Daily Anesthesiology Research Analysis

BACKGROUND: Enteral ventilation is an emerging approach that provides partial systemic oxygenation independent of pulmonary gas exchange, enabling lung rest. Perfluorodecalin, a clinically approved liquid with high oxygen solubility, is a promising vehicle for enteral oxygen delivery. The primary endpoint of this first-in-human trial was to assess the safety and tolerability of intrarectal perfluorodecalin administration. METHODS: This was a phase 1, single-site, open-label, non-controlled, dose-escalation trial in 27 healthy adult males aged 20-45 years. Participants received a single intrarectal dose of non-oxygenated perfluorodecalin (escalating from 25 to 1,500 mL) retained for 60 min. Safety and tolerability were assessed through monitoring of adverse events, vital signs, clinical laboratory tests, and systemic perfluorodecalin exposure. A pharmacokinetic model using large-animal data was employed to predict potential oxygen transfer. FINDINGS: No serious adverse events or dose-limiting toxicities occurred. Mild gastrointestinal symptoms, such as abdominal bloating and pain, were transient, dose dependent, and resolved without intervention. All clinical laboratory parameters, including liver and renal function markers, remained within normal limits. Perfluorodecalin concentrations were undetectable in blood (<1.0 μg/mL). The pharmacokinetic model predicted a dose-dependent oxygenation effect, consistent with a modest increase in peripheral oxygen saturation observed in the higher-dose group. CONCLUSIONS: This first-in-human study demonstrates that intrarectal administration of non-oxygenated perfluorodecalin is safe, feasible, and well tolerated. These findings establish a critical safety foundation and support the continued development of enteral ventilation with fully oxygenated perfluorodecalin as an adjunctive strategy to support respiratory failure patients. FUNDING: This work was funded by EVA Therapeutics, Inc.

BACKGROUND: The therapeutic benefit of corticosteroids in managing sepsis and septic shock remains controversial, particularly concerning optimal dosing strategies and the role of adjunctive fludrocortisone. Recent large-scale trials and updated guidelines underscore the need for a dose-stratified synthesis. This meta-analysis aimed to comprehensively evaluate the effects of corticosteroids on short-term mortality in sepsis, with subgroup analyses by steroid type, dosage, and geographic region. METHODS: This study followed the PRISMA 2020 guidelines. Randomized controlled trials (RCTs) comparing corticosteroids with placebo in adult patients with sepsis or septic shock were included. Subgroup analyses were pre-specified for daily hydrocortisone-equivalent dose (≤ 200 mg, 201-300 mg, > 300 mg), steroid type (hydrocortisone alone vs. hydrocortisone plus fludrocortisone), and region (China vs. non-China). Risk ratios (RRs) with 95% confidence intervals (CIs) were synthesized using a random-effects model. RESULTS: Eighteen RCTs comprising 7,982 patients were included. Corticosteroid therapy was associated with reduced 28-day mortality (RR = 0.88; 95% CI: 0.79-0.98; I² = 39%). The 28-day mortality was 31.0% in the corticosteroid group versus 35.5% in the control group.The most pronounced benefit was seen with 201-300 mg/day regimens (RR = 0.86; I² = 0%) and with combination therapy including fludrocortisone (RR = 0.89). Regional analysis showed weaker effects in trials conducted in China. CONCLUSION: Moderate-dose corticosteroids, especially when used in conjunction with fludrocortisone, significantly reduce short-term mortality in septic shock. Findings support guideline-endorsed steroid use and highlight the importance of individualized treatment strategies.

The European Resuscitation Council (ERC) and the European Society of Intensive Care Medicine (ESICM) have collaborated to produce these post-resuscitation care guidelines for adults, which are based on the International Consensus on Cardiopulmonary Resuscitation Science with Treatment Recommendations (CoSTR) pubished by the International Liaison Committee on Resuscitation (ILCOR). The topics covered include the post-cardiac arrest syndrome, diagnosis of cause of cardiac arrest, control of oxygenation and ventilation, coronary reperfusion, haemodynamic monitoring and management, control of seizures, temperature control, general intensive care management, prognostication, long-term outcome, rehabilitation, and organ donation. The post-resuscitation care of children is described in the ERC guidelines 2025 Paediatric Life Support.