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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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Observed concentrations from the patients included in the validation cohort versus the concentrations predicted by the model for those patients (linear regressionr20.66;P<0.001).
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Fig4: Observed concentrations from the patients included in the validation cohort versus the concentrations predicted by the model for those patients (linear regressionr20.66;P<0.001).

Mentions: Five additional patients (four on VV ECMO and one on VA ECMO) treated with vancomycin during ECMO therapy were identified. Four of the patients were male; the median (IQR) age was 64 (55 to 68) years, weight 71 (70 to 80) kg, and three of the patients were receiving CRRT at an intensity of 21 (21 to 26) mL/kg/h. The patients received a loading dose of 2,485 (2,450 to 2,800) mg of vancomycin and a maintenance continuous infusion of 1,250 (1,050 to 1,750) mg (Table 5). The linear regression analysis confirmed the adequacy of the model by comparing the observed concentrations from the external dataset and those predicted using the model (r2 of 0.67; P <0.001) (Figure 4).Table 5


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)

Observed concentrations from the patients included in the validation cohort versus the concentrations predicted by the model for those patients (linear regressionr20.66;P<0.001).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig4: Observed concentrations from the patients included in the validation cohort versus the concentrations predicted by the model for those patients (linear regressionr20.66;P<0.001).
Mentions: Five additional patients (four on VV ECMO and one on VA ECMO) treated with vancomycin during ECMO therapy were identified. Four of the patients were male; the median (IQR) age was 64 (55 to 68) years, weight 71 (70 to 80) kg, and three of the patients were receiving CRRT at an intensity of 21 (21 to 26) mL/kg/h. The patients received a loading dose of 2,485 (2,450 to 2,800) mg of vancomycin and a maintenance continuous infusion of 1,250 (1,050 to 1,750) mg (Table 5). The linear regression analysis confirmed the adequacy of the model by comparing the observed concentrations from the external dataset and those predicted using the model (r2 of 0.67; P <0.001) (Figure 4).Table 5

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