Lit Matters #3: Ketamine vs Etomidate, round 2. The saga continues.

Etomidate suppresses cortisol synthesis via 11-beta hydroxylase inhibition, but whether a single induction dose worsens outcomes remains unsettled. For emergency intubation, recent data also question a long-held RSI habit: sedative-first drug order may not be superior to paralytic-first for first-pass success or hypoxemia.

Ketamine vs Etomidate for Induction

• Adrenal suppression signal: Etomidate inhibits 11-beta hydroxylase and lowers cortisol production, the biologic concern driving persistent debate about worse outcomes in septic and other critically ill patients.
• Large mortality association: In a massive propensity-matched cohort, etomidate was associated with higher hospital mortality than ketamine, with an absolute difference of about 3%.
• Hemodynamic tradeoff pattern: Ketamine appears to bring more peri-intubation hemodynamic instability, while etomidate tracks with greater downstream vasopressor use rather than cleaner shock physiology.
• Administrative data limits: This was retrospective database work using coding and matching, so the mortality signal is important but still vulnerable to confounding by indication and practice patterns.
• Practical bedside takeaway: Both agents remain reasonable for emergent intubation in a competent system, and the real value is knowing where each drug tends to create trouble. We get into that bedside framing in the episode.

RSI Drug Sequence and First Pass

• Classic teaching challenged: Standard RSI teaching puts the sedative first to avoid awareness during paralysis, but newer data do not show a clear awareness penalty with paralytic-first sequencing.
• First-pass failure result: Paralytic-first RSI did not increase first-attempt failure and may even trend toward fewer failures, though the estimate was not definitive.
• Hypoxemia outcome: Oxygen desaturation was essentially unchanged between paralytic-first and sedative-first approaches, suggesting sequence alone is not the main driver of peri-intubation hypoxemia.
• Low-margin physiology cases: When oxygenation or hemodynamics leave little room for delay, a paralytic-first approach becomes more appealing despite limited evidence. We walk through that decision in the chapter.
• Current practice stance: The cautious default remains sedative first for most patients, with sequence adjustments reserved for select high-risk airways rather than adopted as a universal rule.