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Observational Study
. 2020 Nov 1;202(9):1244-1252.
doi: 10.1164/rccm.202005-2046OC.

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

Rakshit Panwar  1   2 , Fabiana Madotto  3 , John G Laffey  4   5   6 , Frank M P van Haren  7   8   9
Affiliations
Observational Study

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

Rakshit Panwar et al. Am J Respir Crit Care Med. .

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 PaO2/FiO2 and Crs was observed. Of 136 patients with phenotype L, 58 (43%) had a PaO2/FiO2 < 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. PaO2/FiO2 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.

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Figures

Figure 1.
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.
Figure 2.
Distribution of (A) PaO2/FiO2 and (B) Crs in the cohort and the relationship between Crs and the PaO2/FiO2 ratio. Crs = respiratory system compliance; IQR = interquartile range.
Figure 3.
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.
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