Extracorporeal Membrane Oxygenation (ECMO) is a cardiopulmonary bypass device that is used to temporarily support the most critically ill of patients with respiratory and/or cardiac failure. Infection and its sequelae may be an indication for ECMO or infections may be acquired while on ECMO, and are associated with a mortality of greater than 50%.1 Effective therapy requires optimal dosing. However, optimal dosing can be different in patients on ECMO, because the ECMO circuit can alter drug pharmacokinetics. This review assessed the current literature for pharmacokinetic data and subsequent dosing recommendations for anti-infective drugs in patients on ECMO.
We searched the PubMed and EMBASE databases (1965 to February 2016) and included case reports, case series, or studies that provided pharmacokinetic data for anti-infective drugs including antibiotics, antifungals, and antivirals being used to treat patients of all age groups on ECMO. Pharmacokinetic parameters and dosing recommendations based on these data are presented.
The majority of data on this topic come from neonatal studies of antibiotics from the 1980s and 1990s. These studies generally demonstrate a larger volume of distribution (V) due to ECMO and therefore, higher doses are needed initially. More adult data is now emerging, but with a predominance of case reports and case series without comparison to critically ill controls. The available pharmacokinetic analyses do suggest that V and clearance (CL) are unchanged in the adult population and therefore dosing recommendations largely remain unchanged. There are a lack of data in children >1 year of age. The data support the importance of therapeutic drug monitoring (TDM) when available in this population of patients.
This review found reasonably robust dosing recommendations for some drugs and scant or no data for other important anti-infectives. In order to better determine optimal dosing on ECMO, a systematic approach is needed. Approaches that combine ex vivo ECMO experiments, animal studies, specialized pharmacokinetic modeling, and human clinical trials are being developed.