Daily Anesthesiology Research Analysis
Three impactful perioperative and critical care studies stand out today. A multicenter NEJM RCT shows ketamine is not superior to etomidate for induction in critically ill adults and may increase cardiovascular collapse. A JAMA Network Open RCT supports awake prone positioning to lower intubation/death probability in COVID-19 hypoxemia, and a BJA analysis of an RCT reports sustained hemoglobin and ferritin gains with intravenous iron, highlighting the sTfR–log ferritin index as a promising predi
Summary
Three impactful perioperative and critical care studies stand out today. A multicenter NEJM RCT shows ketamine is not superior to etomidate for induction in critically ill adults and may increase cardiovascular collapse. A JAMA Network Open RCT supports awake prone positioning to lower intubation/death probability in COVID-19 hypoxemia, and a BJA analysis of an RCT reports sustained hemoglobin and ferritin gains with intravenous iron, highlighting the sTfR–log ferritin index as a promising predictor of response.
Research Themes
- Airway induction safety in critically ill adults (ketamine vs etomidate)
- Awake prone positioning for hypoxemic respiratory failure
- Perioperative anemia management and biomarker-guided iron therapy
Selected Articles
1. Ketamine or Etomidate for Tracheal Intubation of Critically Ill Adults.
In a multicenter RCT of 2365 critically ill adults, ketamine did not reduce 28-day in-hospital mortality compared to etomidate for rapid sequence induction. Cardiovascular collapse during intubation was more frequent with ketamine, while other safety outcomes were similar.
Impact: This definitive RCT addresses a long-standing controversy on induction agents in critically ill adults and is likely to influence airway management guidelines.
Clinical Implications: Etomidate remains a reasonable induction agent for RSI in critically ill adults. Ketamine should not be chosen with the expectation of mortality benefit and may increase the risk of cardiovascular collapse during intubation; hemodynamic vigilance is warranted.
Key Findings
- 28-day in-hospital mortality: ketamine 28.1% vs etomidate 29.1% (adjusted risk difference -0.8 percentage points; 95% CI -4.5 to 2.9; P=0.65).
- Cardiovascular collapse during intubation was higher with ketamine (22.1%) than etomidate (17.0%); risk difference 5.1 percentage points (95% CI 1.9 to 8.3).
- Prespecified safety outcomes aside from cardiovascular collapse were similar between groups.
Methodological Strengths
- Large multicenter randomized controlled trial with intention-to-treat analysis.
- Clinically meaningful endpoints (28-day mortality, cardiovascular collapse) with site-adjusted estimates.
Limitations
- Blinding to induction agent was likely not feasible, introducing potential performance bias.
- Practice heterogeneity across ED and ICU settings could influence outcomes despite randomization.
Future Directions: Subgroup analyses by shock phenotype and vasopressor use, and pragmatic trials evaluating protocolized hemodynamic support during RSI may refine agent selection.
2. Awake Prone Positioning in Patients With COVID-19 Respiratory Failure: A Randomized Clinical Trial.
In 445 non-intubated adults with COVID-19 hypoxemic respiratory failure, awake prone positioning for at least 6 hours/day had a 93.8% posterior probability of reducing the composite of intubation and/or death (mean OR 0.74). Secondary clinical benefits trended favorably but with overlapping credible intervals.
Impact: Confirms a pragmatic, low-cost intervention that can be widely implemented in wards and ICUs, with robust Bayesian evidence across priors.
Clinical Implications: Encourage structured awake prone positioning protocols targeting ≥6 hours/day for eligible hypoxemic COVID-19 patients, with monitoring for tolerance and adherence.
Key Findings
- Posterior probability of benefit for APP on intubation/death was 93.8% with a mean OR 0.74 (95% CrI 0.48–1.09).
- Trends toward more days alive outside ICU (+1.28 days) and outside hospital (+1.55 days), though CrIs included 0.
- Trial enrolled a mixed ward/ICU population and used intention-to-treat with a Bayesian framework.
Methodological Strengths
- Multicenter randomized design with Bayesian analysis providing full effect distributions.
- Intention-to-treat analysis across ward and ICU settings increases generalizability.
Limitations
- Open-label design and allowance for spontaneous prone positioning in controls may dilute effects.
- COVID-19 era heterogeneity (variants, co-interventions) could affect outcomes.
Future Directions: Define optimal daily duration, adherence strategies, and applicability to non-COVID hypoxemic pneumonia; assess patient-centered outcomes and safety in broader settings.
3. Longitudinal changes in haemoglobin, iron stores, and inflammatory markers following surgery and in critical illness: an analysis from the Practical Anaemia Bundle for Sustained Blood Recovery randomised clinical trial.
In a planned analysis of a randomized trial (n=100), intravenous iron increased hemoglobin and ferritin levels through 3 months after critical illness. Traditional iron studies were confounded by inflammation, while the soluble transferrin receptor–log ferritin index early in illness may help predict treatment response.
Impact: Supports guideline-aligned perioperative anemia management and proposes a practical biomarker strategy to select responders in inflammatory states.
Clinical Implications: Consider early intravenous iron in anemic critically ill or postoperative patients and use the sTfR–log ferritin index to inform candidacy, given the limitations of ferritin and transferrin saturation during inflammation.
Key Findings
- IV iron increased hemoglobin and ferritin over 3 months compared to standard care (adjusted mean hemoglobin difference 0.69 g/dL; 95% CI 0.13–1.25).
- Traditional iron assays were influenced by inflammation, limiting diagnostic utility during critical illness.
- The soluble transferrin receptor–log ferritin index measured early showed potential to identify patients more likely to benefit from IV iron.
Methodological Strengths
- Planned analysis within a randomized clinical trial framework.
- Longitudinal assessment up to 3 months with clinically relevant biomarkers.
Limitations
- Secondary analysis with modest sample size limits power for some endpoints.
- Single-center context (tertiary referral hospital) may constrain generalizability.
Future Directions: Prospective validation of sTfR–log ferritin-guided IV iron strategies and trials integrating anemia bundles with transfusion avoidance in diverse perioperative populations.