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Critical Care Pharmacy Specialist, Department of Pharmacy, Sky Ridge Medical Center, Lone Tree, CO
Assistant Professor, Department of Clinical Pharmacy, School of Pharmacy, University of Colorado Denver, Aurora, CO
Professor, Department of Clinical Pharmacy, School of Pharmacy, University of Colorado Denver
Associate Professor, Department of Clinical Pharmacy, School of Pharmacy, University of Colorado Denver
Reprints: Dr. MacLaren, Department of Clinical Pharmacy, School of Pharmacy, University of Colorado Denver, Mail Stop C238-L15, Academic Office 1, 12631 E. 17th Ave., Rm. L15-1421, Aurora, CO 80045, fax 303/724-0979, rob.maclaren{at}ucdenver.edu
BACKGROUND: Lorazepam is recommended by the Society of Critical Care Medicine as the preferred agent for sedation of critically ill patients. Intravenous lorazepam contains propylene glycol, which has been associated with toxicity when high doses of lorazepam are administered.
OBJECTIVE: To evaluate the accumulation of propylene glycol in critically ill patients receiving lorazepam by continuous infusion and determine factors associated with propylene glycol concentration.
METHODS: A 6-month, retrospective, safety assessment was conducted of adults admitted to the medical intensive care unit who were receiving lorazepam by continuous infusion for 12 hours or more. Propylene glycol serum concentrations were obtained 24–48 hours after continuous-infusion lorazepam was initiated and every 3–5 days thereafter. Propylene glycol accumulation was defined as concentrations of 25 mg/dL or more. Groups with and without propylene glycol accumulation were compared and factors associated with propylene glycol concentration were determined using multivariate correlation regression analyses.
RESULTS: Forty-eight propylene glycol serum samples were obtained
from 33 patients. Fourteen (42%) patients had propylene glycol accumulation,
representing 23 (48%) serum samples. Univariate analyses showed the following
factors were related to propylene glycol accumulation: baseline renal
dysfunction, presence of alcohol withdrawal, sex, age, Acute Physiology and
Chronic Health Evaluation (APACHE II) score, rate of lorazepam continuous
infusion, and 24-hour lorazepam dose. Multivariate linear regression modeling
demonstrated that propylene glycol concentration was strongly associated with
the continuous infusion rate and 24-hour dose (adjusted r2
0.77; p < 0.001). Independent correlation analyses showed that these 2
variables were so strongly associated with propylene glycol concentration
(r2 0.71; p < 0.001) that they alone predicted
propylene glycol concentration. Seven (21%) patients developed renal
dysfunction after continuous-infusion lorazepam was initiated, but associated
causes were indeterminable. Other possible propylene glycol–associated
adverse effects were not observed.
CONCLUSIONS: The continuous infusion rate and cumulative 24-hour lorazepam dose are strongly associated with and independently predict propylene glycol concentrations. Despite the absence of confirmed propylene glycol–associated adverse effects, clinicians should be aware that propylene glycol accumulation may occur with continuous-infusion lorazepam.
Key Words: adverse effects, critical care, lorazepam, propylene glycol, sedation, toxicity
Published Online, November 17, 2009. www.theannals.com, DOI 10.1345/aph.1M313
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