In anesthesia, which induction agents are classified as sedative‑hypnotics and what are their comparative cardiovascular effects?

Sedative-Hypnotic Induction Agents: Cardiovascular Effects Comparison

For anesthesia induction in hemodynamically stable patients, propofol, etomidate, midazolam, thiopental, and ketamine are all acceptable sedative-hypnotic agents, but they differ substantially in their cardiovascular profiles—with ketamine and etomidate providing the most hemodynamic stability, while propofol and thiopental cause the most significant hypotension and myocardial depression. 1, 2

Classification of Sedative-Hypnotic Induction Agents

The primary sedative-hypnotic induction agents used in anesthesia include 1, 3:

• Propofol - GABA agonist 4
• Etomidate - GABA agonist 1
• Midazolam - Benzodiazepine/GABA agonist 1, 5
• Thiopental - Barbiturate/GABA agonist 6
• Ketamine - NMDA receptor antagonist with dissociative properties 1, 2, 3

Comparative Cardiovascular Effects Table

Agent	Blood Pressure Effect	Heart Rate Effect	Cardiac Output	SVR Effect	Mechanism	Clinical Implications
Propofol	Marked decrease (>30% common); arterial hypotension frequent [4]	Minimal change to slight decrease [4,5]	Decreased, especially with positive pressure ventilation [4]	Decreased (vasodilation) [4,7]	Myocardial depression + vasodilation [4,8]	Highest risk of hypotension; contraindicated in hypovolemia [9]; causes coronary vasodilation [8]
Etomidate	Minimal decrease; most hemodynamically stable [1,7]	Minimal change [8]	Minimal decrease [8]	Maintained or increased [7]	Minimal cardiovascular depression [1,8]	Preferred in hemodynamically unstable patients [1,2]; higher nadir MAP vs ketofol [7]
Ketamine	Maintained or increased (sympathomimetic) [2]	Slight increase [1]	Maintained [2]	Maintained or increased [2]	Endogenous catecholamine release [2]	Paradoxical hypotension possible in catecholamine-depleted states (prolonged shock, severe cardiogenic shock) [2,10]; bronchodilation beneficial [2]
Midazolam	Moderate decrease (15% mean decrease) [5]	Minimal change; slow rates may increase slightly [5]	Slight to moderate decrease [5,8]	Decreased [8]	Moderate myocardial depression [8]	Less hypotension than propofol (15% vs 25% decrease) [5]; intermediate cardiovascular effects [8]
Thiopental	Moderate to marked decrease [8,9]	Variable; slow rates may increase [5]	Decreased [8]	Decreased [8]	Myocardial depression + vasodilation [8]	Similar hypotension to propofol [9]; risk of bronchoconstriction [2]; less potent cardiac depressant than propofol on molar basis [8]

Detailed Cardiovascular Profiles

Propofol

• Produces the most significant cardiovascular depression among commonly used induction agents, with arterial hypotension sometimes exceeding 30% decrease from baseline 4
• Cardiac output depression is particularly pronounced with assisted or controlled ventilation 4
• At 100 μM concentration, propofol increased coronary flow by 57% ± 10% (near maximal vasodilation) and decreased myocardial oxygen consumption by 37% ± 5%, indicating marked attenuation of coronary autoregulation 8
• The FDA label explicitly warns that rapid bolus administration should be avoided in elderly, debilitated, or ASA-PS III/IV patients due to hypotension risk 4
• Apneic episodes occur in 23% of propofol recipients compared to 7% with etomidate 11

Etomidate

• The Society of Critical Care Medicine found no mortality difference between etomidate and other induction agents (including ketamine, propofol, midazolam) with respect to hypotension or vasopressor use (conditional recommendation, moderate quality evidence) 1
• Provides superior hemodynamic stability with higher post-induction nadir MAP compared to ketamine-propofol combination by 4.77 mmHg 7
• At 100 μM concentration, etomidate increased coronary flow by 17% ± 6% and decreased myocardial oxygen consumption by 29% ± 7% 8
• The concentration producing 50% reduction in cardiac contractility was 82 ± 2 μM, making it equipotent to propofol (91 ± 4 μM) but more potent than thiopental (156 ± 11 μM) or ketamine (323 ± 7 μM) 8
• Critical caveat: Causes transient adrenal suppression and is explicitly contraindicated in pediatric septic shock 2

Ketamine

• Maintains blood pressure through sympathomimetic activity via endogenous catecholamine release, making it particularly useful in trauma and hemodynamically unstable patients 2
• The American Society of Anesthesiologists recommends ketamine for its ability to preserve blood pressure, which is critical in hypovolemic or shock states 2
• At 100 μM concentration, ketamine decreased coronary flow by only 11% ± 2% and myocardial oxygen consumption by 10% ± 5%, demonstrating minimal direct myocardial depression 8
• Major pitfall: Despite sympathomimetic properties, ketamine can cause paradoxical hypotension in critically ill patients with depleted catecholamine stores (prolonged septic shock, severe cardiogenic shock, adrenal exhaustion) 2, 10
• Provides bronchodilation, beneficial in patients with chest injuries or reactive airway disease 2
• Recommended dosing: 1-2 mg/kg IV for RSI, using lower end (1 mg/kg) in cardiovascular compromise 2, 10

Midazolam

• Produces intermediate cardiovascular effects between propofol and etomidate 8
• In pediatric patients, midazolam (500 mcg/kg) caused mean 15% decrease in systolic blood pressure versus 25% decrease with propofol (2.5 mg/kg) 5
• At 100 μM concentration, midazolam increased coronary flow by 21% ± 5% and decreased myocardial oxygen consumption by 19% ± 5% 8
• Apneic episodes occur in only 7% of midazolam recipients, significantly lower than propofol (23%) or thiopental (28%) 11
• The concentration producing 50% reduction in cardiac contractility was 105 ± 8 μM, making it equipotent to etomidate and propofol 8

Thiopental

• Causes moderate to marked hypotension through combined myocardial depression and vasodilation 8, 9
• At 100 μM concentration, thiopental decreased coronary flow by 5% ± 3% and myocardial oxygen consumption by 8% ± 4% 8
• The concentration producing 50% reduction in cardiac contractility was 156 ± 11 μM, making it less potent as a cardiac depressant than propofol, etomidate, or midazolam but more potent than ketamine 8
• Can cause severe bronchoconstriction in patients with preexisting asthma or cholinergic stimulation, making ketamine a safer choice in these scenarios 2
• Hypotension may contraindicate use in hypovolemic or unfit patients 9

Critical Clinical Considerations

Hemodynamic Instability

• The Society of Critical Care Medicine advises administering a sedative-hypnotic induction agent when a neuromuscular blocking agent is used for intubation, even in hemodynamically unstable patients with depressed consciousness 1
• Vasopressors should be immediately available during RSI with any induction agent, as post-intubation hypotension is common and associated with increased mortality, prolonged ICU stays, and organ dysfunction 10
• In hemodynamically unstable patients, ketamine (1 mg/kg) or etomidate are preferred first-line agents 2, 10

Apnea Risk

• Propofol causes apnea lasting >60 seconds in 12% of adult patients receiving 2-2.5 mg/kg 4
• Apnea rates: propofol 23%, thiopental 28%, etomidate 7%, midazolam 7% 11

Special Populations

• Pompe disease/severe cardiomyopathy: Ketamine and etomidate offer safer profiles; propofol should be avoided due to afterload reduction and risk of myocardial ischemia 1
• Head injury: Ketamine is safe and appropriate for RSI in head-injured patients when used with controlled mechanical ventilation, contrary to historical concerns about increased intracranial pressure 2, 10
• Cardiac surgery (CABG): Though etomidate provides superior hemodynamic profile compared to ketamine-propofol combination, both require similar clinical responses to hypotension during induction 7

Awareness Prevention

• 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 1, 10