title: Short-term lorazepam infusion and concern for propylene glycol toxicity: case report and review.
abstract: A 34-year-old woman with a history of renal insufficiency induced by long-term cocaine use was admitted with acute shortness of breath remarkable for submandibular and anterior throat swelling. She required intubation, mechanical ventilation, and sedation. Sedation was administered with daily infusions of intravenous lorazepam 65, 313, and 305 mg for 3 days, respectively. Forty-eight hours into the infusion the patient experienced anion gap metabolic acidosis with hyperlactatemia, hyperosmolality, and increased osmolal gap. Propylene glycol (PG), a component of lorazepam intravenous formulation, was considered the potential source of the metabolic abnormality. The patient received greater than 40 times the acceptable recommended amount of PG over 72 hours. Cessation of lorazepam produced major improvements in lactic acid, serum osmolality, and anion and osmolal gaps. The large PG exposure associated with long-term cocaine-induced renal insufficiency produced a toxic metabolic state. Agents containing PG should be avoided in patients with compromised renal function (creatinine clearance < or = 30 ml/min) induced by cocaine use.
authors.affiliation: Department of Pharmacy Practice and Pharmacy Administration, Philadelphia College of Pharmacy, University of the Sciences, Pennsylvania 19104-3395, USA. m.cawley@usip.edu
authors.forename: M J
authors.initials: MJ
authors.lastname: Cawley
mesh_terms: D000328:Adult; D019970:Cocaine-Related Disorders / Q000150:complications; D003422:Critical Care; D016883:Diabetic Ketoacidosis / Q000139:chemically induced; D005079:Excipients; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000009:adverse effects*; D007262:Infusions, Intravenous; D007676:Kidney Failure, Chronic / Q000150:complications* / Q000378:metabolism; D008140:Lorazepam / Q000008:administration & dosage / Q000009:adverse effects*; D011409:Propylene Glycols / Q000008:administration & dosage / Q000009:adverse effects*; D012140:Respiratory Tract Diseases / Q000150:complications
chemical_list: D005079:Excipients; D006993:Hypnotics and Sedatives; D011409:Propylene Glycols; D008140:Lorazepam