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

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.

The ex vivo perfused human lung is resistant to injury by high-dose S. pneumoniae bacteremia.

Few patients with bacteremia from a nonpulmonary source develop acute respiratory distress syndrome (ARDS). However, the mechanisms that protect the lung from injury in bacteremia have not been identified. We simulated bacteremia by adding Streptococcus pneumoniae to the perfusate of the ex vivo perfused human lung model. In contrast to a pneumonia model in which bacteria were instilled into the distal air spaces of one lobe, injection of high doses of S. pneumoniae into the perfusate was not associated with alveolar epithelial injury as demonstrated by low protein permeability of the alveolar epithelium, intact alveolar fluid clearance, and the absence of alveolar edema. Unexpectedly, the ex vivo human lung rapidly cleared large quantities of S. pneumoniae even though the perfusate had very few intravascular phagocytes and lacked immunoglobulins or complement. The bacteria were cleared in part by the small number of neutrophils in the perfusate, alveolar macrophages in the airspaces, and probably by interstitial pathways. Together, these findings identify one mechanism by which the lung and the alveolar epithelium are protected from injury in bacteremia.

Severity of inhalation injury and risk of nosocomial pneumonia: a retrospective cohort study.

BACKGROUND: The impact of inhalation injury on risk of nosocomial pneumonia, an important complication in burn patients, is not well established. RESEARCH QUESTION: Is more severe inhalation injury associated with increased risk of nosocomial pneumonia? STUDY DESIGN AND METHODS: We performed a retrospective cohort study of patients with suspected inhalation injury admitted to a regional burn center from 2011 to 2022 who underwent diagnostic bronchoscopy within 48 hours of admission. We estimated the association of high-grade inhalation injury (abbreviated injury score [AIS] 3-4) versus low-grade inhalation injury (AIS 1-2) with nosocomial pneumonia (NP) adjusted for age, burn size, and comorbid obstructive lung disease. Death and hospital discharge were considered competing risks. RESULTS: Of the 245 patients analyzed, 51 (21%) had high-grade injury, 180 (73%) had low-grade injury, and 14 (6%) had no inhalation injury. Among the 236 patients hospitalized for >48 hours, NP occurred in 24/50 (48%) patients in the high-grade group, 54/172 (31%) in the low-grade group, and 2/14 (14%) in the no inhalation injury group. High-grade (vs low-grade) inhalation injury was associated with higher hazard of NP in both the proportional cause-specific hazard model (CSHR 2.04; 95% CI, 1.26-3.30; p=0.004) and Fine-Gray subdistribution hazards model (SHR for NP, 2.24; 95% CI, 1.38-3.64; p=0.001). INTERPRETATION: Among patients with inhalation injury, more severe injury was associated with higher hazard of NP in competing risk analysis. Additional research is needed to investigate mechanisms that may explain the relationship between inhalation injury and NP and to identify more effective prevention strategies.

Ventilatory Ratio Is a Valuable Prognostic Indicator in an Observational Cohort of Patients With ARDS.

BACKGROUND: How indices specific to respiratory compromise contribute to prognostication in patients with ARDS is not well characterized in general clinical populations. The primary objective of this study was to identify variables specific to respiratory failure that might add prognostic value to indicators of systemic illness severity in an observational cohort of subjects with ARDS. METHODS: Fifty subjects with ARDS were enrolled in a single-center, prospective, observational cohort. We tested the contribution of respiratory variables (oxygenation index, ventilatory ratio [VR], and the radiographic assessment of lung edema score) to logistic regression models of 28-d mortality adjusted for indicators of systemic illness severity (the Acute Physiology and Chronic Health Evaluation [APACHE] III score or severity of shock as measured by the number of vasopressors required at baseline) using likelihood ratio testing. We also compared a model utilizing APACHE III with one including baseline number of vasopressors by comparing the area under the receiver operating curve (AUROC). RESULTS: VR significantly improved model performance by likelihood ratio testing when added to APACHE III (P = .036) or the number of vasopressors at baseline (P = .01). Number of vasopressors required at baseline had similar prognostic discrimination to the APACHE III. A model including the number of vasopressors and VR (AUROC 0.77 [95% CI 0.64-0.90]) was comparable to a model including APACHE III and VR (AUROC 0.81 [95% CI 0.68-0.93]; P for comparison = .58.). CONCLUSIONS: In this observational cohort of subjects with ARDS, the VR significantly improved discrimination for mortality when combined with indicators of severe systemic illness. The number of vasopressors required at baseline and APACHE III had similar discrimination for mortality when combined with VR. VR is easily obtained at the bedside and offers promise for clinical prognostication.