Clinical trial NCT06962007: Sugammadex-Induced Clenching During Neuromuscular Blockade Reversal
Official title: A Prospective, Randomized, Double-Blind Study of the Incidence, Severity, and Risk Factors of Clenching Induced by Sugammadex During Neuromuscular Blockade Reversal
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Neuromuscular Blockade Reversal Agent
Perioperative Complications
Anesthesia, General
Sugammadex
Monitoring, Intraoperative
Masseter Muscle Spasm
Keywords: sugammadex
mouth clenching
neuromuscular blockade reversal
Lead sponsor: Wonkwang University Hospital
Sponsor class: OTHER
First posted: 2025-05-08
Enrollment: 240
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The study is not a safety/efficacy verification aimed at drug approval, but a mechanism/dose-related study to evaluate the dose-response and adverse event rate of already approved drugs.
Primary purpose: PREVENTION

Brief summary: Study Objective:

This study aims to evaluate the incidence, severity, and risk factors of sugammadex-induced mouth clenching during neuromuscular blockade (NMB) reversal in adult surgical patients.

Study Design:

This prospective, randomized, double-blind, controlled clinical trial enrolls adult patients (ASA physical status I-II, aged 18-70 years) undergoing elective surgery under general anesthesia with rocuronium. Patients will be randomized into four groups to receive either sugammadex at doses of 1 mg/kg, 2 mg/kg, or 4 mg/kg, or a combination of pyridostigmine and glycopyrrolate.

Primary Outcome:

The primary outcome is the incidence of clenching within 10 minutes after NMB reversal, assessed by clinical observation, masseter EMG, and airway pressure changes, using a novel five-grade severity scale.

Secondary Outcomes:

Secondary outcomes include the severity of clenching, time to TOF ratio ≥0.9, BIS values at clenching onset, complications, and identification of risk factors such as dose, sex, BIS, age, BMI, and rocuronium dose.

Significance:

This study seeks to improve perioperative safety by identifying modifiable risk factors and informing dose adjustments or alternative reversal strategies to prevent sugammadex-induced clenching, particularly in high-risk populations.

Detailed description: This prospective, randomized, double-blind clinical trial aims to investigate the incidence, risk factors, and clinical implications of sugammadex-induced clenching during neuromuscular blockade reversal under general anesthesia. Sugammadex, a selective relaxant binding agent, is widely used for the rapid reversal of rocuronium-induced neuromuscular blockade. However, reports of jaw clenching and masseter muscle contraction following sugammadex administration have raised safety concerns, particularly regarding airway management and patient discomfort during emergence from anesthesia.

A total of 240 adult patients (ASA physical status I-II, aged 18 to 70 years) scheduled for elective surgery under general anesthesia with rocuronium will be enrolled. Participants will be randomly assigned to one of four groups in a 1:1:1:1 ratio: sugammadex 1 mg/kg (S1), 2 mg/kg (S2), 4 mg/kg (S4), or pyridostigmine 0.2 mg/kg with glycopyrrolate 0.01 mg/kg (PG) as the control. Clenching events will be assessed within 10 minutes of drug administration using three criteria: visible jaw clenching, increased masseter electromyographic (EMG) activity (\>50 μV for ≥2 seconds), and a rise in airway pressure (\>5 cm H₂O). Severity will be graded using a novel five-level classification system.

Secondary outcomes include the severity and timing of clenching, time to train-of-four (TOF) ratio ≥0.9, bispectral index (BIS) value at the time of clenching onset, airway-related complications, and risk factor analysis based on dose, sex, BIS, age, BMI, and total rocuronium dose.

P"This study hypothesizes a dose-dependent increase in clenching with higher doses of sugammadex, potentially with a higher incidence in female patients and those with higher BIS values at reversal."

Eligibility criteria: Inclusion Criteria:

* Eligible participants are adults aged 19-70 years, American Society of Anesthesiologists (ASA) physical status I-II, undergoing elective surgery under general anesthesia with rocuronium.

Exclusion Criteria:

* Exclusion criteria include neuromuscular disorders, renal impairment (creatinine clearance \< 30 mL/min), history of clenching or dental disease, allergy to study drugs, or emergency surgery.

Primary outcomes:
measure: Incidence of Mouth Clenching After Neuromuscular Blockade Reversal
timeFrame: Within 10 minutes after administration of neuromuscular blockade reversal agent
Secondary outcomes:
measure: Severity of Mouth Clenching
timeFrame: Within 10 minutes after reversal agent administration
measure: Time to Recovery of Train-of-Four (TOF) Ratio ≥0.9
timeFrame: Up to 10 minutes after administration
measure: Bispectral Index (BIS) at Clenching Onset
timeFrame: At time of clenching event, within 10 minutes post-reversal
measure: Peak Airway Pressure
timeFrame: Within 10 minutes post-reversal
measure: Incidence of Clenching-Related Complications
timeFrame: Within 10 minutes post-reversal
Other outcomes:
Locations:
city: Iksan
country: Korea, Republic of
facility: Wonkwang University hospital
state: Jeonbuk-do
Study officials:
affiliation: Wonkwang University Hospital
name: Cheolhyeong Lee, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hristovska AM, Duch P, Allingstrup M, Afshari A. Efficacy and safety of sugammadex versus neostigmine in reversing neuromuscular blockade in adults. Cochrane Database Syst Rev. 2017 Aug 14;8(8):CD012763. doi: 10.1002/14651858.CD012763.
citation: Naguib M. Sugammadex: another milestone in clinical neuromuscular pharmacology. Anesth Analg. 2007 Mar;104(3):575-81. doi: 10.1213/01.ane.0000244594.63318.fc.
citation: Lee HY, Jung KT. Advantages and pitfalls of clinical application of sugammadex. Anesth Pain Med (Seoul). 2020 Jul 31;15(3):259-268. doi: 10.17085/apm.19099.
citation: Lee S, Chung W. Sugammadex for our little ones: a brief narrative review. Anesth Pain Med (Seoul). 2024 Oct;19(4):269-279. doi: 10.17085/apm.24092. Epub 2024 Oct 31.
citation: Tsur A, Kalansky A. Hypersensitivity associated with sugammadex administration: a systematic review. Anaesthesia. 2014 Nov;69(11):1251-7. doi: 10.1111/anae.12736. Epub 2014 May 22.