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. DESIGN: Prospective study. SETTING: A tertiary care pediatric intensive care unit. PATIENTS: Eleven intubated pediatric intensive care patients receiving continuous lorazepam infusion for sedation. INTERVENTIONS: 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. MEASUREMENTS AND MAIN 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. CONCLUSION: 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.
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. DESIGN: Prospective study. SETTING: A tertiary care pediatric intensive care unit. PATIENTS: Eleven intubated pediatric intensive care patients receiving continuous lorazepam infusion for sedation. INTERVENTIONS: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. MEASUREMENTS AND MAIN 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. CONCLUSION: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: Roosmarijn F W De Cock; Catherijne A J Knibbe; Aida Kulo; Jan de Hoon; Rene Verbesselt; Meindert Danhof; Karel Allegaert Journal: Br J Clin Pharmacol Date: 2013-01 Impact factor: 4.335
Authors: Sydney L Rooney; Alexandra Ehlers; Cory Morris; Denny Drees; Scott R Davis; Jeff Kulhavy; Matthew D Krasowski Journal: J Med Toxicol Date: 2016-06