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

Donadello K, Roberts JA, Cristallini S, Beumier M, Shekar K, Jacobs F, Belhaj A, Vincent JL, de Backer D, Taccone FS - Crit Care (2014)

Bottom Line: The pharmacokinetics of vancomycin were described using non-linear mixed effects modeling.Drug dosing was similar between groups.The pharmacokinetic model (non-linear mixed effects modeling) was prospectively validated in five additional ECMO-treated patients over a 6-month period.

View Article: PubMed Central - PubMed

Affiliation: Department of Intensive Care, Erasme Hospital, Université Libre de Bruxelles, Route de Lennik, 808 - 1070, Brussels, Belgium. katia_doc@yahoo.it.

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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Related in: MedlinePlus

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.
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Fig3: 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.

Mentions: Figures 2 and 3 show vancomycin concentrations obtained through simulations for different loading and maintenance doses in the presence/absence of CRRT (50 years of age, 70 kg of weight and a CrCl of 100 mL/minute). Figure 2 shows that even a loading dose of at least 15 mg/kg was necessary to ensure rapid achievement of target vancomycin concentrations. Using the same loading dose in the presence of CRRT did not significantly influence drug concentrations when compared to no use of CRRT. Figure 3 shows that after a 35 mg/kg loading dose, a maintenance CI dose of at least 10 mg/kg/day was required during CRRT, whereas doses of 10 or 15 mg/kg/day were both able to provide drug concentrations between 20 and 30 mg/L in the case of no need for CRRT.Figure 2


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

Donadello K, Roberts JA, Cristallini S, Beumier M, Shekar K, Jacobs F, Belhaj A, Vincent JL, de Backer D, Taccone FS - Crit Care (2014)

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.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4256896&req=5

Fig3: 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.
Mentions: Figures 2 and 3 show vancomycin concentrations obtained through simulations for different loading and maintenance doses in the presence/absence of CRRT (50 years of age, 70 kg of weight and a CrCl of 100 mL/minute). Figure 2 shows that even a loading dose of at least 15 mg/kg was necessary to ensure rapid achievement of target vancomycin concentrations. Using the same loading dose in the presence of CRRT did not significantly influence drug concentrations when compared to no use of CRRT. Figure 3 shows that after a 35 mg/kg loading dose, a maintenance CI dose of at least 10 mg/kg/day was required during CRRT, whereas doses of 10 or 15 mg/kg/day were both able to provide drug concentrations between 20 and 30 mg/L in the case of no need for CRRT.Figure 2

Bottom Line: The pharmacokinetics of vancomycin were described using non-linear mixed effects modeling.Drug dosing was similar between groups.The pharmacokinetic model (non-linear mixed effects modeling) was prospectively validated in five additional ECMO-treated patients over a 6-month period.

View Article: PubMed Central - PubMed

Affiliation: Department of Intensive Care, Erasme Hospital, Université Libre de Bruxelles, Route de Lennik, 808 - 1070, Brussels, Belgium. katia_doc@yahoo.it.

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.

Show MeSH
Related in: MedlinePlus