What is the comparison between ketamine and etomidate (induction agents) in Rapid Sequence Intubation (RSI)?

Ketamine vs Etomidate for Rapid Sequence Intubation

Both ketamine and etomidate are acceptable first-line induction agents for RSI in critically ill adults with no mortality difference between them, though etomidate demonstrates superior hemodynamic stability with lower rates of post-intubation hypotension. 1, 2, 3

Primary Outcome: Mortality

• No significant difference in 30-day mortality exists between ketamine and etomidate (OR 0.95; 95% CI: 0.72-1.25), based on the most recent 2025 meta-analysis of 23,926 patients 2
• A 2025 meta-analysis of randomized controlled trials confirmed no difference in 28-day mortality (RR 0.95; 95% CI: 0.72-1.25) with moderate certainty of evidence 3
• The 2023 Society of Critical Care Medicine guidelines similarly found no mortality difference between agents 1

Hemodynamic Stability: The Critical Differentiator

Etomidate Advantages

• Etomidate (0.2-0.4 mg/kg IV) provides superior hemodynamic stability with significantly lower rates of post-intubation hypotension compared to ketamine (12.4% vs 18.3%; OR 1.4; 95% CI 1.2-1.7) 1
• Post-intubation hypotension occurred less frequently with etomidate in propensity-matched sepsis patients (73% etomidate vs 51% ketamine; OR 0.39; 95% CI 0.22-0.67) 1
• The 2025 guidelines explicitly state etomidate is preferred in hemodynamically unstable patients due to its favorable hemodynamic profile 4, 5

Ketamine Limitations

• Ketamine (1-2 mg/kg IV) requires more post-intubation vasopressor support (OR 0.71; 95% CI: 0.53-0.96) based on 2025 meta-analysis 2
• Post-induction hypotension was 30% higher with ketamine (RR 1.30; 95% CI: 1.03-1.64) 3
• In critically ill patients with depleted catecholamine stores, ketamine may cause paradoxical hypotension despite its sympathomimetic properties 4, 5

Adrenal Suppression Controversy

• Etomidate causes transient adrenal suppression with significantly higher incidence of adrenal insufficiency (OR 2.43; 95% CI: 1.67-3.53) 2
• However, corticosteroid administration following etomidate is NOT recommended, as etomidate-induced adrenal insufficiency has not been proven to cause negative clinical outcomes 1, 4
• The lack of mortality difference despite documented adrenal suppression suggests this is not clinically significant in adult populations 1

Clinical Outcomes Beyond Mortality

• A 2023 randomized trial found no difference in maximum SOFA scores between ketamine (median 6.5) and etomidate (median 7.0) 6
• First-pass intubation success rates are equivalent between agents (RR 1.00; 95% CI: 0.97-1.03) 3
• Post-intubation cardiac arrest rates show no difference (RR 1.10; 95% CI: 0.62-1.96) 3
• Ketamine was associated with increased ICU-free days in meta-analysis 2

Practical Algorithm for Agent Selection

Choose Etomidate When:

• Hemodynamic instability is present (hypotension, shock, sepsis) 4, 5
• Minimizing vasopressor requirements is a priority 2
• Standard RSI in critically ill adults without specific contraindications 1, 5

Choose Ketamine When:

• Etomidate is contraindicated or unavailable 4, 5
• Status epilepticus requiring intubation (ketamine is safe in controlled ventilation) 7
• Patient has relative cardiovascular stability and can tolerate potential hypotension 4

Dosing Specifications

• Etomidate: 0.2-0.4 mg/kg IV (typically 0.3 mg/kg), titrated in 20 mg increments every 10 seconds until loss of consciousness 1, 5
• Ketamine: 1-2 mg/kg IV, using lower end (1 mg/kg) in cardiovascular compromise 4, 7

Critical Implementation Points

• Always administer the sedative-hypnotic agent BEFORE the neuromuscular blocking agent to prevent awareness during paralysis 4, 5, 7
• Follow induction agent with either succinylcholine (1-1.5 mg/kg IV) or rocuronium (0.9-1.2 mg/kg IV) 4, 5
• Have vasopressors immediately available regardless of agent chosen, as post-intubation hypotension is common and associated with increased mortality 7
• Wait at least 60 seconds after neuromuscular blockade before attempting intubation 4

Common Pitfalls to Avoid

• Do not assume ketamine's sympathomimetic properties guarantee hemodynamic stability - multiple large registry studies demonstrate higher hypotension rates with ketamine 1, 2, 3
• Do not routinely administer corticosteroids after etomidate - this practice is not supported by evidence and is explicitly not recommended 1, 4
• Do not use ketamine preferentially in septic patients - contrary to older teaching, etomidate shows better hemodynamic stability even in sepsis 1