Adverse Effects of Milrinone
Milrinone can cause serious cardiovascular adverse effects including ventricular arrhythmias, atrial fibrillation, hypotension, and in rare cases, torsades de pointes, which can significantly impact morbidity and mortality. 1
Cardiovascular Adverse Effects
Arrhythmias
Ventricular arrhythmias: Occur in 12.1% of patients receiving milrinone 1
- Ventricular ectopic activity (8.5%)
- Non-sustained ventricular tachycardia (2.8%)
- Sustained ventricular tachycardia (1%)
- Ventricular fibrillation (0.2%)
Supraventricular arrhythmias: Reported in 3.8% of patients 1
Hypotension
- Occurs in approximately 2.9% of patients 1
- Results from milrinone's vasodilatory effects
- May require fluid boluses to counteract, especially when loading doses are administered 2
- Particularly concerning in patients with already compromised hemodynamics
Other Adverse Effects
Central Nervous System Effects
Hematologic Effects
- Thrombocytopenia (0.4%) 1
- Requires monitoring of platelet counts during therapy
Electrolyte Disturbances
- Hypokalemia (0.6%) 1
- Can exacerbate arrhythmic risk
Rare but Serious Adverse Effects
- Bronchospasm and anaphylactic shock (isolated reports) 1
- Liver function test abnormalities 1
- Skin reactions such as rash 1
- Infusion site reactions 1
Risk Factors for Adverse Effects
Patient-Specific Factors
- Pre-existing arrhythmias
- Electrolyte abnormalities (especially hypokalemia)
- Abnormal digoxin levels
- Invasive catheter insertion 1
- Renal impairment (milrinone is primarily cleared by renal excretion) 3
- Coronary artery disease (may increase medium-term mortality) 4
Medication-Related Factors
- Higher doses correlate with increased risk of adverse effects
- Long-term oral milrinone therapy increases mortality 2
- In acute heart failure, IV milrinone does not reduce hospitalizations or cardiovascular events but leads to higher incidence of treatment-related hypotension compared to placebo 2
Monitoring Recommendations
To minimize adverse effects, the following monitoring is essential:
- Continuous ECG monitoring during infusion and for 1-2 hours after discontinuation 4
- Daily laboratory monitoring of electrolytes, BUN, and creatinine 4
- Hemodynamic monitoring to assess response to therapy 4
- Facilities for immediate treatment of potential cardiac events must be available 4
Dosing Considerations
For patients with renal impairment, dose adjustment is crucial:
| Creatinine Clearance (mL/min/1.73m²) | Recommended Infusion Rate (mcg/kg/min) |
|---|---|
| 5 | 0.2 |
| 10 | 0.23 |
| 20 | 0.28 |
| 30 | 0.33 |
| 40 | 0.38 |
| 50 | 0.43 |
Clinical Implications
When using milrinone, clinicians should:
- Be aware that milrinone maintains effectiveness in patients on beta-blocker therapy (unlike dobutamine) 4
- Consider that milrinone causes less tachycardia than dobutamine but may cause more hypotension 5
- Recognize that milrinone has a long half-life (1-10 hours depending on organ function), making adverse effects potentially prolonged 2
- Implement gradual tapering when discontinuing milrinone to prevent hemodynamic deterioration 4
- Avoid routine use in normotensive patients with acute decompensated heart failure without evidence of decreased organ perfusion 4
The risk-benefit profile of milrinone requires careful consideration, particularly in patients with pre-existing cardiovascular disease, renal dysfunction, or electrolyte abnormalities, as the adverse effects can significantly impact patient outcomes and survival.