Severe lactic acidosis after an iatrogenic propylene glycol overdose. 2010

Amy Zosel, and Elizabeth Egelhoff, and Kennon Heard
Rocky Mountain Poison and Drug Center-Denver Health,777 Bannock Street, MC 0180, Denver, CO 80204, USA.

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 Fomepizole was discontinued, but the patient's prognosis was poor (anoxic brain injury); thus care was withdrawn and the patient died.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.

UI MeSH Term Description Entries
D007049 Iatrogenic Disease Any adverse condition in a patient occurring as the result of treatment by a physician, surgeon, or other health professional, especially infections acquired by a patient during the course of treatment. Hospital-Acquired Condition,Condition, Hospital-Acquired,Conditions, Hospital-Acquired,Disease, Iatrogenic,Diseases, Iatrogenic,Hospital Acquired Condition,Hospital-Acquired Conditions,Iatrogenic Diseases
D007262 Infusions, Intravenous The long-term (minutes to hours) administration of a fluid into the vein through venipuncture, either by letting the fluid flow by gravity or by pumping it. Drip Infusions,Intravenous Drip,Intravenous Infusions,Drip Infusion,Drip, Intravenous,Infusion, Drip,Infusion, Intravenous,Infusions, Drip,Intravenous Infusion
D008297 Male Males
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000140 Acidosis, Lactic Acidosis caused by accumulation of lactic acid more rapidly than it can be metabolized. It may occur spontaneously or in association with diseases such as DIABETES MELLITUS; LEUKEMIA; or LIVER FAILURE. Lactic Acidosis
D014677 Pharmaceutical Vehicles A carrier or inert medium used as a solvent (or diluent) in which the medicinally active agent is formulated and or administered. (Dictionary of Pharmacy, 1986) Pharmaceutical Vehicle,Vehicle, Pharmaceutical,Vehicles, Pharmaceutical
D019946 Propylene Glycol A clear, colorless, viscous organic solvent and diluent used in pharmaceutical preparations. 1,2-Propanediol,Propan-1,2-Diol,Propylene Glycol Monohydrate,Propylene Glycol Sodium Salt,Propylene Glycol, (+-)-Isomer,Propylene Glycol, (R)-Isomer,Propylene Glycol, (S)-Isomer,1,2 Propanediol,Glycol, Propylene,Monohydrate, Propylene Glycol
D062787 Drug Overdose Accidental or deliberate use of a medication or street drug in excess of normal dosage. Drug Overdoses,Overdose, Drug,Overdoses, Drug

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