Milrinone Side Effects
The most common side effect of milrinone is systemic hypotension, which can significantly impact patient morbidity and mortality when using this inotropic agent. 1, 2
Cardiovascular Side Effects
- Hypotension: The most common and clinically significant side effect of milrinone, occurring due to its vasodilatory properties 1, 2
- Arrhythmias: Ventricular arrhythmias reported in 12.1% of patients in clinical trials, including:
- Ventricular ectopic activity (8.5%)
- Nonsustained ventricular tachycardia (2.8%)
- Sustained ventricular tachycardia (1%)
- Ventricular fibrillation (0.2%) 2
- Supraventricular arrhythmias: Reported in 3.8% of patients 2
- Rare cases of torsades de pointes have been reported in post-marketing surveillance 2
- Atrial fibrillation: Milrinone can increase atrial automaticity and shorten atrial action potential duration/effective refractory period, potentially triggering atrial fibrillation 1
- Angina/chest pain: Reported in 1.2% of patients, particularly concerning in patients with underlying coronary artery disease 2, 3
Central Nervous System Effects
- Headaches: Usually mild to moderate in severity, reported in 2.9% of patients 2
- Tremor: Reported in 0.4% of patients 2
Other Side Effects
- Hypokalemia: Reported in 0.6% of patients 2
- Thrombocytopenia: Reported in 0.4% of patients (much less common than with amrinone) 2, 4
- Bronchospasm and anaphylactic shock: Isolated spontaneous reports in post-marketing surveillance 2
- Liver function test abnormalities: Reported in post-marketing experience 2
- Skin reactions: Including rash, reported in post-marketing experience 2
- Infusion site reactions: Reported in post-marketing experience 2
Clinical Considerations and Risk Factors
- Dosage-related effects: Milrinone is typically administered at 0.25-0.75 μg/kg/min, with higher doses increasing risk of adverse effects 1
- Renal impairment: Increased risk of adverse effects due to reduced clearance, as milrinone is primarily eliminated through the kidneys 4, 5
- Pre-existing arrhythmias: Higher risk of life-threatening arrhythmias 2
- Metabolic abnormalities: Particularly hypokalemia, can increase arrhythmia risk 2
- Abnormal digoxin levels: Can potentiate arrhythmogenic effects 2
- Catheter insertion: Associated with increased risk of arrhythmias during milrinone administration 2
Precautions in Specific Clinical Scenarios
- Heart failure: While milrinone improves cardiac output and reduces pulmonary wedge pressure, long-term use outside of palliative care or as bridge therapy may be harmful 1
- Cardiogenic shock: When used, careful monitoring is required due to risk of hypotension; may be used with vasopressors to maintain coronary perfusion pressure 1
- Right ventricular failure: Can be effective but requires careful dosing to avoid systemic hypotension 1
- Beta-blocker therapy: Milrinone may be preferred over dobutamine in patients on beta-blockers as its mechanism of action is distal to beta-adrenergic receptors 1
Monitoring Recommendations
- Blood pressure: Continuous monitoring during initiation and dose adjustments due to risk of hypotension 2, 6
- Cardiac rhythm: ECG monitoring for detection of arrhythmias 2
- Electrolytes: Particularly potassium levels, as hypokalemia can increase arrhythmia risk 2
- Renal function: As milrinone is primarily cleared by the kidneys 4, 5
- Liver function tests: Due to reported abnormalities in post-marketing surveillance 2