Ex Vivo renal replacement therapy study to quantify the effect of differing RRT settings on antimicrobial clearance.  

Pharmacokinetic studies in critically ill patients receiving renal replacement therapy (RRT) are resource intensive and reliance on this approach to generate clinically relevant antimicrobial doses for the various RRT modalities and settings is problematic. It is also unethical to change RRT settings in ICU patients without clinical justification.

An alternative approach is to measure the effect of changes of RRT modality (haemofiltration, haemodiafiltration) and settings (e.g. blood flow rate, effluent flow rate, filter surface area) in a simulated ex vivo RRT circuit.

This approach can provide accurate surrogate data for pharmacokinetic studies conducted in clinical environments. Using an ex vivo (human blood) RRT model to generate new knowledge of the effect of changing RRT settings on antimicrobial adsorption and clearance is highly appropriate and has previously been conducted successfully with cefpirome in ICU patients where the in vitro findings correlated closely with the ex vivo findings.

This approach, supported by mechanism-based pharmacokinetic modelling may serve to validate this technique for estimating RRT clearance in ICU patients as a substitute for expensive clinical PK studies.

1. Roberts, J., Lefrant, J., & Lipman, J. (2017). What's new in pharmacokinetics of antimicrobials in AKI and RRT? Intensive Care Medicine, 43(6), 904-906.

DOI: 10.1007/s00134-017-4789-x