Can Barbiturates Cause Lactic Acidosis?
Barbiturates themselves do not directly cause lactic acidosis through their pharmacologic mechanism, but propylene glycol—a diluent used in intravenous barbiturate formulations like pentobarbital—can cause severe lactic acidosis when administered in high doses or prolonged infusions.
Direct Barbiturate Effects
Barbiturates are derivatives of barbituric acid that primarily cause respiratory and cardiovascular depression through suppression of medullary centers, but they do not directly induce lactic acidosis as a pharmacologic effect 1.
The main toxic effects of barbiturates include respiratory depression leading to potential tissue hypoxia, cardiovascular depression with hypotension, and CNS depression 1.
While severe barbiturate overdose could theoretically cause secondary type A lactic acidosis through tissue hypoxia from profound respiratory or cardiovascular collapse, this is not a characteristic or commonly reported feature of barbiturate toxicity 1.
Propylene Glycol-Induced Lactic Acidosis: The Real Culprit
The critical issue is that intravenous pentobarbital contains 40% v/v propylene glycol as a vehicle, and this diluent is the actual cause of lactic acidosis in patients receiving continuous pentobarbital infusions 2.
Mechanism of Propylene Glycol Toxicity
Propylene glycol is eliminated through oxidation by alcohol dehydrogenase to form lactic acid, which under normal conditions is converted to pyruvate and metabolized through the Krebs cycle 3.
When propylene glycol accumulates from high-dose or prolonged infusions (particularly in patients with renal dysfunction), it overwhelms metabolic capacity and causes severe lactic acidosis 2, 3.
Clinical Presentation
Propylene glycol toxicity presents with anion gap metabolic acidosis, elevated serum lactate, hyperosmolality, and increased osmolal gap 2.
This typically occurs 12-24 hours after starting continuous pentobarbital infusions, particularly at doses of 10 mg/kg/hour or higher 2.
Management of Propylene Glycol-Induced Lactic Acidosis
Immediately discontinue the pentobarbital infusion when propylene glycol toxicity is suspected 2.
Fomepizole should be initiated to inhibit alcohol dehydrogenase and prevent further conversion of propylene glycol to lactic acid 3.
Continuous venovenous hemofiltration (CVVH) or continuous renal replacement therapy effectively removes both propylene glycol and lactate 3.
Resolution of acidosis typically occurs within 24-72 hours after discontinuation of the offending agent and initiation of appropriate treatment 2, 3.
Clinical Pitfalls and Monitoring
Clinicians must recognize that the pentobarbital formulation itself (50 mg/mL in a vehicle of propylene glycol, alcohol, and water) poses the risk, not the barbiturate molecule 4, 2.
Patients receiving continuous pentobarbital infusions require monitoring for signs of propylene glycol toxicity, including serial lactate levels, osmolal gap calculations, and arterial blood gases 2.
Risk factors include renal dysfunction, prolonged infusions (>24-48 hours), and high infusion rates 2, 3.
Iatrogenic overdoses of lorazepam (another propylene glycol-containing medication) have resulted in propylene glycol levels as high as 659 mg/dL with severe lactic acidosis (pH 6.9, lactate 18.6 mmol/L) 3.