Predictive Modelling of the Intraoperative Train-of-Four (TOF) Ratio

Neuromuscular Blocking Agents (NMBAs) are routinely administered to patients in a multiplicity o anaesthetic settings in order to paralyze and impede (re)active muscular contraction. The availability of monitoring devices allowing an accurate measurement fo the degree of neuromuscular block during anesthesia has raised the standards for a proper evidence-based use of NMBAs.

For this purpose, one of the most widely used methods is the Train of Four (TOF): transcutaneous application of a series of 4 square-wave supra-maximal electrical stimuli over the course of a nerve of choice (most commonly the ulnar nerve). These are applied at a frequency of 2Hz, and each with a duration of 0.2ms. These stimuli elicit a motor response on the adductor pollicis muscle, which on its turn dictates the adduction of the thumb. The acceleration of this movement can be followed by means of an uni/multi-directional accelerometer attached to the thumb. The ratio of the acceleration of the 4th and 1st elicited contractions is called the TOF-Ratio - a clinically and scientifically established method of assessing neuromuscular block recovery. A value of 1 translates a full recovery of the muscular function of a patient. In modern Anesthesia, the bar for deeming a recovery as adequate has been set at a minimum of a TOF-ratio of >0.9, with some authors advocating a ratio of 1 as the only acceptable and complications avoiding result.

Study Overview

• Status: Recruiting
• Conditions: Analyse Neuromuscular Monitoring for Developing a Model to Predict TOF Ratio During Anesthesia
• Intervention / Treatment: Procedure: Elective surgery

• Study Type: Observational
• Enrollment (Estimated): 200

Contacts and Locations

Study Locations

• Belgium
  • Brussels Capital
    • Jette, Brussels Capital, Belgium, 1090
      • Recruiting
      • UZ Brussel
      • Contact: Evelien Vandeurzen, Biomedical Sciences; Phone Number: 024749237; Email: evelien.vandeurzen@uzbrussel.be
      • Principal Investigator: Hugo Carvalho, MD, PhD
  • WV
    • Bruges, WV, Belgium, 8000
      • Not yet recruiting
      • AZ Sint Jan
      • Principal Investigator: Hugo Carvalho, MD, PhD
      • Contact: Hugo Carvalho, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Adult patients (18 years old and above) receiving General Anesthesia for noncardiac surgery requiring the use of a neuromuscular blocking agent.

Description

Inclusion Criteria:

• Adult patients (18 years old and above) receiving General Anesthesia for noncardiac surgery requiring the use of a neuromuscular blocking agent.
• Administration of General Anesthesia by means of Total Intravenous Anesthesia technique.
• Use of Rocuronium as a neuromuscular blocking agent.

Exclusion Criteria:

• Use of different types of neuromuscular blocking agents for the same patient within the same surgical procedure
• Known Neuromuscular diseases/syndromes judged to condition accurate neuromuscular monitoring.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Prospective group	Procedure: Elective surgery; Any patient who needs to undergo an elective surgery.
Retrospective group	Procedure: Elective surgery; Any patient who needs to undergo an elective surgery.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
TOF-ratio	Train of four percentage	1 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
TOF-count	Train of four count	1 day

Collaborators and Investigators

• Sponsor: Universitair Ziekenhuis Brussel

Publications and helpful links

General Publications

• Verdonck M, Carvalho H, Fuchs-Buder T, Brull SJ, Poelaert J. Machine learning based analysis and detection of trend outliers for electromyographic neuromuscular monitoring. J Clin Monit Comput. 2024 Oct;38(5):1163-1173. doi: 10.1007/s10877-024-01141-6. Epub 2024 Apr 4.
• Carvalho H, Verdonck M, Eleveld DJ, Ramirez D, D'Haese J, Flamee P, Geerts L, Wylleman J, Cools W, Barbe K, Struys MMRF, Poelaert J. Neuromuscular end-point predictive capability of published rocuronium pharmacokinetic/pharmacodynamic models: An observational trial. J Clin Anesth. 2023 Nov;90:111225. doi: 10.1016/j.jclinane.2023.111225. Epub 2023 Aug 3.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2020
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: August 14, 2020
• First Submitted That Met QC Criteria: August 14, 2020
• First Posted (Actual): August 19, 2020

Study Record Updates

• Last Update Posted (Actual): April 29, 2026
• Last Update Submitted That Met QC Criteria: April 28, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Surgical Procedures, Operative; Elective Surgical Procedures
• Other Study ID Numbers: TOFPROS02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Publication via medical article.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No