(755) Cyclohexanone Exposure Sources in the PICU

Introduction: Cyclohexanone is an industrial chemical used as a solvent sealer for intravenous (IV) bags and stopcocks to IV tubing. Cyclohexanone has been shown to leach from medical plastics into IV fluids and has been associated with adverse neurodevelopmental outcomes in neonates. Despite its known toxicity, there are currently no medical exposure limits for cyclohexanone, and its exposure levels in critically ill children are unknown. This study aimed to determine exposure sources as well as plasma and urine levels of cyclohexanone and metabolites in children admitted to the intensive care unit (ICU).

Methods: This was a prospective cohort study including 38 children hospitalized in a single center academic pediatric medical-surgical or cardiac ICU. We measured cyclohexanone concentrations from samples of IV crystalloid fluid, IV medication infusions, peritoneal dialysate, and red blood cell tubing from each stopcock, before and after the administration set was connected to and disconnected from patients’ IV catheters. We also collected blood and urine samples and measured concentrations of cyclohexanone and its cyclohexanediol metabolites.

Results: Median [P25-P75] concentrations (µg/mL) of cyclohexanone were: 10.9 [4.2-22.8] (n=29) in IV fluids; 19.3 [10.6-36.6] (n=10) in IV medication infusions; 3.0 [2.2-5.5] (n=3) in dialysate solution; and 4.8 (n=1) in RBC tubing. Plasma concentrations (ng/mL) of cyclohexanone and its metabolites in samples available on the same calendar day as the IV fluid/medication infusion exposure measurements (n=23) were: cyclohexanone 201 [82, 317]; trans 1,2 cyclohexanediol 2031 [774, 3182]; and trans 1,4 cyclohexanediol 635 [330, 1882], respectively. Urine samples from the same subjects and on the same calendar day had median concentrations (ng/mL) of cyclohexanone; trans 1,2 cyclohexanediol; and trans 1,4 cyclohexanediol of 507 [45, 1915], 3653 [1937, 7374], and 5039 [2395, 7376], respectively.

Conclusions: Cyclohexanone was detected from samples across multiple pediatric ICU exposure sources and was present in every patient blood sample, demonstrating a broad exposure risk. Additionally, the high levels of cyclohexanone and its metabolites in urine indicate that renal excretion is a major process for elimination of cyclohexanone and its metabolites.