A prospective evaluation of propylene glycol clearance and accumulation during continuous-infusion lorazepam in critically ill patients.
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.
Department of Emergency Medicine, State University of New York, Upstate Medical University, Syracuse, NY 13210, USA. nelsenj@upstate.edu
Jamie L
JL
Nelsen
Curtis E
CE
Haas
Bahru
B
Habtemariam
David C
DC
Kaufman
Amy
A
Partridge
Stephen
S
Welle
Alan
A
Forrest
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016638:Critical Illness; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage* / Q000633:toxicity; D008140:Lorazepam / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D008962:Models, Theoretical; D019946:Propylene Glycol / Q000493:pharmacokinetics* / Q000633:toxicity; D011446:Prospective Studies
D006993:Hypnotics and Sedatives; D019946:Propylene Glycol; D008140:Lorazepam