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.
Nelsen
Jamie L
JL
Department of Emergency Medicine, State University of New York, Upstate Medical University, Syracuse, NY 13210, USA. nelsenj@upstate.edu
Haas
Curtis E
CE
Habtemariam
Bahru
B
Kaufman
David C
DC
Partridge
Amy
A
Welle
Stephen
S
Forrest
Alan
A
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