Daily Ards Research Analysis

BACKGROUND: To evaluate the association between albumin administration as volume replacement and mortality in adult ARDS patients, we performed this meta-analysis and trial sequential analysis (TSA). METHODS: We searched databases including PubMed, Science Direct, Scopus, Web of Science databases and Cochrane Central Register of Controlled Trials up to 12 December 2024. We screened trials that included adult ARDS patients and compared albumin with crystalloid. The 28-day mortality served as the primary endpoint, while the oxygenation change, the length of ICU stay and the length of hospital stay were designated as secondary outcomes. To clarify the differing concentrations of albumin, we formed two distinct subgroups: the hyper-oncotic albumin subgroup (≥20%) and the iso-oncotic albumin subgroup (4%∼5%). Statistical synthesis was performed with Cochrane Review Manager 5.4.1, employing random-effects models. To mitigate random errors, TSA was implemented with α = 0.05 and β = 0.20 parameters. RESULTS: The analysis incorporated 5 publications: 3 randomized controlled trials (RCTs) and 2 non-randomized studies (NRSs). Overall mortality was lower in the albumin group (33.2%, 97/292) than in the crystalloid group (44.9%, 133/296) (OR = 0.61, 95%CI 0.43-0.85, CONCLUSIONS: Our analysis suggests that hyper-oncotic albumin may reduce mortality and improve early oxygenation in ARDS patients compared to crystalloids. Larger RCTs are urgently needed to validate these findings and define their potential role in clinical management.

BACKGROUND: Recirculation is a major contributor to refractory hypoxemia during veno-venous ECMO (V-V ECMO), yet it remains difficult to measure at the bedside. In an animal study, we applied the trans-ECMO thermodilution (TET) to quantify the phenomenon, identify its determinants and estimate the mixed venous oxygenation non-invasively. METHODS: Eight pigs (65±3 kg) were anesthetized and cannulated for femoral-jugular V-V ECMO. Acute respiratory distress syndrome (ARDS) was induced using oleic (n=4) or hydrochloric acid (n=4) targeting a PaO 2 /FiO 2 of 150 mmHg. The experiment lasted 24 hours, with serial measurements of blood gases, hemodynamics and respiratory mechanics. TET was performed by injecting a bolus of cold saline downstream the membrane lung and by recording the resulting temperature changes in the drainage and return cannulas. Recirculation was calculated as the ratio of the areas under the temperature-time curves (AUCs). The determinants of the recirculation were analyzed with mixed linear models, including a random intercept. The measured recirculation was incorporated in a series of mass-transfer equations to estimate the mixed venous oxygen content and saturation. RESULTS: Median recirculation was 7.4% IQR [1.1-22.0] and presented large inter-subject variability. In 55% of measurements, recirculation was <10% (minimal recirculation, MR). In the remaining measurements, the recirculation measured 27.4 [15.0- 43.5] (significant recirculation, SR). The ratio of extracorporeal blood flow to cardiac output (ECS F ) measured 0.63 [0.55-0.72] and was the only physiological factor correlated with recirculation (overall Pearson correlation coefficient r=0.67, in the SR r =0.81). The distance between the tip of the cannulas was, in our setup, non-significantly associated to the recirculation (p=0.74). An increased recirculation was modestly associated with a decreased mixed venous PO 2 (r=-0.37). The non-invasive estimation of the mixed venous oxygenation was highly accurate (r=0.98, bias +0.48 ml/100 ml for the oxygen content, r=0.98, bias +4% for saturation). CONCLUSIONS: TET is a promising technique to measure the recirculation during V-V ECMO. Increasing the blood flow does not always lead to an improvement in oxygenation given the tight relationship between ECS F and recirculation. The proposed numerical method allows the non-invasive estimation of the mixed venous oxygenation without the need of a pulmonary artery catheter.

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) remain life-threatening conditions with high morbidity and mortality, largely due to excessive reactive oxygen species (ROS) generation and uncontrolled inflammatory cascades. Despite extensive pharmacological investigations, effective and targeted therapies are still lacking. This study develops an innovative hyaluronic acid (HA)-epigallocatechin gallate (EGCG)-amino phenylboronic acid (PBA) based sub-microgel (HAEP sub-microgel) platform capable of integrating multiple dynamic interactions (esterification, boronic ester bonds, and hydrogen bonding) to achieve stability, lung delivery, and antioxidant activity. The HAEP sub-microgel system is employed to deliver the anti-inflammatory agent resatorvid (Res) to the injured lung in a bleomycin-induced ALI mouse model. The HAEP@Res sub-microgels (0.1-1.4 µm) exhibit excellent biocompatibility, effectively scavenge intracellular ROS in human lung fibroblasts in vitro. Moreover, the HAEP@Res intratracheal administration significantly reduces histopathological lung tissue injury, and suppresses pro-inflammatory cytokine secretion (TNF-α, IL-6, IL-1β) and gene expression (Tlr4, Tnf, Il6, Il1b, Nrf2, Nos2, Tgfb, Ccl2) in vivo. Altogether, this study establishes a versatile HAEP sub-microgel-based drug delivery system for anti-inflammatory payloads, effectively alleviating lung inflammation and promoting ALI recovery, thereby demonstrating therapeutic potential for ALI/ARDS and other inflammation-related diseases.