Variation in Early Management Practices in Moderate-to-Severe ARDS in the United States: The Severe ARDS: Generating Evidence Study

Abstract

Background: Although specific interventions previously demonstrated benefit in patients with ARDS, use of these interventions is inconsistent, and patient mortality remains high. The impact of variability in center management practices on ARDS mortality rates remains unknown.

Research question: What is the impact of treatment variability on mortality in patients with moderate to severe ARDS in the United States?

Study design and methods: We conducted a multicenter, observational cohort study of mechanically ventilated adults with ARDS and Pao₂ to Fio₂ ratio of ≤ 150 with positive end-expiratory pressure of ≥ 5 cm H₂O, who were admitted to 29 US centers between October 1, 2016, and April 30, 2017. The primary outcome was 28-day in-hospital mortality. Center variation in ventilator management, adjunctive therapy use, and mortality also were assessed.

Results: A total of 2,466 patients were enrolled. Median baseline Pao₂ to Fio₂ ratio was 105 (interquartile range, 78.0-129.0). In-hospital 28-day mortality was 40.7%. Initial adherence to lung protective ventilation (LPV; tidal volume, ≤ 6.5 mL/kg predicted body weight; plateau pressure, or when unavailable, peak inspiratory pressure, ≤ 30 mm H₂O) was 31.4% and varied between centers (0%-65%), as did rates of adjunctive therapy use (27.1%-96.4%), methods used (neuromuscular blockade, prone positioning, systemic steroids, pulmonary vasodilators, and extracorporeal support), and mortality (16.7%-73.3%). Center standardized mortality ratios (SMRs), calculated using baseline patient-level characteristics to derive expected mortality rate, ranged from 0.33 to 1.98. Of the treatment-level factors explored, only center adherence to early LPV was correlated with SMR.

Interpretation: Substantial center-to-center variability exists in ARDS management, suggesting that further opportunities for improving ARDS outcomes exist. Early adherence to LPV was associated with lower center mortality and may be a surrogate for overall quality of care processes. Future collaboration is needed to identify additional treatment-level factors influencing center-level outcomes.

Trial registry: ClinicalTrials.gov; No.: NCT03021824; URL: www.clinicaltrials.gov.

Keywords: ARDS; corticosteroids; extracorporeal membrane oxygenation; mechanical ventilation; neuromuscular blockade; prone positioning.

Graphical abstract

Figure 1

Flow chart showing patient screening and enrollment.

Figure 2

A, B, Graphs showing ARDS management. A, Mean day 1 tidal volume (Vt) and percentage nonadherence to early lung protective ventilation across centers. B, Variability in frequency of adjunctive therapy use by combinations by center. Twenty-nine different combinations of therapy were used, with different frequencies at each center. ECMO = extracorporeal membrane oxygenation; HFOV = high frequency oscillatory ventilation; LPV = lung protective ventilation; NMB = neuromuscular blockade; PBW = predicted body weight; PVD = pulmonary vasodilator.

Figure 3

Forest plot showing baseline variables associated with 28-day hospital mortality. Results of primary outcome multivariate generalized mixed-effect model for 28-day hospital mortality, with fixed terms for baseline variables and random effect for center to investigate which baseline factors are associated with primary outcome. ESRD = end-stage renal disease; F = female; M = male; P:F = Pao₂ to Fio₂ ratio; SOFA, Sequential Organ Failure Assessment; Tx = transfusion; V_T = tidal volume.

Figure 4

A, B, Graphs showing variability in center mortality. A, Twenty-eight-day hospital mortality by center. Unadjusted 28-day hospital mortality ranged from 16.7% to 73.3%. B, Variation in risk-adjusted mortality by center. Standardized mortality ratios (SMRs) varied by center, between 0.33 and 1.98.

Figure 5

A-D, Scatterplots showing SMR vs center metrics. A, SMR vs day 1 V_T. B, SMR vs rate of day 1 nonadherence to LPV (V_T < 6.5 mL/kg predicted body weight, plateau pressure plateau pressure or peak inspiratory pressure ≤ 30 cm H₂O). C, SMR vs day 1 PEEP. D, SMR vs rate of use of any adjunctive therapy. LPV = lung protective ventilation; PEEP = positive end-expiratory pressure; SMR = standardized mortality ratio; V_T = tidal volume.