Journal of Intensive Care Medicine

 

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Journal of Intensive Care Medicine, Vol. 23, No. 3, 184-194 (2008)
DOI: 10.1177/0885066608315808

A Prospective Evaluation of Propylene Glycol Clearance and Accumulation During Continuous-Infusion Lorazepam in Critically Ill Patients

Jamie L. Nelsen, PharmD

Department of Emergency Medicine, State University of New York, Upstate Medical University, Syracuse, nelsenj{at}upstate.edu

Curtis E. Haas, PharmD, FCCP

Department of Pharmacy, University of Rochester Medical Center, Department of Surgery, School of Medicine and Dentistry, University of Rochester

Bahru Habtemariam, PharmD

Department of Pharmacy Practice and Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences

David C. Kaufman, MD, FCCM

Department of Pharmacy Practice and Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, Department of Biostatistics, School of Medicine and Biomedical Sciences

Amy Partridge, PharmD

University at Buffalo, Department of Surgery, School of Medicine and Dentistry

Stephen Welle, PhD

Department of Medicine, General Clinical Research Center (SW), University of Rochester Medical Center, Rochester, New York

Alan Forrest, PharmD

Department of Pharmacy, Boston Medical Center, Massachusetts

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.

Key Words: propylene glycol • pharmacokinetics • osmolar concentration • lactic acid • lorazepam • adverse effects


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