Comparative polymyxin B pharmacokinetics in patients receiving extracorporeal membrane oxygenation

Abstract

Objectives To describe polymyxin B pharmacokinetics in patients receiving veno-venous extracorporeal membrane oxygenation (ECMO) in comparison with critically ill patients without ECMO support and to explore potential covariates that could affect the pharmacokinetics in this group of patients. Patients and methods In 13 critically ill patients on ECMO and in 21 critically ill patients without ECMO support, 6–8 blood samples were collected during 12 h intervals after reaching steady state. Polymyxin B concentration in serum was determined using a previously developed ELISA. Protein binding was assessed by rapid equilibrium dialysis. Results In 13 critically ill patients on ECMO who received polymyxin B, the median area under the concentration–time curve over 12 h (AUC0–12h) was 48.38 mg/h/L for the total drug and 14.08 mg/h/L for the free drug. The unbound fraction was 0.35. Total body clearance was 1.16 L/h. In non-ECMO patients, the median AUC0–12h was 34.7 mg/h/L and the median CL was 1.76 L/h. The volume of distribution was significantly lower in ECMO patients (19.7 versus 30.4 L, respectively). We found a moderate negative correlation between the ECMO blood flow rate and AUC0–12h, a strong negative correlation between SOFA score and polymyxin B clearance and a moderate correlation between polymyxin B clearance and renal function in ECMO patients. Conclusions Currently recommended polymyxin B dosage regimens are sufficient for patients receiving ECMO and no dosage increase is required. In our study, polymyxin B exposure was higher in ECMO patients compared with the control group.

The population pharmacokinetics and dose optimization of polymyxin B in critically ill patients with or without extracorporeal membrane oxygenation

“…In our study, the mean clearance of all patients and those with ECMO support were 0.026 and 0.027 L/h/kg, respectively, very similar to the results of another study (0.0276 L/h/kg), 12 which used a two‐compartment model to describe the PK profile of 24 critically ill patients without ECMO support, suggesting that the impact of ECMO on the polymyxin B PK was likely to be minimal. Compared with another study that included patients with ECMO support, 24 our study showed a higher polymyxin B CL and a lower Vd, and hypoalbuminemia may be the parameter that may explain such PK differences (34.2 ± 3.1 vs. 29.8 ± 1.6).…”

“…23 To the best of our knowledge, only one study had evaluated the PK variability of polymyxin B in patients with ECMO support. 24 Using a non-compartment PK analysis, this study found that ECMO patients had a significantly higher polymyxin B exposure and a significantly lower Vd than non-ECMO patients. These findings are inconsistent with those of other studies conducted in this patient population.…”

“…12 Consistent with our data, several recent studies support our finding. [14][15][16]24,32 Yu and colleagues 15 examined clinical variable predictors of PK in 32 patients with various renal function (71.9% were critically ill) and found CL CR was the significant covariate on polymyxin B CL. The urinary recovery of polymyxin B was obtained in four patients in their study and the mean (SD) was 23.56% (0.10).…”

“…In addition, the main PK parameters of polymyxin B were similar between patients with and without ECMO support. A non‐compartment PK analysis of 13 critically ill patients with ECMO support by Surovoy 24 showed that currently recommended polymyxin B dosage regimens are sufficient for this patient population and no dosage increase is required. These findings demonstrated that ECMO was not a patient characteristic that influenced polymyxin B PK.…”

“…Apparently, the introduction of ECMO further increases the challenge of appropriately dosing antimicrobials for life‐threatening infections 23 . To the best of our knowledge, only one study had evaluated the PK variability of polymyxin B in patients with ECMO support 24 . Using a non‐compartment PK analysis, this study found that ECMO patients had a significantly higher polymyxin B exposure and a significantly lower Vd than non‐ECMO patients.…”