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Trough Concentrations of Vancomycin in Patients Undergoing Extracorporeal Membrane Oxygenation.

Park SJ, Yang JH, Park HJ, In YW, Lee YM, Cho YH, Chung CR, Park CM, Jeon K, Suh GY - PLoS ONE (2015)

Bottom Line: Early trough levels were obtained within the fourth dosing, and maintenance levels were measured at steady state.Sixteen patients received an initial intravenous dose of 1.0 g vancomycin followed by 1.0 g every 12 hours.Vancomycin clearance was 1.27±0.51 mL/min/kg, vancomycin clearance/creatinine clearance ratio was 0.90 ± 0.37, and elimination rate constant was 0.12 ± 0.04 h-1.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical Services, Samsung Medical Center, Seoul, Korea.

ABSTRACT
To investigate the appropriateness of the current vancomycin dosing strategy in adult patients with extracorporeal membrane oxygenation (ECMO), between March 2013 and November 2013, patients who were treated with vancomycin while on ECMO were enrolled. Control group consisted of 60 patients on vancomycin without ECMO, stayed in medical intensive care unit during the same study period and with the same exclusion criteria. Early trough levels were obtained within the fourth dosing, and maintenance levels were measured at steady state. A total of 20 patients were included in the analysis in ECMO group. Sixteen patients received an initial intravenous dose of 1.0 g vancomycin followed by 1.0 g every 12 hours. The non-steady state trough level of vancomycin after starting administration was subtherapeutic in 19 patients (95.00%) in ECMO group as compared with 40 patients (66.67%) in the control group (p = 0.013). Vancomycin clearance was 1.27±0.51 mL/min/kg, vancomycin clearance/creatinine clearance ratio was 0.90 ± 0.37, and elimination rate constant was 0.12 ± 0.04 h-1. Vancomycin dosingfrequency and total daily dose were significantly increased after clinical pharmacokinetic services of the pharmacist based on calculated pharmacokinetic parameters (from 2.10 ± 0.72 to 2.90 ± 0.97times/day, p = 0.002 and from 32.54 ± 8.43 to 42.24 ± 14.62mg/kg, p = 0.014) in ECMO group in contrast with those (from 2.11 ± 0.69 to 2.37 ± 0.86 times/day, p = 0.071 and from 33.91 ± 11.85 to 31.61 ± 17.50 mg/kg, p = 0.350) in the control group.Although the elimination rate for vancomycin was similar with population parameter of non ECMO patients, the current dosing strategy of our institution for vancomycinin our ICU was not sufficient to achieve the target trough in the initial period in most patients receiving ECMO.

No MeSH data available.


Differences of vancomycin daily total dosage (A) and dosing frequency (B) between initial and maintenance phase.
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pone.0141016.g003: Differences of vancomycin daily total dosage (A) and dosing frequency (B) between initial and maintenance phase.

Mentions: Among the 20 patients in ECMO group, the vancomycin therapeutic target range was set at 15–20 mcg/ml in 19, and only one patient was suitable for a lower target range of 10–15 mcg/ml. Sixteen patients (80.0%) received an initial intravenous dose of 1.0 g, followed by 1.0 g every 12 hours. The mean starting daily dose was 32.54 mg/kg, and the dosing frequency was 2.10 ± 0.72 times/day. The mean elimination rate constant (K) was 0.12± 0.04 h-1, clearance(CL) was 4.62 L/hr, and volume of distribution (Vd) was 0.65 L/kg. The vancomycin clearance/creatinine clearance (Clcr) ratio was 0.90. Pharmacokinetic parameters and clinical parameters of ECMO group are shown in Table 2. The mean initial trough level was as low as 8.80 mcg/ml with a difference of 5.95 mcg/ml compared with the lower limit of the vancomycin target range. Of 20 cases, only one (5%) reached the target range before the fourth dose, and the others were all at sub-therapeutic levels during the initial phase (Fig 2). After the fourth dose, the mean daily dose was increased to 42.24 mg/kg (p = 0.014) and the dosing frequency was increased to 2.90 ± 0.97 times/day. Both of these changes from starting dosing patterns to maintenance dosing patterns were statistically significant (p = 0.002) (Fig 3). Meanwhile, in control group, 40 patients(66.67%) got subtherapeutic vancomycin level before fourth dose and there was significant difference between ECMO and control groups (p = 0.013). Contrast to ECMO group, vancomycin dosingfrequency and total daily dose were not significantly increased after clinical pharmacokinetic services(from 2.11 ± 0.69 to 2.37 ± 0.86 times/day, p = 0.071 and from 33.91 ± 11.85 to 31.61 ± 17.50 mg/kg, p = 0.350) in the control group. Comparison of vancomycin pharmacokinetics between ECMO and control groups were presented in S1 Table. There were no significant differences in Vd, K and CL between the two groups. The average time to achieve the target trough was significantly longer in ECMO group than control group (84.59 hours vs 57.41 hours, p = 0.013). Comparison of pharmacokinetic parameters between veno-venous and veno-arterial ECMO were presented in S2 Table.


Trough Concentrations of Vancomycin in Patients Undergoing Extracorporeal Membrane Oxygenation.

Park SJ, Yang JH, Park HJ, In YW, Lee YM, Cho YH, Chung CR, Park CM, Jeon K, Suh GY - PLoS ONE (2015)

Differences of vancomycin daily total dosage (A) and dosing frequency (B) between initial and maintenance phase.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4636270&req=5

pone.0141016.g003: Differences of vancomycin daily total dosage (A) and dosing frequency (B) between initial and maintenance phase.
Mentions: Among the 20 patients in ECMO group, the vancomycin therapeutic target range was set at 15–20 mcg/ml in 19, and only one patient was suitable for a lower target range of 10–15 mcg/ml. Sixteen patients (80.0%) received an initial intravenous dose of 1.0 g, followed by 1.0 g every 12 hours. The mean starting daily dose was 32.54 mg/kg, and the dosing frequency was 2.10 ± 0.72 times/day. The mean elimination rate constant (K) was 0.12± 0.04 h-1, clearance(CL) was 4.62 L/hr, and volume of distribution (Vd) was 0.65 L/kg. The vancomycin clearance/creatinine clearance (Clcr) ratio was 0.90. Pharmacokinetic parameters and clinical parameters of ECMO group are shown in Table 2. The mean initial trough level was as low as 8.80 mcg/ml with a difference of 5.95 mcg/ml compared with the lower limit of the vancomycin target range. Of 20 cases, only one (5%) reached the target range before the fourth dose, and the others were all at sub-therapeutic levels during the initial phase (Fig 2). After the fourth dose, the mean daily dose was increased to 42.24 mg/kg (p = 0.014) and the dosing frequency was increased to 2.90 ± 0.97 times/day. Both of these changes from starting dosing patterns to maintenance dosing patterns were statistically significant (p = 0.002) (Fig 3). Meanwhile, in control group, 40 patients(66.67%) got subtherapeutic vancomycin level before fourth dose and there was significant difference between ECMO and control groups (p = 0.013). Contrast to ECMO group, vancomycin dosingfrequency and total daily dose were not significantly increased after clinical pharmacokinetic services(from 2.11 ± 0.69 to 2.37 ± 0.86 times/day, p = 0.071 and from 33.91 ± 11.85 to 31.61 ± 17.50 mg/kg, p = 0.350) in the control group. Comparison of vancomycin pharmacokinetics between ECMO and control groups were presented in S1 Table. There were no significant differences in Vd, K and CL between the two groups. The average time to achieve the target trough was significantly longer in ECMO group than control group (84.59 hours vs 57.41 hours, p = 0.013). Comparison of pharmacokinetic parameters between veno-venous and veno-arterial ECMO were presented in S2 Table.

Bottom Line: Early trough levels were obtained within the fourth dosing, and maintenance levels were measured at steady state.Sixteen patients received an initial intravenous dose of 1.0 g vancomycin followed by 1.0 g every 12 hours.Vancomycin clearance was 1.27±0.51 mL/min/kg, vancomycin clearance/creatinine clearance ratio was 0.90 ± 0.37, and elimination rate constant was 0.12 ± 0.04 h-1.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical Services, Samsung Medical Center, Seoul, Korea.

ABSTRACT
To investigate the appropriateness of the current vancomycin dosing strategy in adult patients with extracorporeal membrane oxygenation (ECMO), between March 2013 and November 2013, patients who were treated with vancomycin while on ECMO were enrolled. Control group consisted of 60 patients on vancomycin without ECMO, stayed in medical intensive care unit during the same study period and with the same exclusion criteria. Early trough levels were obtained within the fourth dosing, and maintenance levels were measured at steady state. A total of 20 patients were included in the analysis in ECMO group. Sixteen patients received an initial intravenous dose of 1.0 g vancomycin followed by 1.0 g every 12 hours. The non-steady state trough level of vancomycin after starting administration was subtherapeutic in 19 patients (95.00%) in ECMO group as compared with 40 patients (66.67%) in the control group (p = 0.013). Vancomycin clearance was 1.27±0.51 mL/min/kg, vancomycin clearance/creatinine clearance ratio was 0.90 ± 0.37, and elimination rate constant was 0.12 ± 0.04 h-1. Vancomycin dosingfrequency and total daily dose were significantly increased after clinical pharmacokinetic services of the pharmacist based on calculated pharmacokinetic parameters (from 2.10 ± 0.72 to 2.90 ± 0.97times/day, p = 0.002 and from 32.54 ± 8.43 to 42.24 ± 14.62mg/kg, p = 0.014) in ECMO group in contrast with those (from 2.11 ± 0.69 to 2.37 ± 0.86 times/day, p = 0.071 and from 33.91 ± 11.85 to 31.61 ± 17.50 mg/kg, p = 0.350) in the control group.Although the elimination rate for vancomycin was similar with population parameter of non ECMO patients, the current dosing strategy of our institution for vancomycinin our ICU was not sufficient to achieve the target trough in the initial period in most patients receiving ECMO.

No MeSH data available.