title: Propylene glycol accumulation associated with continuous infusion of lorazepam in pediatric intensive care patients.
abstract: OBJECTIVE
  To determine if propylene glycol accumulates in children receiving continuous lorazepam infusion and, if accumulation occurs, to determine if it is associated with significant laboratory abnormalities.
  
  
  METHODS
  Prospective study.
  
  
  METHODS
  A tertiary care pediatric intensive care unit.
  
  
  METHODS
  Eleven intubated pediatric intensive care patients receiving continuous lorazepam infusion for sedation.
  
  
  METHODS
  Propylene glycol accumulation was determined by comparing concentrations at baseline, after 48 hrs, and at end of therapy. Laboratory abnormalities were determined by comparing serum lactate and osmolar gap at baseline, after 48 hrs, and at end of therapy. Correlation between the cumulative dose of lorazepam received and the propylene glycol concentration measured at the end of therapy was determined.
  
  
  RESULTS
  Patients aged 1-15 months were studied. Lorazepam infusion rates ranged from 0.1 to 0.33 mg.kg.hr and lasted 3-14 days. Propylene glycol accumulated significantly in patients receiving continuous infusion of lorazepam. The propylene glycol concentration increased during the study from 86 +/- 93 microg/mL at baseline to 763 +/- 660 microg/mL at the end of the study ( p=.038). A statistically significant correlation between the cumulative dose of lorazepam received and propylene glycol concentration at the end of therapy was demonstrated ( r(2)=.65, p<.005). However, the propylene glycol accumulation was not associated with significant laboratory abnormalities. Neither serum lactate concentrations nor osmolar gap were significantly elevated over baseline.
  
  
  CONCLUSIONS
  Propylene glycol accumulated significantly in pediatric intensive care patients receiving continuous lorazepam infusion, and propylene glycol concentration correlated with the cumulative lorazepam dose the patient received. However, significant laboratory abnormalities due to propylene glycol accumulation were not observed.
authors.affiliation: Clinical Pharmacy Practice, Auburn University, Auburn, AL, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Chicella
authors.forename: Paul
authors.initials: P
authors.lastname: Jansen
authors.forename: Anitha
authors.initials: A
authors.lastname: Parthiban
authors.forename: Karen F
authors.initials: KF
authors.lastname: Marlowe
authors.forename: F Aladar
authors.initials: FA
authors.lastname: Bencsath
authors.forename: Kem P
authors.initials: KP
authors.lastname: Krueger
authors.forename: Robert
authors.initials: R
authors.lastname: Boerth
mesh_terms: D000704:Analysis of Variance; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007223:Infant; D007262:Infusions, Intravenous; D019344:Lactic Acid / Q000097:blood; D008140:Lorazepam / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D009994:Osmolar Concentration; D019946:Propylene Glycol / Q000097:blood*
chemical_list: D006993:Hypnotics and Sedatives; D019344:Lactic Acid; D019946:Propylene Glycol; D008140:Lorazepam