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Trial registered on ANZCTR


Registration number
ACTRN12619000273189
Ethics application status
Approved
Date submitted
3/02/2019
Date registered
25/02/2019
Date last updated
25/02/2019
Date data sharing statement initially provided
25/02/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
Tetanic 100 or 200 Hz fade ratio to detect residual neuromuscular block.
Scientific title
Investigation protocol was designed to determine the potential benefit of 100 and 200 Hz tetanic stimulation to detect a residual neuromuscular block in anaesthetized patients.
Secondary ID [1] 297191 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
patient undergoing rhinoplasty under general anaesthetic 311356 0
patient undergoing rhinoseptoplasty under general anaesthetic 311679 0
Condition category
Condition code
Anaesthesiology 309992 309992 0 0
Anaesthetics
Respiratory 310104 310104 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
The study protocol was designed to determine the potential benefit of 100 and 200 Hz tetanic stimulation –compared to train-of-four (TOF) ratio 0.9- to detect a residual neuromuscular block (NMB) in anaesthetized patients. A new mechanomyographic device was developed to record the muscle responses in the clinical setting compared to acceleromyography on the contralateral hand.
The Isometric Thumb Force (ITF) monitoring system measures the isometric forces resulting from the thumb muscular activities elicited by electrical stimulations applied by surface electrodes placed above the ulnar nerve location at the wrist. A nerve stimulator (TOF-Watch, Organon-Technika, Copenhagen, Denmark) was dedicated to deliver TOF, PTC and different rates (100, 150, 200 Hz) of 5 seconds tetanic stimulations. In ITF handgrip, the thumb is placed in a tunnelled cradle surmounting a circular handle. The thumb and the rest of the hand are maintained in place by non-elastic straps. The transducer, inserted into the handgrip, transmits linear signals for compression forces ranging from 5 to 22000 N.
The study plan to include a cohort of 20 patients with American Society of Anesthesiologists (ASA) grades I to II (aged 18 to 80 years), who were scheduled to undergo rhinoplasty or rhinoseptoplasty under general anaesthesia. The patient's height, weight, age, and sex were recorded in the protocol, as was their dominant hand (left or right) to define the population investigated.
All patients received oral alprazolam 0.5 mg 60 minutes before arriving in the operating theatre. They were conventionally monitored with a pulse oximeter, a three-lead electrocardiogram, and a non-invasive blood pressure scheduled in automatic mode at 5-minute intervals. An intravenous catheter was inserted into their forearm for crystalloid infusion (side at random). Neuromuscular monitoring was set up according to a specific protocol.
A TOF-Watch SX (Alvesia Pharma, France) (TWX) was set on the left hand. The AMG transducer was taped on the thumb’s pulp and the hand was inserted and held inside a SL TOF-Tube. Another TOF-Watch designed to deliver high frequencies tetanic stimulation (including 100 and 200 Hz) was connected to the electrodes on the right arm which was equipped with the ITF handgrip. Both arms were positioned alongside the body on soft padding to protect nerve structures.
Anaesthesia was induced with continuous intravenous infusion of remifentanil 0.25 µg/kg/min and continuous infusion of propofol 1% to obtain a theoretical plasma concentration of 3 to 6 µg/mL (Diprifusor Cardinal Health, Basingstoke, UK). Lidocaine 1 mg/kg was given as an intravenous bolus. After loss of consciousness, manual ventilation was provided during Neuromuscular Transmission Monitoring (NMTM) calibration and the measurement of the initial baseline. Supra-maximal stimulation and initial calibration were obtained using the TOF-Watch SX internal automatic sequence, and the current intensity was recorded and applied on both sides. Then, TOF stimulations were applied at 15-second intervals during a short stabilization period. On the TWX side, four T4/T1 ratios were recorded to determine the initial baseline. We calculated 90% of the mean value to determine the normalized TOF ratio 0.9 recovery threshold for each monitoring module using the following formula: normalized TOF ratio 0.9 = sum of 4 TOF ratio × 9/40 with a result rounded up. On the ITF side were applied two consecutive tetanic stimulations (100 and 200 Hz at random) with a two minutes interval to avoid any potentiation. The force applied on the mechanomyographic sensor was recorded by ITF monitoring system. The residual force at the end of the contraction (F res) was divided by the maximal value (F max, obtained at the beginning of the contraction) to provide baseline tetanic fade ratios (TFR). Then, consecutive TOF stimulations every 15 seconds were applied on both hands to monitor the NMB, from the onset and during surgery.
Rocuronium 0.45 mg/kg was administered intravenously. Non-invasive automatic blood pressure measurement was suspended during the neuromuscular onset so as not to limit the distribution of the rocuronium in either of the two arms. Onset time was recorded when the TOF count reached zero with both monitors and tracheal intubation was performed. Automatic non-invasive blood pressure measurement was reactivated. Mechanical ventilation (closed circuit, 40% oxygen in air) maintained end-tidal CO2 within the normal range. Anaesthesia was maintained with the continuous intravenous administration of remifentanil 0.15 µg/kg/min and propofol with a target plasma concentration of 2 to 4 µg/mL. Blankets prevented heat loss from the body, and the oropharyngeal temperature was kept stable.
When the spontaneous NMB recovery reached a normalized TOF ratio 0.9 on the TWX side, both tetanic stimulations (same order than previously) were applied again with 2 minutes interval and the F max and TFR were recorded by ITF. Then, to accelerate NMB final recovery, 2 mg/kg of sugammadex was administered. After 3 minutes, two last tetanic stimulations (ITF side) and four consecutive TOF ratio measurements (TWX side) were recorded to determine the final baselines. The investigation did not interfere with intra- and postoperative care.
Intervention code [1] 313530 0
Diagnosis / Prognosis
Comparator / control treatment
Neuromuscular monitoring comparison : The isometric thumb force monitoring system with tetanic delivery and the TOF-Watch SX (considered the reference)
Control group
Active

Outcomes
Primary outcome [1] 318905 0
The Tetanic Fade Ratio (F res / F max) is determined after recording the maximal force (F max) and residual force (F res) by ITF during 100 and 200 Hz tetanic stimulations (composite primary outcome).
Timepoint [1] 318905 0
Before rocuronium administration, when normalized TOF ratio reach 0.9 on TOF-Watch SX, and 3 minutes after sugammadex administration
Secondary outcome [1] 366375 0
Recording fidelity as assessed by number of artefacts logged using ITF monitoring
Timepoint [1] 366375 0
Muscular responses to TOF stimulations are recorded every 15 seconds on both hands during the entire procedure, except during TET stimulations on the ITF side (2 minutes free interval).

Eligibility
Key inclusion criteria
- aged 18 to 80
- classified ASA I or II
- undergoing rhinoplasty or rhinospetoplasty under general anaesthetic
Minimum age
18 Years
Maximum age
80 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- pregnant or breast feeding women
- patients with renal or hepatic insufficiency
- patients with neurological disorders
- patients with a suspected allergy to drugs used in the protocol or receiving medications that could interfere with neuromuscular transmission

Study design
Purpose
Screening
Duration
Cross-sectional
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
The descriptive analysis will present the force measurement profiles after 100 Hz and 200 Hz stimulations in patients at three defined time points (initial baseline, TWX normalized TOF ratio 0.9, final baseline after sugammadex). Main outcomes are Fmax, TFR=Fres/Fmax and the area under the curve at the prespecified time points for the two tetanic stimulations.
Data will be log-transformed if necessary. For each outcome, a generalized linear mixed model (GLMM) will estimate the effects of independent variables (time point, frequency and the interaction) while including a random intercept at the patient level. GLMM results will be presented with 95 percent confidence intervals.
A difference of 10 percent of TFR will be considered clinically significant.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 21245 0
Belgium
State/province [1] 21245 0
Namur

Funding & Sponsors
Funding source category [1] 301745 0
Hospital
Name [1] 301745 0
CHU UCL Namur - Mont-Godinne
Address [1] 301745 0
Gaston Therasse Street,1
5530 Yvoir
Country [1] 301745 0
Belgium
Primary sponsor type
Charities/Societies/Foundations
Name
Fondation pour l'Anesthésie-Réanimation de Vaduz
Address
5, Aeulestrasse
BE FL 9490 Vaduz
Liechtenstein
Country
Liechtenstein
Secondary sponsor category [1] 301489 0
None
Name [1] 301489 0
Address [1] 301489 0
Country [1] 301489 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 302467 0
Ethics Commitee of CHU UCL Namur
Ethics committee address [1] 302467 0
Gaston Therasse Street,1
5530 Yvoir
Ethics committee country [1] 302467 0
Belgium
Date submitted for ethics approval [1] 302467 0
Approval date [1] 302467 0
17/09/2018
Ethics approval number [1] 302467 0
54/2017 B039201732500

Summary
Brief summary
Quantitative neuromuscular transmission monitoring (NMTM) is useful to manage the depth of neuromuscular blockade (NMB) during general anesthesia. In every patient, it determines the individual onset time before tracheal intubation and provides the clinician with post-tetanic count (PTC) and train-of-four (TOF) count to maintain the NMB at the proper depth according to the surgical need. At the time of tracheal extubation, quantitative NMTM is the recommended method to reduce the risk of residual NMB. Among other techniques, acceleromyography (AMG) has been developed to provide the clinician with a simple quantitative NMTM. It has been demonstrated to be a valuable measurement tool in clinical practice. However, when using the TOF stimulation pattern, the threshold of safe recovery is close to the baseline (TOF ratio 0.9 or even 1.0). In clinical practice, this close-to-the-limit performance could cause inadequate determination of NMB recovery and increase the risk of postoperative pulmonary complications. A more sensitive method seems mandatory to detect low levels of residual NMB before tracheal extubation. The present study tries to determine the potential benefit of 100 and 200 Hz tetanic stimulation –compared to TOF- to detect a residual NMB in anaesthetized patients. A new mechanomyographic device was developed to record the muscle responses in the clinical setting. We tested the hypothesis that high frequency tetanic stimulation (100 and 200 Hz) would induce more residual fade than TOF at the 0.9 threshold.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 90322 0
Dr Mitchell John
Address 90322 0
Anaesthesiology department
CHU UCL Namur Godinne
Gaston Therasse Street, 1
5530 Yvoir
Country 90322 0
Belgium
Phone 90322 0
003281423907
Fax 90322 0
003281423920
Email 90322 0
john.mitchell@uclouvain.be
Contact person for public queries
Name 90323 0
Prof Dubois Philippe E
Address 90323 0
Anaesthesiology department
CHU UCL Namur Godinne
Gaston Therasse Street, 1
5530 Yvoir
Country 90323 0
Belgium
Phone 90323 0
003281423929
Fax 90323 0
003281423920
Email 90323 0
phil.dubois@uclouvain.be
Contact person for scientific queries
Name 90324 0
Prof d'Hollander Alain
Address 90324 0
Anaesthesiology Department
University Hospital Geneva
Rue Gabrielle-Perret-Gentil 4,
1205
Geneva


Country 90324 0
Switzerland
Phone 90324 0
004122 372 74 03
Fax 90324 0
Email 90324 0
dhollanderalain@yahoo.fr

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
No other documents available
Summary results
No Results