Effects Of Ketolorac Combined With Low-Dose Nalmefene On Remifentanil-Induced Postoperative Hyperalgesia

Background:Remifentanil is a novel ultra-short-acting μopioid receptor agonist,which is significantly different from other fentanyl analogues.It has the advantages of rapid onset,short maintenance time,rapid metabolism,and no accumulation in continuous infusion.Now it has been widely used in the induction of general anesthesia for various clinical operations and maintenance of analgesia during surgery.However,remifentanil can cause hyperalgesia and drug tolerance in a dose-dependent manner.Therefore,how to prevent and treat postoperative hyperalgesia caused by remifentanil has attracted more and more attention.Studies have shown that low doses of opioid receptor antagonists can reduce and prevent the development of hyperalgesia.In this study,the effect of ketolorac combined with low-dose nalmefene on postoperative hyperalgesia caused by intraoperative remifentanil injection was observed,and the possible mechanism of ketolorac combined with low-dose nalmefene in antagonizing hyperalgesia caused by remifentanil was explored.Methods:1.Sixty patients with elective gynecological laparoscopic surgery,ASAⅠ-A grade,age30-70 years old,weight 45-70 kg,2 hours < operation time <4 hours,were selected.Inclusion criteria: there is no history of alcoholism or drug addiction,no history of mental illness,liver and kidney not seen abnormal lung function,without severe hypertension,cardiovascular disease such as arrhythmia,without using adverse drug reflects the history,there is no history of allergies,did not use analgesics,48 hours without active peptic ulcer,recent not seen in gastrointestinal bleeding or perforation,bleeding tendency.2.All patients fasted from water for at least 8 hours before surgery,without preoperative medication.After the patient entered the operating room,the vein was routinely opened to monitor the patient’s electrocardiogram,blood pressure,pulse oxygen saturation and other basic vital signs.Induction drugs in 2 groups were given as follows: midazolam 0.03mg/kg,etomidate 2mg/kg,atracurium cisesulfonate 0.2mg/kg,sufentanil 0.5μg/kg.Intraoperative maintenance: propofol 4-8mg/kg·h,remifentanil0.25μg/(kg· min),cisatracurium 0.1mg/(kg·h),mechanical ventilation after endotracheal intubation,aspiration/call ratio 1:2.Tidal volume 6-8ml/kg,ventilation frequency 10-15 times /min,end-expiratory partial pressure of carbon dioxide maintained at 35%-42%,heating blanket to maintain body temperature.After induction of intubation,palonosetron was given 0.25 mg intravenously.When bradycardia(heart rate <50 beats /min)occurred during the operation,0.5mg of atropine was injected intravenously.When hypotension(mean arterial pressure <60mm Hg)occurred,intravenous administration of noradrenaline 10μg.The drug was discontinued 5 minutes before the end of surgery.After the operation,the patient was admitted to the ward and requested additional dizocin analgesia.The patients were randomly divided into experimental group(ketolorac + nalmefen)and control group(ketolorac),with 30 cases in each group.Control group: 60 mg ketorolac was injected 30 minutes before the end of surgery.Experimental group: 60 mg ketolorac was given intravenously 30 min before the end of surgery,and nalmephene 0.25μg/kg intravenously 10 min before the end of surgery.3.The time from postoperative anesthesia withdrawal to recovery(T1)and from recovery to extubation(T2)were recorded;Visual Analogue Scale(VAS)at 1h(H1),6h(H6),12h(H12),and 24h(H24)after extubation was used to score the degree of pain after awakening in the two groups:A score of 0 indicates no pain,1 to 3 indicates mild pain,4 to 6 indicates moderate pain,and 7 to 10 indicates severe pain.The higher the score,the higher the pain rating.The incidence of postoperative adverse reactions,such as nausea,vomiting and irritability,and the number of patients requiring additional analgesia were observed.Results:1.Comparison of T1 and T2 after operation between the two groups showed that the experimental group was lower than the control group,the difference was statistically significant(P<0.05).2.VAS scores in the experimental group were lower than those in the control group at different time periods,and the difference was statistically significant(P<0.05).Conclusion:1.Low dose nalmefen combined with ketorolac has a better effect on hyperalgesia after remifentanil surgery than ketorolac alone.2.Ketolorac combined with low dose nalmefen can antagonize the hyperalgesia caused by remifentanil,accelerate the recovery of patients’ consciousness,make patients wake up as soon as possible,and reduce the degree of postoperative pain.