Meropenem and piperacillin pharmacokinetics during extracorporeal membrane oxygenation: A case-control study

INTRODUCTION. Infection is frequent in patients treated by extracorporeal membrane oxygenation (ECMO) and yet pharmacokinetics (PKs) of beta-lactams during ECMO have not been well studied. In critically ill patients, antimicrobial PKs are significantly altered and may result in subtherapeutic drug concentrations [1,2]. ECMO introduces additional confounding factors, which may further alter antibiotic concentrations.OBJECTIVES. We hypothezised that meropenem (MERO) and piperacillin (PIP) PKs parameters are altered in critically ill patients treated with ECMO.METHODS. We reviewed all patients in whom drug levels were measured during MERO or PIP therapy while on ECMO support (from January 2010 to December 2012). Drug concentrations were measured after 2 hours from the onset of a 30-min perfusion and just before (trough, C0) the next dose; PKs were estimated using a one-compartment model. Using a database of all patients having b-lactams level measurements, ECMO patients were matched with non-ECMO patients according to: 1) drug regimen; 2) renal function (i.e. similar measured creatinine clearance or similar intensity of therapy if on continuous renal replacement therapy); 3) total body weight; 4) Sequential Organ Failure Assessment (SOFA) score on the day of drug levels measurement. Drug concentrations were considered as adequate if drug levels remained between 4 and 8 times the clinical breakpoint of the minimal inhibitory concentration (MIC) for Pseudomonas aeruginosa during 50% (PIP) or 40% (MERO) of the dose interval.RESULTS. A total of 41 drug levels (MERO=27; PIP = 14) were obtained in 26 patients treated with ECMO (16 veno-venous and 9 veno-arterial) and 41 matched controls. Patients' characteristics are shown in the table. ECMO patients had higher ICU mortality (58% vs. 26%), longer ICU stay and greater need of mechanical ventilation (93% vs. 66%), but similar need for vasopressors (66% vs. 63%) No significant differences were found between ECMO and non-ECMO patients in serum concentrations and in PKs variables: volume of distribution (0.38 [0.27-0.68] vs. 0.46 [0.33-0.79] L/Kg, p=0.37), half-life time (2.6 [1.8-4.4] vs. 2.9 [1.7-3.7] hours, p=0.96) and total clearance (132 [66-200] vs 141 [93-197] ml/min, p=0.52). This was also true when either MERO or PIP PKs were considered separately. The proportion of insufficient (13/41 vs. 12/41), adequate (15/41 vs. 19/41) and excessive (13/41 vs. 10/41) drug levels was similar in ECMO and control group, respectively.CONCLUSIONS. MERO and PIP drug concentrations and their PKs are not altered by ECMO in critically ill patients.REFERENCE(S).1. Roberts DM, Crit Care 20122. Udy AA, Chest 2012