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The Effect of Timing of Dexamethasone Administration on Its Efficacy as a Prophylactic Antiemetic for Postoperative Nausea and Vomiting

Perioperative Complications
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JHI-JOUNG WANG, SHUNG-TAI HO, JANN-INN TZENG AND CHAO-SHUN TANG

Departments of Anesthesiology, Tri-Service General Hospital, National Defense Medical Center and Cathay General Hospital, Taipei, and Department of Anesthesiology, School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

Anesth. Analg., 91: 136–139, 2000

The timing effect of a 10-mg intravenous administration of dexamethasone was evaluated in terms of its efficacy as a prophylactic antiemetic on postoperative nausea and vomiting (PONV). One hundred twenty women, in three groups of 40 each, who were undergoing abdominal total hysterectomy under general anesthesia were enrolled in this randomized, double-blind, placebo-controlled study. Group 1 was given dexamethasone before induction of anesthesia, group 2 received dexamethasone at the end of anesthesia, and group 3 was given placebo (saline). The incidence of PONV was evaluated. During the 0 to 2-hr postoperative period, patients in group 1 reported fewer incidences of PONV (15%) than those in groups 2 and 3 (45 and 53%, respectively). Patients in group 1 also asked for less rescue antiemetic than those in groups 2 and 3 (30 and 35%, respectively). During the 2 to 24-hr postoperative period, patients in both groups 1 and 2 requested fewer antiemetics (13 and 15%) than those in group 3. It was concluded that the prophylactic administration of dexamethasone immediately before the induction of anesthesia was more effective in preventing PONV than if it was administered at the end of anesthesia.

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Comments:

Postoperative nausea and vomiting (PONV) are strong predictors of protracted postoperative stay and unanticipated hospital admission in the (planned) ambulatory setting. Moreover, PONV are extremely distressing symptoms for patients, affecting not only their postoperative functional level but also their satisfaction with their entire anesthetic/surgical experience. The occurrence of PONV may actually trigger a negative assessment by the patient of the quality of care delivered by his or her anesthesiologist. Although death as a direct result of vomiting is highly unusual, serious morbidity from severe vomiting can occur, including esophageal rupture, pneumothorax, splenic laceration, hematoma, and wound dehiscence. PONV studies abound and educate the clinician about a plethora of issues, including the scope of the problem, associated risk factors, cost issues, and the bevy of choices available in anesthetic technique and maneuvers, traditional pharmacologic antiemetic agents, and nontraditional therapies.

The glucocorticoids dexamethasone and methylprednisolone have antiemetic properties exerted by an as-yet-undetermined mechanism. Postulated mechanisms, however, include prostaglandin antagonism and endorphin release. The glucocorticoids have been used successfully for many years to prevent chemotherapy-induced vomiting. Nonetheless, although the first clinical trial suggesting that dexamethasone may prevent PONV was published in 1993, 1 to date the role of dexamethasone in the surgical arena is less well understood.

The current randomized, double-blinded, placebo-controlled study by Wang and colleagues is the first to determine the optimal timing of IV dexamethasone administration for prevention of PONV. The investigators demonstrated that prophylactic IV administration of 10 mg dexamethasone immediately before induction, rather than after extubation, was more effective in preventing PONV. Moreover, the beneficial antiemetic effect persisted throughout the first 24 hr of the postoperative period.

The results of the current study contrast with the data available concerning the timing of serotonin antagonist administration to achieve maximal PONV efficacy. Recent data, for example, suggest that the effectiveness of ondansetron may be enhanced by administration toward the termination of a surgical procedure rather than at the beginning. 2 Moreover, dose-response studies of dolasetron have indicated that the minimum effective dose is 50 mg if administered at the beginning of surgery, but only 12.5 mg if given at the termination of surgery. 3,4

The current study by Wang and colleagues was well-designed in terms of eliminating confounding variables. However, for the sake of completeness, a few additional issues should be addressed. First, in both children and adults, the literature indicates that the combination of dexamethasone with a serotonin antagonist enhances antiemetic efficacy compared with the use of a serotonin antagonist only. 5–7 This effect seems to be additive rather than synergistic, but optimal doses of this combination therapy need to be established. 8 (Although the minimum effective dose of dexamethasone when given as the sole antiemetic agent for the prevention of PONV was suggested to be 2.5 mg in a recent study, 9 Wang and colleagues used a 10 mg dose because most previous studies administered dexamethasone in the dose range of 8 to 10 mg.)

Finally, it is still unclear whether a single bolus dose of 8 or 10 mg dexamethasone is safe in patients who might be vulnerable to corticosteroid-related adverse effects, nor do we know whether a single dose of dexamethasone would suppress adrenal function in otherwise healthy patients during surgical stress or whether this potential suppression would be clinically relevant (for example, associated with an increased risk of infection or wound dehiscence).

Kathryn E. McGoldrick M.D.

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© 2001 Lippincott Williams & Wilkins, Inc.