Postoperative Urinary Retention in Patients After Noncardiac Surgery and Reversal of Neuromuscular Block

Postoperative Urinary Retention in Patients After Noncardiac Surgery and Reversal of Neuromuscular Block by Neostigmine or Sugammadex: A Randomized Controlled Trial

The investigators propose a randomized trial comparing sugammadex and neostigmine for the reversal of neuromuscular blocks induced by rocuronium or vecuronium in adults having general anesthesia with muscular block for noncardiac surgery.

Study Overview

• Status: Recruiting
• Conditions: Neuromuscular Blockade
• Intervention / Treatment: Drug: Neostigmine with glycopyrrolate; Drug: Sugammadex

Detailed Description

All patients will be asked to void before they are transferred to the operating room. Patients will be seen shortly before anesthetic induction (baseline, Visit 1). As this is a pragmatic trial, no restrictions to anesthetic management other than the random allocation to sugammadex or neostigmine are planned.

As part of local standards, it is recommended to maintain a moderate block of 1 to 2 twitch responses to train-of-four (TOF) stimulation throughout surgery.

Randomized treatments will be implemented by clinicians in collaboration with research personnel. Patients will be randomized shortly before the reversal of the neuromuscular block. At the time of randomization, the administration of either neostigmine or sugammadex need to be possible. If e.g. the neuromuscular block is too deep to be reversed with neostigmine, patients will not be randomized and excluded from the study.

The anesthesiologist in charge will be informed on the patient's allocation to either the sugammadex or neostigmine group by an unblinded investigator. Patients will be monitored for twitch responses towards the end of surgery to determine the timing and dose for the reversal agent. The twitch response will be measured using a quantitative, acceleromyographic monitoring device. For sugammadex, 4 mg/kg is recommended if spontaneous recovery of the twitch response has reached 1 to 2 post-tetanic counts (PTC) and there are no twitch responses to (TOF) stimulation. Alternatively, 2 mg/kg is recommended if spontaneous recovery has reached the reappearance of the second twitch in response to TOF stimulation. In the neostigmine group, neostigmine 2.5 mg with glycopyrrolate 0.5 mg will be administered as an initial dose. Neostigmine and glycopyrrolate are to be administered in a fixed ratio, and only if the second twitch in response to TOF stimulation has appeared. The initial dose can be repeated up to a ceiling dose of 5 mg neostigmine with 1 mg of glycopyrrolate. However, the final decision of the dose will be up to the attending anesthesiologist. The administered dose will be recorded. All patients are required to have a documented TOF ratio > 0.9 before extubation Visit 2 is one hour after surgery in the post anesthesia care unit (PACU). The third Visit is within 4 to 6 hours after surgery on the regular ward. Visit 4 and 5 will be in the morning and afternoon of the first day after surgery (postoperative day (POD) 1). Visit 5 on the afternoon of POD 1 will be the last follow-up and the end of a patient's participation in the study. Thereafter, data will be recorded from electronical medical records until POD 4 or discharge, whichever comes first.

• Study Type: Interventional
• Enrollment (Estimated): 286
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Fabio Rodriguez, MD; Phone Number: 216-444-9950; Email: rodrigf3@ccf.org

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Recruiting
      • Cleveland Clinic
      • Sub-Investigator: Xuan PU, MA/MS
      • Contact: Fabio Rodriguez, MD; Phone Number: 216-444-9950; Email: rodrigf3@ccf.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Informed Consent as documented by signature;
• Adults having noncardiac surgery with expected surgery duration ≥ 2 hours;
• General anesthesia requiring endotracheal intubation and neuromuscular block with rocuronium or vecuronium;
• Planned administration of sugammadex or neostigmine for reversal of the neuromuscular block at the end of surgery;
• American Society of Anesthesiologists (ASA) physical status 1-3;
• Age ≥ 65 years.

Exclusion Criteria:

• Contraindications to the class of drugs under study;
• Preoperative urinary catheter;
• Planned intraoperative insertion of a urinary catheter;
• Neurosurgery (except spine surgery), intraabdominal or retroperitoneal surgeries including but not limited to any kind of laparoscopies, or surgeries in kidneys, ureters or urine bladder.
• Planned postoperative admission to the ICU;
• Severe preoperative hepatic impairment (≥3 times increase in aspartate aminotransferase or alanine aminotransferase as per reference range) or renal impairment (estimated GFR < 30 ml/min or end-stage renal disease requiring scheduled dialysis.);
• History of bladder cancer;
• Presence of a sacral nerve stimulator;
• Current use of anticholinergic medications such as antihistamines, phenothiazines, antidepressants or antipsychotics;
• Urinary tract infections or other urogenital comorbidity (incontinence, cysto-ureteric reflux, known bladder retention) or conditions which promote urinary retention;
• Known or suspected neurological conditions such as Alzheimer's disease, stroke, poliomyelitis, cerebral palsy, multiple sclerosis, spinal lesions, or Parkinson's disease.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Neostigmine; Reversal of Neuromuscular Block by Neostigmine.	Drug: Neostigmine with glycopyrrolate; Administration by intravenous infusion
Active Comparator: Sugammadex; Reversal of Neuromuscular Block by Sugammadex.	Drug: Sugammadex; Administration by intravenous infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Urinary retention	The primary outcome of urinary retention is assessed by post-void bladder volume.	1 hour after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complications related to urinary retention	Complications of interest include need for a urinary catheter and development of urinary tract infections.	end surgery to discharge

Collaborators and Investigators

• Sponsor: The Cleveland Clinic
• Investigators: Principal Investigator: Kurt Ruetzler, MD, The Cleveland Clinic

Study record dates

Study Major Dates

• Study Start (Actual): July 31, 2023
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): February 1, 2025

Study Registration Dates

• First Submitted: September 12, 2022
• First Submitted That Met QC Criteria: September 14, 2022
• First Posted (Actual): September 19, 2022

Study Record Updates

• Last Update Posted (Actual): December 28, 2023
• Last Update Submitted That Met QC Criteria: December 27, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urologic Diseases; Urination Disorders; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urinary Retention; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Enzyme Inhibitors; Adjuvants, Anesthesia; Cholinesterase Inhibitors; Parasympathomimetics; Glycopyrrolate; Neostigmine
• Other Study ID Numbers: 22-745

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No