Safest and cheapest antiemetics should be used first for postoperative nausea
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《英国医生杂志》
Drugs for reducing postoperative nausea and vomiting are equally effective, and so which treatment patients receive should be guided by safety and affordability.
More than 75 million surgical patients worldwide are anaesthetised each year. Without treatment a third will have postoperative nausea, vomiting, or both. The relative benefits of prophylactic antiemetic interventions given alone or in combination, however, remain unknown.
In a randomised controlled trial comparing combinations of six different antiemetics a team of researchers led by Dr Christian Apfel of the Julius-Maximilians University in W黵zburg, Germany, enrolled 5199 patients from 28 different centres who were scheduled to undergo elective surgery under general anaesthesia and who had a high risk of postoperative nausea and vomiting (New England Journal of Medicine 2004;350:2441-51).
The authors concluded: "Because anti-emetic interventions are similarly effective and act independently, the safest or least expensive should be used first. Prophylaxis is rarely warranted in low-risk patients, moderate-risk patients may benefit from a single intervention, and multiple interventions should be reserved for high-risk patients."
The risk of postoperative nausea and vomiting exceeded 40% for all the patients in the study, according to a simplified risk score that was based on the presence of at least two risk factors from among female sex, non-smoking status, a previous history of postoperative nausea and vomiting or motion sickness, and expected use of postoperative opioids.
Patients were randomly assigned to one of 64 possible combinations of six interventions: 4 mg of ondansetron or no ondansetron; 4 mg of dexamethasone or no dexamethasone; 1.25 mg of droperidol or no droperidol; propofol or a volatile anaesthetic; nitrogen or nitrous oxide; and remifentanil or fentanyl. The primary outcome was nausea and vomiting within 24 hours of surgery, which was evaluated blindly.
Overall, 1731 of 5161 patients (34%) had postoperative nausea and vomiting. Increasing the number of antiemetics reduced the incidence of postoperative nausea and vomiting from 52% when no antiemetics were used to 37%, 28%, and 22% when one, two, and three antiemetics, respectively, were administered. This corresponds to a 26% reduction in the relative risk of nausea and vomiting for each additional antiemetic (95% confidence interval 23% to 30%). There were no significant differences among the antiemetics or among any pair of antiemetics.
When the interactions between treatments and potential confounding factors (such as the type of surgery) were analysed, only one significant interaction was detected: between droperidol and sex (P=0.003). Droperidol significantly reduced the risk of postoperative nausea and vomiting among women but not among men: 910 of the 2106 women (43%) who did not receive droperidol had nausea or vomiting, compared with 662 of the 2101 women (32%) who did receive it (odds ratio 0.61 (95% confidence interval 0.53 to 0.69); P<0.001). In contrast 79 of the 482 men (16%) who did not receive droperidol had nausea or vomiting, compared with 80 of the 472 men (17%) who did (odds ratio 1.04 (0.74 to 1.46); P=0.82).
The large number of participants and the trial抯 factorial design allowed simultaneous evaluation of all of the typical combinations of antiemetic and anaesthetic interventions. All the tested antiemetics seemed to be similarly effective. Ondansetron and other 5-hydroxytryptamine type 3 antagonists are considered relatively safe but are more expensive than droperidol and dexamethasone. However, low dose droperidol can cause dysphoria. The US Food and Drug Administration recently added a "black box" warning to the drug抯 labelling to indicate that it may be associated with torsades de pointes.(New York Scott Gottlieb)
More than 75 million surgical patients worldwide are anaesthetised each year. Without treatment a third will have postoperative nausea, vomiting, or both. The relative benefits of prophylactic antiemetic interventions given alone or in combination, however, remain unknown.
In a randomised controlled trial comparing combinations of six different antiemetics a team of researchers led by Dr Christian Apfel of the Julius-Maximilians University in W黵zburg, Germany, enrolled 5199 patients from 28 different centres who were scheduled to undergo elective surgery under general anaesthesia and who had a high risk of postoperative nausea and vomiting (New England Journal of Medicine 2004;350:2441-51).
The authors concluded: "Because anti-emetic interventions are similarly effective and act independently, the safest or least expensive should be used first. Prophylaxis is rarely warranted in low-risk patients, moderate-risk patients may benefit from a single intervention, and multiple interventions should be reserved for high-risk patients."
The risk of postoperative nausea and vomiting exceeded 40% for all the patients in the study, according to a simplified risk score that was based on the presence of at least two risk factors from among female sex, non-smoking status, a previous history of postoperative nausea and vomiting or motion sickness, and expected use of postoperative opioids.
Patients were randomly assigned to one of 64 possible combinations of six interventions: 4 mg of ondansetron or no ondansetron; 4 mg of dexamethasone or no dexamethasone; 1.25 mg of droperidol or no droperidol; propofol or a volatile anaesthetic; nitrogen or nitrous oxide; and remifentanil or fentanyl. The primary outcome was nausea and vomiting within 24 hours of surgery, which was evaluated blindly.
Overall, 1731 of 5161 patients (34%) had postoperative nausea and vomiting. Increasing the number of antiemetics reduced the incidence of postoperative nausea and vomiting from 52% when no antiemetics were used to 37%, 28%, and 22% when one, two, and three antiemetics, respectively, were administered. This corresponds to a 26% reduction in the relative risk of nausea and vomiting for each additional antiemetic (95% confidence interval 23% to 30%). There were no significant differences among the antiemetics or among any pair of antiemetics.
When the interactions between treatments and potential confounding factors (such as the type of surgery) were analysed, only one significant interaction was detected: between droperidol and sex (P=0.003). Droperidol significantly reduced the risk of postoperative nausea and vomiting among women but not among men: 910 of the 2106 women (43%) who did not receive droperidol had nausea or vomiting, compared with 662 of the 2101 women (32%) who did receive it (odds ratio 0.61 (95% confidence interval 0.53 to 0.69); P<0.001). In contrast 79 of the 482 men (16%) who did not receive droperidol had nausea or vomiting, compared with 80 of the 472 men (17%) who did (odds ratio 1.04 (0.74 to 1.46); P=0.82).
The large number of participants and the trial抯 factorial design allowed simultaneous evaluation of all of the typical combinations of antiemetic and anaesthetic interventions. All the tested antiemetics seemed to be similarly effective. Ondansetron and other 5-hydroxytryptamine type 3 antagonists are considered relatively safe but are more expensive than droperidol and dexamethasone. However, low dose droperidol can cause dysphoria. The US Food and Drug Administration recently added a "black box" warning to the drug抯 labelling to indicate that it may be associated with torsades de pointes.(New York Scott Gottlieb)