What are the clinical uses and dosing guidelines for etomidate (amidate) in patients with cardiovascular instability or at risk of hypotension?

Etomidate for Rapid Sequence Intubation in Cardiovascular Instability

Etomidate (0.2-0.4 mg/kg IV) is the preferred induction agent for rapid sequence intubation in hemodynamically unstable patients due to its superior cardiovascular stability, though it should be avoided in septic shock due to increased mortality risk. 1, 2, 3

Clinical Uses and Hemodynamic Profile

Cardiovascular Stability

• Etomidate provides minimal hemodynamic disturbance with little to no effect on myocardial metabolism, cardiac output, peripheral circulation, or pulmonary circulation in patients with severe cardiovascular disease. 4
• The drug causes only slight reductions in mean arterial pressure (approximately 8.5%), with negligible heart rate changes (2.8% increase) and minimal peripheral vascular resistance reduction (3.8%). 5
• In cardiac surgery patients with poor left ventricular function, etomidate maintains more stable hemodynamic parameters compared to propofol, which causes vasodilation and systemic blood pressure drops. 6

Important Caveat for Geriatric Patients

• In elderly patients, particularly those with hypertension, etomidate may paradoxically result in decreases in heart rate, cardiac index, and mean arterial blood pressure. 4
• Insufficient data exists regarding cardiovascular response in patients with recent severe trauma or hypovolemia. 4

Dosing Guidelines

Standard Dosing

• Administer 0.2-0.4 mg/kg IV for induction, with 0.3 mg/kg being the most commonly used dose. 1, 2, 4
• Onset of action occurs within 5-15 seconds (typically within one minute), with duration of 3-5 minutes at standard dosing. 4, 7
• The American Heart Association recommends titrating in 20 mg increments every 10 seconds until loss of consciousness rather than rapid bolus administration. 3

Hemodynamically Unstable Patients

• Use 0.3 mg/kg IV specifically in hemodynamically unstable patients. 2, 3
• Higher doses (>0.3 mg/kg) increase risk of respiratory depression, particularly in older patients. 2

Critical Contraindications and Warnings

Septic Shock - Absolute Contraindication

• Do not use etomidate routinely in pediatric patients with septic shock (Class III, LOE B). 8
• Etomidate should not be routinely used when intubating infants or children with septic shock due to increased mortality risk. 8
• In adult septic patients, meta-analysis of 3,715 patients showed relative risk of death with etomidate was 1.22 (95% CI 1.11-1.35), representing a statistically significant and clinically relevant increase in mortality. 9
• Ketamine should be strongly preferred over etomidate in patients with sepsis or septic shock. 2

Trauma Patients

• In unstable trauma patients, etomidate was associated with increased pneumonia incidence (56.7% vs 25.9%), prolonged ICU stay (6.3 vs 1.5 days), and prolonged hospital stay (11.6 vs 6.4 days). 9
• Etomidate should be avoided in unstable trauma patients based on these randomized controlled trial findings. 9

Adrenal Suppression Concerns

Mechanism and Duration

• Etomidate causes transient adrenal suppression through 11β-hydroxylase inhibition, reducing cortisol plasma levels for approximately 6-8 hours (up to 12-48 hours in some studies), unresponsive to ACTH administration. 4, 9
• Single induction doses cause adrenal dysfunction, but this has not been shown to be clinically significant in non-septic emergency department RSI. 7

Management

• Corticosteroid administration following etomidate is NOT recommended despite transient adrenal suppression. 2, 3
• If etomidate is used in septic shock (which should be avoided), recognize the increased risk of adrenal insufficiency. 8

Proper RSI Sequencing

Critical Timing

• The sedative-hypnotic agent (etomidate) MUST be administered before the neuromuscular blocking agent to prevent awareness during paralysis. 1, 2, 3
• Failure to provide adequate sedation before paralysis results in awareness during paralysis in approximately 2.6% of emergency department intubations. 1

Neuromuscular Blocking Agent Selection

• Follow etomidate with succinylcholine (1-1.5 mg/kg IV) as first-line when no contraindications exist. 2, 3
• Use rocuronium (0.9-1.2 mg/kg IV) when succinylcholine is contraindicated, with sugammadex immediately available for reversal. 2, 3

Alternative Agent: Ketamine

When to Choose Ketamine Over Etomidate

• Ketamine (1-2 mg/kg IV) is the preferred alternative in septic shock and unstable trauma patients where etomidate is contraindicated. 1, 2, 3
• Ketamine's sympathomimetic properties theoretically maintain hemodynamic stability. 1, 2

Ketamine Limitations

• Evidence shows ketamine has higher rates of peri-intubation hypotension compared to etomidate (18.3% vs 12.4%, OR 1.4). 3
• In critically ill patients with depleted catecholamine stores, ketamine may cause paradoxical hypotension despite sympathomimetic properties. 2, 3
• For cardiovascular compromise, consider using the lower end of ketamine dosing range (1 mg/kg) to minimize hemodynamic effects. 2

Common Side Effects

Expected Adverse Effects

• Pain on injection, myoclonic movements on induction (can be somewhat annoying), hiccups, nausea and vomiting occur with etomidate. 7, 5
• Slight elevation in arterial carbon dioxide tension (PaCO2) is the most characteristic respiratory effect. 4
• Vomiting occurs in approximately 4-10% of patients. 2
• Oxygen desaturation requiring supplemental oxygen occurs in approximately 5% of patients, with higher risk in those >55 years receiving doses ≥0.23 mg/kg. 2

Long-Term Outcome Data

Mortality and Morbidity Concerns

• In a large propensity-matched study of 31,148 ASA III-IV patients undergoing noncardiac surgery, etomidate was associated with 2.5 times the odds of 30-day mortality compared to propofol (98% CI 1.9-3.4). 10
• Etomidate patients had significantly greater odds of cardiovascular morbidity (OR 1.5,98% CI 1.2-2.0) and longer hospital stays (HR 0.82,95% CI 0.78-0.87). 10
• These findings suggest that improved hemodynamic stability at induction may be accompanied by substantially worse longer-term outcomes, requiring judicious use. 10

Practical Algorithm for Agent Selection

For hemodynamically unstable patients requiring RSI:

1. If septic shock or unstable trauma → Use ketamine (1-2 mg/kg), NOT etomidate 2, 3, 9
2. If cardiovascular instability without sepsis/trauma → Etomidate (0.3 mg/kg) is preferred 2, 3
3. If elderly with hypertension → Use caution with etomidate; monitor for paradoxical hemodynamic decline 4
4. Always follow with appropriate neuromuscular blocking agent and have vasopressors immediately available 2, 3