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*Department of Anesthesiology, and
Graduate Institute of Medical Science, National Defense Medical Center;
Department of Anesthesiology, Cathay General Hospital, Taipei; and
§Department of Anesthesiology, Veterans General Hospital-Kaohsiung, Kaohsiung, Taiwan
Address correspondence and reprint requests to Jhi-Joung Wang, MD, DMSc, Department of Anesthesiology, Tri-Service General Hospital/National Defense Medical Center, No 8, Sec. 3, Ting-Chow Rd., Taipei, Taiwan. Address e-mail to painlab{at}tpts5.seed.net.tw
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Abstract |
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Implications: We evaluated IV dexamethasone versus saline control in preventing epidural morphine-related nausea and vomiting in patients receiving epidural morphine for postoperative pain control. We found that IV dexamethasone significantly decreased the total incidence of nausea and vomiting after epidural morphine. IV dexamethasone may be a valuable treatment for preventing epidural morphine-related nausea and vomiting.
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Introduction |
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In patients receiving epidural morphine for postoperative pain control, the incidence of side effects such as nausea and vomiting is 30%–62% (16–19). Because dexamethasone provides a significant antiemetic effect in chemotherapy-related emesis and PONV, it may also prevent epidural morphine-related nausea and vomiting. However, prophylaxis with dexamethasone in epidural morphine-related nausea and vomiting has not been reported. The aim of our study was to compare the antiemetic effect of IV dexamethasone with saline control in the prevention of epidural morphine-related nausea and vomiting.
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Methods |
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Before surgery, a randomization table was used to assign patients to one of two groups. At the end of surgery, the dexamethasone group received IV dexamethasone 8 mg (2 mL), and the saline group received IV saline (2 mL). One minute later, 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 randomized process and the identity of the study drugs were blinded from the patients, the anesthetists during surgery, and the investigator who collected the postoperative data.
The incidence of nausea or vomiting was collected for 24 h. Thereafter, the total incidence of nausea and vomiting was calculated. 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, and 2 = vomiting). Vomiting, when it occurred, was treated with IV metoclopramide 10 mg, repeated if necessary. Pain intensity was assessed by using a 10-cm visual analog scale (VAS; 0 = no pain to 10 = most severe pain) and was recorded between 8:00 AM and 10:00 PM. If patients requested rescue analgesia for pain control, IM diclofenac 75 mg every 12 h was available. Pruritus was assessed by using 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 IM diphenhydramine (20 mg every 4 h as needed).
The primary end point of the study was a complete response, as defined by no vomiting and no administration of rescue antiemetics during a 24-h postoperative period. In the study, patients who reported postoperative hemorrhage or epidural catheter failure were excluded from the final analysis.
Sample size was predetermined. We expected a 30% difference in the total incidence of nausea and vomiting between groups, given a SD of 40%. The 
error was set at 0.05 (two-sided) and the ß error at 0.10. The projected sample size was 37 patients (20). Parametric data were analyzed by using an unpaired t-test; the incidence of nausea, vomiting, and pruritus was analyzed by using Fisher's exact test. The VAS data were analyzed by using the Mann-Whitney U-test. A P value <0.05 was considered significant.
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Results |
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After surgery, all patients received epidural morphine for postoperative pain relief. Twelve patients in the dexamethasone group requested rescue analgesia (IM diclofenac 75 mg), compared with 15 patients in the saline group. The number of diclofenac injections was 16 in the dexamethasone group and 19 in the saline group. The median time for rescue analgesia was 14 h in the dexamethasone group and 12 h in the saline group. The differences between groups were not significant. All patients reported low VAS pain scores, and the differences between groups were not significant.
The incidence of nausea was not significantly different between groups, but the incidence of vomiting was significantly different with reporting rates of 5% (2 of 38) in the dexamethasone group and 25% (9 of 36) in the saline group (P < 0.05) (Table 1). Of the patients who vomited, one in the dexamethasone group and six in the saline group requested repeated rescue antiemetics (metoclopramide). The total incidence of nausea and vomiting was also different between groups with reporting rates of 16% in the dexamethasone group and 56% in the saline group (P < 0.001) (Table 1). The incidence of pruritus between groups was not significantly different: 45% in the dexamethasone group and 44% in the saline group (Table 1).
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Discussion |
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Dexamethasone was first reported to be an effective antiemetic in patients undergoing cancer chemotherapy in 1981 (1). Since then, several studies have shown that dexamethasone is equal to or better than other antiemetics, such as metoclopramide, prochlorperazine, droperidol, ondansetron, and granisetron, in preventing nausea and vomiting associated with chemotherapy (2–5). Dexamethasone was also found to be effective in reducing the occurrence of PONV (6–15). In pediatric patients undergoing strabismus repair and tonsillectomy and adenoidectomy (6–10), and in women undergoing major gynecologic surgery (11–15), dexamethasone alone or in combination with other antiemetics (such as ondansetron or granisetron) provided a significant reduction of PONV. Because dexamethasone reduces chemotherapy-related emesis and PONV, it may also be effective in the prevention of epidural morphine-related nausea and vomiting. In our study, we found that dexamethasone significantly decreased the incidence of epidural morphine-related nausea and vomiting.
Because both nausea and vomiting present the same unpleasant physical reaction, the only difference being the severity, we used a total incidence of nausea and vomiting. Although the difference in the incidences of nausea between groups in our study did not reach as significant a level as vomiting did, the difference in the total incidence of nausea and vomiting between groups was significant (P < 0.001). These results suggest that dexamethasone is valuable in the prevention of nausea and vomiting related to epidural morphine.
In our study, we also found that dexamethasone did not influence the intensity of surgical pain. Both the incidence of patients requiring rescue analgesia and the severity of pain (VAS scores) were similar between groups. IV dexamethasone did not influence the occurrence of pruritus related to epidural morphine.
Because the duration of IV dexamethasone is 24–48 h (4,9,21), we did not examine the duration of its antiemetic properties. In patients undergoing cancer chemotherapy, IV dexamethasone demonstrated a prolonged antiemetic effect of 24–48 h and was superior to short-acting antiemetics (e.g., ondansetron and granisetron) in suppressing delayed nausea and vomiting (4,21). IV dexamethasone also demonstrated a prolonged antiemetic effect of >24 h in patients undergoing strabismus surgery (9).
Although a wide dose range of dexamethasone (8–32 mg) has been used in the prophylaxis of chemotherapy-related emesis and PONV, a single 8-mg dose of dexamethasone was most frequently used (2–15). Although this might not be the optimal dose, 8 mg of dexamethasone significantly decreased the incidence of nausea and vomiting related to epidural morphine. The optimal dose of dexamethasone in the prevention of epidural morphine-related nausea and vomiting requires further evaluation. A comparison among different antiemetic regimens in this special setting must also be evaluated.
The long-term administration of corticosteroids causes side effects, such as increased risk of infection, glucose intolerance, delayed wound healing, superficial ulceration of gastric mucosa, and adrenal suppression (22). However, we were unable to find a report of adverse effects related to a single dose of dexamethasone. Although <24 h of steroid therapy is considered safe (6–14), further study is indicated.
Among the antiemetics currently used, 5-HT3 antagonists (e.g., ondansetron, granisetron) possess good efficacy, but cost limits their widespread clinical application (4,5,11,23). Dopamine receptor antagonists (e.g., droperidol, prochlorperazine, metoclopramide) are commonly used antiemetics, but they are associated with a variety of extrapyramidal symptoms (22,23). Antihistaminic and anticholinergic drugs (e.g., scopolamine, hydroxyzine, promethazine) are also effective, but excessive sedation and tachycardia may occur (23,24). 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 conclusion, IV administration of dexamethasone 8 mg may be valuable for preventing epidural morphine-related nausea and vomiting. The optimal dose of dexamethasone was not determined.
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