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Anesth Analg 2002;95:1645-1649
© 2002 International Anesthesia Research Society

ANESTHETIC PHARMACOLOGY

Gastroesophageal Reflux and Tracheal Aspiration in the Thoracotomy Position: Should Ranitidine Premedication be Routine?

Neil M. Agnew, FRCA*, Jonathan B. Kendall, FRCA*, Maria Akrofi, FRCA*, Jane Tran, BTech{dagger}, Ajaib S. Soorae, FRCS{ddagger}, Richard Page, FRCS{ddagger}, Glenn N. Russell, FRCA*, and Stephen H. Pennefather, FRCA*

Departments of *Anaesthesia, {dagger}Respiratory Measurement, and {ddagger}Surgery, The Cardiothoracic Centre, Liverpool, United Kingdom

Address correspondence and reprint requests to Jonathan B. Kendall, FRCA, Department of Anaesthesia, The Cardiothoracic Centre, Thomas Dr., Liverpool L14 3PE, England. Address e-mail to jbkendall{at}doctors.org.uk


   Abstract
Top
 Abstract
Introduction
 Methods
 Results
 Discussion
 References
 
Aspiration of gastric contents may contribute to pulmonary complications after thoracotomy. The incidence of gastroesophageal reflux (GER) and tracheal acid aspiration in patients undergoing thoracotomy in the lateral position is unknown. Ranitidine premedication reduces gastric volume, increases gastric pH, and may reduce GER. We used continuous intraluminal esophageal and tracheal pH monitoring probes to investigate the effect of ranitidine on the incidence of GER and tracheal aspiration in 80 adult patients undergoing thoracotomy. The study was placebo-controlled, randomized, and double-blinded. Patients at high risk of GER were excluded from the study. The incidence of acid GER in the placebo and ranitidine groups was 28.2% and 2.5%, respectively (P = 0.006). Multiple episodes of GER occurred in some patients in the placebo group only. The total number of episodes of GER in the placebo and ranitidine groups was 16 and 1, respectively (P = 0.002). The incidence of tracheal acid aspiration in the placebo and ranitidine groups was 7.7% and 2.5%, respectively (not significant). Patients undergoing thoracotomy are therefore at high risk of acid GER, which may lead to tracheal acid aspiration in an appreciable proportion. Premedication with ranitidine significantly reduces, but does not eliminate, the incidence of this potentially life-threatening complication.

IMPLICATIONS: Gastroesophageal reflux (GER) and tracheal aspiration of acid may increase morbidity and mortality in patients undergoing thoracotomy. This randomized, double-blinded, placebo-controlled study demonstrates frequent incidences of both acid GER and tracheal acid aspiration during surgery that are significantly reduced by premedication with ranitidine.


   Introduction
Top
 Abstract
 Introduction
Methods
 Results
 Discussion
 References
 
Postoperative pulmonary complications are the principle risk factor in patients undergoing lung resection (1). Intraoperative lung contamination may contribute to this risk. Obvious gastroesophageal reflux (GER) is rare during anesthesia in epidemiological studies (2), but when observed for specifically using intraluminal pH probes, acid reflux occurs during 16% of elective surgical procedures (3) and up to 47% of gynecological laparoscopic cases (4). Although gross pulmonary contamination with gastric acid is prevented by an inflated endotracheal cuff, modern high-volume, low-pressure cuffs do not completely protect the lungs from contamination (5). Leakage of oropharyngeal secretions passed endotracheal cuffs is an important cause of ventilator-associated pneumonia (6). If pulmonary aspiration of acidic gastric contents occurs, chemical pneumonitis with a mortality of up to 62% may result (7). Patient position may be a factor in the incidence of GER, but the incidence of acid GER and tracheal acid aspiration in the thoracotomy position is unknown.

Ranitidine premedication increases gastric pH and reduces gastric volume and acid GER (8–10), but current American Society of Anesthesiologists’ guidelines do not recommend its use routinely as premedication in patients at low risk of GER (11). Measurement of intraluminal esophageal and tracheal pH values by continuous pH monitoring probes is a simple and sensitive technique to detect regurgitation of acid material (12–17).

We conducted a randomized, double-blinded, placebo-controlled study in patients undergoing thoracotomy to determine the incidence of both acid GER and tracheal acid aspiration and the effect of ranitidine premedication on these incidences.


   Methods
Top
 Abstract
 Introduction
 Methods
Results
 Discussion
 References
 
After local research ethics committee approval, written informed consent was obtained from 80 adults scheduled for elective thoracotomy. Any patients at high risk of GER, such as those with diabetes, morbid obesity, or hiatus hernia, or any patients already taking acid suppressant medication, were excluded from the study. Any patients unable to have epidural analgesia for any reason or with a known hypersensitivity to ranitidine were also excluded from the study.

Patients were randomly assigned to one of two groups by the shuffled, sealed numbered envelope technique. Group R received 150 mg of ranitidine orally 2 h before surgery, and Group P received a placebo tablet.

A standardized anesthetic technique was used. Patients scheduled for morning surgery were fasted from midnight, whereas patients scheduled for afternoon surgery received a light early breakfast. Patients received 10 mg of oral diazepam and the appropriate trial drug approximately 2 h before surgery. On arrival in the anesthetic room, a 14-gauge IV cannula, a 20-gauge radial arterial cannula, and a thoracic epidural catheter were inserted using local anesthesia with subcutaneous lidocaine 1%. An epidural test dose was given of 3 mL of 0.5% bupivacaine with 1:200,000 epinephrine. Invasive arterial blood pressure, 5-lead electrocardiography, and pulse oximetry were monitored throughout.

After breathing oxygen, general anesthesia was induced in the supine position with propofol 2 mg/kg and fentanyl 1–2 µg/kg. Neuromuscular blockade was achieved using atracurium 0.5 mg/kg. The trachea and dependent bronchus were intubated with an appropriately sized double-lumen endobronchial tube (DLEBT) (Bronchocath, Mallinckrodt, Ireland), to which a pH probe had been attached to the outer surface of the dependent side just above the tracheal cuff. Initially, a size 41F-gauge for men and 37F-gauge for women was used. Correct DLEBT position was confirmed by fiberoptic bronchoscopy. If the position was not acceptable, the tube was changed for a different size.

An esophageal pH probe was inserted via the nose to a distance of 30 cm to lie in the mid to lower third of the esophagus, and a reference electrode for each probe was positioned on the anterior chest wall. All pH probes were calibrated immediately before use with standard solutions of pH 1 and pH 7. The probes and reference electrodes were connected to a Digitrapper II MK device (Medtronic Synectics, Shoreview, MN) that recorded and stored pH values every 5 s. Recording was started immediately after the anesthetic induction with the patients in a supine position to provide initial baseline readings.

Anesthesia was maintained using 1%–2% isoflurane in oxygen. Motor block was monitored with train-of-four response and maintained at 80% using intermittent atracurium boluses. During one-lung ventilation, the tidal volume was set at 8 mL/kg and reduced, if required, to maintain a peak inspiratory pressure of <30 cm H2O. The ventilator frequency was adjusted to maintain normocapnia.

Patients were then turned onto the lateral thoracotomy position before the start of surgery. The position was maintained with a vacuum assisted beanbag, and a bridge was intraoperatively used to facilitate surgical access. An initial loading dose of 0.1 mL/kg of 0.1% bupivacaine with 5 µg/mL of fentanyl was then administered before the start of surgery, followed by an infusion of the same solution at 0.1 mL · kg-1 · h-1. After surgery, neuromuscular block was antagonized using neostigmine 2.5 mg and glycopyrrolate 0.5 mg. The tracheal pH probe was removed with the double-lumen tube at extubation. Patients were positioned in the supine position before extubation with 45-degree elevation. The esophageal probe was left in place, and the correct position was confirmed with routine postoperative chest radiograph in the recovery room before removal.

Data were transferred to a PC for analysis by a blinded observer. Acid GER was defined as an esophageal pH value <4 for longer than 1 min (13). Tracheal aspiration was defined as a tracheal pH value decrease by at least 1 pH unit less than baseline for longer than 1 min after an episode of acid GER (15). A return to baseline for at least 1 min was required to separate episodes. The total numbers of both acid GER and tracheal acid aspiration episodes were recorded. The total duration of reflux episodes in minutes was recorded and also expressed as a percentage of total monitoring times. The side of thoracotomy, times of changes in position, and duration of surgery were recorded.

Because no data from previous studies were available for thoracotomy patients, a power calculation was performed based on a general surgical population. Using an average acid GER incidence of 20%, a reduction in GER to 5% required 120 patients (60 in each group) to achieve a power of 80% and significance of 0.05. In the absence of previous data on the incidence of these potentially life-threatening complications, an interim analysis was performed after recruitment of 80 patients to exclude excess morbidity in either group.

Statistical tests were performed using SPSSTM version 10.0 for MicrosoftTM Windows ’98 (Chicago, IL), and results are reported as absolute values, mean (SE of the mean), or median (range) where appropriate. Normality of continuous data was established with the Kolmogorov-Smirnov test. Normally distributed continuous data were analyzed using Students t-test. Non-normally distributed continuous data were analyzed using Mann-Whitney U-test. Categorical data were examined using {chi}2 analysis or Fisher’s exact test as appropriate. A P value of <0.05 was considered statistically significant.


   Results
Top
 Abstract
 Introduction
 Methods
 Results
Discussion
 References
 
One patient was removed from further data analysis because of inadvertent reversal of the esophageal and tracheal probes causing possible data inaccuracy. Data were analyzed for 79 patients, 40 in Group R and 39 in Group P. The groups were comparable with respect to preoperative characteristics. Table 1 summarizes the preoperative data.


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  		Table 1. Patient Characteristics and Intraoperative Variables
 
Table 2 summarizes the incidence and duration of acid GER and tracheal acid aspiration. Eleven patients in Group P had evidence of acid GER (28.2%), of whom three (7.5%) also had evidence of subsequent tracheal acid aspiration. Only one patient (2.5%) in Group R had evidence of acid GER, and the same patient subsequently went on to demonstrate evidence of tracheal acid aspiration. Several patients in Group P had more than one episode of acid GER, and one patient had more than one episode of tracheal acid aspiration. For the placebo group, no association was found among preoperative smoking status, time of fasting, or side of thoracotomy and the incidence of acid GER. Similarly, the episodes of acid GER did not seem to be related to the repositioning of patients.


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  		Table 2. Acid Gastroesophageal Reflux (GER) and Tracheal Acid Aspiration
 
Figure 1 shows an example of part of a pH trace demonstrating acid GER and tracheal acid aspiration. The tracheal trace in Figure 1 has a baseline pH value of 7.5; the lower line is the esophageal trace with pH 4 indicating part of a continuing reflux episode. After 12 min, a rapid and prolonged dip to pH 1 occurs in the esophageal pH trace indicating a further episode of acid GER. This was followed after 18 min by a small decrease in tracheal pH then after a further 15 min by a prolonged decrease in tracheal pH, which lasted for 30 min. During this period, the esophageal pH was also low, indicating continued acid GER. The postoperative chest radiograph confirmed correct probe position in midesophagus. This patient developed clinical signs and radiological changes consistent with lower lobe pneumonia in the intraoperatively dependent lung within 48 h, which may have been related to aspiration.



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  		Figure 1. An example of part of a pH trace demonstrating acid gastroesophageal reflux (GER) and tracheal acid aspiration.

 

   Discussion
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
References
 
The technique of continuous esophageal pH monitoring has been well validated (12–17). The definition of acid GER with a pH value <4 is standard in most studies. The definition of tracheal acid aspiration is less clear because little work has been done to quantify normal tracheal pH. Because tracheal pH is more stable than esophageal pH, we used the definition of tracheal pH decrease by >1 pH unit from baseline after an episode of acid GER as a marker of a significant event (15). The technique is only able to provide a qualitative measurement of acid GER and tracheal acid aspiration and cannot quantify the amount of acid present. It is likely that probes underestimate the true incidence of tracheal acid aspiration because acid is required to come into contact with the sampling area of the probe, which may not occur on every occasion. Some distinction has been made between two types of tracheal acid aspiration pH traces seen in patients with cystic fibrosis (16): (a) downward drifts lasting 15–75 minutes associated with prolonged esophageal acidification and (b) acute decreases lasting only a few minutes associated with isolated episodes of esophageal reflux. The former may signify continuous low-grade aspiration, and the latter isolated acute episodes of aspiration, but the clinical consequences of these changes are unknown. There has been an association demonstrated between decreases in tracheal pH values and reduction in peak expiratory flow rate in asthmatic patients (12,13), suggesting airway irritation.

The patients selected for this study were considered to be at low risk of GER. It is currently recommended that patients at high risk of GER be given antacid prophylaxis routinely (11). The incidence of acid GER in Group P of 28% is more frequent than previous studies have found for low risk patients undergoing general anesthesia in the supine position (16%) (3). However, the incidence is not as frequent as for studies on patients undergoing some gynecological procedures (47%) (4). This finding suggests that the thoracotomy position may be an independent risk factor for acid GER. This has previously been suggested by studies in dogs, which found decreased esophageal pH values at the level of the thoracic inlet during thoracotomy (18). There is also some evidence from sleep studies of patients with GER disease to suggest that lateral position may also be associated with increased rates of aspiration of gastric contents (19).

Of patients who developed acid GER in the thoracotomy position, 27% went on to demonstrate evidence of tracheal acid aspiration. The presence of a cuffed single-lumen endotracheal tube does not guarantee protection of the airway (5). No work has been done on the protection afforded by DLEBT. Patients undergoing thoracotomy may be at additional risk of gastric acid aspiration if DLEBT are not accurately placed initially or become misplaced during preoperative positioning (20) or with surgical manipulation. During this study, no DLEBT required repositioning, and no cuffs were deflated before extubation. During repositioning with the patient in the lateral position, significant aspiration could occur when the cuffs were deflated if recent GER had occurred. Further, the section of the 1996/1997 report of the National Confidential Enquiry into Perioperative Deaths detailing the management of patients undergoing esophagectomy suggests that intraoperative tube substitution is not uncommon (21) and may subject the patient to additional risks of aspiration. This is of particular concern because the patients in our study, having had a lung resection, were at particular risk of respiratory complications (1). For example, some patients develop adult respiratory distress syndrome after an uneventful pneumonectomy, a condition termed postpneumo- nectomy syndrome. The pathogenesis of this syndrome is poorly understood. An increase in hydrostatic pressure after lung tissue removal is unlikely to be the sole cause in the majority of patients (6). Aspiration of infected material or gastric acid passed the endotracheal cuff could be significant factors in the development of this syndrome in at least some patients (22).

Group R demonstrated that ranitidine premedication significantly reduces but does not eliminate the incidence and severity of acid GER. This finding is consistent with previous studies on patients undergoing general surgical procedures, which showed a reduced incidence but not complete elimination of GER (10). No single drug can provide complete elimination of gastric acid. Ranitidine in various doses and by different routes of administration has been compared with other antacids such as proton-pump inhibitors. A single 150-mg dose administered orally at least 90 minutes before the induction of anesthesia is most effective at reducing gastric acid volume, increasing gastric pH, and hence reducing acid GER (8–10). This effect should last for the duration of surgery, and in our study, there was no evidence of increase in acid GER in Group R with time. However, the effect of increasing pH on outcome after aspiration remains uncertain because aspiration of liquid and particulate matter may still be associated with morbidity and mortality.

Other factors such as increasing age, male sex, obesity, and smoking are associated with increased risk of acid GER (19,23–25). However, studies have not been conducted in anesthetized patients at low risk for GER, which makes comparison with this population difficult. Our patient population was selected to exclude patients who were morbidly obese (body mass index >35 kg/m2). In addition, we tried to limit prolonged fasting times as much as possible because this has been suggested to lead to increased residual gastric volume (11). Otherwise, the population was unselected and represents a standard cohort of patients undergoing thoracotomy on a daily basis in our center. The demographic data show a preponderance of men, average age of 64 years, approximately 40% who continue to smoke. Thus, some may be considered to be at an increased risk of GER compared with the general population, but this observation has not previously been described in patients undergoing thoracotomy. However, it has also been shown that the factors traditionally associated with GER are not always predictive of actual GER episodes (3), so it is not possible to attribute significance to those factors for an individual patient.

In conclusion, this study has demonstrated that patients undergoing thoracotomy have a 28% incidence of acid GER, which leads to tracheal acid aspiration in 27% of patients. Premedication with ranitidine significantly reduces, but does not eliminate, acid GER. The authors suggest consideration of the use of ranitidine as standard premedication in all patients undergoing thoracotomy, even those previously considered to be at low risk of GER.


   References
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 

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Accepted for publication July 30, 2002.




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Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press