1Department of Anaesthesiology, School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. 2Department of Anaesthesiologyand 3Department of Surgery, Tri-Service General Hospital, Taipei, Taiwan. 4Department of Anaesthesiology, Chi-Mei Medical Center, Tainan, Taiwan*Corresponding author: Department of Surgery, Tri-Service General Hospital/National Defense Medical Center, Rm 8113, No. 161, Sec. 6, Minchuan E. Rd., Taipei, Taiwan
Accepted for publication: May 30, 2000
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Abstract |
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Br J Anaesth 2000; 85: 8658
Keywords: vomiting, antiemetics; vomiting, incidence; vomiting, nausea
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Introduction |
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Dexamethasone is an effective antiemetic after single-dose administration. 1115 2023 It is effective in preventing chemotherapy-related emesis and postoperative nausea and vomiting (PONV).1215 2023 Recently, it has also been found to be effective in preventing nausea and vomiting related to epidural morphine in patients undergoing abdominal hysterectomy.11 We conducted a randomized, double-blinded and placebo-controlled study to evaluate whether dexamethasone was also effective in preventing nausea and vomiting after epidural morphine for post-Caesarean section analgesia.
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Patients and methods |
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No premedication was given. Surgical analgesia to T4 dermatome level was provided by a dose of 2% lignocaine 1518 ml (with 1:100 000 epinephrine), followed by intermittent small-dose injections of 2% lignocaine (with epinephrine) as necessary through an epidural catheter in the L34 or L45 interspace. Lactated Ringers solution 500 ml was given i.v. before surgery. After delivery of the baby, 10 units of i.v. oxytocin and 0.2 mg of i.m. ergonovine were given to all parturients. Estimated fluid deficit and maintenance requirements were replaced with lactated Ringers solution i.v. During surgery, i.v. midazolam 2.5 mg was given for sedation after delivery of the baby; no supplementary analgesic was given.
Before surgery, a randomization table was used to assign parturients to one of three groups (n=40 for each group). At the end of surgery, the dexamethasone group received i.v. dexamethasone 8 mg (2 ml), the droperidol group received i.v. droperidol 1.25 mg (2 ml) and the saline group received i.v. saline (2 ml). One minute later, all parturients received 3 mg of preservative-free morphine in 10 ml of normal saline through the epidural catheter for postoperative analgesia. The randomization process and the identity of the study drugs were blinded from the parturients, the anaesthetists during surgery and the investigators who collected the postoperative data.
The incidences of nausea and vomiting were recorded for 24 h. Nausea was defined as a subjectively unpleasant sensation associated with awareness of the urge to vomit; vomiting was the forceful expulsion of gastric contents from the mouth. Nausea and vomiting were evaluated on a 3-point ordinal scale (0=none, 1=nausea, 2=vomiting). The total incidence of nausea and vomiting was calculated. Metoclopramide 10 mg i.v. was available when vomiting occurred or on request. The proportion of parturients requiring rescue antiemetic in each group was recorded.
Pain intensity was assessed with a 10-cm visual analogue scale (VAS; 0=no pain, 10=most severe pain) and was recorded between 8:00 a.m. and 10:00 p.m. If parturients requested rescue analgesia for pain control, i.m. diclofenac 75 mg was available. Pruritus was assessed on a 3-point ordinal scale (0=none, 1=pruritus but only in a small area of the body, 2=generalized pruritus). Pruritus was treated with i.m. diphenhydramine (20 mg every 4 h as needed). Restlessness was also evaluated;16 it was defined as a sensation of nervousness with an inability to keep still. Restlessness was treated with i.m. diphenhydramine 20 mg. The occurrence of any side-effect accompanying dexamethasone usage, such as wound infection or delayed wound healing, was recorded.
Sample size was predetermined.24 We expected a 30% difference among groups in the proportion of parturients requiring rescue antiemetic for nausea and/or vomiting.911 The error was set at 0.05 (two-sided) and the ß error at 0.10. The analysis showed that 37 parturients per group would be sufficient.24 A series of one-way analyses of variance were conducted to examine differences among the three groups with respect to parametric variables. If a significant difference was found, the Bonferroni t-test was used to detect the intergroup differences. The KruskalWallis test was used to determine differences among the three groups with respect to non-parametric variables, and was followed by the MannWhitney rank-sum test for intergroup differences. Categorical variables were analysed with a series of 3x2
2 tests to determine differences among the three groups, followed by a 2x2
2 test for intergroup differences. All follow-up analyses were corrected for the number of simultaneous contrasts using Bonferroni adjustment. A P value less than 0.05 was considered significant.
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Results |
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The total incidence of nausea and vomiting was 18% in the dexamethasone group and 21% in the droperidol group, in comparison with 51% in the saline group (P<0.01 and P<0.05 respectively) (Table 2). The proportions of parturients who required rescue antiemetic (metoclopramide) were 11% in the dexamethasone group and 13% in the droperidol group, in comparison with 41% in the saline group (P<0.05) (Table 2).
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Discussion |
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Dexamethasone is effective in preventing nausea and vomiting associated with chemotherapy.12 13 Recently, dexamethasone has also been reported to be effective in preventing PONV in patients undergoing tonsillectomy, thyroidectomy, cholecystectomy and hysterectomy.17 2023 In a previous study, we also found that dexamethasone is effective in preventing nausea and vomiting associated with epidural morphine in patients undergoing abdominal hysterectomy.11 Because of these data, we hypothesized that dexamethasone might also be effective in preventing nausea and vomiting after epidural morphine for analgesia after Caesarean section.
The exact mechanism by which dexamethasone, a glucocorticoid, exerts an antiemetic action after epidural morphine is not known. Glucocorticoids have been shown to have various effects on the central nervous system; they regulate transmitter levels, receptor densities and neurone configuration.25 26 Numerous glucocorticoid receptors are found in the nucleus of the solitary tract, the nucleus of raphe and the area postrema.26 27 These nuclei are well known to have significant neuronal activity in the regulation of nausea and vomiting.10 19 Dexamethasone may exert its antiemetic action through these nuclei.
We also found that dexamethasone did not influence the efficacy of epidural morphine-related analgesia. Parturients in the three groups required similar amounts of rescue analgesic and reported similar intensities of postoperative pain. Also, i.v. dexamethasone did not influence the occurrence of pruritus related to epidural morphine for post-Caesarean section analgesia.
A wide dose range of dexamethasone (832 mg) has been used in the management of PONV and emesis associated with chemotherapy.1215 1723 A dose of 810 mg has been used most frequently in the prevention of PONV.17 20 23 For example, an 8 mg dose of dexamethasone was effective in the prevention of nausea and vomiting after epidural morphine in patients undergoing abdominal hysterectomy.11 Therefore an 8 mg dose was chosen in this study. However, doseresponse studies are needed to determine the optimal dose of dexamethasone.
The long-term administration of corticosteroids is associated with side-effects, such as increased risk of infection, delayed wound healing, glucose intolerance and adrenal suppression. However, we were unable to find a report of these adverse effects related to a single dose of dexamethasone, and delayed wound healing or wound infection did not occur in our study. Although a single dose of dexamethasone is considered safe, further study is indicated.
Droperidol also has a potent antiemetic effect.28 29 Previous studies have demonstrated that its antiemetic effect is equal to that of ondansetron and superior to that of metoclopramide in preventing PONV.28 29 The recommended dose for this purpose is 1.25 mg.29 In our study, we also found that droperidol 1.25 mg is effective in preventing nausea and vomiting related to epidural morphine for post-Caesarean section analgesia. However, droperidol is not devoid of side-effects. Restlessness, a common droperidol-related side-effect, was found in 16% parturients who received droperidol 1.25 mg in our study. Although this side-effect was relieved by the i.m. diphenhydramine, it nevertheless produced mental distress in our patients. Because dexamethasone demonstrated a significant antiemetic effect without evident adverse effects, it may be a valuable treatment for the prophylaxis of epidural morphine-related nausea and vomiting in parturients receiving Caesarean section.
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References |
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2 Kundra P, Gurnani A, Bhattacharya A. Preemptive epidural morphine for postoperative pain relief after lumbar laminectomy. Anesth Analg 1997; 85: 1358[Abstract]
3 NganKee WD, Lam KK, Chen PP, Gin T. Epidural meperidine after cesarean section. A doseresponse study. Anesthesiology 1996; 85: 28994[ISI][Medline]
4 Grass JA, Sakima NT, Schmidt R, Michitsch R, Zuckerman RL, Harris AP. A randomized, double-blind, doseresponse comparison of epidural fentanyl versus sufentanil analgesia after cesarean section. Anesth Analg 1997; 85: 36571[Abstract]
5 Zakowski MJ, Ramanathan S, Turndorf H. A two-dose epidural morphine regimen for cesarean section patients: therapeutic efficacy. Acta Anaesthesiol Scand 1992; 36: 698701[ISI][Medline]
6 Sanansilp V, Areewatana S, Tonsukchai N. Droperidol and the side effects of epidural morphine after cesarean section. Anesth Analg 1998; 86: 5327[Abstract]
7 Fuller JG, McMorland GH, Douglas MJ, Palmer L. Epidural morphine for analgesia after cesarean section: a report of 4880 patients. Can J Anaesth 1990; 37: 63640[Abstract]
8 Stenseth R, Sellevold O, Breivik H. Epidural morphine for postoperative pain: experience with 1085 patients. Acta Anaesthesiol Scand 1985; 29: 14856[ISI][Medline]
9 Kotelko DM, Rottman RL, Wright WC, Stone JJ, Yamashiro AY, Rosenblatt RM. Transdermal scopolamine decreases nausea and vomiting following cesarean section in patients receiving epidural morphine. Anesthesiology 1989; 71: 6758[ISI][Medline]
10 Chaney MA. Side effects of intrathecal and epidural opioids. Can J Anaesth 1995; 42: 891903[Abstract]
11 Wang JJ, Ho ST, Liu YH, Ho CM, Liu K, Chia YY. Dexamethasone decreases epidural morphine-related nausea and vomiting. Anesth Analg 1999; 89: 11720
12 Italian Group for Antiemetic Research. Dexamethasone, granisetron, or both for the prevention of nausea and vomiting during chemotherapy for cancer. N Engl J Med 1995; 332: 15
13 Italian Group for Antiemetic Research. Ondansetron versus metoclopramide, both combined with dexamethasone, in the prevention of cisplatin-induced delayed emesis. J Clin Oncol 1997; 15: 12430
14 López-Olaondo LL, Carrascosa F, Pueyo FJ, Monedero P, Busto N, Sáez A. Combination of ondansetron and dexamethasone in the prophylaxis of postoperative nausea and vomiting. Br J Anaesth 1996; 76: 83540
15 Fujii Y, Tanaka H, Toyooka H. Granisetrondexamethasone combination reduces postoperative nausea and vomiting. Can J Anaesth 1995; 42: 38790[Abstract]
16 Jiménez-Jiménez FJ, Garcia-Ruiz PJ, Molina JA. Drug-induced movement disorder. Drug Safety 1997; 16: 180204[ISI][Medline]
17 Wang JJ, Ho ST, Lee SC, Liu YC, Liu YH, Liao YC. The prophylactic effect of dexamethasone on postoperative nausea and vomiting in women undergoing thyroidectomy: a comparison of droperidol with saline. Anesth Analg 1999; 89: 2003
18 Brunton LL. Drugs affecting gastrointestinal function. In: Hardman JG, Limbird LE, Molinoff PB, Ruddon RW, Gillman AG, eds. Goodman and Gillmans The Pharmacological Basis of Therapeutics. 9th edn. New York: McGraw-Hill, 1996; 899936
19 Watcha MF, White PF. Postoperative nausea and vomiting. Its etiology, treatment and prevention. Anesthesiology 1992; 77: 16284[ISI][Medline]
20 Splinter WM, Robert DJ. Dexamethasone decreases vomiting by children after tonsillectomy. Anesth Analg 1996; 83: 9136[Abstract]
21 Splinter WM, Robert DJ. Prophylaxis for vomiting by children after tonsillectomy: dexamethasone versus perphenazine. Anesth Analg 1997; 85: 5347[Abstract]
22 Wang JJ, Ho ST, Liu YH, et al. Dexamethasone reduces nausea and vomiting after laparoscopic cholecystectomy. Br J Anaesth 1999; 83: 7725
23 Fujii Y, Tanaka H, Toyooka H. The effects of dexamethasone on antiemetics in female patients undergoing gynecologic surgery. Anesth Analg 1997; 85: 9137[Abstract]
24 Lerman J. Study design in clinical research: sample size estimation and power analysis. Can J Anaesth 1996; 43: 18491[Abstract]
25 Schimmer BP, Parker KL. Adrenocorticotropic hormone; adrenocortical steroids and their synthetic analogs; inhibitors of the synthesis and actions of adrenocortical hormones. In: Hardman JG, Limbird LE, Molinoff PB, Ruddon RW, Gillman AG, eds. Goodman and Gillmans The Pharmacological Basis of Therapeutics. 9th edn. New York: McGraw-Hill, 1996; 145686
26 Morimoto M, Morita N, Ozawa H, Yokoyama K, Kawata M. Distribution of glucocorticoid receptor immunoreactivity and mRNA in the rat brain: an immunohistochemical and in situ hybridization study. Neurosci Res 1996; 26: 23569[ISI][Medline]
27 Funder JW. Mineralcorticoid receptors and glucocorticoid receptors. Clin Endocrinol 1996; 45: 6516[ISI][Medline]
28 Sniadach MS, Alberts MS. A comparison of the prophylactic antiemetic effect of ondansetron and droperidol on patients undergoing gynecologic laparoscopy. Anesth Analg 1997; 85: 797800[Abstract]
29 Pandit SK, Kothary SP, Pandit UA, Randel G, Levy L. Doseresponse study of droperidol and metoclopramide as antiemetics for outpatient anesthesia. Anesth Analg 1989; 68: 798802[ISI][Medline]