How does continuous venovenous hemofiltration theoretically expose (ex-vivo models) inpatients to diethylhexyladipate, a plasticizer of PVC medical devices?

Abstract

Continuous venovenous hemofiltration (CVVH) is widely used in intensive care units to treat patients with acute kidney injury requiring renal replacement therapy. The medical devices (MD) used for CVVH include a hemofilter and tubings made of plasticized PVC. Due to its known reprotoxicity, diethylhexyl phthalate (DEHP) has been replaced by alternatives such as diethylhexyladipate (DEHA) in some of these tubings. The migration of DEHA from hemofiltration systems has not been assessed and thus the level of patient exposure to this DEHP-alternative remains unknown. In this study, 2 CVVH models were used to evaluate the potential migration of DEHA from PVC tubings, allowing the determination of (Rachoin and Weisberg, 2019) the highest rates of DEHA able to migrate into a simulant flowing in a marketed adult CVVH circuit by disregarding any metabolisation and (Krieter et al., 2013) the clinical-reflecting exposure of patients to this plasticizer and its metabolites by assessing their migration into blood. In the first model, we showed that patients undergoing a CVVH procedure may be exposed to high rates of DEHA. Moreover, DEHA is continuously hydrolyzed into its primary metabolite MEHA (monoethylhexyladipate), which may reach cytotoxic level in the patients' blood. When looking from a « safer » MD perspective, DEHA might not be the best alternative plasticizer for CVVH tubings. However, to reflect clinical conditions, this study should be completed by an in-vivo evaluation (biomonitoring) of the oxidized metabolites of DEHA in urines of inpatients undergoing CVVH.

Keywords: Continuous venovenous hemofiltration; Diethylhexyladipate; Medical devices; Plasticizer.