Development and Evaluation of a Guideline for Monitoring Propylene Glycol Toxicity in Pediatric Intensive Care Unit Patients Receiving Continuous Infusion Lorazepam

Abstract

OBJECTIVES: To develop and determine the safety of a guideline, by using osmol gap as an indicator of propylene glycol toxicity for pediatric patients receiving continuous infusion lorazepam. METHODS: From existing adult data, a guideline was developed for the use of continuous infusion lorazepam in pediatric critical care patients with recommendations for using osmol gap as an indicator of propylene glycol toxicity. A retrospective medical chart review was performed of patients receiving continuous infusion lorazepam from February 2012 to September 2012 for whom the guideline was used. RESULTS: Twenty-one patients received continuous infusion lorazepam for sedation in the pediatric intensive care unit during the 9-month study period for a total of 23 infusions. Eight patients (34.8%) had an osmol gap of ≥ 12 mOsm/kg during lorazepam infusion, and 7 patients (30.4%) did not have an elevated osmol gap at any point during the infusion. Two patients (8.6%) had clinical toxicity as indicated by elevated anion gap or lactate in addition to an osmol gap ≥ 12 mOsm/kg, while no patients experienced clinical toxicity with an osmol gap < 12 mOsm/kg. CONCLUSIONS: A guideline for the use of lorazepam infusion in pediatric critical care patients was developed and evaluated for safety. Lorazepam continuous infusions appeared to be associated with minimal toxicity in pediatric intensive care unit patients when the osmol gap monitoring guideline was used.

<p>Preparation and evaluation of tacrolimus-loaded thermosensitive solid lipid nanoparticles for improved dermal distribution</p>

“…In each group, the rabbits that received the highest score and the lowest score for rabbit skin are presented. The skin treated with reference product displayed severe erythema; it is thought that the irritation occurs owing to the various excipients in the ointment 58,59. In contrast, the images after TCR-SLN-1 application to rabbit skin yielded no irritation.…”

Propylene Glycol Toxicity in Adolescent with Refractory Myoclonic Status Epilepticus

“…We present a case of acute, refractory, distributive shock with hyperosmolar anion gap metabolic lactic acidosis secondary to PG toxicity in a patient receiving PG at doses previously believed to be associated with low risk of toxicity. While toxicity has been reported to occur at PG serum levels above 18–25 mg/dL [ 3 , 4 , 7 , 8 ], osmol gap has been suggested as a more useful surrogate measurement given the relative speed at which an osmol gap can be obtained relative to PG levels [ 9 , 10 ]. In pediatric patients receiving continuous lorazepam infusions, a guideline for monitoring the osmol gap was recently developed with the recommendation to switch to an alternative sedative if the osmol gap is ≥12 mOsm/kg [ 10 ].…”

“…While toxicity has been reported to occur at PG serum levels above 18–25 mg/dL [ 3 , 4 , 7 , 8 ], osmol gap has been suggested as a more useful surrogate measurement given the relative speed at which an osmol gap can be obtained relative to PG levels [ 9 , 10 ]. In pediatric patients receiving continuous lorazepam infusions, a guideline for monitoring the osmol gap was recently developed with the recommendation to switch to an alternative sedative if the osmol gap is ≥12 mOsm/kg [ 10 ]. Since 30% of PG is excreted via the kidneys as a glucuronide conjugate and the remainder excreted unchanged in the urine or metabolized to intermediary byproducts (lactate, CO 2 ), renal impairment is a known risk factor for the development of clinical toxicity [ 1 ].…”

Status Epilepticus due to Intraperitoneal Injection of Vehicle Containing Propylene Glycol in Sprague Dawley Rats

“…Developmental issues and age in both humans and rats may result in complications when using drugs or food containing propylene glycol [ 1 , 3 , 14 , 21 – 23 ]. Administration of pharmaceuticals containing 300 mg–3 g of propylene glycol per day for 14 days to premature newborn babies resulted in rapid progression of hyperbilirubinemia, seizures, and renal failure [ 22 ].…”