Dose-Response Relationship Of Butorphanol Combined With Dexmedetomidine On Preventing Postoperative Hyperalgesia Induced By Remifentanil In Patients

Remifentanil is selectively mu opioid agonist. Due to its reliability, rapid onset and predictable rapid recovery profile, remifentanil has been widely used in clinical practice.In a previous study performed in patients undergoing remifentanil anesthesia, the dose of remifentanil 0.1 to 0.5 ?g· kg^-1·min^-1, can increase the incidence of opioids induced hyperanalgesia?OIH?, but the mechanism of OIH is unclear. Therefore, the prevention of OIH is necessary to improve with comfort and satisfaction on the postoperative patients. Butorphanol as a mixed agonist-antagonist opioid is partial ? antagonists and full ? agonists. Dexmedetomidine is a highly selective ?2-adrenoceptor agonist with sedative and analgesic properties. It has been applied in the sedation outsidethe operating room,ICU sedation,combined anesthesia and so on. Numerous studies have demonstrated that both Butorphanol and Dexmedetomidine can prevent postoperative hyperanalgesia induced by remifentani, the result of studies were different because of using differentclinical data, drugs, and assessment. This study is aimed to investigate the ED₅₀ and ED₉₅ of Butorphanol combined with Dexmedetomidine on preventing postoperative hyperanalgesia induced by remifentanil in patientsundergoing laparoscopic gynecological surgery.Part one:Effect of butorphanol combined with dexmedetomidine on postoperative hyperalgesia induced by remifentanilObjective Numerous studies have demonstrated that Butorphanol or dexmedetomidine can prevent postoperative hyperalgesia induced by remifentani, there is no study about investigating the effectof Butorphanol combined with Dexmedetomidine on preventing postoperative hyperalgesia induced by remifentanil in patients.Methods One hundred and twenty patients?ASA I-II, 20-65yr? undergoing laparoscopic gynecological surgery were randomly allocated into four groups?n=30?: In Group C, the normal saline equal to the volume of butorphanol was injected before incision; In Group B, Butorphanol20?g/kg was injected before incision; In Group D, Dexmedetomidine was administrated at continuous infusionof0.7?g·kg^-1·h^-1 until the closure of skin followed by infusionof1?g/kg for 10 min before induction of anesthesia; In Group B+D, Dexmedetomidine was administrated at continuous infusionof0.5?g·kg^-1·h^-1 until the closure of skin followed by infusionof0.5?g/kg for 10 min before induction of anesthesia, and sequential method was used to intravenously Butorphanol before incision, initial dose is 15?g/kg and gradient is 2.5?g. Tactile pain threshold in right inner forearm was measured at 24 h preoperatively and repeated at 24 h postoperatively. The pain score?VAS? and the dose of sufentanyl comsumption were also recorded 30min?60min?6h?12h and 24 h after surgery. Logistic regression was used to calculate ED₅₀?ED₉₅ and 95%CI of Butorphanol.Results Compared with group C,the sufentanil consumption and incidence of nausea and vomiting were Significantly decreased in B,Dand B+D groups,the incidence of dizziness and somnolence was increased in group B,and the incidence of bradycardia and hypotensionwas increased in group D.There was no significant difference in sufentanil consumption between B,D and B+D groups.The incidence of dizziness and somnolence was significantly lower in group B+D than in group B.The incidence of bradycardia,hypotension and somnolence was significantly lower in group B+D than in group D.Conclusion Butorphanol 20?g/kg was injected before incision canalleviate postoperative hyperalgesia induced by remifentanil;Dexmedetomidine 0.5?g/kg was infused at 10 min before induction of anesthesia,followed by continuous infusion at 0.5?g·kg^-1·h^-1 until the end of operation,and butorphanol 15?g/kg was injected immediately before skin incision,can alleviate postoperative hyperalgesia induced by remifentanil;Butorphanol combined with dexmedetomidine provides better efficacy than either alone in reducing postoperative hyperalgesia induced by remifentanil inpatientsundergoing laparoscopic gynecological surgery. Part two: Dose-response relationship of Butorphanol combined with Dexmedetomidine on preventing postoperative hyperalgesia induced by remifentanil in patientsObjective To investigate the ED₅₀ and ED₉₅ of Butorphanol combined with Dexmedetomidine on preventing postoperative hyperalgesia induced by remifentanil in patients.Methods Therewerethirty patients?ASA I-II, 20-65yr? undergoing laparoscopic gynecological surgery, Dexmedetomidine was administrated at continuous infusionof0.5?g·kg^-1·h^-1 until the closure of skin followed by infusionof0.5?g/kg for 10 min before induction of anesthesia, and sequential method was used to intravenously Butorphanol before incision, initial dose is 15?g/kg and gradient is 2.5?g.Directed patients to assess pain scores with VAS. 15 minafter extubation,recorded the VAS of patients. If effect of butorphanol combined with dexmedetomidine on postoperative hyperalgesia induced by remifentanil in one case of patients was effectively, VAS score < 4,the next case reduced 1 gradient dose of butorphanol;if effect is invalid, VAS score ? 4, the next case elevated1 gradient dose of butorphanol.Logistic regression was used to calculate ED₅₀?ED₉₅ and 95%CI of Butorphanol.Results The ED₅₀ of Butorphanol combined with Dexmedetomidine is 7.5?g/kg,95%CI?4.7¹1.9??g/kg;ED₉₅ is 12.4?g/kg,95%CI?7.8¹9.7??g/kg.Conclusion The ED₅₀ and ED₉₅ of Butorphanol combined with Dexmedetomidine on preventing postoperative hyperalgesia induced by remifentanil in patients are 7.5?g/kg and 12.4?g/kg...