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

Abstract

Background: Neuromuscular blocking agents may improve outcomes in specific conditions, including the early phase of acute respiratory distress syndrome. However, neuromuscular blocking agents are associated with side effects and uncertainty persists regarding their optimal dosing and efficacy. Our objective was to describe the use of neuromuscular blocking agents in a real-world setting.

Methods: We conducted a multicenter, prospective observational study, including adult patients who underwent invasive mechanical ventilation and received a continuous infusion of neuromuscular blocking agents. Patients were recruited across 19 intensive care units in France and Belgium.

Results: From November 16, 2019, to February 19, 2020, a total of 2248 patients were hospitalized and mechanically ventilated in 19 participating ICUs. Of these, 270 (12%) patients received at least one dose of neuromuscular blocking agents, and 232 (10.3%) received a continuous infusion. The main indications for neuromuscular blocking agents use were acute respiratory distress syndrome (61%), prevention of shivering during therapeutic hypothermia (16%) and patient-ventilator asynchrony (12%). Infusion was initiated in median at 0 [0-2] days after ICU admission, with a median duration of 38 [22-71] hours. Cisatracurium was the preferred agent (74%). Neuromuscular blocking agents monitoring by train-of-four was employed in 48% of patients. Intensive care unit-acquired weakness was diagnosed in 25% of patients, pressure ulcers in 14% and ventilator-associated pneumonia in 26%. The median lengths of mechanical ventilation and ICU stay were 9 [4-16] and 13 [6-22] days, and ICU mortality was 41%. In multivariable analyses, a duration of neuromuscular blocking agents infusion exceeding 48 hours was associated with a lower cumulative incidence of weaning success (SHR 0.83 [0.76, 0.91], p < 0.001) and higher incidences of ventilator-associated pneumonia, while neuromuscular blocking agents monitoring was associated with both increased intensive care unit-acquired weakness (OR 2.90 [1.2, 7.01], p = 0.018) and reduced ICU mortality (HR 0.55 [95%CI 0.32, 0.95], p = 0.032).

Conclusion: In our study, the prevalence of continuous neuromuscular blocking agents infusion among mechanically ventilated patients in the intensive care unit was 10.3%. While acute respiratory distress syndrome was the main indication, over one-third of patients received neuromuscular blocking agents for other reasons. A duration of neuromuscular blocking agents infusion exceeding 48 hours was associated with longer mechanical ventilation and increased complications. The role of neuromuscular blocking agents monitoring remains unclear. Trial registration ClinicalTrials.gov: NCT04028362 Registered on 18 July 2019, https://clinicaltrials.gov/study/NCT04028362 . The study was conducted by the French Intensive Care Society/Société de Réanimation de Langue Française Trial Group.

Keywords: Acute respiratory distress syndrome; Critical care; Mechanical ventilation; Neuromuscular blockade.

Fig. 1.

Flowchart

Fig. 2

Indications of continuous NMBA infusion and duration and doses of infusion according to indications. A Indications of continuous NMBA infusion. B Hourly and cumulative doses and duration of continuous NMBA infusion according to indications. Overall statistical comparisons were performed with the Kruskall-Wallis test and post-hoc comparisons were performed with pairwise Wilcoxon tests with false-discovery rate corrected p-values (ns: p≥0.05, *p < 0.05, **p < 0.01, ***p < 0.001 and ****p < 10^-4). ARDS: acute respiratory distress syndrome; ICP: intra-cranial pressure; P/V: patient-ventilator

Fig. 3

ICU and hospital outcomes according to continuous NMBA infusion duration. Outcomes according to continuous NMBA duration (less than 24h, 24h to 48h and more than 48h) in the whole population [upper panels, categorical (A) and continuous (B) outcomes] and in the ARDS population [lower panels, categorical (C) and continuous (D)]. Post-hoc comparisons were performed with pairwise Chi-square tests for the categorical outcome and pairwise Wilcoxon tests for the continuous outcome. All p-values were corrected for multiple comparisons using the false-discovery rate method (ns: p ≥ 0.05, *p < 0.05, **p < 0.01, ***p < 0.001 and ****p < 10^-4). FDR: false-discovery rate; ICU: intensive care unit; ICU-AW: ICU-acquired weakness; IMV: invasive mechanical ventilation; NMBA: neuromuscular blocking agents; VAP: ventilator-associated pneumonia