Effects Of Eskatamine Combined With Hydromorphone On Postoperative Analgesia And Quality Of Recovery In Patients Undergoing Thoracoscopic Surgery

BackgroundThe main source of postoperative pain in thoracic surgery is the injury of chest wall and pleura caused by intercostal nerve mediated skin incision,thoracic drainage tube insertion,muscle injury,rib traction,etc.,and the release of central terminal neurotransmitters(glutamic acid,substance P,calcitonin gene-related peptide and brain-derived growth factor)from spinal dorsal horn neurons along with sustained traumatic somatic afferentation Increase.Through signal transduction(such as glutamate with N-methyl-D-aspartate receptors(NMDAR)),these neurotransmitters produce a state of neuronal hyperactivity and hyperexcitation in the spinal cord and brain called central sensitization.In addition,the activation of NMDA receptors not only increases the cellular response to pain stimuli,but also reduces the neuronal sensitivity to opioid receptor agonists.Whether esketamine,as an NMDA receptor antagonist combined with hydromorphone,can reduce the incidence of postoperative moderate-severe pain in patients,whether fewer opioids are used with fewer side effects,and whether it can play more roles in multi-mode analgesia under the concept of accelerated rehabilitation surgery.Further research is needed to initially explore the optimal dose with minimal side effects and whether it can improve the quality of postoperative recovery in patients undergoing thoracic surgery.ObjectiveA single-center,randomized,controlled,double-blind study was conducted to investigate the effects of different doses of eskatamine combined with hydromorphone on postoperative analgesia and recovery quality in patients undergoing thoracoscopic surgery,with a view to reducing postoperative opioid dosage and side effects,and accelerating postoperative recovery of patients.MethodsA total of 220 patients aged 18 to 65 years with BMI≥18kg/m2 and ≤30kg/m2 were selected for thoracoscopic(VATS)assisted thoracic surgery under bronchial intubation and general anesthesia from May 2022 to February 2023.Random numbers were generated by Excel and random block design was adopted,with block length of8.Randomly divided into 4 groups according to the 1:1:1:1 ratio: 0.5mg/kg esketamine combined with hydromorphone group(S1 group,55 cases),1.0mg/kg esketamine combined with hydromorphone group(S2 group,55 cases),2.0mg/kg esketamine combined with hydromorphone group(S3 group,55 cases)and hydromorphone alone group(H group,55 cases).Intraoperative anesthesia management and intraoperative analgesia were uniform,and postoperative analgesia was as follows:Group S1: Esketamine 0.5mg/kg + hydromorphone 0.1mg/kg + toranisetron(0.2mg/kg)+ normal saline was configured into 150 ml solution.S2 group: Esketamine 1.0mg/kg + hydromorphone 0.1mg/kg + toranisetron(0.2mg/kg)+ normal saline was configured into 150 ml solution.S3 group: Esketamine 2.0mg/kg + hydromorphone 0.1mg/kg + toranisetron(0.2mg/kg)+ normal saline was configured into 150 ml solution.Group H: Hydromorphone 0.1mg/kg + tolanisetron(0.2mg/kg)+ normal saline was configured into 150 ml solution.OutcomeThere was a statistically significant difference in the proportion of patients with moderate to severe pain within 48 hours after surgery between the hydromorphone alone group and the esketamine combined group(H group: 35 cases,63.6%;Group S:59 cases,35.8%,RR value 3.1,95% confidence interval 1.7 to 5.9,p < 0.05).The moderate to severe pain rate of esketamine in each dose group was 49.1%(27 cases),respectively.30.9%(17 cases);27.3%(15 cases).By Cochran-Armitage test,the difference among the four groups was statistically significant(P < 0.001).The esketamine combined group improved the quality of recovery at 24 and 48 hours and30 days after surgery compared with the hydromorphone group,with median differences(95% confidence intervals)of 6(5,7),6(5,8)and 2(0,3),respectively.Compared with hydromorphone group,esketamine combined group decreased NRS scores at 24 and 48 hours after surgery,but there was no significant difference in NRS scores between the groups at 4 hours and 30 days after surgery.Postmortem analysis showed that except for the difference between S2 and S3 groups,there was no statistical significance,and esketamine of different dose groups in other groups reduced NRS score 24 hours and 48 hours after surgery to different degrees,showing a certain dose dependence.There was no significant difference in the RASS of esketamine combined group compared with hydromorphone group at 4h after surgery,and the difference between 24 h and 48 h after surgery was statistically significant.Compared with hydromorphone group,esketamine combined group decreased postoperative opioid dosage,prolonged first PCIA time,reduced PCIA compression frequency,and showed a dose correlation between different dose groups.Compared with hydromorphone group,esketamine combined group decreased the BDI-II score24 and 48 hours after surgery,but the difference was not statistically significant at 30 days after surgery.In a postmortem analysis,esketamine showed a dose-dependent decrease in BDI-II scores at 24 and 48 hours after surgery.There was no significant difference in MMSE scores between esketamine group and hydromorphone group at24 h,48 h and 30 days after surgery.According to the results of RASS score,the proportion of RASS score-1(drowsiness)in S3 group was higher than that in other groups,and the difference was statistically significant.Other complications such as hallucination,agitation,nightmares,delirium,diplopia and secretions during awakening period were not found in the study.There was no significant difference in the incidence of postoperative nausea and vomiting between the two groups and the four groups.ConclusionDifferent doses of eskatamine combined with hydromorphone could reduce the proportion of patients with moderate to severe pain within 48 hours after surgery,improve postoperative recovery quality scores,and improve postoperative depression tendency.Eskatamine combined with hydromorphone as postoperative analgesic pump did not increase the incidence of adverse reactions such as hallucination,agitation,nightmares,delirium,double vision,increased secretion and postoperative nausea and vomiting during the recovery period.In view of the similar clinical effects of 1mg/kg and 2mg/kg,considering the sleepiness risk brought by 2mg/kg,it is recommended to add 1mg/kg eskatamine into postoperative hydromorphone patient-controlled intravenous analgesia pump to improve analgesia and recovery quality according to the three doses in the experimental group in the study.