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© 2000 International Anesthesia Research Society
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Abstract |
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Implications: We studied 180 female patients undergoing breast surgery. The patients were randomly allocated to receive one of three anesthetic techniques. Compared with either propofol or sevoflurane alone, sevoflurane with ondansetron resulted in a decreased incidence of postoperative nausea and vomiting. Sevoflurane with ondansetron prophylaxis is a good alternative to propofol with respect to avoiding postoperative nausea and vomiting.
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Introduction |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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Propofol has been associated with a small incidence of postoperative nausea and vomiting (PONV) compared with inhaled anesthetics (1). Some studies suggest that propofol acts as an antiemetic when used to treat chemotherapy-induced emesis (2) and PONV in subhypnotic doses (3,4).
Ondansetron is effective in the prevention and treatment of PONV with few side effects (5). Compared with ondansetron, propofol more effectively prevents PONV in the early phase of recovery (6).
We tested the hypothesis that the overall incidence of PONV after sevoflurane with ondansetron prophylaxis is smaller compared with propofol.
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Methods |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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After we obtained the approval of the local ethics committee, this randomized, controlled trial was performed in two centers. Written, informed consent was obtained from 180 adult female inpatients (ASA physical status I–III) scheduled for breast surgery. Patients were randomly assigned to one of three anesthetic treatment groups.
All patients were premedicated with midazolam 7.5 mg orally. Anesthesia was induced with glycopyrrolate 0.2 mg, fentanyl 2–4 µg/kg and propofol 1–2 mg/kg IV. Intubation was facilitated with rocuronium 0.5 mg/kg IV. All patients had controlled mechanical ventilation with oxygen-enriched air.
After the induction, the patients in the propofol group (Group P) received propofol infusion 3–10 mg · kg-1 · h-1. In the sevoflurane and sevoflurane-ondansetron groups (Groups S and SO), the patients received sevoflurane up to the end-tidal concentration of 2%. The patients in Group SO were administered an IV injection of ondansetron 8 mg at the end of surgery. In all groups, increments of fentanyl 1–2 µg/kg IV were given as required during the operation. Neuromuscular reversal drugs were not used.
During the administration of anesthesia, standard monitoring (electrocardiogram, noninvasive blood pressure, ETCO2, and pulse oximetry) was used. Postoperatively, pain relief was provided by oxycodone 0.05 mg/kg IV in the postanesthesia care unit (PACU), and 0.1 mg/kg IM on the ward. Paracetamol 1 g was given orally at 8-h intervals. Rescue antiemetic treatment was provided with droperidol 0.75 mg IV. All patients were monitored for a period of at least 2 h in the PACU.
After 2 h and 24 h, the patients were interviewed by a nurse or one of the authors, who were blinded as to the method of anesthesia used. The occurrence of PONV, the need for rescue antiemetic treatment, the intensity of postoperative pain, opioid pain therapy, and any adverse events were recorded. Average postoperative pain during the study period was assessed by the patients’ using an 11-point scale in which 0 was no pain at all and 10 represented the worst pain imaginable.
Sample size (60 patients in each group) was estimated by using a two-sided 
level of 0.05 and a power of 0.80. The incidence of nausea was assumed to be 60% after inhaled anesthesia and 35% after ondansetron prophylaxis. The outcomes were statistically compared by calculating the 95% confidence interval for the differences in proportions by using the CIA program (7) and by calculating a P value for the null hypothesis of no difference by using the 
2 or Fisher’s exact test, when appropriate. One-way analysis of variance, the median test, or the Kruskal-Wallis test was used to compare the continuous variables. If a significant difference was noted, post hoc analysis (least significant difference adjustment) was performed to determine intergroup differences. The SPSS for Windows (versions 7.5 and 8.0) (SPSS, Chicago, IL) statistical package was used.
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Results |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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One hundred eighty patients participated in the study, 60 in each group; 107 patients were studied in Lapland Central Hospital and 73 patients in Oulu University Hospital. The distribution among the groups was equal in both centers. The treatment groups were also similar demographically (Table 1). The intraoperative fentanyl dose was significantly larger in Group P compared with other groups (Table 1). Mean propofol dose was 7.5 mg · kg-1 · h-1 (±2.6) in Group P, and the mean end-tidal concentration for sevoflurane was 1.5% (±0.43) in Group S and 1.6% (±0.46) in Group SO.
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The incidence of PONV and need for rescue antiemetic medication in the PACU, after the PACU, and during the whole 24-h period is summarized in Table 2. The mean time from the end of anesthesia administration to the first episode of emesis did not differ among the three groups (7 h 3 min in Group P vs 5 h 7 min in Group S vs 5 h 13 min in Group SO; not significant). The mean time to the first antiemetic dose was the same in all three groups (7 h 25 min in Group P vs 6 h 14 min in Group S vs 7 h 39 min in Group SO; not significant). The median postoperative pain score was significantly higher in Group S (3.0 [2.0–4.0, lower-upper quartiles]) compared with Group SO (2.0 [1.0–3.0, lower-upper quartiles]), but was equal in Group P (3.0 [1.0–4.0, lower-upper quartiles]) in comparison with the other groups. Oxycodone consumption did not differ among the three groups. The side effect profile did not differ after the three anesthetic techniques.
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Discussion |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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Our results suggest that the prophylactic antiemetic property of propofol is short-lasting and does not cover the period after PACU discharge. This finding is consistent with the studies of Gan et al. (6,8), according to whom propofol antiemetic efficacy is related to the concentration of propofol.
Ondansetron is more effective against vomiting than nausea (5). The 8-mg dose of ondansetron was based on the findings of Tramer et al.’s meta-analysis (5). Ondansetron was administered at the end of surgery on the basis of the results of two studies (9,10), according to which the timing should be near the end of surgery (11).
The patients in the propofol group received significantly larger doses of fentanyl during the administration of anesthesia, which may have resulted in an increased overall incidence of PONV and need of antiemetics. The use of nitrous oxide might have reduced the intraoperative need for fentanyl and thereby reduced the incidence of PONV, as suggested by Tang et al. (12). However, there is evidence that fentanyl, when used in analgesic doses during anesthesia administration, does not increase PONV (13,14).
In conclusion, the incidence of postoperative nausea in the PACU did not differ after propofol and sevoflurane-ondansetron anesthesia, but was significantly increased after sevoflurane anesthesia. The incidence of vomiting in the PACU did not differ among the three anesthetic techniques. Compared with either propofol or sevoflurane alone, the combination of sevoflurane and ondansetron resulted in a smaller incidence of PONV during the 24-hour study period.
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Acknowledgments |
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We wish to thank Kari T. Korttila, MD, PhD, for his valuable comments on the manuscript. We want to thank Outi Törmänen, RN, and other assisting nurses in our hospitals. We are grateful to Risto Bloigu, Biostatistician in Medical Informatics Group in Medical Faculty of the University of Oulu, for the assistance in statistical analysis and Kevin W. Harris, MD, PhD, for revision of the language.
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References |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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- Sneyd JR, Carr A, Byrom WD, Bilski AJT. A meta-analysis of nausea and vomiting following maintenance of anaesthesia with propofol or inhalational agents. Eur J Anaesth 1998; 15: 433–45.[Web of Science][Medline]
- Borgeat A, Wilder-Smith OHG, Wilder-Smith CH, et al. Propofol improves patient comfort during cisplatin chemotherapy. Oncology 1993; 50: 456–9.[Web of Science][Medline]
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Borgeat A, Wilder-Smith OHG, Saiah M, Rifat K. Subhypnotic doses of propofol possess direct antiemetic properties. Anesth Analg 1992; 74: 539–41.
[Abstract/Free Full Text] - Gan TJ, El-Molem H, Ray J, Glass PSA. Patient-controlled antiemesis; a randomized, double-blind comparison of two doses of propofol versus placebo. Anesthesiology 1999; 90: 1564–70.[Web of Science][Medline]
- Tramer MR, Reynolds DJM, Moore RA, McQuay HJ. Efficacy, dose-response, and safety of ondansetron in prevention of postoperative nausea and vomiting. Anesthesiology 1997; 87: 1277–89.[Web of Science][Medline]
- Gan TJ, Ginsberg B, Grant AP, Glass PSA. Double-blind, randomized comparison of ondansetron and intraoperative propofol to prevent postoperative nausea and vomiting. Anesthesiology 1996; 85: 1036–42.[Web of Science][Medline]
- Gardner MJ, Altman DG. Statistics with confidence: confidence intervals and statistical guidelines. Br Medical J 1989:29–30.
- Gan TJ, Glass PSA, Howell ST, et al. Determination of plasma concentrations of propofol associated with 50% reduction in postoperative nausea. Anesthesiology 1997; 87: 779–84.[Web of Science][Medline]
- Sun R, Klein KW, White PF. The effect of timing of ondansetron administration in outpatients undergoing otolaryngologic surgery. Anesth Analg 1997; 84: 331–6.[Abstract]
- Tang J, Wang B, White PF, et al. 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.[Abstract]
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White PF, Watcha MF. Postoperative nausea and vomiting: prophylaxis versus treatment. Anesth Analg 1999; 89: 1337–8.
[Free Full Text] - Tang J, White PF, Wender RH, et al. Use of propofol for office-based anesthesia: effect of nitrous oxide on recovery profile. J Clin Anesth 1999; 11: 226–30.[Web of Science][Medline]
- Jakobsson J, Davidson S, Andreen M, Westgreen M. Opioid supplementation to propofol anesthesia for outpatient abortion: a comparison between alfentanil, fentanyl and placebo. Acta Anaesthesiol Scand 1991; 35: 767–70.[Web of Science][Medline]
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Ding Y, White PF. Comparative effects of ketorolac, dezocine, and fentanyl as adjuvants during outpatient anesthesia. Anesth Analg 1992; 75: 566–71.
[Abstract/Free Full Text]
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