Does Electromyography Improve Precision and Reliability of Neuromuscular Monitoring in Paediatric Patients (ETCETERA)

Original Title: Does ElecTromyography Improve preCision and Reliability of nEuromuscular moniToring in paEdiatRic pAtients - A Monocentric Randomized Prospective Agreement Study - ETCETERA

Neuromuscular monitoring is used as a standard surveillance method of neuromuscular function to ensure full recovery at the end of anaesthesia. The currently available devices properly provide respective information in adults but not in children. Furthermore, response to neuromuscular blocking agents differs between adults and children due to age-related differences in body composition, physiological function, and acetylcholine receptor density.

Recently, electromyographic (EMG) technologies to monitor neuromuscular function were increasingly developed including disposables for nerve stimulation and measurement of the compound muscle action potential in children. However, it is still unclear whether the precision and reliability of these devices is superior to the currently available neuromuscular monitoring for children based on kinemyography (KMG).

The ETCETERA study will test the hypothesis that neither EMG nor KMG provides inferior train-of-four readings to the respective reference method in infants and children below five years.

Study Overview

• Status: Recruiting
• Conditions: Postoperative Complications; Neuromuscular Blockade, Residual
• Intervention / Treatment: Device: Electromyography (EMG); Device: Kinemyography (KMG)

Detailed Description

The ETCETERA trial is a randomized clinical agreement study which will prospectively enrol sixty-four children below five years of age scheduled for elective, non-cardiac surgery requiring general anaesthesia and neuromuscular blockade for optimisation of surgical conditions.

The children's neuromuscular function is measured on one hand with EMG and on the other hand with KMG in a randomised fashion. Additionally, randomisation will be stratified upon age groups: 1) neonates: birth to <28 days, 2) infants 28 days to ≤3 months, 3) toddlers: >3 months to ≤2 years, 4) children >2 years to <5 years.

Based on the high failure rate of currently available neuromuscular monitoring devices in infants and neonates, in this randomised agreement study we will primarily compare precision and reliability of EMG and KMG-measured Train-of-Four (TOF) values during spontaneous recovery from a rocuronium-induced neuromuscular blockade in neonates, infants, toddlers, and children <5 years using the age-appropriate paediatric sensors.

• Study Type: Observational
• Enrollment (Estimated): 64

Contacts and Locations

• Study Contact: Name: Sebastian Schmid, MD PD; Phone Number: (+49) 731 500 60000; Email: s.schmid@uni-ulm.de
• Study Contact Backup: Name: Flora Scheffenbichler, MD; Phone Number: (+49) 731 500 60284; Email: flora.scheffenbichler@uni-ulm.de

Study Locations

• Germany
  • Baden-Württemberg
    • Ulm, Baden-Württemberg, Germany, 89073
      • Recruiting
      • University Hospital Ulm
      • Contact: Flora Scheffenbichler; Email: flora.scheffenbichler@uni-ulm.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

The ETCETERA study will be performed in children <5 years of age scheduled for elective, non-cardiac surgery requiring general anaesthesia and neuromuscular blockade.

Description

Inclusion Criteria:

• children and infants < 5 years
• non-cardiac surgery requiring general anaesthesia and neuromuscular blockade
• signed informed written consent
• American Society of Anesthesiologists physical status <4
• intraoperative positioning with access to both arms

Exclusion Criteria:

• allergy to neuromuscular blocking agents
• allergy to neuromuscular monitoring adhesive electrode
• neurologic disease
• surgical procedures outside the operating room
• children receiving neuromuscular blocking agents immediately before surgery

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
neonates; birth to <28 days	Device: Electromyography (EMG); Measurement of the compound muscle action potential for the assessment of neuromuscular function; Device: Kinemyography (KMG); Measurement of the muscle velocity for the assessment of neuromuscular function
infants; 28 days to ≤3 months	Device: Electromyography (EMG); Measurement of the compound muscle action potential for the assessment of neuromuscular function; Device: Kinemyography (KMG); Measurement of the muscle velocity for the assessment of neuromuscular function
toddlers; >3 months to ≤2 years	Device: Electromyography (EMG); Measurement of the compound muscle action potential for the assessment of neuromuscular function; Device: Kinemyography (KMG); Measurement of the muscle velocity for the assessment of neuromuscular function
children; >2 years to <5 years	Device: Electromyography (EMG); Measurement of the compound muscle action potential for the assessment of neuromuscular function; Device: Kinemyography (KMG); Measurement of the muscle velocity for the assessment of neuromuscular function

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Precision of TOF (train of four) measurements	The primary endpoint is the repeatability coefficient "r" defined as 1.96 times the standard deviation of the differences between two consecutive TOF ratio measurements on the same patient under identical conditions. The repeatability coefficient and its confidence intervals will be calculated using a linear mixed regression model for EMG and KMG measured TOF ratios independently at baseline and at complete neuromuscular recovery, i.e., at TOF ratio > 0.9 and compared between techniques using F-tests with a non-inferiority approach.	intraoperatively

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Agreement of TOF values during spontaneous recovery of neuromuscular function	Agreement of TOF during spontaneous recovery of neuromuscular function, agreement of TOF at baseline and agreement of the final TOF at >0.9 and 1.0 will be verified. The repeatability coefficient and its confidence intervals will be calculated using a linear mixed regression model for EMG and KMG measured TOF ratios independently at baseline and at complete neuromuscular recovery, i.e., at TOF ratio > 0.9 and compared between techniques using F-tests with a non-inferiority approach.	intraoperatively

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tactile TOF-count measurement	Tactile measurement of TOF response (EMG and KMG)	intraoperatively
Postoperative pulmonary events	Including upper airway obstruction, hypoxemia, respiratory distress, aspiration, reintubation (Murphy et al.)	on the day of surgery in the recovery room
Skin lesions, redness and pressure points on the forearms	Clinical safety outcome	on the day of surgery in the recovery room and at hospital discharge or on postoperative day 7, whichever occurs earlier
Pain associated with the EMG and KMG measurement	Assessment through child discomfort and pain scale (KUSS) (Bittner et al.)	on the day of surgery in the recovery room and at hospital discharge or on postoperative day 7, whichever occurs earlier

Collaborators and Investigators

• Sponsor: University Hospital Ulm
• Investigators: Principal Investigator: Flora Scheffenbichler, MD, Department of Anesthesiology and Intensive Care Medicine, University of Ulm, Ulm, Germany.

Publications and helpful links

General Publications

• Murphy GS, Szokol JW, Marymont JH, Greenberg SB, Avram MJ, Vender JS. Residual neuromuscular blockade and critical respiratory events in the postanesthesia care unit. Anesth Analg. 2008 Jul;107(1):130-7. doi: 10.1213/ane.0b013e31816d1268.
• Buttner W, Finke W, Hilleke M, Reckert S, Vsianska L, Brambrink A. [Development of an observational scale for assessment of postoperative pain in infants]. Anasthesiol Intensivmed Notfallmed Schmerzther. 1998 Jun;33(6):353-61. doi: 10.1055/s-2007-994263. German.

Study record dates

Study Major Dates

• Study Start (Actual): September 20, 2023
• Primary Completion (Estimated): June 30, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: August 15, 2023
• First Submitted That Met QC Criteria: September 27, 2023
• First Posted (Actual): October 2, 2023

Study Record Updates

• Last Update Posted (Actual): October 6, 2023
• Last Update Submitted That Met QC Criteria: October 3, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Electromyography; Postoperative Complications; Neuromuscular Blockade
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Delayed Emergence from Anesthesia
• Other Study ID Numbers: ETCETERA

Drug and device information, study documents

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