Remifentanil-induced Hyperalgesia In Patients With Cirrhosis And Undergoing Orthopaedic Operation

At present,remifentanil is the main opioid used in clinical anesthesia because of its stable aging-half-life curve and no accumulation effect.However,Opioid-induced hyperalgesia（OIH）can increase the amount of other analgesics after surgery,which leads to an increase in the incidence of related complications.In view of the OIH phenomenon of remifentanil,early intervention with sufentanil,ketamine and analgesia after operation with electronic pump injection of sufentanil compound formula（combined use of non-steroidal analgesics）was used in clinical anesthesia,which avoided the pain and discomfort caused by remifentanil OIH,and controlled the dangerous complications such as respiratory depression within a safe range.However,patients with liver cirrhosis often have autonomic and sensory nerve dysfunction.It has been reported that the sensory threshold of patients with liver cirrhosis is significantly lower than that of normal people,and they are more sensitive to pain stimuli.Therefore remifentanil may be more likely to cause the incidence and severity of post-operative hyperalgesia in patients with liver cirrhosis.Full analgesia may increase the incidence of adverse reactions such as post-operative respiratory depression,which needs to be studied urgently.Orthopaedic surgery patients have severe pain after operation.When combined with hyperalgesia,it may significantly increase the use of analgesics after operation,increase the possibility of respiratory depression,which is not conducive to the recovery of patients after operation.Recent studies have shown that remifentanil withdrawal can prevent hyperalgesia.The purpose of this study was to observe the effect of remifentanil on the occurrence of post-operative hyperalgesia and adverse reactions such as post-operative respiratory depression in patients with liver cirrhosis,so as to lay a foundation for providing safer perioperative use of opioids for patients with l iver cirrhosis.At the same time,the study evaluated the effect of remifentanil withdrawal on postoperative hyperalgesia in patients with orthopaedic Orthopaedics,and aims to provide new ideas for postoperative analgesia in clinical orthopedic patients.Part one:Reasearch of remifentanil-induced hyperalgesia in patients with cirrhosisObjective At present,clinical data suggest that remifentanil-induced hyperalgesia only increases acute pain 24 hours after surgery,and increases the dosage of postoperative analgesics,but does not increase the incidence of postoperative analgesic-related complications.Methods 30 patients with cirrhosis who underwent abdominal surgery in our hospital and 30 patients with non-cirrhosis who underwent elective abdominal surgery were enrolled from March 2017 to October 2018.Patients with cirrhosis and non-cirrhotic patients were divided into two groups.Patients in the two group were treated with remifentanil in combination with propofol(propofol 6-8 mg﹒kg^-1﹒h^-1 and remifentanil0.08 to 0.20μg﹒kg^-1﹒min^-1)to maintain anesthesia.The threshold of electrical pain was detected before induction of anesthesia and 2、4h after surgery.The VAS score were recorded at 2、4h after surgery and the sufentanil consumption were recorded simultaneously.The cases of adverse reactions such as nausea,vomiting,respiratory inhibition,hypotension and chills after operation were recorded.Result The pain threshold at 2h and 4h after liver cirrhosis and non-cirrhosis group was significantly lower than that before operation（P<0.05）,and the pain threshold was lower in patients with cirrhosis than in non-cirrhosis group.The VAS score of patients with non-cirrhosis was significantly lower than that of patients with cirrhosis（P<0.05）.In the cirrhosis group,the dose of sufentanil was higher than that in the non-cirrhosis group（P<0.05）,and the postoperative PACU sufentanil was significantly higher than the non-cirrhosis group（P<0.05）.The incidence of respiratory depression（SpO2<85%）in the postoperative cirrhosis group was higher than that in the non-cirrhosis group（P<0.05）.Conclusion Cirrhosis increases the hyperalgesic effect induced by remifentanil,which leads to increased postoperative pain,increased doses of analgesics,and increased incidence of respiratory depression.Part Two:Gradual withdrawal of remifentanil in the end of operation may prevent opioid-induced hyperalgesia in patients undergoing orthopaedic operationObjective To investigate the effect of gradual withdrawal of remifentanil on remifentanil-induced postoperative hyperalgesia in patients undergoing orthopaedic operation.Methods Eighty patients undergoing elective cervical spine surgery were assigned into two groups according to the table of random number:the gradual withdrawal group（group G）and the abrupt withdrawal group（group A）,45 males and 35 females,aged 20-55years,BMI 18.5-24 kg/m²,ASA II or III.The vital signs were monitored and the intravenous anesthesia was performed.All the patients were give intravenous injection of0.2μg﹒kg^-1﹒min^-1 remifentanil and 4-12 mg﹒kg^-1﹒h^-1 propofol to maintain the anesthesia.At the end of the surgery,group A stopped remifentanil abruptly while group G gradually reduced the amount of anesthesia maintenance by one-third per five-minute pump.The threshold of mechanical pain was detected before induction of anesthesia and 1,2,6and 24h after surgery.The VAS score were recorded at 1,2,6 and 24h after surgery and the sufentanil consumption were recorded simultaneously.The awakening time,consciousness recovery time and extubation time of patients were recorded.The cases of adverse reactions such as nausea,vomiting,respiratory inhibition,hypotension and chills after operation were recorded.Result The mechanical pain threshold at 1h and 2h after operation in group A was significantly decreased（P<0.05）,and returned to normal at 6h after surgery（P>0.05）,while the mechanical pain thresholds at 1h,2h,6h and 12h after operation in group G were not significantly changed（P>0.05）.The VAS scores of patients in group A were significantly higher than those in group G at 1 and 2 hours after operation（P<0.05）.Compared with group A,the postoperative consumption of sufentanil was significantly reduced in0-1h,1-2h and 2-6h periods after surgery in group G,There was no significant difference in awakening time,consciousness recovery time,postoperative extubation time between the two groups（P>0.05）.Compared with group A the incidence of nausea and respiratory inhibitionwas significantly decreased in group G.Conclusion Gradual withdrawal of remifentanil in the end of operation may prevent opioid-induced hyperalgesia in patients undergoing orthopaedic operation.