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. 2014 Nov 22;18(6):632.
doi: 10.1186/s13054-014-0632-8.

Vancomycin population pharmacokinetics during extracorporeal membrane oxygenation therapy: a matched cohort study

Katia Donadello  1 , Jason A Roberts  2 , Stefano Cristallini  3 , Marjorie Beumier  4 , Kiran Shekar  5 , Frédérique Jacobs  6 , Asmae Belhaj  7 , Jean-Louis Vincent  8 , Daniel de Backer  9 , Fabio Silvio Taccone  10
Affiliations

Vancomycin population pharmacokinetics during extracorporeal membrane oxygenation therapy: a matched cohort study

Katia Donadello et al. Crit Care. .

Abstract

Introduction: The aim of this study was to describe the population pharmacokinetics of vancomycin in critically ill patients treated with and without extracorporeal membrane oxygenation (ECMO).

Methods: We retrospectively reviewed data from critically ill patients treated with ECMO and matched controls who received a continuous infusion of vancomycin (35 mg/kg loading dose over 4 hours followed by a daily infusion adapted to creatinine clearance, CrCl)). The pharmacokinetics of vancomycin were described using non-linear mixed effects modeling.

Results: We compared 11 patients treated with ECMO with 11 well-matched controls. Drug dosing was similar between groups. The median interquartile range (IQR) vancomycin concentrations in ECMO and non-ECMO patients were 51 (28 to 71) versus 45 (37 to 71) mg/L at 4 hours; 23 (16 to 38) versus 29 (21 to 35) mg/L at 12 hours; 20 (12 to 36) versus 23 (17-28) mg/L at 24 hours (ANOVA, P = 0.53). Median (ranges) volume of distribution (Vd) was 99.3 (49.1 to 212.3) and 92.3 (22.4 to 149.4) L in ECMO and non-ECMO patients, respectively, and clearance 2.4 (1.7 to 4.9) versus 2.3 (1.8 to 3.6) L/h (not significant). Insufficient drug concentrations (that is drug levels < 20 mg/dL) were more common in the ECMO group. The pharmacokinetic model (non-linear mixed effects modeling) was prospectively validated in five additional ECMO-treated patients over a 6-month period. Linear regression analysis comparing the observed concentrations and those predicted using the model showed good correlation (r(2) of 0.67; P < 0.001).

Conclusions: Vancomycin concentrations were similar between ECMO and non-ECMO patients in the early phase of therapy. ECMO treatment was not associated with significant changes in Vd and drug clearance compared with the control patients.

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Figures

Figure 1
Figure 1
Goodness-of-fit plots for the final covariate vancomycin pharmacokinetic model. The top panel presents the population predicted concentrations versus the observed concentrations. The lower panel presents the individual predicted concentrations versus the observed concentrations. For both graphs, the solid line represents the linear correlation (r 2 = 0.60 population predicted concentrations and r 2 = 0.99 for the individual predicted concentrations using linear regression).
Figure 2
Figure 2
Effect of different loading doses (LD) on rapid attainment of target vancomycin concentrations (≥20 mg/L). Daily continuous infusion regimen (MD) was 15 mg/kg/day. The dashed line presents simulations for patients on continuous renal replacement therapy (CRRT) and the solid line those for patients not receiving CRRT.
Figure 3
Figure 3
Effect of different maintenance doses (MD) on rapid attainment of target vancomycin concentrations (≥20 mg/L) after a loading dose of 35 mg/kg. The dashed line presents simulations for patients on continuous renal replacement therapy (CRRT) and the solid line those for patients not receiving CRRT, who had an estimated creatinine clearance of 100 mL/minute.
Figure 4
Figure 4
Observed concentrations from the patients included in the validation cohort versus the concentrations predicted by the model for those patients (linear regression r 2 0.66; P <0.001).
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