Impact of extracorporeal membrane oxygenation (ECMO) support on piperacillin exposure in septic patients: a case-control study.

OBJECTIVES: To describe the impact of extracorporeal membrane oxygenation (ECMO) devices on piperacillin exposure in ICU patients. METHODS: This observational, prospective, multicentre, case-control study was performed in the ICUs of two tertiary care hospitals in France. ECMO patients with sepsis treated with piperacillin/tazobactam were enrolled. Control patients were matched according to SOFA score and creatinine clearance. The pharmacokinetics of piperacillin were described based on a population pharmacokinetic model, calculating the proportion of time the piperacillin plasma concentration was above 64 mg/L (i.e. 4× MIC breakpoint for Pseudomonas aeruginosa). RESULTS: Forty-two patients were included. Median (IQR) age was 60 years (49-66), SOFA score was 11 (9-14) and creatinine clearance was 47 mL/min (5-95). There was no significant difference in the proportion of time piperacillin concentrations were ≥64 mg/L in patients treated with ECMO and controls during the first administration (P = 0.184) or at steady state (P = 0.309). Following the first administration, 36/42 (86%) patients had trough piperacillin concentrations <64 mg/L. Trough concentrations at steady state were similar in patients with ECMO and controls (P = 0.535). Creatinine clearance ≥40 mL/min was independently associated with piperacillin trough concentration <64 mg/L at steady state [OR = 4.3 (95% CI 1.1-17.7), P = 0.043], while ECMO support was not [OR = 0.5 (95% CI 0.1-2.1), P = 0.378]. CONCLUSIONS: ECMO support has no impact on piperacillin exposure. ICU patients with sepsis are frequently underexposed to piperacillin, which suggests that therapeutic drug monitoring should be strongly recommended for severe infections.