Effect of Dexmedetomidine and Esketamine on Catheter-related Bladder Discomfort

Official title

Effect of Dexmedetomidine and Esketamine on Catheter-related Bladder Discomfort in Patients Undergoing Transurethral Surgery: a 2 x 2 Factorial Randomized Trial

Overview

Catheter-related bladder discomfort (CRBD) is common in patients awaking from general anesthesia with an urinary catheter. We suppose that that use of dexmedetomidine and/or esketamine during anesthesia may reduce the occurrence of CRBD. This 2x2 factorial randomized trial is designed to explore the effects of esketamine, dexmedetomidine, and their combination on the occurrence CRBD in patients undergoing transurethral urological surgery.

Detailed description

Urethral catheterization is commonly used during and after surgery. However, patients with indwelling urinary catheters often present with catheter-related bladder discomfort (CRBD) after awakening from anesthesia. CRBD is characterized by pain and discomfort in the suprapubic area or symptoms like overactive bladder, characterized by frequent and urgent urination, with or without acute incontinence. The incidence of CRBD is relatively high, ranging from 47% to 90%. The development of CRBD not only reduces patients' perioperative satisfaction, but also increases the incidence of postoperative complications, affects patients' postoperative rehabilitation, and prolongs the length of hospital stay. It also increases the workload of medical staff.

The occurrence of CRBD is affected by many factors, such as gender, size of urinary tube, and type of surgery. Studies show that the use of ≥18F catheter increases the incidence of CRBD. After transurethral surgery, such as transurethral resection of bladder tumor (TUR-Bt), transurethral resection of prostate (TURP), and transurethral holmium laser resection of prostate (HoLRP), a 20F catheter is often required for bladder irrigation; the catheter carrying time may be extended for bladder perfusion. Therefore, the incidence of CRBD is higher after such operations.

Dexmedetomidine is a highly selective α2 receptor agonist with analgesic, anxiolytic, and sedative effects. Several randomized trial confirmed that intraoperative use of 0.3-1.0 μg/kg dexmedetomidine reduces the incidence and severity of postoperative CRBD, and the effect persists up to 6 hours after surgery. Ketamine is a non-competitive N-methyl-D-aspartate receptor antagonist and produces analgesic and anti-hyperalgesia effects. A recent meta-analysis found that subanesthetic doses of ketamine (0.25 mg/kg or 0.5 mg/kg) reduce the severity of CRBD within 1-2 hours after surgery and the incidence of CRBD within 2-6 hours after surgery. Esketamine is the S-enantiomer of racemic ketamine and has a higher affinity for NMDA receptors; it is twice as potent as racemic ketamine.

The investigators hypothesize that the combination of dexmedetomidine and esketamine may improve the efficacy in preventing CRBD. This 2x2 factorial trial is designed to observe the effect of dexmedetomidine, esketamine, and dexmedetomidine-esketamine combination on the occurrence of CRBD in patients following transurethral urological surgery.

Interventions

• Drug Normal saline
  20 ml of normal saline is infused intravenously at 80 ml/h after anesthesia induction but before surgery.
• Drug Dexmedetomidine
  Dexmedetomidine 0.5 μg/kg, diluted with normal salinet o 20 ml, is infused intravenously at 60 ml/h after anesthesia induction but before surgery.
• Drug Esketamine
  Esketamine 0.25 mg/kg, diluted with normal saline to 20 ml, is infused intravenously at 80 ml/h after anesthesia induction but before surgery.
• Drug Combined dexmedetomidine-esketamine
  Dexmedetomidine 0.5 μg/kg and esketamine 0.25 mg/kg, diluted with normal saline to 20 ml, is infused intravenously at 80 ml/h after anesthesia induction but before surgery.

Primary outcome measures

• Incidence of catheter-related bladder discomfort (CRBD) within 24 hours after surgery. [Time frame: Up to 24 hours after surgery.]

Secondary outcome measures (8)

• Prevalence of CRBD at various time points within 24 hours after surgery. [Time frame: Up to 24 hours after surgery.]
• Severity of CRBD at various time points within 24 hours after surgery. [Time frame: Up to 24 hours after surgery.]
• Intensity of pain at various time points within 24 hours after surgery. [Time frame: Up to 24 hours after surgery.]
• Subjective sleep quality on the night of surgery. [Time frame: On the morning of the first postoperative day (8:00-10:00).]
• Patient satisfaction at 6 hours after surgery. [Time frame: At 6 hours after surgery.]
• Anxiety at hospital discharge or 2 days after surgery. [Time frame: Up 2 days after surgery.]
• Depression at hospital discharge or 2 days after surgery. [Time frame: Up 2 days after surgery.]
• Sleep quality at 30 days after surgery. [Time frame: At 30 days after surgery.]

Eligibility criteria

Inclusion criteria

• Aged 18 years or above;
• Scheduled to undergo transurethral bladder or prostate surgery (including transurethral resection of bladder tumor, transurethral resection of prostate, and transurethral thulium laser prostatectomy) under general anesthesia;
• Required postoperative retention of a three-chamber urinary catheter.

Exclusion criteria

• Indwelling urinary catheters or chronic analgesic therapy for ≥1 month before surgery;
• Uncontrolled hypertension before surgery (resting ward systolic pressure >180 mmHg or diastolic pressure >110 mmHg);
• Severe bradycardia (heart rate ≤50 beats per minute), sick sinus syndrome, or atrioventricular block of degree II or above without pacemaker, or having myocardial infarction, severe heart insufficiency (New York Heart Association class ≥3), or tachyarrhythmia within a year;
• Preoperative history of schizophrenia, epilepsy, Parkinson's disease, myasthenia gravis, or intracranial hypertension;
• Preoperative history of hyperthyroidism and pheochromocytoma;
• Inability to communicate due to coma, severe dementia, or language barrier before surgery;
• Severe liver dysfunction (Child-Pugh grade C), severe renal dysfunction (receiving dialysis before surgery), or Amercian Society of Anesthesiologists classification ≥IV;
• Scheduled admission to the intensive care unit with endotracheal intubation after surgery;
• Other conditions that are considered unsuitable for study participation.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Factorial

Masking

Triple blind

Primary purpose

Treatment

Study locations

China · 2 centers

• Peking University First Hospital — Beijing
• Peking University Shenzhen Hospital — Shenzhen

Publications

• Anderson KE. Pharmacology of lower urinary tract smooth muscles and penile erectile tissues. Pharmacol Rev. 1993 Sep;45(3):253-308. No abstract available. PMID 8248281
• Binhas M, Motamed C, Hawajri N, Yiou R, Marty J. Predictors of catheter-related bladder discomfort in the post-anaesthesia care unit. Ann Fr Anesth Reanim. 2011 Feb;30(2):122-5. doi: 10.1016/j.annfar.2010.12.009. Epub 2011 Jan 31. PMID 21277735
• Bai Y, Wang X, Li X, Pu C, Yuan H, Tang Y, Li J, Wei Q, Han P. Management of Catheter-Related Bladder Discomfort in Patients Who Underwent Elective Surgery. J Endourol. 2015 Jun;29(6):640-9. doi: 10.1089/end.2014.0670. Epub 2014 Dec 9. PMID 25335575
• Mitobe Y, Yoshioka T, Baba Y, Yamaguchi Y, Nakagawa K, Itou T, Kurahashi K. Predictors of Catheter-Related Bladder Discomfort After Surgery: A Literature Review. J Clin Med Res. 2023 Apr;15(4):208-215. doi: 10.14740/jocmr4873. Epub 2023 Apr 28. PMID 37187710
• Moataz A, Chadli A, Wichou E, Gallouo M, Jandou I, Saber S, Serhier Z, Dakir M, Debbagh A, Aboutaieb R. [Predictors of catheter-related bladder discomfort]. Prog Urol. 2020 Dec;30(16):1045-1050. doi: 10.1016/j.purol.2020.09.014. Epub 2020 Sep 30. French. PMID 33011083
• Goger YE, Ozkent MS, Goger E, Kilinc MT, Ecer G, Piskin MM, Erol A. A randomised-controlled, prospective study on the effect of dorsal penile nerve block after TURP on catheter-related bladder discomfort and pain. Int J Clin Pract. 2021 May;75(5):e13963. doi: 10.1111/ijcp.13963. Epub 2021 Jan 11. PMID 33368991
• Wang SY, Qiu Q, Shen X. Effect of Pudendal Nerve Block on the Prevention of Postoperative Bladder Spasm and Catheter-Related Bladder Discomfort in Male Patients Undergoing Transurethral Holmium Laser Enucleation of the Prostate. Clin Interv Aging. 2022 Nov 30;17:1729-1738. doi: 10.2147/CIA.S384612. eCollection 2022. PMID 36474581
• Agarwal A, Yadav G, Gupta D, Singh PK, Singh U. Evaluation of intra-operative tramadol for prevention of catheter-related bladder discomfort: a prospective, randomized, double-blind study. Br J Anaesth. 2008 Oct;101(4):506-10. doi: 10.1093/bja/aen217. Epub 2008 Jul 24. PMID 18653496

Identifiers

NCT: NCT06399185 · 2024-105

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗