Dosing of anti-infective drugs in patients undergoing therapeutic plasma exchange - considerations for practical...

Therapeutic plasma exchange (TPE) is used in a wide range of indications and patient populations. The current guidelines of the American Society for Apheresis on the use of therapeutic apheresis in clinical practice list 166 graded indications for TPE. Many indications are related to the treatment of critically ill patients. Indeed, two multicenter trials are currently investigating the role of TPE in the treatment of early septic shock.

During TPE, usually 1.0-1.5 times the calculated plasma volume is exchanged using albumin solution or fresh frozen plasma as replacement fluid, although considerable deviations from this recommended exchange volume have been reported. Depending on the TPE modality (membrane-based or centrifugal), the duration of the procedure ranges between 90 and 140 min. TPE removes not only unwanted substances such as inflammatory mediators or pathological antibodies but may also remove drugs that are essential for the treatment of the underlying disease. Furthermore, changes in plasma protein concentrations due to TPE may affect the volume of distribution (Vd) and the concentrations of protein-bound drugs. The objective of the current narrative review is to introduce general principles of TPE-associated drug removal as well as the current literature on the dosing of anti-infectives in patients undergoing TPE.

Pharmacokinetic characteristics, including volume of distribution, plasma protein binding, endogenous clearance, and redistribution kinetics, have been demonstrated to influence the susceptibility of a drug to TPE-associated removal. TPE may substantially affect plasma levels of drugs with low volume of distribution and high protein binding, including aminoglycosides and glycopeptides. Further studies are needed because direct evidence on the pharmacokinetics of anti-infective drugs undergoing TPE in sepsis remains limited. Specific timing or dosing strategies are therefore not supported by sufficient evidence and should be individualized according to drug-specific pharmacokinetics, TPE characteristics, and clinical situation.