Sepsis 2026: HFNC vs intubation | Part 4

How do we support breathing in sepsis without adding lung injury? Part four connects the 2026 Surviving Sepsis Campaign respiratory recommendations with the studies behind them: oxygen assessment and targets, high-flow nasal oxygen, recognition of treatment failure, awake proning, protective ventilation, PEEP, prone ventilation, neuromuscular blockade and VV ECMO. We distinguish recommendation strength from evidence certainty, primary from secondary outcomes, and trial populations from the patient in front of us. Key examples include UK-ROX, FLORALI, SOHO, ARDSNet, ART, PROSEVA, ROSE and EOLIA. SOHO is presented as a later evidence update, beyond the guideline's June 2025 evidence horizon. Its primary 28-day mortality result did not establish a survival benefit; intubation was a secondary outcome. Awake-proning evidence largely came from COVID-19 populations. These distinctions matter when applying the findings to sepsis. Presented by Stefan Porubcin, MD, PhD., Associate Professor of Internal Medicine. The Evidence Explained — Beyond the abstract. From trial to practice. CHAPTERS 00:00 Opening 00:41 Scope: respiratory support in sepsis 01:17 Alveolar injury 01:37 Assessing oxygenation 02:39 Oxygen targets and UK-ROX 03:58 High-flow nasal oxygen 05:01 FLORALI: primary versus secondary findings 05:37 SOHO 2026: mortality and intubation 06:18 Recognizing failure of non-invasive support 07:09 Awake prone positioning 08:16 Ventilation with and without ARDS 09:06 Predicted body weight 09:41 ARDSNet and pressure limitation 10:40 PReVENT: patients without ARDS 11:13 PEEP: recruitment and overdistension 11:42 Higher PEEP: overall and subgroup evidence 12:17 ART: interpreting the harmful package 12:56 Prone ventilation and PROSEVA 13:54 Neuromuscular blockade and ROSE 14:39 VV ECMO and EOLIA 15:24 Bedside pathway 16:02 Practice implications 16:41 Sources and educational context SOURCES Prescott HC, Antonelli M, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock 2026. Intensive Care Medicine. 2026;52:863–936. https://doi.org/10.1007/s00134-026-08... UKROX (2025): All-cause mortality, 90 days. https://doi.org/10.1001/jama.2025.9663 FLORALI (2015): Intubation, 28 days. https://doi.org/10.1056/NEJMoa1503326 SOHO_MORT (2026): All-cause mortality, 28 days. https://doi.org/10.1056/NEJMoa2516087 AWAKE (2021): Intubation OR death, 28 days. https://doi.org/10.1016/S2213-2600(21... ARDSNET (2000): Death before discharge home breathing without assistance, Follow-up up to 180 days; not 28-day mortality. https://doi.org/10.1056/NEJM200005043... PREVENT (2018): Ventilator-free and alive days, 28 days. https://doi.org/10.1001/jama.2018.14280 PEEP_IPD (2010): Hospital mortality, Hospital stay. https://doi.org/10.1001/jama.2010.218 ART (2017): All-cause mortality, 28 days. https://doi.org/10.1001/jama.2017.14171 PROSEVA (2013): All-cause mortality, 28 days. https://doi.org/10.1056/NEJMoa1214103 ROSE (2019): In-hospital death, 90 days. https://doi.org/10.1056/NEJMoa1901686 EOLIA (2018): All-cause mortality, 60 days. https://doi.org/10.1056/NEJMoa1800385 Supplement SDC6 respiratory evidence profiles and relevant original outcome tables were checked. The publisher correction concerns author names: https://doi.org/10.1007/s00134-026-08... This is not a claim that every full trial protocol or disclosure was independently audited. Educational review for clinicians. Clinical decisions require assessment of the individual patient, available resources and the expertise of the treating team. #Sepsis #CriticalCare #EvidenceBasedMedicine