A prospective evaluation of propylene glycol clearance and accumulation during continuous-infusion lorazepam in critically ill patients.

Author(s): Nelsen JL, Haas CE, Habtemariam B, Kaufman DC, Partridge A, Welle S, Forrest A

Affiliation(s): Department of Emergency Medicine, State University of New York, Upstate Medical University, Syracuse, NY 13210, USA. nelsenj@upstate.edu

Publication date & source: 2008-05, J Intensive Care Med., 23(3):184-94.

Publication type: Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

Propylene glycol is a commonly used diluent in several pharmaceutical preparations, including the sedative lorazepam. Fifty critically ill patients receiving continuous-infusion lorazepam for a minimum of 36 hours were prospectively evaluated to determine the extent of propylene glycol accumulation over time, characterize propylene glycol clearance in the presence of critical illness, and develop a pharmacokinetic model that would predict clearance based on patient-specific clinical, laboratory, and demographic factors. In this cohort, the median lorazepam infusion rate was 2.1 mg/h (0.5-18). Propylene glycol concentration correlated poorly with osmolality, osmol gap, and lactate. In all, 8 patients (16%) had significant propylene glycol accumulation (>25mg/dL). When propylene glycol concentrations were >25 mg/dL, the median lorazepam infusion rate before sample collection was higher, 6.4 (1.9-11.3) versus 2.0 (0.5-7.4) mg/h (P =.0003). A linear first-order model with interoccasion variability on clearance adjusted for total body weight and Acute Physiology and Chronic Health Evaluation II score predicted propylene glycol concentration.