Compliance Phenotypes in Early Acute Respiratory Distress Syndrome before the COVID-19 Pandemic

Abstract

Rationale: A novel model of phenotypes based on set thresholds of respiratory system compliance (Crs) was recently postulated in context of coronavirus disease (COVID-19) acute respiratory distress syndrome (ARDS). In particular, the dissociation between the degree of hypoxemia and Crs was characterized as a distinct ARDS phenotype.Objectives: To determine whether such Crs-based phenotypes existed among patients with ARDS before the COVID-19 pandemic and to closely examine the Crs-mortality relationship.Methods: We undertook a secondary analysis of patients with ARDS, who were invasively ventilated on controlled modes and enrolled in a large, multinational, epidemiological study. We assessed Crs, degree of hypoxemia, and associated Crs-based phenotypic patterns with their characteristics and outcomes.Measurements and Main Results: Among 1,117 patients with ARDS who met inclusion criteria, the median Crs was 30 (interquartile range, 23-40) ml/cm H₂O. One hundred thirty-six (12%) patients had preserved Crs (≥50 ml/cm H₂O; phenotype with low elastance ["phenotype L"]), and 827 (74%) patients had poor Crs (<40 ml/cm H₂O; phenotype with high elastance ["phenotype H"]). Compared with those with phenotype L, patients with phenotype H were sicker and had more comorbidities and higher hospital mortality (32% vs. 45%; P < 0.05). A near complete dissociation between Pa_O2/Fi_O2 and Crs was observed. Of 136 patients with phenotype L, 58 (43%) had a Pa_O2/Fi_O2 < 150. In a multivariable-adjusted analysis, the Crs was independently associated with hospital mortality (adjusted odds ratio per ml/cm H₂O increase, 0.988; 95% confidence interval, 0.979-0.996; P = 0.005).Conclusions: A wide range of Crs was observed in non-COVID-19 ARDS. Approximately one in eight patients had preserved Crs. Pa_O2/Fi_O2 and Crs were dissociated. Lower Crs was independently associated with higher mortality. The Crs-mortality relationship lacked a clear transition threshold.

Keywords: acute respiratory distress syndrome; intensive care; mechanical ventilation; phenotype; respiratory system compliance.

Figure 1.

Patient flowchart to show subset selection. *Patients who developed ARDS within 1–2 days of developing acute hypoxemic respiratory failure and who were managed with invasive mechanical ventilation. **Volume Assist-Control ventilation, pressure-controlled ventilation, airway pressure release ventilation, or pressure-regulated volume control were considered as controlled modes of mechanical ventilation. ^#No spontaneous ventilation was considered when the set respiratory rate was equal to actual respiratory rate ± 1. ARDS = acute respiratory distress syndrome; Crs = respiratory system compliance; ECMO = extracorporeal membrane oxygenation; PEEP = positive end-expiratory pressure.

Figure 2.

Distribution of (A) Pa_O2/Fi_O2 and (B) Crs in the cohort and the relationship between Crs and the Pa_O2/Fi_O2 ratio. Crs = respiratory system compliance; IQR = interquartile range.

Figure 3.

(A) Locally estimated scatterplot smoothing curves and (B) predicted marginal probabilities with 95% confidence intervals for hospital mortality versus Crs. Crs = respiratory system compliance; OR = odds ratio.