# Role of Cyclohexanone Toxicity in Mediating Congenital Cardiac Surgery Outcomes

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2022 · $729,168

## Abstract

Congenital heart defects (CHD) are the leading cause of birth defect-associated illness and death.
Neurodevelopmental delays and disabilities are the most frequent and significant consequence for CHD
survivors. Efforts to reduce morbidity and improve outcomes have primarily focused on surgical techniques,
cardiopulmonary bypass (CPB) strategies and pharmacologic therapies without much success. Exposure to
industrial chemicals in the health care environment are increasingly being recognized as harmful, and maybe a
mechanism for these poor outcomes in CHD. Cyclohexanone, is a hazardous organic industrial solvent used
principally in health care as a joining compound in the fabrication of plastic medical devices. Cyclohexanone has
been shown to leach from IV infusion sets and the CPB circuit and in animal studies, with significant
cardiovascular effects. Therefore, our hypothesis is that cyclohexanone derived from medical plastics is
associated with adverse cardiovascular and neurodevelopmental outcomes in congenital cardiac surgery. We
now have significant and compelling pilot data in neonates undergoing cardiac surgery that there is a) substantial
cyclohexanone exposure from IV infusions and CPB and b) with adjusted analysis, cyclohexanone levels were
significantly associated with adverse post-operative cardiovascular outcomes, and worse 12 month
neurodevelopmental outcomes, thus supporting our hypothesis. Our long-term goal is to develop new prevention
strategies and more precise treatments to improve outcomes for neonates undergoing surgery with CPB. We
will approach this hypothesis using samples and outcomes from the discovery cohort: the completed NHLBI
multicenter Trial NCT01579513, entitled “Corticosteroid Therapy in Neonates Undergoing Cardiopulmonary
Bypass (MP trial)”, Eric Graham, PI (n=190, randomized to MP (methylprednisolone) therapy or placebo) and
the completed external validation cohort the University of Toronto, “Clinical Assessment of Thrombosis in
Children After Heart Surgery: The CATCH Study” (NCT01435473), Brian McCrindle and Cedric Manlhiot (PIs)
(N=327, <5 years old) and a neonatal cardiac surgery from the University of Michigan (N=59), Mark Russell, PI.
With the following Specific Aims we propose to: Aim 1) Determine if serum perioperative cyclohexanone levels
are associated with perioperative morbidity, mortality, and neurodevelopmental outcomes. Aim 2) Determine
cyclohexanone exposure sources and removal using zeolite molecular sieves. Finally, Aim 3) Determine
cyclohexanone neural toxicity, blood brain barrier and learning/memory effects. These Aims describe a paradigm
shift in the mechanism of reduced neonatal heart surgery outcomes. Innovation includes discovery of the novel
role of the industrial organic solvent contaminant cyclohexanone from medical plastic fabrication on neonatal
cardiac surgery clinical outcomes and methods for removal. Reduction of organic solvent exposure from medical
plastics offers an immediate ...

## Key facts

- **NIH application ID:** 10444513
- **Project number:** 1R01HL158593-01A1
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** ALLEN D EVERETT
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $729,168
- **Award type:** 1
- **Project period:** 2022-06-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10444513

## Citation

> US National Institutes of Health, RePORTER application 10444513, Role of Cyclohexanone Toxicity in Mediating Congenital Cardiac Surgery Outcomes (1R01HL158593-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10444513. Licensed CC0.

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