Plastic Exposure During Cardiopulmonary Bypass May Contribute to Post-operative Complications in Neonates and Infants

Background: Plasticizers have transformed clinical care through their ability to make plastic medical devices flexible and prolong red blood cell storage duration; however, questions have arisen over their safety. The most common plasticizer in polyvinylchloride (PVC) medical devices is di(2-ethylhexyl) phthalate (DEHP). DEHP is lipophilic and not covalently bound to PVC allowing it to leach into lipid-rich solutions such as blood. Patients undergoing cardiopulmonary bypass (CPB) can be exposed to significant levels of plasticizers from blood products, circuit tubing, bypass cannulas, endotracheal tubes, foley catheters, central lines, etc. We aimed to quantify iatrogenic plasticizer exposure during pediatric CPB, and to determine the extent to which chemical exposures may contribute to post-operative complications.

Methods: A single-center study was conducted with IRB approval; plasma samples were collected from remnant specimens from n=81 patients. Post-operative samples were drawn upon arrival to the CICU immediately following surgery. Phthalate levels (DEHP, MEHP, MECPP, MEHHP, MEOHP) were quantified using an ultra-performance liquid chromatography-tandem mass spectrometer (UHPLC-MS). Clinical data was retrospectively collected from patients’ medical records.

Results: Neonates and infants undergoing CPB had significantly increased phthalate concentrations in their blood immediately after surgery (Figure 1); which may be linked to immature glucuronidation pathways in patients <6 months of age. At our institution, patients <1 month old also receive methylprednisolone in the CPB priming fluid, which may increase lipase activity and the conversion of DEHP to its more toxic metabolite, MEHP. Total phthalate sum in neonates and infants receiving 10 mg/kg methylprednisolone was 24.8 +/- 7.3 vs 11.7 +/- 7.6 uM in patients without steroids (p < 0.0001). Neonates and infants with higher phthalate levels tended to have increased post-operative complications (hypotension, junctional ectopic tachycardia, cardiac arrest; Figure 2) and glucose elevation (post-op day 1: 180 +/- 30.8 vs 120 +/- 14.6 mg/dL (p=0.003); top vs lowest tertile respectively in methylprednisolone treated patients). Of interest, experimental animal studies have documented hypotension and cardiac arrest following MEHP exposure.

Conclusion: Cardiopulmonary bypass is a significant source of iatrogenic plasticizer exposure for neonates and infants; when compounded with underlying health conditions, operative phthalate accumulation may contribute to post-operative outcomes in this sensitive population. The data suggests efforts should be made to use DEHP-free medical devices (ex: tubing, cannulas, blood bags) and limit the use of blood products when feasible.