Glycols intravenous lorazepam

A 34-year-old woman with a history of renal insufficiency induced by long-term use of cocaine developed respiratory failure and was intubated and sedated with intravenous lorazepam (65 mg, 313 mg, and 305 mg on 3 consecutive days). After 2 days she had a metabolic acidosis, with hyperlactatemia and hyperosmolality. Propylene glycol, a component of the lorazepam intravenous formulation, was considered as a potential source of the acidosis, as she had received more than 40 times the recommended amount over 72 hours. Withdrawal of lorazepam produced major improvements in lactic acid and serum osmolality. 

A 57-year-old man with a history of alcohol abuse developed acute respiratory failure and was given lorazepam up to 18 mg/hour during alcohol withdrawal (17). On day 43 (cumulative intravenous lorazepam dose 4089 mg, containing about 220 ml of polyethylene glycol 400), he developed oliguric acute tubular necrosis with proteinuria and granular casts. 

Lame GA, Hossain SM, Solis RT, Adams SC. Polyethylene glycol nephrotoxicity secondary to prolonged high-dose intravenous lorazepam. Ann Pharmacother 1995 29(11) 1110-14. 

Hayman M, Seidl EC, Ah M, Malik K. Acute tubular necrosis associated with propylene glycol from concomitant administration of intravenous lorazepam and trimethoprim-sulfamethoxazole. Pharmacotherapy 2003 23 1190-1194. 

Horinek EL, Kiser TH, Fish DN, MacLaren R. Propylene glycol accumulation in critically ill patients receiving continuous intravenous lorazepam infusions. Ann Pharmacother 2009 43(12) 1964—71. 

Pentobarbital contains 40% v/v propylene glycol, which was thought to have caused this patient s metabolic derangements. Reports of toxicity with drugs containing propylene glycol, particularly intravenous lorazepam, have been well described, but this is one of few reports involving intravenous pentobarbital. 

Polyethylene glycol has been associated with raised creatinine concentrations in eight patients who were given a continuous intravenous infusion of lorazepam (range 2-28 mg/hour) (16). 

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