Dexmedetomidine And Nalmefene Reduces Remifentanil-induced Hyperalgesia:A Clinical Trial

Objectives The aim of the present research was to investigate the effect of combined dexmedetomidine with low-dose nalmefene on remifentanil-induced hyperalgesia.Methods This study is a a randomized double-blind controlled trial.120 patients were chosen from Tianjin Medical University General Hospital,who underwent elective laparoscopic gynecological surgery between March 2017 and December2017.Patients with American Society of Anesthesiologist physical status I or?,aged 20~64yr,BMI 18~25kg/m~2 were selected.They were randomly assigned into four groups(n=30)as follows:Group R(control group,normal saline 3ml),Group N(nalmefene0.3?g/kg),GroupD(dexmedetomidine0.4?g/kg/h),Group DN(dexmedetomidine 0.4?g/kg/h and nalmefene 0.3?g/kg).Each of them injected normal saline or nalmefene or dexmedetomidine 10 min before the induction of anesthesia.General anesthesia was induced with midazolam 0.05 mg/kg,sufentanil0.3?g/kg,etomidate 0.3mg/kg,and rocuronium 0.6mg/kg was given to facilitate tracheal intubation.Anesthesia was maintained with inhalation of desflurane concentration at 4%~6%,remifentanil was intravenously infused continuously(0.30?g/kg/min)as intraoperative analgesic.Anesthetic depth was controlled within a bispectral index of 45–60.And rocuronium 0.3mg/kg was administered intermittently to maintain muscular relaxation during operation.The patients were recovered at the end of surgery and admitted to postanesthesia care unit(PACU)with patient-controlled analgesia,using sufentanil(100?g)in normal saline in a total volume of 100 ml,and PCA pump was set to deliver a basal infusion of 2 ml/hand bolus doses of 0.5 ml with a 15 min lockout period.Visual analogue scale score was maintained less than 4.Those measurements were observed:(1)We recorded the patients characteristics:ASA status,age,BMI,duration of surgery,duration of remifentanil infusion,the consumption of desflurane during surgery and the proportion of patients administered vasoactive agents.(2)We recorded postoperative eye opening time and extubation time,and sedation levels at 5 min,10min,15min,30min,60min in PACU.(3)We recorded the mechanical pain threshold on the peri-incisional area and the dominant inner forearm at 24h preoperation and postoperation,and the normalized area of hyperalgesia around the incision was measured at 24h after surgery.(4)We recorded postoperative pain intensity at rest and after movement at 1h,3h,6h,12h.(5)We recorded the first demanding time and dosage of postoperative sufentanil,and sufentanil consumption was recorded at 1,3,6,12 and 24h after surgery.(6)The incidence of postoperative side-effects was monitored during the 24h after surgery.Results 1.There were no significant differences between the four groups with respect to age,BMI,ASA status,duration of surgery,duration of remifentanil infusion and the proportion of patients administered atropine(P>0.05).The consumption of desflurane during surgery was significantly lower in Group D and Group DN.The proportion of patients administered phenylephrine was higher in Group D compared with other groups(P<0.05).2.Compared with Group R,Groups N and DN exhibited shorter eye opening time and extubation time(P<0.01),Group D exhibited delayed eye opening time and extubation time(P<0.01).Concurrently,the Ramsay score of Group D and Group DN at 5 min,10min,15min after arrival at the PACU was higher than Group R(P<0.01).However,There was no difference between Group D and Group DN in Ramsay score(P>0.05).3.The baseline mechanical pain threshold on the dominant inner forearm and around the incision was similar among all the groups(P>0.05).Compared with baseline,remifentanil anesthesia resulted in a dramatic decrease in pain threshold on the forearm(P<0.01)and around the incision(P<0.01).Furthermore,compared with Group R,higher levels of threshold on the forearm and around the incision were recorded in Group N,Group D and Group DN.Compared with Group N,threshold on the forearm and around the incision was increased in Group D and DN(P<0.05).Besides,there was no significant difference between Group D and DN(P>0.05).Compared with Group R,the normalized area of hyperalgesia around the incision in Groups N,D and DN were reduced(P<0.01).Compared with Group N,it was reduced in Group D and DN(P<0.01).However,there was no significant difference between GroupD and DN(P>0.05).4.Compared with Group R,the NRS scores at rest were lower in Group N at 1h,3h,while Group D and Group DN at all time points(P<0.05).Compared with Group N,NRS scores at rest were lower in Group D at 3-12h and in Group DN at all time points(P<0.05).After movement,there was no significant difference between Group N and Group R in NRS scores(P>0.05).NRS scores in Group D and Group DN decreased at all time points.No significant difference in NRS scores was observed between Group D and Group DN(P>0.05).5.Compared with Group R,the first demanding time of postoperative sufentanil was longer and the amount of sufentanil titrated was significantly lower in Groups N,D and DN(P<0.01).Sufentanil consumption by PCA in Group N at 3h,6h as well as Group D and Group DN at all time points was significantly less than that in Group R(P<0.01).6.The incidence of nausea,vomiting,and shivering were higher in Group R.compared with other groups(P<0.05).Furthermore,Group D presented a higher incidence of hypotension and bradycardia compared with Group R.Conclusion 1.Pretreatment with nalmefene 0.3?g/kg or dexmedetomidine0.40?g/kg/h or both together relieved postsurgical RIH.2.Pretreatment with nalmefene 0.3?g/kg exhibited shorter eye opening time and extubation time,which was opposite to dexmedetomidine pretreatment.3.The preoperative combination of nalmefene 0.3?g/kg and dexmedetomidine0.4?g/kg/h showed significant antihyperalgesic properties and might reduce dexmedetomidine-related side-effects.