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June 1998
The Effect of Timing of Ondansetron Administration on Its Efficacy, Cost-Effectiveness, and Cost-Benefit as a Prophylactic Antiemetic in the Ambulatory Setting.
Tang J, Wang B, White PF, Watcha MF, Qi J, Wender RH.
Anesth Analg. 1998;86:274-82.
[ see abstract below ]
Postoperative nausea and vomiting (PONV) remains a persistent cause of morbidity after ambulatory anesthesia and surgery. There are several antiemetics which can be used to reduce the incidence of PONV, but they all have a price - whether side effects, dollar cost, or both. Ondansetron, a 5-HT3 receptor antagonist, is a highly effective antiemetic with few side effects, but a considerably high cost. It is therefore important to identify the optimum dose and timing of dosing in order to achieve the highest degree of benefit for the money spent. This study evaluated 164 women, ASA status 1 or 2, who were scheduled for outpatient laparoscopic procedures. Subjects were randomly assigned, in a double-blind fashion, to receive either pre-and post-operative saline, pre-and post-operative ondansetron (2 mg), preoperative ondansetron (4 mg) plus postoperative saline, or postoperative ondansetron (4 mg) with saline before induction.
Anesthesia was induced with fentanyl (1-1.5 mg/kg), propofol (1.5-2 mg/kg), and intubation with either succinylcholine or vecuronium. Anesthesia was maintained with desflurane (3-6%) with 60-70% nitrous oxide. The amount of intravenous fluids and need for reversal agents were similar among the groups, as were incidences of previous PONV, previous motion sickness, and anesthetic and surgery times. During the recovery phase, there were no significant differences in the times to eye opening, response to verbal command or orientation, nor were there differences in the VAS scores for sedation, fatigue, comfort or pain. In the PACU, the incidence of nausea was lower in both groups receiving ondansetron 4 mg in a single dose compared to the placebo group (38% and 49% vs. 74%) whereas the incidence of vomiting was significantly reduced from placebo only when the drug was given at the end of surgery (15% vs. 36%). The need for rescue antiemetics in the PACU was similar in all treatment groups (20-42%). The groups who received ondansetron 4 mg at the end of surgery had significantly shorter times to first oral intake, ambulation, and readiness for discharge. The patients who received 4 mg of ondansetron at either time had significantly earlier actual discharge times compared to the placebo and split dose groups. The survival curve analysis identified the time from end of anesthesia until 25% of patients developed PONV. This was significantly longer in the group receiving ondansetron 4 mg at end of surgery: > 1440 min rather than 178-421 min. After discharge, more patients who received ondansetron at the end of surgery were able to resume fluid and normal food intake on the day of surgery, and this patient group reported a higher satisfaction score.
The overall weighted cost per patient for management of PONV (including administering prophylactic and rescue antiemetics, emesis cleanup and cost of managing side effects), was $21 + $7. The authors defined the cost effectiveness ratio as the cost per patient with complete response and no side effects from prophylactic antiemetics. From the hospital's perspective, the cost effectiveness ratios were $53 (placebo), $64 (split-dose ondansetron), $46 (ondansetron 4 mg before induction) $36 (ondansetron 4 mg after surgery). If nursing care was excluded, the cost effectiveness ratios were $21, $25, $35 and $28, respectively. However, if the incidence of PONV before discharge from the ambulatory care center was less than 30% (instead of the 36% actually seen), the cost effectiveness ratio for the placebo treated patients was lower than that of the ondansetron group. This highlights the importance of reserving prophylactic antiemetics for patients at high risk for PONV. Patients stated that they were willing to a pay mean of $117 + $82 to prevent PONV if they underwent a similar operation in the future, and 80% of patients were willing to pay some additional amount.
This study demonstrates that ondansetron 4 mg at the end of surgery appears to be the best dosing regimen. Ondansetron 4 mg given preoperatively is somewhat less effective, and a split dose of 2 mg before- 2 mg after was no better than placebo. This study also supports data obtained using another 5-HT3 antagonist, dolasetron, that suggest drugs in this class appear to be most effective when given at the end of surgery. The authors also point out that this may be true for metoclopramide. Finally, the cost of ondansetron remains a major concern. Tang et al used a willingness-to-pay method to assess monetary benefits from the patient's point of view. This is a standard technique, but the results may be skewed by the relatively affluent patients enrolled in this study, who knew that the additional costs would indeed be paid by their insurance. Nonetheless, the underlying point remains highly valid. Patient satisfaction is an important, although often not evaluated, measure of the success of an anesthetic technique.
Return to the Current Literature Review Front Page, or read the abstract:
ABSTRACT
Although ondansetron (4 mg I.V.) is effective in the prevention and treatment of postoperative nausea and vomiting (PONV) after ambulatory surgery, the optimal timing of its administration, the cost-effectiveness, the cost-benefits, and the effect on the patient's quality of life after discharge have not been established.
In this placebo-controlled, double-blind study, 164 healthy women undergoing outpatient gynecological laparoscopic procedures with a standardized anesthetic were randomized to receive placebo (Group A), ondansetron 2 mg at the start of and 2 mg after surgery (Group B), ondansetron 4 mg before induction (Group C), or ondansetron 4 mg after surgery (Group D). The effects of these regimens on the incidence, severity, and costs associated with PONV and discharge characteristics were determined, along with the patient's willingness to pay for antiemetics.
Compared with ondansetron given before induction of anesthesia, the administration of ondansetron after surgery was associated with lower nausea scores, earlier intake of normal food, decreased incidence of frequent emesis (more than two episodes), and increased times until 25% of patients failed prophylactic antiemetic therapy (i.e., had an emetic episode or received rescue antiemetics for severe nausea) during the first 24 h postoperatively. This prophylactic regimen was also associated with the highest patient satisfaction and lowest cost-effectiveness ratios. Compared with the placebo group, ondansetron administered after surgery significantly reduced the incidence of PONV in the postanesthesia care unit and during the 24-h follow-up period and facilitated the recovery process by reducing the time to oral intake, ambulation, discharge readiness, resuming regular fluid intake and a normal diet.
When ondansetron was given as a "split dose," its prophylactic antiemetic efficacy was not significantly different from that of the placebo group. In conclusion, the prophylactic administration of ondansetron after surgery, rather than before induction, may be associated with increased patient benefits.
Implications: Ondansetron 4 mg I.V. administered immediately before the end of surgery was the most efficacious in preventing postoperative nausea and vomiting, facilitating both early and late recovery, and improving patient satisfaction after outpatient laparoscopy.
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