What is the role of perioperative Levosimendan (Levosimendan) in off-pump Coronary Artery Bypass Grafting (CABG)?

Perioperative Levosimendan in Off-Pump CABG

Primary Recommendation

Perioperative levosimendan should be considered in patients with reduced left ventricular ejection fraction (LVEF <40%) undergoing off-pump CABG to reduce the risk of low cardiac output syndrome (LCOS), with the strongest evidence supporting preoperative administration at 0.1 μg/kg/min for 24 hours or a single bolus of 12-24 μg/kg over 10 minutes. 1

Evidence-Based Indications

Patients Who Benefit Most

• Patients with LVEF <30-40% undergoing isolated CABG represent the primary target population, as perioperative levosimendan reduces LCOS risk in this group (Class IIa recommendation, Level A evidence) 1
• Patients with poor LV function and perioperative LCOS may benefit from levosimendan to improve survival following cardiac surgery (Class IIb recommendation, Level B evidence) 1
• Prophylactic use in high-risk patients with reduced LVEF shows reduced incidence of postoperative atrial fibrillation (36.6% vs 6.6%), LCOS (30% vs 6%), and acute kidney injury (23.3% vs 6.7%) 2

Clinical Outcomes in Off-Pump CABG

Hemodynamic improvements include:

• Increased cardiac index and stroke volume throughout the perioperative period 3, 2, 4
• Reduced pulmonary capillary wedge pressure 3, 2
• Decreased systemic vascular resistance without significant changes in mean arterial pressure 4
• Lower serum lactate concentrations indicating improved tissue perfusion 2

Operational benefits include:

• Reduced conversion rate to cardiopulmonary bypass (10% in controls vs 0% with levosimendan) 2
• Decreased requirement for additional inotropes, IABP support, and CPB 3
• Shorter ICU stay 3
• Reduced time to tracheal extubation and lower postoperative troponin I concentrations 5

Dosing Strategies

Preoperative Prophylactic Approach (Preferred for High-Risk Patients)

• Start infusion 24 hours before surgery at 0.1 μg/kg/min, continuing through the operative period for total 24-hour duration 3, 2
• Alternative: 200 μg/kg total dose over 24 hours 3
• This approach shows superior outcomes in preventing LCOS compared to rescue therapy 2

Intraoperative Bolus Approach

• Single dose of 12-24 μg/kg over 10 minutes administered before or during surgery 5, 6, 4
• Low-dose (12 μg/kg) may be preferable to high-dose (24 μg/kg) as it produces better hemodynamic response in patients with good preoperative LV function 4
• Can be followed by continuous infusion of 0.1-0.2 μg/kg/min for 24 hours 6

Rescue Therapy for Difficult Weaning

• Loading dose of 12-24 μg/kg over 10 minutes when conventional inotropes and IABP prove insufficient 6
• Followed by continuous infusion of 0.1-0.2 μg/kg/min for 24 hours 6
• Success rate of 93.3% for weaning from CPB when used as rescue therapy 6

Important Contraindications and Limitations

When NOT to Use Levosimendan

• Prophylactic infusion to reduce adverse events and mortality is NOT recommended in general cardiac surgery populations (Class III recommendation, Level A evidence) 1
• Adding levosimendan to other inotropes/vasopressors in patients requiring hemodynamic support after cardiac surgery is NOT recommended (Class III recommendation, Level B evidence) 1
• These restrictions are based on three large multicenter trials showing no survival benefit with prophylactic use in unselected populations 1

Critical Caveat

The evidence shows a clear distinction: levosimendan benefits are specific to isolated CABG patients with reduced LVEF 1, particularly in the off-pump setting 3, 2, 4. The negative trials that led to Class III recommendations involved broader cardiac surgery populations and different clinical contexts 1.

Monitoring Requirements

Essential Parameters

• Cardiac output and stroke volume to assess inotropic response 5, 7
• Systemic and pulmonary vascular resistance to monitor vasodilatory effects 5, 7
• Heart rate and blood pressure continuously, as vasodilation may require vasopressor support 5, 7
• Pulmonary artery catheter measurements are valuable for monitoring pulmonary pressures and cardiac output 7

Vasopressor Support

• Maintain mean arterial pressure >60 mmHg with vasopressors (typically norepinephrine) as needed due to levosimendan's vasodilatory effects 2
• This is a common requirement and should be anticipated, not considered a complication 2

Mechanism-Based Advantages

Levosimendan's unique mechanism provides specific benefits in off-pump CABG:

• Calcium sensitization increases contractility without raising intracellular calcium, avoiding increased myocardial oxygen consumption 1, 5
• ATP-sensitive potassium channel opening provides coronary and peripheral vasodilation 5
• Reduced arrhythmogenic potential compared to catecholamines like dobutamine 1, 7
• Decreased incidence of postoperative atrial fibrillation and myocardial infarction compared to dobutamine 1, 7

Practical Algorithm for Off-Pump CABG

For patients with LVEF <40%:

1. Consider preoperative levosimendan infusion (0.1 μg/kg/min × 24h starting night before surgery) 3, 2
2. Ensure vasopressor availability (norepinephrine) for blood pressure support 2
3. Monitor cardiac index, PCWP, and lactate levels perioperatively 2

For patients with LVEF 30-50% (moderate dysfunction):

1. Consider intraoperative bolus (12 μg/kg over 10 minutes) before critical anastomoses 4
2. Reserve continuous infusion for those showing hemodynamic instability 4

For rescue situations (failure to maintain hemodynamics):

1. Administer loading dose 12-24 μg/kg over 10 minutes 6
2. Follow with continuous infusion 0.1-0.2 μg/kg/min × 24h 6
3. Expect 93% success rate for hemodynamic stabilization 6