TwichView-guided Atricurium Dose Adjustment Trial

Overview

The goal of this clinical trial is to learn if using a monitor that measures muscle response can lower the amount of muscle relaxant medicine needed in adults who are treated in an intensive care unit (ICU) and need a continuous drip of a muscle relaxant called atracurium for more than 48 hours. The main questions it aims to answer are: Does using the monitor lower the infusion rate and total amount of atracurium given over 72 hours? Does using the monitor lower the complications related to atracurium use? Researchers will compare a group whose dose is guided by a muscle response monitor, aiming for a moderate level of muscle relaxation, to a group whose dose is guided by the usual bedside checks, to see if the monitor lowers the amount of medicine needed while keeping the same quality of care. Participants will: Receive atracurium as a continuous drip as part of their usual ICU treatment Have a small sensor placed on the wrist and hand to measure muscle response, if they are in the monitor group Be checked regularly by a nurse and a respiratory therapist, who will adjust the dose following a written plan Be observed closely for 72 hours, then followed until they leave the hospital .

Objectives： To determine whether targeting a moderate level of paralysis using the TwitchView® electromyography (EMG)-based quantitative TOF monitor can achieve adequate clinical effectiveness while reducing the cumulative dose and infusion rate of atracurium in ICU patients receiving continuous atracurium infusion, compared with routine care guided by clinical assessment alone. Background： Continuous infusions of intermediate-acting neuromuscular blocking agents (NMBAs) such as atracurium are frequently administered in intensive care unit (ICU) patients with acute respiratory distress syndrome (ARDS), in post-cardiac arrest care with targeted temperature management (TTM), or during extracorporeal membrane oxygenation (ECMO) support. Although adequate paralysis is essential for treatment efficacy, prolonged or excessive NMBA exposure has been associated with pneumonia, deep vein thrombosis, and ICU-acquired weakness. Train-of-four (TOF) monitoring is widely used in the operating room to guide NMBA titration toward complete paralysis (\> 90% block); however, although several publications support its use in the ICU, the optimal depth of paralysis and the appropriate monitoring modality in this setting remain unresolved. Previous studies that used TOF-guided titration targeting near-total paralysis (\> 90% block) have paradoxically reported higher cumulative NMBA doses than clinical assessment alone. Such monitoring devices have recently been introduced into our ICU, and based on our clinical experience, a moderate level of paralysis corresponding to a TOF count of 2-3 (65-85% block) may be sufficient for adequate clinical effect and may reduce total drug exposure. Study Design： This is a single-center, prospective, cluster-randomized controlled trial using cluster randomization by calendar month, to be conducted in the ICUs of Fu Jen Catholic University Hospital for 1 year after institute review board (IRB) approved. Methods： Adult patients (≥ 20 years) requiring continuous atracurium infusion for more than 48 hours due to moderate-to-severe ARDS (PaO₂/FiO₂ ≤ 150), post-cardiac arrest care with TTM, or ECMO support will be enrolled. Patients will be allocated to the intervention group (TwitchView®-guided titration targeting a TOF count of 2-3) or the routine care group (clinical assessment by a bedside nurse and respiratory therapist). All patients will be sedated to a Richmond Agitation-Sedation Scale (RASS) score of -3 to -4, or to a Bispectral Index (BIS) of 40-60 when BIS monitoring is available. The primary outcome is the mean cumulative dose and mean infusion rate of atracurium over 72 hours. Secondary outcomes include the frequency of inadequate-paralysis events, survival, ventilator dependence, drug-related adverse events, ICU-acquired weakness, and favorable neurological outcomes. Approximately 120 patients are expected to be enrolled, with the group sizes determined by randomization. Continuous variables will be analyzed using the Student's t test or the Mann-Whitney U test, and categorical variables using Pearson's chi-square test or Fisher's exact test. Multivariable analyses will be performed using logistic regression. A two-tailed p value \< 0.05 will be considered statistically significant. Effect： This trial will provide prospective evidence on whether a moderate-paralysis strategy guided by EMG-based quantitative TOF monitoring can optimize atracurium dosing in ICU patients. To date, studies using EMG-based monitors in the ICU setting remain relatively scarce. If our hypothesis is confirmed, this strategy may help balance treatment efficacy and safety by minimizing unnecessary drug exposure and the associated risk of ICU-acquired weakness, while still effectively preventing patient-ventilator dyssynchrony and treatment failure. The findings may also serve as a reference for the development of future evidence-based clinical guidance on neuromuscular blockade monitoring in critically ill patients.