Ketamine Infusion in Anesthesia for HFrEF: Evidence Summary

Pharmacological Background

• Stimulates central sympathetic outflow and inhibits catecholamine reuptake
• Raises heart rate, mean arterial pressure, cardiac output, and SVR
• Increases myocardial oxygen consumption

• Negative inotrope at the cellular level
• In patients with severe HF who are already maximal on endogenous/exogenous catecholamines, this direct depression dominates

Key Evidence

1. The Landmark RCT - Christ et al. 1997 (PMID: 9209606)

2. Textbook Consensus (Multiple Sources)

• Cummings Otolaryngology / Barash Clinical Anesthesia (9e): "Ketamine is a sympathomimetic agent and may be useful for induction in children displaying hemodynamic instability; however, in children who are catecholamine-depleted, such as those with severe heart failure or shock, induction doses of ketamine can cause myocardial depression and hypotension."
• Roberts and Hedges' Clinical Procedures in Emergency Medicine: "Ketamine presents potential risk to patients with coronary artery disease because it is sympathomimetic and produces mild to moderate increases in blood pressure, heart rate, and myocardial oxygen consumption. Accordingly, other sedatives are preferred in the setting of known or possible ischemic heart disease, congestive heart failure, or hypertension."

3. Dilated Cardiomyopathy / HFrEF Anesthesia Review (Li & Huang 2023, PMID: 37763685)

4. Case Report - Peripartum Cardiomyopathy (LVEF 10-15%) (Kawamoto et al. 2021, PMID: 34898316)

5. Current HFrEF Anesthesia Practice (2024 Data)

6. Esketamine (S-ketamine) - Emerging Data

Mechanistic Interpretation for HFrEF

1. Catecholamine depletion: HFrEF patients are often chronically maximally adrenergically stimulated. There is no sympathetic reserve for ketamine to "recruit" - its direct myocardial depression goes unopposed.
2. Afterload intolerance: The +38% increase in SVR seen in the Christ et al. trial is particularly dangerous in HFrEF, where the failing ventricle is exquisitely sensitive to afterload increases. This worsens cardiac output by the Frank-Starling mechanism operating on the flat portion of the curve.
3. Pulmonary pressure elevation: The observed increase in PCWP and mPAP can precipitate acute pulmonary edema.
4. Contrast with tamponade/RV failure: In obstructive shock (tamponade, severe RV failure with pulmonary hypertension), ketamine's sympathomimetic effect is advantageous - it maintains afterload and prevents cardiac decompensation. HFrEF represents the opposite hemodynamic profile.

Clinical Recommendations Derived from Evidence

• Etomidate (minimal cardiovascular depression, first-choice induction in hemodynamically unstable patients)
• Remimazolam (emerging evidence for maintained hemodynamics in HFrEF)
• Ketamine in combination (very low-dose ketamine with propofol/opioid, sometimes used for induction, but requires close monitoring)
• Regional anesthesia whenever feasible

Bottom Line

• The best available controlled data (Christ et al. 1997 RCT) demonstrate significant worsening of cardiac index (-21%), elevated filling pressures, and increased SVR (+38%) in patients with LVEF ~30% on catecholamine support.
• Major textbooks and reviews consistently list CHF/HFrEF as a relative-to-absolute contraindication for ketamine infusion, particularly prolonged sedation.
• A brief single induction dose may be defensible in specific high-risk emergency scenarios (life-threatening hypotension, no alternatives), but sustained infusion should be avoided.
• The 2024 AHA/ACC perioperative guidelines (PMID: 39316661) address HF as a major perioperative risk factor but do not specifically endorse ketamine in HFrEF.
• Evidence gap: There are no large RCTs or prospective cohort studies specifically examining ketamine induction (not infusion) in HFrEF for noncardiac surgery. The field is extrapolating from the ICU infusion data and physiologic principles.

Sevoflurane vs. Ketamine vs. Propofol in HFrEF Anesthesia: Head-to-Head Evidence Review

Important framing: No head-to-head RCT has compared all three agents specifically in HFrEF/reduced-EF patients. The evidence is assembled from: (1) pharmacological studies in general populations, (2) cardiac surgery trials (CABG, valve), (3) specific HFrEF/low-EF studies, and (4) physiologic extrapolation. The closest direct comparison in low-EF patients is the propofol-ketamine vs. etomidate-midazolam study in CABG with EF <40%.

Head-to-Head Hemodynamic Profile in HFrEF

1. SEVOFLURANE

Hemodynamic Effects

Cardioprotective Properties (Key Differentiator)

• Diffusion through myocardial cell membranes
• Mitochondrial electron transport alteration → reactive oxygen species generation
• Protein kinase C activation → KATP channel opening
• ~30-40% of cardioprotection related to reduced calcium loading during ischemia

Summary for HFrEF

2. PROPOFOL INFUSION (TIVA)

Hemodynamic Effects (from Miller's Anesthesia 10e, p.2479-2481)

• -25% to -40% systolic BP from a 2.0-2.5 mg/kg induction dose
• Cardiac index -15%, stroke volume index -20%, LVSWI -30%
• SVR -15 to -25% (vasodilation - favorable for LV afterload, but simultaneous CO depression is net negative)
• Blunts the baroreflex - the tachycardic response to hypotension is attenuated, a dangerous feature in HFrEF where HR compensation is critical
• Hemodynamic depression lags the hypnotic effect by 2-7 minutes (effect-site equilibration) - blood pressure drops further after the patient loses consciousness

Propofol Infusion Syndrome (PRIS) Risk

Cardioprotective Properties

Summary for HFrEF

3. KETAMINE INFUSION

Hemodynamic Effects in HFrEF - The Critical Evidence

Comparative Summary Table

Preferred Anesthetic Approach in HFrEF (Evidence-Integrated)

• Sevoflurane (low MAC, 0.5-1.0): Best cardiovascular profile for HFrEF - modest afterload reduction, cardioprotective properties, titratable
• Propofol infusion (low rates, with hemodynamic monitoring): Acceptable, but no cardioprotective advantage; avoid high-dose prolonged infusion
• Ketamine infusion: Avoid based on direct RCT evidence of cardiac index reduction and increased filling pressures in the HFrEF population

• Christ et al. 1997 (PMID: 9209606) - Ketamine infusion RCT in HF (EF 30%)
• Jiao et al. 2019 (PMID: 31661512) - Volatile vs. TIVA meta-analysis in CABG
• Guinot et al. 2020 (PMID: 33327246) - Sevoflurane did not reduce myocardial injury vs. propofol
• Zarbock et al. 2025 (PMID: 41093687) - Propofol attenuates RIPC; sevoflurane preserves conditioning
• Miller's Anesthesia 10e, p.2479-2482 - Propofol cardiovascular pharmacology
• Barash Clinical Anesthesia 9e, p.1428-1429 - Volatile cardioprotection