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General anesthesia may predispose patients to aspiration of gastroesophageal contents because of depression of protective reflexes during loss of consciousness. In addition, some patients may be at increased risk of pulmonary aspiration because of retention of gastric contents caused by pain, inadequate starvation, or gastrointestinal pathology resulting in reduced gastric emptying and gastroesophageal reflux. Despite increasing knowledge of the problems associated with aspiration, the relatively small incidence and associated mortality rates in the perioperative period do not appear to have changed markedly over the last few decades. In this review article, the physiological factors associated with an increased risk of gastroesophageal reflux and aspiration are considered together with some of the methods that are used to prevent aspiration. In particular, preoperative starvation, the use of drugs designed to increase gastric pH, recent developments in airway devices, and appropriate application of cricoid pressure are critically appraised.
Examination of the literature suggests that the incidence of pulmonary aspiration in the perioperative period is relatively infrequent and that there has been little change in the last few years. In 1986, a study of Scandinavian Teaching Hospitals suggested that the incidence of aspiration varied between 0.7 and 4.7 per 10,000 general anesthetics (1). A report published one decade later suggested that the incidence was 2.9 per 10,000 at a Norwegian hospital (2). Studies from the Mayo Clinic indicated that the incidence of aspiration is similar in adults (3.1 per 10,000) (3) and children (3.8 per 10,000) (4) although another study from the United States suggested that the incidence of aspiration in children was more frequent (10.2 per 10,000) (5). It is generally held that obstetric anesthetic practice is a high-risk area for aspiration and also that the mortality rate is likely to be more frequent during obstetric aspiration than during general surgery. However, a recent study examining obstetric procedures (excluding cesarean delivery) between 1979 and 1993 demonstrated only one case of aspiration in 1870 general anesthetics, an incidence of 5.3 per 10,000. Of particular interest in this study sent from Israel is the fact that despite the universal recommendation for tracheal intubation, general anesthesia was administered via a face mask (6). In low-risk cases, where the standard contraindications to the use of the laryngeal mask airway (LMA) were followed (e.g., absence of gastrointestinal pathology, obesity, history of reflux, or emergency surgery), the use of the LMA from the time of its introduction into clinical practice in 1988 until 1993 was examined by using a metaanalysis. There were only three reported cases of aspiration in 12,901 anesthetics, an incidence of 2.3 per 10,000 (7). There is little doubt that the incidence of aspiration after trauma is markedly increased owing to the risk of both recent ingestion of food, depression of consciousness and airway reflexes, and gastric stasis induced by raised sympathoadrenal tone. A study confirming these views was undertaken recently and showed that in 53 adults with a Glasgow Coma Scale score <8 and whose tracheae were intubated by members of the London Helicopter Emergency Medical Service, the incidence of gross aspiration was 38% (8). Studies on the incidence of aspiration in the perioperative period are summarized in Table 1. It may be seen that, over the last few decades, there is no evidence to suggest that the incidence of this important anesthetic complication has changed. Although they have not been subjected to formal evaluation, it is suggested that the factors that contribute to the likelihood of aspiration include the urgency of surgery, airway problems, inadequate depth of anesthesia, use of the lithotomy position, gastrointestinal problems, depressed consciousness, increased severity of illness, and obesity.
Although the incidence of aspiration has remained infrequent and relatively constant, many anesthesiologists would opine that there has been a marked increase in the extent of surgery undertaken in the sick, more elderly population. In such a population, the incidence of regurgitation and aspiration would be expected to increase and the failure to demonstrate any change in the incidence of aspiration possibly results from improvements in clinical management.
Morbidity and Mortality Attributable to Aspiration In the Australian Incident Monitoring Study, the death rate in patients who aspirated was 3.8% (9); whereas at the Mayo Clinic from 1985 to 1991, the death rate in adults was 4.5% (3). This value compares well with the death rate of 4.6% in Sweden from 1967 to 1970 and 19751985 (1). In obstetric practice in the United Kingdom, more accurate data on mortality after aspiration are available as a result of the careful audit by the Confidential Enquiry into Maternal Deaths (10). In this particular branch of anesthesia, it is clear that the number of maternal deaths arising from anesthesia and specifically caused by aspiration has decreased over the last four decades. Despite an increase in the total number of anesthetics administered over this period, the number of deaths associated with anesthesia has declined markedly because of an increasing instrumental rate and delivery rate by cesarean delivery. Of the causes of death attributable to anesthesia, the proportion resulting from aspiration has also declined progressively, from 52%65% 50 yr ago to 0%12% in the last 10 yr. In the last two decades in the UK, the decrease in the proportion of anesthetic deaths is undoubtedly a result of the shift that has occurred from general anesthesia toward spinal and epidural anesthesia.
Factors Predisposing to Aspiration Pneumonitis
Gastric Contents.
However, there is some evidence to support a dose-response relationship for both the gastric volume instilled directly into the lung and gastric acidity. Aspiration of 0.8 mL/kg and 1.0 mL/kg at pH 1 were associated with increasingly severe pneumonitis in monkeys compared with 0.4 mL/kg and 0.6 mL/kg (15). In another study (16), hydrochloric acid was injected into the tracheae of 336 rats. Extreme acidity was associated with a much higher mortality. The late mortality rates were 90% with a volume of 0.3 mL/kg at pH 1 and 14% with a volume of 12 mL/kg at pH The effect of milky products on the lung has been studied in animals (17). The severity of lung injury after administration of milk was assessed in rabbits by measuring alveolar-arterial oxygen tension gradient and pulmonary compliance (18). Human breast milk acidified to pH 1.8 with hydrochloric acid increased the severity of aspiration pneumonitis compared with 5% dextrose, acidified to a pH of 1.8 with hydrochloric acid (19). Acidification of human breast milk with gastric juice instead of hydrochloric acid did not increase the severity of lung injury. In addition, less acidic human breast milk (at pH values of 3.0 and 7.0) caused a similar severity of injury. It was shown in rabbits that the type of milk had an effect on the severity of lung injury. Consequently, it appears that human milk is particularly noxious although other types of milk are less so. Direct instillation of a soya-based formula, for example, caused a less severe form of acute lung injury than human breast milk or a dairy milk formula (20).
The LES. The LES possesses variable features, including its basal pressure, axial length, asymmetry, and the location of the high-pressure zone relative to the diaphragmatic hiatus. In a study of seven patients with a hiatus hernia, the maximum pressure at the gastroesophageal junction was lower in patients with hiatus hernia than it was in seven healthy volunteers (Fig. 1) (24). In the volunteers, the mean (SEM) maximal pressure was 28 (1.2) mm Hg and was 34% asymmetric at the level of the diaphragm. The squamocolumnar junction was 0.5 (0.1) cm below the diaphragmatic hiatus and the axial length of the high-pressure zone was 4 cm. In patients with hiatus hernia there were two areas of high pressure. The proximal zone was above the squamocolumnar junction and the distal zone was at the level of the diaphragmatic hiatus below the squamocolumnar junction. The mean (± SEM) pressure and axial length (± SEM) were 17.1 ± 1.0 mm Hg and 2.8 ± 0.2 cm in the proximal zone and 13 ± 2.0 mm Hg and 2.7 ± 0.3 cm in the distal zone. The pressure in the proximal zone above the diaphragm was symmetrical, whereas the pressure in the distal zone was asymmetrical. These asymmetric spatial results at the distal level suggest that the diaphragm contributes to the asymmetric component of the high-pressure zone. The symmetry at the proximal zone above the level of the diaphragm demonstrates the symmetrical characteristics of the muscle wall of the lower esophagus.
Patients who present for anesthesia may have coexisting gastroesophageal pathology that predisposes to reflux. In most instances, the prevailing mechanism for reflux is transient relaxation of the LES (25,26). In addition, anesthetics and techniques may reduce LES pressure and therefore promote gastroesophageal reflux because of a reduction of barrier pressure (27). In general antiemetics, cholinergic drugs, succinylcholine, and antacids increase LES pressure. LES pressure is reduced by anticholinergics, thiopental, opioids, and inhaled drugs; whereas atracurium, vecuronium, ranitidine, and cimetidine have no effect on LES pressure (27). A study of propofol in 8 healthy volunteers breathing air and oxygen in the supine position with the head covered by a canopy demonstrated that a dose of 2 mg/kg had no effect of barrier pressure at 1, 3, 5, 10, and 20 min. Both LES pressure and gastric pressure decreased at 1 min and then returned to their basal values (28). Table 2 summarizes the effect of anesthetic drugs and techniques on barrier pressure. It may be seen that a typical anesthetic in which a patient is given opioids, modern muscle relaxant drugs, nitrous oxide, and inhaled drugs is likely to be associated with a reduction in barrier pressure and therefore an increased tendency to regurgitation that is greater with increasing concentrations of inhaled drugs. Although LES tone and barrier pressure change concomitantly, it is noteworthy that barrier pressure can be maintained in cirrhotic patients with ascites. In this study, LES tone showed adaptive changes, increasing with abdominal compression and decreasing with diuresis (29).
The UES The cricopharyngeus muscle acts as the functional UES. It is one of the two inferior constrictor muscles of the pharynx. It extends around the pharynx from one side of the cricoid arch to the other and is continuous with the circular muscular coat of the esophagus (30). In conscious healthy patients, the UES helps to prevent aspiration by sealing off the upper esophagus from the hypopharynx. There is evidence to indicate that its function is impaired during anesthesia and during normal sleep (31). UES tone alters during the induction of anesthesia. Thiopental 4 mg/kg and midazolam 0.05 mg/kg (32) cause a significant reduction in upper esophageal tone. With thiopental, mean (± SD) sphincter pressure decreased from 43 ± 19 to 9 ± 7 mm Hg, and with midazolam it decreased from 38 ± 2 to 7 ± 3 mm Hg. There was some reduction in tone from 31 ± 15 to 24 ± 13 mm Hg with 1% end-tidal halothane (33), whereas there was no change in tone with ketamine 2 mg/kg. Administration of succinylcholine 1 mg/kg caused a reduction in UES tone to 7 ± 4 mm Hg after the induction of anesthesia with halothane (33). Nondepolarizing muscle relaxants were studied in 102 healthy patients undergoing general anesthesia for varicose vein surgery (34). UES tone was measured using a 6-cm oil-filled sphinctometer and the presence of reflux was assessed by using pH electrodes at the level of the lower esophagus and the hypopharynx. In patients who received atracurium there was a significantly lower UES tone compared with patients who did not receive a nondepolarizing relaxant. Despite this difference, the incidence of reflux into the lower esophagus (19% vs 13%) and the hypopharynx (6% vs 8%) was similar in both groups. Furthermore, during anesthesia, there was no reflex change in UES pressure when reflux occurred into either the lower esophagus or hypopharynx. Another issue that has been investigated in awake volunteers aged 22 to 49 concerns the effect of residual neuromuscular blockade on the risk of aspiration. Using manometry and fluoroscopy, the behavior of the UES and pharyngeal constrictor muscles above were studied at train-of-four ratios (TOF) of 0.6, 0.7, 0.8, and 0.9 with the patients lying in the right lateral position. In the trial involving vecuronium (35), resting UES tone decreased significantly at TOF of 0.8 and below, whereas in the trial involving atracurium (36), resting UES tone decreased significantly from control at any level of neuromuscular blockade. By assessing the relationship of pharyngeal muscle function to UES function, these investigations were able to demonstrate abnormalities in swallowing, including impaired coordination of pharyngeal and upper esophageal muscles. In the clinical setting, it was shown in 693 patients (37) that the incidence of postoperative residual neuromuscular blockade, defined as a TOF <0.7, was significantly more frequent in patients who had pancuronium (1.5 x 95% effective dose [ED95]) compared with those who had vecuronium (1.52 x ED95) or atracurium (1.52 x ED95). There was no significant difference in the incidence of pulmonary complications among the three groups. However, by multiple regression analysis, increasing age, anesthetics longer than 200 min, and abdominal surgery were associated with increased risk of postoperative pulmonary complications. Therefore, with the exception of ketamine, most anesthetic techniques are likely to reduce UES tone and increase the likelihood of regurgitation of material from esophagus into the hypopharynx. In addition, patients who have received neuromuscular blocking drugs may be at risk of aspiration, even with a TOF of 0.7, because of reduction in UES tone and impaired swallowing. Other factors such as duration of anesthetic, type of surgery, and patient age may also influence the risk of postoperative pulmonary complications.
Protective Airway Reflexes. Apnea with laryngospasm. During this reflex, there is closure of both the false and true cords. If laryngospasm is prolonged, the false cords relax while the true cords remain constricted. Coughing. This reflex is a forceful expiratory effort preceded by a brief period of inspiration. The false cords open wider during expiration than inspiration. Expiration. This reflex is a forceful expiratory effort without a preceding inspiration. Sudden opening of the glottis follows closure of the false cords. Spasmodic panting. This reflex involves shallow breathing at a frequency of 60 breaths per minute for <10 s. The glottis opens and closes rapidly. These protective airway reflexes have been studied in 22 healthy patients anesthetized with propofol (38) by instilling 0.2 mL of distilled water onto the laryngeal mucosa around the vocal cords. It was found that the expiration reflex was the most common protective reflex elicited. Incremental doses of fentanyl progressively reduced the incidence of the expiration reflex, spasmodic panting, and cough reflex, but laryngospasm was not abolished with the larger doses of fentanyl that tended to induce apnea. The larynx and trachea are more sensitive than the bronchus in eliciting these protective airway reflexes. In 11 female adults anesthetized with sevoflurane, the airway reflexes were lessened when distilled water was administered into the bronchus compared with both larynx and trachea (39). The expiratory reflex, the cough reflex, and spasmodic panting were not observed after bronchial stimulation. Furthermore, the occurrence of apnea after laryngeal and tracheal stimulation was significantly more frequent than after bronchial stimulation. In addition to the bronchus, trachea, and larynx, the esophagus is also thought to be a sensory site for the initiation of coughing. By using 24-h ambulatory monitoring of esophageal pH and gastroesophageal reflux, it was shown that coughing was initiated by episodes of reflux (40,41). The type of airway reflex induced by physiological stimuli changes over time. After a period of 2 to 7 h of anesthesia with sevoflurane, it was shown in 14 intubated patients that although apnea and forceful expiratory efforts were more prominent at the beginning of anesthesia, the swallowing reflex predominated at the end (42).
Unconscious patients are at risk of aspiration because of impaired airway reflexes, but the relationship between a reduced conscious level and these reflexes is not straightforward. The cough reflex was examined in 47 patients with a reduced Glasgow Coma Scale score of Protective airway reflexes may be impaired at any stage in the perioperative period. The sensitivity of these reflexes has been studied using inhaled ammonia (44). Using this technique, oral diazepam 10 mg in 10 healthy male volunteers reduced upper airway reflex sensitivity 30 to 150 min after administration (45). In another study of 102 healthy nonsmoking volunteers aged 17 to 96, there was a progressive decrease in upper airway reflex sensitivity with increasing age (46). Two hours after recovery from general anesthesia for day case surgery, upper airway reflex sensitivity had not returned to baseline values. However, the auditory reaction time, a measure of recovery from general anesthesia, had returned to normal at this time and the patients were allowed to go home (47). It seems therefore that patients may have reduced airway reflex sensitivity, not only in the intraoperative but also in the preoperative period if premedicated, and also after recovery from anesthesia, perhaps for longer than may be estimated from objective tests of recovery. Furthermore, the elderly have less active airway reflexes and should be considered at increased risk of aspirating pharyngeal material.
Methods to Minimize Regurgitation and Aspiration
Control of Gastric Contents
Methods of Assessment of Gastric Emptying of Clear Fluids, Milk and Solids.
The relative risk of regurgitation and possible aspiration in more recent studies on preoperative starvation have involved a comparison of the volume of aspirated gastric contents after a shorter fasting period after clear fluids, milk, or solids with the traditional fasting period of 6 h.
Clear Fluids It has also been observed that a large proportion of patients given fluids up to 2 h preoperatively and those starved for longer periods had a pH <2.5 and a gastric volume >0.4 mL/kg (73,74). Thus there seems to be little difference between the gastric contents of those starved of clear fluids for up to 2 h and those who had undergone longer periods of starvation. Such studies were the basis of the statement in the guidelines of the ASA (75) that it is appropriate for clear fluids to be allowed up to 2 h preoperatively. Clear fluids include water, fruit juices without pulp, carbonated beverages, clear tea, and black coffee. In a survey of members of the Association of Pediatric Anaesthetists in the UK (76), there seems to be agreement on a 2-h fasting time for clear fluids in neonates and children.
Adolescents and Adults.
Milk Different types of milk vary considerably in their constituents. Milk may be casein or whey based. Whey-based milk is emptied more quickly from the stomach. Casein is insoluble and is formed from caseinogen under the influence of rennin. Whey is the liquid that separates from the clot in cheese making and it contains lactalbumin but almost no casein or fat. Whey proteins are eliminated quickly from the stomach but casein forms curds that are digested more slowly. Thus, there are two phases to the elimination of milk: an initial rapid liquid phase followed by a constant zero-order solid phase (79). The three main types of milk available for babies are human breast milk, cows milk, and a variety of formula milk for infants. Formula milk may be either whey-predominant or casein-predominant; the former mimics human breast milk and the latter conforms more closely to cows milk. In a study of 201 infants using sulfur-colloid Tc and cinegastroscintigraphy, the rate of emptying was faster with human milk and slower with cows milk. One-hundred-twenty minutes after ingestion, the percentage gastric residual activity was 19 ± 16% (mean ± SD) for human milk, 25 ± 18% for the whey-predominant formula, 38 ± 21 for the casein-predominant formula, and 48 ± 19% for cows milk (60). Another study using a different technique to assess gastric emptying in 29 infants supports previous observations that breast milk empties quickly (61). Using 13C-octanoic acid breath tests it was found that gastric emptying was significantly faster after human milk than formula milk. The half-emptying time (range) was 65 (2798) min for the formula-fed infants and 47 (1686) min for the breast-fed infants. Fortification of human breast milk increases its energy, protein, carbohydrate, vitamin, and mineral content, and it is becoming more common for infants of low birth weight. To evaluate if this practice induces a delay in gastric emptying, a blinded cross-over study of 22 low-birth-weight infants was undertaken using ultrasonography to measure gastric antral cross-sectional area. There was no significant difference in gastric emptying; thus it seems that the fortifier used in this study had no effect on gastric emptying of human breast milk (66).
Solids Gastric emptying of solids depends on type and quantity. In a study of 50 healthy volunteers, gastric emptying was assessed by scintigraphic techniques after ingestion of digestible and indigestible material (62). The digestible and indigestible materials were two eggs and ten polyvinyl capsules respectively. The mean (SD) half-life of gastric emptying was 59.4 (7.7) min for the eggs. Assuming that five half-lives are required, it can be expected that up to 5 h are required for the stomach to empty after a light digestible meal. In the case of the indigestible material, 4 h elapsed before the capsules were emptied. These results concur with those from a study of healthy female volunteers who had a light breakfast comprising a slice of buttered toast with jam, one cup of coffee without milk or sugar, and one glass of pulp-free orange juice (67). Ultrasonography showed that 4 h elapsed before the stomach was considered to be clear of solid particles. This period cannot be applied to a heavy meal, which takes more than 9 h to empty from the stomach (81).
Altered Physiological States. The other issue in labor is that of mobile epidural infusions, which are currently in vogue. In the maintenance phase, these epidurals are administered by a continuous infusion of a small dose of local anesthetic with an opioid. The important clinical question is how much epidural opioid needs to be administered before there is delayed gastric emptying and hence an increase risk of aspiration. This issue has been made clearer using the paracetamol absorption technique in a randomized controlled study of 55 women who were given either a small-dose bupivacaine infusion without fentanyl or a dose with fentanyl (52). In comparison with the control group, gastric emptying was significantly delayed in the patients who had fentanyl after it had been infused epidurally for a mean time of 4.5 h when approximately 113 ± 8.5 µg of fentanyl (± SD) had been given. The time (SD) to maximum plasma concentration of paracetamol was significantly increased in this group: 76.1 (23.9) min compared with 54.2 (27.8) min in the control group. In obstetric practice, anesthesia may also be required for a postpartum patient. After delivery, the time at which the risk of aspiration returns to normal is an important clinical consideration. Gastric emptying was studied by using electrical impedance tomography in the postpartum period in 14 healthy mothers. The gastric emptying of 400 mL of distilled water was assessed at 37 to 40 wk of pregnancy, 23 days postpartum, and 6 wk postdelivery (58). The respective mean gastric emptying times (SD) were 15 (6.05), 11 (5.9), and 15 (5.5) min. It would appear therefore that there is no impairment of gastric emptying of clear fluids 3 days after delivery. However, there is insufficient evidence to clarify changes in risk in the first 24 h of the postpartum period, when operative procedures are common. During this period, the anesthesiologist would need to take into account several factors, such as feeding practice during labor, analgesia used, case mix, and surgical factors, in the clinical decision-making process. Caution is required when assessing gastric emptying in patients with gastrointestinal pathology. Clearly, there is a very high risk of aspiration in patients with bowel obstruction or peritonitis, but in the absence of a definitive diagnosis, anesthesiologists may encounter patients with less definitive symptoms of abdominal pain, vomiting, or reflux. Schwartz et al. (14) observed that children with abdominal pain had significantly larger gastric volumes than those whose primary problems were vomiting or reflux. In this study, gastric contents were obtained from 155 of 248 children presenting for upper gastrointestinal endoscopy. All patients were starved for 8 h except infants <6 mo of age who were starved for 6 h. However, larger gastric volumes in this study were comparable with the volumes observed in healthy patients in other studies. Despite these recent published observations, it would still seem prudent to manage patients with abdominal symptoms as if they were at high risk of aspiration. In Type I diabetic patients, gastric emptying is delayed as assessed by radioisotopic techniques and electrical impedance tomography. Digestible material consisting of two eggs emptied from the stomach with a half-life (SD) of 88.1 (8.9) min in Type I diabetic patients compared with 59.4 (7.7) min in healthy volunteers (62). The indigestible material of 10 capsules was emptied in 82% of diabetic patients after 6 h whereas they were emptied in all the healthy volunteers at 4 h. In another study, the residual radioactivity 50 min after a semisolid meal was 71.3 ± 15% (mean ± SD) in 83 Type I diabetic patients compared with 53.5 ± 13% in 48 healthy volunteers (63). In this latter study, the delay in gastric emptying correlated with the presence of autonomic neuropathy but not with the degree of peripheral neuropathy, preprandial blood glucose HbA1C, duration of diabetes, or age. In another study, gastric emptying measured by electrical impedance tomography was also delayed in Type I diabetic patients (59). After ingestion of a semisolid meal, the mean half-time of gastric emptying was 54.8 ± 26.6 min in diabetic patients compared with 40.4 ± 8.6 min in healthy volunteers. Thus there is considerable evidence to suggest that these diabetic patients require a longer fasting period than healthy patients do.
Guidelines and Clinical Practice. There is now good evidence that for clear fluids the period of preoperative starvation may be reduced from that traditionally recommended. After a Norwegian National consensus on fasting times in 1993, 69% of hospitals were shown to have changed their local guidelines by 1996. Ninety-three percent and 79% of hospitals allowed <6 h of preoperative fasting for clear fluids in children and adults respectively in 1996, compared with 71% and 63% respectively in 1993 (82). Surveys have shown that US and UK pediatric anesthesiologists are becoming more relaxed in their fasting policy on clear fluids (76,83).
On the issue of milk, the American Society of Anesthesiologists (ASA) supports a fasting period of four hours for breast milk, and six hours for infant formula and nonhuman milk (75). These recommendations for formula milk have erred on the side of caution, treating all types of formula milk in the same way as cows milk. In a survey in the US of pediatric preoperative fasting practices (84), there is general agreement with a 4-h fasting time for breast milk in the majority of hospitals despite a wide range of two to eight hours. For formula milk, there is agreement with a Solids take longer than fluids to empty from the stomach. The current ASA recommendation for solids for adults is 6 h of fasting after a light meal (75). Further guidance is required for the starvation time after a heavy meal.
Reducing Gastric Acidity. H2 antagonists are histamine analogues that bind competitively to receptors on the parietal cell basal membrane (85). Important pharmacological features concerning this class of drug are the considerable interindividual variation of acid inhibition with the same plasma concentration, the reversible development of tolerance within a few days of therapy, and the lack of a direct temporal relationship between the peak plasma concentration of drug and maximum inhibition of acid secretion (86).
PPIs are pyridyl methylsulfinyl benzamidazoles, which are converted to sulfenamides on the acidic luminal side of the gastric parietal cell. They form disulphide covalent bonds with cysteine residues of the In anesthetic practice, there have been many double-blinded randomized controlled clinical trials of H2 antagonists and the PPIs in healthy patients to assess their effect on gastric pH and volume. The methods used in these studies have usually been blind aspiration via a nasogastric tube with the patients in various positions (88). Alternative methods are more complex, involving dye dilution and also aspiration under direct vision with a gastroscope. The former is time consuming and provides results similar to those of the blind aspiration technique although the latter method may stimulate gastric secretion. Administration of a single dose of ranitidine 150 mg a few hours before the induction of anesthesia significantly increases gastric pH and reduces gastric volume (8890). Ranitidine has been compared with famotidine in a double-blinded randomized control study of children aged 28 yr (91). It was observed that gastric pH and gastric volume were significantly increased and reduced respectively with famotidine 0.5 mg/kg compared with ranitidine 2 mg/kg. Prescription of PPIs, however, requires knowledge of their pharmacodynamic effects in the preoperative setting. Clinical trials have shown that rabeprazole, lansoprazole, and omeprazole (8890) are most effective when given in two successive doses, the evening before and on the morning of anesthesia. When a single dose of rabeprazole or lansoprazole was given to patients on the evening before anesthesia, the gastric volumes and pH measured during anesthesia on the next morning were 0.22 ± 0.20 mL at pH 3.8 ± 2.2 and 0.31 ± 0.28 mL at pH 2.7 ± 1.3 respectively, compared with 0.18 ± 0.21 mL at pH 4.2 ± 2.4 and 0.21 ± 0.18 mL at pH 4.5 ± 1.8 respectively when given on the morning of anesthesia. Different results were obtained with a single dosing of omeprazole. The gastric volume and pH measured during anesthesia were 0.31 ± 0.21 mL at pH 3.7 ± 2.1 when omeprazole was administered on the evening before anesthesia, compared with 0.43 ± 0.20 mL at pH 2.9 ± 1.5 when it was given on the morning of anesthesia. It is suggested from these clinical studies that PPIs should be used in two successive doses. If, however, they are used as a single dose, then rabeprazole and lansoprazole should be given on the morning of anesthesia, as they are not sufficiently effective when given the night before. Omeprazole as a single dose, however, is not effective if it is given on the morning of anesthesia; it should be given on the previous night. However, it should be noted that a single dose of ranitidine is just as effective as two doses of any of the PPIs in the preoperative setting in healthy patients. Although H2 antagonists are effective in healthy patients in the preoperative setting, their use in patients with peptic ulcers and reflux esophagitis needs further clarification. In many double-blinded randomized control trials symptomatic relief, healing rates, and recurrence rates are significantly better with PPIs than with H2 antagonists (92,93). In the preoperative setting, when there is time to optimize significant coexisting disease, the evidence is clearly in favor of the PPIs rather than the H2 antagonists. The effectiveness of ranitidine and omeprazole has been studied in obstetric practice. In 384 patients (94) undergoing emergency cesarean deliveries, different combinations of sodium citrate, metoclopramide, ranitidine, and omeprazole were used. The proportion of patients with a gastric pH <3.5 and volume >25 mL was significantly larger in patients who had a combination with either ranitidine or omeprazole. This proportion was 43/185 in patients who had citrate and citrate-metoclopramide compared with 18/199 in patients who had combinations of omeprazole-citrate, raniditine-citrate, omeprazole-citrate-metoclopramide, and ranitidine-citrate-metoclopramide. Although it is possible to show that these drugs increase gastric pH and reduce gastric volumes, there is no evidence to support their routine use because of the infrequent incidence of aspiration and the multiplicity of factors that are associated with this complication. If it were possible to demonstrate a significant reduction in morbidity and mortality from increasing the pH of gastric contents, the number of patients who would have to be treated to obtain benefit in one patient would be enormous. Indeed, the routine prescription of these drugs has not been recommended in the ASA guidelines (75). The level of evidence for the use of these drugs in a clinical situation is largely opinion-based. In addition, clinical trials have been conducted mostly in healthy patients and not in those patients who would be likely to regurgitate and aspirate.
Reducing Gastric Volume In the emergency situation, it has become standard practice to apply cricoid pressure during a rapid sequence induction. Although the nasogastric tube is inserted to empty the stomach before anesthesia and may impair UES and LES function (95), there is evidence from two cadaver studies (96,97) to show that the efficacy of cricoid pressure is not diminished by its presence. In addition, the lumen of the nasogastric tube is thought to provide a passageway for the drainage of gastroesophageal contents when effective cricoid pressure is applied. On the basis of this evidence, it would be our recommendation that the nasogastric tube be left in situ during a rapid sequence induction. There is some evidence to suggest that a nasogastric tube may facilitate regurgitation. In a study of 15 patients undergoing elective abdominal surgery, the number of episodes of reflux defined as a lower esophageal pH of <4 was significantly greater in patients with a nasogastric tube in situ. In addition, the mean LES pressure was lower in these patients compared with those who were without a nasogastric tube (98). As this clinical trial was published in abstract form, further operative and patient details were unavailable for review. In a cross-over study involving 17 intubated patients in the intensive care unit (99), the incidences of gastroesophageal reflux and aspiration were assessed using two sizes of nasogastric tube, 2.85 mm and 6.0 mm. Using a radioactive technetium technique, it was found that there was no significant difference in the incidence of gastroesophageal reflux (67% vs 81%) and aspiration (20% vs 31%) between the small- and large-gauge tubes respectively. It seems therefore that in this clinical situation, reducing the size of the nasogastric tube does not reduce the risk of aspiration. To reduce regurgitation in the presence of a nasogastric tube, a device has been designed to occlude the gastric cardia with an inflatable balloon (Fig. 2) (100). Using this nasogastric tube with a gastric balloon, it was shown in 12 pigs that were provoked to regurgitate by gastric filling, head-down positioning, external gastric compression, drug-induced vomiting, and pyloric ligation that gastroesophageal reflux did not occur. This finding has been confirmed in 26 healthy volunteers who ingested 1 L of mineral water (100). In addition, gastroesophageal reflux did not occur in 42 surgical patients who were considered to be at risk of aspiration and in whom a rapid sequence induction was not performed (100).
Using dye indicator as evidence of gastroesophageal reflux into the oropharyngeal space, the gastric balloon tube has also been studied in conjunction with the LMA. It was found that the tube did not interfere with insertion of the LMA in one group and that the LMA did not impede insertion of the tube in the other group (101). In addition, by inspection of the LMA and oropharynx, it was observed that gastroesophageal reflux did not occur. The implication from these findings is that the nasogastric balloon tube may reduce the risk of aspiration when a LMA has to be used to manage a difficult airway in a patient who is likely to have gastroesophageal reflux.
Cricoid Pressure
Effect of Cricoid Pressure on the LES.
Magnitude of Cricoid Pressure. The force traditionally suggested is 44N, but cricoid occlusion and vocal cord closure may occur at pressures <30N (110). Furthermore, cricoid pressure is effective in preventing regurgitation at forces <44N. In a study using the double-lumen Salem sump tube in 20 females undergoing emergency cesarean delivery under general anesthesia (111), the mean gastric pressure was 11 (range, 419) mm Hg. It was predicted that 99% of women undergoing emergency cesarean delivery are likely to have a gastric pressure of <25 mm Hg. Evidence from a study of 10 cadavers (96) suggests that a force of 20N is likely to prevent regurgitation of esophageal fluid at 25 mm Hg. In view of the possible occlusive effects of cricoid pressure, the next clinical question is this: what force would be appropriate for children of different age groups? There are no data available to clarify this issue. However, a bench-top model has been designed to investigate the force that would be applied to a 5-yr-old child in clinical practice (112). This observational study showed that the mean (SD) force applied would be 25.1 (2.7) N and 22.4 (1.7) N by anesthesiologists of all grades and anesthetic assistants respectively.
Timing of Cricoid Pressure
Direction of Cricoid Pressure.
Cricoid Pressure in Clinical Practice An important clinical scenario to consider is the situation of failed intubation with cricoid pressure in the presence of a full stomach. In these circumstances, a LMA might facilitate oxygenation and ventilation, but the key clinical question is whether cricoid pressure obstructs the correct placement of the LMA and therefore impedes ventilation and tracheal intubation through the LMA. In clinical trials, cricoid pressure significantly impeded the correct placement of the LMA (118,119) and decreased mean expiratory tidal volume (105,119). Fiberoptic tracheal intubation through the LMA with cricoid pressure applied is significantly more difficult (120), even if cricoid pressure is applied only after correct placement of the LMA (121). It has been clearly demonstrated in a study of 50 patients that cricoid pressure may impair successful tracheal intubations through the intubating LMA (ILMA) (122). If the decision is made to use a LMA during a failed intubation, it may be necessary to release cricoid pressure temporarily to facilitate oxygenation, ventilation, and tracheal intubation through the LMA. This release would seem reasonable in view of the evidence demonstrating that cricoid pressure may become ineffective after a few minutes of application.
The Effect of Method of Airway Control on the Risk of Aspiration However, despite possible improvements in cuff design, lung infection continues to be a problem in patients undergoing mechanical ventilation. It is believed that one mechanism involves microaspiration of secretions passing below the glottis through small channels between the cuff and tracheal mucosa. To test this hypothesis, a tracheal tube with a separate dorsal lumen ending proximal to the cuff has been compared with a standard tracheal tube in 190 patients undergoing ventilation (127). This new tube was designed to allow continuous aspiration of subglottic secretions. The incidence of ventilator-associated pneumonia was reduced significantly (19.9 episodes per 1000 ventilator days compared with 39.9 per 1000 ventilator days) in the patients who had their subglottic secretions aspirated continuously. The cuffed tracheal tube is currently the standard device used for airway protection during mechanical ventilation. However, conventional tracheal tubes cause epithelial inflammation when in situ for several days. A new cuffless tube (Fig. 3), which has a low pressure sealing system consisting of 1220 toroidal layers of a thin polyurethane film termed gills, has been designed to obviate tracheal damage. This tube is oval-shaped at the level of the gills and its contour provides a matching fit for the pentagonal-shaped glottic opening. In a study in sheep comparing this cuffless tube with a standard cuffed tracheal tube (128), methylene blue was used to detect aspiration. The dye was observed in the tracheae of 2 of 11 sheep intubated with a standard cuffed tube but was not found when the tracheal tube with gills was used. In addition, histology showed that epithelial injury was increased in tracheae intubated with a cuffed tube rather than in those in which the tube with gills was used. If this new tube is to be adopted, extensive clinical trials will be required to assess its safety and its role in anesthetic and intensive care practice.
In obstetric practice, where difficulty with intubation may be encountered, regional anesthesia is the technique of choice for operative procedures. In a 6-yr prospective review from 1993 to 1998 in the South Thames region in the UK, the percentage of cesarean deliveries performed under general anesthesia has been declining while cesarean deliveries as a proportion of the total number of deliveries have been increasing. There were 36 cases of failed intubation, giving an incidence of 1/249 (95% confidence interval, 1/370 to 1/187). No cases of aspiration or other adverse outcome were reported after these incidents (129). A similar clinical scenario is the situation in which some anesthesiologists elect to avoid tracheal intubation in patients who may be at risk of aspiration. Obstetric patients in the peripartum period are an important population that has been reviewed retrospectively (6). There was one mild case of aspiration of 1870 patients who underwent general anesthesia for obstetric procedures except cesarean delivery. No precautions were made in terms of cricoid pressure and tracheal intubation. Although these patients were potentially at risk of aspiration, it is surprising that the incidence of aspiration was not more frequent. In the emergency situation, there may be occurrences when a difficult airway is encountered and awake fiberoptic intubation is performed. From the foregoing, it is clear that the risk of regurgitation and aspiration is increased with sedation and local anesthesia of the respiratory tract. The clinical decision-making process is influenced by many factors, not only the risk of aspiration but also the presence of a difficult airway, patient cooperation, and the experience of the anesthesiologist. The evidence available in this situation is insufficient for any definitive recommendations to be made.
Airway Devices
Laryngeal Mask Airway. In slightly more complex studies, measurements of pH were performed simultaneously at two esophageal levels. In 55 patients (133), it was found that the proportion of patients with reflux at the lower esophageal level was significantly more in a LMA group (53.5%) than in a Face Mask group (22.2%). In addition, in a study by Roux et al (134) who measured lower esophageal pH, the incidence of gastroesophageal reflux was 50% and 65% in females and males respectively anesthetized using a LMA, compared with 15% in the patients in whom a face mask and oropharyngeal airway were used. At the midesophageal level, the incidence of gastroesophageal reflux was much less in both studies and there was no significant difference in the incidence of reflux between the LMA and Face Mask groups. The reason for the association between gastroesophageal reflux with the LMA is unclear. There is insufficient direct evidence to support the hypothesis that the reduction in lower esophageal pH is influenced directly by either the pressure or the volume in the cuff of the LMA (134). However, because application of cricoid pressure causes a reduction in LES pressure (108), a similar reflex caused by increased pharyngeal pressure may also be induced by the LMA. Bapat and Verghese (135) studied pH at the level of the larynx in 100 patients undergoing anesthesia with a LMA and positive pressure ventilation for gynecological laparoscopy. Methylene blue and fiberoptic laryngoscopy were used in addition to the pH electrode to assess regurgitation. There was no evidence of regurgitation in 99 of 100 patients. There was one case of regurgitation but not aspiration, as demonstrated by the presence of methylene blue in the laryngopharynx. This study supports the findings of Joshi et al. (136) who placed a pH electrode in the hypopharynx of spontaneously breathing patients in whom a LMA or tracheal tube was present. The hypopharyngeal pH did not decrease to below four in either group. The infrequent incidence of gastroesophageal reflux in these two studies conflicts with observations in 20 healthy patients undergoing general anesthesia with the LMA (137). In this study in which the patients were breathing spontaneously, the incidence of gastroesophageal reflux was 60% and 20% at the lower esophageal level and at the bars of the LMA respectively. The reduction in pH at the level of the LMA occurred only in patients who were in the lithotomy position. It would seem, therefore, that although the LMA may reduce barrier pressure and pH at the lower esophageal level during general anesthesia, the upper esophagus and larynx are spared, provided that the patient is supine and not in the lithotomy position. Other authors have suggested that the use of the LMA during either spontaneous ventilation (133) or positive pressure ventilation (138) may promote gastroesophageal reflux. It has been suggested that during spontaneous ventilation, a high negative intrathoracic pressure may be generated during inspiration and that during positive pressure ventilation, gastric insufflation may occur and cause increased intragastric pressures. In a study by Skinner et al. (139) using esophageal pH electrodes to compare reflux in 40 patients undergoing gynecological laparoscopies, there was no significant difference in the incidence in regurgitation between a group breathing spontaneously and one undergoing intermittent positive pressure ventilation. In a study by Akhtar and Street (138) involving 50 patients undergoing a variety of surgical procedures, methylene blue was used to assess regurgitation. During both spontaneous ventilation and intermittent positive pressure ventilation there was an incidence of regurgitation of 1:25. From these studies, it may be deduced that the mode of ventilation does not appear to unduly influence the small risk of pharyngeal regurgitation in patients undergoing anesthesia with the LMA. The timing of the removal of the LMA at the end of general anesthesia has been studied in a prospective, randomized controlled trial of 63 healthy patients (140). Lower esophageal pH was measured to assess the incidence of gastroesophageal reflux. The pH was significantly increased in patients in whom the LMA remained in situ until mouth opening occurred to command, compared with those in whom the LMA was removed when signs of rejection, such as restlessness, swallowing, and struggling, were observed. It is suggested therefore that the LMA should be removed when patients are able to open the mouth to command. The distal end of the LMA sits in the hypopharynx at the junction with the esophagus and it has been suggested that it may inhibit regurgitation of material from esophagus into pharynx. This question has been examined in a study of 25 female and 25 male cadavers (141). Flexible and standard LMA 4 and LMA 5 were evaluated in a supine position with the head and neck in the neutral position. The regurgitation pressure, defined as the esophageal pressure at which fluid was first seen above the cuff or within the bowl of the LMA, was 19 cm H2O at 0 mL of cuff volume, 47 cm H2O at 10 cuff volume, and 51 cm H2O at 20 mL cuff volume. In the control group without a LMA, the regurgitation pressure when fluid was noted in the hypopharynx was 7 cm H2O. The position of the LMAs was checked with the fiberoptic laryngoscope at various airway sealing pressures and cuff volumes, and it was demonstrated that displacement of the LMA did not occur. Therefore, it may be concluded that LMAs that are placed correctly and that remain undisplaced attenuate liquid flow between the esophagus and pharynx of cadavers. However, the application of these results to clinical practice requires caution, as cadavers do not mimic the same conditions present in anesthetized patients. Indeed there have been reports of pulmonary aspiration after the use of the LMA (7,142,143). If a standard LMA is not thought to protect the airway from aspiration in the event of regurgitation of gastric contents, would a redesigned LMA with an esophageal vent be useful? Such a device has recently been developed and is termed the ProSeal LMA(PLMA) (Laryngeal Mask Company, Henley-on-Thames, UK); this has an esophageal vent that allows the passage of a small orogastric tube, as shown in Figure 4 (144). The cuff of the PLMA has a flat dorsal component that has been manufactured to allow the ventral elliptical part to reside firmly in the periglottic tissues. In a study of 32 healthy patients, the PLMA provided a better seal than the LMA, with lower oropharyngeal leak pressures measured at zero cuff volume (145). Although the role of the PLMA in clinical practice has not yet been evaluated, it is possible to predict that the PLMA may be useful in a patient with a potentially full stomach when attempts to intubate the trachea have failed. The drainage tube may allow controlled drainage of gastric contents, and the more effective oropharyngeal seal of the airway would minimize the possibility of gastric insufflation during positive pressure ventilation.
In the Australian Incident Monitoring Study (9), the presence of a difficult airway and inadequate anesthesia have been included within the list of factors predisposing to regurgitation, vomiting, and aspiration. The importance of an unobstructed airway and adequate anesthesia cannot be overstated. To facilitate these objectives when other simple measures to obtain an airway have been unsuccessful, the ILMA, the COPA, the ETC, and the laryngeal tube may be useful. The ILMA does not protect the airway from aspiration, but it allows airway maintenance and facilitates tracheal intubation (146) with a cuffed tube, as shown in Figure 5. In two studies (146,147) of 100 and of 60 blind intubations through the ILMA in patients without a difficult airway, the success rate was 93%. In a multicenter clinical study (148) of 500 patients, the success rate of blind intubations was 96.2%. In other studies of 12 patients (149) and 6 patients (150) who were suspected of having a difficult airway, all underwent successful intubation via the ILMA. In each Mallampati grade, from 1 to 4, there were intubation failures of 3.2%, 4.9%, 3.8%, and 0.0% respectively, in the multicenter clinical trial of 500 patients (148). Another study has shown that the use of a lightwand-guide improves the success rate of intubation via the ILMA and so minimizes the possibility of esophageal intubation (150). In a clinical trial in which healthy patients without neck abnormalities simulated a trauma scenario by wearing a semirigid neck collar, the ILMA was difficult to insert. Ventilation was difficult and tracheal intubation was successful in only 2 of the 10 patients. Fifty patients were planned for this trial but only ten were enrolled owing to the difficulties experienced (151).
One case report cited a death attributable to the ILMA and several attempts at intubation. This patient was involved in a clinical trial and had an esophageal rupture (152). Other reported complications with the ILMA have not been life threatening. The most common airway complication was mucosal injury
COPA. The COPA has often been compared with the LMA and not the standard Guedel airway (155,157). In a randomized cross-over study of the COPA and the LMA, the LMA performed better than the COPA. The oropharyngeal leak pressure was higher for the LMA than the COPA, demonstrating that the LMA provided a better seal than the COPA (153). The implication of this difference with the COPA is that in the presence of ventilation with positive pressure, the possibility of gastric insufflation and hence gastric aspiration may be increased.
ETC. Although this device may protect against regurgitation and allows drainage of gastric contents, if required, its use requires sufficient training and it is associated with some complications. In a prospective, randomized controlled study of 75 patients who were within 20% of their ideal body weight and who did not have a history of difficult intubation (160), complications were assessed after the use of the ETC, tracheal tube, and LMA. The four participating anesthesiologists were thoroughly familiar with all three devices. Despite this experience, the incidence of complications associated with the ETC, such as sore throat, dysphagia, and hematoma, was significantly more than that associated with tracheal intubation or LMA insertion. The main exception was the significantly frequent incidence of hoarseness associated with tracheal intubation. Another more serious complication has been reported in a series of 1139 patients resuscitated with the ETC by basic emergency technicians (161). Autopsies were performed in four of the eight patients who had subcutaneous emphysema. In three of the four autopsies, esophageal lacerations were found. It has been suggested that these lacerations may be the pathway for the development of the subcutaneous emphysema. In addition, a case report of a midesophageal perforation and subcutaneous emphysema has been described during a clinical trial involving the ETC (162). Despite these complications produced by blind insertion, one study of 10 emergency patients did not report any significant problems caused by the ETC (163). In other studies in which the ETC was inserted under direct vision, not blindly, major complications were avoided (159,164). In view of the seriousness of esophageal lacerations and the frequent incidence of sore throat, dysphagia, and hematoma, the ETC is not recommended for routine use unless it is inserted under direct vision. In the emergency situation when airway protection is required, the potential function of the ETC needs to be balanced against the problems that it might create.
Laryngeal Tube. To conclude, relevant past and present trials on the methods to minimize the risk of regurgitation and pulmonary aspiration have been presented. In particular, control of gastric contents, use of cricoid pressure, and methods of airway control have been discussed in detail. It is envisaged that the available evidence will help the anesthesiologist in clinical decision-making and hence lead to improvements in anesthetic management (64,71).
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