Clinical trial NCT05718934: Low Dose of Sugammadex vs Neostigmine and Glycopyrrolate for the Reversal of Rocuronium
Official title: A Randomized Clinical Study to Compare Low Dose of Sugammadex to Standard Dose of Neostigmine and Glycopyrrolate for the Reversal of Rocuronium Induced Moderate Neuromuscular Block
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Neuromuscular Blockade
Keywords: sugammadex
neostigmine
general anesthesia
Lead sponsor: Ciusss de L'Est de l'Île de Montréal
Sponsor class: OTHER
First posted: 2023-02-08
Enrollment: 144
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Two groups of patients randomized into Group "N" for neostigmine and group "S" for sugammadex for a total of 144 participants.
Primary purpose: TREATMENT

Brief summary: The aim of this study is to compare the use of a low dose sugammadex and neostigmine combined to glycopyrrolate to reverse a rocuronium induced moderate neuromuscular blockade.

Detailed description: Neuromuscular blocking agents (NMBAs) are administered by anesthesiologists for general anesthesia to facilitate endotracheal intubation and/or surgical conditions. Unfortunately, postoperative residual neuromuscular blockade (rNMB), is an adverse event usually observed after extubation in the postanesthesia care unit (PACU) after surgery. rNMB is associated with upper airway obstruction, reduced pharyngeal muscle coordination, decreased functional residual capacity, and impaired hypoxic ventilatory response and may lead to critical cardiopulmonary complications.To prevent those complications, monitoring NMBAs activity as well as appropriate reversal are crucial.

In the light of the strong evidence proving the superiority of sugammadex for the reversal of NMB, the investigators chose to examine whether a quarter dose (0.5 mg.kg-1) of sugammadex would be superior to neostigmine for the reversal of moderate NMB (TOF 1 to 3). The investigators believe that this strategy will encourage the routine use of sugammadex because of a drastically reduced cost per patient with an increased safety and less adverse events compared to neostigmine reversal.

This study will be conducted in a single center, double blinded, randomized controlled study.

Type of surgery: any surgery under general anesthesia in ASA 1-3 patients, fully consented.

In the OR, the investigators will place a standardized monitoring: ECG, non-invasive blood pressure and SpO2. The investigators will monitor the depth of anesthesia using the BIS index (Medtronic, Canada) and the intraoperative nociception balance using the NOL index (Medasense Ltd., Ramat Gan, Israel). Finally, the investigators will monitor neuromuscular blockade using TOF-scan® (Draeger, Mississauga, Canada). The stimulation electrodes will be placed on the forearm of the patient to monitor the response to ulnar stimulation of the adductor pollicis muscle.

The investigators will use adjusted body weight for the administration of the drugs used in our anesthesia protocol except for rocuronium, sugammadex and neostigmine that will be given based on the real actual body weight.

The primary objective of the study:

To compare the mean time for recovery of the TOF ratio to 0.9 (90%) at the end of the surgery for rocuronium induced moderate neuromuscular blockade (TOF 1 to 3 at the end of the surgery) in two groups: Group "N" for neostigmine and group "S" for sugammadex. Group N will receive the standard reversal (neostigmine 50 µg.kg-1 and glycopyrrolate 7 µg.kg-1) and group S will receive sugammadex 0.5 mg.kg-1.

Secondary objectives are listed below.

Based on a 2-sided alpha \< 0.05 and 80% power, the investigators calculated that 64 patients per group was required to detect a clinically relevant effect size of 0.5 favouring S group. The sample size will be inflated to 144 (72 per group) to account for 10% withdrawals and loss of follow-up.

Study Duration: 12 months.

Study Center: Maisonneuve-Rosemont Hospital, CIUSSS de l'Est de l'Ile de Montreal (CEMTL), University of Montreal, Montreal, Quebec, Canada.

Adverse Events: None expected.

Eligibility criteria: Inclusion Criteria:

* ASA 1-3 patients,
* Undergoing general anesthesia with rocuronium induced NMB,
* TOF 1-3 at the end of surgery,
* BMI \< 36 kg.m-2,
* Age \> 18 years old

Exclusion Criteria:

* History of coronary artery disease and unstable before surgery
* History of serious cardiac arrhythmia (including atrial fibrillation)
* Renal or hepatic dysfunction
* Obstructive sleep apnea requiring continuous positive airway pressure (CPAP) machine
* Neuromuscular disease
* Allergy to any drug used in the study protocol

Primary outcomes:
measure: Time for recovery from moderate NMB
timeFrame: Intra-operative (from T0 = incision until Tend = start dressing)
Secondary outcomes:
measure: Time for awakening and extubation
timeFrame: Intra-operative (from T0 = incision until Tend = start dressing)
measure: Incidence of reoccurrence of NMB
timeFrame: Intra-operative (from T0 = incision until Tend = start dressing)
measure: Incidence of critical respiratory event
timeFrame: Every 15 minutes until discharge from PACU, up to 2 hours
measure: Vital signs changes - Mean arterial pressure
timeFrame: Every 15 minutes until discharge from PACU, up to 2 hours
measure: Vital signs changes - Heart rate
timeFrame: Every 15 minutes until discharge from PACU, up to 2 hours
measure: Vital signs changes - Oxygen saturation
timeFrame: Every 15 minutes until discharge from PACU, up to 2 hours
measure: Vital signs changes - Respiratory rate
timeFrame: Every 15 minutes until discharge from PACU, up to 2 hours
measure: PACU scores - Aldrete
timeFrame: Every 15 minutes until discharge from PACU, up to 2 hours
measure: PACU scores - Maisonneuve-Rosemont PACU score
timeFrame: Every 15 minutes until discharge from PACU, up to 2 hours
measure: PACU scores - PONV score
timeFrame: Every 15 minutes until discharge from PACU, up to 2 hours
measure: PACU scores - POSS score
timeFrame: Every 15 minutes until discharge from PACU, up to 2 hours
measure: PACU scores - NRS pain score
timeFrame: Every 15 minutes until discharge from PACU, up to 2 hours
measure: Time spent in PACU
timeFrame: Every 15 minutes until discharge from PACU, up to 2 hours
measure: Cost of reversal agent
timeFrame: Intra-operative (from T0 = incision until Tend = start dressing)
measure: Overall cost
timeFrame: Intra-operative (from T0 = incision until Tend = start dressing) to PACU discharge, up to 2 hours
Other outcomes:
Locations:
city: Montreal
country: Canada
facility: CIUSSS de l'Est de l'Ile de Montreal
state: Quebec
Study officials:
affiliation: CIUSSS Est de l'île de Montréal
name: Philippe PR Richebé, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: