Elastance May Determine the Neuromuscular Blockade Effect on Mortality in Acute Respiratory Distress Syndrome

Rationale: Patients with acute respiratory distress syndrome (ARDS) have a reduction in functional lung volume that results in increased respiratory system elastance (Ers); however, the extent of this increase varies by patient. Patients with high Ers are at risk of excess lung-distending pressures and may derive greater clinical benefit from neuromuscular blockade (NMB). Objectives: We sought to evaluate whether the effect of early NMB administration on mortality varies according to baseline physiological and biological biomarkers of lung injury, including Ers. Methods: We conducted a secondary analysis of the Reevaluation of Systemic Early Neuromuscular Blockade, or ROSE, trial. Bayesian logistic regression modeling was used to estimate the posterior probability of NMB effect moderation by baseline Ers, ventilatory ratio, and select ARDS plasma biomarkers on 90-day mortality. Measurements and Main Results: The probability of mortality benefit with NMB increased substantially with higher baseline Ers (posterior probability of interaction, 92%; interaction odds ratio = 0.76; 90% credible interval = 0.59–0.99). In patients with an Ers ≥2 cm H₂O/(ml/kg), the posterior probability of benefit was 96% (median absolute risk reduction, 9%; 90% credible interval = 0.5–17.9). The effect of NMB did not vary meaningfully according to ventilatory ratio (posterior probability of interaction, 62%) or baseline plasma levels of receptor for advanced glycation end-products, tumor necrosis factor receptor-1, IL-6, or IL-8 (posterior probabilities of interaction: 12%, 18%, 44%, and 22% respectively). Conclusions: These findings suggest that the mortality benefit of NMB varies with baseline Ers. High Ers may represent a physiological phenotype of acute respiratory distress syndrome. Future prospective testing to confirm benefit in this potentially treatment-responsive group is needed.