What is the recommended dose of levosimendan (Simdax) for a preoperative patient undergoing Coronary Artery Bypass Grafting (CABG)?

Levosimendan Dosing for Preoperative CABG Patients

Recommended Dosing Regimen

For preoperative CABG patients with reduced left ventricular ejection fraction (LVEF ≤40%), administer levosimendan as a continuous infusion of 0.1 μg/kg/min for 24 hours, starting after anesthesia induction, without a loading bolus. 1, 2

Evidence-Based Dosing Protocols

Standard Preoperative Protocol

• Infusion rate: 0.1 μg/kg/min continuous infusion for 24 hours 3, 4
• Timing: Start after anesthesia induction, before cardiopulmonary bypass 2, 3
• Loading dose: Omit the loading bolus to minimize hypotension risk 4, 5
• Total dose: This regimen delivers approximately 12.5 mg over 24 hours for a 70 kg patient 6, 5

Alternative Single-Dose Protocol

• Single bolus: 24 μg/kg administered over 10 minutes before cardiopulmonary bypass 2
• This simplified approach has demonstrated reduced time to extubation, shorter ICU stay, and lower postoperative troponin levels 2

Low-Dose Individualized Approach

• Initial dose: 1.25 mg after anesthesia induction 5
• Subsequent dosing: Repeat 1.25 mg increments postoperatively based on hemodynamic monitoring until cardiovascular stability achieved 5
• In 73.2% of patients, cumulative doses of 5 mg or less were sufficient 5

Clinical Indications and Patient Selection

Primary Indication

• LVEF ≤40%: Perioperative levosimendan should be considered to reduce the risk of low cardiac output syndrome in patients with reduced LVEF undergoing isolated CABG 1

High-Risk Patients Who Benefit Most

• LVEF <25%: Patients with severe left ventricular dysfunction show the most dramatic mortality reduction (3.9% vs 12.8% in controls) 3
• History of heart failure: Symptomatic heart failure patients benefit from preoperative optimization 2, 6
• Risk factors for LCOS: Those at elevated risk for developing postoperative low cardiac output syndrome 2

Clinical Outcomes and Benefits

Mortality and Major Complications

• Preoperative levosimendan reduces 30-day mortality from 12.8% to 3.9% in patients with LVEF <25% 3
• Decreases complicated weaning from cardiopulmonary bypass (2.4% vs 9.6%) 3
• Reduces incidence of LCOS (7.1% vs 20.8% in controls) 3

Reduced Need for Support Therapies

• Lower requirement for inotropes (7.9% vs 58.4%) 3
• Decreased need for vasopressors (14.2% vs 45.6%) 3
• Reduced intra-aortic balloon pump use (6.3% vs 30.4%) 3

Additional Benefits

• Decreased postoperative atrial fibrillation, myocardial infarction, and ventricular arrhythmias compared to dobutamine 2
• Reduced ICU length of stay and acute renal dysfunction 2
• Improved LVEF on postoperative day 7 (from 35.8% to 42.8%) 4

Hemodynamic Monitoring Parameters

Essential Monitoring During Infusion

• Cardiac output and stroke volume: Should increase progressively 2, 6
• Systemic vascular resistance: Expect decrease from vasodilation 2, 6
• Pulmonary vascular resistance and wedge pressure: Should decrease 2
• Heart rate and blood pressure: Monitor for hypotension 2
• Central venous or mixed venous oxygen saturation: Should improve 5
• Lactate clearance: Monitor for tissue perfusion 5

Expected Hemodynamic Changes

• Cardiac index increases from approximately 2.4 to 3.2 L/min/m² within 24 hours 6
• Stroke volume index increases from 27 to 37 mL/m² 6
• Systemic vascular resistance decreases from 2718 to 1964 dyn·s·cm⁻⁵·m⁻² 6
• Effects persist up to 48 hours due to active metabolites 6

Critical Pitfalls and Management Strategies

Hypotension Management

• Avoid loading bolus: The standard 10 μg/kg loading dose frequently causes hypotension; omit it in preoperative patients 4, 5
• Vasopressor readiness: Have vasopressors immediately available, as vasodilation is expected 2
• Fluid management: Monitor for increased extravascular lung water during first 24 hours postoperatively 4

Timing Considerations

• Start minimum 2 hours before surgery: Allows hemodynamic optimization before surgical stress 6
• Continue through surgery: The 24-hour infusion should span the perioperative period 3, 4
• Do not discontinue prematurely: Full 24-hour infusion provides optimal benefit from active metabolites 3

Drug Interactions

• Reduced arrhythmogenic potential: Safer than dobutamine in this regard 2
• Coordinate with anesthesia team: Ensure communication about ongoing infusion and hemodynamic goals 2

Guideline Recommendations Summary

The 2025 European Association for Cardio-Thoracic Surgery guidelines provide the most current evidence-based recommendations:

• Class IIa recommendation: Perioperative levosimendan should be considered to reduce LCOS risk in patients with reduced LVEF undergoing isolated CABG 1
• Class IIb recommendation: May be considered to improve survival in patients with poor LV function and perioperative LCOS 1

These recommendations reflect Level A and Level B evidence, indicating robust clinical trial data supporting levosimendan use in this population 1.