HOCl Production Modelling for an Electrochemical Catheter

Abstract

Intravascular catheters are used in critically ill patients to deliver fluids and lifesaving medications, and for hemodynamic monitoring. These catheters are at risk for infection, especially when in place for prolonged periods of time. The management of catheter-related infections are challenged by both the presence of biofilms and the frequent association with multidrug-resistant organisms. Efforts to mitigate central line-associated bloodstream infections (CLABSIs) have focused on preventive measures. Several strategies to prevent intraluminally sourced CLABSI have been developed and used, including antimicrobial agent locks and antimicrobial-impregnated catheter lumens. Although antimicrobial locks have reduced CLABSI rates, this strategy is prone to complications, including resistance selection, allergic reactions, catheter damage, and host toxicity due to the high concentrations of agents needed. Largely because of these factors, antimicrobial locks are infrequently used for CLABSI prevention in clinical practice. Antimicrobial impregnated catheter lumens have also shown variable effects against CLABSI and are likewise not regularly used. Therefore. innovative therapeutic solutions are necessary, especially those that allow catheter retention. In this context, the integration of electrochemical technologies for hypochlorous acid (HOCl) production within intravascular catheters emerges as a promising strategy to combat CLABSIs. HOCl is a strong oxidizing agent that damages microbial cells by interacting with lipids, nucleic acids, sulfur-containing amino acids, and membrane components. It is found in all mammals as an endogenous substance produced by the immune system to protect the body from pathogens. In this study, electrochemical generation of HOCl in an electrochemical catheter (e-catheter) was simulated using a model called Electrochemical Hypochlorous Acid Production (EHAP), implemented in COMSOL Multiphysics®. The e-catheter has two components, a hub and a tube, both filled with 0.9% saline solution. Titanium wires are used as working and counter electrodes.The model was used to define critical variables that may impact HOCl generation and distribution. In addition to predicting HOCl concentrations, the EHAP model was used to monitor effects of 1) a waiting period after constant polarization, 2) operational voltage, 3) working electrode length and 4) working electrode surface area. Findings using the EHAP model revealed the following: 1) Diffusion limitations predominate when the electrodes are localized to the hub, yielding a lower HOCl concentration in the tube compared to the hub. Increasing the voltage between the working and the reference electrodes increases HOCl generation, however concentrations are not enough to deliver HOCl to the tube. 2) HOCl concentrations are higher in the tube compared to hub when the working electrode extends the entire length of the tube. 3) HOCl concentration distributions can be tuned by changing the surface area of the working electrode within different compartments of the e-catheter.