Cyclohexanone and metabolites exposure in critically Ill neonates and children

Cyclohexanone is a volatile organic compound known to be toxic to humans and animals, used in the medical setting as a solvent sealer for intravenous (IV) fluid administration devices. We aimed to determine exposure sources as well as plasma and urine levels of cyclohexanone and metabolites in critically ill infants and children.

We prospectively enrolled children in a single center pediatric intensive care unit (ICU) (n = 66), and conducted a secondary analysis of a multicenter trial in premature neonates (n = 69). Cyclohexanone and its predominant metabolites, trans-1,2-cyclohexanediol and trans-1,4-cyclohexanediol, were measured serially in medical fluids, plasma, and urine.

Cyclohexanone was detected in all IV solutions used in standard ICU care (IV fluids, medications, dialysate and red blood cell bags, n = 53 fluid samples). Cyclohexanone and metabolites were higher in urine versus plasma in both cohorts. In premature neonates, plasma and urine cyclohexanone concentrations were highest on day of randomization, while metabolite concentrations were highest on days 7-14.

Currently, cyclohexanone may represent an inevitable exposure to children who require intensive care inclusive of IV fluid and medication administration devices. Further studies are needed to develop replacement or mitigation strategies for cyclohexanone exposure in the vulnerable neonatal and pediatric ICU populations.

Direct bloodstream exposure to cyclohexanone in the hospital environment has been poorly described in the healthcare setting. Cyclohexanone was present in all tested types of intravenous solutions used in standard intensive care (intravenous fluids, medications, dialysate and stored red blood cell bags). In a single center pediatric intensive care unit cohort and a multicenter neonatal intensive care unit cohort, cyclohexanone and its metabolites were detected in every blood and urine sample tested. In a multicenter neonatal intensive care unit cohort, plasma and urine cyclohexanone concentrations were highest on day 1 of admission and metabolite concentrations were highest on days 7-14.