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Departments of *Anesthesiology and Obstetrics and Gynecology, Tri-Service General Hospital, National Defense Medical Center, Taipei; Department of Anesthesiology, Chi-Mei Medical Center, Tainan; and §Department of Anesthesiology, Municipal Women’s and Children’s General Hospital, Kaohsiung, Taiwan
Address correspondence and reprint requests to Shung-Tai Ho, MD, MS, Department of Anesthesiology, National Defense Medical Center, Rm. 8113, No. 161, Sec. 6, Minchuan E Rd., Taipei, Taiwan. Address e-mail to painlab{at}tpts5.seed.net.tw
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Abstract |
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Implications: We conducted a dose-ranging study of dexamethasone for preventing nausea and vomiting within the first 24 h after the administration of epidural morphine. We found that dexamethasone 5 mg was as effective as 10 mg. We recommend the smaller dose for this purpose.
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Introduction |
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Dexamethasone is an effective antiemetic agent with minimum side effects after a single-dose administration (15–20). Its antiemetic effect is equal to or better than other antiemetics, such as metoclopramide, perphenazine, droperidol, and ondansetron (8,15,17,20). Many investigators suggest the use of dexamethasone as a prophylactic antiemetic agent for postoperative nausea and vomiting in patients recovering from general anesthesia (15–20). The commonly used doses are 8 to 10 mg. Recently, dexamethasone 8 mg was also found to be effective in preventing nausea and vomiting associated with epidural morphine (7,8); nevertheless, a dose-ranging study of dexamethasone for this purpose has not been determined. We, therefore, performed a randomized and double-blinded study to evaluate three doses of dexamethasone (10 mg, 5 mg, and 2.5 mg) compared with droperidol (1.25 mg) and saline, in preventing epidural morphine-related nausea and vomiting. The effect of dexamethasone on the analgesic efficacy of epidural morphine 3 mg was also evaluated.
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Methods |
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When the incision closure was completed, patients were randomly assigned to one of five groups of 45 patients to receive IV dexamethasone, at doses of 10 mg, 5 mg, or 2.5 mg; IV droperidol 1.25 mg; or saline 2 mL. The drug for injection was prepared as 2 mL of clear solution in identical syringes. One minute after the IV injection of the medication, all patients received 3 mg of preservative-free morphine in 10 mL of isotonic sodium chloride solution through the epidural catheter for postoperative analgesia. The epidural catheters were aspirated before the injection of morphine to eliminate the possibility of catheter failure. Patients, anesthetists, and investigators who collected the postoperative data were blinded to the identity of the study drug.
Postoperatively, patients were observed for 24 h. A team of specially trained nurse anesthetists collected the postoperative data. During the observation period, arterial blood pressure, heart rate, and respiratory rate were monitored every 4 h except when patients were sleeping.
Nausea and vomiting was evaluated by using the following variables: the incidences of nausea and vomiting, the number of episodes of vomiting, rescue antiemetics, and the total number of patients with no vomiting and/or no antiemetic medication. Nausea was defined as the subjectively unpleasant sensation associated with awareness of the urge to vomit. It was assessed while patients were lying still. Vomiting was defined as the forceful expulsion of gastric content from the mouth. For the purpose of data collection, retching (the same as vomiting but without expulsion of gastric content) was considered vomiting. A vomiting episode was defined as the events of vomiting that occurred in a rapid sequence (<1 min between events). If events of vomiting were separated by more than 1 min, they were considered to be separate episodes. Vomiting which occurred more than 4 times within 24 h was considered as severe vomiting. Rescue antiemetics (IV ondansetron 4 mg) were given if vomiting occurred, or at the patient’s complaint of intolerable nausea. The treatment was repeated if necessary. The complete response was defined as no vomiting and no antiemetic medication during a 24-h postoperative period, and this was also the primary efficacy end point of the study.
Postoperative wound pain at rest was assessed with a 10-cm visual analog scale (VAS; 0= no pain to 10= most severe pain) score. When patients complained of "excessive" pain and requested analgesia, IM diclofenac 75 mg (every 12 h) was given.
The postoperative data (e.g., nausea, vomiting, and pain) were collected every 4 h (between 8:00 AM and 10:00 PM) by direct questioning by a team of specially trained nurse anesthetists or by patient complaint.
The occurrence of side effects accompanying dexamethasone usage, such as wound infections or delayed wound healing, was evaluated and reported by the surgeon. The duration of the hospital stay was recorded. Restlessness, a common droperidol-related side effect, was also evaluated (12). Restlessness was defined as a sensation of nervousness with an inability to keep still and was treated with IM diphenhydramine 20 mg (12).
Sample size was predetermined by using a power analysis based on the assumptions that (a) the total incidence of nausea and vomiting in the Saline group would be 60% (7), (b) a 40% reduction in the total incidence of nausea and vomiting (from 60% to 36%) in the Treatment group would be of clinical relevance, and (c) 
= 0.05, ß = 0.2 (21). The analysis showed that 40 patients per group would be sufficient to detect the antiemetic effect a small dose of dexamethasone (2.5 mg). A series of one-way analyses of variance were conducted to examine differences among the five groups with respect to parametric variables. If a significant difference was found, the Bonferroni t-test was used to detect the intergroup differences. The Kruskal-Wallis test was used to determine differences among the five groups with respect to nonparametric variables, followed by the Mann-Whitney ranked sum test for intergroup differences. Categorical variables were analyzed by using a series of 5x2 
2 tests to determine differences among the five groups, followed by 2x2 2 tests or Fisher’s exact tests, as appropriate, for intergroup differences. All follow-up analyses were corrected for the number of simultaneous contrasts by using the Bonferroni adjustments. A P value <0.05 was considered significant.
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Discussion |
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We also found that dexamethasone did not influence the efficacy of epidural morphine-related analgesia. Patients who received dexamethasone 2.5 mg, 5 mg, or 10 mg requested similar amounts of rescue analgesic and reported similar intensities of postoperative pain.
Droperidol, a potent antiemetic, has demonstrated an antiemetic effect equal to ondansetron and superior to metoclopramide for preventing nausea and vomiting after general anesthesia (22,23). The recommended dose for this purpose is 1.25 mg (23). We found that droperidol 1.25 mg was also effective in preventing nausea and vomiting after epidural morphine for postoperative analgesia. However, restlessness, a common droperidol-related side effect, was found in 14% of the patients. Although this side effect was relieved by the IM administration of diphenhydramine, it nevertheless produced mental distress in our patients.
The long-term administration of corticosteroids causes side effects, such as an increased risk of infection, glucose intolerance, delayed wound healing, superficial ulceration of gastric mucosa, and adrenal suppression (13). However, these side effects are not seen with a single dose of dexamethasone (15–20). In the current study, no side effects were noted with a single dose of dexamethasone 2.5 to 10 mg (e.g., wound infection or delayed wound healing).
In conclusion, IV dexamethasone 5 mg was as effective as dexamethasone 10 mg and droperidol 1.25 mg, and was more effective than saline control in preventing epidural morphine-related nausea and vomiting. Dexamethasone 2.5 mg was ineffective. Because dexamethasone 5 mg was as effective as 10 mg as an antiemetic, we recommend the smaller dose for preventing nausea and vomiting associated with epidural morphine.
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