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. 2025 Aug 6.
doi: 10.1007/s00134-025-08064-z. Online ahead of print.

Heterogenous treatment effect of neuromuscular blocking agents for moderate-to-severe ARDS: a post hoc Markov model re-analysis of the ACURASYS trial

Michael Brunini  1 , Jean-Marie Forel  2   3 , Xavier Muracciole  4 , Antoine Roch  2   3 , Dominique Barbolosi  5 , Laurent Papazian  6   7
Affiliations

Heterogenous treatment effect of neuromuscular blocking agents for moderate-to-severe ARDS: a post hoc Markov model re-analysis of the ACURASYS trial

Michael Brunini et al. Intensive Care Med. .

Abstract

Purpose: The beneficial effects of systematic cisatracurium administration observed in the ACURASYS randomized, multicenter, double-blinded trial may depend on patient-specific factors. This post hoc analysis aimed to explore whether the impact of cisatracurium on mortality varies with baseline characteristics.

Methods: A Markov chain analysis was conducted using daily clinical states from inclusion to day 90: death (state 0), under mechanical ventilation (state 1), or weaned and alive at day 90 (state 2). Patient trajectories were modeled accordingly.

Results: Among the 321 included patients, subgroup analysis following univariate analysis focused on 130 individuals under 60 years with non-fatal McCabe scores. Within this subgroup, cisatracurium administration and absence of vasopressor use significantly reduced the probability of remaining ventilated. Estimated survival increased therefore from 0.63 (placebo group, N = 62) to 0.93 (cisatracurium group, N = 68). In contrast, among patients with a rapidly or ultimately fatal prognosis according to McCabe score, the probability of survival did not differ substantially between the placebo and cisatracurium groups. Among patients with a PaO2:FiO2 ratio ≤ 100 mmHg at inclusion (N = 65), the estimated survival rate at day 90 was 0.93 in the cisatracurium arm compared with 0.63 in the placebo arm. For patients with a PaO2:FiO2 ratio > 100 mmHg at inclusion (N = 98), the corresponding survival rates were 0.92 and 0.63, respectively. In patients aged ≥ 60 years (N = 158), the daily probability of remaining mechanically ventilated was not influenced by any covariate, including the administration of cisatracurium. These results were confirmed by the performed simulations.

Conclusion: The systematic and short-term administration of cisatracurium in patients with moderate-to-severe ARDS appears to confer greater survival benefit in those with a higher baseline life expectancy. Further validation through retrospective and prospective studies is warranted.

Keywords: Acute respiratory distress syndrome (ARDS); Cisatracurium; Markov chain analysis; Mechanical ventilation; Mortality predictors.

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Conflict of interest statement

Declarations. Conflicts of interest: LP received consultancy fees from Air Liquide MS, Maquet, Faron, and MSD. MB, JMF, XM, AR, and DB have no conflicts of interest. Financial support: No financial support. Ethics approval: Not applicable. The ACURASYS study has been independently reviewed and approved by an Institutional Review Board. Consent to participate: Not applicable. Consent for publication: Not applicable.

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