A Randomized Controlled Crossover Study Comparing Sugammadex and Placebo

Effect of Reversal of Neuromuscular Blockade on the Amplitude of Motor Evoked Potentials: A Randomized Controlled Crossover Study Comparing Sugammadex and Placebo

Intraoperative monitoring of the motor evoked potentials has been shown to be both a sensitive and specific indicator for detecting intraoperative neurological injuries during spine surgery.(Fehlings, Brodke et al. 2010) It is utilized whenever there is risk for injury of nerve roots or the spinal cord during the procedure.

Anesthetic agents, especially the inhaled volatile anesthetics and muscle relaxants, are con-founders for motor evoked potential monitoring as they have deleterious effects on the amplitude of motor evoked potentials.(Sekimoto, Nishikawa et al. 2006) Hence, total intravenous anesthesia with no intraoperative muscle relaxants, are the standard anesthetic technique for these surgeries.

Muscle relaxants are usually required during the induction of anesthesia and endotracheal intubation of larynx. Current practice is to wait for the resolution of residual neuromuscular blockade before the motor evoked potential recordings (MEP) are initiated and this makes it difficult to assess if there was any neurological injury associated with positioning of the patient. A previous case series has shown that reversal of muscle relaxant can improve the amplitude of MEPs.(Batistaki, Papadopoulos et al. 2012) The aim of this study is to perform a randomized controlled trial to study the changes in motor evoked potential amplitudes comparing sugammadex and placebo.

Study Overview

• Status: Completed
• Conditions: Posterior Cervical Decompression and Fusion
• Intervention / Treatment: Drug: Sugammadex Injection [Bridion]; Drug: Placebo

Detailed Description

Motor evoked potential monitoring is a well-established and safe intervention to assist in prevention of intraoperative injury during spine surgery.(Schwartz, Sestokas et al. 2011) Patients with cervical myelopathy often present with neurological deficits and recording of the motor evoked potentials are often challenging in these patients. In addition, anesthetic agents especially muscle relaxants can abolish the motor response making it difficult to know when the baseline MEP can be recorded.

The usual anesthetic practice for patients undergoing posterior cervical spine surgery is to administer muscle relaxation to aid intubation at the start of the case . The neuromuscular blockade is then allowed to wear off and the neurophysiologist will attempt to record their baseline motor evoked potentials during or just prior to surgical exposure.

The issues with this current technique are;

1. Patients cannot be monitored for neurological changes during their transfer into the prone position
2. There is likely residual neuromuscular blockade decreasing the amplitude of motor evoked potentials.

Investigators plan to perform a randomized controlled cross-over trial comparing the change in MEP amplitudes with administration of sugammadex or placebo. This will be performed on at risk patients (e.g. cervical myelopathy) undergoing posterior cervical spine surgery where MEPs can be more difficult to attain but of higher utility.

The purpose of this study is to determine if reversal of residual neuromuscular blockade with Sugammadex can increase the amplitude of the motor evoked potentials.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5T 2S8
      • TWH/UHN

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• All adult patients aged 18-80 years with American Society of Anesthesiologist (ASA) classification I-III undergoing cervical spine surgery in the prone position with intraoperative motor evoked potential monitoring.
• Operation time greater than 3 hours

Exclusion Criteria:

• Allergy to propofol or documented egg allergy
• Known allergy to sugammadex
• Severe renal dysfunction (EGFR<30)
• British Research Medical Council (BRMC) motor grading <3 in any peripheral muscle group preoperatively. This is inability to move the muscle group against gravity.
• Surgical requirement of strict muscle relaxation for surgical exposure
• Lack of informed consent
• Pregnancy
• Loss of MEP signals during washout period (or intraoperative spinal cord injury resulting in irreversible loss of MEP)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Initial Arm; The study participants will receive either Sugammadex (2 mg/kg in 10 ml 0.9% normal saline) or placebo (10 ml of 0.9% normal saline).	Drug: Sugammadex Injection [Bridion]; The study participants will receive 10 ml syringe containing Sugammadex (2mg/kg) in the first phase followed by Placebo 10 ml syringe containing of 0.9% of normal saline in the second phase.; Other Names: Sugammadex; Drug: Placebo; The study participants will receive Placebo 10 ml syringe containing of 0.9% of normal saline in the first phase followed by 10 ml syringe containing Sugammadex (2mg/kg) in the second phase.; Other Names: Normal Saline
Active Comparator: Crossover Arm; The study participants will receive the study medication that was not given in the initial arm (either Sugammadex (2 mg/kg in 10 ml 0.9% normal saline) or placebo (10 ml of 0.9% normal saline) .	Drug: Sugammadex Injection [Bridion]; The study participants will receive 10 ml syringe containing Sugammadex (2mg/kg) in the first phase followed by Placebo 10 ml syringe containing of 0.9% of normal saline in the second phase.; Other Names: Sugammadex; Drug: Placebo; The study participants will receive Placebo 10 ml syringe containing of 0.9% of normal saline in the first phase followed by 10 ml syringe containing Sugammadex (2mg/kg) in the second phase.; Other Names: Normal Saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes Motor Evoked Potentials (MEPs) Amplitude at 3 Minutes	Changes in the amplitude of the Motor Evoked Potentials from the baseline in the first dorsal interosseous muscle at 3 minutes in sugammadex group compared to placebo group	Baseline and 3 minutes after the study intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MEPs Amplitude Changes in Both Sugammadex and Placebo Groups	Changes in the amplitude of the MEPs from the baseline in the first dorsal interosseous muscle at 6 minutes	Baseline to 6 minutes
MEPs Amplitude Changes From Baseline at 9 Minutes	Comparison of changes in MEP amplitudes from baseline at 9 minutes between sugammadex and placebo groups	Baseline to 9 minutes
Patient Movement	Number of patients moved and observed by the surgeon. From the study intervention to the surgeon observed patient movements	From 0 to 15 minutes
Surgical Grading of Relaxation of the Surgical Field	Surgical grading of relaxation of the surgical field as per the Likert-4 point surgical grading of surgical field. During surgical exposure and closure.	approximatelt 1 hour - 30 min during surgical exposure and 30 minutes during closure

Collaborators and Investigators

• Sponsor: University Health Network, Toronto
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Principal Investigator: Lashmi Venkatraghavan, University Health Network, Toronto

Publications and helpful links

General Publications

• Venkatraghavan L, Royan N, Boyle SL, Dinsmore M, Lu N, Cushman K, Massicotte EM, Prabhu A. Effect of reversal of residual neuromuscular blockade on the amplitude of motor evoked potentials: a randomized controlled crossover study comparing sugammadex and placebo. Neurol Sci. 2022 Jan;43(1):615-623. doi: 10.1007/s10072-021-05318-8. Epub 2021 May 26.

Study record dates

Study Major Dates

• Study Start (Actual): February 5, 2018
• Primary Completion (Actual): December 30, 2019
• Study Completion (Actual): April 30, 2020

Study Registration Dates

• First Submitted: March 6, 2017
• First Submitted That Met QC Criteria: March 16, 2017
• First Posted (Actual): March 22, 2017

Study Record Updates

• Last Update Posted (Actual): June 17, 2020
• Last Update Submitted That Met QC Criteria: June 2, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: Motor Evoked Potentials, Spine surgery, Muscle relaxants
• Other Study ID Numbers: 16-5926-B

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No