Role of Milrinone and Levophed (Norepinephrine) in Cardiogenic Shock
In cardiogenic shock, norepinephrine is recommended as the preferred vasopressor when mean arterial pressure needs pharmacologic support, while milrinone may be particularly beneficial in patients on beta-blockers or with right ventricular dysfunction. 1
Definition and Pathophysiology
- Cardiogenic shock is defined as hypotension (SBP <90 mmHg) despite adequate filling status with signs of hypoperfusion, including low urine output, cold extremities, altered mental status, elevated lactate levels, and low mixed venous oxygen saturation 1
- It represents a state of low cardiac output leading to tissue hypoperfusion and organ dysfunction, most commonly caused by acute myocardial infarction but also by other etiologies 2
Initial Management Approach
- Immediate comprehensive assessment, including ECG and echocardiography, is required in all patients with suspected cardiogenic shock 1
- Invasive monitoring with an arterial line is recommended for continuous blood pressure monitoring 1
- Fluid challenge should be administered as first-line treatment if there are no signs of overt fluid overload 1
- All patients with cardiogenic shock should be rapidly transferred to a tertiary care center with 24/7 cardiac catheterization capabilities and dedicated ICU with availability of mechanical circulatory support 1
Role of Milrinone in Cardiogenic Shock
Mechanism and Indications
- Milrinone is a phosphodiesterase-3 inhibitor that increases cardiac output and stroke volume while reducing pulmonary artery pressure, pulmonary wedge pressure, and systemic and pulmonary vascular resistance 1
- It works through a mechanism independent of beta-adrenergic receptors, making it particularly valuable in patients on beta-blocker therapy 1
- Milrinone is especially useful in right ventricular failure and pulmonary hypertension due to its pulmonary vasodilatory effects 1
Clinical Evidence and Recommendations
- Retrospective analyses suggest similar outcomes with dobutamine and milrinone in cardiogenic shock 1
- A recent randomized controlled trial (DOREMI) found no significant difference between milrinone and dobutamine with respect to a composite outcome of in-hospital death, resuscitated cardiac arrest, mechanical circulatory support, myocardial infarction, stroke, or renal replacement therapy 3
- Milrinone may cause more hypotension compared to dobutamine (49.2% vs 40.3%), requiring careful monitoring and potentially concomitant vasopressor support 4
- Milrinone is associated with fewer arrhythmias compared to dobutamine (32.8% vs 62.9%) 4
Role of Levophed (Norepinephrine) in Cardiogenic Shock
Mechanism and Indications
- Norepinephrine functions as a peripheral vasoconstrictor (alpha-adrenergic action) and as an inotropic stimulator of the heart (beta-adrenergic action) 5
- It is indicated when mean arterial pressure needs pharmacologic support after initial inotropic therapy fails to restore adequate blood pressure and organ perfusion 1
Dosing and Administration
- Initial dilution: Add 4 mg/4 mL of norepinephrine to 1,000 mL of 5% dextrose solution (resulting in 4 mcg/mL) 5
- Starting dose: 2-3 mL/minute (8-12 mcg/minute) with adjustment to maintain systolic blood pressure 80-100 mmHg 5
- Average maintenance dose ranges from 0.5-1 mL/minute (2-4 mcg/minute) 5
- Administration requires a central venous catheter and continuous blood pressure monitoring 5
Clinical Evidence and Recommendations
- Limited data support norepinephrine as the preferred first-line vasopressor in cardiogenic shock 1
- Norepinephrine is recommended when the combination of an inotropic agent and fluid challenge fails to restore SBP >90 mmHg with inadequate organ perfusion 1
- Subgroup analysis from a randomized controlled trial showed that patients with cardiogenic shock treated with norepinephrine versus dopamine had improved survival at 28 days 1
Combination Therapy Approach
- In patients with LV-dominant cardiogenic shock, milrinone can improve cardiac output by reducing afterload, while norepinephrine maintains coronary and systemic perfusion pressure 1
- When using milrinone, concomitant use of agents that increase systemic afterload without increasing pulmonary vascular resistance, such as norepinephrine, may be needed to maintain right ventricular perfusion 1
- In right ventricular failure, the combination is particularly beneficial as milrinone reduces RV afterload while norepinephrine maintains RV perfusion pressure 1
Special Considerations
Right Ventricular Failure
- The RV prefers euvolemia with a central venous pressure of 8-12 mmHg; inappropriate volume loading can worsen RV dilation and tricuspid regurgitation 1
- Milrinone is preferred in RV failure due to its pulmonary vasodilatory effects 1
- Concomitant norepinephrine may be needed to maintain RV perfusion during milrinone therapy 1
Patients on Beta-Blockers
- Milrinone has mechanisms of action independent of beta-adrenergic receptors, making it valuable in patients on beta-blocker therapy 1
- Higher doses of inotropes may be required to overcome beta-blockade effects 6
Monitoring Parameters
- Continuous blood pressure monitoring (target SBP >90 mmHg) 1
- Cardiac output and cardiac index (target >2 L/min/m²) 6
- Signs of improved organ perfusion: urine output, mental status, lactate clearance 6
- Heart rate and rhythm (watch for tachyarrhythmias) 6
- Consider pulmonary artery catheterization for tailored therapy based on hemodynamic parameters 1
Important Caveats
- All inotropes should be used at the lowest possible doses for the shortest duration due to their propensity to increase myocardial oxygen demand, ischemic burden, and risk of arrhythmias 1
- When vasopressors are needed, they should be used with caution and discontinued as soon as possible, as cardiogenic shock is usually associated with high systemic vascular resistance 1
- Consider mechanical circulatory support rather than combining multiple inotropes in patients not responding adequately to pharmacologic therapy 6