Clinical Study Of Poorly Controlled Postoperative Pain After Single-port Video-assisted Thoracoscopic Surgery

Objectives:At present,pneumonectomy under single-port video-assisted thoracoscopic surgery(VATS)is widely used as the treatment of lung diseases.Although the trauma of this type of surgery is relatively small and multimodal analgesia is routinely applied,some patients still experience poorly controlled postoperative pain,which seriously affects the outcomes of the patients.Early identification of high-risk patients with poorly controlled postoperative pain is a prerequisite for individualized postoperative pain management.Firstly,the retrospective analysis was conducted to explore the clinical characteristics associated with poorly controlled postoperative pain in patients undergoing single-port VATS and establish a relevant prediction model.Secondly,genetic factors may affect individual pain perception and analgesic effect,causing variances in the occurrence of poorly controlled postoperative pain in different patients.We further explored the correlation between single nucleotide polymorphisms(SNP)in pain-related genes and the occurrence of poorly controlled postoperative pain in patients under this kind of surgery.Finally,considering the high incidence of poorly controlled postoperative pain and the shortcomings of current applied analgesic drugs,a randomized controlled trial was performed to verify the analgesic effect and explore the usage strategy of hydromorphone in patient controlled intravenous analgesia(PCIA)for patients after single-port VATS in order to optimize the patients' postoperative pain management and minimize the occurrence of poorly controlled postoperative pain.Methods:Part I: A retrospective analysis was performed on medical records of patients who underwent single-port VATS between January 2015 and December 2016.According to the occurrence of poorly controlled postoperative pain within 24 hours postoperatively(static pain visual analogue scale(VAS)? 40 and/or additional analgesics required and/or unsatisfactory with analgesia according to follow-up),the patients were divided into two groups: poorly controlled postoperative pain group(Group Pos)and analgesia sufficiency group(Group Neg).The risk factors of poorly controlled postoperative pain were analyzed by univariate analysis,and the related risk factors were analyzed by multivariate logistic regression analysis.The corresponding prediction model was constructed according to the results of the analysis.The prediction ability of the model was verified by discrimination and calibration.Part II: The blood samples of the patients who underwent elective single-port VATS of lung lesions in our hospital from October 2017 to March 2018 were prospectively collected and the results of postoperative analgesia were followed up.DNA was extracted from patients' blood samples and 31 SNPs were genotyped by Taq Man Genotyper.According to the occurrence of poorly controlled postoperative pain within 24 hours postoperatively(static pain VAS ? 40 and/or additional analgesics required and/or unsatisfactory with analgesia according to follow-up),the patients were divided into two groups: poorly controlled postoperative pain group(Group Pos)and analgesia sufficiency group(Group Neg).Multivariate logistic regression analysis was used to explore the SNPs associated with poorly controlled postoperative pain.Part III: Patients who underwent elective single-port VATS of lung lesions in our hospital from May 2018 to November 2018 were randomly divided into three groups:VIII Group Mb received morphine bolus only for postoperative analgesia(n = 57);Group Hb received hydromorphone bolus only(n = 57);Group Hb+i received hydromorphone background infusion plus bolus(n = 57).Follow-up was performed at 8 a.m.and 8 p.m.postoperatively until 3 days after operation or discharged from hospital.The primary outcomes were patient-reported static pain VAS and dynamic pain VAS.The secondary outcomes included bolus times,analgesia rescue rate,poorly controlled postoperative pain rate,nausea and vomiting rate,antiemetic rescue rate,postoperative sleep quality,cacation within 2 days,out-of-bed activity time,chest tube extubation time,overall pain management satisfaction,and length of stay in hospital after surgery.Results:Part I: 1099 patients underwent single-port VATS were included in the final analysis,of which 369 patients(33.6%)developed poorly controlled postoperative pain within 24 hours postoperatively.After multivariate logistic analysis,the prediction model was established.The results indicated that higher age,more senior surgeon,and routine application of analgesic had protective effect on poorly controlled postoperative pain following this type of surgery with 24 hours postoperatively.Female,higher Body Mass Index(BMI),and preoperative pain within 1 month were the risk factors.The area under curve(AUC)was 0.73(0.70-0.76)(p < 0.001)and the calibration curve is a smoothed curve with the slope approximate 1 and the intercept approximate 0 which means the prediction model had moderate discrimination and moderate calibration.Part II: A total of 198 patients' blood samples were collected and the follow-up results of postoperative analgesia were obtained.Patients were allocated into two groups according to criteria,Group Pos(n = 90)and Group Neg(n =108).Significant factors such as age and education level were incorporated into multivariate logistic regression analysis.The results suggested that the patients with SCN11 A rs33985936 T minor allele,SCN10 A rs6795970 A minor allele,and SCN9 A 3312G>T T minor allele had higher risk experiencing poorly controlled postoperative pain,while the patients with SCN11 A rs11709492 T minor allele had lower risk experiencing poorly controlled postoperative pain.Part III: In total,171 patients were randomly allocated into three groups: Group Mb(n = 57),Group Hb(n = 57),and Group Hb+i(n = 57).Comparisons of primary outcomes and secondary outcomes among Group Mb and Group Hb resulted in no significant difference.Compared with Group Mb and Group Hb,patients in Group Hb+i experienced lower VAS in both static pain and dynamic pain(all p < 0.001)in the days following surgery,fewer bolus times(all p < 0.05),higher rate of better sleep quality during the first night only(all p < 0.05),and higher rate of better overall satisfaction of pain management(all p < 0.05).At each follow-up point,the analyses of resuce analgesic,poorly controlled postoperative pain rate,nausea and vomiting rate,antiemetic rescue rate,sleep quality of the second night,cacation within 2 days,out-of-bed activity time,chest tube extubation time,and length of stay in hospital after surgery showed no significant difference among groups.Conclusion:Poorly controlled postoperative pain following single-port VATS is prevalent.Age,gender,BMI,preoperative pain within 1 month,surgeon with different seniority,and routine application of analgesic could influnce poorly controlled postoperative pain in patients within 24 hours after single-port VATS.The prediction model incorporating these factors has moderate prediction ability.In addition,four loci(SCN11A(rs11709492,rs33985936),SCN10A(rs6795970),SCN9A(3312G>T))may correlate with poorly controlled postoperative pain in patients and may partially influence poorly controlled postoperative pain.There is no advantage in analgesic effect or side effects to administering hydromorphone under bolus only model over morphine after single-port VATS,while background infusion plus bolus with hydromorphone can significantlyreduce the static pain VAS and dynamic pain VAS without increasing the incidence of adverse effects,significantly improve patients' sleep quality of postoperative first night and pain management satisfaction.Therefore,background infusion plus bolus should be considered as standard protocol of PCIA before 8 a.m.at first postoperative day.After the follow-up point,whether background infusion continues should be adjusted according to the expectancy of pain,actual pain intensity,and adverse effects of the patients.