Severe Lactic Acidosis After an Iatrogenic Propylene Glycol Overdose

Abstract

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 Fomepizole was discontinued, but the patient's prognosis was poor (anoxic brain injury); thus care was withdrawn and the patient died.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. Key Words: propylene glycol, lorazepam, iatrogenic overdose, severe lactic acidosis, critical care, fomepizole.

Efficacy and Tolerability of a High Loading Dose (25,000 IU Weekly) Vitamin D₃ Supplementation in Obese Children with Vitamin D Insufficiency/Deficiency

“…Most vitamin D supplementations are administered orally, however caution is necessary with oral vitamin D preparations containing propylene glycol such as Drisdol, because propylene glycol can be toxic at very high doses [11,12]. In this study, a cholecalciferol drink was used to prevent this type of toxicity.…”

Type B Lactic Acidosis Associated With Venlafaxine Overdose

“…8 Propylene glycol is also metabolized by the above pathway (alcohol dehydrogenase and aldehyde dehydrogenase) to lactic acid in addition to causing accumulation of NADH in a mechanism similar to ethanol. 11 It is commonly used as a stabilizing agent for intravenous infusions of lorazepam, phenobarbitol, and phenytoin; and type B lactic acidosis has been described in accidental overdose of these agents. 11 Alcohol has also been shown to cause buildup of mitochondrial reactive oxygen species and decreased reactive oxygen species detoxification by decreasing glutathione import and glutathione peroxidase activity.…”

“…11 It is commonly used as a stabilizing agent for intravenous infusions of lorazepam, phenobarbitol, and phenytoin; and type B lactic acidosis has been described in accidental overdose of these agents. 11 Alcohol has also been shown to cause buildup of mitochondrial reactive oxygen species and decreased reactive oxygen species detoxification by decreasing glutathione import and glutathione peroxidase activity. This leads to mitochondrial protein, lipid, and DNA damage that accumulates with repeated insults.…”

“…[4][5][6][7] The pathogenesis for this abnormal accumulation of lactate is diverse and ranges from derangements in enzymatic processes, 3,8 preferential switches in catabolic pathways, 9,10 and various levels of mitochondrial dysfunction. [11][12][13][14][15] We report the first case of type B lactic acidosis that was caused by the overdose of the serotonin-norepinephrine reuptake inhibitor, venlafaxine. 1 …”

Is Serum Lactate Level a Prognostic Factor for the Incidence and Mortality of Ventilator-Associated Pneumonia Among Poisoned ICU-Admitted Patients?

“…On the other hand, methanol was the second rampant toxicant among patients in the present study. Also, alcohols (propylene glycol and methanol) have been implicated in enhanced lactate level, and lactate can be falsely increased in such cases (30)(31)(32)(33)(34).…”