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

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.