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Aspiration pneumonia: A clinical and experimental review
Current Research Review
ASPIRATION A Clinical JOHN
L.
CAMERON,
PNEUMONIA and Experimental
M.D., GEORGE
RICHARD D.
CLINICALLY significant aspiration of gastric contents during anesthesia is not frequent, but when it occurs it is a catastrophic event carrying a high mortality. The potential risk of aspiration, however, is great and only the recognition of this risk keeps its incidence low. Its occurrence is highest among obstetrical patients and among general surgical patients who undergo surgery for trauma or acute abdominal crises, in which adequate preanesthetic preparation is not always possible. In a large series of maternal deaths during childbirth, approximately 2% were due to aspiration [20]. Of all general anesthetic deaths that occur, those due to aspiration account for at least 11% [9]. By 1962 there were 700 deaths recorded in the medical literature due to aspiration pneumonia [2], and one might suppose that the majority of aspiration deaths are not deemed reportable. Because of the gravity of this complication of general surgical anesthesia, features of its clinical course, pathogenesis, and treatment will be reviewed, and comments made on need for further clinical and experimental observations. From the Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, Md. Supported by National Institutes of Health Grant 5 TO1 GM 01541. Submitted for publication Oct. 6, 1966. 44
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HISTORICAL
ASPECTS
The first death attributed to aspiration allegedly occurred in 475 B.C. when the Greek poet Anacreon died from the inhalation of a grape seed [22]. Hippocrates realized the dangers of aspiration and in 400 B.C. warned that “For drinking to provoke a slight cough, or for swallowing to be forced, is bad” [ 141. The first published death under an anesthetic occurred under chloroform in January, 1848, fifteen months after the introduction of general anesthesia. The death, just two months after the introduction of chloroform, was attributed by at least one observer to aspiration of brandy being used for resuscitation. According to Sir James Simpson “the girl died, then, as I conceive, . . . . choked or asphyxiated by the very means intended to give her life” [25]. Of the first 51 cases of death under chloroform anesthesia reported in 1861, at least 2 resulted from aspiration
[lOI. Experimental investigation of aspiration pneumonia, although sparse, had an early beginning. In 1781 John Hunter stated in a court of law, “It is in the mouth of everybody that a little brandy will kill a cat. I have made the experiment; in all those cases where it kills the cat, it kills the cat by getting into her lungs, not her stomach’ [lo]. Although knowledge of aspiration dates from
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antiquity, and experimental investigation from the 1700’s it remained for Mendelson, in 1946, to separate adequately and to describe the major clinical and pathological features of aspiration [ 191. He described two clinical situations observed in patients who aspirated under general anesthesia at the New York Lying-In Hospital. The first was associated with the aspiration of solid material; the second, which Mendelson described as an “asthmatic-like” reaction, with the aspiration of liquid material. He showed experimentally that this second clinical picture was caused by the hydrochloric acid present in gastric aspirate. Because of this pioneering report, aspiration pneumonia has been referred to as Mendelson’s syndrome.
CLINICAL
FEATURES
Studies by Culver et al. [6] and Berson and Adriani [4] both suggest that aspiration will occur in a small percentage of anesthetized general surgical patients even under the most ideal circumstances. It is essential, therefore, to be able to recognize this event immediately. In some instances the signs of imminent vomiting are present-irregular respiration, breath-holding, increased salivation, and swallowing. Usually, however, the anesthetist’s first warning is the appearance of gastric contents in the pharynx or mouth. At the other extreme, aspiration may go undetected, and postoperative cyanosis may be the presenting sign. The clinical picture produced by aspiration of gastric contents depends on the nature of the material aspirated. When solid particulate matter is aspirated, the presentation is often acute and catastrophic. If the aspirated material is of sufficient size, acute respiratory obstruction, asphyxia, and death may rapidly ensue. If the particulate matter lacks sufficient mass, or is not so located as to cause immediate asphyxiation, then dyspnea, cyanosis, and tachycardia occur. Chest x-ray will reveal atelectasis in the area supplied by the involved bronchus or
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bronchi, and mediastinal shift toward the involved area will be present. The aspiration of liquid contents during anesthesia is more frequent [19]. Again, the clinical picture that ensues depends upon the volume and nature of the aspiration. In Berson and Adriani’s [4] study of 926 general surgical patients, none of the 66 patients who were proven to have occult aspiration of small amounts displayed acute clinical signs or developed aspiration pneumonia. However, if sufficient volume of low pH gastric juice is aspirated, a distinct clinical picture evolves. The actual aspiration may be unnoticed. The onset of symptoms is not always acute, as in the aspiration of solid material. Dyspnea, cyanosis, and tachycardia occur, but occasionally are not of a degree to cause concern until several hours after operation. Some observers have described the immediate appearance of numerous wheezes, rales, and rhonchi over the involved areas, and likened the event to an attack of asthma, while other investigators describe few early auscultatory changes. Dines [7] reports that as long as five hours may elapse between the time of aspiration and the onset of auscultatory findings. The most frequent clinical picture, however, is one of dyspnea, cyanosis, and tachycardia in the immediate postaspiration period. The cyanosis is refractory to oxygen therapy, and mild hypotension may be present for a short time. Patients may die during this acute phase with pulmonary edema but generally the hypotension abates and the patient remains stable for 24 to 36 hours. Except for persistent cyanosis and mild respiratory distress, the clinical picture is not alarming. Subsequently the patient either improves or progressively deteriorates and dies from respiratory causes, with hypotension only a late event. Chest x-rays reveal patchy infiltrates which are indistinguishable from bronchopneumonia. The right lower lobe is most often involved because the more nearly linear pathway of the trachea and the right lower lobe bronchus offers the least resistance to the aspirated material. The right upper lobe is 45
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also frequently affected, probably because the patient’s supine or Trendelenburg position permits drainage of the aspirate into the upper lobe. When the aspiration is massive, both lungs can be involved radiologically, and the clinical picture is one of pulmonary edema from the massive pulmonary injury, with large volumes of bloody froth issuing from the patient’s mouth or endotracheal tube. It is in these patients that early mortality can occur. In patients surviving for hours or days, the extent of the radiographic abnormality does not necessarily parallel the clinical course. The role of infection in aspiration pneumonia is unclear. Many patients spike an early fever, which is probably unrelated to sepsis. After a period of days some patients do develop an infectious component and lung abscesses have been reported as a late sequela [ 191. In patients with intestinal obstruction and high bacterial contamination of gastric contents, sepsis may be an acute similar to gram-negative factor. A picture sepsis has been demonstrated experimentally in this situation [5]. The mortality rate from aspiration is difficult to assess. In Mendelson’s original report of 66 cases of aspiration two deaths occurred [19]. The mortality obviously depends on the volume and character of the material aspirated. When a significant volume of low pH material is aspirated, so that aspiration pneumonia follows involving the entire right lung or is present bilaterally, the mortality is great. Awe [l] reported 81 patients who had aspirated liquid gastric contents, with a mortality of 702.
PATHOPHYSIOLOGY Predisposing
Factors
The stage for pulmonary aspiration is set whenever liquid or particulate material enters the pharynx and the normal protective mechanisms of glottic closure are attenuated or absent. These mechanisms may be impaired in various specific neuromuscular disorders as well as in general debilitation or 46
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intoxication. However, it is primarily their ablation by anesthesia that is significant in the surgical patient. The primary source of aspirated material is the incompletely emptied stomach. In patients who have not or cannot be suitably prepared preoperatively, the vomiting or regurgitating of substantial volumes may oca massive pneumonitis. cur and produce Thus, patients in particular danger include those who have recently ingested food or drink prior to anesthesia or those in whom a large gastric volume results from ileus, intestinal obstruction, hemorrhage, gastric dilatation, or excessive gastric secretion. Scarring and inflammation about the pylorus produced by peptic ulcer disease may severely impair gastric emptying and lead to the retention of large volumes. Pain and fear are recognized as emotions which particularly influence gastric motility and reduce emptying time of the stomach. Virtually all preoperative patients are adversely influenced in this respect. Vomiting
and Regurgitation
The act of vomiting is a basic protective reflex which can be initiated by various stimuli. Vomiting during the excitement stage of inhalation anesthesia is a well-recognized hazard. Ordinarily, secure glottic the event in the conclosure accompanies scious state. The bending of the trunk, depression of the head, inversion of the glottis, and opening of the mouth all aid vigorous muscular contraction in expelling material from the pharynx. During inhalation anesthesia, SUpine position, extension of the neck, presence of a face mask, and depressed level of consciousness impede the clearance of material from the pharynx and promote its entry into the tracheobronchial system. The current practice in anesthesiology of combining an ultra-short-acting barbiturate with a muscle relaxant for the induction of anesthesia has virtually eliminated the excitement stage seen formerly with the use of the classical inhalation agents. While the incidence of active vomiting during anesthetic induction has been concomitantly decreased,
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regurgitation of stomach contents may occur and is equally hazardous. The mechanisms of regurgitation are not as well understood as those of vomiting. Culver et al. [6] and Berson and Adriani [4] have shown that regurgitation leading to occult aspiration occurs frequently during otherwise uneventful general anesthesia. These investigators placed dyes in the stomachs of preoperative patients and observed their sulbsequent appearance in the tracheobronchial tree in 16% and 7% of cases, respectively. Regurgitation is a more passive phenomenon than vomiting and seems to depend upon two features: the pressure gradients between the stomach, esophagus, and pharynx, and incompetence of the various “valves” that separate these structures. The presence of a valve-like mechanism at the cardioesophageal junction is now widely accepted, although there is still considerable conjecture about the relative importance of various anatomical structures to the normal functioning of this mechanism [2]. Opening of this valve during anesthetic induction can allow flow of gastric contents into the esophagus if a suitable pressure gradient exists. O’Mullane [21] observed the opening of the gastroesophageal junction in association with partial airway obstruction during general anesthesia. In addition, he noted that the esophagus of an anesthetized patient can retain a large volume of liquid which immediately enters the pharynx when the cricopharyngeal sphincter is paralyzed by administration of a muscle-relaxing drug. Robson and Welt [23] found that gastric dilatation markedly reduced the pressure necessary to produce reflex from the stomach into the esophagus. Elevated intragastric pressures may also be brought about by the gravid uterus or other intra-abdominal tumors. Two particularly hazardous clinical situations which produce significant regurgitation deserve special emphasis. In the first instance, anesthesia is induced by the intravenous administration of an ultra-fast-acting barbiturate, and the lungs are then ventilated by positive pressure through a tight-fitting face mask. If partial airway obstruction occurs and is uncorrected while ventilation contin-
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ues, large amounts of gas are forced into the stomach. The administration of the muscle relaxant, preparatory to tracheal intubation, will then cause relaxation of the gastroesophageal and cricopharyngeal valves. The gastric content, impelled by the elevated intragastric pressure, immediately floods the esophagus, inundates the pharynx, and readily enters the tracheobronchial tree through the relaxed glottis. The second hazard results from the apparently universal and irresistible impulse of the unwary to palpate the abdomen deeply just as the muscle-relaxing drug is being adof this ministered. External compression nature can produce surprising amounts of regurgitation, even from a fairly well prepared stomach. Character
of the Aspirate
Given a sufficient volume, the character of the aspirated material will generally determine the type of injury produced and thus the clinical course. Mendelson [19] observed different responses to the aspiration of solid and liquid material. Large particulate solids tend to occlude major bronchi producing lobar atelectasis or massive collapse of lung with attendant cyanosis, dyspnea, tachycardia, tachypnea, mediastinal shift, and consolidation. There is great variability, however, in the response to aspiration of liquids, depending upon their composition. Acidity Although Winternitz [28], in 1920, originally described pathological changes in the lungs of rabbits following the intratracheal introduction of hydrochloric acid, Teabeaut [26] was the first to emphasize the importance of the hydrogen ion concentration. He showed that when the pH exceeded 2.4, the response elicited simulated that following injection of water. As the pH of the aspirate WAS lowered, the tissue reaction increased progressively until at pH 1.5 a maximal response was obtained which could not be enhanced by more concentrated acid. When filtered gastric juice of known pH was compared with hydrochloric acid of similar pH, 47
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there was no significant difference in tissue response, suggesting that the influence of the peptic activity of gastric juice upon the pathological process was negligible. Subsequently, many investigators [l, 3, 12, 15, 161 have confirmed the observation that liquid with pH less than 2.5, given in suitable amounts, produces both clinical and pathological signs of aspiration pneumonitis. In addition, the data suggest that aspiration of fluid at pH 1.5 or less is fatal within 24 hours in most experimental dogs. This response is probably independent of the volume of liquid aspirated at dose levels greater than 2 ml. per kilogram of weight. Hamelberg and Bosomworth [12] studied the rate of distribution of pH 1.75 gastric juice instilled into the trachea of excised, ventilated, and perfused canine lungs, and noted that when dye was added to the aspirate it appeared on the surface of the lungs in 12 to 18 seconds, and within 3 minutes patchy areas of atelectasis were present. In a study of the rapidity of bronchial neutralization of aspirated 0.1 N HCl in dogs, Awe and coworkers [l] found that bronchial pH reached a level of 2 to 4 within 10 minutes, 4 to 5 within 15 minutes, and had returned to control levels by 30 minutes. They contended that in their preparation the damage was analogous to that produced by a chemical burn in that it was produced at contact, and the extent depended upon the surface area involved and the strength of the acid. Fecal Contaminated
Aspirate
Although large numbers of pathogenic microorganisms are not ordinarily found in the stomach and small intestine, intestinal obstruction may permit the presence of such bacteria. Aspiration of intestinal fluid which has been contaminated with fecal organisms may produce a particularly virulent clinical picture. Hamelberg and Bosomworth [ 121 noted a 100% mortality in dogs following the intratracheal administration of fecal-contaminated gastric juice from a patient with low intestinal obstruction. This effect was independent of pH, but could be markedly attenuated by prior boiling of the aspirate.
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They postulated the response was produced by an endotoxin which was destroyed by boiling. Pathology Many authors have described pathological changes in the lungs characteristic of the aspiration of gastric contents. Large particles can obstruct the trachea and major or minor bronchi, and produce varying degrees of atelectasis. Histological changes noted in such lesions are typical of nonspecific atelectasis. Materials of smaller size lodging in the segmental bronchi or bronchioles may produce a foreign body reaction, the severity of which depends upon the differences in chemical composition of the materials. Teabeaut [26] found that injected meat particles were readily disorganized and dispersed by phagocytosis while vegetable fibers could be found up to several weeks. Liquid acid aspirate has been found to provoke an extensive acute inflammatory reaction. Grossly, the lungs appear heavy and wet. Patchy areas of hemorrhage are noted on the lung surfaces, and consolidated areas are interspersed with areas of normal crepitation. Large and small bronchi are severely affected with destruction of the epithelium, hemorrhage, acute inflammation and an out-pouring of proteinrich fluid. The initial parenchymal infiltrations are primarily in the peribronchial distribution In more extensive involvement, the lung parenchyma appears to be almost completely destroyed and the alveolar spaces filled with necrotic debris, hemorrhage, and inflammatory cells. In later stages there may be lung abscess. There is good evidence [12, 261 that early bacterial infection of lung damaged by the aspiration of gastric juice does not occur. However, in both patients and experimental animals who survive significant aspiration beyond a few days, a bacterial pneumonitis is sometimes seen and may progress to lung abscess or empyema. Respiratory and Hemodynamic Alterations Pertinent information regarding the functional disturbances noted in experimental
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dogs following the aspiration of acid solutions comes mainly from the reports of Hamelberg and Bosomworth [ 121, Lawson et al. [ 151, and Awe et al. [ 11. An immediate fall of systemic arterial pressure to shock levels is noted following the introduction of acid into the tracheobronchial tree. This is associated with a brief period of apnea and a transient mild elevation of pulmonary artery pressure. In preparations which are lethal the systemic arterial pressure returns to control levels during the first hour and falls slowly during the next few hours. No definite data are available on the pressure response in animals which survive for several days or longer. The pulmonary artery pressure, following a return to control levels within 30 minutes, tends to fall progressively as does the right atria1 pressure. These observations are not consistent with previous clinical impressions which suggested the development of congestive heart failure. Following aspiration there is an immediate fall of ~0,. The subsequent behavior of this parameter seems to depend upon the magnitude of the injury and the supportive treatment utilized. For example, Lawson et al. [15] noted an immediate fall in ~0, from 80 mm. Hg to 40 mm. Hg, with a gradual increase beginning four hours after injury and slowly improving until control values were again attained at 14 days. The administration of 40?, oxygen during spontaneous ventilation in the hypoxic stage produced only a small increase in pOZ, suggesting the presence of significant right to left shunting at the pulmonary level. Awe and co-workers [ 11, however, produced a greater pulmonary injury through the use of stronger acid and found an immediate, rapid, and profound depression of ~0, which persisted and could only be reversed by the institution of positive-pressure ventilation and oxygen. Changes noted in arterial blood pH and pC0, seem also to be determined by the extent of damage produced. Thus, in the more lethal experimental preparations, a fall in pH, either rapid or gradual, is noted with a mild increase in pCO.,. However, in prepa-
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rations in which chronic survival occurs, a slight increase in pH and decrease in pC0, are noted on the day of aspiration but subsequently there is a return to normal levels. This response is most likely associated with hyperventilation following injury. After aspiration, Hamelberg and Bosomworth [12] placed their animals on a mechanical ventilator with fixed pressure and variable volume and noted a 50% decrease in ventilating volume. Although this response is compatible with either an increase in airway resistance or decrease in lung volume, they reported that clinical signs of bronchospasm were not present in their animals. Lawson et al. [15] measured respiratory rate and minute volume following aspiration. In animals surviving for two weeks the respiratory rate tripled immediately after injury, then slowly declined beginning at four hours until control values were again reached at 14 days. The minute volume initially doubled, then began a slow decrease until control was reached at 4 days. The presence of bloody froth is noted in the trachea of virtually all dogs which die within a few hours after aspiration. The studies of Awe et al. [l] have shown that this is associated with a progressive increase in hematocrit, decrease in plasma volume, and marked increase in weight of the affected lung. Volume replacement temporarily corrected both hemoconcentration and hypotension but did not affect hypoxia, which ultimately caused death. Awe et al. emphasized the role of hypovolemia in early death following aspiration.
TREATMENT The major effort in dealing with aspiration pneumonia should be directed toward prevention. Any patient undergoing general anesthesia within eight hours after eating or drinking should have his stomach emptied with a large-bore nasogastric tube. Patients should be properly premeditated to relieve anxiety and thus decrease gastric acid pro49
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duction and prevent delayed gast.ic emptying. Macintosh [17] and Gilman and Abrams [ll] have devised tubes which provide a mechanical blockade in the esophagus to prevent regurgitation during anesthesia, but these have not gained popularity. Intubation under local anesthesia [29] or “crash induction” using thiopental and muscle relaxant are used in patients in which risk of vomiting is high. Cuffed endotracheal tubes should be used to lessen the risk of aspiration after intubation. Antiemetic drugs, although effective, have side effects that may make their use undesirable. Emetics have also been used preoperatively to insure an empty stomach [27] ; but this also has not gained popularity. If vomiting and aspiration occur despite due precaution, the institution of therapy should be immediate. The treatment of aspiration of particulate matter is well established. Occasionally the patient, if unanesthetized or under light anesthesia, will remedy the situation himself by coughing up the aspirated material and thus relieve his bronchial obstruction. This occurred in 3 of the 5 patients in MendelObviously this should son’s original report. not be counted upon, and immediate endotracheal suction should be instituted to remove the particulate aspirate and any liquid aspirate that might have accompanied it. If this is unsuccessful, bronchoscopy should be undertaken promptly to remove the obstructing aspirate. If the material is lodged in the larynx or trachea, this is a life-saving procedure, and one may have only minutes in which to carry it out. If the obstruction is in one of the main or lobar bronchi, more time is available, but rapid relief lessens the chance of subsequent pulmonary complications such as persistent atelectasis, pneumonia, and lung abscess. The treatment of the patient who has aspirated a significant quantity of gastric fluid of is neither as well establow pH, however, lished nor as effective. In 1952 Teabeaut [26] stressed the importance of continual and repeated efforts to clear the tracheobronchial tree after aspiration. Gardner [lo], in 1958, stressed the importance of bronchoscopy in 50
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all patients, believing it was helpful even if the aspirate did not contain solid material. Bernstein [lo], in 1953, and Scurr [lo], in 1954, both recommended pulmonary lavage with large quantities of saline. However, Bannister et al. [3] in 1961, Lewinski [16] in 1965, and Awe et al. [1] in 1966, have all shown that immediate saline pulmonary lavage, as well as lavage with neutralizing agents such as sodium bicarbonate, are not only ineffective but often actually harmful following aspiration. It has been suggested that the fluid used for lavage forces the acid further down into the bronchioles and alveoli and increases the area of injury. Contrasting data has been reported by Simenstad et al. [24] who, on the basis of experimental work on a small number of dogs, thought immediate pulmonary lavage was helpful. In view of the present information, single 10 ml. injections of saline with prompt removal should be used to clear aspirate and increased bronchial secretions, with large volume lavages avoided. Mendelson [19], in his work in 1946, believed bronchiolar spasm and peribronchiolar exudation and congestion were the main pathological changes and that treatment should be directed toward combating bronchospasm and cardiac embarrassment, Thus, he recommended oxygen, atropine, epinephrine, and aminophylline. If pulmonary edema ensued, rapid intravenous digitalization and rotating tourniquets were instituted, since the pulmonary edema was thought to result from cardiac failure due to pulmonary vascular changes. Subsequent work by Lawson et al. [15] and Awe et al. [ 11, however, has shown that the pulmonary edema associated with aspiration of acid is accompanied by no increase in central venous or pulmonary artery pressure. Thus, cardiac decompensation as a causative factor seems unlikely. In fact, Awe et al. [l] showed that hypovolemia resulted because of fluid loss into the lung, and argued convincingly against rotating tourniquets or phlebotomy in the treatment of aspiration pulmonary edema. Although digitalis might be indicated for a patient with borderline cardiac reserve, it is not likely to be effective in most cases
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of pulmonary edema associated with aspiration. Oxygen administration has been recommended by all interested in the problem of aspiration pneumonia. The cyanosis, however, often remains refractory to oxygen therapy-probably because it results from blood shunted through nonventilated lung. Nevertheless, it usually results in some clinical improvement and should always be administered. Bosomworth and Hamelberg [5] and Awe et al. [ 11, among others, have recommended positive-pressure respiration to improve the clinical status. Awe et al. [l] showed experimentally a striking improvement in the blood gases after instituting positive-pressure respiration, although mortality was not affected. In the more severe cases, tracheostomy is not only of value in administering positive-pressure respiration but also in keeping the tracheobronchial tree cleared of secretions. Following Dougherty and Schneebeli’s [ 81 article in 1955 on the anti-inflammatory effects of steroids, these agents became popular in the treatment of aspiration pneumonia. In 1955 Hausman and Lunt [13] reported two patients and Marshall and Gordon [ 181, in 1958, reported eight patients treated with steroids; both studies indicated clinical improvement from the use of these drugs. Subsequently, other investigators [3, 5, 151 have confirmed these clinical impressions experimentally. Lewinski [ 161, in 1965, showed experimentally that hydrocortisone injected directly into the tracheobronchial tree was extremely effective in protecting against the development of the harmful pulmonary inflammatory reaction following aspiration. In 1966 Awe et al. [l] were unable to demonstrate the effectiveness of steroid therapy using a very lethal experimental model. The treatment of shock associated with aspiration has provoked a controversy. Mendelson [19] and Bannister [2], both important contributors in the field, believed that cardiac failure was responsible. However, Lawson et cd. [15] and Awe et al. [l] have not found acute cardiac decompensation in experimental preparations, and Awe et al. [ 11
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have shown that hypovolemia may occur. Therefore, any persistent shock associated with aspiration is probably best treated with volume expanders. Mendelson [19] thought that the process was primarily irritative rather than infectious but believed that antibiotics might prevent the sequelae of secondary infection. This advice has been repeated by others [3, 51, although it has been shown experimentally that in the acute phase, antibiotic therapy does not affect the picture produced by aspiration. Most authors recommend the use of antibiotics to avoid secondary infection. The other accepted supportive therapeutic adjuncts in respiratory problems such as expectorants and aerosols are probably also of benefit. The role of bronchospasm remains a controversy, but most writers favor the use of a bronchodilator such as aminophylline. The results of the above regimen in severe cases of aspiration pneumonia have been poor, however, with mortality figures ranging from 70c/r to 80:x.
COMMENTS A high level of awareness of the everpresent risk of aspiration, mutually shared by surgeon and anesthesiologist, is necessary to reduce the incidence of this complication to the absolute minimum. When aspiration unexpectedly or unavoidably occurs, however, it should be recognized that its treatment is based upon empiricism and upon experimental observations in models which may not accurately simulate the clinical situation. Very few clinical data, except for gross observations, are available with which to reconstruct the pathophysiology or evaluate the treatment in man. Fortunately, the means for making pertinent physiological observations of the aspiration syndrome in man are now available in most hospitals. Their timely employment will not only increase understanding of the disorder but should also prove to be of significant benefit in planning therapy. For example, since the degree of pulmonary injury
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seems to be pH-dependent, measuring the pH of the liquid that is returned via endotracheal suction in the immediate postaspiration period could prove to have prognostic value. The recovery and analysis of aspirated intestinal obstruction fluid and correlation with the subsequent clinical course may permit the definition of an entirely different response from that associated with the injury produced by acid fluids and thus suggest modification of standard therapy. If the condition of the patient deteriorates immediately following aspiration, or if substantial amounts of fluid of pH 2 or less are recovered from the trachea, marked respiratory and hemodynamic alterations are probably imminent. In this event, the prompt insertion of a small plastic cannula in a peripheral artery will provide a means for precise and constant blood pressure recording, utilizing an appropriate monitoring system, and also give access to arterial blood so that serial ~02, pH, and pCOz determinations may be performed. A falling ~0, as a premonitory sign of impending anoxemia strongly suggests institution of tracheostomy and positive-pressure ventilation with oxygen, In a disease in which exudation and transudation through a large pulmonary surface appear to play such an important role in the physiological abnormality, ‘this form of treatment should help to keep pulmonary units unobstructed and aerating, thus improving oxygenation and reducing the abnormal shunting of blood. Serial measurement of central venous pressure and blood volume permits a clear distinction to be made between the development of congestive heart failure and the hypovolemia resulting from pulmonary plasma losses. This differentiation is critical if developing shock is to be combated effectively. Although pulmonary lavage in the immediate postaspiration period has been shown experimentally by most investigators to increase the severity of pulmonary injury, the use of this procedure later in the course of the disease has not been fully evaluated. Pulmonary lavage performed after the period of 52
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inflammatory exudation might help in clearing involved bronchi and bronchioles of obstructing debris. It has been suggested that deaths due to aspiration pneumonitis result from anoxia which is enhanced by the shunting of blood through pulmonary units being perfused but not ventilated. In severe cases, the pulmonary injury may be irreversible and pneumonectomy might be considered if only one lung were affected. Since the mortality rate in severe cases approaches loo%, such a radical treatment might be reasonable. In order to justify such an approach and properly select candidates, more experimental and clinical data are required.
SUMMARY The history, clinical features, pathophysiology, and treatment of aspiration pneumonia have been briefly reviewed. Emphasis has been placed on the discussion of the aspiration of liquid gastric contents of low pH. Comments have been made on the efficacy of present therapy and areas of future clinical and experimental investigation explored.
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Awe, W. C., Fletcher, W. S., and Jacob, S. W. The pathophysiology of aspiration pneumonitis. Surgery 60:232, 1966. Bannister, W. K., and Sattilaro, A. J. Vomiting and aspiration during anesthesia. Anesthesiology 23:251, 1962. Bannister, W. K., Sattilaro, A. J., and Otis, R. D. Therapeutic aspects of aspiration pneumonitis. Anesthesiology 22~440, 1961. Berson, W., and Adriani, J. “Silent” regurgitation and aspiration during anesthesia. Anesthesiology 15:644, 1954. Bosomworth, P. P., and Hamelberg, W. Etiologic and therapeutic aspects of aspiration pneumonitis. Surg. Forum 13:158, 1962. Culver, G. A., Makel, H. P., and Beecher, H. K. Frequency of aspiration of gastric contents by lungs during anesthesia and surgery. Ann. Surg. 133:289, 1951. Dines, D. E., Baker, W. G., and Scantland, W. A. Aspiration pneumonitis: Mendelson’s syndrome. I.A.M.A. 176:229, 1961.
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Dougherty, T. F., and Schneebeli, G. L. Use of steroids as anti-inflammatory agents. Ann. N.Y. Acad. Sci. 61:328, 1955. Edwards, G., Morton, H. J. V., Pask, E. A., and Wylie, W. D. Deaths associated with anesthesia: Report of 1,000 cases. Anuesthesia 11: 194, 1956. Gardner, A. M. N. Aspiration of food and vomit. Qumt. J. Med. 271227, 1958. Gilman, S., and Abrams, A. L. Prevention of aspiration of gastric contents during general anesthesia. New Eng. .l. Med. 255:508, 1956. Hamelberg, W., and Bosomworth, P. P. Aspiration pneumonitis: Experimental and clinical observations. Anesth. An&g. (Cleveland) 43:669, 1964. Hausman, W., and Lunt. R. L. Problem of treatment of peptic aspiration pneumonia following obstetric anesthesia ( Mendelson’s syndrome). .I. Obstet. Gynuec. Brit. Emp. 62:509, 1955. Hippocrates. Medical Works of Hippocrates, trans. J. Chadwick and W. N. Mann. Springfield: Charles C Thomas, 1950, p. 250. Lawson, D. W., Defalco, A. J., Phelps, J. A., Bradley, B. E., and McClenathan, J. E. Corticostrroids as treatment for aspiration of gastric contents: An experimental study. Surgery 59:845, 1966. Lewinski, A. Evaluation of methods employed in the treatment of the chemical pneumonitis of aspiration. Anesthesiology 26: 37, 1965. Macintosh, R. R. Cuffed stomach tube. Brit. A4ed. J. 2:545, 1951. Xlarshall, B. M., and Gordon, R. A. Vomiting,
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regurgitation, and aspiration in anesthesia. Canad. Anuesth. Sot. J. 5:438, 1958. Mendelson, C. L. The aspiration of stomach contents into the lungs during obstetric anesthesia. Amer. J. Obstet. Gynec. 52:191, 1946. Merrill, R. B., and Hingson, R. A. Study of incidence of maternal mortality from aspiration of vomitus during anesthesia occurring in major obstetric hospitals in United States. Anesth. Analg. (Cleveland) 30:121, 1951. O’Mullane, E. J. Vomiting and regurgitation during anesthesia. Lancet 1: 1209, 1954. Paris, J. A., and Fonblanque, J. S. Ivf. Medical Jurisprudence, Vol. II, London: 1823. P. 57. Robson, J. G., and Welt, P. Regurgitation in anesthesia: Report on some exploratory work with animals. Canad. Anuesth. Sot. J. 6:4, 1959. Simenstad, J. O., Galway, C. R., and Mac Lean, L. D. Tracheobronchial lavage for treatment of aspiration and atelectasis. Surg. Forum 13: 155, 1962. Simpson, J. Y. The alleged care of death from chloroform. Lancet 1: 175, 1848. Teabeaut, J. R. Aspiration of gastric contents: Experimental study. Amer. J. Path. 28:51, 1952. White, R. T. Apomorphine as emetic prior to obstetric anesthesia, prevention of inhaled vomitus. Obstet. Gynec. 14:111, 1959. Winternitz, M. C., Smith, G. H., and McNamara, F. P. Effect of intrabronchial insufflation of acid. J. Exp. Med. 32:199, 1920. Wycoff. C. C. Aspiration during induction of anesthesia. Anesth. A&g. (Cleveland) 38:5, i939.
53
ASPIRATION A Clinical JOHN
L.
CAMERON,
PNEUMONIA and Experimental
M.D., GEORGE
RICHARD D.
CLINICALLY significant aspiration of gastric contents during anesthesia is not frequent, but when it occurs it is a catastrophic event carrying a high mortality. The potential risk of aspiration, however, is great and only the recognition of this risk keeps its incidence low. Its occurrence is highest among obstetrical patients and among general surgical patients who undergo surgery for trauma or acute abdominal crises, in which adequate preanesthetic preparation is not always possible. In a large series of maternal deaths during childbirth, approximately 2% were due to aspiration [20]. Of all general anesthetic deaths that occur, those due to aspiration account for at least 11% [9]. By 1962 there were 700 deaths recorded in the medical literature due to aspiration pneumonia [2], and one might suppose that the majority of aspiration deaths are not deemed reportable. Because of the gravity of this complication of general surgical anesthesia, features of its clinical course, pathogenesis, and treatment will be reviewed, and comments made on need for further clinical and experimental observations. From the Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, Md. Supported by National Institutes of Health Grant 5 TO1 GM 01541. Submitted for publication Oct. 6, 1966. 44
Review P.
ZUIDEMA,
ANDERSON,
M.D.,
AND
M.D.
HISTORICAL
ASPECTS
The first death attributed to aspiration allegedly occurred in 475 B.C. when the Greek poet Anacreon died from the inhalation of a grape seed [22]. Hippocrates realized the dangers of aspiration and in 400 B.C. warned that “For drinking to provoke a slight cough, or for swallowing to be forced, is bad” [ 141. The first published death under an anesthetic occurred under chloroform in January, 1848, fifteen months after the introduction of general anesthesia. The death, just two months after the introduction of chloroform, was attributed by at least one observer to aspiration of brandy being used for resuscitation. According to Sir James Simpson “the girl died, then, as I conceive, . . . . choked or asphyxiated by the very means intended to give her life” [25]. Of the first 51 cases of death under chloroform anesthesia reported in 1861, at least 2 resulted from aspiration
[lOI. Experimental investigation of aspiration pneumonia, although sparse, had an early beginning. In 1781 John Hunter stated in a court of law, “It is in the mouth of everybody that a little brandy will kill a cat. I have made the experiment; in all those cases where it kills the cat, it kills the cat by getting into her lungs, not her stomach’ [lo]. Although knowledge of aspiration dates from
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antiquity, and experimental investigation from the 1700’s it remained for Mendelson, in 1946, to separate adequately and to describe the major clinical and pathological features of aspiration [ 191. He described two clinical situations observed in patients who aspirated under general anesthesia at the New York Lying-In Hospital. The first was associated with the aspiration of solid material; the second, which Mendelson described as an “asthmatic-like” reaction, with the aspiration of liquid material. He showed experimentally that this second clinical picture was caused by the hydrochloric acid present in gastric aspirate. Because of this pioneering report, aspiration pneumonia has been referred to as Mendelson’s syndrome.
CLINICAL
FEATURES
Studies by Culver et al. [6] and Berson and Adriani [4] both suggest that aspiration will occur in a small percentage of anesthetized general surgical patients even under the most ideal circumstances. It is essential, therefore, to be able to recognize this event immediately. In some instances the signs of imminent vomiting are present-irregular respiration, breath-holding, increased salivation, and swallowing. Usually, however, the anesthetist’s first warning is the appearance of gastric contents in the pharynx or mouth. At the other extreme, aspiration may go undetected, and postoperative cyanosis may be the presenting sign. The clinical picture produced by aspiration of gastric contents depends on the nature of the material aspirated. When solid particulate matter is aspirated, the presentation is often acute and catastrophic. If the aspirated material is of sufficient size, acute respiratory obstruction, asphyxia, and death may rapidly ensue. If the particulate matter lacks sufficient mass, or is not so located as to cause immediate asphyxiation, then dyspnea, cyanosis, and tachycardia occur. Chest x-ray will reveal atelectasis in the area supplied by the involved bronchus or
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bronchi, and mediastinal shift toward the involved area will be present. The aspiration of liquid contents during anesthesia is more frequent [19]. Again, the clinical picture that ensues depends upon the volume and nature of the aspiration. In Berson and Adriani’s [4] study of 926 general surgical patients, none of the 66 patients who were proven to have occult aspiration of small amounts displayed acute clinical signs or developed aspiration pneumonia. However, if sufficient volume of low pH gastric juice is aspirated, a distinct clinical picture evolves. The actual aspiration may be unnoticed. The onset of symptoms is not always acute, as in the aspiration of solid material. Dyspnea, cyanosis, and tachycardia occur, but occasionally are not of a degree to cause concern until several hours after operation. Some observers have described the immediate appearance of numerous wheezes, rales, and rhonchi over the involved areas, and likened the event to an attack of asthma, while other investigators describe few early auscultatory changes. Dines [7] reports that as long as five hours may elapse between the time of aspiration and the onset of auscultatory findings. The most frequent clinical picture, however, is one of dyspnea, cyanosis, and tachycardia in the immediate postaspiration period. The cyanosis is refractory to oxygen therapy, and mild hypotension may be present for a short time. Patients may die during this acute phase with pulmonary edema but generally the hypotension abates and the patient remains stable for 24 to 36 hours. Except for persistent cyanosis and mild respiratory distress, the clinical picture is not alarming. Subsequently the patient either improves or progressively deteriorates and dies from respiratory causes, with hypotension only a late event. Chest x-rays reveal patchy infiltrates which are indistinguishable from bronchopneumonia. The right lower lobe is most often involved because the more nearly linear pathway of the trachea and the right lower lobe bronchus offers the least resistance to the aspirated material. The right upper lobe is 45
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also frequently affected, probably because the patient’s supine or Trendelenburg position permits drainage of the aspirate into the upper lobe. When the aspiration is massive, both lungs can be involved radiologically, and the clinical picture is one of pulmonary edema from the massive pulmonary injury, with large volumes of bloody froth issuing from the patient’s mouth or endotracheal tube. It is in these patients that early mortality can occur. In patients surviving for hours or days, the extent of the radiographic abnormality does not necessarily parallel the clinical course. The role of infection in aspiration pneumonia is unclear. Many patients spike an early fever, which is probably unrelated to sepsis. After a period of days some patients do develop an infectious component and lung abscesses have been reported as a late sequela [ 191. In patients with intestinal obstruction and high bacterial contamination of gastric contents, sepsis may be an acute similar to gram-negative factor. A picture sepsis has been demonstrated experimentally in this situation [5]. The mortality rate from aspiration is difficult to assess. In Mendelson’s original report of 66 cases of aspiration two deaths occurred [19]. The mortality obviously depends on the volume and character of the material aspirated. When a significant volume of low pH material is aspirated, so that aspiration pneumonia follows involving the entire right lung or is present bilaterally, the mortality is great. Awe [l] reported 81 patients who had aspirated liquid gastric contents, with a mortality of 702.
PATHOPHYSIOLOGY Predisposing
Factors
The stage for pulmonary aspiration is set whenever liquid or particulate material enters the pharynx and the normal protective mechanisms of glottic closure are attenuated or absent. These mechanisms may be impaired in various specific neuromuscular disorders as well as in general debilitation or 46
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intoxication. However, it is primarily their ablation by anesthesia that is significant in the surgical patient. The primary source of aspirated material is the incompletely emptied stomach. In patients who have not or cannot be suitably prepared preoperatively, the vomiting or regurgitating of substantial volumes may oca massive pneumonitis. cur and produce Thus, patients in particular danger include those who have recently ingested food or drink prior to anesthesia or those in whom a large gastric volume results from ileus, intestinal obstruction, hemorrhage, gastric dilatation, or excessive gastric secretion. Scarring and inflammation about the pylorus produced by peptic ulcer disease may severely impair gastric emptying and lead to the retention of large volumes. Pain and fear are recognized as emotions which particularly influence gastric motility and reduce emptying time of the stomach. Virtually all preoperative patients are adversely influenced in this respect. Vomiting
and Regurgitation
The act of vomiting is a basic protective reflex which can be initiated by various stimuli. Vomiting during the excitement stage of inhalation anesthesia is a well-recognized hazard. Ordinarily, secure glottic the event in the conclosure accompanies scious state. The bending of the trunk, depression of the head, inversion of the glottis, and opening of the mouth all aid vigorous muscular contraction in expelling material from the pharynx. During inhalation anesthesia, SUpine position, extension of the neck, presence of a face mask, and depressed level of consciousness impede the clearance of material from the pharynx and promote its entry into the tracheobronchial system. The current practice in anesthesiology of combining an ultra-short-acting barbiturate with a muscle relaxant for the induction of anesthesia has virtually eliminated the excitement stage seen formerly with the use of the classical inhalation agents. While the incidence of active vomiting during anesthetic induction has been concomitantly decreased,
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regurgitation of stomach contents may occur and is equally hazardous. The mechanisms of regurgitation are not as well understood as those of vomiting. Culver et al. [6] and Berson and Adriani [4] have shown that regurgitation leading to occult aspiration occurs frequently during otherwise uneventful general anesthesia. These investigators placed dyes in the stomachs of preoperative patients and observed their sulbsequent appearance in the tracheobronchial tree in 16% and 7% of cases, respectively. Regurgitation is a more passive phenomenon than vomiting and seems to depend upon two features: the pressure gradients between the stomach, esophagus, and pharynx, and incompetence of the various “valves” that separate these structures. The presence of a valve-like mechanism at the cardioesophageal junction is now widely accepted, although there is still considerable conjecture about the relative importance of various anatomical structures to the normal functioning of this mechanism [2]. Opening of this valve during anesthetic induction can allow flow of gastric contents into the esophagus if a suitable pressure gradient exists. O’Mullane [21] observed the opening of the gastroesophageal junction in association with partial airway obstruction during general anesthesia. In addition, he noted that the esophagus of an anesthetized patient can retain a large volume of liquid which immediately enters the pharynx when the cricopharyngeal sphincter is paralyzed by administration of a muscle-relaxing drug. Robson and Welt [23] found that gastric dilatation markedly reduced the pressure necessary to produce reflex from the stomach into the esophagus. Elevated intragastric pressures may also be brought about by the gravid uterus or other intra-abdominal tumors. Two particularly hazardous clinical situations which produce significant regurgitation deserve special emphasis. In the first instance, anesthesia is induced by the intravenous administration of an ultra-fast-acting barbiturate, and the lungs are then ventilated by positive pressure through a tight-fitting face mask. If partial airway obstruction occurs and is uncorrected while ventilation contin-
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ues, large amounts of gas are forced into the stomach. The administration of the muscle relaxant, preparatory to tracheal intubation, will then cause relaxation of the gastroesophageal and cricopharyngeal valves. The gastric content, impelled by the elevated intragastric pressure, immediately floods the esophagus, inundates the pharynx, and readily enters the tracheobronchial tree through the relaxed glottis. The second hazard results from the apparently universal and irresistible impulse of the unwary to palpate the abdomen deeply just as the muscle-relaxing drug is being adof this ministered. External compression nature can produce surprising amounts of regurgitation, even from a fairly well prepared stomach. Character
of the Aspirate
Given a sufficient volume, the character of the aspirated material will generally determine the type of injury produced and thus the clinical course. Mendelson [19] observed different responses to the aspiration of solid and liquid material. Large particulate solids tend to occlude major bronchi producing lobar atelectasis or massive collapse of lung with attendant cyanosis, dyspnea, tachycardia, tachypnea, mediastinal shift, and consolidation. There is great variability, however, in the response to aspiration of liquids, depending upon their composition. Acidity Although Winternitz [28], in 1920, originally described pathological changes in the lungs of rabbits following the intratracheal introduction of hydrochloric acid, Teabeaut [26] was the first to emphasize the importance of the hydrogen ion concentration. He showed that when the pH exceeded 2.4, the response elicited simulated that following injection of water. As the pH of the aspirate WAS lowered, the tissue reaction increased progressively until at pH 1.5 a maximal response was obtained which could not be enhanced by more concentrated acid. When filtered gastric juice of known pH was compared with hydrochloric acid of similar pH, 47
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there was no significant difference in tissue response, suggesting that the influence of the peptic activity of gastric juice upon the pathological process was negligible. Subsequently, many investigators [l, 3, 12, 15, 161 have confirmed the observation that liquid with pH less than 2.5, given in suitable amounts, produces both clinical and pathological signs of aspiration pneumonitis. In addition, the data suggest that aspiration of fluid at pH 1.5 or less is fatal within 24 hours in most experimental dogs. This response is probably independent of the volume of liquid aspirated at dose levels greater than 2 ml. per kilogram of weight. Hamelberg and Bosomworth [12] studied the rate of distribution of pH 1.75 gastric juice instilled into the trachea of excised, ventilated, and perfused canine lungs, and noted that when dye was added to the aspirate it appeared on the surface of the lungs in 12 to 18 seconds, and within 3 minutes patchy areas of atelectasis were present. In a study of the rapidity of bronchial neutralization of aspirated 0.1 N HCl in dogs, Awe and coworkers [l] found that bronchial pH reached a level of 2 to 4 within 10 minutes, 4 to 5 within 15 minutes, and had returned to control levels by 30 minutes. They contended that in their preparation the damage was analogous to that produced by a chemical burn in that it was produced at contact, and the extent depended upon the surface area involved and the strength of the acid. Fecal Contaminated
Aspirate
Although large numbers of pathogenic microorganisms are not ordinarily found in the stomach and small intestine, intestinal obstruction may permit the presence of such bacteria. Aspiration of intestinal fluid which has been contaminated with fecal organisms may produce a particularly virulent clinical picture. Hamelberg and Bosomworth [ 121 noted a 100% mortality in dogs following the intratracheal administration of fecal-contaminated gastric juice from a patient with low intestinal obstruction. This effect was independent of pH, but could be markedly attenuated by prior boiling of the aspirate.
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They postulated the response was produced by an endotoxin which was destroyed by boiling. Pathology Many authors have described pathological changes in the lungs characteristic of the aspiration of gastric contents. Large particles can obstruct the trachea and major or minor bronchi, and produce varying degrees of atelectasis. Histological changes noted in such lesions are typical of nonspecific atelectasis. Materials of smaller size lodging in the segmental bronchi or bronchioles may produce a foreign body reaction, the severity of which depends upon the differences in chemical composition of the materials. Teabeaut [26] found that injected meat particles were readily disorganized and dispersed by phagocytosis while vegetable fibers could be found up to several weeks. Liquid acid aspirate has been found to provoke an extensive acute inflammatory reaction. Grossly, the lungs appear heavy and wet. Patchy areas of hemorrhage are noted on the lung surfaces, and consolidated areas are interspersed with areas of normal crepitation. Large and small bronchi are severely affected with destruction of the epithelium, hemorrhage, acute inflammation and an out-pouring of proteinrich fluid. The initial parenchymal infiltrations are primarily in the peribronchial distribution In more extensive involvement, the lung parenchyma appears to be almost completely destroyed and the alveolar spaces filled with necrotic debris, hemorrhage, and inflammatory cells. In later stages there may be lung abscess. There is good evidence [12, 261 that early bacterial infection of lung damaged by the aspiration of gastric juice does not occur. However, in both patients and experimental animals who survive significant aspiration beyond a few days, a bacterial pneumonitis is sometimes seen and may progress to lung abscess or empyema. Respiratory and Hemodynamic Alterations Pertinent information regarding the functional disturbances noted in experimental
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dogs following the aspiration of acid solutions comes mainly from the reports of Hamelberg and Bosomworth [ 121, Lawson et al. [ 151, and Awe et al. [ 11. An immediate fall of systemic arterial pressure to shock levels is noted following the introduction of acid into the tracheobronchial tree. This is associated with a brief period of apnea and a transient mild elevation of pulmonary artery pressure. In preparations which are lethal the systemic arterial pressure returns to control levels during the first hour and falls slowly during the next few hours. No definite data are available on the pressure response in animals which survive for several days or longer. The pulmonary artery pressure, following a return to control levels within 30 minutes, tends to fall progressively as does the right atria1 pressure. These observations are not consistent with previous clinical impressions which suggested the development of congestive heart failure. Following aspiration there is an immediate fall of ~0,. The subsequent behavior of this parameter seems to depend upon the magnitude of the injury and the supportive treatment utilized. For example, Lawson et al. [15] noted an immediate fall in ~0, from 80 mm. Hg to 40 mm. Hg, with a gradual increase beginning four hours after injury and slowly improving until control values were again attained at 14 days. The administration of 40?, oxygen during spontaneous ventilation in the hypoxic stage produced only a small increase in pOZ, suggesting the presence of significant right to left shunting at the pulmonary level. Awe and co-workers [ 11, however, produced a greater pulmonary injury through the use of stronger acid and found an immediate, rapid, and profound depression of ~0, which persisted and could only be reversed by the institution of positive-pressure ventilation and oxygen. Changes noted in arterial blood pH and pC0, seem also to be determined by the extent of damage produced. Thus, in the more lethal experimental preparations, a fall in pH, either rapid or gradual, is noted with a mild increase in pCO.,. However, in prepa-
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rations in which chronic survival occurs, a slight increase in pH and decrease in pC0, are noted on the day of aspiration but subsequently there is a return to normal levels. This response is most likely associated with hyperventilation following injury. After aspiration, Hamelberg and Bosomworth [12] placed their animals on a mechanical ventilator with fixed pressure and variable volume and noted a 50% decrease in ventilating volume. Although this response is compatible with either an increase in airway resistance or decrease in lung volume, they reported that clinical signs of bronchospasm were not present in their animals. Lawson et al. [15] measured respiratory rate and minute volume following aspiration. In animals surviving for two weeks the respiratory rate tripled immediately after injury, then slowly declined beginning at four hours until control values were again reached at 14 days. The minute volume initially doubled, then began a slow decrease until control was reached at 4 days. The presence of bloody froth is noted in the trachea of virtually all dogs which die within a few hours after aspiration. The studies of Awe et al. [l] have shown that this is associated with a progressive increase in hematocrit, decrease in plasma volume, and marked increase in weight of the affected lung. Volume replacement temporarily corrected both hemoconcentration and hypotension but did not affect hypoxia, which ultimately caused death. Awe et al. emphasized the role of hypovolemia in early death following aspiration.
TREATMENT The major effort in dealing with aspiration pneumonia should be directed toward prevention. Any patient undergoing general anesthesia within eight hours after eating or drinking should have his stomach emptied with a large-bore nasogastric tube. Patients should be properly premeditated to relieve anxiety and thus decrease gastric acid pro49
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duction and prevent delayed gast.ic emptying. Macintosh [17] and Gilman and Abrams [ll] have devised tubes which provide a mechanical blockade in the esophagus to prevent regurgitation during anesthesia, but these have not gained popularity. Intubation under local anesthesia [29] or “crash induction” using thiopental and muscle relaxant are used in patients in which risk of vomiting is high. Cuffed endotracheal tubes should be used to lessen the risk of aspiration after intubation. Antiemetic drugs, although effective, have side effects that may make their use undesirable. Emetics have also been used preoperatively to insure an empty stomach [27] ; but this also has not gained popularity. If vomiting and aspiration occur despite due precaution, the institution of therapy should be immediate. The treatment of aspiration of particulate matter is well established. Occasionally the patient, if unanesthetized or under light anesthesia, will remedy the situation himself by coughing up the aspirated material and thus relieve his bronchial obstruction. This occurred in 3 of the 5 patients in MendelObviously this should son’s original report. not be counted upon, and immediate endotracheal suction should be instituted to remove the particulate aspirate and any liquid aspirate that might have accompanied it. If this is unsuccessful, bronchoscopy should be undertaken promptly to remove the obstructing aspirate. If the material is lodged in the larynx or trachea, this is a life-saving procedure, and one may have only minutes in which to carry it out. If the obstruction is in one of the main or lobar bronchi, more time is available, but rapid relief lessens the chance of subsequent pulmonary complications such as persistent atelectasis, pneumonia, and lung abscess. The treatment of the patient who has aspirated a significant quantity of gastric fluid of is neither as well establow pH, however, lished nor as effective. In 1952 Teabeaut [26] stressed the importance of continual and repeated efforts to clear the tracheobronchial tree after aspiration. Gardner [lo], in 1958, stressed the importance of bronchoscopy in 50
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all patients, believing it was helpful even if the aspirate did not contain solid material. Bernstein [lo], in 1953, and Scurr [lo], in 1954, both recommended pulmonary lavage with large quantities of saline. However, Bannister et al. [3] in 1961, Lewinski [16] in 1965, and Awe et al. [1] in 1966, have all shown that immediate saline pulmonary lavage, as well as lavage with neutralizing agents such as sodium bicarbonate, are not only ineffective but often actually harmful following aspiration. It has been suggested that the fluid used for lavage forces the acid further down into the bronchioles and alveoli and increases the area of injury. Contrasting data has been reported by Simenstad et al. [24] who, on the basis of experimental work on a small number of dogs, thought immediate pulmonary lavage was helpful. In view of the present information, single 10 ml. injections of saline with prompt removal should be used to clear aspirate and increased bronchial secretions, with large volume lavages avoided. Mendelson [19], in his work in 1946, believed bronchiolar spasm and peribronchiolar exudation and congestion were the main pathological changes and that treatment should be directed toward combating bronchospasm and cardiac embarrassment, Thus, he recommended oxygen, atropine, epinephrine, and aminophylline. If pulmonary edema ensued, rapid intravenous digitalization and rotating tourniquets were instituted, since the pulmonary edema was thought to result from cardiac failure due to pulmonary vascular changes. Subsequent work by Lawson et al. [15] and Awe et al. [ 11, however, has shown that the pulmonary edema associated with aspiration of acid is accompanied by no increase in central venous or pulmonary artery pressure. Thus, cardiac decompensation as a causative factor seems unlikely. In fact, Awe et al. [l] showed that hypovolemia resulted because of fluid loss into the lung, and argued convincingly against rotating tourniquets or phlebotomy in the treatment of aspiration pulmonary edema. Although digitalis might be indicated for a patient with borderline cardiac reserve, it is not likely to be effective in most cases
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of pulmonary edema associated with aspiration. Oxygen administration has been recommended by all interested in the problem of aspiration pneumonia. The cyanosis, however, often remains refractory to oxygen therapy-probably because it results from blood shunted through nonventilated lung. Nevertheless, it usually results in some clinical improvement and should always be administered. Bosomworth and Hamelberg [5] and Awe et al. [ 11, among others, have recommended positive-pressure respiration to improve the clinical status. Awe et al. [l] showed experimentally a striking improvement in the blood gases after instituting positive-pressure respiration, although mortality was not affected. In the more severe cases, tracheostomy is not only of value in administering positive-pressure respiration but also in keeping the tracheobronchial tree cleared of secretions. Following Dougherty and Schneebeli’s [ 81 article in 1955 on the anti-inflammatory effects of steroids, these agents became popular in the treatment of aspiration pneumonia. In 1955 Hausman and Lunt [13] reported two patients and Marshall and Gordon [ 181, in 1958, reported eight patients treated with steroids; both studies indicated clinical improvement from the use of these drugs. Subsequently, other investigators [3, 5, 151 have confirmed these clinical impressions experimentally. Lewinski [ 161, in 1965, showed experimentally that hydrocortisone injected directly into the tracheobronchial tree was extremely effective in protecting against the development of the harmful pulmonary inflammatory reaction following aspiration. In 1966 Awe et al. [l] were unable to demonstrate the effectiveness of steroid therapy using a very lethal experimental model. The treatment of shock associated with aspiration has provoked a controversy. Mendelson [19] and Bannister [2], both important contributors in the field, believed that cardiac failure was responsible. However, Lawson et cd. [15] and Awe et al. [l] have not found acute cardiac decompensation in experimental preparations, and Awe et al. [ 11
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have shown that hypovolemia may occur. Therefore, any persistent shock associated with aspiration is probably best treated with volume expanders. Mendelson [19] thought that the process was primarily irritative rather than infectious but believed that antibiotics might prevent the sequelae of secondary infection. This advice has been repeated by others [3, 51, although it has been shown experimentally that in the acute phase, antibiotic therapy does not affect the picture produced by aspiration. Most authors recommend the use of antibiotics to avoid secondary infection. The other accepted supportive therapeutic adjuncts in respiratory problems such as expectorants and aerosols are probably also of benefit. The role of bronchospasm remains a controversy, but most writers favor the use of a bronchodilator such as aminophylline. The results of the above regimen in severe cases of aspiration pneumonia have been poor, however, with mortality figures ranging from 70c/r to 80:x.
COMMENTS A high level of awareness of the everpresent risk of aspiration, mutually shared by surgeon and anesthesiologist, is necessary to reduce the incidence of this complication to the absolute minimum. When aspiration unexpectedly or unavoidably occurs, however, it should be recognized that its treatment is based upon empiricism and upon experimental observations in models which may not accurately simulate the clinical situation. Very few clinical data, except for gross observations, are available with which to reconstruct the pathophysiology or evaluate the treatment in man. Fortunately, the means for making pertinent physiological observations of the aspiration syndrome in man are now available in most hospitals. Their timely employment will not only increase understanding of the disorder but should also prove to be of significant benefit in planning therapy. For example, since the degree of pulmonary injury
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seems to be pH-dependent, measuring the pH of the liquid that is returned via endotracheal suction in the immediate postaspiration period could prove to have prognostic value. The recovery and analysis of aspirated intestinal obstruction fluid and correlation with the subsequent clinical course may permit the definition of an entirely different response from that associated with the injury produced by acid fluids and thus suggest modification of standard therapy. If the condition of the patient deteriorates immediately following aspiration, or if substantial amounts of fluid of pH 2 or less are recovered from the trachea, marked respiratory and hemodynamic alterations are probably imminent. In this event, the prompt insertion of a small plastic cannula in a peripheral artery will provide a means for precise and constant blood pressure recording, utilizing an appropriate monitoring system, and also give access to arterial blood so that serial ~02, pH, and pCOz determinations may be performed. A falling ~0, as a premonitory sign of impending anoxemia strongly suggests institution of tracheostomy and positive-pressure ventilation with oxygen, In a disease in which exudation and transudation through a large pulmonary surface appear to play such an important role in the physiological abnormality, ‘this form of treatment should help to keep pulmonary units unobstructed and aerating, thus improving oxygenation and reducing the abnormal shunting of blood. Serial measurement of central venous pressure and blood volume permits a clear distinction to be made between the development of congestive heart failure and the hypovolemia resulting from pulmonary plasma losses. This differentiation is critical if developing shock is to be combated effectively. Although pulmonary lavage in the immediate postaspiration period has been shown experimentally by most investigators to increase the severity of pulmonary injury, the use of this procedure later in the course of the disease has not been fully evaluated. Pulmonary lavage performed after the period of 52
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inflammatory exudation might help in clearing involved bronchi and bronchioles of obstructing debris. It has been suggested that deaths due to aspiration pneumonitis result from anoxia which is enhanced by the shunting of blood through pulmonary units being perfused but not ventilated. In severe cases, the pulmonary injury may be irreversible and pneumonectomy might be considered if only one lung were affected. Since the mortality rate in severe cases approaches loo%, such a radical treatment might be reasonable. In order to justify such an approach and properly select candidates, more experimental and clinical data are required.
SUMMARY The history, clinical features, pathophysiology, and treatment of aspiration pneumonia have been briefly reviewed. Emphasis has been placed on the discussion of the aspiration of liquid gastric contents of low pH. Comments have been made on the efficacy of present therapy and areas of future clinical and experimental investigation explored.
REFERENCES 1. 2. 3.
4.
5.
6.
7.
Awe, W. C., Fletcher, W. S., and Jacob, S. W. The pathophysiology of aspiration pneumonitis. Surgery 60:232, 1966. Bannister, W. K., and Sattilaro, A. J. Vomiting and aspiration during anesthesia. Anesthesiology 23:251, 1962. Bannister, W. K., Sattilaro, A. J., and Otis, R. D. Therapeutic aspects of aspiration pneumonitis. Anesthesiology 22~440, 1961. Berson, W., and Adriani, J. “Silent” regurgitation and aspiration during anesthesia. Anesthesiology 15:644, 1954. Bosomworth, P. P., and Hamelberg, W. Etiologic and therapeutic aspects of aspiration pneumonitis. Surg. Forum 13:158, 1962. Culver, G. A., Makel, H. P., and Beecher, H. K. Frequency of aspiration of gastric contents by lungs during anesthesia and surgery. Ann. Surg. 133:289, 1951. Dines, D. E., Baker, W. G., and Scantland, W. A. Aspiration pneumonitis: Mendelson’s syndrome. I.A.M.A. 176:229, 1961.
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Dougherty, T. F., and Schneebeli, G. L. Use of steroids as anti-inflammatory agents. Ann. N.Y. Acad. Sci. 61:328, 1955. Edwards, G., Morton, H. J. V., Pask, E. A., and Wylie, W. D. Deaths associated with anesthesia: Report of 1,000 cases. Anuesthesia 11: 194, 1956. Gardner, A. M. N. Aspiration of food and vomit. Qumt. J. Med. 271227, 1958. Gilman, S., and Abrams, A. L. Prevention of aspiration of gastric contents during general anesthesia. New Eng. .l. Med. 255:508, 1956. Hamelberg, W., and Bosomworth, P. P. Aspiration pneumonitis: Experimental and clinical observations. Anesth. An&g. (Cleveland) 43:669, 1964. Hausman, W., and Lunt. R. L. Problem of treatment of peptic aspiration pneumonia following obstetric anesthesia ( Mendelson’s syndrome). .I. Obstet. Gynuec. Brit. Emp. 62:509, 1955. Hippocrates. Medical Works of Hippocrates, trans. J. Chadwick and W. N. Mann. Springfield: Charles C Thomas, 1950, p. 250. Lawson, D. W., Defalco, A. J., Phelps, J. A., Bradley, B. E., and McClenathan, J. E. Corticostrroids as treatment for aspiration of gastric contents: An experimental study. Surgery 59:845, 1966. Lewinski, A. Evaluation of methods employed in the treatment of the chemical pneumonitis of aspiration. Anesthesiology 26: 37, 1965. Macintosh, R. R. Cuffed stomach tube. Brit. A4ed. J. 2:545, 1951. Xlarshall, B. M., and Gordon, R. A. Vomiting,
PNEUMONIA:
19.
20.
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24.
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29.
A CLINICAL
AND
EXPERIMENTAL
REVIEW
regurgitation, and aspiration in anesthesia. Canad. Anuesth. Sot. J. 5:438, 1958. Mendelson, C. L. The aspiration of stomach contents into the lungs during obstetric anesthesia. Amer. J. Obstet. Gynec. 52:191, 1946. Merrill, R. B., and Hingson, R. A. Study of incidence of maternal mortality from aspiration of vomitus during anesthesia occurring in major obstetric hospitals in United States. Anesth. Analg. (Cleveland) 30:121, 1951. O’Mullane, E. J. Vomiting and regurgitation during anesthesia. Lancet 1: 1209, 1954. Paris, J. A., and Fonblanque, J. S. Ivf. Medical Jurisprudence, Vol. II, London: 1823. P. 57. Robson, J. G., and Welt, P. Regurgitation in anesthesia: Report on some exploratory work with animals. Canad. Anuesth. Sot. J. 6:4, 1959. Simenstad, J. O., Galway, C. R., and Mac Lean, L. D. Tracheobronchial lavage for treatment of aspiration and atelectasis. Surg. Forum 13: 155, 1962. Simpson, J. Y. The alleged care of death from chloroform. Lancet 1: 175, 1848. Teabeaut, J. R. Aspiration of gastric contents: Experimental study. Amer. J. Path. 28:51, 1952. White, R. T. Apomorphine as emetic prior to obstetric anesthesia, prevention of inhaled vomitus. Obstet. Gynec. 14:111, 1959. Winternitz, M. C., Smith, G. H., and McNamara, F. P. Effect of intrabronchial insufflation of acid. J. Exp. Med. 32:199, 1920. Wycoff. C. C. Aspiration during induction of anesthesia. Anesth. A&g. (Cleveland) 38:5, i939.
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