Daily Ards Research Analysis

RATIONALE: Neuromuscular blocking agents (NMBAs) show potential benefits on mortality and other complications of acute respiratory distress syndrome (ARDS) in adult patients. Evidence-based decisions and processes ensure appropriate use of neuromuscular blockade in adult patients with ARDS. OBJECTIVES: The objective of these guidelines was to develop evidence-based recommendations for the administration of NMBAs in critically ill adult patients with ARDS. DESIGN: The American College of Critical Care Medicine Board convened a 21-member multidisciplinary panel of experts in critical care medicine, nursing, respiratory therapy, pharmacology, surgery, neurology, and anesthesiology. The panel included two expert methodologists specialized in developing evidence-based recommendations in alignment with the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. Conflict-of-interest policies were strictly followed during all phases of guidelines development including task force selection and voting. METHODS: The panel members identified and formulated five Population, Intervention, Comparison, and Outcome questions. We conducted a systematic review for each question to identify the best available evidence, statistically analyzed the evidence, and assessed the certainty of the evidence using the GRADE methodology. We used the GRADE evidence-to-decision framework to formulate the recommendations. RESULTS: The panel generated two conditional recommendations. One recommendation is to use NMBAs in adults with ARDS with Pao2/Fio2 less than 150. For the other recommendations, there was equipoise in the recommendation for and against using titratable vs. fixed-dose NMBA dosing, a monitoring-based strategy for assessing depth of sedation and analgesia in adults with ARDS before initiating or while receiving neuromuscular blockade, and administration of NMBAs for patients who are proned, due to overall lack of evidence in critically ill patients and due to considerations of patient safety and experience concerns. CONCLUSIONS: These guidelines provide additional perspectives on the use of NMBA in patients with ARDS, recognizing that institutional and patient-specific considerations must help to guide the decision-making process.

IMPORTANCE: Despite continuous improvements in neonatal resuscitation and stabilization in the last decades, thermal management immediately after birth remains an unresolved issue in preterm infants. OBJECTIVE: To compare 2 strategies of thermal management (plastic wrapping with or without drying) for preventing heat loss at birth in very preterm infants. DESIGN, SETTING, AND PARTICIPANTS: This multicenter, unblinded, randomized clinical trial was conducted among very preterm infants (birth weight <1500 g and/or gestational age ≤30 weeks 6 days) at 21 tertiary care hospitals in Italy from February 21, 2023, to July 18, 2024. INTERVENTIONS: Eligible neonates were randomly allocated to either drying before plastic wrapping in the delivery room (intervention arm) or plastic wrapping without drying (control arm). MAIN OUTCOMES AND MEASURES: The primary outcome was the proportion of participants with normothermia (36.5-37.5 °C) at admission to the neonatal intensive care unit (NICU). The secondary outcomes included hypothermia (<36.5 °C), moderate to severe hypothermia (<36.0 °C), and hyperthermia (>37.5 °C) at NICU admission, temperature at 1 hour after NICU admission, intraventricular hemorrhage, respiratory distress syndrome, late-onset sepsis, bronchopulmonary dysplasia, and mortality before hospital discharge. RESULTS: Overall, 354 very preterm infants were randomized (180 [50.8%] female; mean [SD] gestational age, 28.6 [2.5] weeks); all received the allocated intervention and were included in the analysis. Normothermia at NICU admission was achieved in 81 of 177 dried infants (45.8%) and 82 of 177 undried infants (46.3%; risk ratio, 0.99; 95% CI, 0.79-1.24). The mean (SD) neonatal temperature at NICU admission was 36.4 °C (0.8 °C) in dried neonates and 36.5 °C (0.7 °C) in undried neonates (mean difference, -0.1 °C; 95% CI, -0.2 °C to 0.1 °C). In-hospital mortality included 26 of 177 dried neonates (14.7%) and 10 of 177 undried neonates (5.6%) (unadjusted risk ratio, 2.60; 95% CI, 1.29-5.23). The other secondary outcome measures were not different between the 2 arms. CONCLUSIONS AND RELEVANCE: In this multicenter randomized clinical trial, drying before plastic wrapping provided no benefit to very preterm infants in maintaining normothermia at NICU admission. Most deaths could be expected due to the compromised profile of the neonates, with no pathophysiological explanation related to the trial interventions. Approximately half of the infants were outside the normal thermal range at NICU admission; hence, thermal management remains a challenge requiring further investigations. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05740072.

Veno-venous extracorporeal membrane oxygenation (VV-ECMO) is a critical intervention for acute respiratory distress syndrome, yet its application is frequently associated with brain injury, which significantly impacts patient prognosis. Heat shock protein B1 (HSPB1) is strongly involved in neuroinflammatory responses; however, its role in brain injury related to VV-ECMO remains to be elucidated. We established a VV-ECMO rat model to evaluate the neuroprotective effects of inhibiting the HSPB1-NF-κB axis (HSPB1 inhibitor J2, 1 mg/kg, ip). Serum levels of the brain injury biomarkers S100β and NSE were measured using ELISA, histopathological features of brain injury were evaluated by hematoxylin and eosin staining, and microglial and astrocyte activation was assessed through immunofluorescence staining. Western blotting and real-time quantitative PCR were employed to examine the effects of J2 on the expression of Il-1β, Il-6, Tnf-α, and the activation of the NF-κB signaling pathway. We observed that, following the establishment of the VV-ECMO model, brain injury was associated with an increase in neuroinflammatory responses, with both HSPB1 expression and the NF-κB signaling pathway being significantly upregulated. Administration of J2 alleviated brain injury, as indicated by reduced activation of microglia and astrocytes, decreased levels of Il-1β, Il-6, and Tnf-α, and significant suppression of the NF-κB signaling pathway. Our findings suggest that the HSPB1-NF-κB axis serves as a key mediator of neuroinflammation during VV-ECMO, providing important insights into the molecular mechanisms underlying VV-ECMO-related brain injury and offering a rationale for future studies.