What is the preferred choice between ketamine and etomidate for rapid sequence intubation (RSI) or sedation in patients with cardiovascular comorbidities or adrenal insufficiency?

Ketamine versus Etomidate for Rapid Sequence Intubation

For most critically ill patients requiring rapid sequence intubation, there is no significant difference in mortality between ketamine and etomidate, and either agent is appropriate based on the 2023 Society of Critical Care Medicine guidelines. 1

Primary Recommendation

The Society of Critical Care Medicine suggests no difference between etomidate and other induction agents (including ketamine) with respect to mortality or the incidence of hypotension or vasopressor use in the peri-intubation period (conditional recommendation, moderate quality of evidence). 1 A 2025 meta-analysis of 23,926 patients confirmed no significant difference in 30-day survival between etomidate and ketamine (OR 0.92,95% CI: 0.68-1.24). 2

Clinical Decision Algorithm

Choose Etomidate (0.2-0.3 mg/kg) when:

• Hemodynamic stability is the primary concern - Etomidate provides the most reliable hemodynamic profile with minimal effect on blood pressure. 1, 3
• The patient has depleted catecholamine stores - This includes prolonged septic shock, severe cardiogenic shock, or adrenal exhaustion, where ketamine's sympathomimetic effects may paradoxically cause hypotension and cardiac arrest. 1, 4
• Cost and availability matter - Etomidate is readily available, clinicians have extensive experience with it, and it has low cost. 1

Choose Ketamine (1-2 mg/kg) when:

• The patient has septic shock - While mortality is equivalent, avoiding etomidate-induced adrenal suppression is prudent in sepsis despite lack of proven clinical harm. 1, 5
• Bronchodilation is beneficial - Ketamine causes bronchodilation, useful in patients with chest trauma, aspiration risk, or reactive airway disease. 6
• Pediatric critical illness - The American College of Critical Care Medicine explicitly recommends against etomidate in critically ill children, particularly those with septic shock. 1, 7

Critical Hemodynamic Considerations

Post-intubation hypotension occurs commonly with both agents and is associated with increased mortality, prolonged ICU stays, and organ dysfunction. 1 Observational data shows ketamine has slightly higher rates of post-intubation hypotension (18.3%) compared to etomidate (12.4%), though ketamine patients often had more difficult airways and higher baseline hypotension risk. 8, 2

• Always have vasopressors immediately available during RSI with either agent. 1, 8
• Use the lower ketamine dose (1 mg/kg) in patients with cardiovascular compromise. 8, 6
• Reduce etomidate to 0.15 mg/kg in hemodynamically compromised patients. 6

The Adrenal Insufficiency Controversy

Etomidate causes adrenal suppression lasting 6-8 hours through 11-beta-hydroxylase inhibition, but this does not translate to worse clinical outcomes. 1, 3 A 2025 meta-analysis confirmed etomidate increases adrenal insufficiency risk (OR 2.43,95% CI: 1.67-3.53), yet mortality remains equivalent. 2 A 2011 systematic review showed increased mortality with etomidate (RR 1.19), but this was driven entirely by sepsis patients and predated modern sepsis management. 9

• Do NOT routinely administer corticosteroids following etomidate for RSI - The Society of Critical Care Medicine suggests against this practice (conditional recommendation, low quality of evidence). 1, 6
• Multiple RCTs showed no mortality benefit from hydrocortisone administration after etomidate (28-day mortality: 13% with hydrocortisone vs 12% control). 1

Essential Safety Measures

Always administer the sedative-hypnotic agent BEFORE the neuromuscular blocking agent to prevent awareness during paralysis, which occurs in approximately 2.6% of emergency intubations. 8, 7 This applies even in hemodynamically unstable patients with depressed consciousness. 8

Specific Dosing Protocol:

1. Ketamine: 1-2 mg/kg IV (use 1 mg/kg if cardiovascular compromise) 8, 6
2. Etomidate: 0.2-0.3 mg/kg IV (use 0.15 mg/kg if hemodynamic compromise) 1, 6
3. Immediately follow with NMBA: Succinylcholine 1-1.5 mg/kg or rocuronium 1.0-1.2 mg/kg 7

Common Pitfalls to Avoid

The most dangerous misconception is that ketamine is universally "safer" hemodynamically. 4 Two case reports document cardiac arrest following ketamine administration in critically ill patients with catecholamine depletion. 4 Ketamine's cardiovascular stability depends entirely on endogenous catecholamine release - when stores are depleted, direct myocardial depression predominates. 1, 4

Historical concerns about ketamine increasing intracranial pressure are outdated. 8 Ketamine is safe in head-injured patients when used with controlled mechanical ventilation. 8, 6

Propofol should be avoided in critically ill, hemodynamically unstable patients - it has the most profound effect on blood pressure among all induction agents. 1, 6

Special Populations

Geriatric Patients with Hypertension:

• Etomidate may cause decreases in heart rate, cardiac index, and mean arterial blood pressure in this population. 3
• Consider ketamine at reduced dosing (1 mg/kg). 8

Patients with Cirrhosis:

• Etomidate volume of distribution and elimination half-life approximately double in cirrhotic patients. 3
• No specific dosing adjustments recommended in guidelines, but clinical judgment warranted. 3

Status Epilepticus:

• Ketamine maintains cardiovascular stability, which is critical in hemodynamically compromised seizure patients. 7
• Etomidate may activate seizures in patients with epileptogenic foci. 10

Secondary Outcomes

Ketamine requires more post-intubation vasopressor support (OR 0.71,95% CI: 0.53-0.96) but is associated with increased ICU-free days. 2 No significant differences exist in intubation difficulty, cardiovascular collapse, or systemic steroid use between agents. 2, 5