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

Phase 4
Completed
Conditions
Neuromuscular Blockade
Interventions
Registration Number
NCT05718934
Lead Sponsor
Ciusss de L'Est de l'Île de Montréal
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
144
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Group "S" for SugammadexSugammadexSugammadex 0.5 mg.kg-1 IV will be performed at the end of surgery (when surgeons finish deep tissues closure) with starting TOF 1-3.
Group "N" for Standard reversalNeostigmine and glycopyrrolateStandard reversal of 50 µg.kg-1 neostigmine (up to a maximum dose of 5mg) and 7 µg.kg-1 glycopyrrolate at the end of surgery (when surgeons finish deep tissues closure) with starting TOF 1-3.
Primary Outcome Measures
NameTimeMethod
Time for recovery from moderate NMBIntra-operative (from T0 = incision until Tend = start dressing)

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).

Secondary Outcome Measures
NameTimeMethod
Incidence of reoccurrence of NMBIntra-operative (from T0 = incision until Tend = start dressing)

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)

Vital signs changes - Heart rateEvery 15 minutes until discharge from PACU, up to 2 hours

Difference between pre-reversal values and values for heart rate (bpm) obtained 2, 5, 10 and 30 min after reversal.

PACU scores - PONV scoreEvery 15 minutes until discharge from PACU, up to 2 hours

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

1. Nausea without the need of a treatment

2. Nausea needing a treatment

3. Nausea and vomiting

Time for awakening and extubationIntra-operative (from T0 = incision until Tend = start dressing)

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.

Incidence of critical respiratory eventEvery 15 minutes until discharge from PACU, up to 2 hours

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

Vital signs changes - Mean arterial pressureEvery 15 minutes until discharge from PACU, up to 2 hours

Difference between pre-reversal values and values for mean arterial pressure (mmHg) obtained 2, 5, 10 and 30 min after reversal.

Vital signs changes - Respiratory rateEvery 15 minutes until discharge from PACU, up to 2 hours

Difference between pre-reversal values and values for respiratory rate (respiration per minute) obtained 2, 5, 10 and 30 min after reversal.

PACU scores - AldreteEvery 15 minutes until discharge from PACU, up to 2 hours

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

PACU scores - Maisonneuve-Rosemont PACU scoreEvery 15 minutes until discharge from PACU, up to 2 hours

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

PACU scores - POSS scoreEvery 15 minutes until discharge from PACU, up to 2 hours

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

1. Awake and alert

2. Sometimes drowsy, easy awakening

3. Drowsy, wakes up but falls asleep during conversation

4. Sleeps soundly, wakes up with difficulty or not at all to stimulation

Time spent in PACUEvery 15 minutes until discharge from PACU, up to 2 hours

Total time, in minutes spent in PACU

Vital signs changes - Oxygen saturationEvery 15 minutes until discharge from PACU, up to 2 hours

Difference between pre-reversal values and values for SpO2 (%) obtained 2, 5, 10 and 30 min after reversal.

Overall costIntra-operative (from T0 = incision until Tend = start dressing) to PACU discharge, up to 2 hours

Cost evaluation, in CAD, associated with extubation time in the operating room and PACU stay.

PACU scores - NRS pain scoreEvery 15 minutes until discharge from PACU, up to 2 hours

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"

Cost of reversal agentIntra-operative (from T0 = incision until Tend = start dressing)

Cost, in CAD, associated with reversal agent

Trial Locations

Locations (1)

CIUSSS de l'Est de l'Ile de Montreal

🇨🇦

Montreal, Quebec, Canada

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