What are the symptoms of milrinone toxicity?

Milrinone Toxicity: Symptoms and Clinical Findings

Milrinone toxicity primarily manifests as cardiovascular complications including hypotension, arrhythmias (especially atrial fibrillation), and thrombocytopenia, which can significantly impact patient morbidity and mortality.

Cardiovascular Manifestations

Arrhythmias

• Ventricular arrhythmias (12.1% of patients) 1:

  • Ventricular ectopic activity (8.5%)
  • Nonsustained ventricular tachycardia (2.8%)
  • Sustained ventricular tachycardia (1%)
  • Ventricular fibrillation (0.2%)

• Supraventricular arrhythmias (3.8% of patients) 1:

  • Atrial fibrillation is particularly common
  • Milrinone increases atrial automaticity and shortens atrial action potential duration 2
  • Shortens AV node conduction time, potentially increasing ventricular response rate in atrial flutter/fibrillation 1

• Life-threatening arrhythmias may occur, especially with:

  • Pre-existing arrhythmias
  • Metabolic abnormalities (especially hypokalemia)
  • Abnormal digoxin levels
  • During catheter insertion 1
  • Rare cases of torsades de pointes have been reported 1

Hypotension

• Significant hypotension (2.9% of patients) due to vasodilatory effects 1
• Excessive vasodilation can lead to profound hypotension, especially:
  • After loading doses
  • In hypovolemic patients
  • In patients with pre-existing low systemic vascular resistance 3
  • When used with other vasodilators

Other Significant Toxicities

Hematologic Effects

• Thrombocytopenia (0.4% of patients) 1
• Requires regular monitoring of platelet counts during therapy

Neurological Effects

• Headaches (2.9% of patients), usually mild to moderate in severity 1
• Tremor (0.4% of patients) 1

Electrolyte Abnormalities

• Hypokalemia (0.6% of patients) 1
• Can worsen arrhythmic potential, especially in digitalized patients

Hypersensitivity Reactions

• Bronchospasm and anaphylactic shock (rare, isolated reports) 1
• Skin reactions such as rash (post-marketing reports) 1

Hepatic Effects

• Liver function test abnormalities (post-marketing reports) 1

Risk Factors for Toxicity

• Renal impairment: Milrinone is primarily cleared by the kidneys; impaired renal function leads to drug accumulation 3
• Pre-existing cardiovascular disease: Patients with coronary artery disease may have increased medium-term mortality 3
• Concomitant medications: Digitalis glycosides may increase risk of arrhythmias 1
• Electrolyte abnormalities: Especially hypokalemia 1

Monitoring Recommendations

• Continuous ECG monitoring during infusion and for 1-2 hours after discontinuation 3
• Blood pressure monitoring with readiness to slow or stop infusion if excessive hypotension occurs 1
• Daily laboratory monitoring:
  • Electrolytes (especially potassium)
  • BUN and creatinine
  • Complete blood count (for thrombocytopenia) 3
• Infusion site monitoring to avoid extravasation 1

Clinical Pearls

• Toxicity risk increases with higher doses and longer duration of therapy
• Patients with acute renal failure or end-stage renal disease require significant dose adjustments 4
• The combination of hypotension and arrhythmias can rapidly lead to hemodynamic collapse
• Milrinone's long half-life (1-10 hours depending on organ function) means toxicity may persist after discontinuation 2
• Avoid administering furosemide in the same IV line as milrinone due to precipitation 1

By recognizing these signs and symptoms early, clinicians can intervene promptly to prevent serious complications from milrinone toxicity.