibrosis.-This is the gravest of the postintubation sequelae, since surgi- cal correction is limited. Fibrous tissue for- mation leads to laryngeal stenosis, be it by

narrowing of the subglottic lumen or by im- mobilization of the vocal cords due to anky- losis of the cricoarytenoid joints. The result is always respiratory obstruction. Symptoms come late (45 to 60 days after extubation) and children are more susceptible than adults.6

Sudaka and colleagues report 9 cases, 5 women and 4 children, Minnigerade adding another case.

Tracheal Stenosk-Dixon and associates report 1 case among 342 patients with pro- longed tracheal intubation. Pearson and co- workers found that in 7 out of 25 cases the stenosis was at the cuff site, and Fishman and colleagues found the same in 9 out of 12 cases.

Shelly and associates, in 10 dogs, showed that tracheal stenosis favors the cuff site all the more that the cuff pressure is elevated, and stated that induced hemorrhagic shock is not particularly a predisposing factor to such a complication.

Greisen relates 9 cases of tracheal stenosis to the use of intermittent positive pressure ventilation.

Miller and Gulsha feel so strongly about the fact that the cuff level is the preferred site of tracheal stenosis that they have re- placed the cuff by Teflon rings. The Kamen- Wilkinson endotracheal and tracheostomy tubes were also conceived to eliminate the pressure effects of the cuff.

ETIOLOGY OF THE SEQUELAE OF TRACHEAL INTUBATION

Campbell and Bryce and colleagues give classifications of the causes of the sequelae of tracheal intubation. Salem and associates classify the factors favoring vocal cord paral- ysis in pediatric patients submitted to anes- thesia under tracheal intubation. Lindholm,' in one of the most exhaustive studies on the pathologic consequences of prolonged tra- cheal intubation, gives recommendations for their prevention.

We have divided this chapter into three classes of factors (table 4) , as follows:

1. Predisposing factors: Those factors ir- remediably present which render the patient more liable to the adverse effects of other factors.

2. Adjuvant factors: Those factors or causes which, when present, enhance the

210 ANESTHESIA AND ANALGESIA . . . Current Researches VOI.. 53. No. 2, MARCH-APRIL, 1974

TABLE 4 Etiology of the Sequelae of Tracheal Intubation

1. Predisposing factors: Age Sex Fragility of the laryngotracheal mucosa Anatomic characteristics

2. Adjuvant factors: Circumstances affecting healing Circumstances favoring edema formation Upper respiratory obstruction State of hydration Nasogastic or duodenal tubes Stasis of septic secretions Surgery of the neck Postintubation vocal abuse

Traumatic intubation Duration of intubation Traction and rubbing of the tube Cuff pressure Material of construction of tubes Other irritants

3. Decisive factors:

action of decisive factors. They are not ir- remediably present in the patient and, as such, can be treated or prevented.

3. Decisive factors: Those factors which, by themselves (as opposed to the two for- mer ones ) , can cause sequelae of tracheal in- tubation. They are determinant factors.

1. Predisposing Factors. a. Age.--Children appear to withstand

prolonged tracheal intubation better than adults. However, children are more apt to sustain glottic edema, while subglottic sten- osis afflicts newborns and infants especially. The reasons for this have been beautifully described by EckenhoP who underlines the anatomic peculiarities of the larynges of neonates and infants: a higher and more an- terior larynx; a larger, stiffer epiglottis, which forms a more acute angle with the glottic opening; a more fragile epithelium.

Since Bayeux (1897), it is known that the infant cricoid is the narrowest part of his larynx.

Adults appear to be more prone than in- fants and children to develop granulomatous reactions to intubation.

b. Sex. - Postintubation sore throat is clearly more common in women.4~1~)~1~ Tonkin and H a r r i ~ o n ' ~ show that 36.5 per- cent of the patients in their series with mild or absent sequelae were female but that 72.4 percent of those with moderate to severe laryngeal sequelae were women. Granulomas also are much more common in women."-':<

This overwhelming difference in incidence of postintubation granulomas in women ap- pears related to the greater resistance of the male laryngeal epithelium to trauma and to the unfortunate use of oversized tracheal tubes in females.

c. Fragility of the Laryngotracheal Mu- cosa.-The first study found under this heading is that of Ryan and coworkers, who noted no relation between the thickness of the mucosa and the age of the patients but who underlined that males have a thicker mucosa than females. Hilding and Hilding,'T in dogs, chickens, and cows, showed that this tissue is very susceptible to the least trauma, such as the presence of a tracheal tube. Farmati and associates, using exfolia- tive cytology before and after intubation, concluded that the respiratory epithelium in children is easily damaged by tracheal in- tubation.

d. Anatomic Characteristics. - Congeni- tal or acquired anomalies of the larynx (la- ryngeal webs or bands, cysts, tumors) are obvious predisposing factors of laryngotra- cheal sequelae. Facial or cervical anomalies, as well as short neck, receding chin, obesity, can render the laryngoscopy particularly dif- ficult and so predispose the patient to trau- matic intubation.

2. Adjuvant Factors.-In 1932, Griffithlg stated that for apparently equal conditions certain patients were more susceptible to sequelae from tracheal intubation than others. The following pathologic conditions must be considered:

Complications . . . Blanc and Tremblay 21 1

a. Circumstances Affecting Healing. - Chronic and debilitating diseases, anemia, hypovitaminosis, hypoproteinemia, steroid treatment, alcoholism.

b. Circumstances Favoring Edema For- mation.-Upper respiratory infections, no doubt, favor the development of glottic ede- ma and of other sequelae from tracheal in- tubation. Other factors include hyperhydra- tion (see below: state of hydration), cardiac failure, renal and hepatic diseases, angioneu- rotic edema, allergies.

c. Upper Respiratory Obstruction.-One would not seriously consider using prolonged tracheal intubation in laryngeal obstruction due to tumor, tuberculosis or laryngeal ab- scess.

d. State of Hydration.-Dehydration, by diminishing mucus secretion, makes the la- ryngotracheal mucosa more susceptible to trauma. Chalon and colleagues, in an ex- foliative cytology study, showed that the de- gree of damage to the mucous membrane is related to the length of exposure to dry anesthetic gases.

Overhydration by excessive intravenous fluids facilitates the development of laryn- geal edema. The same is probably true with hyponatremia.

e. Nasogastric and Nasoduodenal Tubes. -As noted earlier (glottic edema), gastro- duodenal tubes can, by themselves, cause laryngeal edema and stenosis. Sore throat is significantly more frequent when use d nasogastric tubes accompanies tracheal in- tubation.' Furthermore, such tubes can pro- duce esophageal ulcerations a t the level of the cricoid sphincter, thereby opening the route for infection of the nearby laryngo- tracheal structures.

f. Stasis of Septic Secretions.-Bergstrim and associates report that even with serious damage from tracheal intubation, there may be no evidence of infection at necropsy. Other authors, however, consider such infec- tion likely to be spread if intubation is per-

h. Postintubation Vocal Abuse. - With Fields,' we consider this an adjuvant factor. Farrior reports a laryngeal ulcer related to vocal abuse in a 60-year-old woman.

3. Decisive or Determinant Factors.

a. Traumatic Intubation. - Blind naso- tracheal intubation can be particularly trau- matic and associated with complications. Be the cause in the operator (inexperience, hur- ry, poor muscle relaxation, too light anes- thesia, etc.) or in the patient (predisposing and/or adjuvant factors), traumatic intuba- tion is associated much more frequently with sequelae than a correctly performed in- tubation.

b. Duration of the Intubation.-Wyliel and Iovannovich describe laryngeal granu- lomas after only 15 and 21 minutes of intu- bation, respectively, while Smith reports two examples (an infant and a boy of 14) in which intubation lasted 6 weeks without complications.

Evidently, these are extremes, for Dwyer and associates and Bergstrom showed a di- rect correlation between the gravity of laryn- gotracheal lesions and the duration of the intuba t ion.

The maximal permissible time for safe prolonged tracheal intubation is not easily determined, for many variables are involved ( age, tube caliber, underlying pathology, ex- perience of the performer, etc.) . Harrison and Tonkin and Bain summarize the maxi- mal safe permissible times suggested in the literature, in addition to which we have found a reported range in adults of from 8 hours to 1 week and in children from 48 hours to 3 weeks.

We feel the maximal safe permissible time of prolonged tracheal intubation to be that time when the incidence of sequelae in- creases significantly, and this in that partic- ular center where the patient is treated! The aim is to decrease such complications to their lowest, by ever improving the overall care of the patient.

formed during upper respiratory tract infec- tions. Donnelly found microscopic evidence of bacterial infection in every larynx or der the following headings:

c. Traction and Rubbing of the Tube on the Larynx and Trachea will be studied un-

trachea intubated for more than 48 hours. It is logical to expect more serious complica- tions from an ulcer in contact with septic secretions than from a clean one.

External Diameter of Tube. - Brunelle and colleagues.' found that the incidence of sore throat increases with increased tube bore. Many others have found a similar

g. Surgery of the Neck.-This can pre- dispose the intubated patient to complica- tions from intubation."

relationship with the development of post- intubation tracheal stenosis or increased in- cidence of laryngeal sequelae.

212 ANESTHESIA AND ANALGESIA . . . Current Researches VOL. 53, No. 2, MARCH-APRIL, 1974

In 1950, Beecher proved that relatively small tracheal tubes can be used to main- tain normal blood gases with spontaneous respiration.

Shape of Tube.-Tubes in current use do not correspond anatomically to the airways and thereby exert traction on some of the laryngotracheal structures,’ disregarding the fact that the trachea is not round on cross- section but rather more imperfectly circular with a flattened posterior segment. Linholm7 shows beautifully how ordinary tubes exert pressure on the arytenoids, on the posterior half of the vocal cords, and on the dorsal wall of the trachea. From these findings he constructs a more anatomic tracheal tube.

Movements of Vocal Cords and Trachea. -During spontaneous ventilation, the vocal cords open and close, the lower airways dilate and lengthen, then passively constrict and shorten with each inspiration and ex- piration, rtqectively. With controlled res- piration, the tracheal tube moves along its longitudinal axis. All these movements cause the tube to rub against the airway surface. Identical ronditions exist with bucking, coughing, swallowing. Debain and associ- ates,” in intubated patients with recurrent unilateral vocal cord paralysis, found a strong predominance of lesions on the tonic vocal cord.

Artificial ventilatiofi seems to contribute to the frequency and to the gravity of post- intubation sequelae. Lindholm’ showed that if patients are well sedated and did not re- sist the ventilator, they were less likely to suffer from such damage.

The position of the patient’s head is also of great moment.” Barton, in comparing the absence of laryngeal lesions from broncho- scopy to the presence of such lesions from tracheal intubation, shows that in the later instance the tube rubs on the posterior re- gion of the larynx. He accordingly concludes that during the second period of intubation, the patient’s head should be hyperextended.

d. Cuff Pressure.-Smith and Knowlson and Bassett have noted that, at minimal occlusive volume (the least volume of air required to make the airway air leakproof) the cuff pressure in a Latex tube equals 18 to 22 mm. Hg. As the temperature of the cuff-enclosed air rises from room tempera- ture to the patient’s temperature, the cuff pressure rises still further. As the mean ca- pillary pressure lies between 25 to 30 mm. Hg (arterial end) and 9 mm. Hg (venous

end), it follows that the cuff pressure brings about capillary stasis with tissue anoxia and edema, particularly in conditions of hyper- thermia, arterial hypotension and/or a hy- per-inflated cuff. Intracuff pressures above 400 mm. Hg and C-T pressures (pressures between cuff and tracheal wall) above 200 mm. Hg were recorded by Kamen and Wilkinson.

Several authors agree in considering direct pressure from a distended balloon on the tracheal wall as the major factor of tracheal sequelae.G

The following corrections against exces- sive pressure on the tracheal wall have been proposed: a new cuff design ( McGinnis and associates); a low-pressure soft teflon cuff (Lomholt) ; replacing the cuff altogether by soft teflon rings (Miller and Gulsha) ; automatic intermittent cuff inflation; a polyurethane foam-filled cuff (Kamen and Wilkinson) .

e. Construction Material.-Whereas clin- ical experience has shown that rubber tubes give rise to more secretions than plastic tubes, laboratory investigation has crumbled the myth of the “innocuity” of plastics. Little and Parkhouse demonstrated that polyvinyl chloride, like most plastics, can produce fibrosing reaction when implanted in rabbit paravertebral muscles. Other arti- cles have warned of the possible dangers from plastic tracheal tubes. In 1970, Stetson and Guessz5 gave a thorough account of the causes of the possible damage from such tubes and of the ingredients used in their manufacture. Such ingredients include cata- lyzers (to facilitate polymerization), vul- canizers or accelerators (to facilitate solidi- fication), stabilizers or antioxidants (against the deterioration of the material in the presence of heat and/ or oxygen), plasticiz- ers (to soften) , fillers (to harden), pigments (to color), etc. Now, phenolnaphthylamine derivatives (antioxidants) have cancerigenic properties; triorthocresyl phosphate ( plas- ticizer) is a powerful neurotoxin; organotin (stabilizer) has necrotizing actions and cell- growth-inhibiting properties. Certain non- polymerized monomers (with free radicals) can cause tissue damage, while certain poly- mers contain chemical bonds which tissue enzymes can attack and split off.

f . Other Irritants.-Glues employed to fasten cuffs to tubes can be considered as irritants insofar as they possess strong bac- teriostatic activity.

Complications . . . Blanc and Tremblay 213

Several cases of vocal cord paralysis have been related to tubes sterilized in ethylene oxide." According to Andersen, this gas dis- solves relatively well in polyvinyl chloride and is then released in concentrations high enough to damage tissues. Hence, any ma- terial sterilized by ethylene oxide should be well aerated before contact with live tissues.

Gamma irradiation of polyvinyl chloride tubes releases chloride ions which can com- bine with ethylene oxide to form the very toxic, not easily removed, liquid ethylene chlorohydrin. In the presence of moisture, ethylene oxide forms ethylene glycol, a tis- sue irritant which, like ethylene chlorohy- drine, is absorbed into the polyvinyl chloride and dissipates very slowly.

Tracheitis has been reported due to errors in the cleansing of tracheal tubes by the use of ethylene glycol, phenol, or mercury bini- odine.

As others have stressed, it is hoped that manufacturers providing medical equipment to be used for prolonged contact with human tissue will ensure that their products are nontoxic, and also warn very clearly on the package label against sterilization or other procedures which may enhance tissue irri- tation.

ACKNOWLEDGMENT We are grateful to Mrs. Monique Tremblay

and Mrs. Maria Emilia Lopes for assistance in manuscript preparation.

Generic and Trade Names of Drugs Cinchocaine chloride-Nupercaine Dexamethasone-Decadron Noradrenaline-Levophed Phentolamine-Regitine

REFERENCES 1. Wylie WD: Hazards of intubation. Anaes-

2. Fields JA: Injuries and sequelae associated with endotracheal anesthesia. Laryngoscope 69: 509-518, 1959

3. Lewis RN, Swerdlow M: Hazards of endo- tracheal anaesthesia. Brit J Anaesth 36:504-515, 1964

thesia 5: 143-148, 1950

4. Brunelle JP, Boucher J, Cossette G, et al: L'intubation orotrachtiale et les maux de gorge post-op6ratoires. Canad Anaesth Soc J 8:581-585, 1961

5. Mehta S: The risk of aspiration in the pres- ence of d e d endotracheal tubes. Brit J Anaesth

6. Debain JJ, Lebrigand H, Binet JB. et al: Quelques incidents et accidents de l'intubation trachtiale prolongbe. Ann Otolaryng (Paris) 85: 379- 386, 1968

7. Lindholm DE: Prolonged endotracheal in- tubation (a clinical investigation with specific refer- ence to its consequences for the larynx and the trachea and to its place as an alternative to intuba- tion through a tracheostomy). Acta Anaesth Scand Suppl 33, 1969

8. Conway CM, Miller JS, Sagden FLH: Sore throat after anaesthesia. Brit J Anaesth 32:219-223, 1960

9. Baron SH, Kahlmoos HW: Laryngeal se- quelae of endotracheal anesthesia. Ann Otol 60: 767-792, 1951 10. Wolfson B: Minor laryngeal sequelae from

endotracheal intubation. Brit J Anaesth 30: 326-332, 1958 11. Jones GOM. Hale DE, Wasmuth CE, et al:

A survey of acute complications associated with endotracheal intubation. Cleveland Clin Quart 35: 23-31, 1968 12. Borchet K: Die Haufigkeit postoperative Hals-

beschwerdewn nach endotrachealen Intubationsnarko- sen. Anesth Prox 4:91-95, 1960 13. Paykoc R, Akkartol B, Savkilioglu E: Sore

throat and upper respiratory infection following endotracheal intubation. Tip Fak Mec (Istanbul) 14:72-77, 1971 14. Tonkin JP, Harrison GA: The effect on the

larynx of prolonged endotracheal intubation. Med J Aust 2:581-587, 1966 15. Jackson C: Contact ulcer granuloma and

other laryngeal complications of endotracheal anes- thesia. Anesthesiology 14:425-436, 1953 16. Donnelly WA, Grossman AA, Grem FM:

Imcal sequelae of endotracheal anesthesia. Anes- thesiology 9: 490-497, 1948

17. Hilding AC, Hilding JA: Tolerance of the respiratory mucous membrane to trauma: surgical swabs and intratracheal tubes. Ann Otol 71:455- 479, 1962 18. Clausen RJ: Unusual sequelae of tracheal

intubation. Proc Roy SOC Med 25:1507, 1932 19. Griffith HR: Futher experiences with endo-

tracheal gas-oxygen anesthesia. Anesth & Analg 11 : 206-209, 1932 20. Epstein SS, Winston P: Intubation granu-

loma. J Laryng 71:37-48, 1957 21. Snow JC, Harano M, Balogh K: Postintuba-

tion granuloma of the larynx. Anesth & Analg 45: 425-429, 1966 22. Howland WS, Lewis JS: Post-intubation

granulomas of the larynx. Cancer 9:1244-1247, 1965 23. Myerson MC: Granulomatous polyp of the

larynx following intratracheal anesthesia. Arch Otolaryng 62: 182-186, 1955 24. Eckenhoff JE : Some anatomic considerations

of the infant larynx influencing endotracheal anes- thesia. Anesthesiology 12:401-410, 1951 25. Stetson JB, Guess WL: Causes of damage

to tissues by polymers and elastomers used in the fabrication of tracheal devices. Anesthesiology 33:

44:601-605, 1972 635-652, 1970