Does biocompatibility contribute to transfusion-related adverse effects?

Children'S Research Institute, Washington DC

Investigators

Linked publications, trials & patents

Abstract

Project Summary Plastics are commonly used to manufacture consumer goods and disposable medical products, nevertheless, there is increasing concern over the ubiquity of plastics and human exposure to plastic chemical contaminants. Health concerns are primarily directed toward phthalates, which are used to produce flexible polyvinyl chloride materials (e.g., blood storage bags, medical-grade tubing), and bisphenols that are used to build resilient polycarbonate plastics and membranes (e.g., cardiotomy reservoirs, oxygenators, hemoconcentrators). Studies have shown that plastic chemicals leach from medical products in large quantities. As a result, pediatric patients can be exposed to these chemicals at levels that exceed safety thresholds by >1,000-fold. Although the direct effect of these exposures remains unclear – epidemiological studies have reported alarming associations between plastic chemical exposures and ~40-75% increased risk of all-cause and cardiovascular mortality. Accordingly, we hypothesize that the postoperative complications experienced by cardiac surgery patients are likely exacerbated by incidental plastic chemical exposure. We will use a multipronged approach, with both preclinical models and human data, to test our hypothesis using the following aims: 1) Elucidate the mechanisms by which plastic chemical exposures contribute to cardiac dysfunction. 2) Determine the extent to which plastic chemicals impact red blood cell quality and tissue oxygenation in the context of cardiac surgery. 3) Evaluate the risk of plastic chemical exposures in pediatric cardiac surgery patients. Results of this study will influence the clinical care of ~25 million patients/year receiving critical care via medical procedures that employ plastics, including heavily transfused patients. Knowledge established by this study will inform and incentivize the adoption of alternative materials, and prompt manufacturers to utilize new fabrication techniques, surface coatings, or alternative chemicals for medical and consumer products. Further, the results of this study can serve as preclinical guidance for a future randomized clinical trial in which patients are assigned to different mitigation strategies to reduce chemical exposures (e.g., red blood cell washing or ultrafiltration to remove contaminants, non-phthalate or non-bisphenol medical products). Finally, the knowledge gleaned from this work can be applied to broader public health concerns regarding daily environmental plastic chemical exposures and links to chronic health conditions, including cardiovascular and cardiometabolic disorders.