Department of Anesthesiology, University Hospital Hamburg-Eppendorf, Martinistrasse 52, D-20246 Hamburg, Germany
Corresponding author. E-mail: burmeister@uke.uni-hamburg.de
Declaration of interest. The work was supported by Aventis Pharma, Germany and included payment of patients insurance and the fee of the local ethics committee. Results of this work have been presented at the German Congress of Anesthesiology in Munich, May 2000 and at the Annual Meeting of the ASA, in San Francisco, October 2000.
Accepted for publication: September 26, 2002
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Abstract |
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Methods. This prospective, randomized, double-blind study was performed to evaluate the efficacy of prophylaxis with dolasetron in reducing the frequency of postoperative nausea and duration of discharge time. Forty urological patients, undergoing elective ambulatory extracorporeal shock wave lithotripsy (ESWL) received randomly either dolasetron 12.5 mg i.v. (Group 1) or placebo (Group 2) 10 min before a patient-adapted continuous infusion of remifentanil 0.150.4 µg kg1 min1 was administered. Frequency and intensity (VAS 0100 mm) of nausea, retching, and vomiting were assessed by patients and blinded investigators during and after the procedure.
Results. Patient characteristics, baseline values, duration of ESWL, and total dose of remifentanil did not differ between groups. The frequency (Group 1/Group 2; 20/55%; P<0.05) and mean (SD) maximal intensity [15 (9)/45 (14) mm; P<0.05] of nausea during 24 h was significantly reduced after dolasetron and discharge times in Group 1 were less than Group 2 [22 (14)/45 (28) min; P<0.05].
Br J Anaesth 2003; 90: 1948
Keywords: analgesics opioid, remifentanil; vomiting, nausea; vomiting, antiemetics
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Introduction |
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Midazolam and propofol have shown to reduce these symptoms when infused in combination with remifentanil.2 9 Because the emetic effect of remifentanil seems to be dose-dependent,5 part of the antiemetic effect of these agents could be explained by the remifentanil dose sparing effect. Also, propofol itself may have antiemetic effects. However, the combination of these drugs with remifentanil increases the rate and severity of respiratory depression. An alternative is the prophylactic use of an antiemetic such as the 5-HT3 antagonist dolasetron, which has good antiemetic efficacy without sedative side-effects.1013 Therefore, in a prospective, randomized and double-blind trial we tested the hypothesis that dolasetron 12.5 mg before remifentanil infusion may reduce the frequency and intensity of nausea and time to home readyness after ambulatory ESWL.
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Methods |
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On the basis of retrospective data from our institution and the literature in the same patient population, a power analysis was performed by using the proportion of complete responders following the procedure as the primary outcome variable. Complete responders were defined as patients with no emetic episodes, no rescue medication and a maximum VAS of 5 mm (VAS ranging from 0 to 100 mm) within 24 h according to the published data of other study groups.10 15 We set 50% as the predicted value for the placebo group. We defined the smallest difference to be clinically significant as 25% (
=0.05, ß=0.20). This analysis indicated that a sample size of at least 56 patients per group was necessary. An interim analysis was performed after every 10 patients. The study was stopped for ethical reasons when the difference of the primary outcome variable reached significance (P<0.05). The randomization was done by using a MS Excel macro (Microsoft Corp., USA). We did a blockwise randomization (blocks consisting of 10 patients) to ensure that for interim analysis, which was performed after every 10 patients, the groups did not differ in size. Computerized statistical analysis was performed using SPSS 9.0 (SPSS Inc.) and Instat 2.1 (Graphpad Inc.). Data are given as mean (SD) unless otherwise indicated. Statistical analysis was performed using Students t-test (patient characteristics), Fischers exact test (categorical data) and MannWhitney U-test (discharge time, VAS values). A value of P<0.05 was considered to be statistically significant.
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Results |
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Discussion |
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Studies have13 20 found that i.v. dolasetron 12.5 mg was the maximally effective dose for preventing PONV so we chose this dose for our present study. In addition this regimen was found to be as effective as i.v. dolasetron 25 mg, i.v. ondansetron 4 mg, or i.v. ondansetron 8 mg in preventing emetic symptoms after otolaryngologic surgery.21 In common with others,13 15 we chose the proportion of complete responders [no emetic episodes in 24 h (5 mm VAS)] and the maximum nausea (VAS), following the procedure as the primary outcome variable. As expected, antiemetic prophylaxis with dolasetron 12.5 mg did not completely prevent PONV after remifentanil infusion for ESWL in our study, but was able to reduce the incidence and intensity of postoperative nausea and retching significantly with an increased total response in comparison with placebo during the first 24 h. As with other studies of remifentanil for monitored anaesthesia care in patients undergoing ESWL, the frequency of persisting nausea and vomiting was low. Joo and collegues2 described 27% of patients with nausea but only 3% of them vomited during postoperative period. Nausea and vomiting do not usually occur during remifentanil infusion. Therefore, remifentanil infusion is still a suitable technique. The incidence of PONV in the placebo group in our present study was comparable with the incidence we found in a previous trial with remifentanil for MAC during ESWL.7 As in this study, the onset of the symptoms was early (<60 min) and the duration was relatively short in most patients. The severity of the symptoms decreased over time. The majority of studies reported incidences of PONV in the range of 1442%.1 2 8 The lower doses of remifentanil and the combination with propofol or midazolam can probably explain the lower incidences of PONV in these studies in comparison with our data.
The potential benefit of the ultra-short-acting remifentanil with respect to an earlier discharge from the PACU in comparison to long-acting analgesics and sedatives is limited by its emetic side-effect when given as a sole agent. In our study, PONV symptoms were the main reason preventing earlier discharge. As a consequence, the dolasetron prohylaxis directly improved postoperative recovery and decreased the time to readiness for discharge.
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Acknowledgements |
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References |
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