Background
The clearance of antibiotics during continuous venovenous hemofiltration (CVVH) is calculated by multiplying the sieving coefficient (SC) (defined as the ratio of drug concentration in the ultrafiltrate to plasma) and the ultrafiltration rate (Quf). For most antibiotics the SC is unknown. It was suggested that the SC can be substituted by the non-protein-bound fraction (fu). However, fu values as reported in the literature are determined in healthy volunteers and not during critical illness. We compared measured and estimated CVVH clearance (ClCVVH) of five antibiotics.
Methods
In 40 patients with ARF undergoing CVVH (predilution, cellulose-triacetate filter, Quf 36 ± 8 ml/min), prefilter, postfilter and ultrafiltrate samples were collected and drug concentrations were determined by HPLC or by immunoassay. The prefilter concentration (Cpre) was corrected using the dilution factor (Qb/Qb + Qinf), where Qb is the blood flow rate and Qinf is the substitution fluid infusion rate. The SC was calculated as follows: SC = 2 × Cuf / (Cpre + Cpost).
Results
Data (mean ± standard deviation) are presented in Table 1. ClCVVH (ml/min) was calculated by multiplying the SC (or the fu) and the Quf.
Table 1.
| Drug (n) | Measured SC | Measured ClCVVH | Non-protein-bound fraction | Estimated ClCVVH |
|---|---|---|---|---|
| Ceftazidim (4) | 2.14 ± 2.64 | 75 ± 92 | 0.79 | 28 ± 1 |
| Ciprofloxacine (16) | 0.89 ± 0.33 | 31 ± 12 | 0.60 | 21 ± 1 |
| Flucloxacilline (5) | 0.37 ± 0.38 | 13 ± 14 | 0.20 | 7 ± 0 |
| Fluconazol (9) | 0.86 ± 0.09 | 30 ± 2 | 0.88 | 31 ± 1 |
| Vancomycine (6) | 0.71 ± 0.19 | 27 ± 5 | 0.70 | 28 ± 9 |
SC, sieving coefficient; ClCVVH, continuous venovenous hemofiltration clearance.
Conclusions
Measured and estimated ClCVVH corresponded well for fluconazol and vancomycine, but not for ceftazidim, ciprofloxacine and flucloxacilline, possibly due to changes in protein binding induced by critical illness or drug–membrane interactions. Therefore, for antibiotics with a narrow therapeutic range, monitoring drug concentrations remains mandatory.