Hasselbring Holger H.
Sydow Michael
Immediate Concerns
Major Problems
Aspiration is a potentially critical event, occurring in patients often suffering from reduced consciousness with decreased protective airway reflexes. Signs and symptoms of aspiration depend on the quantity and the nature of the aspirate. Owing to a large number of aspiration events involving gastric contents, a high awareness is essential in those situations in which patients are at higher risk for this problem (i.e., ileus, trauma, pregnancy, etc.). The pulmonary pathophysiologic changes observed depend on the type of aspiration. In general, particulate obstructive aspiration results in significant hypoxemia, which rapidly progresses to cardiovascular collapse if the obstruction is unrelieved. As in any anoxic-ischemic event, the resultant sequelae depend on the degree and duration of the hypoxemia. Particulate nonobstructive and the various forms of liquid aspiration result in a broad spectrum of pathophysiologic changes. The initial major problem may only be bronchospasm. However, aspiration of particulate irritant, such as gastric acid, leads to an additional problem consisting of chemically induced pulmonary tissue injury with an associated inflammatory response. Thus, an initially mild hypoxemia and tachypnea may commonly progress to the acute respiratory distress syndrome (ARDS) and respiratory failure. On the other hand, microaspiration of oropharyngeal secretions in endotracheally intubated patients does not damage the lung directly, but is the major cause of ventilator-associated pneumonia (VAP).
This chapter deals only with pulmonary aspiration of substances other than water. Water aspiration (i.e., near-drowning) is discussed in Chapter 138. Furthermore, inhalational injury by noxious gases is discussed elsewhere.
Stress Points
1. Inhalation of any amount of fluid with a pH less than 2.5 is likely to damage lung tissue extensively by chemical inflammation.
2. Blood in the lungs may occur as a consequence of hematemesis, intrapulmonary hemorrhage, and surgical procedures involving the upper airway, pharynx, or maxillofacial areas. Immediately after aspiration of blood, patients will have an increased pulse and respiratory rate, and may become cyanotic if the amount of inhaled blood is sufficient to cause significant intrapulmonary shunting. Otherwise, blood is relatively harmless.
3. Ingestion of hydrocarbons such as kerosene, furniture polish, lighter fluid, gasoline, and other petroleum solvents account for 18% of accidental poisonings in children. Pulmonary toxicity occurs only if the hydrocarbon is aspirated either during ingestion or after it is regurgitated (1).
Essential Diagnostic Tests and Procedures
1. Success in diagnosing pulmonary aspiration depends on maintaining a high index of suspicion for its occurrence in at-risk patients. In 63% of cases, regurgitation is witnessed; 37% of patients have either silent or unwitnessed aspirations.
2. When clinical findings suggest pulmonary aspiration, further evaluation is essential. Arterial blood gas and pH analysis affords the most useful initial laboratory test.
3. Approximately 88% to 94% of people who aspirate gastric contents eventually demonstrate pulmonary infiltrates on chest radiograph (2). Thus, a normal finding on chest radiograph does not completely exclude the possibility of aspiration.
4. Because the initial physical findings and blood gas volumes may be identical in acid and nonacid aspiration, determination of the pH of any remaining gastric or pharyngeal fluid can be helpful. If the fluid is highly acidic, anticipate a worsening course.
Initial Therapy
1. Initial management depends on whether aspiration is imminent, occurring, or completed. When regurgitation occurs in an obtunded patient, the airway must be cleared, and the patient's head must be tilted down and to the side.
2. Suction equipment must be available and ready to use in areas where this problem is likely to occur (e.g., the operating, delivery, and emergency rooms; postanesthesia care unit; and intensive care unit [ICU]).
3. Oxygen should be administered immediately to all patients suspected of pulmonary aspiration.
4. The airway should be secured by intubating the trachea, and then one must attempt to clean the airway immediately by suctioning any particulate aspirate. Suctioning has no beneficial effect with acid aspiration because the injury is immediate.
5. No benefit is derived from alkaline tracheal lavage. In fact, the practice is detrimental.
6. Removal of large particulate matter usually requires rigid bronchoscopy. Fiberoptic techniques permit only the removal of small particles.
Historical Background
Beginning with Aristotle's observation of the association between meconium staining of the amniotic fluid and a sleepy fetal state (3), aspiration pneumonia was recognized as a clinical problem as early as 400 BC when Hippocrates realized “Dangers of Aspiration” (4). More than 2,000 years later, in 1848, Simpson reported the first anesthetic death under chloroform caused by pulmonary aspiration and asphyxia (5). In 1946, Mendelson presented 66 cases of aspiration occurring among 44,016 obstetric patients undergoing general anesthesia for vaginal deliveries (6). His description was so complete that aspiration in this setting is commonly termed the “Mendelson syndrome.” Subsequently, his laboratory investigations led him to the conclusion that two entirely separate clinical entities existed. One followed the aspiration of solid food and resulted in a clinical picture of laryngeal or bronchial obstruction, whereas the other resulted from direct acid injury to the lung and caused the “asthma-like” syndrome (7). Teabeaut, in 1952, showed that a liquid aspirate with a pH below 2.5 would produce pneumonitis in rabbits (8). The concept of a critical pH and a certain aspirate volume was introduced in 1974 by Roberts and Shirley from data obtained in rhesus monkeys (9). The results were calculated for humans in order to identify patients at risk of pulmonary aspiration. Subsequent animal studies demonstrated that larger volumes of acidic aspirates produced higher morbidity and mortality (10). The critical pH of 2.5 and critical volume of 0.4 mL/kg body weight (or approximately 25 mL in an adult) have since been challenged as inducing aspiration pneumonitis.
Risk Factors
In a healthy and conscious subject, effective protective laryngeal and cough reflexes prevent pulmonary aspiration. Since the reflex status depends on the level of consciousness, it is obvious that aspiration is predisposed by any reduction of consciousness, which, therefore, is the major risk factor for aspiration (11). Common causes of reduced consciousness include different kinds of neurologic pathology such as head injury, stroke, and cerebral hemorrhage, as well as infectious causes such as meningitis or sepsis, or metabolic sources such as diabetes or thyroid crisis, and so forth. Drug and alcohol overdose and the use of sedative medication increase the risk of pulmonary aspiration; interestingly, even during normal sleep, aspiration is not uncommon (12). Another group of patients with an increased risk of aspiration are those with laryngeal incompetence caused by neurologic disturbances such as multiple sclerosis or muscular dystrophy, or by surgery of the hypopharynx and larynx itself. The protecting closure reflex of the larynx against aspiration is also impaired with age (13).
General anesthesia not only reduces the level of consciousness, but also suppresses airway reflexes. Therefore, general anesthesia is a risk factor for aspiration, particularly in emergency cases. Certain patient conditions increase the risk of aspiration in the perioperative setting. Best known is pregnancy, with its associated increased abdominal pressure and delayed gastric emptying. Another condition is morbid obesity (14), with issues of increased gastric volume and increased abdominal pressure, at least in the supine position. However, more recent studies have questioned the assumption that obesity is a risk factor for pulmonary aspiration during anesthesia (15). An absolute high-risk situation is small bowel obstruction with high gastric pressure. In this condition, the stomach sometimes contains far more than 1 liter of bile and jejunal secretions, and the distended bowel causes abdominal hypertension. Other conditions predisposing to pulmonary aspiration include disorders resulting in (a) reduced lower esophageal sphincter tone, such as gastroesophageal reflux disease; (b) increased lower esophageal sphincter tone (achalasia); (c) increased pyloric tone, such as pyloric stenosis; and (d) diseases with delayed gastric emptying (e.g., diabetes). Each situation, leading to increased gastric pressures, may amplify the incidence of regurgitation and vomiting and, consequently, the risk of pulmonary aspiration.
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Table 139.1 Risk factors for pulmonary aspiration |
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In the perioperative period, aspiration occurs most often during the induction of anesthesia, when the patient is already unconscious and the endotracheal tube is not yet in place. Some measures can even increase the aspiration risk. For example, mask ventilation with high pressures can further insufflate the already full stomach with air and, thus, increase the intragastric pressure. The fast-acting muscle relaxant, succinylcholine, can cause abdominal muscle contractions and consequently increases the abdominal, and thus gastric, pressure if the patient has not been properly precurarized. A nasogastric tube in place at the time of induction of anesthesia reduces the patency of the esophageal sphincter and promotes gastroesophageal reflux. The body position of the patient influences the intra-abdominal pressure and, thus, affects the risk of regurgitation and aspiration as well. The flat, supine position is probably the worst position, whereas the semirecumbent position decreases abdominal pressure.
It seems obvious that the risk of aspiration is also increased at the end of anesthesia when the endotracheal tube has been removed but recovery of consciousness is not completed. Patients at special risk include those having undergone laryngeal or hypopharyngeal surgery, resulting in laryngeal incompetence. These patients need close observation postoperatively.
Critically ill patients with ventilatory insufficiency or failure are at particular risk of pulmonary aspiration. Muscle weakness, tachypnea, immobility, and impaired consciousness depress the normal airway-clearing mechanisms. Even in patients whose airway is protected by a cuffed endotracheal tube, aspiration is common. Although a properly inflated tube cuff can prevent macroaspiration, microaspiration of pooled subglottic secretions occurs because the cuff configuration does not provide complete sealing of the trachea; this may be obviated to a great extent by an endotracheal tube with a subglottic suction port incorporated into the tube. Other factors increasing the risk of aspiration in endotracheally intubated patients include reintubation, tracheostomy, frequent ventilator circuit changes, low intracuff pressure, and patient transport from the ICU (16). Further risk factors pertaining to the gastrointestinal tract include enteral nutrition, supine positioning, and stress ulcer prophylaxis with gastric pH-altering agents (17).
A nasogastric feeding tube not only promotes gastroesophageal reflux, but also eventually leads to oropharyngeal swallowing defects. An endotracheal tube causes vocal cord dysfunction and impairs the sensorimotor function of the pharynx and the larynx temporarily. After long-term intubation, swallowing defects are frequent, with a considerable risk of aspiration after extubation (18). A synopsis of the various risk factors is shown in Table 139.1.
Incidence, Morbidity, and Mortality
Aspiration in the Perioperative Period
Although general anesthesia is principally a risk factor for pulmonary aspiration, carefully developed strategies during the past decades have reduced the risk of aspiration during elective surgery. Several large studies were concerned primarily with the incidence of aspiration and its associated mortality during general anesthesia (19). In a retrospective study of 215,488 general anesthetics for elective and emergency surgery, Warner et al. (20) found an incidence of pulmonary aspiration of 1 in 3,216 (0.03%) and a mortality rate of 1 in 71,829 patients (0.0014%); the incidence of aspiration was found to be four times higher in patients undergoing emergency surgery. There was no serious morbidity from pulmonary aspiration in the immediate perioperative period in nearly 120,000 elective procedures and general anesthetics in American Society of Anesthesiologists (ASA) physical status I and II patients. The incidence of pulmonary aspiration and severity of pulmonary outcomes were highly associated with the presence of comorbidity (ASA physical status III and higher) and procedures performed emergently. Finally, Warner et al. concluded that patients with clinically apparent aspiration who do not develop symptoms within 2 hours of aspiration or completion of the procedure are unlikely to have respiratory sequelae.
Olsson et al. in 1986 (19) studied 185,385 patients undergoing general anesthesia and found an aspiration rate of 1 in 2,131 (0.05%). Forty-seven percent of the patients with reported aspiration developed aspiration pneumonitis, with a mortality rate of 1 in 45,454 (0.002%) (16). In 1996, Mellin-Olsen et al. studied 85,594 anesthetics prospectively. They reported 25 cases of aspiration, presenting an overall incidence of 1 in 3,424. All occurred in patients receiving general anesthesia, with an incidence of 1 in 2,106. Of the 25 aspiration cases, 13 occurred during elective procedures with an incidence of 1 in 3,303, and 12 in emergency procedures with an incidence of 1 in 809. There were no aspirative events in patients receiving regional anesthesia nor in those patients who were under IV sedation and analgesia but breathing spontaneously (21). In a report on the epidemiology and impact of aspiration pneumonia in patients undergoing surgery in Maryland between 1999 and 2000 (22), the prevalence of aspiration pneumonia was approximately 1% of hospitalized surgical patients, remarkably higher than in the other studies. However, in a letter to the editors (23), it was noted that the authors of the Maryland study did not distinguish between aspiration pneumonitis and aspiration pneumonia. The fact that all patients with postoperative nosocomial pneumonia were included in the aspiration group most likely explains the higher incidence of aspiration in this study.
Aspiration pneumonitis associated with pediatric anesthesia occurred in up to 1 in 1,162 (0.09%) children in Olsson's study (19). In a prospective study in 1999, Warner et al. reported an aspiration incidence of 3.8 per 10,000 (1:2,632; 0.04%) anesthetics in children (20). In a prospective survey carried out in France of 40,240 general anesthetics in children, only four aspirations were reported (0.01%). No morbidity or mortality was reported (24).
Aspiration in Obstetrics
Even though anesthesia-related maternal mortality rates have improved, anesthesia still remains prominent among the leading causes of maternal mortality; it is the seventh leading cause of maternal mortality in the United States (25). General anesthesia in the obstetric patient is more likely to be associated with maternal mortality than is regional anesthesia. Airway management tends to be more difficult in pregnant patients compared to the general population. Moreover, general anesthesia is indicated in emergency delivery surgery, with minimal time left for adequate preoperative evaluation and preparation for anesthesia. Several anatomic and physiologic alterations during pregnancy cause a difficult airway. Mucosal edema is common in expectant mothers due to hormonal effects and relative fluid overload, particularly in eclampsia (26).
The Closed Claims Analysis of the ASA revealed that respiratory events accounted for the single largest class of injury (27). According to the study by Chadwick et al., difficult tracheal intubation and esophageal intubation comprised 23% of harmful events associated with obstetric general anesthesia (28). Complications leading to anesthesia-related deaths due to airway management problems included aspiration of gastric contents, problems during intubation, esophageal intubation, and inadequate ventilation.
The pregnant woman is at special risk for aspiration of gastric contents for a variety of reasons, including mechanical, hormonal, and iatrogenic factors (26). The gravid uterus increases intra-abdominal and intragastric pressure, which may increase even more during delivery. The distortion of the esophagogastric junction and the stomach through the gravid uterus promotes esophageal reflux, and gastric emptying time is prolonged (29). Hormonal factors specific to pregnancy include higher levels of gastrin, which increases gastric acidity and volume, and progesterone, which can decrease gastroesophageal sphincter tone. Iatrogenic factors include the administration of sedatives and narcotics during labor, which further prolongs gastric emptying and also may depress protective airway reflexes. Moreover, the lithotomy position and manual abdominal compression for delivery additionally increase intragastric pressure. The incidence of aspiration in obstetric patients for cesarean section under general anesthesia was 1 in 1,431 (0.07%) in an Italian study (30). A Scandinavian report noted aspiration in 4 of 3,600 cesarean sections (0.11%) and in 4 of 36,800 parturients (0.01%), with no fatalities (31).
“Silent Aspiration” during Anesthesia
During the induction of anesthesia, when protective reflexes are diminished, the risk of aspiration is greatest. However, even after having successfully completed induction of anesthesia, pulmonary aspiration is not uncommon. Owing to the fact that this kind of aspiration is usually not detected by the anesthesiologist, it is called “silent” aspiration (32). Despite the tube being correctly placed in the trachea, with an appropriately inflated cuff to “seal” the airways, aspiration may still occur. Nevertheless, during short-term endotracheal intubation, the incidence of silent aspiration is relatively low. In older studies, an incidence of 8% to 25% during anesthesia was reported (33). In 1970, Blitt et al. detected “silent” aspiration in less than 1% of 900 studied anesthetized patients (34). These clinicians attributed the low incidence of aspiration to their use of cuffed endotracheal tubes and the exclusive use of fast-acting intravenous induction in contrast to the induction with inhalation anesthetics, which was still popular in those times. Moreover, they reported that only 1 out of the 900 patients (0.1%) may have developed pulmonary complications as a possible consequence of silent aspiration. However, even in this patient, the pulmonary complication may have been from other reasons (34). It is remarkable that there is no further, more recent study about silent aspiration during anesthesia. This fact and the very low incidence of serious consequences of aspiration underline that silent aspiration during short-term endotracheal intubation, as during anesthesia, is only of minor concern.
Aspiration in the Early Postoperative Period
There are no specific data about the incidence of aspiration in surgical patients in the early postoperative period or its sequel, aspiration pneumonia. Postoperative nausea and vomiting (PONV) is a frequent phenomenon after anesthesia and surgery (35) and has been well reviewed in large prospective multicenter studies. However, none of these studies revealed pulmonary aspiration associated with PONV as a significant problem. Nevertheless, as impaired consciousness is a major risk factor for pulmonary aspiration in all patients who are not fully recovered, the need for close observation is evident in the early postoperative period.
Pulmonary Aspiration in Critical Care
Pulmonary aspiration during induction of anesthesia or in an emergency case is generally witnessed, and the consequences of aspiration, such as bronchospasm and hypoxemia, develop early. In contrast, aspiration is usually silent in critical care patients and frequently chronic without early and clear signs of the event. Thus, estimating the incidence of aspiration in critical care patients is difficult. Markers like glucose, pepsin, radioisotope-labeled feeds, or dye in tracheobronchial secretions have been used to detect aspiration in these patients (36,37,38). With these methods, pulmonary aspiration was detected in up to 89% in mechanically ventilated, tube-fed patients (38). Other studies, reported in patients with tracheostomies, noted a positive aspiration rate between 33% (40) and 50% (39). The methods mentioned above identified minimal amounts of aspirated material, even if no clinical symptoms could be detected. In fact, 87% and 77% of the events, respectively, were classified as “silent aspiration” (39,40). Even in healthy subjects, tracheal aspiration during sleep is not uncommon (12). However, in healthy subjects, immune competence together with efficient airway-clearing mechanisms (coughing, mucociliary transport, etc.) and the low pathogenicity of the normal oropharyngeal flora prevent the development of airway infection. On the other hand, if the physiologic defense and clearing mechanisms are impaired—as in the critically ill and particularly in sedated, endotracheally intubated patients—pneumonia may follow, even if the amount of the aspirated substance is small and the number of bacteria low. Furthermore, recurrent aspiration of bacterially contaminated oropharyngeal secretions is frequent in these patients and increases the likelihood of respiratory tract infection. This explains the correlation between the duration of critical illness—and especially the time of intubation—with occurrence of respiratory tract infections. In a large European multicenter study, the incidence of pneumonia in endotracheally intubated patients was 15.8% at day 7 and 23.4% at day 14 (41). In critically ill patients, the immunocompromised state and previous antibiotic therapy lead to a shift of the oropharyngeal flora from physiologically less virulent bacteria to a pathogenic population consisting mostly of Staphylococcus aureus, Gram-negative enteric bacilli, Pseudomonas aeruginosa, and Candida species (42). Since aspiration pneumonia is one of the most common and relevant results of the aspiration of oropharyngeal secretions or gastric contents in critically ill patients, its occurrence can be used as a surrogate indicator of aspiration. However, the incidence of aspiration pneumonia is often submerged within the incidence of VAP. VAP incidence, as it is defined, refers only to endotracheally intubated, mechanically ventilated patients, and does not include the aspiration pneumonia of nonintubated patients, such as those having suffered a stroke or with swallowing defects of other origins. Thus, there is uncertainty as to the exact incidence of aspiration pneumonia. Even the incidence of VAP varies between 9% and 70%, depending upon the case mix of patients, the setting of the studies, and the criteria used for the diagnosis of pneumonia (43).
Pulmonary Aspiration in Medical Emergencies
Medical emergency situations are often accompanied by reduced consciousness and impaired protective reflexes. Thus, tracheobronchial aspiration is common in these cases. Although the exact incidence is uncertain, the overall risk of aspiration during emergency intubations is in the range of 20% (44). However, this number varies depending on the patient's condition—mainly the level of consciousness—and the situation during which airway management or airway protection measures are performed. Pulmonary aspiration during endotracheal intubation in emergency surgery, even though performed in the operating suite, takes place in 1 of 895 (0.1%) cases, which is about four times more frequent than in elective surgery (20). The risk of aspiration increases with the degree of unconsciousness, as measured by the Glasgow coma scale (45). In prehospital emergency care, aspiration prior to airway management occurs in about one third of severely head-injured patients—those with a Glasgow coma scale score between 3 and 8 (46,47). Although no specific data have been described in the patient with central nervous system (CNS) injury, some authors estimated the incidence of gastric aspiration to be up to 30-fold more likely in emergency—as compared to scheduled—cases (48). Another study revealed aspiration of gastric contents in 50% of the patients who needed to be intubated because of respiratory insufficiency in the prehospital setting, as opposed to 22% in those patients who required subsequent tracheal intubation in the emergency department (49). Even though different methods have been used to investigate the incidence of pulmonary aspiration in emergency care, it seems relatively clear that aspiration in emergencies occurs less frequently in a well-prepared setting such as the operating suite, with doctors highly skilled in airway management, as compared to the difficult situations seen in prehospital emergency care. Furthermore, it can be presumed that endotracheal intubation in an emergency situation per se might increase the risk of aspiration: if reflexes are not deeply suppressed, laryngoscopy stimulates the gag reflex caused by contact of the instrument with the pharyngeal wall and can induce vomiting.
Gastric contents will then be aspirated because of disturbed protective reflexes and discoordinated cough reflexes. In many trauma patients, the stomach is acutely dilated (50), which further promotes vomiting, regurgitation, and, finally, aspiration. Cardiopulmonary resuscitation also poses a high risk for aspiration. In an autopsy series of unsuccessfully resuscitated patients, nearly half of them had full stomachs, and the overall incidence of pulmonary aspiration was 29% (51). This underlines the high incidence of pulmonary aspiration in emergency patients.
Pathophysiology of Pulmonary Aspiration
Definition
Aspiration is defined as the misdirection of oropharyngeal or gastric contents into the larynx and lower respiratory tract (52). Aspiration of gastric contents results from either active vomiting or passive regurgitation, both associated with impairment or depression of protective laryngeal and cough reflexes. Aspiration can be composed of materials from the following groups, depending on the nature of the aspirated material (53):
1. Noxious fluids—acid, bile, jejunal secretions, and other chemical substances
2. Solid particles—food, teeth, and other foreign bodies
3. Miscellaneous fluids—blood, water, alcohol, meconium, milk, pus, etc.
4. Microbiologically contaminated secretions
Table 139.2 lists substances that are known to be aspirated.
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Table 139.2 Substances known to be aspirated |
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Aspiration Pneumonitis versus Aspiration Pneumonia
To better understand the problem of aspiration, it is important to distinguish between aspiration pneumonitis and aspiration pneumonia. Aspiration pneumonitis is caused by chemically injurious agents (e.g., acid). Such agents destroy the lung tissue directly, as by chemical burn. It most commonly occurs in patients with a decreased level of consciousness who aspirate gastric contents. By way of contrast, aspiration pneumonia occurs in a different group of patients, mainly elderly with dysphagia or gastric dysmotility, or in critically ill patients who are usually endotracheally intubated and mechanically ventilated. These patients often aspirate only small amounts of bacterially contaminated secretions. Furthermore, in this kind of aspiration, lung damage develops collaterally to aspiration, when bacterial invasion leads to pneumonia. Although the distinction is somewhat arbitrary, there clearly are different population groups at risk for the two potential aspiration-induced lung disorders. It is important to examine these two conditions separately to better define the prognosis and treatment of at-risk populations (54).
The outcome after pulmonary aspiration is dependent on the toxicity or virulence of the aspirate, the volume of the aspirate, and the effectiveness of the defense mechanisms of the organism. For example, small amounts of aspirated autologous blood will cause no harm to lung tissue. In contrast, a relatively small volume of gastric acid with low pH produces harmful damage to the alveolar tissue (i.e., pneumonitis). Although saliva is a neutral liquid and is aspirated only in small amounts, its bacterial contamination may cause serious pneumonia because of the impaired clearing mechanisms and decreased immune defense in critically ill patients.
Aspiration of Gastric Contents and Aspiration Pneumonitis
The major source of aspirated material is the stomach and upper gastrointestinal tract. The content is variable, consisting of gastric acid, food particles, or a mixture of both. In case of small bowel obstruction, the stomach may also contain jejunal secretions and bile. The aspect of solid food will be discussed in a later section.
Gastric acid is very deleterious to lung tissues. Most authors agree that a pH less than 2.5 and a volume of gastric aspirate greater than 0.4 mL/kg body weight—approximately 25 to 50 mL in adults—are required for the development of aspiration pneumonitis (6,8,10). Experimental studies have indicated that the instillation of low pH hydrochloric acid solutions results in a dose-related and pH-dependent acute lung injury (ALI). The severity of the injury is directly related to three variables: (a) the acidity of the instilled fluid, (b) the volume of the instilled fluid, and (c) the tonicity of the fluid (55). Hypotonic fluids cause a more severe lung injury than isotonic fluids; gastric contents have approximately one-third the osmolality of plasma. Most clinical and experimental studies demonstrate that there is an initial lung injury whose clinical presentation is airway constriction, arterial hypoxemia, and the development of pulmonary edema. In some experimental models, there is progression of the acid-induced lung injury, with the most serious injury seen at approximately 6 to 8 hours after the acid administration (56).
Small bowel obstruction often leads to massive (greater than 1 liter) reflux of bile and jejunal secretions into the stomach. This produces an increased gastric pressure with a high risk of regurgitation. Bile has an inflammatory potential comparable to acid (57). Owing to the direct chemical destruction of the lung tissue by aspiration of either gastric acid or bile, this kind of lung damage is termed aspiration pneumonitis.
Aspiration of Solid Particles
Aspirate containing large particles accounted for 7.5% of aspiration in Mendelson's series (6). While two of his five patients who aspirated solid material died of suffocation, most perioperative gastric aspirates do not contain large particles.
Solid particles obstruct the airways depending on their size. The bigger they are, the larger is the obstructed lung area behind the foreign body, and the higher the degree of the intrapulmonary right-to-left shunt, resulting in hypoxemia or even suffocation. In the zone around the foreign body, local inflammation will occur with infiltration of mononuclear cells and granulomatous reaction of the lung tissue. If the solid particle is not removed, permanent atelectasis and lung consolidation will develop downstream from the obstruction. Conversely, air trapping and emphysema may develop behind the obstruction (58). Depending on the bacterial content of the aspirate or of the airways behind the obstruction, local pneumonia or even a lung abscess may develop.
Teeth are sometimes accidentally aspirated in craniofacial trauma, and may be detected only by a routine chest radiograph postoperatively or during examination in the emergency room. Foreign body aspiration is a serious problem in children, with the ability to cause critical respiratory insufficiency (59). More than 17,000 children under the age of 14 were admitted to emergency departments in the United States in 2001, resulting in 160 deaths (60). More than 50% foreign body aspirations occur in children aged between 1 and 3 years, less than 10% in children younger than 1 year of age (61), and only occasionally in adults, usually secondary to impaired consciousness. A Medline search revealed that nearly anything that would fit into a pediatric trachea has been detected there. Aspiration of foreign bodies can occur very dramatically, with a full-blown picture of acute choking, or more subclinically with recurrent coughing or wheezing episodes mimicking respiratory infection or asthma (62). Nuts, especially peanuts, are occasionally aspirated by children and cause a special problem. These often break into small pieces when attempting to remove them bronchoscopically. Generally, removal of the aspirated foreign body by bronchoscopy is the therapy of choice.
Aspiration of Miscellaneous Fluids
Blood
During craniofacial trauma and, to a lesser extent, during ear–nose–throat surgery and maxillofacial surgery, the aspiration of blood is common. Blood is harmless in terms of its inflammatory property to tissue or mucosal structures. Depending on the volume aspirated, it will cause a certain degree of intrapulmonary right-to-left shunt and hypoxemia. About 400 mL of blood in the alveolar space may be sufficient to cause significant hypoxemia (63). Only a large amount of blood can obstruct the airways sufficiently to cause life-threatening hypoxemia and death through suffocation. Smaller volumes normally can easily be treated with the application of continuous positive airway pressure or positive end-expiratory pressure (PEEP) ventilation (64). Most often, the blood is reabsorbed without further harmful consequences, with the only hazard of aspirated blood being airway obstruction.
Alcohol
The pH of alcohol is similar to that of saliva—pH 6 to 7—and its destructive properties on lung tissue have been considered minimal. In an animal study, however, aspirated ethanol has been shown to produce marked pulmonary inflammation and bronchiolitis obliterans (65). How this might be adjudicated in the context of a human aspiration of alcohol is unclear, and only one study concerning ethanol aspiration in the literature underlines the fact that aspiration of ethanol is a rare event.
Hydrocarbons
Materials such as gasoline, kerosene, gasoil, furniture polish, and other light oil products are sometimes ingested—mainly accidentally—by children. If vomited or regurgitated, hydrocarbons can be aspirated, resulting in a rapid onset of hypoxemia caused by intrapulmonary shunt (66). The intrapulmonary shunt after aspiration of hydrocarbons results from pulmonary edema and mucosal bleeding (67).
Polyethylene Glycol
This material is generally used to clean the bowel prior to endoscopic examinations. Since it is given in relatively large quantities, pulmonary aspiration may occur in at-risk patients, such as children and the elderly (68). Polyethylene glycol induces mucosal inflammation, interstitial edema, and, consequently, hypoxemia.
Oropharyngeal Secretions
Oral secretions per se are innocuous to airway mucosa. If aspirated, oropharyngeal secretions are usually small in volume and will not cause significant obstruction of the airways. However, the oropharynx is heavily contaminated with a variety of microbes, which may cause a problem if aspirated. In healthy individuals, the normal oropharyngeal flora consists mostly of anaerobes and, to a small degree, aerobic bacteria (Staphylococcus and Haemophilus species, among others) (69), which only have a minor infectious potential in the immunocompetent subject. In the presence of an immunocompromised state, the normal flora may be overgrown by pathogens such as Gram-negative rods, S. aureus, and yeasts. Aspirated oropharyngeal secretions contaminated with these pathogenic microbes are usually the source of aspiration pneumonia. However, the development of pneumonia depends on the pathogen's virulence and the quantity aspirated, as well as the patient's defense mechanisms such as mucociliary clearance and cellular and humoral immunocompetence. Repeated aspiration of even small amounts of secretions from above the cuff of the endotracheal tube, as often takes place in mechanically ventilated patients, increases the likelihood of VAP.
Meconium
The aspiration of meconium (pH 5.5–7) in newborn infants can cause mechanical obstruction, depending on the amount and consistency of the material; it also induces a chemical pneumonitis (70). Meconium aspiration occurs in slightly less than 1% of the newborn infants (71). Of the infants who develop a meconium aspiration syndrome, more than 4% die, accounting for 2% of all perinatal deaths (72). In laboring women with thick meconium staining of the amniotic fluid, amnioinfusion did not reduce the risk of moderate to severe meconium aspiration syndrome, perinatal death, or other maternal or neonatal disorders (73). Routine oropharyngeal and nasopharyngeal suctioning during delivery of term newborns through meconium-stained amniotic fluid is a frequent therapy, but it has recently been suggested that this does not prevent the meconium aspiration syndrome (74).
Milk
Milk may be aspirated either directly after ingestion or subsequent to regurgitation or vomiting. The effects of pulmonary aspiration of milk have been studied in animals (75). Vomited milk is usually acidic due to gastric acid admixture. However, instillation of human breast milk into rabbit lung at a pH of 7 and 1.8 results in comparable tissue damage and pneumonitis, whereas instilled 5% dextrose solution at a pH of 1.8 did not cause significant lung injury. It appears, based on this study, that human breast milk may be harmful to the lung. Nevertheless, this interpretation from animal experimentation must been taken with caution, as no data exist on the effect of aspirated human breast milk on human lung tissue.
Pus
Aspiration of pus is a very rare event, occurring during surgery for lung abscess or rupture of a peritonsillar abscess. The consequence may be transmission of the infection to other regions of the respiratory tract.
Diagnosis of Aspiration and Its Sequelae
Patients who have aspirated gastric material may present with dramatic clinical signs and symptoms. The clinical features may include an abrupt onset of wheezing, coughing, dyspnea, and tachycardia. Patients may exhibit low-grade fever, bronchospasm, or cyanosis, with pink, frothy sputum. A severely decreased PaO2 and hypoxemia also occur. If not witnessed, the diagnosis of acid pneumonitis is usually presumptive based upon the clinical picture. After an aspiration, the chest radiograph often shows localized or diffuse patchy alveolar infiltrates or, in severe cases, opacification of large lung fields; these changes are usually noted within 2 hours. Aspiration most often is localized in the right lower lobe, as this is the straightest path from the trachea, or in the most dependent lung area—frequently the right upper lobe in supine patients (76).
As a consequence of the aspiration-induced alveolar capillary membrane damage, capillary leak occurs with loss of intravascular fluid into the interstitial tissue of the lung, resulting in increased extravascular lung water, systemic hemoconcentration, hypotension, tachycardia, and, possibly, hypovolemic shock aggravating the hypoxemia. Pulmonary hypertension may occur secondary to bronchospasm, loss of alveolar function, and left ventricular dysfunction (77). In patients with neurologic injuries, pulmonary aspiration can contribute to secondary CNS injury through hypoxia, hypotension, and pulmonary hypertension, with decreased cerebral venous return causing an acute increase of intracranial pressure (48).
Interestingly, many patients do not have clinical progression to lung injury, only a cough or a wheeze. Some patients have silent aspiration, which may manifest only as arterial desaturation with subsequent radiologic evidence of aspiration or pneumonia (20). Subclinical aspiration can be detected only through additional measures. Several markers have been used to ascertain subclinical aspiration with various success. Such markers include glucose, radioisotope-labeled feeds, or dye (37,78,79). Recently, the presence of pepsin as a sensitive and specific marker of gastric contents has been suggested as a useful marker of occult aspiration (80,81).
If a patient is considered as having suffered clinically relevant aspiration, measuring the pH in the larynx may be used to confirm the diagnosis (82). We usually measure the pH with simple litmus paper, which is adequately sensitive, as gastric contents require a pH of less than 2.5 to produce chemical pneumonitis. Bronchoscopy supplies only limited additional information. If aspiration of solid particles is suspected or witnessed, bronchoscopy can confirm the type and size of the particle. However, for the removal of particles, rigid bronchoscopy may be necessary. In case of gastric acid aspiration, bronchoscopy is only able to show the amount of inflamed mucosa. It is useless to attempt to remove acid from the bronchi via bronchoscopic lavage and suctioning.
The diagnostic criteria of aspiration pneumonia (not to be confused with aspiration pneumonitis) are not different from the usual criteria of pneumonia, consisting of the typical clinical findings such as new pulmonary infiltrates, fever, deterioration of pulmonary function, and laboratory infectious findings such as leucocytosis and identification of the causative agent (83,84).
Therapy for Aspiration
Witnessing the aspiration of gastric secretions into the pharynx should immediately prompt lateral head positioning, assuming integrity of the cervical spine, suctioning, and consideration of endotracheal intubation. The success of treatment may depend on immediate and vigorous measures to relieve airway obstruction. Tracheal suctioning may stimulate cough, bringing up some aspirated material, and thus help confirm a suspected diagnosis. Immediate bronchoscopy is performed only when solid particles, which may obstruct airways, are thought to have been aspirated. Removal of larger material requires rigid bronchoscopy. Bronchoscopic suctioning will not, however, protect the lungs from chemical injury, which essentially occurs immediately. Bronchial lavage may be deleterious, as it may result in surfactant washout and spread noxious aspirated material to uninvolved lung areas. Attempted neutralization of the acid aspirate is of no help, as the acid is rapidly neutralized physiologically.
The major therapeutic approach is to maintain pulmonary function, thus ensuring adequate gas exchange and minimizing further damage to the lungs. In an awake, alert, and cooperative patient, continuous positive airway pressure (CPAP) may be administered by mask, but more often, mechanical ventilation with PEEP in a lung-protective manner must be applied. Recent work also indicates that mechanical ventilation of acid-injured rat lungs with low tidal volumes of 6 mL/kg reduces the severity of lung injury compared to mechanical ventilation with higher tidal volumes of 12 mL/kg (85). These studies confirm the results of the ARDS Network trial in which low tidal volume ventilation decreased mortality in patients with ALI (86). Aerosolized β2 agonists may reduce the severity of lung endothelial injury and augment active ion transport mechanisms, which are responsible for the removal of edema from distal alveoli and airways of the lung (87). Owing to the deleterious increase of pulmonary vascular resistance caused by acid injury, the use of selectively acting vasodilators, such as inhaled nitric oxide (iNO), sildenafil, and prostacyclin, may be helpful in improving lung function and cardiac performance.
Meconium aspiration syndrome (MAS) remains a relevant cause for respiratory distress syndrome in premature infants, and is characterized by severe impairment of pulmonary gas exchange, surfactant inactivation, and pronounced inflammatory changes. Surfactant replacement therapy has been established for years as one of the most important therapeutic interventions in the management of premature infants with ARDS (88,89). Owing to the fact that aspiration and ARDS include the loss of pulmonary surfactant function, there is considerable interest in surfactant replacement therapy in adult patients. An international, multicenter, industry-sponsored study showed no improvement in either oxygenation or mortality when replacement surfactant was used in these patients (90). The study had enrolled 498 patients when it was discontinued, after interim analysis revealed a 41% mortality rate in both groups. Clinical experience has shown exogenous surfactant inconsistent as a therapeutic modality for adult patients with ARDS. However, current data do suggest that patients with primary ARDS (e.g., pneumonia, aspiration) may benefit more from surfactant replacement therapy than patients with secondary ARDS (e.g., sepsis, trauma); there has been no large, randomized, clinical trial conclusively showing that exogenous surfactant improves outcome in ARDS (91). The value of surfactant replacement in near-drowning is discussed elsewhere.
Steroids in aspiration syndromes have been shown to be clinically ineffective and, indeed, impede recovery in animal models (92), and likely in humans as well (93,94,95).
Antibiotic Therapy
Aspiration Pneumonitis
Although common practice, the prophylactic use of antibiotics in patients with suspected or witnessed aspiration is not recommended (96). Prophylactic antibiotics may increase late mortality by promoting the growth of resistant bacteria (97). However, empiric antibiotic therapy is appropriate for patients who aspirate gastric contents consisting of small bowel secretions or in other conditions associated with high bacterial colonization of the aspirate. Specific antibiotic therapy should be initiated in the setting of a secondary bacterial infection and should also be considered for patients with aspiration pneumonitis that fails to recover within 48 hours after aspiration (23).
Aspiration Pneumonia
The antibiotic therapy of aspiration pneumonia depends on the expected causative agent. However, distinctions are made between early- and late-onset pneumonia, which have different epidemiology and pathogenesis, and thus each type requires different strategies for therapy and prevention.
Early-onset Pneumonia
Early-onset pneumonia occurs typically in trauma patients and acute illness a few days after admission (98). The mechanism is mostly aspiration of oropharyngeal secretions before or during endotracheal intubation. Thus, the causative microbial organisms of early-onset pneumonia are usually identical with those potentially pathogen microbes, which can frequently be found in the oropharyngeal flora of healthy subjects, such as methicillin-susceptible S. aureus, Haemophilus influenzae, or Streptococcus pneumoniae. Since these organisms are also responsible for community-acquired pneumonias, the antibiotic treatment of early-onset pneumonia is not different from that of community-acquired pneumonia.
Late-onset Pneumonia
As late-onset pneumonia occurs more than 4 to 7 days after admission (99), the spectrum of the causative organisms is usually nosocomial, often consisting of Pseudomonas aeruginosa, among others. The principles of antibiotic therapy of late-onset pneumonia are the same as those of nosocomial pneumonia. Both issues—therapy of community-acquired and nosocomial pneumonia—are discussed separately in Chapter 111.
Prevention of Aspiration and Its Sequelae
Prevention of Aspiration in the Perioperative Period
The ritualistic preoperative fasting over the past decades has been questioned, given that fasting can cause dehydration, diminishes the energy reservoir, and increases patient anxiety. Moreover, the amount of gastric secretions may be increased through hunger and emotional stimuli (100,101,102,103).
Many studies have attempted to identify patients at risk before induction of general anesthesia with various fasting durations in various settings. It is generally agreed upon that clear fluid given up to 2 hours before elective surgery does not adversely affect gastric contents in healthy patients (100,104). This knowledge is one of the keystones of the “fast-track surgery” approach (105). One study found gastric volume and pH unchanged in children who had received 6 or 10 mL/kg apple juice 2.5 hours before anesthesia; in addition, they were less thirsty and less irritable than the control children who received no juice (107). However, the preoperative fast should not be lessened for anything other than clear liquids, as aspiration of particulate material (106) or human breast milk are grave, regardless of acidity (75), nor should fasting be abated in obstetric patients or patients awaiting emergency procedures. The current ASA guidelines for preoperative fasting (108) list fasting times for clear liquids, human breast milk, infant formula, nonhuman milk, and a light meal. Depending on the substance ingested, a preoperative fasting time between 2 and 6 hours is considered safe. However, the recommended fasting periods apply to healthy patients awaiting elective surgery; exceptions have been defined for other circumstances (Table 139.3).
Preoperative Administration of Antacids
The large retrospective review of 215,488 general anesthetics found no difference between patients who received or did not receive prophylaxis for acid aspiration. This leads to the author's question, “Should these medications have been used routinely?” (20). The potential value of the preoperative administration of antacids is based on the unproven presumption that drug-induced increases in gastric pH will decrease the likelihood of severe acid pneumonitis (20). Despite the known ability of antacids to increase gastric fluid pH, it has not been documented that prophylactic administration to a high-risk patient population (e.g., parturients) decreases mortality (109,110). Furthermore, antacids and other drugs, such as H2 antagonists or proton pump inhibitors, have no impact on the incidence of regurgitation and aspiration. The duration of antacid action highly depends on gastric emptying time, which can be shortened by prokinetic drugs like metoclopramide. However, this effect is blocked by atropine or opioids. Opioids slow gastric motility and thus prolong the pH-elevating effects of antacids. The administration of antacids (e.g., to the parturient who has also received opioids) may result in greatly increased gastric fluid volume at the time general anesthesia is induced. With this in mind, it seems more prudent to administer nonparticulate (clear) antacids, such as 15 to 30 mL sodium citrate as a single dose, approximately 30 minutes before the anticipated induction of general anesthesia (111,112,113).
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Table 139.3 Practice guidelines for preoperative fastinga |
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The pH of a 0.3 molar sodium citrate solution is 8.4, which reliably increases gastric fluid pH in pregnant and nonpregnant patients. If time permits, aspiration prophylaxis should be considered in all patients with a so-called “full stomach.” However, in emergency cases, neutralization of gastric secretion with sodium citrate shortly before intubation is often not possible if an adequate level of consciousness or a gag reflex is missing (48). Because of the slow onset of action, the use of H2 antagonists or proton pump inhibitors does not provide adequate suppression of acid production, nor does metoclopramide enhance gastric emptying in these emergency cases.
Based on the arguments mentioned above, the ASA Task Force on Preoperative Fasting (108) does not recommend the routine administration of antacids, gastric acid secretion blockers, antiemetics, or anticholinergics in patients who have no apparent increased risk for aspiration. Only nonparticulate antacids should be used when indicated for selected patients to decrease gastric acidity during the perioperative period (e.g., prior to cesarean section).
Rapid Sequence Induction
Protection against acid aspiration in patients at risk relies mainly upon rapid sequence induction (RSI). Injection of intravenous agents and the simultaneous application of effective cricoid pressure are followed immediately by tracheal intubation. The Sellick maneuver should be used when regional anesthesia is not feasible in patients thought to be at high risk for aspiration. The cricoid pressure is used to produce a collapse of the esophageal lumen and should be maintained until the endotracheal tube is visualized passing through the vocal cords, the cuff has been inflated, appropriate breath sounds are confirmed, mist is noted to be present in the endotracheal tube, and end-tidal CO2 presence is verified (29). Most anesthesiologists prefer an elevated head-up position during RSI. The rationale for this maneuver is that an intragastric pressure higher than 20 cm H2O is required to overcome the lower esophageal sphincter. The head-up position exceeding this distance impedes passive regurgitation, as in the case of muscle paralysis. In contrast, the head-down, Trendelenburg position would enable the regurgitated gastric contents to drain out of the oropharynx passively or be suctioned actively with a suction system. However, since endotracheal intubation usually is easier with the patient in an elevated, semirecumbent position, we would recommend it rather than the head-down position.
Despite taking all precautions, aspiration may still occur regardless of the patient's position or the applied cricoid pressure. Moreover, the ability to maintain adequate cricoid pressure for the necessary length of time and the accuracy in the delivery of cricoid pressure are uncertain. The application of cricoid pressure is a nonevidence-based, but clinically widespread, method in aspiration prophylaxis. Although there is little scientific evidence to support the widely held belief that the application of cricoid pressure reduces the incidence of aspiration during RSI (114), we recommend its use because of the minimal detrimental effects of application.
Because of the drawbacks to general anesthesia, many anesthesiologists prefer regional anesthesia for cesarean section. The use of these techniques for cesarean delivery has greatly increased due to the far lower incidence of aspiration. Accordingly, the incidence of maternal pulmonary aspiration has decreased greatly in the past decades—from 43 per 100,000 live births to 1.7 per 100,000 live births (115). The absolute number of deaths due to regional anesthesia has been decreased by 80%, down to 1.9 per 1,000,000 regional anesthetics. However, when general anesthesia is thought necessary for any reason, RSI and insertion of a cuffed endotracheal tube are obligatory.
When general anesthesia is indicated in patients at risk for pulmonary aspiration, airway management is one of the most important issues. Failed intubation occurs in the general surgical population at a rate of 1 in 2,330 (0.04%) (116), and is approximately eightfold higher in the obstetric population (117). Most airway catastrophes occur when airway difficulty is not recognized before the induction of anesthesia, and the anesthesiologist is not prepared to manage the difficult airway. Thus, meticulous preanesthetic examination is necessary to identify the patient at risk for airway difficulty as well as for aspiration; additionally, every airway should be considered a difficult airway, and backup plans should be in place if needed. The difficult airway is discussed elsewhere (Chapter 38).
Prevention of Aspiration in Critical Care
Several studies have demonstrated that regurgitation and aspiration is increased in tube-fed, critically ill patients lying in the supine position, as compared to the semirecumbent position (118,119,120). A fourfold higher VAP incidence was found in the supine position (34%) as compared to the semirecumbent group (8%) (120); there was also a significant association with gastric feeding and the occurrence of VAP. However, the risks of enteral feeding have to be balanced against its benefits. Thus, it seems prudent to avoid large gastric volumes rather than abandon gastric feeding per se in critically ill patients (17).
Theoretically, a cuff sealing the endotracheal tube against the tracheal wall will prevent aspiration of even the smallest amounts of oropharyngeal secretions, so-called microaspiration. Low-volume, high-pressure cuffs increase the risk of tracheal mucosal damage and, thus, are not appropriate for long-term endotracheal intubation. Instead, endotracheal tubes with high-volume, low-pressure cuffs are preferred if long-term intubation is expected. However, an endotracheal tube with a high-volume, low-pressure cuff does not prevent microaspiration from the subglottic area (121). Leakage of subglottic secretions occurs down longitudinal channels caused by folds within the inflated cuff wall. The reason for these folds is that the cuff must be larger than the cross-section of the trachea so it can adjust to the tracheal wall. Over the past several years, attempts have been made to improve the fit of the cuff in the tracheal wall by changing the shape and material of the cuff (122). Although some laboratory studies have demonstrated decreased leakage using improved cuff configurations, the problem of VAP is still not clinically solved with this approach.
Since pooled, bacterially contaminated secretions above the cuff are the reservoir for microaspiration, drainage of these secretions should reduce the incidence of aspiration and, consequently, the risk for VAP. However, conventional oropharyngeal suctioning techniques are usually not able to access this subglottic area, which is below the vocal cords and above the cuff of the tube. The removal of secretions from the subglottic region requires a specially designed endotracheal tube with a separate dorsal suctioning lumen, which opens into the subglottic region just above the cuff (123). This extra dorsal lumen is connected to an evacuation system, and the subglottic region is either drained intermittently or continuously with a gentle negative pressure—about 30 mm Hg suction. In four randomized controlled trials, which included more than 800 patients, the use of subglottic suction tubes was compared to conventional endotracheal tubes in critically ill patients (124,125,126,127). Only two of the four trials revealed a significant reduction of VAP in the subglottic suction group. There was no decrease in either mortality, length of stay, or duration of mechanical ventilation by the method tested (128). Moreover, in a recent animal study, it was shown that continuous subglottic suctioning may even be deleterious to the tracheal mucosa, while only marginally lowering the bacterial colonization of the lung (129). A recently published study revealed that the use of continuous subglottic suctioning did not modify the level of oropharyngeal and tracheal colonization in long-term ventilated critically ill patients. Two of five patients who had received subglottic suctioning developed laryngeal edema immediately after extubation, and required reintubation (130). A recent meta-analysis (131) studied the effects of subglottic drainage by evaluating the four studies mentioned above (124,125,126,127) and a fifth study (132). Subglottic suctioning in patients expected to require more than 72 hours of mechanical ventilation resulted in a significant reduction of the incidence of early-onset pneumonia (that occurring 5–7 days after endotracheal intubation). Furthermore, the duration of mechanical ventilation was shortened by 2 days, and the length of stay in the ICU was shortened by 3 days in these patients. These results suggest that subglottic suctioning may play a role in patients expected to be ventilated for prolonged periods, and only by reducing the incidence of early-onset pneumonia. However, the method (i.e., the specially designed tube) is expensive and may damage the tracheal mucosa. This risk must be weighed against the expected reduction of the incidence of VAP.
Prevention of Aspiration Pneumonia
Pneumonia depends on lung contamination with pathogenic micro-organisms as well as their virulence (i.e., their ability to overcome the host defense and cause an infection). Thus, another approach to avoid aspiration pneumonia is to prevent the consequences of microaspiration in endotracheally intubated patients rather than the microaspiration itself. The aspiration of small amounts of oropharyngeal secretions would be harmless for the lung if the sputum was sterile or only contaminated with nonpathogenic microbes. However, several factors—mainly the immunosuppression caused by severe illness, as well as antibiotic therapy itself, etc.—disturb the physiologic microbial balance, causing a shift in the microbiology of the oropharynx. Within a few days, the low-pathogenic and physiologic oropharyngeal microflora changes into a high-pathogenic abnormal flora, consisting mainly of Gram-negative bacilli (133). Therefore, the oropharynx of critically ill patients, and particularly the pooled secretions in the subglottic region, is heavily contaminated with potentially pathogenic microorganisms. Aspiration of oropharyngeal secretions contaminated with these pathogenic microbes is usually the source of aspiration pneumonia (134,135,136). Therefore, any approach to reduce the bacterial burden of the aspirated oropharyngeal secretions, as well as the virulence of the abnormal microbial flora, might reduce the morbidity of microaspiration and decrease VAP. Topically administered antibiotics at the contamination site (i.e., the oropharynx and the airway) eradicate the micro-organisms, or at least reduce their number and, thus, impede the development of aspiration pneumonia. However, there is a considerable controversy about such prophylactic administration of antimicrobial agents given that it enhances the risk of developing resistant bacterial strains. During the last decades, two approaches have been used in mechanically ventilated, critical care patients. One method is the nebulization of antibiotics into the airways via the endotracheal tube to reduce the colonization of bacteria in the bronchial tract (137,138,139). The other approach is the decontamination of the sources of the pathogenic microbes (i.e., decontamination of the oropharynx as well as the gastrointestinal tract). Usually nonabsorbable antibiotics are used in both methods to allow the application of supra-high local antibiotic concentrations at the target site (i.e., the airways or the oropharynx and gastrointestinal tract) without unwanted systemic toxic side effects. The use of supra-high local antibiotic concentrations may prevent or, at least, impede the development of antibiotic resistance.
Most often, aminoglycosides have been used for nebulization. Besides their use in the critically ill, there is substantial experience in patients suffering from mucoviscidosis and cystic fibrosis with the application of nebulized aminoglycosides.
Although some data on the use of nebulized antibiotics in mechanically ventilated patients are promising, a final conclusion cannot be made because the studies vary in their methodology and are inadequately powered. Moreover, application of nebulized antibiotics is only effective in preventing pneumonia, and seems not to benefit patients with active pneumonia, particularly when compared to the use of potent systemic antibiotics (140). Mortality was not decreased by the use of nebulized antibiotics in mechanically ventilated patients. Three recently published reviews extensively discuss this topic (137,138,139).
Another approach to reduce the bacterial colonization of the respiratory tract is the decontamination of the patient's internal bacterial sources (i.e., the gut, the stomach, and the oropharynx). However, while total decontamination of the oropharyngeal cavity and the gastrointestinal tract is not possible, selective decontamination of the oropharynx and the digestive tract (SDD) has been shown to reduce aspiration pneumonia in critically ill patients (141). The concept of SDD is the elimination of the main pathogenic bacilli (especially Gram-negative bacteria and S. aureus) as well as yeasts by oral and enteral application of a combination of nonabsorbable antibiotics and antimycotics (142). These microbes are very often involved in major infections in critically ill patients, whereas they play virtually no role in the physiologic intestinal ecosystem. SDD, as a means of infection prophylaxis, should suppress/eliminate as many potentially pathogenic micro-organisms as possible, leaving the relatively harmless and even protective anaerobic microflora unchanged (143). SDD has been studied in various critically ill patient populations, and several meta-analyses have been published (141,144,145). To date, randomized controlled trials have only demonstrated a significant decrease of VAP and mortality in trauma and liver transplant patients (146,147,148). SSD requires meticulous microbial surveillance to monitor the effects of the applied agents (i.e., the successful selective decontamination), as well as the possible emergence of antibiotic resistance. Owing to the risk–benefit controversy, the use of SDD is not commonplace in the United States, and it is routinely used only in selected centers in Europe (149).
Pearls
1. The major risk factor for aspiration is a reduced level of consciousness. General anesthesia is a risk factor, particularly in emergency cases. Furthermore, any situation that leads to increased gastric pressure or increased gastric content may amplify the incidence of regurgitation and vomiting and, consequently, the risk of pulmonary aspiration.
2. Critically ill patients with ventilatory insufficiency are at particular risk of pulmonary aspiration. Even in patients whose airway is protected by a cuffed endotracheal tube, microaspiration is common, because the cuff configuration does not provide a complete sealing of the trachea.
3. In general anesthetics, the overall incidence of pulmonary aspiration is approximately 1 in 3,000. The pregnant patient is at higher risk for aspiration of gastric contents (about 1 in 900 to 1 in 1,400) for a variety of reasons, including mechanical, hormonal, and iatrogenic factors.
4. Silent aspiration during short-term endotracheal intubation, such as during anesthesia, is only of minor concern.
5. Silent aspiration in long-term intubated and mechanically ventilated patients is common and has been detected in up to 90% of patients. Since aspiration is the main cause of pneumonia in critically ill patients, this issue is of major concern.
6. In emergency medicine, aspiration is a common event due to a reduced consciousness and the impaired protective reflexes of emergency patients. The less prepared, prehospital setting further increases the risk of aspiration.
7. It is important to distinguish between aspiration pneumonitis and aspiration pneumonia. Aspiration pneumonitis is caused by chemically injurious agents (e.g., acid). Such agents destroy the lung tissue directly (e.g., by chemical burn). In contrast, aspiration pneumonia occurs as a result of microaspiration of bacterially contaminated, subglottic secretions in critically ill patients who are usually endotracheally intubated and mechanically ventilated.
8. The pulmonary consequence of aspiration depends on the nature of the aspirated substance:
a. Acid-related aspiration causes pneumonitis, a chemical injury to the lung parenchyma.
b. Aspiration of solid particles leads to acute airway obstruction or reflex airway closure with arterial hypoxemia, depending on the size of the particles and the obstructed lung area downstream of the obstruction.
c. Aspiration of blood is harmless in most circumstances.
d. Microaspiration of subglottic secretions is the major cause of ventilator-associated pneumonia. The harm of microaspiration depends on the virulence and the amount of bacteria contaminating the oropharyngeal secretions.
9. Bronchoscopy, most effective rigid, should only be used to remove solid particles from the airway. Bronchoscopy does not improve the course and outcome of patients who aspirated only liquid acid gastric contents.
10. Bronchial lavage after aspiration of gastric acid is rather deleterious, because it may spread the aspirate to previously unaffected lung areas and can wash out surfactant.
11. Steroids in the treatment of aspiration pneumonitis have been shown to be clinically ineffective. The administration of corticosteroids is controversial and most likely does not yield benefit or improvement of long-term outcome after aspiration. Application of β2 sympathomimetics improves bronchospastic symptoms and may improve the removal of airway edema.
12. The cornerstones of the treatment of the harmful consequences of pulmonary aspiration are symptomatic measures, such as oxygen application, mechanical ventilation with PEEP, and antibiotic therapy only in case of pneumonia.
13. Prevention of macroaspiration during general anesthesia include the following principles:
a. Identification of the patient at risk
b. Skilled and well-prepared personnel (staff anesthesiologist and specialized nurse)
c. Relief of gastric pressure in case of increased contents (i.e., ileus)
d. Maintaining lower esophageal sphincter competence (i.e., removal of the nasogastric tube before induction of anesthesia)
e. In the obstetric patient, alkalization of gastric acid prior to induction
f. Rapid sequence induction including application of cricoid pressure
References
1. Dice WH, Ward B, Kelly J, et al. Pulmonary toxicity following gastrointestinal absorption of kerosene. Ann Emerg Med. 1982;11:138.
2. Bynum K, Pierce AK. Pulmonary aspiration of gastric contents. Am Rev Respir Dis. 1976;114:1129.
3. Grand RJ, Watkins JB, Torti FM. Development of the human gastrointestinal tract. A review. Gastroenterology. 1976;70:790–810.
4. Chadwick J, Mann WN. Medical Works of Hippocrates. Oxford: C& J Adlard; 1950.
5. Simpson JY. Remarks on the alleged case of death from the action of chloroform. Lancet. 1848;1:175.
6. Mendelson CL. The aspiration of stomach contents into the lungs during obstetric anesthesia. Am J Obstet Gynecol. 1946;52:191.
7. Goodwin SR: Aspiration syndromes. In: Civetta JM, Taylor RW, Kirby RR, eds. Critical Care. 3rd ed. Philadelphia: Lippincott-Raven; 1997:1861–1873.
8. Teabeaut JR II. Aspiration of gastric contents: an experimental study. Am J Pathol. 1952;24:51.
9. Roberts RB, Shirley MA. Reducing the risk of acid aspiration during cesarean section [no abstract available]. Anesth Analg. 1974;53:859–868.
10. James CF, Modell JH, Gibbs CP, et al. Pulmonary aspiration—effects of volume and pH in the rat. Anesth Analg. 1984;63:665–668.
11. Bynum LJ, Pierce AK. Pulmonary aspiration of gastric contents. Am Rev Respir Dis. 1976;114:1129–1136.
12. Gleeson K, Eggli DF, Maxwell SL. Quantitative aspiration during sleep in normal subjects. Chest. 1997;111:1266.
13. Pontoppidan H, Beecher HK. Progressive loss of protective reflexes in the airway with the advance of age. JAMA. 1960;174:2209.
14. Vaughan RW, Bauer S, Wise L. Volume and pH of gastric juice in obese patients. Anesthesiology. 1975;43:686–689.
15. Illing L, Duncan PG, Yip R. Gastroesophageal reflux during anaesthesia. Can J Anaesth. 1992;39:466–470.
16. Cook D. Ventilator associated pneumonia: perspectives on the burden of illness [review]. Intensive Care Med. 2000;26(Suppl 1):S31–37.
17. McClave SA, DeMeo MT, DeLegge MH, et al. North American Summit on aspiration in the critically ill patient: consensus statement. JPEN J Parenter Enteral Nutr. 2002;26(6 Suppl):S80–85.
18. Barquist E, Brown M, Cohn S, et al. Postextubation fiberoptic endoscopic evaluation of swallowing after prolonged endotracheal intubation: a randomized, prospective trial. Crit Care Med. 2001;29:1710–1713.
19. Olsson GL, Hallen B, Hambraeus-Jonzon K. Aspiration during anaesthesia: a computer-aided study of 185,358 anaesthetics. Acta Anaesthesiol Scand. 1986;30:84–92.
20. Warner MA, Warner ME, Weber JG. Clinical significance of pulmonary aspiration during the perioperative period. Anesthesiology. 1993;78:56–62.
21. Mellin-Olsen J, Fasting S, Gisvold SE. Routine preoperative gastric emptying is seldom indicated. A study of 85,594 anaesthetics with special focus on aspiration pneumonia. Acta Anaesthesiol Scand. 1996;40:1184–1188.
22. Jeffrey H, Kozlow BA, Berenholtz SM, et al. Epidemiology and impact of aspiration pneumonia in patients undergoing surgery in Maryland, 1999–2000. Crit Care Med. 2003;31:1930.
23. Marik PE. Aspiration pneumonia: mixing apples with oranges and tangerines. Crit Care Med. 2004;32:1236.
24. Tiret L, Nivoche Y, Hatton F, et al. Complications related to anaesthesia in infants and children. A prospective survey of 40240 anaesthetics. Br J Anaesth. 1988;61:263–269.
25. Hawkins JL. Anesthesia-related maternal mortality [review; no abstract available]. Clin Obstet Gynecol. 2003;46:679–687.
26. Munnur U, de Boisblanc B, Suresh MS. Airway problems in pregnancy. Crit Care Med. 2005;33(10 Suppl):S259–S268.
27. Cheney FW. The American Society of Anesthesiologists Closed Claims Project: what have we learned, how has it affected practice, and how will it affect practice in the future? Anesthesiology. 1999;91:552.
28. Chadwick HS, Posner K, Caplan RA, et al. A comparison of obstetric and nonobstetric anesthesia malpractice claims. Anesthesiology. 1991;74:242–249.
29. James CF. Cesarean section. In: Lobato EB, Gravenstein N, Kirby RR, eds. Complications in Anesthesiology. Philadelphia: Lippincott Williams & Wilkins; 2008:673–690.
30. La Rosa M, Piva L, Ravanelli A, et al. Aspiration syndrome in cesarean section. Our experience from 1980 to 1990 [Italian]. Minerva Anestesiol. 1992;58:1213.
31. Soreide E, Bjornestad E, Steen PA. An audit of perioperative aspiration pneumonitis in gynaecological and obstetric patients. Acta Anaesthesiol Scand. 1996;40:14–19.
32. Berson W, Adriani J. Silent regurgitation and aspiration during anesthesia. Anesthesiology. 1954;15:644–649.
33. Stark DC. Aspiration in the surgical patient. Int Anesthesiol Clin. 1977;15:13–48.
34. Blitt CD, Gutmann HL, Cohen DD, et al. “Silent” regurgitation and aspiration during general anesthesia. Anest Analg. 1970;49:707–713.
35. Hirsch J. Impact of postoperative nausea and vomiting in the surgical setting. Anaesthesia. 1994;49(Suppl):30–33.
36. Kinsey GC, Murray MJ, Swensen SJ, et al. Glucose content of tracheal aspirates: implications for the detection of tube feeding aspiration. Crit Care Med. 1994;22:1557–1562.
37. Heyland DK, Drover JW, MacDonald S, et al. Effect of postpyloric feeding on gastroesophageal regurgitation and pulmonary microaspiration: results of a randomized controlled trial. Crit Care Med. 2001;29:1495–1501.
38. Metheny NA, Clouse RE, Chang YH, et al. Tracheobronchial aspiration of gastric contents in critically ill tube-fed patients: frequency, outcomes, and risk factors. Crit Care Med. 2006;34:1007–1015.
39. Elpern EH, Scott MG, Petro L, et al. Pulmonary aspiration in mechanically ventilated patients with tracheostomies. Chest. 1994;105:563–566.
40. Leder S-B. Incidence and type of aspiration in acute care patients requiring mechanical ventilation via a new tracheotomy. Chest. 2002;122:1721–1726.
41. Chevret S, Hemmer M, Carlet J, et al. Incidence and risk factors of pneumonia acquired in intensive care units. Results from a multicenter prospective study on 996 patients. European Cooperative Group on Nosocomial Pneumonia. Intensive Care Med. 1993;19:256–264.
42. Rello J, Diaz E. Pneumonia in the intensive care unit. Crit Care Med. 2003;31:2544–2551.
43. George DV. Epidemiology of nosocomial ventilator-associated pneumonia. Infect Control Hosp Epidemiol. 1993;14:163–169.
44. LoCicero J 3rd. Bronchopulmonary aspiration [review]. Surg Clin North Am. 1989;69:71–76.
45. Gentleman D, Dearden M, Midgley S, et al. Guidelines for resuscitation and transfer of patients with serious head injury [review; no abstract available]. BMJ. 1993;307(6903):547–552.
46. Vadeboncoeur TF, Davis DP, Ochs M, et al. The ability of paramedics to predict aspiration in patients undergoing prehospital rapid sequence intubation. J Emerg Med. 2006;30:131–136.
47. Lockey DJ, Coats T, Parr MJ. Aspiration in severe trauma: a prospective study. Anaesthesia. 1999;54:1097–1098.
48. Gabrielli A, Layon AJ. Airway management in the neurointensive care unit. In: Layon AJ, Gabrielli A, Friedman WA, eds. Textbook of Neurointensive Care. Philadelphia: Saunders; 2004:499–531.
49. Ufberg JW, Bushra JS, Karras DJ, et al. Aspiration of gastric contents: association with prehospital intubation. Am J Emerg Med. 2005;23:379–382.
50. Cogbill TH, Bintz M, Johnson JA, et al. Acute gastric dilatation after trauma. J Trauma. 1987;27:1113–1117.
51. Lawes EG, Baskett PJ. Pulmonary aspiration during unsuccessful cardiopulmonary resuscitation. Intensive Care Med. 1987;13:379–382.
52. Marik PE. Aspiration pneumonitis and aspiration pneumonia. N Engl J Med. 2001;344:665–671.
53. Engelhardt T, Webster NR. Pulmonary aspiration of gastric contents in anaesthesia. Br J Anaesth. 1999;83:453–460.
54. Isbister GK, Downes F, Sibbritt D, et al. Aspiration pneumonitis in an overdose population: frequency, predictors, and outcomes. Crit Care Med. 2004;32:88–93.
55. Mattay MA, Mednick G, Matthay ZA. Aspiration-induced lung injury: experimental and human studies. In: Vincent JL, ed. Yearbook of Intensive Care and Emergency Medicine. Berlin: Springer; 2006:349–365.
56. Folkesson HG, Matthay MA, Hebert CA, et al. Acid aspiration-induced lung injury in rabbits is mediated by interleukin-8-dependent mechanisms. J Clin Invest. 1995;96:107–116.
57. Porembka DT, Kier A, Sehlhorst S, et al. The pathophysiologic changes following bile aspiration in a porcine lung model. Chest. 1993;104:919–924.
58. Midulla F, Guidi R, Barbato A, et al. Foreign body aspiration in children. Pediatr Int. 2005;47:663–668.
59. Cotton E, Yasuda K. Foreign body aspiration. Pediatr Clin North Am. 1984;31:937–941.
60. Center for Disease Control (CDC). Nonfatal choking-related episodes among children—United States, 2001. MMWR Morb Mortal Wkly Rep. 2002;51:945–948.
61. Aytac A, Yurdakul Y, Ikizler C, et al. Inhalation of foreign bodies in children. Report of 500 cases. J Thorac Cardiovasc Surg. 1977;74:145–151.
62. Ayed AK, Jafar AM, Owayed A. Foreign body aspiration in children: diagnosis and treatment. Pediatr Surg Int. 2003;19:485–488.
63. Szidon JP, Fishman AP. Approach to the pulmonary patient with respiratory signs and symptoms. In: Pulmonary Diseases and Disorders. 2nd ed. New York: McGraw-Hill; 1988:346–351.
64. Perel A, Downs JB, Crawford CA, et al. Continuous positive airway pressure improves oxygenation in dogs after the aspiration of blood. Crit Care Med. 1983;11:868–871.
65. Moran TJ, Hellstrom HR. Experimental aspiration pneumonia. V. Acute pulmonary edema, pneumonia, and bronchiolitis obliterans produced by injection of ethyl alcohol. Am J Clin Pathol. 1957;27:300–308.
66. Dice WH, Ward G, Kelley J, et al. Pulmonary toxicity following gastrointestinal ingestion of kerosene. Ann Emerg Med. 1982;11:138–142.
67. Goodwin SR, Berman LS, Tabeling BB, et al. Kerosene aspiration: immediate and early pulmonary and cardiovascular effects. Vet Hum Toxicol. 1988;30:521–524.
68. de Graaf P, Slagt C, de Graaf JL, et al. Fatal aspiration of polyethylene glycol solution. Neth J Med. 2006;64:196–198.
69. Mackowiak PA. The normal microbial flora. N Engl J Med. 1982;307:83–93.
70. Vidyasagar D, Harris V, Pildes RS. Assisted ventilation in infants with meconium aspiration syndrome. Pediatrics. 1975;56(2):208–213.
71. Ross MG. Meconium aspiration syndrome-more than intrapartum meconium [no abstract available]. N Engl J Med. 2005;353:946–948.
72. Wiswell TE, Tuggle JM, Turner BS. Meconium aspiration syndrome: have we made a difference? Pediatrics. 1990;85:715–721.
73. Fraser WD, Hofmeyr J, Lede R, et al. Amnioinfusion Trial Group. Amnioinfusion for the prevention of the meconium aspiration syndrome. N Engl J Med. 2005;353:909–917.
74. Vain NE, Szyld EG, Prudent LM, et al. Oropharyngeal and nasopharyngeal suctioning of meconium-stained neonates before delivery of their shoulders: multicentre, randomised controlled trial. Lancet. 2004;364:597–602.
75. O'Hare B, Chin C, Lerman J, et al. Acute lung injury after instillation of human breast milk into rabbits' lungs: effects of pH and gastric juice. Anesthesiology. 1999;90:1112–1118.
76. Leighton BL. Intraoperative anesthetic complications. In: Noris MC, ed. Obstetric Anesthesia. 2nd ed. Philadelphia: Lippincott Williams & Wilkins; 1999:539–618.
77. Kinni ME, Stout MM. Aspiration pneumonitis: predisposing conditions and prevention. J Oral Maxillofac Surg. 1986;44:378–384.
78. Kinsey GC, Murray MJ, Swensen SJ, et al. Glucose content of tracheal aspirates: implications for the detection of tube feeding aspiration. Crit Care Med. 1994;22:1557–1562.
79. Metheny NA, Clouse RE, Chang YH, et al. Tracheobronchial aspiration of gastric contents in critically ill tube-fed patients: frequency, outcomes, and risk factors. Crit Care Med. 2006;34:1007–1015.
80. Badellino MM, Buckman RF Jr, Malaspina PJ, et al. Detection of pulmonary aspiration of gastric contents in an animal model by assay of peptic activity in bronchoalveolar fluid. Crit Care Med. 1996;24:1881–1885.
81. Ufberg JW, Bushra JS, Patel D, et al. A new pepsin assay to detect pulmonary aspiration of gastric contents among newly intubated patients. Am J Emerg Med. 2004;22:612–614.
82. Spurrier EJ, Clancy MJ, Deakin CD. Laryngopharyngeal pH measurement. Emerg Med J. 2004;21:493–494.
83. Artigas AT, Dronda SB, Vallés EC, et al. Risk factors for nosocomial pneumonia in critically ill trauma patients. Crit Care Med. 2001;29:304–309.
84. Torres A, Aznar R, Gatell JM, et al. Incidence, risk, and prognosis factors of nosocomial pneumonia in mechanically ventilated patients. Am Rev Respir Dis. 1990;142:523–528.
85. Frank JA, Gutierrez JA, Jones KD, et al. Low tidal volume reduces epithelial and endothelial injury in acid-injured rat lungs. Am J Respir Crit Care Med. 2002;165:242–249.
86. The Acute Respiratory Distress Syndrome Network. Efficacy of low tidal volume ventilation in patients with different clinical risk factors for acute lung injury and the acute respiratory distress syndrome. Am J Respir Crit Care Med. 2001;64:231.
87. McAuley DF, Frank JA, Fang X, et al. Clinically relevant concentrations of beta2-adrenergic agonists stimulate maximal cyclic adenosine monophosphate-dependent airspace fluid clearance and decrease pulmonary edema in experimental acid-induced lung injury. Crit Care Med. 2004;32:1470–1476.
88. Musante G, Schnitzler E. Different therapeutic perspectives for novel exogenous surfactant preparations. Crit Care Med. 2006;34:260–261.
89. Hilgendorff A, Doerner M, Rawer D, et al. Effects of a recombinant surfactant protein-C-based surfactant on lung function and the pulmonary surfactant system in a model of meconium aspiration syndrome. Crit Care Med. 2006;34:203–210.
90. Anzueto A, Baughman R, Guntupalli K, et al. An international randomized, placebo-controlled trial evaluating the efficacy of aerosolized surfactant in patients with sepsis-induced ARDS. Am J Resp Crit Care. 1994;149:A567.
91. Lauer S, Fischer L, Stubbe H, et al. (K)eine Surfactant-Therapie bei Patienten mit “acute respiratory distress syndrome”? Der Anaesthesist. 2006;55:433–442.
92. Wynne JW, DeMarco FJ, Hood CI. Physiological effects of corticosteroids in foodstuff aspiration. Arch Surg. 1981;116:46–49.
93. Lee M, Sukumaran M, Berger HW, et al. Influence of corticosteroid treatment on pulmonary function after recovery from aspiration of gastric contents [no abstract available]. Mt Sinai J Med. 1980;47:341–346.
94. Lowrey LD, Anderson M, Calhoun J, et al. Failure of corticosteroid therapy for experimental acid aspiration [no abstract available]. J Surg Res. 1982;32:168–172.
95. Bernard GR, Luce JM, Sprung CL, et al. High-dose corticosteroids in patients with the adult respiratory distress syndrome. N Engl J Med. 1987;317:1565–1570.
96. Ott SR, Lode H. Diagnostik und Therapie der Aspirationspneumonie. Dtsch Med Wochenschr. 2006;131:624–628.
97. LeFrock JL, Clark TS, Davies B, et al. Aspiration pneumonia: a ten-year review. Am Surg. 1979;45:305–313.
98. Brun-Buisson C. Advances and controversies in the epidemiology, diagnosis, and prevention of nosocomial pneumonia in the ICU. Curr Opin Crit Care. 1995;1:341–348.
99. Ewig S, Torres A, El-Ebiary M, et al. Bacterial colonization patterns in mechanically ventilated patients with traumatic and medical head injury. Incidence, risk factors, and association with ventilator-associated pneumonia. Am J Respir Crit Care Med. 1999;159:188–198.
100. Kallar SK, Everett LL. Potential risks and preventive measures for pulmonary aspiration: new concepts in preoperative fasting guidelines. Anesth Analg. 1993;77:171–182.
101. Sutherland AD, Maltby JR, Sale JP, et al. The effect of preoperative oral fluid and ranitidine on gastric fluid volume and pH. Can J Anaesth. 1987;34:117–121.
102. McGrady EM, Macdonald AG. Effect of the preoperative administration of water on gastric volume and pH. Br J Anaesth. 1988;60:803–805.
103. Hutchinson A, Maltby JR, Reid CR. Gastric fluid volume and pH in elective inpatients. Part I: coffee or orange juice versus overnight fast. Can J Anaesth. 1988;35:12–15.
104. Warner MA, Warner ME, Warner DO, et al. Perioperative pulmonary aspiration in infants and children. Anesthesiology. 1999;90:66–71.
105. Kehlet H, Wilmore DW. Multimodal strategies to improve surgical outcome. Am J Surg. 2002;183:630–641.
106. Schwartz DJ, Wynne JW, Gibbs CP, et al. The pulmonary consequences of aspiration of gastric contents at pH values greater than 2.5. Am Rev Respir Dis. 1980;121:119–126.
107. Splinter WM, Stewart JA, Muir JG. Large volumes of apple juice preoperatively do not affect gastric pH and volume in children. Can J Anaesth. 1990;37:36–39.
108. American Society of Anesthesiologist Task Force on Preoperative Fasting. Practice guidelines for preoperative fasting and the use of pharmacologic agents to reduce the risk of pulmonary aspiration: application to healthy patients undergoing elective procedures: a report by the American Society of Anesthesiologist Task Force on Preoperative Fasting. Anesthesiology. 1999;90:896–905.
109. Taylor G. Acid pulmonary aspiration syndrome after antacids. A case report. Br J Anaesth. 1975;47:615–617.
110. Tompkinson J, Turnbull A, Robson R, et al. Report on confidential enquiries into maternal deaths in England and Wales 1976–1978. London: Her Majesty's Stationery Office. 1982;79.
111. Gibbs CP, Spohr L, Schmidt D. The effectiveness of sodium citrate as an antacid [no abstract available]. Anesthesiology. 1982;57:44–46.
112. Holdsworth JD, Johnson K, Mascall G, et al. Mixing of antacids with stomach contents. Another approach to the prevention of the acid aspiration (Mendelson's) syndrome. Anaesthesia. 1980;35:641–650.
113. Viegas OJ, Ravindran RS, Shumacker CA. Gastric fluid pH in patients receiving sodium citrate. Anesth Analg. 1981;60:521–523.
114. Butler J, Sen A. Best evidence topic report. Cricoid pressure in emergency rapid sequence induction [review]. Emerg Med J. 2005;22:815–816.
115. Hawkins JL, Koonin LM, Palmer SK, et al. Anesthesia-related deaths during obstetric delivery in the United States, 1979–1990. Anesthesiology. 1997;86:277–284.
116. Samsoon GL, Young JR. Difficult tracheal intubation: a retrospective study. Anaesthesia. 1987;42:487–490.
117. Lyons G. Failed intubation. Six years' experience in a teaching maternity unit. Anaesthesia. 1985;40:759–762.
118. Torres A, Serra-Batlles J, Ros E, et al. Pulmonary aspiration of gastric contents in patients receiving mechanical ventilation: the effect of body position. Ann Intern Med. 1992;116:540–543.
119. Ibanez J, Penafiel A, Raurich JM, et al. Gastroesophageal reflux in intubated patients receiving enteral nutrition: effect of supine and semirecumbent positions. JPEN J Parenter Enteral Nutr. 1992;16:419–422.
120. Drakulovic MB, Torres A, Bauer TT, et al. Supine body position as a risk factor for nosocomial pneumonia in mechanically ventilated patients: a randomised trial. Lancet. 1999;354:1851–1858.
121. Seegobin RD, van Hasselt GL. Aspiration beyond endotracheal cuffs. Can Anaesth Soc J. 1986;33:273–279.
122. Young PJ, Blunt MC. Improving the shape and compliance characteristics of a high-volume, low-pressure cuff improves tracheal seal. Br J Anaesth. 1999;83:887–889.
123. Diaz E, Rodriguez AH, Rello J. Ventilator-associated pneumonia: issues related to the artificial airway. Respir Care. 2005;50:900–906; discussion 906–909.
124. Kollef MH, Skubas NJ, Sundt TM. A randomized clinical trial of continuous aspiration of subglottic secretions in cardiac surgery patients. Chest. 1999;116:1339–1346.
125. Mahul PH, Auboyer C, Jospe R, et al. Prevention of nosocomial pneumonia in intubated patients: respective role of mechanical subglottic secretions drainage and stress ulcer prophylaxis. Intensive Care Med. 1992;18:20–25.
126. Smulders K, van der Hoeven H, Weers-Pothoff I, et al. A randomized clinical trial of intermittent subglottic secretion drainage in patients receiving mechanical ventilation. Chest. 2002;121:858–862.
127. Valles J, Artigas A, Rello J, et al. Continuous aspiration of subglottic secretions in preventing ventilator-associated pneumonia. Ann Intern Med. 1995;122:179–186.
128. van Saene HK, Ashworth M, Petros AJ, et al. Do not suction above the cuff. Crit Care Med. 2004;32:2160–2162.
129. Berra L, De Marchi L, Panigada M, et al. Evaluation of continuous aspiration of subglottic secretion in an in vivo study. Crit Care Med. 2004;32:2071–2078.
130. Girou E, Buu-Hoi A, Stephan F, et al. Airway colonisation in long-term mechanically ventilated patients. Effect of semi-recumbent position and continuous subglottic suctioning. Intensive Care Med. 2004;30:225–233.
131. Dezfulian C, Shojania K, Collard HR, et al. Subglottic secretion drainage for preventing ventilator-associated pneumonia: a meta-analysis. Am J Med. 2005;118:11–18.
132. Bo H, He L, Qu J. Influence of the subglottic secretion drainage on the morbidity of ventilator associated pneumonia in mechanically ventilated patients [in Chinese]. Zhonghua Jie He He Hu Xi Za Zhi. 2000;23:472–474.
133. Johanson WG, Pierce AK, Sanford JP. Changing pharyngeal bacterial flora of hospitalized patients. Emergence of gram-negative bacilli. N Engl J Med. 1969;281:1137–1140.
134. Johanson WG Jr, Pierce AK, Sanford JP, et al. Nosocomial respiratory infections with gram-negative bacilli. The significance of colonization of the respiratory tract. Ann Intern Med. 1972;77:701–706.
135. van Uffelen R, van Saene HK, Fidler V, et al. Oropharyngeal flora as a source of bacteria colonizing the lower airways in patients on artificial ventilation. Intensive Care Med. 1984;10:233–237.
136. Bonten MJ, Gaillard CA, de Leeuw PW, et al. Role of colonization of the upper intestinal tract in the pathogenesis of ventilator-associated pneumonia. Clin Infect Dis. 1997;24:309–319.
137. Cole PJ, et al. The role of nebulized antibiotics in treating serious respiratory infections. J Chemother. 2001;13:354–362.
138. Falagas ME, Siempos II, Bliziotis IA, et al. Administration of antibiotics via the respiratory tract for the prevention of ICU-acquired pneumonia: a meta-analysis of comparative trials. Crit Care. 2006;10(4):R123.
139. Wood GC, Boucher BA. Aerosolized antimicrobial therapy in acutely ill patients. Pharmacotherapy. 2000;20:166–181.
140. Schaad UB, Wedgwood-Krucko J, Suter S, et al. Efficacy of inhaled amikacin as adjunct to intravenous combination therapy (ceftazidime and amikacin) in cystic fibrosis. Pediatrics. 1987;111:599–605.
141. van Saene HK, Petros AJ, Ramsay G, et al. All great truths are iconoclastic: selective decontamination of the digestive tract moves from heresy to level 1 truth. Intensive Care Med. 2003;29:677–690.
142. van der Waaij D, Manson WL, Arends JP, et al. Clinical use of selective decontamination: the concept. Intensive Care Med. 1990;16(Suppl 3):S212–216.
143. van der Waaij D. History of recognition and measurement of colonization resistance of the digestive tract as an introduction to selective gastrointestinal decontamination. Epidemiol Infect. 1992;109:315–326.
144. Nathens AB, Marshall JC. Selective decontamination of the digestive tract in surgical patients: a systematic review of the evidence. Arch Surg. 1999;134:170–176.
145. Safdar N, Said A, Lucey MR. The role of selective digestive decontamination for reducing infection in patients undergoing liver transplantation: a systematic review and meta-analysis. Liver Transpl. 2004;10:817–827.
146. Stoutenbeek CP, van Saene HK, Miranda DR, et al. The effect of selective decontamination of the digestive tract on colonisation and infection rate in multiple trauma patients. Intensive Care Med. 1984;10:185–192.
147. Ledingham IM, Alcock SR, Eastaway AT, et al. Triple regimen of selective decontamination of the digestive tract, systemic cefotaxime, and microbiological surveillance for prevention of acquired infection in intensive care. Lancet. 1988;1(8589):785–790.
148. de Jonge E, Schultz MJ, Spanjaard L, et al. Effects of selective decontamination of digestive tract on mortality and acquisition of resistant bacteria in intensive care: a randomised controlled trial. Lancet. 2003;362:1011–1016.
149. Misset B, Artigas A, Bihari D, et al. Short-term impact of the European Consensus Conference on the use of selective decontamination of the digestive tract with antibiotics in ICU patients. Intensive Care Med. 1996;22:981–984.