October 2000

The Effect of Timing of Dexamethasone Administration on Its Efficacy As a Prophylactic Antiemetic for Postoperative Nausea and Vomiting
Wang JJ, Ho ST, Tzeng JI, Tang CS. Anesth Analg 2000; 91:136-9
[see abstract below]

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Commentary by Katherine Grichnik, M.D.

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 if a single dose of dexamethasone would suppress adrenal function in otherwise healthy patients during surgical stress or if this potential suppression would be clinically relevant (for example, associated with an increased risk of infection or wound dehiscence).

References:

1. Baxendale BR, Vater M, Lavery KM. Dexamethasone reduces pain and swelling following extraction of third molar teeth. Anaesthesia 1993;48:961-4.
Click here for abstract

2. Tang J, Wang B, White PF, Watcha MF, Qi J, Wender RH. The effect of timing of ondansetron administration on its efficacy, cost-effectiveness, and cost-benefit as a prophylactic antiemetic in the ambulatory setting. Anesth Analg 1998;86:274-82. Click here for abstract
3. Diemunsch P, Leeser J, Feiss P, et al. Intravenous dolasetron mesilate ameliorates postoperative nausea and vomiting. Can J Anaesth 1997; 44:173-81. Click here for abstract
4. Korttila K, Clergue F, Leeser J, et al. Intravenous dolasetron and ondansetron in prevention of postoperative nausea and vomiting: a multicenter, double-blind, placebo-controlled study. Acta Anaesthesiol Scand 1997;41:914-22. Click here for abstract
5. Fujii Y, Tanaka H, Toyooka H. Granisetron and dexamethasone provide more improved prevention of postoperative emesis than granisetron alone in children. Can J Anaesth 1996;43:1229-32. Click here for abstract
6. Lopez-Olaondo L, Carrascosa F, Pueyo FJ, Monedero P, Busto N, Saez A. Combination of ondansetron and dexamethasone in the prophylaxis of postoperative nausea and vomiting. Br J Anaesth 1996;76:835-40. Click here for abstract
7. Fujii Y, Saitoh Y, Tanaka H, Toyooka H. Prophylactic therapy with combined granisetron and dexamethasone for the prevention of postoperative vomiting in children. Eur J Anaesth 1999;16:376-9.
8. Henzi I, Walder B, Tram�r MR. Dexamethasone for the prevention of postoperative nausea and vomiting: a quantitative systematic review. Anesth Analg 2000;90:186-94. Click here for abstract
9. Liu K, Hsu CC, Chia YY. The effective dose of dexamethasone for antiemesis after major gynecological surgery. Anesth Analg 1999;89:1316-8. Click here for abstract

ABSTRACTS The Effect of Timing of Dexamethasone Administration on Its Efficacy As a Prophylactic Antiemetic for Postoperative Nausea and Vomiting AUTHORS: Wang JJ, Ho ST, Tzeng JI, Tang CS SOURCE: Anesth Analg 2000; 91:136-9 ABSTRACT: We evaluated the timing effect of a 10-mg IV administration of dexamethasone on its efficacy as a prophylactic antiemetic on postoperative nausea and vomiting (PONV). One hundred twenty women (n = 40 in each of three groups) undergoing abdominal total hysterectomy under general anesthesia were enrolled in this randomized, double-blinded, placebo-controlled study. Group 1 received dexamethasone before the induction of anesthesia, Group 2 received dexamethasone at the end of anesthesia, and Group 3 received placebo (saline). The incidence of PONV was evaluated. During the postoperative period of 0-2 h, patients in Group 1 reported a less frequent incidence of PONV (15%) than those in Groups 2 and 3 (45% and 53%, respectively). Patients in Group 1 also requested less rescue antiemetic (8%) than those in Groups 2 and 3 (30% and 35%, respectively). During the postoperative period of 2-24 h, patients in both Groups 1 and 2 reported less frequent incidences of PONV (25% and 28%) and requested fewer rescue antiemetics (13% and 15%) than those in Group 3 (55% and 38%, respectively). In conclusion, the prophylactic IV administration of dexamethasone immediately before the induction, rather than at the end of anesthesia, was more effective in preventing PONV. IMPLICATIONS: We evaluated the effect of timing of dexamethasone administration on its efficacy as a prophylactic antiemetic on postoperative nausea and vomiting. We found that dexamethasone, when given immediately before the induction of anesthesia, was more effective than when given at the end of anesthesia.