Respiratory drive heterogeneity associated with systemic inflammation and vascular permeability in acute respiratory distress syndrome
Elias Baedorf-Kassis, Michael Murn, Amy Dzierba, Alexis Serra, Ivan Garcia, Emily Minus, Clarissa Padilla, Todd Sarge, Valerie Banner‐Goodspeed, Michael A. Matthay, Michelle N. Gong, Deborah Cook, Stephen H. Loring, Daniel Talmor, Jeremy R. Beitler, for the EPVent-2 Study Group, Daniel Talmor, Todd Sarge, Valerie Banner‐Goodspeed, Emily Fish, Sayuri P. Jinadasa, R Ritz, Joseph Previtera, Michelle N. Gong, Lawrence Lee, Jeremy R. Beitler, Deborah Cook, France Clarke, Tom Piraino, Joseph E. Levitt, Rosemary Vojnik, Pauline Park, Kristin Brierley, Carl F Haas, Andrew Weirauch, Eddy Fan, Andrea Matté, R. Scott Harris, Mamary Kone, Stephen O. Heard, Karen Longtine, François Lellouche, Pierre-Alexandre Bouchard, Lewis Rubinson, Jennifer McGrain, Donald Griesdale, Denise Foster, Richard A. Oeckler, Amy Amsbaugh, Edgar Jiménez, Valerie Danesh
Abstract
Abstract Background In acute respiratory distress syndrome (ARDS), respiratory drive often differs among patients with similar clinical characteristics. Readily observable factors like acid–base state, oxygenation, mechanics, and sedation depth do not fully explain drive heterogeneity. This study evaluated the relationship of systemic inflammation and vascular permeability markers with respiratory drive and clinical outcomes in ARDS. Methods ARDS patients enrolled in the multicenter EPVent-2 trial with requisite data and plasma biomarkers were included. Neuromuscular blockade recipients were excluded. Respiratory drive was measured as P ES 0.1, the change in esophageal pressure during the first 0.1 s of inspiratory effort. Plasma angiopoietin-2, interleukin-6, and interleukin-8 were measured concomitantly, and 60-day clinical outcomes evaluated. Results 54.8% of 124 included patients had detectable respiratory drive (P ES 0.1 range of 0–5.1 cm H 2 O). Angiopoietin-2 and interleukin-8, but not interleukin-6, were associated with respiratory drive independently of acid–base, oxygenation, respiratory mechanics, and sedation depth. Sedation depth was not significantly associated with P ES 0.1 in an unadjusted model, or after adjusting for mechanics and chemoreceptor input. However, upon adding angiopoietin-2, interleukin-6, or interleukin-8 to models, lighter sedation was significantly associated with higher P ES 0.1. Risk of death was less with moderate drive (P ES 0.1 of 0.5–2.9 cm H 2 O) compared to either lower drive (hazard ratio 1.58, 95% CI 0.82–3.05) or higher drive (2.63, 95% CI 1.21–5.70) ( p = 0.049). Conclusions Among patients with ARDS, systemic inflammatory and vascular permeability markers were independently associated with higher respiratory drive. The heterogeneous response of respiratory drive to varying sedation depth may be explained in part by differences in inflammation and vascular permeability.