Low Dose of Sugammadex vs Neostigmine and Glycopyrrolate for the Reversal of Rocuronium

Neuromuscular Blockade Clinical Trial

— SUGANEO  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05718934
• Other study ID #: 2023-3091
• Status: Completed
• Phase: Phase 4
• Start date: November 8, 2022
• Est. completion date: December 19, 2023

Study information

• Verified date: February 2024
• Source: Ciusss de L'Est de l'Île de Montréal
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 144
• Est. completion date: December 19, 2023
• Est. primary completion date: December 19, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Neuromuscular Blockade

Intervention

Drug:
• Neostigmine and glycopyrrolate
See arm descriptions
• Sugammadex
See arm descriptions

Locations

Country	Name	City	State
Canada	CIUSSS de l'Est de l'Ile de Montreal	Montreal	Quebec

Sponsors (1)

Lead Sponsor	Collaborator
Ciusss de L'Est de l'Île de Montréal

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time for recovery from moderate NMB	Time, in minutes, for recovery of the TOF ratio to 0.9 at the end of the surgery for rocuronium induced moderate neuromuscular blockade (TOF 1 to 3 at the end of the surgery).	Intra-operative (from T0 = incision until Tend = start dressing)
Secondary	Time for awakening and extubation	The time, in minutes for awakening and extubation. Time for awakening will start at the injection of the reversal agent and end when the patient is opening his eyes. Time for extubation will start at the same time point and will end when extubation is complete.	Intra-operative (from T0 = incision until Tend = start dressing)
Secondary	Incidence of reoccurrence of NMB	The incidence of rNMB (defined as TOF ratio < 0.9 30 min after the end of reversal agent administration) and the incidence of NMB reoccurrence (defined as a decrease in TOF ratio from = 0.9 to < 0.8 for at least 3 consecutive TOF values)	Intra-operative (from T0 = incision until Tend = start dressing)
Secondary	Incidence of critical respiratory event	The incidence of critical respiratory event (CRE). A CRE will be defined as the occurrence of one of the following criteria: Upper airway obstruction requiring an intervention; Moderate hypoxemia: SpO2 of 90-93% on 2 L.min-1 nasal cannula O2 that was not improved after active interventions; Severe hypoxemia: SpO2 < 90% on 2 L.min-1 nasal cannula O2 that was not improved after active interventions; Signs of respiratory distress or impeding ventilatory failure; Inability to beath deeply when requested to by a PACU nurse; Patient complaining of symptoms of respiratory or upper airway muscle weakness; Patient requiring reintubation in the PACU; Clinical evidence or suspicion of pulmonary aspiration after tracheal extubation	Every 15 minutes until discharge from PACU, up to 2 hours
Secondary	Vital signs changes - Mean arterial pressure	Difference between pre-reversal values and values for mean arterial pressure (mmHg) obtained 2, 5, 10 and 30 min after reversal.	Every 15 minutes until discharge from PACU, up to 2 hours
Secondary	Vital signs changes - Heart rate	Difference between pre-reversal values and values for heart rate (bpm) obtained 2, 5, 10 and 30 min after reversal.	Every 15 minutes until discharge from PACU, up to 2 hours
Secondary	Vital signs changes - Oxygen saturation	Difference between pre-reversal values and values for SpO2 (%) obtained 2, 5, 10 and 30 min after reversal.	Every 15 minutes until discharge from PACU, up to 2 hours
Secondary	Vital signs changes - Respiratory rate	Difference between pre-reversal values and values for respiratory rate (respiration per minute) obtained 2, 5, 10 and 30 min after reversal.	Every 15 minutes until discharge from PACU, up to 2 hours
Secondary	PACU scores - Aldrete	Difference in Aldrete's score at rest between group and time to reach scores to discharge between groups.; 5 criterias : I-Consciousness level II-Respiration III- Hemodynamics IV-Motricity V- Oxygen saturation; Minimum score : 0 Maximum score : 10	Every 15 minutes until discharge from PACU, up to 2 hours
Secondary	PACU scores - Maisonneuve-Rosemont PACU score	Difference in Maisonneuve-Rosemont PACU score at rest between groups and time to reach scores to discharge between groups.; 8 criterias : I-Consciousness level II-Respiration III- Hemodynamics IV-Motricity V- Oxygen saturation VI- Pain VII- Nausea/Vomiting VIII- Surgical bleeding; Minimum score : 0 Maximum score : 16	Every 15 minutes until discharge from PACU, up to 2 hours
Secondary	PACU scores - PONV score	Difference in Postoperative nausea and vomiting (PONV) score at rest between groups and time to reach scores to discharge between groups.; 0- No nausea/vomiting; Nausea without the need of a treatment; Nausea needing a treatment; Nausea and vomiting	Every 15 minutes until discharge from PACU, up to 2 hours
Secondary	PACU scores - POSS score	Difference in Pasero Opioid-induced Sedation Scale (POSS) score at rest between groups and time to reach scores to discharge between groups.; S- Normal sleep easy awakening; Awake and alert; Sometimes drowsy, easy awakening; Drowsy, wakes up but falls asleep during conversation; Sleeps soundly, wakes up with difficulty or not at all to stimulation	Every 15 minutes until discharge from PACU, up to 2 hours
Secondary	PACU scores - NRS pain score	Difference in Nnumeric Rating Scale (NRS) pain score at rest between groups and time to reach scores to discharge between groups.; Scale between 0 meaning "no pain" and 10 meaning "the worst pain imaginable"	Every 15 minutes until discharge from PACU, up to 2 hours
Secondary	Time spent in PACU	Total time, in minutes spent in PACU	Every 15 minutes until discharge from PACU, up to 2 hours
Secondary	Cost of reversal agent	Cost, in CAD, associated with reversal agent	Intra-operative (from T0 = incision until Tend = start dressing)
Secondary	Overall cost	Cost evaluation, in CAD, associated with extubation time in the operating room and PACU stay.	Intra-operative (from T0 = incision until Tend = start dressing) to PACU discharge, up to 2 hours