Daily Ards Research Analysis

BACKGROUND: This study aimed to evaluate the safety and efficacy of inhaled pegylated adrenomedullin (PEG-ADM) for the management of acute respiratory distress syndrome in critically ill patients on mechanical ventilation. METHODS: A Phase 2a/b randomised, double-blind, placebo-controlled multicentre trial was conducted. Patients with acute respiratory distress syndrome were assigned to receive PEG-ADM 960 μg or 1920 μg, or placebo. The primary endpoints were safety, efficacy, and ventilator-free survival at Day 28. Efficacy was assessed using ventilator-free survival and the clinical utility index, a composite endpoint that includes extravascular lung water index, oxygenation index, non-pulmonary Sequential Organ Failure Assessment score. RESULTS: Ninety patients were randomised (PEG-ADM 960 μg: n = 29; PEG-ADM 1920 μg: n = 30; placebo: n = 31). Both dosages of PEG-ADM were well tolerated, with adverse event profiles similar to placebo. However, no significant efficacy was observed on the clinical utility index. Ventilator-free survival at Day 28 was lower in the PEG-ADM 960 μg group (52%) compared with the PEG-ADM 1920 μg (67%) and placebo (65%) groups. No significant differences were noted in overall mortality or the need for continued ventilation at Days 28 and 60. CONCLUSION: Inhaled PEG-ADM was well tolerated in patients with acute respiratory distress syndrome, but it did not improve clinical outcomes, which led to the early discontinuation after the first part of the trial for futility. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04417036 (date of registration: 4 June 2020).

BACKGROUND: The use of antenatal corticosteroids (ACS) in mothers less than 34 weeks' period of gestation has shown promising results with significant reduction in neonatal mortality and morbidities in high income settings. This study was carried out to assess the effectiveness of ACS in terms of neonatal outcome in less than 34 weeks in resource limited settings. METHODS: A prospective study was conducted from 15 March 2022 to 14 March 2023 among the babies born before 34 weeks' period of gestation (POG), in Paropakar maternity hospital, Nepal. Descriptive statistics using frequency and percentages was used to describe the socio-demographic, obstetric and neonatal characteristics. Multi-variable logistic regression analysis was done to assess the significance of ACS against various neonatal conditions. RESULTS: Out of 358 preterm neonates (<34 weeks), 206 were born to mothers who received ACS and 152 to mothers who did not. Mothers having any complications during delivery were more likely to receive ACS, (69.7% vs 50.0%, p = 0.002). Newborns of mothers who received ACS had significantly lower rates of respiratory distress syndrome (21.8% vs 61.8%, p < 0.001), necrotizing enterocolitis (5.8% vs 19.7%, p < 0.001), perinatal asphyxia (18.4% vs 35.5%, p < 0.001), neonatal sepsis (32.0% vs 43.4%, p < 0.027), and need for mechanical ventilation (15.5% vs 41.4%, p < 0.001). Newborn of mothers who did not receive ACS had higher odds of respiratory distress syndrome (adjusted odds ratio (a0R): 4.181, 95% CI: 2.462-7.100) and the need for mechanical ventilation (a0R: 2.266, 95% CI: 1.300-3.950). Lack of exposure to ACS was associated with higher odds of prolonged hospital stay (aOR: 3.321, 95% CI: 1.957-5.638) and mortality (aOR: 5.731, 95% CI: 3.199-10.266). CONCLUSION: ACS was more frequently used in mothers of less than 34 weeks POG having some complications during pregnancy. Use of ACS in deliveries of less than 34 weeks POG was associated with reduced risk of RDS, NEC and need for Mechanical Ventilation along with decrease hospital stay and neonatal mortality. Strengthening national guidelines with recommendation for the use of ACS in mothers less than 34 weeks POG can avert deaths due to complications of prematurity and help save more newborns.

OBJECTIVES: Limited data exist on outcomes in COVID-19- vs. influenza A (H1N1)-associated acute respiratory distress syndrome (ARDS) patients when supported on venovenous extracorporeal membrane oxygenation (ECMO). We aimed to compare acute brain injury (ABI) frequency, thrombotic, and hemorrhagic complications and mortality in COVID-19- vs. H1N1-associated ARDS patients on venovenous ECMO. DESIGN: Retrospective multicenter observational cohort study. SETTING: Data reported to the Extracorporeal Life Support Organization by up to 534 ECMO centers from 2009 to 2021. PATIENTS: Patients 18 years or older with COVID-19 or H1N1 requiring venovenous ECMO support. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We conducted a retrospective analysis on 2253 venovenous ECMO patients (1916 COVID-19 and 337 H1N1). We employed propensity score matching followed by multivariable logistic regression to compare outcomes. The primary outcome was ABI and secondary outcomes were thrombosis, hemorrhage, and mortality. After matching, 674 patients (337 COVID and 337 H1N1) remained (median age = 41, 55% male). In the matched cohort, 10% of COVID-19 patients experienced ABI compared with 12% of H1N1 patients, with no significant difference between the groups (adjusted odds ratio [aOR], 0.83; 95% CI, 0.44-1.54; p = 0.53). There was no difference in thrombotic complications (aOR, 0.67; 95% CI, 0.44-1.02; p = 0.06), but COVID-19 patients had fewer hemorrhagic complications (aOR, 0.27; 95% CI, 0.17-0.42; p < 0.001) compared with H1N1. Mortality was higher in COVID patients (aOR, 2.17; 95% CI, 1.45-3.23; p < 0.001). In both groups, however, patients with ABI had higher mortality than those without, with 94% vs. 40% ( p < 0.001) for COVID and 75% vs. 29% ( p < 0.001) for H1N1, respectively. CONCLUSIONS: COVID-19 and H1N1 patients on venovenous ECMO exhibited similar ABI frequency, which was twice that observed in the general historical ARDS patients supported on venovenous ECMO population. Our findings highlight that both COVID and H1N1 ARDS increase ABI frequency in ECMO patients. Finally, the presence of ABI doubled mortality among both COVID and H1N1.