A Non-Inferiority Study Of Lidocaine Combined With Penehyclidine Hydrochloride Bladder Instillation For Catheter-Related Bladder Discomfort

ObjectiveThe purpose of this experiment was to investigate the non-inferiority of lidocaine combined with penehyclidine hydrochloride bladder instillation relative to intravenous oxycodone in the treatment of catheter-related bladder discomfort during recovery from general anesthesia,and to evaluate its effectiveness and safety,and to find new ideas for the prevention and treatment of catheter-related bladder discomfort.MethodsThis study is a randomized,double-blind,parallel-controlled trial of positive drugs in a non-inferiority design.The trial was approved by the Ethics Committee of China-Japan Union Hospital of Jilin University（Ethics Number:20220804010）and registered in China Clinical Trial Registry（Chi CR2200064136）,with the consent of the patients and signed the informed consent.We selected 106 male patients,aged18-70 years,ASA class I-II,with no contraindications to the use of lidocaine,penehyclidine hydrochloride,or oxycodone,who were proposed to undergo non-urinary surgery under general anesthesia from September 2022 to December2022 and had catheter-related bladder discomfort（CRBD）after the awakening period at our hospital.Using a computerized random sequence generator,patients with complaints of CRBD after awakening from anesthesia were randomly divided into a control group（Group C）and a test group（Group T）in a 1:1 ratio,with 53cases in each group,for a total of 106 cases.The grouping results were concealed in an opaque sealed envelope.A 14Fr disposable sterile double-lumen balloon latex catheter was selected for all patients who might be enrolled after induction of anesthesia,and the catheter was left in place by a surgeon with extensive experience in urinary catheterization.Intraoperatively,the depth of anesthetic sedation BIS was adjusted according to the situation to maintain it between 40 and 60.A uniform self-administered intravenous analgesia（PCIA）was used postoperatively.Patients were admitted to the anesthesia recovery room（PACU）after surgery.Patients were followed by nurse anesthetist C until CRBD occurred.After CRBD occurred,patients were randomized into two groups:control group（group C n=53）was given0.06 mg/kg oxycodone injection intravenously along with 11 ml of saline retrograde via the urethra;test group（group T n=53）was given 0.06 mg/kg saline intravenously and 2%lidocaine retrograde via the urethra 10 ml and 1 ml of saline pentaerythritol mixture.Primary efficacy indexes were observed and recorded:the decreased value of NRS score from baseline 2h（T3）after drug administration;secondary efficacy indexes:the CRBD at baseline（T0）,0.5 h（T1）,1h（T2）,2h（T3）,and 6h（T4）after drug administration severity（including NRS100 method and four-point scale method）,urethral pain VAS method score,surgical site pain VAS method score,sedation Ramsay score,urine volume increment at each time point;safety indicators:occurrence of adverse effects（including dry mouth,blurred vision,facial flushing,delirium,respiratory depression SPO₂<90%,postoperative nausea and vomiting）.Statistical analysis of the data was completed using SPSS26.0software.ResultsThere was no statistical difference in the general data profile of the subjects,including age,height,weight,BMI,ASA classification,type of surgery,ureter type,duration of anesthesia and surgery（P>0.05）.Main efficacy indicators:（1）In both the intention-to-treat analysis（ITT）and the conforming protocol set analysis（PP）,the difference in NRS scores at the moment of T3 from the baseline decline valueΔT3 was statistically significant in both groups（t=4.517,P<0.001/t=4.373,P<0.001）,and the lower limit of the one-sided 97.5%confidence interval for the difference in both groups was greater than-9（non-inferiority cut-offδ=9）,and the non-inferiority validity conclusion holds.（2）Based on the ITT analysis,the lower limit of the 97.5%confidence interval of the difference,9.37>9（the superiority boundδ=9）,the conclusion of superiority holds.Secondary efficacy indicators:（1）NRS scores were lower in group T at T2,T3,and T4 compared with group C（P<0.05）.（2）The incidence of severe CRBD was lower in group T at T1 compared with group C（P<0.05）;the percentage of no CRBD was higher in group T at T4 compared with group C（P<0.05）;the differences between the two groups at the remaining time points were not statistically significant（P>0.05）.（3）The urethral VAS score was lower in group T than group C at T4（P<0.05）;there was no statistically significant difference between the remaining time points（P>0.05）.（4）There was no statistically significant difference in surgical pain VAS scores between the two groups at each time point（P>0.05）.（5）The Ramsay score in group T at T0 was lower than that in group C（P<0.05）;there was no statistical difference between the two groups at all other time points（P>0.05）.（6）The incremental urine volume in group T at T1,T2,T3 and T4 was greater than that in group C（P<0.05）;there was no statistically significant difference in the intraoperative rehydration volume between the two groups（P>0.05）.Safety indexes:The difference in adverse reactions between the two groups was not statistically significant（P>0.05）.ConclusionLidocaine 2%hydrochloride 10 ml combined with 1 mg of penehyclidine hydrochloride bladder instillation is non-inferior to intravenous 0.06 mg/kg oxycodone in the treatment of moderate and severe catheter-related bladder discomfort while having the advantages of increased bladder compliance,no systemic adverse effects,and convenient postoperative environmental administration.