ICU Study Links Prolonged Muscle Paralysis to Complications

A large multicenter observational study published in Annals of Intensive Care has detailed the real-world use of neuromuscular blocking agents in intensive care units across France and Belgium. The study highlights that while these agents are frequently used for acute respiratory distress syndrome, their application extends to other critical care scenarios, and prolonged infusion is associated with increased complications.

The study, registered as NCT04028362, was a prospective observational investigation involving 19 intensive care units. Data were collected between November 16, 2019, and February 19, 2020, a period just before the onset of the COVID-19 pandemic. During this timeframe, 2,248 adult patients underwent invasive mechanical ventilation in the participating centers. Of this total cohort, 270 patients, representing 12% of the mechanically ventilated population, received at least one dose of neuromuscular blocking agents. Specifically, 232 patients, or 10.3%, received continuous infusions of these agents, which was the primary focus of the analysis.

In the intensive care setting, they are often used to facilitate mechanical ventilation by preventing patient-ventilator asynchrony, reducing the work of breathing, and improving oxygenation in severe cases of acute respiratory distress syndrome. Other indications include preventing shivering during therapeutic hypothermia and managing intracranial hypertension. The study aimed to describe the epidemiology of these agents and identify factors associated with ICU outcomes, providing a snapshot of clinical practices that may differ from the protocolized use seen in randomized controlled trials.

The primary indication for continuous neuromuscular blocking agent infusion in this cohort was acute respiratory distress syndrome, accounting for 58% of cases. Prevention of shivering during therapeutic hypothermia was the second most common reason, observed in 19% of patients, followed by patient-ventilator asynchrony in patients without ARDS, which accounted for 12%. Cisatracurium was the most frequently used molecule, administered to 74% of the patients. The median duration of infusion was 38 hours, with an interquartile range of 22 to 71 hours. Notably, the duration of infusion varied significantly depending on the clinical indication, with ARDS patients receiving the longest infusions and highest cumulative doses.

Monitoring of neuromuscular blockade was inconsistent across the participating centers. Only 37% of the 19 centers had a specific protocol for monitoring the depth of paralysis, and all of these protocols were based on train-of-four monitoring. Train-of-four monitoring involves stimulating a peripheral nerve, typically the ulnar or facial nerve, to assess the strength of muscle contractions in response to electrical impulses. Among the patients who received continuous infusions, 47.8% had at least one train-of-four recording during their treatment. However, patients who underwent monitoring had significantly longer infusion durations and received higher cumulative doses compared to those who were not monitored.

The study found that prolonged infusion of neuromuscular blocking agents, defined as exceeding 48 hours, was associated with a higher incidence of adverse outcomes. ICU-acquired weakness was diagnosed in 25% of patients, pressure ulcers in 14%, and ventilator-associated pneumonia in 26%. In multivariable analyses, a duration of infusion exceeding 48 hours was associated with a lower cumulative incidence of weaning success and higher incidences of ventilator-associated pneumonia. The sub-distribution hazard ratio for weaning success was 0.83, indicating that each additional day of exposure was linked to a reduced likelihood of successful liberation from the ventilator. These findings suggest that while short-term use may have a more favorable safety profile, extended exposure contributes to increased morbidity.

The relationship between train-of-four monitoring and patient outcomes was complex and somewhat paradoxical. In multivariable analyses, the use of monitoring was associated with both an increased incidence of ICU-acquired weakness and a reduced risk of ICU mortality. The odds ratio for ICU-acquired weakness was 2.90, while the hazard ratio for ICU mortality was 0.55. The authors suggest that this discrepancy may be due to residual confounding, where patients who are more severely ill and require longer paralysis are more likely to be monitored. Alternatively, centers that adopt structured monitoring protocols may provide a higher overall quality of care, leading to improved survival rates independent of the specific effects of the monitoring itself.

The study underscores the heterogeneity of neuromuscular blocking agent use in real-world settings. Unlike randomized controlled trials, which often limit the duration of paralysis to 48 hours, this observational study found that in half of the patients, the infusion exceeded this threshold. In a quarter of patients who were monitored, the infusion extended beyond 100 hours. This deviation from protocolized trial conditions highlights the gap between clinical trial evidence and daily practice. The authors emphasize that the decision to continue paralysis beyond 48 hours should be made with caution, given the associated risks of complications and prolonged mechanical ventilation.

Limitations of the study include its observational design, which prevents the establishment of causality between the duration of paralysis or monitoring practices and patient outcomes. The population was heterogeneous, with various admission diagnoses and indications for treatment, which complicates the interpretation of survival data. Additionally, the data were collected prior to the widespread changes in ICU practices brought about by the pandemic and the publication of recent large-scale randomized trials. The study did not collect data on corticosteroid use, which can also contribute to ICU-acquired weakness, nor did it detail the specific reasons for paralysis within the ARDS subgroup, such as whether it was used as early protocolized therapy or as rescue treatment.

Despite these limitations, the study provides valuable insights into the current landscape of neuromuscular blocking agent use in Europe. It reinforces the need for standardized management protocols to optimize the use of these agents and minimize associated complications. The findings suggest that while monitoring is a recommended practice, its implementation in real-world settings may inadvertently contribute to overuse if not carefully managed. Future research should focus on randomized controlled trials to determine the true role of monitoring strategies in improving patient outcomes and on the long-term functional consequences of prolonged paralysis in critically ill patients.

The data highlight the necessity for ongoing evaluation of monitoring technologies and protocols to ensure that these powerful tools are used safely and effectively in the intensive care unit.

Subject of Research: Use and monitoring of neuromuscular blocking agents in intensive care units

Article Title: Neuromuscular blockade and their monitoring in the intensive care unit: a multicenter observational prospective study

Article References: Hermann, B., Decormeille, G., Gobé, T., Mangeard, N., Maamar, A., Sayadi, S., Pernod, B., Robquin, N., Ponthus, J.-P., Le Potier, S., Bouju, P., Balabanian, A., Frouin, A., Moschietto, S., Jacq, G., Villemont, E., Houbé, C., Queyreau, A., Morand, C., … Barbar, S. D. (2025). Neuromuscular blockade and their monitoring in the intensive care unit: a multicenter observational prospective study. Annals of Intensive Care, 15(1), Article 167. https://doi.org/10.1186/s13613-025-01591-4

Image Credits: AI Generated

DOI: 10.1186/s13613-025-01591-4

Keywords: neuromuscular blocking agents, intensive care unit, mechanical ventilation, acute respiratory distress syndrome, train-of-four monitoring, ICU-acquired weakness, observational study, critical care, Neuromuscular, blockade, monitoring, intensive