Efficacy of nalmefene antagonizing postoperative respiratory depression induced by opioids:a multicenter,randomized,double-blind,positive drug-controlled study

Objective To evaluate the efficacy of nalmefene antagonizing postoperative respiratory depression induced by opioids.Methods Two hundred and forty ASA Ⅰ orⅡpatients aged 18-64 yr with body weight fluctuating within 20% of the standard body weight were included in this multicenter,randomized,double-blind,positive drug-controlled study.Anesthesia was induced with etomidate 0.3 mg/kg and TCI of sufentanil(effect-site concentration 0.4.ng/ml).Tracheal intubation was facilitated with vecuronium 0.1 mg/kg or rocuronium 0.6mg/kg.The patients were mechanically ventilated.PETCO2 was maintained at 35-45 mm Hg.Anesthesia was maintained with sevoflurane+ sufentanil TCI(Ce=0.1-0.4 ng/ml).Patients undergoing neurosurgery and liver or kidney operation were excluded.The operation time was within 3 h.The residual effects of muscle relaxants were reversed after operation.The patients were randomly divided into 2 groups(n=120 each):group Ⅰneloxone andgroup Ⅱ nalmefene.Naloxone 0.1 mg or nalmefene 0.25 μg/kg was injected iv over 30 s and was repeated 5 min later if necessary until the respiratory rate＞10 bpm,PETCO2＜45 mm Hg and apnea time＜15 s.The total amount of naloxone was≤0.4 mg while that of nalmefene≤1 μg/kg.BP,HR,SpO2,PETCO2,respiratory rate and apnea time were recorded immediately before and at 2 and 5 min after haloxone/nalmefene administration and then every 5 min until 5 min after extubation.The recovery of spontaneous breathing within 30 min after naloxone/nalmefene administration,extubation time and Ramsay sedation score at 5 min after extubation were recorded.The patients were also observed for adverse reactions.Results Spontaneous breathing recovered within 30 min after naloxone/nalmefene administration in all patients in both groups.The extubation time was significantly shorter in nalmefene group than in naloxone group.There was no significant difference in Ramsay sedation score,BP,HR,SpO2 and incidence of adverse reactions between the 2 groups.Conclusion Nalmefene is better than naloxone in antagonizing opioid-induced postoperative respiratory depression. Key words: Nalmefene; Sufentanil; Respiratory insufficiency