August 2000

A Comparison of the Costs and Efficacy of Ondansetron Versus Dolasetron for Antiemetic Prophylaxis
Zarate E, Watcha MF, White PF, Klein KW, Sa Rego M, Stewart DG.
Anesth Analg 2000:90;1352-8

[see abstract below]

Commentary by Beverly Philip, M.D.

Post operative nausea and vomiting are common problems after outpatient surgery, and antiemetics are often necessary. In the class of serotonin [5-HT3] antagonist antiemetics, both ondansetron and dolasetron are clinically available in the USA. The optimum dose and timing of the administration of these drugs for antiemetic prophylaxis have not been settled. In addition, the comparative cost effectiveness has not been determined. The primary aim of this study was to compare the relative efficacy and costs associated with the use of dolasetron vs. ondansetron for routine prophylaxis against PONV in a high-risk ENT population. A secondary aim was to compare the antiemetic efficacy of different doses of ondansetron (4 or 8 mg IV) and dolasetron (12.5 or 25 mg IV) when administered at the end of surgery.

Two hundred patients ASA I and II, ages 20 � 75 yrs, undergoing ENT procedures were studied in a randomized double-blinded protocol. Patients were excluded if they were pregnant, had clinically significant organ disease, had a history of drug abuse, or were greater than 100 % over their ideal body weight. Patients were asked to provide a detailed medical history and demographic information including age, weight, height, alcohol and/or drug consumption, as well as history of PONV or motion sickness.

Before entering the operating room, patients completed baseline visual analog scales (VAS) for sedation, fatigue, comfort, pain, and nausea, using a 100mm scale. Patients received midazolam for premedication and anesthesia was induced with propofol 1.5mg/kg and remifentanil 1ug/kg. Tracheal intubation was facilitated with rocuronium and anesthesia was maintained with sevoflurane 0.75% end-tidal concentration in air and oxygen. An infusion of remifentanil was administered at an initial rate of 0.125ug/kg/min and subsequently varied from 0.0625 to 0.375ug/kg/min to maintain heart rate and blood pressure values within 15% of baseline. Patients were randomly assigned to receive one of four antiemetic study medications: 1) 12.5 mg dolasetron, 2) 25 mg dolasetron, 3) 4 mg ondansetron, 4) 8 mg ondansetron. The antiemetics were delivered within 30 minutes before the end of surgery. A blinded observer recorded the time elapsed from the end of surgery until when patients were able to open their eyes, follow commands and became oriented. Additional recovery parameters, including times to sitting, standing, tolerating oral fluid, ambulating, duration of recovery stay and discharge, were assessed at 15-min intervals. VAS scores were repeated at 30-min intervals. All side effects during the perioperative period as well as the requirement for any rescue medications were recorded. When the patient vomited or requested treatment for persistent nausea, 6.25mg promethazine was administered. When symptoms persisted, patients were administered 1.25 mg droperidol. Patients who complained of pain in the PACU received 25ug of fentanyl IV bolus doses until they were comfortable. Pain in the second stage recovery area was managed with oral hydrocodone/acetaminophen. A trained interviewer contacted all patients by telephone twenty-four hours after discharge to inquire about post-discharge side effects and the need for any therapeutic interventions at home.

The perspective used in the cost analysis was of a freestanding surgicenter in a managed care environment, although the study had been performed in a tertiary care teaching hospital. Direct cost for the management of emesis including the costs for "emesis cleanup," rescue antiemetics, management of the side effects of prophylactic and rescue antiemetic drugs, as well as the costs of the drugs, supplies and labor. In this model all costs were based on the acquisition costs of the drugs, and included the cost of wasted drugs. Nursing labor costs were adjusted to the level of care, with higher costs assigned to the more labor-intensive PACU recovery area. A complete response to antiemetic prophylaxis was defined as a patient completely free of emesis and without need for antiemetic drugs to control nausea.

Overall, there were no significant differences among the four treatment groups with respect to demographic data, length of procedure, drugs given during the procedure, or duration of recovery or discharge. There were also no significant differences in PONV related outcomes. The in-hospital rate of nausea was 11�15% in all groups, vomiting 0-4%, and lack of complete response with the antiemetic regimen 10�15% [all NSD]. There were also no significant differences among groups in post-discharge symptoms: 6-9% nausea, 1-3% vomiting and 5-10% lack of complete response. Similarly, there were no differences in symptoms reported at the twenty-four hour follow-up: 12-19% nausea, 3-6% vomiting and 12-15% lack of complete response. The incidence of repeated emetic symptoms (greater or equal to two episodes) and the need for rescue antiemetics similarly did not differ among the groups.

However, significant differences were found in the costs related to the management of PONV among the four groups. The total costs related to manage the PONV were significantly reduced in the group receiving 12.5 mg of dolasetron compared with the other three regimens. This difference could be accounted for by the difference in the acquisition cost of dolasetron, since there were no significant differences in the incidence of side effects and therefore no differences in the costs of treatment [emesis cleanup, nursing labor, or rescue antiemetics]. The total costs for managing PONV were significantly larger with prophylactic 8mg of ondansetron compared with the other three groups, due to the higher acquisition costs; there were no cost differences among the 25 mg of dolasetron and 4 mg of ondansetron groups. Finally, there were no significant differences in the VAS scores on discharge or the number of patients who were completely satisfied with their anesthetic management.

In conclusion, 12.5 mg of dolasetron IV is as effective as 25 mg of dolasetron, 4 mg of ondansetron and 8 mg of ondansetron, when given at the end of surgery to prevent PONV. It achieves the same degree of patient satisfaction at a lower cost. Therefore, in situations where prophylaxis with a 5-HT3 antagonist is appropriate, 12.5 mg of dolasetron administered at the end of surgery appears to be the more cost effective approach.

ABSTRACTS A Comparison of the Costs and Efficacy of Ondansetron Versus Dolasetron for Antiemetic Prophylaxis AUTHORS: Zarate E, Watcha MF, White PF, Klein KW, Sa Rego M, Stewart DG. SOURCE: Anesth Analg 2000:90;1352-8 The optimal dose and timing of 5-HT(3) antagonist administration for prophylaxis against postoperative nausea and vomiting (PONV) remains controversial. Although 5-HT(3) antagonists seem to be most effective when administered near the end of surgery, there are no data on the comparative efficacy or costs associated with the 5-HT(3) antagonists dolasetron and ondansetron when administered at the end of the operation. In this double-blinded study, 200 outpatients undergoing otolaryngologic procedures with a standardized general anesthetic received 4 (O4) or 8 mg (O8) of ondansetron or 12.5 (D12.5) or 25 mg (D25) of dolasetron IV within 30 min before the end of surgery. A blinded observer recorded the emetic episodes, maximum nausea score, recovery room resource and drug use, nursing time spent managing PONV, times to achieve discharge criteria from the Phase 1 and 2 recovery units, postdischarge emesis, and patient satisfaction. Total costs were calculated by using the perspective of a free-standing surgicenter. There were no differences in patient demographics, incidence of PONV, need for rescue medications, time spent in the recovery areas, unanticipated hospital admissions, or patient satisfaction among the four treatment groups. The mean total costs (95% confidence intervals) to prevent PONV in one patient were lowest in the D12.5 group: $23.89 (17.18-28.79) vs $37.81 (30.29-45.32), $33.91 (28.92-39.35), and $75.18 (61.13-89.24) for D25, O4, and O8, respectively. Excluding nursing labor costs did not alter this finding: $18.51 (14.18-22.85), $34.77 (28.03-41.49), $31.77 (28. 92-39.35), and $71.76 (58.17-85.35) for D12.5, D25, O4, and O8, respectively. We conclude that 12.5 mg of dolasetron IV is more cost effective than 4 mg of ondansetron IV for preventing PONV after otolaryngologic surgery and is associated with similar patient satisfaction. Implications: When administered at the end of surgery, 12.5 mg of dolasetron IV is as effective as 25 mg of dolasetron IV, 4 mg of ondansetron IV, and 8 mg of ondansetron IV in preventing emetic symptoms after otolaryngologic surgery and was associated with similar patient satisfaction at a reduced cost. There were no differences in the antiemetic efficacy of the 4 and 8 mg doses of ondansetron.