Prevention of Postoperative Nausea and Vomiting — A Multimodal Solution to a Persistent Problem
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《新英格兰医药杂志》
Despite the introduction of new antiemetic agents, short-acting anesthetics, and minimally invasive surgical techniques, the incidence of postoperative nausea and vomiting has remained largely unchanged over the past two decades.1 The high incidence of postoperative nausea and vomiting has persisted in part because of the tremendous growth in ambulatory surgery and the increased emphasis on earlier mobilization and discharge after both minor and major operations.
Prophylactic use of antiemetics has become the standard approach to minimizing emetic symptoms after surgery because patients are more satisfied with this approach than with the treatment of symptoms when they occur in the postoperative period.2,3 In fact, patients have expressed a willingness to pay out of pocket to avoid the discomfort of postoperative nausea and vomiting.3,4 With the introduction of newer, more expensive antiemetics (e.g., 5-hydroxytryptamine3 [5-HT3] antagonists and neurokinin-1 antagonists), controversy has arisen as to the most cost-effective antiemetic for routine prophylaxis.
In this issue of the Journal, Apfel and colleagues5 report the results of a trial assessing the relative efficacy of three commonly used antiemetics: droperidol, dexamethasone, and ondansetron. Not surprisingly, the investigators found that the three drugs possessed similar antiemetic efficacy. This large, multicenter European study confirmed the results of previous clinical studies in the United States that showed that droperidol and ondansetron have similar efficacy when administered for antiemetic prophylaxis.6,7,8 In addition, this study, which used multifactorial analysis, confirmed previous work that demonstrated the antiemetic effect of propofol (as compared with volatile agents) for maintenance of anesthesia.9 In contrast to an earlier meta-analysis,10 the current study found that whereas the effect of nitrous oxide and oxygen on postoperative nausea and vomiting was of statistical significance, it was of limited clinical significance.
What important new information is provided by this large trial? First, the multifactorial study design allowed the investigators to evaluate combinations of antiemetic drugs and therapeutic interventions. The resulting data suggest that antiemetics with different mechanisms of action have additive (rather than synergistic) effects on the incidence of postoperative nausea and vomiting. Therefore, there were no significant interactions among the various antiemetic and anesthetic interventions. When combinations of interventions were used, the benefit of the subsequent antiemetic intervention was always less than that of the initial intervention. The low cost and excellent safety profile of both droperidol11 and dexamethasone12 make the combination of these two drugs a highly cost-effective strategy for preventing postoperative nausea and vomiting.2,13 Given the overall efficacy of this combination, it is not surprising that the addition of a 5-HT3 antagonist resulted in only a small incremental benefit when administered to a high-risk surgical population undergoing ambulatory surgery.13
Second, Apfel and colleagues found that total intravenous anesthesia (involving the use of propofol in place of a volatile anesthetic and nitrous oxide) was essentially equivalent to the use of a volatile anesthetic with a prophylactic antiemetic drug, confirming the findings reported by Tang et al.14 in patients undergoing ambulatory surgery. Finally, the use of remifentanil, an ultra–short-acting opioid analgesic, as an alternative to fentanyl was not found to be associated with a significant reduction in postoperative emetic symptoms. The likely explanation for the failure of the shorter-acting opioid analgesic to reduce the risk of postoperative nausea and vomiting was the use of a highly emetogenic opioid analgesic (morphine) at the end of the operation.
Droperidol has recently been the subject of tremendous controversy because of a change mandated by the Food and Drug Administration (FDA) in the drug's package insert.11 Although a recent analysis suggested that even low doses of droperidol (1.25 mg or less, given intravenously) would be expected to prolong the QT interval,15 the degree of QT-interval prolongation associated with antiemetic doses of the drug appears to be of no clinical significance. Despite the absence of any scientific data to support the recommendations of the FDA regarding additional electrocardiographic monitoring before and after the administration of low-dose droperidol, many hospital pharmacies have removed this highly cost-effective drug from anesthesiologists' armamentarium.
In summary, several conclusions of the current study have importance for practitioners. First, the efficacy of prophylactic antiemetic drug therapy is dependent on the patient's overall risk of postoperative nausea and vomiting. Second, the benefit of using two inexpensive antiemetics (e.g., droperidol and dexamethasone) is significantly greater than the benefit of using an expensive 5-HT3 antagonist (e.g., ondansetron). Third, with the addition of each successive therapeutic intervention, the incremental antiemetic benefit diminishes. Finally, from a societal cost–benefit perspective, the current data do not support the use of 5-HT3 antagonists for routine antiemetic prophylaxis.
Dr. White reports having served as a consultant to Merck and Akorn and having received grant support from Merck.
Source Information
From the Department of Anesthesiology and Pain Management, University of Texas Southwestern Medical Center, Dallas.
References
Watcha MF, White PF. Postoperative nausea and vomiting: its etiology, treatment, and prevention. Anesthesiology 1992;77:162-184.
White PF, Watcha MF. Postoperative nausea and vomiting: prophylaxis versus treatment. Anesth Analg 1999;89:1337-1339.
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;86:274-282.
Gan TJ, Sloan F, Dear Gde L, El-Moalem HE, Lubarsky DA. How much are patients willing to pay to avoid postoperative nausea and vomiting? Anesth Analg 2001;92:393-400.
Apfel CC, Korttila K, Abdalla M, et al. A factorial trial of six interventions for the prevention of postoperative nausea and vomiting. N Engl J Med 2004;350:2441-2451.
Tang J, Watcha MF, White PF. A comparison of costs and efficacy of ondansetron and droperidol as prophylactic antiemetic therapy for elective outpatient gynecologic procedures. Anesth Analg 1996;83:304-313.
Fortney JT, Gan TJ, Graczyk S, et al. A comparison of the efficacy, safety, and patient satisfaction of ondansetron versus droperidol as antiemetics for elective outpatient surgical procedures. Anesth Analg 1998;86:731-738.
Hill RP, Lubarsky DA, Phillips-Bute B, et al. Cost-effectiveness of prophylactic antiemetic therapy with ondansetron, droperidol, or placebo. Anesthesiology 2000;92:958-967.
Tang J, Chen L, White PF, et al. Recovery profile, costs, and patient satisfaction with propofol and sevoflurane for fast-track office-based anesthesia. Anesthesiology 1999;91:253-261.
Divatia JV, Vaidya JS, Badwe RA, Hawaldar RW. Omission of nitrous oxide during anesthesia reduces the incidence of postoperative nausea and vomiting: a meta-analysis. Anesthesiology 1996;85:1055-1062.
White PF. Droperidol: a cost-effective antiemetic for over thirty years. Anesth Analg 2002;95:789-790.
Henzi I, Walder B, Tramer MR. Dexamethasone for the prevention of postoperative nausea and vomiting: a quantitative systematic review. Anesth Analg 1999;90:186-194.
Tang J, Chen X, White PF, et al. Antiemetic prophylaxis for office-based surgery: are the 5-HT3 receptor antagonists beneficial? Anesthesiology 2003;98:293-298.
Tang J, White PF, Wender RH, et al. Fast-track office-based anesthesia: a comparison of propofol versus desflurane with antiemetic prophylaxis in spontaneously breathing patients. Anesth Analg 2001;92:95-99.
Zhang Y, Luo Z, White PF. A model for evaluating droperidol's effect on the median QTc interval. Anesth Analg 2004;98:1330-1335.(Paul F. White, Ph.D., M.D)
Prophylactic use of antiemetics has become the standard approach to minimizing emetic symptoms after surgery because patients are more satisfied with this approach than with the treatment of symptoms when they occur in the postoperative period.2,3 In fact, patients have expressed a willingness to pay out of pocket to avoid the discomfort of postoperative nausea and vomiting.3,4 With the introduction of newer, more expensive antiemetics (e.g., 5-hydroxytryptamine3 [5-HT3] antagonists and neurokinin-1 antagonists), controversy has arisen as to the most cost-effective antiemetic for routine prophylaxis.
In this issue of the Journal, Apfel and colleagues5 report the results of a trial assessing the relative efficacy of three commonly used antiemetics: droperidol, dexamethasone, and ondansetron. Not surprisingly, the investigators found that the three drugs possessed similar antiemetic efficacy. This large, multicenter European study confirmed the results of previous clinical studies in the United States that showed that droperidol and ondansetron have similar efficacy when administered for antiemetic prophylaxis.6,7,8 In addition, this study, which used multifactorial analysis, confirmed previous work that demonstrated the antiemetic effect of propofol (as compared with volatile agents) for maintenance of anesthesia.9 In contrast to an earlier meta-analysis,10 the current study found that whereas the effect of nitrous oxide and oxygen on postoperative nausea and vomiting was of statistical significance, it was of limited clinical significance.
What important new information is provided by this large trial? First, the multifactorial study design allowed the investigators to evaluate combinations of antiemetic drugs and therapeutic interventions. The resulting data suggest that antiemetics with different mechanisms of action have additive (rather than synergistic) effects on the incidence of postoperative nausea and vomiting. Therefore, there were no significant interactions among the various antiemetic and anesthetic interventions. When combinations of interventions were used, the benefit of the subsequent antiemetic intervention was always less than that of the initial intervention. The low cost and excellent safety profile of both droperidol11 and dexamethasone12 make the combination of these two drugs a highly cost-effective strategy for preventing postoperative nausea and vomiting.2,13 Given the overall efficacy of this combination, it is not surprising that the addition of a 5-HT3 antagonist resulted in only a small incremental benefit when administered to a high-risk surgical population undergoing ambulatory surgery.13
Second, Apfel and colleagues found that total intravenous anesthesia (involving the use of propofol in place of a volatile anesthetic and nitrous oxide) was essentially equivalent to the use of a volatile anesthetic with a prophylactic antiemetic drug, confirming the findings reported by Tang et al.14 in patients undergoing ambulatory surgery. Finally, the use of remifentanil, an ultra–short-acting opioid analgesic, as an alternative to fentanyl was not found to be associated with a significant reduction in postoperative emetic symptoms. The likely explanation for the failure of the shorter-acting opioid analgesic to reduce the risk of postoperative nausea and vomiting was the use of a highly emetogenic opioid analgesic (morphine) at the end of the operation.
Droperidol has recently been the subject of tremendous controversy because of a change mandated by the Food and Drug Administration (FDA) in the drug's package insert.11 Although a recent analysis suggested that even low doses of droperidol (1.25 mg or less, given intravenously) would be expected to prolong the QT interval,15 the degree of QT-interval prolongation associated with antiemetic doses of the drug appears to be of no clinical significance. Despite the absence of any scientific data to support the recommendations of the FDA regarding additional electrocardiographic monitoring before and after the administration of low-dose droperidol, many hospital pharmacies have removed this highly cost-effective drug from anesthesiologists' armamentarium.
In summary, several conclusions of the current study have importance for practitioners. First, the efficacy of prophylactic antiemetic drug therapy is dependent on the patient's overall risk of postoperative nausea and vomiting. Second, the benefit of using two inexpensive antiemetics (e.g., droperidol and dexamethasone) is significantly greater than the benefit of using an expensive 5-HT3 antagonist (e.g., ondansetron). Third, with the addition of each successive therapeutic intervention, the incremental antiemetic benefit diminishes. Finally, from a societal cost–benefit perspective, the current data do not support the use of 5-HT3 antagonists for routine antiemetic prophylaxis.
Dr. White reports having served as a consultant to Merck and Akorn and having received grant support from Merck.
Source Information
From the Department of Anesthesiology and Pain Management, University of Texas Southwestern Medical Center, Dallas.
References
Watcha MF, White PF. Postoperative nausea and vomiting: its etiology, treatment, and prevention. Anesthesiology 1992;77:162-184.
White PF, Watcha MF. Postoperative nausea and vomiting: prophylaxis versus treatment. Anesth Analg 1999;89:1337-1339.
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;86:274-282.
Gan TJ, Sloan F, Dear Gde L, El-Moalem HE, Lubarsky DA. How much are patients willing to pay to avoid postoperative nausea and vomiting? Anesth Analg 2001;92:393-400.
Apfel CC, Korttila K, Abdalla M, et al. A factorial trial of six interventions for the prevention of postoperative nausea and vomiting. N Engl J Med 2004;350:2441-2451.
Tang J, Watcha MF, White PF. A comparison of costs and efficacy of ondansetron and droperidol as prophylactic antiemetic therapy for elective outpatient gynecologic procedures. Anesth Analg 1996;83:304-313.
Fortney JT, Gan TJ, Graczyk S, et al. A comparison of the efficacy, safety, and patient satisfaction of ondansetron versus droperidol as antiemetics for elective outpatient surgical procedures. Anesth Analg 1998;86:731-738.
Hill RP, Lubarsky DA, Phillips-Bute B, et al. Cost-effectiveness of prophylactic antiemetic therapy with ondansetron, droperidol, or placebo. Anesthesiology 2000;92:958-967.
Tang J, Chen L, White PF, et al. Recovery profile, costs, and patient satisfaction with propofol and sevoflurane for fast-track office-based anesthesia. Anesthesiology 1999;91:253-261.
Divatia JV, Vaidya JS, Badwe RA, Hawaldar RW. Omission of nitrous oxide during anesthesia reduces the incidence of postoperative nausea and vomiting: a meta-analysis. Anesthesiology 1996;85:1055-1062.
White PF. Droperidol: a cost-effective antiemetic for over thirty years. Anesth Analg 2002;95:789-790.
Henzi I, Walder B, Tramer MR. Dexamethasone for the prevention of postoperative nausea and vomiting: a quantitative systematic review. Anesth Analg 1999;90:186-194.
Tang J, Chen X, White PF, et al. Antiemetic prophylaxis for office-based surgery: are the 5-HT3 receptor antagonists beneficial? Anesthesiology 2003;98:293-298.
Tang J, White PF, Wender RH, et al. Fast-track office-based anesthesia: a comparison of propofol versus desflurane with antiemetic prophylaxis in spontaneously breathing patients. Anesth Analg 2001;92:95-99.
Zhang Y, Luo Z, White PF. A model for evaluating droperidol's effect on the median QTc interval. Anesth Analg 2004;98:1330-1335.(Paul F. White, Ph.D., M.D)