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Print version ISSN 0034-7094
Rev. Bras. Anestesiol. vol.54 no.2 Campinas Mar./Apr. 2004
Prevention of pulmonary gastric contents aspiration*
Prevención de la aspiración pulmonar del contenido gástrico
Eduardo Toshiyuki Moro, TSA, M.D.
Anestesiologista dos Hospitais Santa Lucinda e UNIMED; Instrutor do CET do Conjunto Hospitalar de Sorocaba/PUC - SP
BACKGROUND AND OBJECTIVES: Despite its
low incidence, aspiration of pulmonary gastric contents may have devastating
consequences. Esophageal sphincter function and protective airway reflexes decrease
caused by conscience depression, predisposes patients to this severe complication.
This article is a review of physiological aspects associated to gastroesophageal
reflux, as well as of the methods to prevent it.
CONTENTS: Comments are made about the mechanisms involved in gastric contents aspiration, its consequences and preventive methods, including recent preoperative fasting guidelines developed after review of the literature, the reasonable use of drugs acting on gastric pH and volume, and finally the effects of different airway control methods on pulmonary aspiration prevention.
CONCLUSIONS: Aspiration of pulmonary gastric contents, despite its low frequency, demands special preventive care. Recently developed preoperative fasting guidelines suggest shorter fasting periods especially for liquids, allowing more comfort to patients and less risk of hypoglycemia and dehydration, without increasing the incidence of perioperative pulmonary aspiration. The routine use of drugs decreasing gastric acidity and volume seems to be indicated only for poor risk patients. The best method to protect airways against aspiration is still tracheal intubation. Other airway control methods have been adopted, but their efficacy in preventing aspiration is lower, although representing major alternatives in cases of intubation failure.
Key Words: COMPLICATIONS: pulmonary aspiration
JUSTIFICATIVA Y OBJETIVOS: No obstante
de la baja incidencia, la aspiración pulmonar del contenido gástrico
puede tener consecuencias devastadoras para el individuo. La disminución
en la función del esfínter esofágico y de los reflejos
protectores de las vías aéreas causada por la depresión
de la conciencia, predispone los pacientes a esta grave complicación.
En este articulo, se realizo una revisión de los aspectos fisiológicos
asociados al reflujo gastroesofágico, bien como los métodos utilizados
CONTENIDO: Fueron hechos comentarios sobre los mecanismos envueltos en la aspiración del contenido gástrico, sus consecuencias y métodos de prevención, incluyendo recientes guías de ayuno pre-operatorio elaborados después de revisión de la literatura, el uso racional de drogas que actúan y el pH y volumen gástrico, y, finalmente, el efecto de diferentes métodos de manutención de la vía aérea en la prevención de la aspiración pulmonar.
CONCLUSIONES: La aspiración pulmonar del contenido gástrico, no obstante sea poco frecuente, exige cuidados especiales para su prevención. Guías de ayuno pre-operatorio elaborados recientemente sugieren períodos menores de ayuno, principalmente para líquidos, permitiendo más comodidad a los pacientes y menor riesgo de hipoglicemia y deshidratación, sin aumentar la incidencia de aspiración pulmonar perioperatoria. El uso rutinario de drogas que diminuyen la acidez y volumen gástrico parece estar indicado apenas para pacientes de riesgo. El mejor método de protección de la vía aérea contra la aspiración continua siendo la intubación traqueal. Otros métodos de manutención de la vía aérea están siendo adoptados, más la eficacia en la prevención de la aspiración aun es inferior, aun cuando representen importante alternativa en casos de falla de intubación traqueal.
Recent studies have suggested that perioperative pulmonary aspiration is an uncommon event however with devastating impact 1. In 1946, Mendelson has already established a relationship between feeding and aspiration of pulmonary gastric contents during labor under general anesthesia. He has described two syndromes: the first would be the inhalation of solid food leading to airways obstruction and death or massive atelectasis. The second, named after him, would be liquid contents aspiration when laryngeal reflexes are depressed by general anesthesia 2. These patients would develop cyanosis, tachycardia and tachypnea. Mendelson has shown in rabbits that the development of the syndrome would depend on the acid pH of aspired material 3.
In this article, mechanisms involved in regurgitation and aspiration of pulmonary gastric contents are evaluated together with some preventive methods.
A review of the literature suggests that the incidence of perioperative pulmonary aspiration is relatively low and has suffered minor changes in recent years. In 1986, a study of the Scandinavian Teaching Hospital has observed that the incidence of aspiration varied from 0.7 to 4.7 per 10 thousand anesthesias 4. A publication 10 years later has observed an incidence of 2.5 per 10 thousand in the Norwegian Hospital 5.
Mayo Clinic studies have observed similar incidence in adults (3.1 per 10 thousand) 6 and children (3.8 per 10 thousand) 7. Another North-American study has observed a higher incidence in children (10.2 per 10 thousand) 8.
Frequency varies widely among patients. So, elderly, higher ASA physical status patients, pregnant women, patients suffering from gatroesophageal reflux, obese and patients submitted to urgency surgeries are at higher risk for aspiration 1,9. In addition, pain, anxiety, diabetes mellitus, renal failure, conscience depression, alcohol and drugs (opioids, benzodiazepines, anticholinergic) which delay gastric emptying 3,9.
Based on recently available data, pulmonary gastric contents aspiration seems to be only slightly more frequent in children as compared to adults. Children also seem to be less severely affected by aspiration 10.
MORBIDITY AND MORTALITY
Morbidity attributed to aspiration is characterized by the presence of pulmonary infiltrates at chest X-rays, by the need for antibiotics or bronchodilators and by ventilatory support duration 9 (Table I).
In a Mayo Clinic study 6, 27% of pulmonary aspiration patients needed ventilatory support for more than 24 hours.
Major retrospective studies performed in different centers have shown mortality rates varying from zero to 4.5% 4-8.
In the UK, the "Confidential Enquirer into Maternal Deaths" has presented accurate data on post-gastric content aspiration mortality in obstetrics, from 1957 to 1998 11. For anesthesia-related deaths, the proportion attributed to pulmonary aspiration has progressively decreased from 50% to 65% fifty years ago, to up to 12% in recent 10 years. This decrease is clearly the result of replacing general anesthesia by spinal blocks in obstetric anesthesia 11.
Physiological mechanisms preventing gastric contents regurgitation and aspiration include lower esophageal sphincter, upper esophageal sphincter and laryngeal reflexes.
Critical values for aspiration pneumonitis risk derived from animal models are gastric contents volume above 0.4 ml.kg-1 and pH lower than 2.5 12. However, a study performed with cats has shown that gastric volume necessary for spontaneous regurgitation was 20.8 mL.kg-1 13. Other investigators consider residual gastric volume between 0.8 and 8 mL.kg-1 as a risk factor for aspiration 13-16.
A critical review of the literature has revealed that lower pH and higher gastric volume are major risk factors for pulmonary aspiration in animal models. However, differences among species make human extrapolation difficult and inaccurate 17. In addition, healthy patients with prolonged preoperative fasting often have gastric volume above 0.4 mL.kg-1 and pH below 2.5 18-21.
So, in spite of evidences of direct relationship between aspired volume and pneumonitis severity 14, the ratio between gastric and aspired volume has been questioned and its validity needs further studies 22.
In 1833, Beaumont has already recorded that after fluid ingestion, stomach would empty in less than 1 hour, while emptying time for solids was much longer 23. The dependence on gastric motility for solid material emptying explains this difference, since in case of fluids there is no such dependence 24. Water and fluids cross the stomach very fast. Half of 500 ml isotonic saline solution bolus is emptied and/or absorbed by the stomach in 12 minutes 25,26. Half of 750 ml bolus disappears in 20 minutes 21,27,28 and 80% to 95% of ingested fluids disappear in one hour 29,30.
However, gastric emptying time for solids varies considerably.
Among types of ingested food, lipids emptying is slower, proteins emptying is faster and carbohydrates emptying is intermediate 31. There is no absolute definition of solid food. In practical terms, solid is every food in this state in the stomach 23. So, gelatin is solid before ingestion, but is not in solid state in the stomach. On the other hand, milk forms solid components in the stomach and takes hours to be emptied.
Lower Esophageal Sphincter
Seemingly there is no true anatomic sphincter, but muscle fibers of the junction of esophagus and stomach, which are disposed in circle acting as a true sphincter.
The trend to regurgitation is not directly dependent on lower esophageal sphincter pressure, but on the difference between this pressure and intra-gastric pressure. Antiemetics, cholinergic drugs, succinylcholine and antacids increase lower esophageal sphincter pressure, while anticholinergics, thiopental, opioids and inhalational anesthetics decrease it. Atracurium, vecuronium, ranitidine and cimetidine have no effect on lower esophageal sphincter 32.
Upper Esophageal Sphincter
Helps preventing aspiration by acting on the transition exerted by the cricopharyngeal muscle between esophagus and hypopharynx. During anesthesia, and even during normal sleep, there is a change in its function and tone 33.
With the exception of ketamine, anesthetic drugs decrease upper esophageal sphincter tone. In addition, patients receiving neuromuscular blockers may be at risk of aspiration, even with TOF (train of four) of 0.7, because upper esophageal sphincter tone and swallowing are still decreased 34-36.
Airway reflexes protect lungs against aspiration. There are four well-defined reflexes 10: apnea with laryngospasm, cough, expiration (forced expiration without preceding inspiration) and Spasmodic Panting (superficial breathing with frequency of 60 movements per minute for less than 10 seconds).
Two hours after outpatient general anesthesia recovery, upper airway reflexes sensitivity has not returned to normal 37. This decrease in reflexes seems to be present not only in the intraoperative period, but also in premedicated patients and in the postoperative period, probably for a long than expected period. In addition, elderly people have less active airway reflexes and should be considered at increased risk for aspiration 37-40.
Methods to prevent pulmonary aspiration include gastric contents control, gastroesophageal reflux decrease and airway protection. This is achieved with preoperative fasting, gastric acidity decrease, gastric emptying stimulation and esophageal sphincter competence maintenance 41. Airway protection requires cricoid cartilage pressure (Sellick's maneuver) 42, adequate patient positioning, tracheal intubation under rapid sequence induction or with awaken patient and nasogastric tube aspiration before anesthetic induction 43.
GASTRIC CONTENTS CONTROL
The objective of preoperative fasting is to decrease gastric contents regurgitation risk and degree, thus preventing pulmonary aspiration and its consequences.
The old orientation "nothing by mouth after midnight" has been replaced by shorter preoperative fasting periods. There are several benefits when patients, especially children, ingest fluids before anesthesia, including higher satisfaction and less irritability, gastric pH increase, decreased risk for lipolysis hypoglycemia and dehydration 15,21,44-46.
Studies in different centers involving children ingesting different types of clear fluids (water, tea, coffee, fruit juice without pulp, all without alcohol and with little sugar) in variable volumes have concluded that fluid ingestion, without volume limitation, may be safely allowed 2 hours or more after surgery 23,47.
In general, stomach acid secretion production rate is 0.6 mL.kg-1.h-1 21, but it may reach 500 ml.h-1 with fasting and hunger 19,30,48. It has been observed in many cases a decrease in gastric pH with increased preoperative fasting duration 49. Anxiety is an emotional stimulation able to increase HCI production, similarly to the cephalic phase of gastric secretion 17,48,50,51, which explains increased volume and decreased gastric pH after prolonged fasting 17,27,49,52,53. Increased gastric pH in patients receiving fluids 2 to 3 hours before surgery could be result of the dilution of acid secretions and/or decrease in their production by the decrease in anxiety and hunger levels. Gastric volume decrease in patients receiving fluids few hours before surgery could be due to gastric motility stimulation by cold fluid entrance and/or physical stomach distension 15,17,27,54.
In spite of all knowledge obtained to date, it is not possible to surely predict gastric contents. Healthy patients under prolonged fasting may, during surgery, present vomiting with contents of previous day meal. Others may present hypoglycemia, dehydration and irritability. However it seems reasonable to conclude that unrestricted ingestion of clear fluids for healthy patients 2 hours or more before surgery has a more than acceptable risk/benefit ratio 7,8,11,21,55,56.
The American Society of Anesthesiologists, through the ASA Task Force on Preoperative Fasting 57, has developed practical guidelines for preoperative fasting and for the use of drugs involved in decreasing gastric volume and acidity. Based on an extensive literature review, guidelines are aimed at healthy patients of all ages submitted to elective procedures, and do not include patients at increased aspiration risk. Such recommendations may be adopted, modified or rejected according to individual clinical needs and are subject to periodic reviews according to the evolution of knowledge on the subject.
Recommendations are summarized as follows (Table II):
- Clear fluids (water, tea, coffee, fruit juice without pulp, all without alcohol and with little sugar): 2 hours fasting for all ages;
- Breast milk: 4 hours fasting for neonates and infants;
- Light diet (tea and toasts) and non breast milk: up to 6 hours fasting is accepted for children and adults;
- Pediatric formula: 6 hours fasting for neonates and infants;
- Solids: 8 hours fasting for children and adults.
Many investigators have studied the implementation of new preoperative fasting guidelines to replace the old recommendation "nothing by mouth after midnight". Ferrari 58 has evaluated 51 institutions in the USA and Canada and has concluded that the approach preconized by the American Society of Anesthesiologists represents most pediatric institutions in North America. Investigations in the UK, Scotland, Germany and Norway have also shown that more flexible preoperative fasting measures have been adopted by most institutions in those countries without increasing complication rates 59-62.
Some points should also be mentioned:
Studies in adults have shown no difference in gastric contents of patients chewing sugarless gums immediately before surgery 16,63. Even so, Splinter 23 suggests 2 hours fasting for chewing gum and sweets.
A recent study with healthy non obese pregnant women who were not in labor, has not found difference in gastric contents after the ingestion of 300 ml of water as compared to prolonged fasting 64.
The American Society of Anesthesiologists Task Force on Obstetrical Anesthesia 65 recommends that moderate clear fluid ingestion may be allowed for pregnant women in uncomplicated labor. When there is other associated risk factor (diabetes, morbid obesity, difficult airway), or patients are at high risk to evolve to C-section, fluid restriction should be determined in a case-by-case basis. As to solids, the committee agrees that 8 hours or more for elective C-sections is the most adequate period.
Labor patients should not ingest solids.
Mechanisms involved in increased pulmonary aspiration risk in obese patients do not include increase in gastric contents because it is not higher as compared to the volume of non-obese patients. Other factors, such as intra-gastric, abdominal and lower esophageal sphincter pressures probably play a more important role in aspiration pathophysiology of obese patients 66.
According to the Norwegian National Consensus, preanesthetic medication may be ingested by adults with 150 ml of water up to one hour before anesthesia. The same is true for children but with the limitation of 75 ml of water 23.
Gastric Acidity Decrease
Many clinical studies have been performed in Anesthesia about the use of H2 receptor antagonists and proton pump blockers in healthy patients to evaluate their effects on gastric volume and pH 67.
A single 150 mg ranitidine dose few hours before anesthetic induction significantly increases gastric pH, in addition to decreasing its volume 67-69.
Protons pump blockers prescription, however, requires the understanding of its pharmacology. Studies have shown that such drugs are more effective if administered in two successive doses: one the night before and the other in the morning of anesthesia 67-69.
Although being possible to show that these drugs increase gastric pH and decrease its volume, the ASA Task Force considers that there are no evidences supporting their routine use in healthy patients, but only in risk patients, since there is no proven decrease in aspiration, morbidity or mortality rate with the use of such drugs in healthy patients 57.
The efficacy of preoperative antacids to decrease gastric acidity is proven but there are no evidences that these solutions act on gastric volume. Particulate antacids may increase the risk for pulmonary injury in case of aspiration and should be avoided. So, preoperative antacids (non-particulate such as sodium citrate) should only be prescribed to risk patients 57.
Anti-emetics (e.g.: droperidol and ondansetron) are also solely indicated for patients at higher risk for aspiration 57.
Nasogastric tubes are commonly inserted in risk patients before anesthesia, aiming at stomach emptying. However, it seems that upper and lower esophageal sphincters function is impaired as compared to the function in patients without nasogastric tubes 42,70. Sellick recommends in his original study 42 that the tube should be removed before anesthetic induction. However, two studies with cadavers have shown that the efficacy of the Sellilck's maneuver is not decreased with its presence 71,72. So, the tube would act as a safe passage for gastric contents when effective cricoid cartilage compression is applied. Based on these data, Smith 9 suggests that the tube should be left in situ during rapid sequence induction associated to Sellick's maneuver.
There are no significant differences in pulmonary aspiration rate when different tube sizes are used 73.
A cuff associated to the tube has been successfully used aiming at occluding the cardia, thus gastroesophageal reflux 74. This tube with gastric cuff has been studied together with laryngeal mask. It has been observed that the tube does not interfere with laryngeal mask insertion and that this would not prevent tube insertion. So, this association represents a good option for difficult airways manipulation in patients at risk for aspiration 75.
Cricoid Cartilage Pressure
Cricoid cartilage pressure (Sellick's maneuver) has become universal practice during anesthetic induction in patients with potentially full stomach 76. Such maneuver, when correctly performed, prevents gastric inflation in children 77 and adults 78,79, in addition to increasing upper esophageal sphincter tone 80. Lower esophageal sphincter tone decreases with such compression 81, suggesting the presence of pharyngeal mechanoreceptors promoting reflex relaxation of this sphincter. This effect, however, does not seem to cause gastroesophageal reflux 82.
The incorrect application of the maneuver may deform cricoid cartilage, close vocal cords and impair ventilation, especially in women 83. Strength applied should be sufficient to prevent aspiration, but not so strong to cause airway obstruction or allow for esophageal rupture in case of vomiting. Cephalad and backward direction of the strength applied seems to improve laryngoscopic visualization 84.
A major scenario to be considered is tracheal intubation failure in patients with full stomach under cricoid cartilage compression. In this situation, a laryngeal mask may help ventilation and oxygenation, but studies have shown that Sellick's maneuver prevents its correct positioning 85,86. So, if laryngeal mask is used during tracheal intubation failure, it may be necessary to temporarily interrupt the maneuver to help ventilation, oxygenation and intubation through the laryngeal mask. Interruption seems to be a reasonable option since cricoid cartilage compression may become ineffective after few minutes of application 87.
EFFECTS OF DIFFERENT AIRWAY CONTROL METHODS ON ASPIRATION RISK
Tracheal intubation is the most effective method to protect airways in anesthetized patients. However, some studies performed with intubated patients in intensive care units, have shown that high volume and low pressure cuffs have allowed the leakage of stain to the trachea 88,89. Mechanism involved might be microaspiration through the glottis by small channels between the cuff and tracheal mucosa 90. The lubrication of cuffs with gel has significantly decreased leakage 90,91.
Laryngeal mask is associated to decrease in pressure barrier represented by lower esophageal sphincter 92. A study of patients under general anesthesia with positive pressure ventilation has shown that in the group using laryngeal mask there has been a significant increase in gastroesophageal reflux as compared to the group using tracheal tube with cuff 93. There is also reflux in patients under spontaneous ventilation and laryngeal mask 94. In fact, there are no significant differences in regurgitation rate between groups spontaneously ventilating or under positive pressure ventilation 95,96. Time for laryngeal mask removal at the end of general anesthesia seems to influence reflux rate since those who had the mask removed when able to spontaneously open their mouths had a lower incidence of reflux as compared to those who had their masks removed before consciousness recovery 97.
The development of a new laryngeal mask model, ProSeal (Laryngeal Mask Company, Henley on Thames, UK), allows the introduction of orogastric tube through an esophageal opening for better gastric contents drainage, in addition to a better gastric inflation blockade during positive pressure ventilation. A recent study has shown that ProSeal is more effective than traditional laryngeal masks to prevent reflux, what makes it a good option for patients at aspiration risk and failed tracheal intubation 98,99.
COPA and Combitube
"COPA" (Cuffed Oropharyngeal Airway) is even less effective than the laryngeal mask to prevent regurgitation 100, thus not being indicated for patients at aspiration risk.
Combitube, although protecting against regurgitation and allowing gastric contents drainage, requires a trained professional, since its use is associated to complications such as sore throat, dysphagia and hematomas. So, in emergency situations when airway protection is needed, combitube benefits should be counterbalanced with possible associated complications 9.
OTHER PREVENTIVE GASTRIC ASPIRATION MEASURES
Forecasting of Difficult Tracheal Intubation
The first step of difficult airway algorithm, developed by the American Society of Anesthesiologists is the identification of patients with potential difficult tracheal intubation 101. In some cases, such as facial trauma, some congenital syndromes or morbid obesity, difficulty may be easily identified. However, in less evident cases, intubation difficulty may only appear after anesthetic induction, when protective reflexes are abolished, and may expose patients to aspiration risks. So, the forecasting of difficult intubation may be done through some parameters, such as Mallampati's test 102, thyroginean distance or other tests available in the literature 103.
Patients Positioning 3
Patients at risk for aspiration should be placed in the horizontal position with elevated dorsum approximately 30º with relation to the rest of the body. This position will prevent regurgitation, but if it happens, table position should be immediately changed so that the head is positioned below the trunk, thus preventing aspiration.
TRACHEAL INTUBATION WITH AWAKEN PATIENT OR UNDER RAPID SEQUENCE INDUCTION
Once a potential difficult airway is identified, the safest intubation method is with the patient awaken and under spontaneous ventilation 103.
Tracheal intubation may be performed after mild sedation, maintaining airways protective reflexes. Antisialogogues, such as atropine or scopolamine, should be administered and oropharynx should be topically anesthetized with spray lidocaine (10%). Glossopharyngeal and upper laryngeal nerves blockade might be useful for those mastering the technique 101.
Rapid sequence induction traditionally involves preparing the equipment, which should include, in addition to tracheal intubation material, one aspirator, one backup laryngoscope and equipment for intubation failure (laryngeal mask, fastrack, fibroscope); 100% oxygen administration under facial mask for 1 minute; short onset and duration intravenous opioid and anesthetics (e.g.: propofol and alfentanil) and finally an also short onset and duration neuromuscular blocker 3,104.
Succinylcholine has been used for 50 years by most anesthesiologists as the neuromuscular blocker of choice to intubate full stomach patients, since it is the drug which best meets the above-mentioned criteria. However, complications such as malignant hyperthermia, fatal hyperkalemia, bradyarhythmias, intragastric and intraocular pressure increase have encouraged the search for adepolarizing neuromuscular blockers with shorter onset and duration, without succinylcholine side-effects, hence, the introduction of rocuronium as an alternative for patients under pulmonary aspiration risk. To assure onset and intubation conditions similar to succinylcholine, preconized dose is 1 mg.kg-1 or more, which implies longer duration, impairing its use for short procedures or those with possibilities of difficult intubation 105-108.
Succinylcholine or rocuronium, intubation with awaken patient, fibroscopy etc., all have advantages and disadvantages. The anesthesiologist should decide the best alternative on a case-by-case basis 109.
Pulmonary aspiration is defined as inhalation of oropharynx or stomach contents through the larynx to low respiratory tract 110,111. Several pulmonary syndromes may be present after aspiration, depending on quantity and nature of the material. Aspiration pneumonitis (Mendelson's syndrome) is a chemical injury caused by sterile gastric contents aspiration, while aspiration pneumonia is an infection caused by inhalation of colonized material especially coming from oropharynx. Other syndromes include mechanical airway obstruction, pulmonary abscess and chronic interstitial fibrosis 110,111.
Gastric material aspiration causes intensive pulmonary inflammation. Patient may present with cough, wheezing, tachypnea, cyanosis, pulmonary edema, hypoxemia and arterial hypotension, with rapid progression to respiratory distress syndrome and death. Many patients may present only with cough or wheezing and decreased oxygen saturation associated to radiological evidences of aspiration 112.
Treatment includes oxygen administration and/or ventilatory support, when necessary. Preventive antibiotics are not indicated because they may turn patient susceptible to secondary infection by more resistant organisms. Antibiotics are indicated for patients with aspiration pneumonitis not resolved 48 hours after aspiration 113. Steroids are not recommended because multicentric randomized and controlled studies have failed in proving their benefits 114,115.
Bronchoscopy should be performed in patients under suspicion of solid material aspiration causing airway obstruction. Pulmonary washing under direct view is also indicated for solid material aspiration 3.
Pulmonary gastric contents aspiration, although uncommon, requires special preventive care. Recently developed preoperative fasting guidelines suggest shorter fasting periods, especially for fluids, allowing more comfort to patients and less risk for hypoglycemia and dehydration, without increasing the incidence of perioperative pulmonary aspiration. The routine use of drugs decreasing gastric acidity and volume seems to be indicated only for risk patients. The best way to protect airways against aspiration is still tracheal intubation. Other airways maintenance methods have been used but their efficacy in preventing aspiration is still lower, although representing major alternatives for tracheal intubation failure. Cricoid cartilage compression, rapid sequence induction or induction with awaken patient, in addition to patient's positioning, play an important role in preventing pulmonary aspiration.
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Dr. Eduardo T. Moro
Rodovia Raposo Tavares, Km. 113
Avenida Araçoiaba SR 2 - US 85 - Condomínio Fazenda Lago Azul
18190-000 Araçoiaba da Serra, SP
Apresentado (Submitted) em 01 de
abril de 2003
Aceito (Accepted) para publicação em 24 de junho de 2003
* Recebido do (Received from) Hospital Santa Lucinda, Sorocaba, SP