What type of arrhythmia may propylene glycol cause?

Propylene Glycol Can Cause Cardiac Arrhythmias Including Torsades de Pointes and Ventricular Tachycardia

Propylene glycol can cause serious cardiac arrhythmias, most notably torsades de pointes and other ventricular tachyarrhythmias, particularly when administered at high doses or in patients with risk factors. 1, 2

Mechanism and Presentation of Propylene Glycol-Induced Arrhythmias

Propylene glycol is commonly used as a diluent in many intravenous and oral medications, particularly in parenteral formulations of lorazepam and other benzodiazepines. The cardiac effects occur through several mechanisms:

1. Direct cardiac toxicity: Propylene glycol can directly affect cardiac conduction
2. QT prolongation: Similar to other QT-prolonging agents, it can predispose to torsades de pointes 1
3. Metabolic derangements: Propylene glycol is metabolized to lactic acid, causing metabolic acidosis that can trigger arrhythmias 3, 4
4. Hyperosmolarity: Creates an electrolyte imbalance that affects cardiac conduction 2

Risk Factors for Propylene Glycol-Induced Arrhythmias

Certain patient populations are at higher risk for developing arrhythmias from propylene glycol:

• Renal dysfunction: Reduced clearance leads to accumulation 1, 4
• Hepatic dysfunction: Impaired metabolism increases toxicity 4
• High doses: Total daily IV doses as low as 1 mg/kg of propylene glycol-containing medications can cause toxicity 1
• Prolonged infusions: Continuous administration increases risk 3
• Concomitant QT-prolonging medications: Additive effects increase arrhythmia risk 1
• Pre-existing cardiac disease: Increases susceptibility to arrhythmogenic effects 2

Monitoring and Detection

Early detection of propylene glycol toxicity is crucial to prevent serious arrhythmias:

• ECG monitoring: Watch for QT prolongation and other conduction abnormalities
• Serum osmol gap: An osmol gap >10-12 mOsm/L suggests significant propylene glycol accumulation 1
• Metabolic parameters: Monitor for metabolic acidosis, elevated lactate levels, and anion gap 3, 2
• Clinical symptoms: Watch for hypotension, CNS depression, and seizures that may accompany cardiac effects 2

Management of Propylene Glycol-Induced Arrhythmias

When arrhythmias occur due to propylene glycol toxicity:

1. Immediate discontinuation of the propylene glycol-containing medication 1
2. Specific arrhythmia management:
   • For torsades de pointes: IV magnesium sulfate, cardiac pacing, or isoproterenol 1
   • For ventricular tachycardia: Standard ACLS protocols with consideration of beta blockers 1
3. Elimination enhancement:
   • Hemodialysis or continuous renal replacement therapy effectively removes propylene glycol 3, 4
   • Consider fomepizole in severe cases to block metabolism to toxic metabolites 3
4. Supportive care:
   • Correction of electrolyte abnormalities
   • Management of acidosis
   • Hemodynamic support as needed

Prevention Strategies

To prevent propylene glycol-induced arrhythmias:

• Use alternative formulations when possible in high-risk patients
• Limit cumulative doses of propylene glycol-containing medications 1
• Regular monitoring of ECG, osmol gap, and metabolic parameters in patients receiving high doses or prolonged therapy 2
• Early recognition of risk factors and symptoms of toxicity

Clinical Pitfalls and Caveats

• Propylene glycol toxicity can mimic sepsis or other critical illnesses, leading to delayed diagnosis 5
• Symptoms may be attributed to the underlying condition rather than to the medication vehicle
• Toxicity can occur at lower doses than previously recognized, especially in patients with renal dysfunction 1
• The combination of propylene glycol with other cardiotoxic medications may have synergistic effects on arrhythmogenesis

Remember that propylene glycol toxicity is often overlooked as a cause of new-onset arrhythmias in critically ill patients. Maintaining a high index of suspicion, especially in patients receiving medications known to contain propylene glycol (such as lorazepam, diazepam, and phenytoin), is essential for early recognition and management.