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SPA Newsletter.
By Thomas J. Mancuso, MD, FAAP A factorial trial of six interventions for the prevention of postoperative nausea and vomiting.Apfel CC, et al. N Engl J Med 2004; 50:2441-2451 This randomized, controlled trial enrolled over 5000 adult patients at high risk for PONV. The design was factoral, allowing the evaluation of the interaction of up to three separate interventions for PONV. The subject's scheduled surgical procedures were such that they were expected to receive at least one hour of general anesthesia. Four thousand subjects were randomized to receive one of 64 possible combinations of six possible antiemetic therapies: 4 mg or no ondansetron, 4 mg or no dexamethasone, 1.25 mg or no droperidol; propofol or a volatile anesthetic; nitrogen or nitrous oxide and remifentanil or fentanyl. The remaining subjects were randomized among the first 4 therapies. PONV within the first 24 hours following surgery was evaluated. The authors found that ondansetron, dexamethasone and droperidol each reduced the risk of PONV by approximately 26%. Propofol reduced the risk by 19% and nitrogen by 12%. All interventions reduced risk of PONV independently. An important point the authors make is that the decrease in risk for PONV depends "critically" on the patient's initial risk. Thus the absolute risk reduction for PONV in a patient with a 10% risk for PONV who is given dexamethasone will be approximately 3% but the same therapy given to a patient with an 80% risk for PONV will decrease that person risk by 21%. The resulting relative risk of nausea and vomiting associated with a combination of interventions can be estimated as the product of the individual relative risks. The absolute reduction of risk for PONV is, then, less for each additional intervention and even with the administration of TIVA and three treatments for PONV the maximum risk reduction for PONV is approximately 70%. The authors conclude that, since each intervention reduced the risk of PONV to a similar extent, safer and less expensive therapies should be chosen first. Combination therapy increases the risk of side effects and, as mentioned above, each additional therapy lessens the risk of PONV to a smaller degree. In an analysis of the demographics of the patient population and surgical procedures the authors noted that with the exception of hysterectomy, the relative risk for PONV was similar for all types of procedures, when corrected for the known risk factors in adults; gender, nonsmoking status, a history of PONV, and the use of opioids in the postoperative period. Commentary Although the subjects in this large, very well done investigation were adults, I think the results may have an impact on my practice. The authors confirmed that droperidol and ondansetron have similar efficacy as anti-emetic agents, the anti-emetic effect of propofol and increased incidence of PONV due to the administration of nitrous oxide. A study of this magnitude will likely never be done in pediatrics. As the authors recommend n their conclusion, I may use TIVA more often in children when I am particularly concerned about PONV and, when not contraindicated by the child's medical conditions, administer dexamethasone Intraop as my first-line antiemetic, and use ondansetron in the PACU as a rescue therapy when needed. I also will more carefully choose the patients for whom I use more than one therapy for PONV, basing that decision on my assessment of the child's initial risk for PONV. Table of Contents
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