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 comes from neonatal studies of antibiotics from the 1980s and 1990s. These studies generally demonstrate a larger volume of distribution due to ECMO and therefore higher doses are needed initially. More adult data are now emerging, but with a predominance of case reports and case series without comparison with critically ill controls. The available pharmacokinetic analyses do suggest that volume of distribution and clearance are unchanged in the adult population, and therefore dosing recommendations largely remain unchanged. There is a lack of data on children older than 1 year of age. The data support the importance of therapeutic drug monitoring 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 for patients 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.