Daily Ards Research Analysis

BACKGROUND: Invasive ventilation saves lives but carries major risks, including ventilation-associated lung damage and long-term functional impairment. Data from recent studies compel reassessment of the evidence for every step of the clinical treatment pathway. METHODS: This updated clinical practice guideline is based on pertinent publications retrieved by a systematic search in Medline, Embase, and the Cochrane Library up to April 2023, supplemented by further high-quality studies published up to June 2024. The recommendations were developed in evidence-to-decision-frameworks (EtDF) according to GRADE, with the participation of intensive-care nurses and early career clinician-scientists. RESULTS: For patients in acute respiratory failure, it is suggested that noninvasive respiratory support techniques should be used so that intubation can be avoided. It is further suggested that spontaneous breathing should be enabled early on during invasive ventilation. For the first time, the use of various techniques for titrating the positive end-expiratory pressure (PEEP) is suggested for patients with moderate to severe acute respiratory distress syndrome (ARDS). In such patients, techniques aiming at a higher PEEP can lower mortality by 9% in absolute terms (95% confidence interval [1; 16]) compared to lower-PEEP strategies. Strong recommendations are given against the routine use of muscle relaxation or corticosteroid therapy in moderate to severe ARDS. For patients with ARDS with a persistent, severe gas exchange disturbance after conservative options have been exhausted, veno-venous extracorporeal membrane oxygenation should be considered. VvECMO for patients with severe ARDS should be carried out at centers that are experienced in treating patients with severe ARDS and that fulfill specific structural requirements. CONCLUSION: The goals of ventilator therapy should be to enable spontaneous breathing as soon as possible, keep respiratory parameters in the protective range, and adjust PEEP individually. Muscle relaxation or corticosteroids should not be part of the routine treatment of moderately severe ARDS.

OBJECTIVES: Paediatric acute respiratory distress syndrome (PARDS) is a heterogeneous condition and identifying a specific biomarker remains a challenge. We aimed to validate the association of plasma soluble receptor for advanced glycation end-products (sRAGE) and angiopoietin-2 (Ang-2) with PARDS diagnosis, and its prognostic performance. METHODS: This prospective observational study included children with PARDS and non-PARDS critical illness. Plasma sRAGE and Ang-2 levels were measured using enzyme-linked immunosorbent assays. Comparisons were made between PARDS versus non-PARDS critical illness and survivors versus non-survivors. Multivariable logistic regression was used to determine the association between biomarkers and intensive care unit (ICU) mortality after adjusting for age and the Pediatric Index of Mortality 3 score. RESULTS: 93 and 117 patients with PARDS and non-PARDS critical illness, respectively, were included in this study. Plasma sRAGE was higher in PARDS versus non-PARDS critical illness (2981 (1027 to 6198) vs 1575 (864 to 2994) pg/mL; p=0.002) and in non-survivors vs survivors (5323 (1647 to 8261) vs 1601 (864 to 3572); p<0.001). Plasma Ang-2 was elevated in non-survivors versus survivors (3054 (1760 to 6808) vs 1748 (845 to 3868); p=0.002), though there was no difference between PARDS and non-PARDS groups. In the multivariable model, sRAGE demonstrated an independent association with PARDS diagnosis (adjusted OR (aOR) 1.01 95% CI 1.01 to 1.02; p=0.003) and ICU mortality (aOR 1.02 (95% CI 1.01 to 1.03); p<0.001), whereas there was no association observed with Ang-2. CONCLUSION: Within an ICU cohort, only sRAGE demonstrated an association with the diagnosis of PARDS and ICU mortality, which remained after controlling for confounders.

RATIONALE: The unmet need for effective therapeutic strategies to address the bidirectional perturbation of the lung-brain axis following traumatic brain injury (TBI) or associated with Acute Lung Injury/Acute Respiratory Distress Syndrome (ALI/ARDS) is increasingly recognized. Contributing to this unmet need is the absence of reliable biomarkers that reflect the severity of lung-brain axis disruption. We assessed specific potential lung-brain axis biomarkers in TBI and ALI/ARDS subjects and explored the specific influence of exposure to mechanical ventilation. METHODS: Serum biomarker levels from TBI (n=97) and ARDS subjects (n=39) and healthy controls (n=46) were analyzed (MesoScale Discovery ELISA) utilizing a critical illness lung-brain axis biomarker panel (CILBA) that included DAMPS (eNAMPT, S100A8), inflammatory cytokines (IL-6, IL-1β, IL-1RA, TNF-α), vascular biomarkers (PSGL-1, ANG-2), and neurotrauma biomarkers (GFAP or Glial fibrillary acidic protein, NFL or neurofilament light chain, Tau). RESULTS: TBI and ARDS subjects demonstrated significant elevations in each biomarker (compared to controls) with two exceptions: PSGL-1 was exclusively elevated in ARDS and GFAP exclusively elevated in TBI. Mechanically ventilated subjects exposed exhibited significantly DAMP, vascular and neurotrauma biomarker elevations compared to unexposed subjects. With the exception of GFAP, Ang-2, and S100A8, biomarker elevations were linked to ICU days or mortality. CONCLUSIONS: These results highlight overlapping innate immunity dysregulation as a manifestation of lung-brain axis disruption in both TBI- and ARDS-exposed subjects with amplified dysregulation with mechanical ventilation. Additional longitudinal studies of well-phenotyped TBI and ARDS subjects may substantiate the prognostic value of biomarker analyses in assessing the severity of bidirectional lung-brain axis injuries.