Reversal of Residual Neuromuscular Blockade at Train-of-four Ratio 0.3 With Sugammadex and Neostigmine

Dose Finding Study for Reversal of Vecuronium-induced Neuromuscular Blockade at Train-of-four Ratio 0.3 With Sugammadex and Neostigmine

The aim of this study is to estimate the optimal dose of sugammadex and neostigmine reversal of a vecuronium-induced residual neuromuscular block at train-of-four ratio 0.3.

Study Overview

• Status: Completed
• Conditions: Neuromuscular Blockade
• Intervention / Treatment: Drug: Sugammadex; Drug: Neostigmine; Drug: Saline 0.9%

Detailed Description

Sugammadex is a modified γ-cyclodextrin compound that reverses the neuromuscular blockade produced by steroidal nondepolarizing muscle relaxants such as rocuronium,vecuronium and pipecuronium by encapsulating them, making them unavailable to interact with the nicotinic acetylcholine receptors at the neuromuscular junction.However, residual neuromuscular blocks between reappearance of T4 and train-of-four ratio (TOFR)=0.5 are more frequent in clinical practice compared with profound or deep blocks and have not been investigated for sugammadex previously.

Unlike neostigmine, sugammadex is efficacious in reversing profound (no responses to either train-of-four (TOF) or posttetanic count stimulation) or deep (posttetanic count of 1 or 2) neuromuscular block (NMB) in doses of 16 and 4 mg/kg, respectively. However, shallow neuromuscular blocks are more frequent in clinical practice compared with profound or deep blocks and have not been investigated for sugammadex previously.

• Study Type: Observational
• Enrollment (Actual): 121

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510010
      • Guangzhou Military Region General Hospital, Department of Anesthesiology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

people scheduled for elective surgery

Description

Inclusion Criteria:

• 1 age of 18 to 65 yr,
• 2 body mass index 18.5 to 25.0 kg/m2,
• 3 American Society of Anesthesiologists physical status I to III
• 4 scheduled for elective surgery with an expected duration of at least 60min under general anesthesia with intubation of the trachea or laryngeal mask
• 5 patients having given informed consent to the study

Exclusion Criteria:

• 1 patients who had participated in another clinical trial within 1 month
• 2 Patients with suspected difficult airway, bronchial asthma, chronic obstructive pulmonary disease
• 3 known neuromuscular disease
• 4 suspected malignant hyperthermia
• 5 hepatic or renal dysfunction
• 6 glaucoma
• 7 allergy to the medication that used in this trial
• 8 taking medicaments that might influence the effect of NMB agents
• 9 pregnant, or breastfeeding state
• 10 taking medication known to alter the effect of neuromuscular blocking agents( toremifene .etc)

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

11

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
sugammadex 0.125; Sugammadex group: sugammadex 0.125 mg/kg IV once at the reappearance of TOF 0.3	Drug: Sugammadex; At the end of surgical procedure at a depth of neuromuscular blockade at the reappearance of train-of-four 0.3, single intravenous injection of either : Sugammadex 0.125 mg/kg (sugammadex 0.125) Sugammadex 0.25 mg/kg (sugammadex 0.25) Sugammadex 0.5 mg/kg (sugammadex 0.5) Sugammadex 1.0 mg/kg (sugammadex 1.0) Sugammadex 2.0 mg/kg (sugammadex 2.0); Other Names: Bridion; Org 25969
Sugammadex 0.25; Sugammadex group: sugammadex 0.25 mg/kg IV once at the reappearance of TOF 0.3	Drug: Sugammadex; At the end of surgical procedure at a depth of neuromuscular blockade at the reappearance of train-of-four 0.3, single intravenous injection of either : Sugammadex 0.125 mg/kg (sugammadex 0.125) Sugammadex 0.25 mg/kg (sugammadex 0.25) Sugammadex 0.5 mg/kg (sugammadex 0.5) Sugammadex 1.0 mg/kg (sugammadex 1.0) Sugammadex 2.0 mg/kg (sugammadex 2.0); Other Names: Bridion; Org 25969
Sugammadex 0.5; Sugammadex group: sugammadex 0.5 mg/kg IV once at the reappearance of TOF 0.3	Drug: Sugammadex; At the end of surgical procedure at a depth of neuromuscular blockade at the reappearance of train-of-four 0.3, single intravenous injection of either : Sugammadex 0.125 mg/kg (sugammadex 0.125) Sugammadex 0.25 mg/kg (sugammadex 0.25) Sugammadex 0.5 mg/kg (sugammadex 0.5) Sugammadex 1.0 mg/kg (sugammadex 1.0) Sugammadex 2.0 mg/kg (sugammadex 2.0); Other Names: Bridion; Org 25969
Sugammadex 1.0; Sugammadex group: sugammadex 1.0 mg/kg IV once at the reappearance of TOF 0.3	Drug: Sugammadex; At the end of surgical procedure at a depth of neuromuscular blockade at the reappearance of train-of-four 0.3, single intravenous injection of either : Sugammadex 0.125 mg/kg (sugammadex 0.125) Sugammadex 0.25 mg/kg (sugammadex 0.25) Sugammadex 0.5 mg/kg (sugammadex 0.5) Sugammadex 1.0 mg/kg (sugammadex 1.0) Sugammadex 2.0 mg/kg (sugammadex 2.0); Other Names: Bridion; Org 25969
Sugammadex 2.0; Sugammadex group: sugammadex 2.0 mg/kg IV once at the reappearance of TOF 0.3	Drug: Sugammadex; At the end of surgical procedure at a depth of neuromuscular blockade at the reappearance of train-of-four 0.3, single intravenous injection of either : Sugammadex 0.125 mg/kg (sugammadex 0.125) Sugammadex 0.25 mg/kg (sugammadex 0.25) Sugammadex 0.5 mg/kg (sugammadex 0.5) Sugammadex 1.0 mg/kg (sugammadex 1.0) Sugammadex 2.0 mg/kg (sugammadex 2.0); Other Names: Bridion; Org 25969
Neostigmine 10; Neostigmine group: neostigmine 10 µg/kg IV once at the reappearance of TOF 0.3	Drug: Neostigmine; At the end of surgical procedure at a depth of neuromuscular blockade at the reappearance of train-of-four 0.3, single intravenous injection of either : Neostigmine 10 µg/kg (Neostigmine 10) Neostigmine 25 µg/kg (Neostigmine 25) Neostigmine 40 µg/kg (Neostigmine 40) Neostigmine 55 µg/kg (Neostigmine 55) Neostigmine 70 µg/kg (Neostigmine 70) Atropine will be administered with Neostigmine at a half dose of Neostigmine administered through an intravenous line with brisk flow.; Other Names: Prostigmin
Neostigmine 25; Neostigmine group: neostigmine 25 µg/kg IV once at the reappearance of TOF 0.3	Drug: Neostigmine; At the end of surgical procedure at a depth of neuromuscular blockade at the reappearance of train-of-four 0.3, single intravenous injection of either : Neostigmine 10 µg/kg (Neostigmine 10) Neostigmine 25 µg/kg (Neostigmine 25) Neostigmine 40 µg/kg (Neostigmine 40) Neostigmine 55 µg/kg (Neostigmine 55) Neostigmine 70 µg/kg (Neostigmine 70) Atropine will be administered with Neostigmine at a half dose of Neostigmine administered through an intravenous line with brisk flow.; Other Names: Prostigmin
Neostigmine 40; Neostigmine group: neostigmine 40 µg/kg IV once at the reappearance of TOF 0.3	Drug: Neostigmine; At the end of surgical procedure at a depth of neuromuscular blockade at the reappearance of train-of-four 0.3, single intravenous injection of either : Neostigmine 10 µg/kg (Neostigmine 10) Neostigmine 25 µg/kg (Neostigmine 25) Neostigmine 40 µg/kg (Neostigmine 40) Neostigmine 55 µg/kg (Neostigmine 55) Neostigmine 70 µg/kg (Neostigmine 70) Atropine will be administered with Neostigmine at a half dose of Neostigmine administered through an intravenous line with brisk flow.; Other Names: Prostigmin
Neostigmine 55; Neostigmine group: neostigmine 55 µg/kg IV once at the reappearance of TOF 0.3	Drug: Neostigmine; At the end of surgical procedure at a depth of neuromuscular blockade at the reappearance of train-of-four 0.3, single intravenous injection of either : Neostigmine 10 µg/kg (Neostigmine 10) Neostigmine 25 µg/kg (Neostigmine 25) Neostigmine 40 µg/kg (Neostigmine 40) Neostigmine 55 µg/kg (Neostigmine 55) Neostigmine 70 µg/kg (Neostigmine 70) Atropine will be administered with Neostigmine at a half dose of Neostigmine administered through an intravenous line with brisk flow.; Other Names: Prostigmin
Neostigmine 70; Neostigmine group: neostigmine 70 µg/kg IV once at the reappearance of TOF 0.3	Drug: Neostigmine; At the end of surgical procedure at a depth of neuromuscular blockade at the reappearance of train-of-four 0.3, single intravenous injection of either : Neostigmine 10 µg/kg (Neostigmine 10) Neostigmine 25 µg/kg (Neostigmine 25) Neostigmine 40 µg/kg (Neostigmine 40) Neostigmine 55 µg/kg (Neostigmine 55) Neostigmine 70 µg/kg (Neostigmine 70) Atropine will be administered with Neostigmine at a half dose of Neostigmine administered through an intravenous line with brisk flow.; Other Names: Prostigmin
Placebo; Placebo group: Saline 0.9% IV once at the reappearance of TOF 0.3	Drug: Saline 0.9%; At the end of surgical procedure at a depth of neuromuscular blockade at the reappearance of train-of-four 0.3, single intravenous injection of saline 0.9%.; Other Names: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to TOF 0.9 after the administration of reversal agent	The time to achieve TOF (Train of Four stimulation) ratio to 0.9 following the investigational drug or placebo administration.	the general anesthesia time 1 hour at least

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
incidence of reparalysis	Determining whether patients receiving reversal agent will have a train-to-four ratio <0.8 during total recovery time (from TOF reach 0.9 first time to post-anaesthesia care unit (PACU) departure)	approximately 1 hour
incidence of adverse event	Documenting whether patients will have some adverse events(such as hypoxia bradycardia nausea and vomiting) from anesthesia commence to PACU departure.	the general anesthesia and recovery time 2 hours at least

Collaborators and Investigators

• Sponsor: Guangzhou General Hospital of Guangzhou Military Command

Publications and helpful links

General Publications

• Pongracz A, Szatmari S, Nemes R, Fulesdi B, Tassonyi E. Reversal of neuromuscular blockade with sugammadex at the reappearance of four twitches to train-of-four stimulation. Anesthesiology. 2013 Jul;119(1):36-42. doi: 10.1097/ALN.0b013e318297ce95.
• Schaller SJ, Fink H, Ulm K, Blobner M. Sugammadex and neostigmine dose-finding study for reversal of shallow residual neuromuscular block. Anesthesiology. 2010 Nov;113(5):1054-60. doi: 10.1097/ALN.0b013e3181f4182a.
• Kaufhold N, Schaller SJ, Stauble CG, Baumuller E, Ulm K, Blobner M, Fink H. Sugammadex and neostigmine dose-finding study for reversal of residual neuromuscular block at a train-of-four ratio of 0.2 (SUNDRO20)dagger, Br J Anaesth. 2016 Feb;116(2):233-40. doi: 10.1093/bja/aev437.
• He J, He H, Li X, Sun M, Lai Z, Xu B. Required dose of sugammadex or neostigmine for reversal of vecuronium-induced shallow residual neuromuscular block at a train-of-four ratio of 0.3. Clin Transl Sci. 2022 Jan;15(1):234-243. doi: 10.1111/cts.13143. Epub 2021 Nov 2.

Study record dates

Study Major Dates

• Study Start (Actual): July 26, 2018
• Primary Completion (Actual): June 28, 2019
• Study Completion (Actual): June 30, 2019

Study Registration Dates

• First Submitted: July 10, 2018
• First Submitted That Met QC Criteria: August 30, 2018
• First Posted (Actual): September 4, 2018

Study Record Updates

• Last Update Posted (Actual): August 11, 2020
• Last Update Submitted That Met QC Criteria: August 9, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: sugammadex neostigmine
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Agents; Enzyme Inhibitors; Cholinesterase Inhibitors; Parasympathomimetics; Neostigmine
• Other Study ID Numbers: Reversal Neuromuscular Block