Pharmacokinetics and posology of vancomycin in adults receiving ECMO
Date Issued
2007
Date
2007
Author(s)
Wu, Chien-Chih
DOI
zh-TW
Abstract
Aims:
Extracoporeal membrane oxygenation (ECMO) is indicated for patients with reversible cardiopulmonary failure. Due to the increasing infection rate of methicillin-resistant staphylococcus aureus (MRSA), vancomycin is often empirically used in patients receiving ECMO. Patients on ECMO required priming fluid (centrifugal pump: 850 mL, roller pump: 2000 mL). Studies showed that renal function in patients receiving ECMO altered transiently and vancomycin might be sequestrated by the circuit of ECMO. The objective of this study was to understand the effects of ECMO on pharmacokinetics of vancomycin in adult patients, so as to establish a dosing guildline for patients on ECMO and in ICU and decide the appropriate sampling time for monitoring peak concentration.
Methods:
This is a control study. Both ECMO and control groups recruited 12 patients. The inclusion criteria for ECMO group were patients greater than or equaled to 18 years-old and received ECMO and vancomycin simultaneously. Those who were on continuous renal replacement therapy (CRRT) or hemodialysis, or having severe burn (involved 30-40% body surface area) were excluded. The inclusion and exclusion criteria for control group were the same as ECMO group, except that they did not use ECMO. Control group was matched with ECMO group by age, sex and renal function.
Vancomycin therapy might be initiated with or without a loading dose (LD) of 15 mg/kg. The maintenance dose was determined by Rodvold method. In patients with a creatinine clearance (CLCr) ≥ 50 mL/min, 500 mg q6h and 1000 mg q12h could be given. Serum vancomycin concentrations were determined after at least the fourth dose. Five to nine samples were taken depending on dosing interval and pharmacokinetic (PK) parameters were determined by fitting the data to non-compartment model.
The PK parameters determined by Sawchuk and Zaske’s method were compared with those determined by non-compartment model. Through this comparison, the most appropriate sampling time for routine monitor of peak concentration was determined.
Results and Discussion:
The elimination rate constant (k), half life (t1/2), clearance (CLvancomycin) and volume distribution at steady state (Vss) of ECMO and control group were 0.088 ± 0.055 vs. 0.125 ± 0.096 hr-1, 11.13 ± 9.08 vs. 10.15 ± 9.08 hr, 1.18 ± 0.71 vs. 1.45 ± 0.82 mL/min/kg, 0.84 ± 0.24 vs. 0.83 ± 0.30 L/kg, respectively, and there was no statistically significant difference between the 2 groups. Priming volume of ECMO did not have important influence on Vss of ECMO. Reducing renal perfusion could reduce CLvancomycin and make t1/2 longer.
After stratifing ECMO group according to centrifugal and roller pump, there was a significant difference in k (0.110 ± 0.057 vs. 0.049 ± 0.021, p=0.035) and t1/2 (7.99 ± 3.88 vs. 16.62 ± 8.30, p=0.04). Although Vss tended to be greater in patients using roller pump, there were no statistically significant differences between these 2 groups. There were also no statistically differences in PK parameters between the individual groups and their control.
CLCr was a good predictor of CLvancomycin. Linear regression using all patient’s data showed that CLvancomycin = 0.019*CLCr – 0.18 (r=0.73, R2= 0.53, p <0.001). The linear relationship was more significant in control group (r = 0.78) than in ECMO group (r = 0.61).
In National Taiwan University Hospital, Rodvold method was used to calculate empirical vancomycin maintenance dose. Due to the poor predictivity of the method, we recommended that a 15 mg/kg loading dose be given and an empirical maintenance dose determined by equation: maintenance dose (mg/kg/24hr) = 0.5472*CLCr (mL/min/1.73m2) – 5.184 developed according to CLCr and CLvancomycin in all patients in this study. The dosing intervals were determined according to CLCr (mL/min/1.73m2) : 6 hrs for CLCr ≥ 100; 8 hrs for 80 ≤ CLCr ≤ 99; 12 hrs for 40 ≤ CLCr ≤ 79. This equation could only be applied to patients with a CLCr greater than 40 mL/min/1.73m2. From this study, PK parameters might be estimated by CL(mL/min/kg) = 0.019*CLCr(mL/min/1.73m2) – 0.18、k(hr-1) = 0.0017*CLCr(mL/min/1.73m2) – 0.029、Vd(L/kg) = CL*60/(k*1000) and used these PK parameters to determine appropriate dose for individual patients.
. After empirical dosing of vancomycin, pharmacokinetic monitoring should be performed after at least four doses, especially for patients receiving ECMO. The most appropriate sampling time for peak concentration was 2 hours after completion of infusion of vancomycin. After obtaining peak and trough concentration, Sawchuk and Zaske’s method provides a good estimate of PK parameters for adjusting vancomycin dosage.
Key words：vancomycin、pharmacokinetics (PK)、extracoporeal membrane oxygenation (ECMO)、critical care、dosage、adult
Subjects
萬古黴素
藥品動態學(藥動學)
體外膜氧合術
重症照護
劑量學
成人
vancomycin
pharmacokinetics (PK)
extracoporeal membrane oxygenation (ECMO)
critical care
dosage
adult
Type
text
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