What is the preferred induction agent for Deep Sedation Intubation (DSI) between ketamine, etomidate, and benzodiazepines, particularly in critically ill patients with potential hypotension or other cardiovascular complications?

Ketamine or Etomidate for Deep Sedation Intubation (DSI)

For Deep Sedation Intubation, use either ketamine (1-2 mg/kg IV) or etomidate (0.2-0.3 mg/kg IV) as first-line induction agents, with ketamine preferred in hemodynamically unstable patients, septic patients, and those requiring bronchodilation, while etomidate remains suitable for hemodynamically stable patients when cardiovascular neutrality is the primary concern. 1, 2

Benzodiazepines are not recommended as primary induction agents for DSI due to longer onset of action, profound venodilation at RSI doses, and inferior hemodynamic profiles compared to ketamine or etomidate. 3

Evidence-Based Selection Algorithm

Ketamine is Preferred When:

• Hemodynamic instability or shock is present - Ketamine's sympathomimetic properties maintain blood pressure through endogenous catecholamine release, critical in hypovolemic or shocked patients 1

• Sepsis or septic shock - The American College of Critical Care Medicine explicitly recommends avoiding etomidate in septic patients, particularly children, making ketamine the preferred choice despite etomidate's adrenal suppression not demonstrating proven clinical harm 2

• Bronchospasm or reactive airway disease - Ketamine provides bronchodilation, particularly beneficial in patients with chest trauma, aspiration risk, COPD, or underlying reactive airway disease 1, 3

• Trauma patients with hypovolemia - The American College of Critical Care Medicine specifically recommends ketamine over etomidate in hypovolemic trauma patients 1

Etomidate Remains Acceptable When:

• Hemodynamic stability is the sole priority - Etomidate provides the most reliable hemodynamic profile with minimal blood pressure effects 2, 4

• Patients have depleted catecholamine stores - In this scenario, ketamine's sympathomimetic effects may paradoxically cause hypotension and cardiac arrest, making etomidate safer 2, 3

• No specific contraindications exist - The Society of Critical Care Medicine found no mortality difference between etomidate and ketamine in critically ill patients (conditional recommendation, moderate quality evidence) 1, 2

Critical Mortality Data

Recent high-quality evidence favors ketamine for survival outcomes. A 2025 Brazilian multicenter cohort study of 1,810 critically ill adults found etomidate associated with significantly higher 28-day mortality compared to ketamine (60.5% vs 54.4%; RR 1.14,95% CI 1.03-1.27; absolute risk difference 7.6%) and higher 7-day mortality (35.2% vs 30.1%; RR 1.19,95% CI 1.04-1.35). 5

This contradicts earlier 2023 Society of Critical Care Medicine guidelines stating no mortality difference, highlighting evolving evidence. 1, 2 A 2022 single-center RCT also demonstrated superior Day 7 survival with ketamine (85.1% vs 77.3%, p=0.005), though Day 28 survival was not significantly different. 6

Practical Dosing Guidelines

Ketamine Dosing:

• Standard dose: 1-2 mg/kg IV 1
• Reduced dose: 1 mg/kg IV in patients with cardiovascular compromise, chronic cor pulmonale, right ventricular dysfunction, or geriatric hypertensive patients to minimize hemodynamic effects while maintaining adequate sedation 1, 3

Etomidate Dosing:

• Standard dose: 0.2-0.3 mg/kg IV 1, 4
• Reduced dose: 0.15 mg/kg IV in patients with hemodynamic compromise 1

Essential Safety Measures and Pitfalls

Universal Precautions (Apply to Both Agents):

• Always have vasopressors immediately available - Post-intubation hypotension occurs commonly with both agents and is associated with increased mortality, prolonged ICU stays, and organ dysfunction 1, 2

• Administer sedative before neuromuscular blocker - This prevents awareness during paralysis, which occurs in approximately 2.6% of emergency intubations 1

• Optimize preoxygenation - Use high-flow nasal oxygen (HFNO) when laryngoscopy is expected to be challenging, or noninvasive positive pressure ventilation (NIPPV) in patients with severe hypoxemia (PaO2/FiO2 < 150) 3

Ketamine-Specific Pitfalls:

• Never assume hemodynamic stability - Despite sympathomimetic properties, ketamine can cause paradoxical hypotension in patients with depleted catecholamine stores from prolonged respiratory distress, chronic hypoxemia, or concurrent sepsis 2, 3

• Manage increased secretions in COPD - Ketamine significantly increases upper airway secretions; pretreat with anticholinergic agents (glycopyrrolate 0.2 mg or atropine 0.5 mg) 3-5 minutes before administration and ensure aggressive suctioning capability 3

• Safe in head injury - Historical concerns about ketamine increasing intracranial pressure have been refuted; it is safe when used with controlled mechanical ventilation 1

Etomidate-Specific Considerations:

• Adrenal suppression is not clinically significant - Despite causing transient adrenal insufficiency (OR 2.43,95% CI 1.67-3.53), no evidence demonstrates negative clinical outcomes, and the Society of Critical Care Medicine recommends against administering corticosteroids following etomidate 1, 2, 7

• Minor side effects - May cause pain on injection, myoclonic movements, hiccups, nausea, and vomiting 4

Why Benzodiazepines Are Inferior

Midazolam and other benzodiazepines have longer onset of action compared to both ketamine and etomidate, are potent venodilators at RSI doses, and provide no disease-specific advantages, severely limiting their utility as primary induction agents for DSI. 3