Propylene glycol is a diluent found in many intravenous and oral drugs, including
phenytoin,
diazepam, and
lorazepam.
Propylene glycol is eliminated from the body by oxidation through
alcohol dehydrogenase to form
lactic acid. Under normal conditions, the body converts
lactate to
pyruvate and metabolizes
pyruvate through the Krebs cycle.
Lactic acidosis has occurred in patients, often those with renal dysfunction, who were receiving prolonged infusions of drugs that contain
propylene glycol as a diluent. We describe a 50-year-old man who experienced severe
lactic acidosis after receiving an accidental overdose of
lorazepam, which contains
propylene glycol. The patient was acutely intoxicated, with a serum
ethanol concentration of 406 mg/dl. He had choked on a large piece of meat and subsequently experienced pulseless electrical activity with
ventricular fibrillation cardiac arrest. He was brought to the emergency department; within 2 hours, he was admitted to the intensive care unit for initiation of the
hypothermia protocol. The patient began to experience
generalized tonic-clonic seizures 12 hours later, which resolved after several boluses of
lorazepam. A
lorazepam infusion was started; however, it was inadvertently administered at a rate of 2 mg/minute instead of the standard rate of 2 mg/hour. Ten hours later, the administration error was recognized and the infusion stopped. The patient's peak
propylene glycol level was 659 mg/dl, pH 6.9, serum
bicarbonate level 5 mEq/L, and
lactate level 18.6 mmol/L.
Fomepizole was started the next day and was continued until hospital day 3.
Continuous renal replacement therapy was started and then replaced with
continuous venovenous hemofiltration (CVVH) for the remainder of the
hospital stay. The patient's
acidosis resolved by day 3, when his
propylene glycol level had decreased to 45 mg/dl.
Fomepizole was discontinued, but the patient's prognosis was poor (anoxic
brain injury); thus care was withdrawn and the patient died. Although the patient's outcome was death, his
lactic acidosis was treated successfully with
fomepizole and CVVH. Clinicians should be aware that an iatrogenic overdose of
lorazepam may result in severe
propylene glycol toxicity, which may be treated with
fomepizole and CVVH.