Abstract
Background. Acute respiratory distress syndrome (ARDS) mortality is lower among subjects participating in randomized controlled trials (RCT) versus those in observational studies. Excluding potential subjects with inordinately high mortality risk is necessary to prevent masking the impact of potentially effective treatments. We inquired whether observed mortality differed between RCT-eligible and RCT-ineligible subjects managed with varying degrees of lung-protective ventilation (LPV) in a non-research setting.
Methods. This single-center, retrospective, observational study utilized quality assurance data for monitoring LPV practices based upon National Institutes of Health ARDS Network (ARDSNet) protocols. Between 2002-2017, 1975 subjects meeting 1994 consensus criteria for ALI/ARDS (later reclassified by the Berlin definition) were prospectively identified and classified as RCT-eligible or RCT-ineligible based upon the original ARDSNet exclusion criteria for co-morbidities or moribund condition. Demographic and physiologic data from the day of ARDS onset and outcome data were. Survival was modeled by mixed-effect Cox proportional hazard model adjusted for age, both illness and lung injury severity plateau pressure (Pplat) and formal use of the ARDSNet ventilator protocol. The primary outcome of interest was all-cause mortality during the first 90 days following ARDS onset.
Results. Day 90 mortality was 27.6% in RCT-eligible patients vs. 50.4% in RCT-ineligible patients: HR (95% CI) of 0.47 (0.41-0.54), P < 0.001. Regardless of RCT-eligibility or ineligibility criteria, achieving a Pplat < 30 cmH2O was associated with lower mortality. Overall, mortality risk was lower in patients managed by protocol vs. clinician-directed LPV (HR = 0.60 (95%CI = 0.52 - 0.69), p < 0.001), even among those in whom Pplat was < 30 cmHH2O (HR = 0.64 (0.54-0.76), p<0.001).
Conclusion. Mortality in non-research, RCT-eligible patients was substantially lower compared to RCT-ineligible patients. Managing non-research ARDS patients by keeping Pplat < 30 cmH2O and formal use of a lung-protective ventilation protocol significantly reduces mortality risk.
Footnotes
- Correspondence Author:
Richard Kallet, 2070 Fell St #1 San Francisco, CA. 94117, richkallet{at}gmail.com
- Received March 18, 2021.
- Accepted April 21, 2021.
- Copyright © 2021 by Daedalus Enterprises