2024

Respiratory drive heterogeneity associated with systemic inflammation and vascular permeability in acute respiratory distress syndrome

Baedorf-Kassis, Elias; Murn, Michael; Dzierba, Amy L.; Serra, Alexis L.; Garcia, Ivan; Minus, Emily; Padilla, Clarissa; Sarge, Todd; Goodspeed, Valerie M.; Matthay, Michael A.; Gong, Michelle N.; Cook, Deborah; Loring, Stephen H.; Talmor, Daniel; Beitler, Jeremy R.

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 PES0.1, 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 (PES0.1 range of 0–5.1 cm H₂O). 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 PES0.1 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 PES0.1. Risk of death was less with moderate drive (PES0.1 of 0.5–2.9 cm H₂O) 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.