Nalmefene Hydrochloride Against Postanaesthetic Respiratory Depression Induced By Sufentanil Hydrochloride

Objective:To evaluate the efficacy and safety of nalmefene hydrochloride injection against postoanaesthetic respiratory depression in adult patients undergoing sufentanil combined general anesthesia clnically in order to supply a reseanable evidence to clinical practice.Method:A randmized,double-blind,parallelism,contrast with a positive durg experiment was adoptted.64 adult patients of both sexes,aged 18-65,with body mass index 18～25 kg-1·m2, ASAⅠorⅡ, who would receive elective surgery undergoing sufentanil combined general anaesthesia and with sufentanil-induced respiratory depression postanaesthesia, were intraduced in the study.They were randomly devided into 2 groups(32 cases in each):Nalmefene or naloxone group.All patients were inducted with etomidate 0.3 mg·kg-1, sufentanil 0.2～0.5μg·kg-1 and rocuronium 0.6 mg·kg-1 stepwise. Their tracheal was intubated after local asperse with 2% lidocaine, then ventilated mechanically (VT 8～10 ml·kg-1, RR 10～15 bpm, I:E=1:1.5). Anesthesia was maintained with sevoflurane inhalled (end-tidalconcentration of 1.7%～2.2%),continuous infusion of propofol (50～100μg·kg-1·min-1) and intermittent intravenous boluses of sufentanil (0.2～0.6μg·kg-1·h-1), rocuronium was administered if necessary during the operation.Infusion of proplfol and inhalatiaon of sevoflurane were ceased 5 min prior to the end of operation. Heart rate and blood pressure fluctuated up-and-down less than 30% of the baseline.PetCO2 was maintained between 35-45 mmHg. Either nalmefene or naloxone was randomly administered intravenously in each patient when muscle relaxation and awareness recoverd, sufentanil—induced respiratory depression simultaneously occurred postoperatively. The same increments can be repeated 5 min later till spontaneous respiration recovered. Vital parametres were recorded before and 2,5 min after administration, and every 5 min afterward until 5 min postextubation,including mean arterial blood pressure (MAP), heart rate (HR),tidal volume(VT), respiratory rate(RR), duration of apnea, PetCO2 and the saturation of blood oxygen(SpO2), breathing recorvery time and extubation time after administration; Ramsay sedation score befor administration and 5 min after extubation;the rate of breathing recovery 10 min after administration;total dosage and dosage at 10 min after administration of the two drugs. ECG and laboratory examinations were practised,that were blood routine (RBC, HGB, WBC, PLT), urine routine (RBC, WBC, PRO), liver and renal function(ALT,AST, BUN, Cr) within 24 hours after the initial dose. Inverse events during the study were recorded.Results:There were no significant differences in general state of health between the two groups(P>0.05).The anaesthesia duration,cumulative sufentanyl consumption were similar in both groups(P>0.05). There were no significant differences in breathing recorvery and extubation time after administration between two groups: (4.74±0.58) vs (5.06±0.39) min and (6.29±0.74) vs (6.83±1.02) min, respectively (P>0.05).There was no significant difference in ratio of breathing recovery at 10 min after administration in both groups:96.88 vs 93.75%, respectively (P>0.05). There were no significant differences in whole consumption and the consumption 10 min postadministration (P>0.05). MAP was significantly higher than that of preadministration (P<0.05),and no differences between the two groups (P>0.05). There were significant differences in ventilation values (RR,PetCO2 and Apnea interval) pre and post administration in both groups (P<0.05).There was significant difference in Ramsay sedation score preadministration and 5 min postextubation but similar in the two groups (P<0.05).Incidence of inverse events during the study was no difference in both groups, respectively 3.13% and 6.25%(P>0.05). Severe inverse events were not observed during the study.Conclusions:Compared with equipotent dose of naloxone, nalmefene has the same effectiveness against sufentanil-induced postanesthetic respiratory depression.There are no remarkable organs'poisonous or inverse effects found in clinical rutine dosage.