Cyclohexanone and metabolites exposure in critically Ill neonates and children

Authors

Suneetha Desiraju, Department of Pediatrics, Division of Neonatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Emily Zhao, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Jordan Kuiper, Department of Environmental and Occupational Health, The George Washington University Milken Institute School of Public Health, Washington, DC, USA.
Cynthia F. Salorio, Kennedy Krieger Institute, Baltimore, MD, USA.
David Graham, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Jessie P. Buckley, Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA.
Mark W. Russell, Department of Pediatrics, University of Michigan, Ann Arbor, MI, USA.
Eric M. Graham, Department of Pediatrics, Division of Pediatric Cardiology, Medical University of South Carolina, Charleston, SC, USA.
Danielle Gottlieb Sen, Department of Surgery, Division of Pediatric Cardiac Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Gregory Ellis, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Maureen Gilmore, Department of Pediatrics, Division of Neonatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Lauren Jantzie, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Sandra E. Juul, Department of Pediatrics, University of Washington, Seattle, WA, USA.
Kamala Simkhada, Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Allen D. Everett, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Melania M. Bembea, Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA. mbembea1@jhmi.edu.

Document Type

Journal Article

Publication Date

4-5-2025

Journal

Pediatric research

DOI

10.1038/s41390-025-04027-8

Abstract

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. IMPACT: 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.

APA Citation

Desiraju, Suneetha; Zhao, Emily; Kuiper, Jordan; Salorio, Cynthia F.; Graham, David; Buckley, Jessie P.; Russell, Mark W.; Graham, Eric M.; Gottlieb Sen, Danielle; Ellis, Gregory; Gilmore, Maureen; Jantzie, Lauren; Juul, Sandra E.; Simkhada, Kamala; Everett, Allen D.; and Bembea, Melania M., "Cyclohexanone and metabolites exposure in critically Ill neonates and children" (2025). GW Authored Works. Paper 7092.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/7092

Department

Environmental and Occupational Health