Utilization and effect of neuromuscular blockade in a randomized trial of high-frequency oscillation.

Abstract

We evaluated characteristics associated with neuromuscular blockade (NMB) use, center-level variation, and whether NMB mediated excess mortality among patients assigned to high-frequency oscillatory ventilation (HFOV) in the OSCILLATE trial. NMB exposure was defined as receipt after randomization; the primary outcome was hospital mortality. Descriptive analyses compared NMB-exposed vs unexposed patients. Multivariable analyses included patients not on baseline NMB. Cox regression evaluated associations of patient- and center-level variables with NMB use. A log-normal frailty model evaluated center effects. Mediation analysis examined the effect of NMB in HFOV-assigned patients. 376/548 patients (39 centers) received post-randomization NMB, of whom 165 received baseline NMB. Patients receiving post-randomization NMB (vs. not) had worse lung mechanics and gas exchange, received more sedation and vasopressors (p<0.05), and had higher hospital mortality (44% vs. 34%, p=0.03). Mean airway pressure≥24 cmH2O, randomization to HFOV, and intensive care unit size ≥ 31 beds were associated with post-randomization NMB. After adjustment, center had a negligible effect on post-randomization NMB (median hazard ratio 1.01, p=0.047). NMB use did not mediate excess mortality among HFOV-allocated patients (p=0.80). In OSCILLATE, receipt of post-randomization NMB was associated with worse outcomes, but NMB use did not mediate HFOV-associated higher mortality.