Effects Of Mu-opioid Receptor,CYP3A5 Genetic Polymorphisms On Hydromorphone Consumption In Postoperatve Clavicle Fracture Patients

Objective To investigate the relationship between postoperative analgesia of hydromorphone hydrochloride and genetic polymorphisms of mu-opioid receptor(OPRM1),CYP3A5*3 in unilateral clavicle fracture patients.Methods One hundred and twenty patients with unilateral clavicle fracture treated with open reduction and internal fixation under general anesthesia were selected,with ASA grade ? or ?,age 20-65 years old,and gender unlimited.All patients were scored with the General Anxiety Scale(GAD-7)before surgery,and the results of ALT,AST and A/G were recorded.After entering the operating room,5 ml of venous blood was sampled for specimens,and a unified anesthesia protocol was implemented.All anesthetic drugs were stopped at the end of the operation,and hydromorphone was given for intravenous controlled analgesia(PCIA).The pain score(NRS score),sedation score(Ramsay score)and cumulative consumption of hydromorphone were recorded at 1 h,6 h,12 h,24 h and 36 h postoperatively.Postoperative nausea and vomiting score(PONV grade)and the number of compressions for patient-controlled analgesia(PCA)were recorded at each time period.Multiplex PCR was used to detect and genotype the OPRM1 A118G(rs 1799971)and CYP3A5*3(rs776746)variant alleles in blood samples.Statistical analysis of the relationship between OPRM1 A118G,CYP3A5*3 gene polymorphisms and Cumulative hydromorphone consumption for postoperative analgesia while evaluate the effects of non-genetic and genetic factors on the analgesic effect of hydromorphone.Results There was no significant difference in the NRS score and hydromorphone cumulative consumption between OPRM1 A118G genotype groups at each postoperative time point(1 h,6 h,12 h,24 h,36 h)(P>0.05).The NRS score of CYP3A 5*3 AA(*1/*1)group at 12 h after operation was higher than that of AG(*1/*3)and GG(*3/*3)groups(P<0.05),and the cumulative consumption of hydromorphone at 12 h,24 h and 36 h after operation was higher than that of AG(*1/*3)and GG(*3/*3)groups(P<0.05).The cumulative consumption of hydromorphone at 1,6,12 and 24 hours after operation was positively correlated with the times of patient-controlled analgesia((?=0.152,P<0.05;?=0.137,P<0.05;?=0.181,P<0.05;?=0.185,P<0.05).The cumulative consumption of hydromorphone at 24 h and 36 h after operation was positively correlated with the length of operation(? 0.003,P<0.05;?=0.005,P<0,05),positively correlated with the NRS score at 24 h and 36 h after operation(?=0.061,P<0.05;?=0.100,P<0.05),and negatively correlated with age(?=-0.034,P<0.05;?=-0.063,P<0.05).Preoperative AST measurements were independent factors associated with cumulative consumption of hydromorphone at 6 h postoperatively.For every 1 U/L increase in AST,cumulative consumption of hydromorphone increased by an average of 0.005 mg.Conclusions Hydromorphone 0.08 mg/ml can effectively control pain after unilateral clavicular fracture surgery in selected adults.The polymorphism of OPRM1 A118G had no significant effect on the postoperative analgesic effect of hydromorphone.CYP3A5*3(*1/*1)was associated with increased hydromorphone analgesic consumption 12,24,and 36 h after surgery,and CYP3A5*3 gene polymorphism was associated with the analgesic effect of hydromorphone PCIA after general anesthesia for unilateral clavicular fracture in selected adults.The analgesic effect of hydromorphone PCIA after elective unilateral clavicular fracture in adults was positively correlated with the length of operation and negatively correlated with age.