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Anesth Analg 2002;95:476-479
© 2002 International Anesthesia Research Society

GENERAL ARTICLES

Perioperative Gastric Emptying Is Not a Predictor of Early Postoperative Nausea and Vomiting in Patients Undergoing Laparoscopic Cholecystectomy

M. Wattwil, MD PhD*{ddagger}, S.-E. Thörn, MD PhD*, A Lövqvist*, L. Wattwil*, H. Klockhoff, MD{dagger}, L.-G. Larsson, MD{dagger}, and I. Näslund, MD PhD{dagger}

Departments of *Anesthesiology and Intensive Care and {dagger}Surgery, Örebro University Hospital, Örebro; and {ddagger}Department of Medicine and Care, Faculty of Health Sciences, Linköping, Sweden

Address correspondence and reprint requests to Magnus Wattwil, MD, PhD, Department of Anesthesiology and Intensive Care, Örebro University Hospital, SE-701 85 Örebro, Sweden. Address e-mail to magnus.wattwil{at}orebroll.se


   Abstract
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 Abstract
Introduction
 Methods
 Results
 Discussion
 References
 
It is not known whether patients with postoperative nausea and vomiting (PONV) have delayed gastric emptying compared with patients without PONV. We compared the perioperative rate of gastric emptying in patients experiencing PONV with the rate in those without PONV immediately after laparoscopic cholecystectomy. Gastric emptying was studied by the acetaminophen method. Acetaminophen is not absorbed from the stomach but is rapidly absorbed from the small intestine, and the rate of gastric emptying therefore determines the rate of absorption of acetaminophen administered into the stomach. Forty patients (ASA physical status I and II) were included in the study. After the induction of anesthesia, a gastric tube was positioned in the stomach and 1.5 g of acetaminophen dissolved in 200 mL of water was administered. Venous blood samples for the determination of serum acetaminophen concentrations were taken before and at 15-min intervals during a period of 180 min after the administration of acetaminophen. Twenty-six patients experienced nausea during the first 4 h postoperatively. The other 14 patients had no nausea. There were no statistically significant differences in the maximal acetaminophen concentration, the time taken to reach the maximal concentration, or the area under the serum acetaminophen concentration time curves from 0 to 60, 0–120, and 0–180 min between the groups of patients with or without PONV. We did not find any relationship between postoperative gastric emptying and PONV, and therefore gastric emptying is not a predictor of PONV.

IMPLICATIONS: The incidence of postoperative nausea and vomiting is frequent after laparoscopic cholecystectomy. This study has shown that perioperative gastric emptying is not a predictor of early postoperative nausea and vomiting in patients undergoing laparoscopic cholecystectomy.


   Introduction
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 Abstract
 Introduction
Methods
 Results
 Discussion
 References
 
Postoperative nausea and vomiting (PONV) is a common clinical problem. The genesis of PONV is multifactorial (1), involving three major pathophysiologic pathways: the chemoreceptor trigger zone, the vestibulocochlear pathway, and the gastrointestinal pathway. Disturbances in gastrointestinal motility may result in nausea and vomiting, but yet nausea may influence gastric emptying (2–4). The incidence of PONV is frequent after abdominal surgery regardless of the type of anesthesia used.

Whether patients with PONV have delayed gastric emptying compared with patients without PONV has not previously been evaluated. Therefore, the purpose of this study was to compare the perioperative rate of gastric emptying in patients experiencing PONV with the rate in those without PONV immediately after laparoscopic cholecystectomy. Gastric emptying was studied by the acetaminophen method.


   Methods
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 Abstract
 Introduction
 Methods
Results
 Discussion
 References
 
Perioperative gastric emptying was studied in 40 patients (ASA physical status I and II) undergoing elective day case laparoscopic cholecystectomy. The study protocol was approved by the Ethics Committee of the Örebro County Council. The patients entered the study after verbal and written informed consent. Postoperatively, the patients were divided into two groups: patients experiencing PONV (n = 26) within 4 h postoperatively, and patients without any PONV (n = 14) during the same time period. Patient characteristics are presented in Table 1.


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  		Table 1. Table 1. Patient Characteristics
 
Acetaminophen absorption was used as an indirect measure of gastric emptying. Acetaminophen is not absorbed from the stomach but is rapidly absorbed from the small intestine. Consequently, the rate of gastric emptying determines the rate of absorption of acetaminophen administered into the stomach. The acetaminophen method is a well accepted method for studying the liquid phase of gastric emptying. The area under the serum acetaminophen concentration time curve from 0 to 60 min (AUC60) correlates very well with measurements of gastric emptying performed with isotope techniques (5,6). After the administration of acetaminophen, venous blood samples were taken at 15-min intervals during a period of 180 min. Serum acetaminophen was determined by an immunologic method including fluorescence polarization (TDx® acetaminophen; Abbott Laboratories, North Chicago, IL). Acetaminophen concentration curves were produced, and the maximal acetaminophen concentration (Cmax), the time taken to reach the maximal concentration (Tmax), and the AUC60, AUC120, and AUC180 were calculated.

The patients were allowed to drink clear fluids up to 2 h before premedication. Diazepam 10 mg orally was given for premedication. Anesthesia was induced with propofol (2.0–2.5 mg/kg) and was maintained with sevoflurane in oxygen/air (O2 30%). Fentanyl was given before induction (100 µg) and during surgery (50 µg) when clinically indicated. The patients’ tracheas were intubated after they received rocuronium (0.6 mg/kg) and were ventilated to an end-tidal CO2 of 4.8%–5.5%. All patients received glycopyrrolate and neostigmine (0.4 mg/2.5 mg) for reversal of the neuromuscular blockade. The patients received ketorolac (Toradol®) 15–30 mg IV for postoperative pain relief, and after this ketobemidone (2.5–5.0 mg) was given IV if requested.

After the induction of anesthesia, immediately before surgery, a gastric tube was positioned in the stomach. The correct position was verified by injection of 20 mL of air into the tube during auscultation with a stethoscope over the stomach area. After suction of the gastric tube (pH and volumes not measured), 1.5 g of acetaminophen dissolved in 200 mL of water was administered into the stomach. Thereafter, the gastric tube was rinsed with 20 mL of water and removed. Venous blood samples for determination of serum acetaminophen concentrations were taken before and at 15-min intervals during a period of 180 min after the administration of acetaminophen.

The patients stayed in the recovery room for at least 4 h. During this period, both nausea and pain were evaluated every hour by means of a visual analog scale (VAS) (0–10 cm). During the next 20 h, the patients themselves completed a questionnaire including VAS evaluation of PONV. All emetic episodes were noted by the staff during the first 4 h and by the patients during the next 20 h. Dixyrazine 5–10 mg IV was given as rescue antiemetic on request according to the routines of the department. A telephone interview was performed by a nurse on the first postoperative day.

The number of patients with PONV or no PONV during the first 4 postoperative hours are presented, and the {chi}2 test was used for statistical analysis of these results. The acetaminophen serum concentrations were presented as means ± SEM. Student’s t-test was used for statistical analysis of these results. A P value < 0.05 was considered statistically significant.


   Results
Top
 Abstract
 Introduction
 Methods
 Results
Discussion
 References
 
Forty patients were included in the study and 26 experienced nausea during the first 4 h postoperatively (PONV group). The other 14 patients (no-PONV group) had no nausea during the first 4 h, but later 3 of these patients experienced nausea. Two patients in the PONV group vomited during the first 4 h, 1 patient 74 min after acetaminophen administration and the other 125 min after acetaminophen. The first of these patients had no detectable acetaminophen in serum during the measurements. The other had Tmax after 135 min, Cmax 15.9 mmol/L, and AUC180 1177 min · mmol/L.

There were no statistically significant differences in Cmax, Tmax, AUC60, AUC120, or AUC180 between the groups (Table 2). The serum concentrations of acetaminophen (Fig. 1) and the number of patients without any detectable serum acetaminophen after 60, 120, and 180 min and during surgery are presented (Table 3). Sixteen of 26 patients in the PONV group received dixyrazine as rescue antiemetic.


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  		Table 2. Table 2. Mean and Ranges of Cmax, Tmax, and AUCs
 


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  		Figure 1. Serum concentrations (mmol/L, mean ± SEM) of acetaminophen during 180 min after the administration. PONV = postoperative nausea and vomiting.

 

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  		Table 3. Table 3. Number of Patients Without Detectable Serum Acetaminophen (No Gastric Emptying) at Different Time Periods
 
All patients received fentanyl (100–150 µg) during surgery and all but 4 patients, 2 in each group, received ketobemidone for postoperative pain relief during the first 4 h. There were no differences between the groups in postoperative pain measured by VAS.


   Discussion
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
References
 
In the present study, there was no difference in postoperative gastric emptying between patients experiencing PONV during the first four postoperative hours and patients without any PONV symptoms. In an experimental study in volunteers, gastric emptying was significantly delayed during vection and there was a highly significant correlation between gastric emptying and the intensity of nausea (2). However, an examination of gastric emptying profiles did not support any direct association between altered gastrointestinal motor activity and symptoms (2). In a study by Clevers et al. (7), patients undergoing abdominal surgery had abnormal enteral myoelectrical activity (measured noninvasively with electrogastrography), but this did not seem to have a major role in the genesis of PONV. Similarly, the present study did not demonstrate any relationship between gastric emptying and nausea. There were patients without any detectable acetaminophen in serum, indicating no emptying from the stomach, both in the group of patients with nausea and in the group of patients without nausea. Likewise, there were patients in both groups with large serum concentrations of acetaminophen, indicating very good gastric emptying. It is difficult to compare the results in the present study with other gastric emptying studies, because the first part of the measurements were performed during anesthesia and surgery. However, in a study by Thörn et al. (8) AUC60 was about 8000 min · µmol/L in patients three weeks after open cholecystectomy. Compared with those results, it is apparent that gastric emptying was delayed in most of the patients in our study, both during surgery and in the immediate postoperative period.

The patients received 200 mL of water (with acetaminophen) through a gastric tube after the induction of anesthesia. Fluid in the stomach could perhaps contribute to PONV. Nine patients had no gastric emptying during surgery but there were no differences between the groups. However, in a recently performed PONV study at our hospital in patients undergoing abdominal surgery, primarily laparoscopic cholecystectomy, with the same anesthesia technique as in the present study but without the administration of water and acetaminophen, the incidence of PONV was 63% compared with 65% in the present study (9). The incidence of PONV is frequent in patients undergoing laparoscopic cholecystectomy (10). Because the incidence did not increase in the present study, it seems unlikely that the fluid in the stomach contributed to PONV. In patients undergoing abdominal hysterectomy, Hovorka et al. (11) found that gastric aspiration at the end of surgery had no major effect on the incidence or severity of PONV. However, in patients with oropharyngeal surgery, placement of a nasogastric tube before termination of the surgical procedure was effective in decreasing the incidence of postoperative emesis, but all patients had swallowed blood from the surgical field, so blood in the stomach may have contributed to PONV (12).

There are no previous studies evaluating gastric emptying during abdominal surgery. Surgical time was rather short, but even during this period there was gastric emptying in 11 (28%) of the patients. During nonabdominal surgery, inhaled anesthetics do not totally abolish gastroduodenal motility, and gastric emptying may exist even if it is delayed (13). Only 40 patients were included in our study, but calculations from the results show that several hundreds of patients are needed to get statistical significance, and in that case, the results are probably not of any greater clinical significance.

Diazepam was used for premedication, but it does not influence gastric emptying (14). In the present study, moderate doses of fentanyl were given during surgery to all patients and opioids were needed for postoperative pain relief in most of them. Both systemic and spinal opioids delay gastric emptying (15), and the use of opioids is associated with an increased incidence of PONV (16). Glycopyrrolate and neostigmine were used to reverse the muscle-relaxant effect, and these drugs may also have contributed to PONV (17,18). During manipulation of the gut, serotonin may be released from the enterochromaffin cells in the mucosa. Serotonin may influence the chemoreceptor trigger zone, both through systemic circulation and by stimulation of the afferent parts of the vagal nerves (19), but the surgical technique was the same in all patients, and there was no difference in the duration of surgery between the groups.

In summary, this study has not demonstrated any relationship between immediate postoperative gastric emptying and PONV, and therefore gastric emptying is not a predictor of PONV.


   Acknowledgments
 
This study was supported by grants from Örebro County Council and "Nyckelfonden," Örebro University Hospital.

The authors thank Ing-Marie Dimgren for secretarial assistance.


   References
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 

  1. Watcha MF, White PF. Postoperative nausea and vomiting: its etiology, treatment, and prevention. Anesthesiology 1992; 77: 162–84.[Web of Science][Medline]
  2. Reid K, Grundy D, Khan MI, Read NW. Gastric emptying and the symptoms of vection-induced nausea. Eur J Gastroenterol Hepatol 1995; 7: 103–8.[Web of Science][Medline]
  3. Wengrower D, Zaltzman S, Karmeli F, Goldin E. Idiopathic gastroparesis in patients with unexplained nausea and vomiting. Dig Dis Sci 1991; 36: 1255–8.[Web of Science][Medline]
  4. Kerlin P. Postprandial antral hypomotility in patients with idiopathic nausea and vomiting. Gut 1989; 30: 54–9.[Abstract/Free Full Text]
  5. Nimmo WS, Heading RC, Wilson J, et al. Inhibition of gastric emptying and drug absorption by narcotic analgesics. Br J Clin Pharmacol 1975; 2: 509–13.[Web of Science][Medline]
  6. Medhus AW, Lofthus CM, Bredesen J, Husebye E. Gastric emptying: the validity of the paracetamol absorption test adjusted for individual pharmacokinetics. Neurogastroenterol Motil 2001; 13: 179–85.[Web of Science][Medline]
  7. Clevers GJ, Smout AJ, van der Schee EJ, Akkermans LM. Myo-electrical and motor activity of the stomach in the first days after abdominal surgery: evaluation by electrogastrography and impedance gastrography. J Gastroenterol Hepatol 1991; 6: 253–9.[Web of Science][Medline]
  8. Thörn SE, Wattwil M, Näslund I. Postoperative epidural morphine, but not epidural bupivacaine, delays gastric emptying on the first day after cholecystectomy. Reg Anesth 1992; 17: 91–4.[Web of Science][Medline]
  9. Hammas B, Thörn SE, Wattwil M. Superior prolonged antiemetic prophylaxis with a four drug multimodal regimen: comparison with propofol or placebo. Acta Anaesthesiol Scand 2002; 46: 232–7.[Web of Science][Medline]
  10. Thune A, Appelgren L, Haglind E. Prevention of postoperative nausea and vomiting after laparoscopic cholecystectomy. Eur J Surg 1995; 161: 265–8.[Web of Science][Medline]
  11. Hovorka J, Korttila K, Erkola O. Gastric aspiration at the end of anaesthesia does not decrease postoperative nausea and vomiting. Anaesth Intensive Care 1990; 18: 58–61.[Web of Science][Medline]
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  13. Schurizek BA, Willacy LHO, Kraglund K, et al. Effects of general anaesthesia with halothane on antroduodenal motility, pH and gastric emptying rate in man. Br J Anaesth 1989; 62: 129–37.[Abstract/Free Full Text]
  14. Adelhoj B, Petring OU, Brynnum J, et al. Effect of diazepam on drug absorption and gastric emptying in man. Br J Anaesth 1985; 57: 1107–9.[Abstract/Free Full Text]
  15. Thörn SE, Wattwil M, Lindberg G, Säwe J. Systemic and central effects of morphine on gastroduodenal motility. Acta Anaesthesiol Scand 1996; 40: 177–86.[Web of Science][Medline]
  16. Apfel CC, Laara E, Koivuranta M, et al. A simplified risk score for predicting postoperative nausea and vomiting: conclusions from cross-validations between two centers. Anesthesiology 1999; 91: 693–700.[Web of Science][Medline]
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Accepted for publication April 22, 2002.




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Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins and Stanford University Libraries' HighWire Press®. Copyright 2002 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press