Mechanistic Considerations and Pharmacokinetic Implications on Concomitant Drug Administration During CytoSorb Therapy

OBJECTIVE: The CytoSorb hemoadsorption device (CytoSorbents Inc, Monmouth Junction, NJ) is increasingly used in many critical disease states. The potential impact on the pharmacokinetic (PK) of concomitantly administered drugs must be considered in clinical practice. The current review summarizes relevant mechanistic principles, available preclinical and clinical data, and provides general guidance for the management of concomitant drug administration during CytoSorb therapy. DATA SOURCES: Detailed search strategy using the PubMed and OVID MEDLINE databases, as well as presented congress abstracts for studies on drug removal by the CytoSorb device. STUDY SELECTION: Human, animal, and bench-top studies with PK or drug-removal data during CytoSorb therapy were selected for inclusion. Publications reporting on CytoSorb treatments for drug overdose were not considered. DATA EXTRACTION: Relevant PK data were examined and synthesized for narrative review. DATA SYNTHESIS: To date, PK data during CytoSorb hemoadsorption are available for more than 50 drugs, including analgesics, antiarrhythmics, anticonvulsants, antidepressants, antihypertensives, antiinfectives, antithrombotics, anxiolytics, and immunosuppressants. Based on available PK data, drugs were categorized into low (<30%), moderate (30-60%), or high rates of removal (>60%), or, alternatively, according to clearance increase relative to endogenous clearance: negligible (<25%), low (25-100%), moderate (100-400%), or high (>400%). In most reports, additional impact of the extracorporeal platform where CytoSorb was integrated was not available. Based on available data and considering drug, patient, and setup-specific aspects, general dosing guidance for clinical practice was developed. CONCLUSIONS: CytoSorb therapy may increase drug elimination through active removal. However, the extent of removal is heterogeneous, and its clinical significance, if any, depends on the broader clinical context, including a patient's specific endogenous drug clearance and the underlying extracorporeal platform used. The available data, although not definitive, allow for general guidance on dosing adjustments during CytoSorb therapy; however, any treatment decisions should always be complemented by clinical judgment and therapeutic drug monitoring, when available.