Weekly ReportDec 8–14, 2025
Anesthesiology, week 50 edition
We read 21 papers and selected 3.
Summary
This week’s most consequential findings centered on precision critical care, safer airway management, and evidence-based selection of anesthetic techniques. The ImmunoSep randomized trial showed that biomarker-guided anakinra or interferon-γ improved short-term organ dysfunction in selected sepsis phenotypes, although mortality was unchanged. A large randomized trial found no mortality benefit for ketamine over etomidate during emergency intubation and identified more cardiovascular collapse with ketamine. The GA-CARES trial also challenged the presumed oncologic advantage of propofol, while digital monitoring and opioid-sparing strategies continued to expand the role of technology and multimodal perioperative care.
Selected Articles
1. Precision Immunotherapy to Improve Sepsis Outcomes: The ImmunoSep Randomized Clinical Trial.
In a multinational double-blind randomized trial of 276 patients with sepsis, biomarker-guided treatment with anakinra for macrophage activation-like syndrome or interferon-γ for sepsis-induced immunoparalysis increased the proportion of patients achieving a clinically meaningful SOFA-score decrease by day 9. The benefit was observed without a statistically significant reduction in 28-day mortality, and anemia or hemorrhage signals require monitoring.
Impact: This trial provides high-level evidence that sepsis immunotherapy can be matched to biologically defined host-response phenotypes rather than administered uniformly.
Clinical Implications: Selected patients may benefit from phenotype-directed anakinra or interferon-γ in addition to standard sepsis care. Implementation requires reliable ferritin and monocyte HLA-DR testing, careful safety surveillance, and further trials focused on mortality and patient-centered outcomes.
Key Findings
- The primary SOFA-response endpoint occurred in 35.1% with precision immunotherapy versus 17.9% with placebo.
- There was no statistically significant difference in 28-day mortality.
- Anemia was more frequent with anakinra and hemorrhage was a safety signal with interferon-γ.
2. Ketamine or Etomidate for Tracheal Intubation of Critically Ill Adults.
In a multicenter randomized trial of 2,365 critically ill adults undergoing tracheal intubation, ketamine did not reduce 28-day in-hospital mortality compared with etomidate. Cardiovascular collapse during intubation was more common with ketamine, occurring in 22.1% versus 17.0% with etomidate.
Impact: This large definitive trial directly addresses a long-standing controversy in emergency airway management and may alter induction-agent recommendations in critically ill patients.
Clinical Implications: Etomidate remains a reasonable induction option for critically ill adults. Ketamine should not be selected with the expectation of improved survival, and clinicians should anticipate possible cardiovascular instability during induction.
Key Findings
- Twenty-eight-day mortality was 28.1% with ketamine versus 29.1% with etomidate.
- Cardiovascular collapse occurred in 22.1% with ketamine versus 17.0% with etomidate.
- The trial included 2,365 patients across 14 emergency departments and ICUs.
3. Anesthesia Type during Cancer Surgery: Results of the GA-CARES Randomized, Multicenter Trial.
The GA-CARES pragmatic randomized trial included 1,763 patients undergoing resection of high-risk cancers and found no overall-survival benefit for propofol compared with volatile anesthetics. At two years, disease-free survival was also not improved, and the per-protocol analysis suggested higher mortality with propofol.
Impact: This trial challenges a widely held hypothesis that propofol-based anesthesia improves cancer recurrence or survival through favorable immune effects.
Clinical Implications: Routine switching to propofol solely for presumed oncologic benefit is not supported. Anesthetic selection should instead be individualized according to hemodynamics, surgical requirements, recovery goals, and the broader perioperative cancer pathway.
Key Findings
- Intent-to-treat analysis showed no survival advantage with propofol versus volatile anesthesia.
- Two-year mortality was 26.1% with propofol versus 22.9% with volatile agents.
- Disease-free survival was not improved with propofol.