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Critical Care Clinical Trials Summary

Jun 29, 2025

Overview

This podcast episode, hosted by JAMA Editor-in-Chief Dr. Kirsten Bibbins-Domingo with Drs. Christopher Seymour and Derek Angus, reviews four major clinical trials in critical care, focusing on sepsis alerts, oxygen strategies in trauma, respiratory support, and biomarker-guided antibiotic duration.

Electronic Sepsis Screening (SCREEN Trial)

  • The SCREEN trial randomized hospital wards to activate or withhold electronic sepsis alerts based on QSOFA criteria.
  • Alerts notified both nurses and physicians and were accompanied by quality improvement efforts.
  • Over 60,000 patients participated across 45 wards over 1.5 years.
  • The trial found a significant reduction in hospital mortality (risk ratio 0.85) with the alert system.
  • Alerts led to more lactate tests and IV fluid orders, but not to increased antibiotic prescribing.
  • No mortality change was seen among just those patients who triggered alerts.
  • The intervention affected workflows and overall vigilance on wards.

Early Restrictive vs. Liberal Oxygen for Trauma (Traumox 2 Trial)

  • This large, multi-center trial randomized trauma patients to restrictive or liberal oxygen strategies.
  • No differences were observed in 30-day death or respiratory complications between the groups.
  • Findings suggest that neither a strictly restrictive nor liberal approach offers a clear benefit.
  • Current guidelines remain vague on optimal oxygen targets for trauma patients.
  • More individualized approaches and further research are needed.

High Flow Nasal Oxygen vs. Non-Invasive Ventilation (RENOVATE Trial)

  • The RENOVATE trial enrolled ≈1,800 patients in acute respiratory failure, randomizing to high flow nasal oxygen or non-invasive ventilation.
  • High flow nasal oxygen was found largely non-inferior and as effective as non-invasive ventilation.
  • High flow was more practical and easier to use, but some uncertainty remains for small subgroups (e.g., immunocompromised).
  • Editorials explore implications for both emergency and ICU settings, noting persistent subgroup concerns.

Biomarker-Guided Antibiotic Duration (ADAPT Sepsis Trial)

  • The ADAPT Sepsis trial tested whether antibiotic duration in sepsis could be safely reduced using procalcitonin, CRP, or standard care protocols.
  • Procalcitonin guidance reduced antibiotic duration by about one day without compromising safety (non-inferior mortality).
  • CRP guidance did not significantly affect antibiotic duration and nearly missed the non-inferiority threshold for mortality.
  • The findings support daily procalcitonin for guiding antibiotic discontinuation but raise questions about the use of CRP.

Key Dates / Deadlines

  • Morris Fishbine Fellowship application deadline: January 5th, 2025.

Recommendations / Advice

  • Electronic sepsis alerts may improve hospital mortality on a population basis.
  • No clear benefit for restrictive versus liberal oxygen in trauma; guideline recommendations should remain flexible.
  • High flow nasal oxygen is a practical alternative to non-invasive ventilation for acute respiratory failure.
  • Consider procalcitonin for safer reduction of antibiotic use in sepsis, but more evidence is needed for CRP guidance.

Questions / Follow-Ups

  • What are the optimal alert criteria and implementation methods for electronic sepsis alerts?
  • How should clinicians individualize oxygen therapy in trauma patients based on current evidence?
  • Are there specific patient subgroups where high flow nasal oxygen may not be appropriate?
  • What are the cost-effectiveness and logistical implications of routine procalcitonin testing in sepsis care?