Effect of tetanic stimulation prior to Train-of-Four sequence on stabilization time of muscle response in patients aged 60-80

Published: 12 December 2022| Version 1 | DOI: 10.17632/fyhpfpk5cm.1
Angela Henrique Silva Ribeiro,


Neuromuscular blocking agents (NBAs) are widely used in health care settings around the world. They are used for general anesthesia, facilitation of orotracheal intubation, and maintenance of controlled mechanical ventilation in intensive care and anesthesia. Objective monitoring of neuromuscular blockade (NB) is the only reliable way to ensure the degree of NB and its reversal, avoiding complications and reducing hospital costs, and should therefore be used routinely, as part of the safe surgery protocol. In clinical practice, the most commonly used stimulation pattern is the four-stimulus sequence, commonly known as Train-of-Four (TOF) by acceleromyography, which assesses the degree of muscle strength by the ratio of the last muscle contraction over the first contraction (T4/T1). In the latest guideline for good practice for clinical research in pharmacodynamic studies for NBA II, it is recommended that before its injection, calibration (obtaining the T1 height of 100%) and stabilization of the muscle response to electrical stimulation must be performed, for a reliable and accurate interpretation of the data. Stabilization represents a maximum variation of 5% of T1 high maintained for a minimum period of 2 minutes before the injection of NBA. This time can take up to 20 minutes to occur, too long a time in clinical studies. To decrease the settling time, a 50 Hz tetanic stimulus should then be applied for 5s before calibration. The pharmacokinetics and pharmacodynamics of NBAs are altered with aging, but studies in this age group become difficult to perform due to multiple comorbidities. No pharmacodynamic studies of their using tetanic stimulation in patients over 60 years of age have been found in the databases up to the present moment. In this regard, the primary objective of this study was to determine the time to stabilization of the muscle response with the use of tetanic stimulation prior to TOF monitoring in patients over 60 years of age. Secondary objectives are to determine the onset of action of NBA, clinical duration, pharmacological duration, initial and final T1 height, and recovery from NB.


Steps to reproduce

Prospective, randomized, single-blind, multicenter, clinical trial, approved by the ethics committees of Hospital Universitário Federal Gaffrée e Guinle (CAAE 03260918.4.0000.5253) and Hospital Universitário Pedro Ernesto (CAAE 03260918.4.3001.5259), Rio de Janeiro, Brazil, and registered at clinical trials Brazilian platform REBEC (RBR-35msdt). Sixty patients to undergo elective surgery under general anesthesia, with routine preoperative evaluation, were consecutively recruited and informed consents obtained. Randomization into two groups was performed using the program GraphPad Prism QuickCalcs (GraphPad software, Inc. La Jolla, California, USA). Patients were then allocated into one of two groups: one that received tetanic stimulus (n=30) or one that did not receive tetanic stimulus (n=30). A single researcher conducted the data collection and was aware of the group randomly assigned. The complementary exams prior to surgery were: Blood cell count, coagulogram, urea, creatinine clearance, sodium, potassium, glucose, chest teleradiography, and electrocardiogram. This study followed the protocol recommended by the "Good Clinic Research Practice in pharmacodynamic studies of neuromuscular blocking agents II: the Stockholm Revision" guideline. Inclusion criteria were patients between 60 to 80 years old, all genders, ASA (American Society of Anesthesiology) physical status I to III, BMI (Body Mass Index) between 18.5 to 29, undergoing total venous general anesthesia with an presumed surgical duration over 1h. Exclusion criteria were presence of neuromuscular diseases, renal or hepatic dysfunction, use of furosemide, aminoglycosides, aminophylline, azathioprine, cyclophosphamide, anti-inflammatory drugs, and magnesium, allergy to the drugs used in the study, and history or predictors of difficult airway. More about the steps to reproduce is in the documents TOF Methods Description.docx, the Dataset and the Data Description..docx.


Universidade Federal do Estado do Rio de Janeiro, Universidade Federal do Rio de Janeiro, Universidade Federal Fluminense


Anesthesiology, General Anesthesia, Neuromuscular Blocking Agent, Analgesia Practice, Neuromuscular Block Monitoring, Neuromuscular Blockade