Obstetrics & Gynecology:
Dexamethasone for the Prevention of Nausea and Vomiting After Dilatation and Curettage: A Randomized Controlled Trial
Fujii, Yoshitaka MD; Uemura, Aki MD
Department of Anesthesiology, University of Tsukuba Institute of Clinical Medicine, Tsukuba City, Ibaraki, Japan.
Address reprint requests to: Yoshitaka Fujii, MD, Department of Anesthesiology, University of Tsukuba Institute of Clinical Medicine, 2–1‐1 Amakubo, Tsukuba City, Ibaraki 305–8576, Japan; E‐mail: firstname.lastname@example.org.
Received July 10, 2001. Received in revised form September 10, 2001. Accepted September 17, 2001.
OBJECTIVE: To evaluate the efficacy and safety of dexamethasone administered intravenously at three different doses (4 mg, 8 mg, 16 mg) for the prevention of nausea and vomiting after dilatation and curettage.
METHODS: In a prospective, randomized, double‐masked, placebo‐controlled trial, 120 women received placebo or dexamethasone intravenously at doses of 4 mg, 8 mg, or 16 mg immediately before induction of anesthesia (n = 30 in each group). Propofol‐based general anesthetic was used. Emetic episodes and safety assessments were performed. To estimate a sufficient sample size, it was calculated that 30 patients per group would be required with α = .05 and β = .2.
RESULTS: The rate of patients who were emesis‐free (no nausea, retching, or vomiting) 0–24 hours after anesthesia was 57% with dexamethasone 4 mg (P = .796), 87% with dexamethasone 8 mg (P = .005), and 87% with dexamethasone 16 mg (P = .005), compared with placebo (50%). Patients who had received dexamethasone 8 mg or 16 mg were more satisfied than those who had received placebo (P < .05). No clinically important adverse events were observed in any of the groups.
CONCLUSION: Dexamethasone 8 mg is an effective antiemetic for preventing postoperative nausea and vomiting 0–24 hours after anesthesia in women undergoing propofol‐based general anesthesia for termination of pregnancy. Increasing the dose to 16 mg provided no additional benefit.
Postoperative nausea and vomiting are common and unpleasant complications after surgery performed under general anesthesia,1 with a high incidence in women undergoing general anesthesia for dilation and curettage.2,3 Most of the currently used antiemetics, antihistamines (eg, hydroxyzine), butyrophenones (eg, droperidol), and dopamine receptor antagonists (eg, metoclopramide), have occasional undesirable adverse effects, such as excessive sedation, hypotension, dry mouth, dysphoria, hallucinations, and extrapyramidal symptoms. Ondansetron, a selective 5‐hydroxytryptamine type 3 receptor antagonist, is a prophylactic antiemetic in the prevention of nausea and vomiting after general anesthesia for dilatation and curettage.4 However, several investigators have criticized the use of prophylactic antiemetic therapy with ondansetron because of its high cost.5,6 In our hospital, dexamethasone, a corticosteroid, is less expensive than ondansetron ($5.30 for dexamethasone 8 mg versus $100.30 for ondansetron 3 mg), and has a potent prophylactic antiemetic effect against postoperative nausea and vomiting.7 In a quantitative systematic review by Henzi et al,8 the commonly used doses are 8–10 mg for adults and 1–1.5 mg/kg for children. However, there have been no reports to evaluate the efficacy of dexamethasone for preventing postoperative nausea and vomiting in women undergoing propofol‐based general anesthesia for elective termination of pregnancy. This prospective, randomized, double‐masked, placebo‐controlled study was undertaken to evaluate the efficacy and safety of dexamethasone in the prevention of nausea and vomiting after dilatation and curettage.
MATERIALS AND METHODS
The study was approved by our institutional ethics committee, and the procedures followed were in accordance with the ethic standards for human experimentation established by the Declaration of Helsinki of 1975, revised in 1983. Informed consent was obtained from all subjects who were American Society of Anesthesiologists physical status 1, age 19–47, and underwent elective termination of pregnancy. A total of 135 patients were approached between September 1999 and March 2001 to obtain a sample population of 120 patients. Exclusion criteria were antiemetics given 24 hours before surgery, gastrointestinal disease, a history of motion sickness, and/or previous postoperative emesis.
Patients were allocated randomly to one of four groups (n = 30 in each group) using computer‐generated random numbers concealed in envelopes, to receive placebo or dexamethasone intravenously at three different doses (4 mg, 8 mg, 16 mg) immediately before induction of anesthesia. Identical syringes containing each drug were prepared by personnel not involved in the study.
Patients received no preanesthetic medication. Anesthesia was induced with propofol 2 mg/kg and maintained in spontaneous ventilation with propofol 3–5 mg/kg per hour and nitrous oxide 66% in oxygen. If required, analgesia during the surgical procedure was achieved with fentanyl 50–100 μg intravenously. The tracheas were not intubated, and stomachs were not suctioned. During the operation, no patients received any antiemetic medication. The same anesthetic technique was performed by a staff anesthesiologist who did not know which treatment each patient had received. Postoperatively, all patients were admitted to the hospital for 1 day. After surgery, patients received diclofenac sodium 50 mg given rectally when they complained of pain, and did not take any other analgesics.
Postoperatively, emetic episodes 0–24 hours after anesthesia were recorded every 6 hours by a researcher who was masked to the antiemetic that patients had received. She asked the patients if retching or vomiting had occurred and if they felt nausea, with only two possible answers (yes/no). Nausea was defined as a subjectively unpleasant sensation associated with awareness of the urge to vomit.1 Retching was defined as the labored spasmodic, rhythmic contraction of the respiratory muscles without the expulsion of gastric contents.1 Vomiting was defined as the forceful expulsion of gastric contents from the mouth.1 Patients evaluated the severity of nausea and satisfaction with the study drug at the end of the observation period. The evaluation was performed on a linear numerical scale ranging from 0 (no nausea; complete satisfaction) to 10 (severe nausea; complete dissatisfaction). The details of any other adverse events were recorded, as were a list of any other complaints (eg, extrapyramidal signs). After the patients were discharged from the hospital, follow‐up medical examination was performed 5 days after surgery to assess normal daily activity.
Patient demographic data were analyzed by using analysis of variance with Bonferroni correction for multiple comparison (continuous variables) and χ2 test (discrete variables). The number of patients experiencing emetic episodes and the incidence of adverse events were compared with Fisher exact probability test (two‐tail). The severity of nausea and satisfaction were analyzed with the Kruskal‐Wallis test. P < .05 was considered significant. Values were mean ± standard deviation, number (%), or median (range). Sample size was predetermined by using a power analysis based on the assumption that the incidence of an emesis‐free episode, which was regarded as the primary endpoint, in a patient receiving placebo would be 50%. An improvement from 50% to 85% was considered of clinical importance, with α = .05 with a power (1‐β) of 0.8. The analysis showed that 30 patients per group would be sufficient to detect the antiemetic effect of dexamethasone.
Fifteen patients were excluded from the study, according to the exclusion criteria. Patient profile and information on surgery and anesthesia are summarized in Table 1. There were no differences in patient demographics among the treatment groups. No differences were observed among the groups with regard to the number of patients with only nausea, retching, or vomiting. The difference was found in the incidence of patients who were emesis free (no nausea, retching, or vomiting) 0–24 hours after anesthesia, which occurred in 15 (50%), 17 (57%), 26 (87%), and 26 (87%) of 30 patients who had received placebo, dexamethasone 4 mg, dexamethasone 8 mg, and dexamethasone 16 mg, respectively. Thus, emesis‐free episodes were greater among patients who had received dexamethasone 8 mg or dexamethasone 16 mg compared with those who had received placebo (P < .05). However, there was no difference between the patients who had received dexamethasone 4 mg and those who had received placebo. Severity of nausea was not different among groups. Patients who received dexamethasone 8 mg or dexamethasone 16 mg were more satisfied than those who received placebo (P < .05) (Table 2). Clinically important adverse events (eg, extra‐pyramidal symptoms) were not observed in any of the groups. No patients reported disturbed normal daily activity (eg, infection).
The reported incidence of nausea and vomiting after dilatation and curettage in women varies from 47% to 56% when no prophylactic antiemetic is given.2,3 This incidence justifies the use of prophylactic antiemetics after dilatation and curettage. The etiology of postoperative nausea and vomiting in women undergoing general anesthesia for termination of pregnancy remains unclear, but is probably multifactorial.1 A number of factors, including age, obesity, a history of motion sickness and/or previous postoperative emesis, time of the menstrual cycle, surgical procedure, anesthetic technique, and postoperative pain are considered to affect the incidence of postoperative nausea and vomiting. In this study, however, there were no differences among the treatment groups with regard to patient demographics, types of operation, anesthetics administered, or analgesics used postoperatively, and patients with a history of motion sickness and/or previous postoperative emesis were excluded because they had a remarkably high incidence of postoperative nausea and vomiting.1 Therefore, the difference among the groups in the rate of emesis‐free patients can be attributed to the study drug.
Dexamethasone is effective for preventing nausea and vomiting in patients receiving chemotherapy for cancer.9 Recently, several investigations have demonstrated that dexamethasone reduces the incidence of nausea and vomiting after major gynecologic surgery (ie, hysterectomy), laparoscopic cholecystectomy, thyroidectomy, or pediatric tonsillectomy.10–13 The exact mechanism of dexamethasone for the prevention of postoperative nausea and vomiting is not known, but there have been some suggestions, such as central or peripheral inhibition of the production or secretion of serotonin,14 central inhibition of the synthesis of prostaglandins,15 and changes in the permeability of the blood‐brain barrier to serum proteins.16 In this study, prophylactic dexamethasone is also effective for preventing nausea and vomiting after dilatation and curettage, without any clinically serious adverse effects.
We found no report to determine the minimum effective dose of dexamethasone for the prevention of postoperative nausea and vomiting in women undergoing dilatation and curettage. In this clinical trial, we demonstrated that the antiemetic efficacy of dexamethasone 8 mg was similar to dexamethasone 16 mg, and also demonstrated no difference in emesis‐free episodes between patients who had received placebo and those who had received dexamethasone 4 mg. This suggests that dexamethasone 8 mg may be an effective antiemetic for preventing nausea and vomiting after termination of pregnancy, and that increasing the dose to 16 mg provides no demonstrable benefit.
When there is a high risk of postoperative nausea and vomiting, prophylactic antiemetic therapy with dexamethasone can be efficacious. The effective dose of dexamethasone is 8–10 mg in adults and 1–1.5 mg/kg in children.8 In the current study, dexamethasone, in doses more than 8 mg, is effective for the prevention of nausea and vomiting after dilatation and curettage. However, in a recent report by Wang et al,17 dexamethasone 5 mg is the minimum effective dose for preventing postoperative nausea and vomiting in women undergoing thyroidectomy. The exact reason for this difference is unknown, but may be attributed to the difference in surgical procedure.
Dexamethasone lacks the sedative, dysphoric, and extrapyramidal signs associated with two other commonly used and well‐established antiemetics, droperidol and metoclopramide.1 The long‐term administration of dexamethasone may cause undesirable adverse effects, such as an increased risk of infection, glucose intolerance, delayed wound healing, superficial ulceration of gastric mucosa, and adrenal suppression.18 However, these side effects were not related to a single dose of dexamethasone administered in this study. Adverse events attributable to the study drug that were observed in the present study were not clinically important in any of the groups. Thus, dexamethasone for prophylaxis against postoperative nausea and vomiting is considered to be relatively free of side effects.
An increased rate of postoperative nausea and vomiting is associated with nitrous oxide, as demonstrated by Hartung's analysis19 comparing the incidence of emesis in patients who received nitrous oxide and in those who received anesthetics or analgesics without nitrous oxide. However, this is still widely debated.20 In this clinical trial, general anesthetic, consisting of propofol and nitrous oxide in oxygen, was used. Arellano et al21 have recently demonstrated that omitting nitrous oxide from a propofol‐based anesthetic for ambulatory gynecologic surgery does not affect the incidence of postoperative nausea and vomiting up to 24 hours after discharge from the hospital.
Our hospital pharmacy pays $5.30 for dexamethasone 8 mg. Dexamethasone is a little more expensive than droperidol ($1.80 for 1.25 mg) and metoclopramide ($0.60 for 10 mg). However, the use of droperidol and metoclopramide as antiemetics has been limited because these drugs occasionally cause excessive sedation and/or extrapyramidal symptoms.1 Among the currently used antiemetics, prophylactic ondansetron is effective for preventing postoperative nausea and vomiting in women undergoing general anesthesia for dilatation and curettage,4 but the high cost of ondansetron ($103.00 for 3 mg in Japan) limits its widespread clinical application.
1. Watcha MF, White PF. Postoperative nausea and vomiting: Its etiology, treatment, and prevention. Anesthesiology 1992;77:162–84.
2. McKenzie R, Wadhwa RK, Uy NTL, Phitayakorn P, Tantisira B, Sinchioco C, et al. Antiemetic effectiveness of intramuscular hydroxyzine compared with intramuscular droperidol. Anesth Analg 1981;60:783–8.
3. Madej TH, Simpson KH. Comparison of the use of domperidone, droperidol, and metoclopramide in the prevention of nausea and vomiting following gynaecological surgery in day cases. Br J Anaesth 1986;58:879–83.
4. Alon E, Himmelseher S. Ondansetron in the treatment of postoperative vomiting: A randomized, double-blind comparison with droperidol and metoclopramide. Anesth Analg 1992;75:561–5.
5. White PF, Watcha MF. Are new drugs cost-effective for patients undergoing ambulatory surgery? Anesthesiology 1993;78:2–5.
6. Lerman J. Are antiemetics cost-effective for children? Can J Anaesth 1995;42:263–6.
7. Liu K, Hsu CC, Chia YY. Effect of dexamethasone on postoperative nausea and vomiting. Br J Anaesth 1996;76:835–40.
8. Henzi I, Walder B, Tramer MR. Dexamethasone for the prevention of postoperative nausea and vomiting: A quantitative systematic review. Anesth Analg 2000;90:186–94.
9. Sehine I, Nishiwaki Y, Kakinuma R, Kibota K, Hojo F, Matsumoto T, et al. Phase II study of high-dose dexamethasone-based association in acute and delayed high-dose cisplatin-induced emesis — JCOG study 9413. Br J Cancer 1997;76:90–2.
10. Liu K, Hsu CC, Chiba YY. Effect of dexamethasone on postoperative emesis and pain. Br J Anaesth 1998;80:85–6.
11. Wang JJ, Ho ST, Liu YH, Lee SC, Liu YC, Liao YC, et al. Dexamethasone reduces nausea and vomiting after laparoscopic cholecystectomy. Br J Anaesth 1999;83:772–5.
12. 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;89:200–3.
13. Splinter WM, Roberts DJ. Dexamethasone decreases vomiting by children after tonsillectomy. Anesth Analg 1996;83:913–6.
14. Fredrikson M, Mursti T, Furst C, Steineck G, Borjeson S, Wikblom M, et al. Nausea in cancer chemotherapy is inversely related to urinary cortisol excretion. Br J Cancer 1992;65:779–80.
15. Aapro MS, Plezia PM, Alberts DS, Graham V, Jones SE, Surwit EA, et al. Double-blind cross-over study of the antiemetic efficacy of high dose dexamethasone versus high dose metoclopramide. J Clin Oncol 1984;2:466–71.
16. Livrea P, Trojano M, Simone IL, Zimatore GB, Logroscino GC, Pisicchio L, et al. Acute changes in blood-CSF barrier permselectivity to serum proteins after intrathecal methotrexate and CNS irradiation. J Neurol 1985;231:336–9.
17. Wang JJ, Ho ST, Lee SC, Liu YC, Ho CM. The use of dexamethasone for preventing postoperative nausea and vomiting in females undergoing thyroidectomy: A dose-ranging study. Anesth Analg 2000;91:1404–7.
18. 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, Gilman AG, eds. Goodman and Gillmann's the pharmacological basis of therapeutics. 9th ed. New York: McGraw-Hill, 1996:1459–86.
19. Hartung J. Twenty-four of twenty-seven studies show a greater incidence of emesis with nitrous oxide than with alternative anesthetics. Anesth Analg 1996;83:114–6.
20. Fisher DM. Does nitrous oxide cause vomiting? Anesth Analg 1996;83:4–5.
21. Arellano RJ, Pole ML, Rafuse SE, Fletcher M, Saad YG, Friedlander M, et al. Omission of nitrous oxide from a propofol-based anesthetic does not affect the recovery of women undergoing outpatient gynecologic surgery. Anesthesiology 2000;93:332–9.
© 2002 by The American College of Obstetricians and Gynecologists.
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