Adsorption of amikacin, a significant mechanism of elimination by hemofiltration

Abstract

We used an in vitro model of continuous venovenous hemofiltration (CVVH) to characterize amikacin adsorption by polyacrylonitrile (PAN) and polyamide filters. A blood-crystalloid mixture dosed with amikacin was pumped from a reservoir through a hemofiltration circuit and back to the reservoir. All ultrafiltrate was also returned to the reservoir. The level of adsorption was calculated from the fall in the amikacin concentration. The dose and the initial concentration of amikacin were varied, as were the pH, the type of hemofilter, and the hemofilter surface area. The reversibility of adsorption and the effect of repeated dosing were also studied. The level of adsorption by 0.6-m2 PAN filters was significantly greater than that by 0.6-m2 polyamide filters. Adsorption was increased by increasing the dose of amikacin even when the initial concentration was unchanged. It was unaffected by the pH (pH 6.8 or 7.4) or the hemofilter surface area (0.6 m2 or 0.9 m2). Repeated doses of amikacin resulted in further adsorption. In a saturation experiment, the maximum adsorptive capacity of 0.6-m2 PAN hemofilters was at least 546.9 mg (range, 427.6 to 577.5 mg). The adsorption of amikacin by hemofilters is irreversible and was associated with the dose and the hemofilter material but not the hemofilter surface area. Close monitoring of peak amikacin levels should be considered for patients receiving CVVH with PAN hemofilters.

FIG. 1.

In vitro model.

FIG. 2.

Amikacin adsorption by PAN filters against time. Immediately after 90 min, 500 ml of Ringer's solution was infused into the mixing chamber. P was <0.05 for group 1 versus group 3, and P was <0.01 for group 1 versus group 4. All data are shown as medians (ranges).

FIG. 3.

Amikacin adsorption by hemofilters against time. Immediately after 90 min, the second dose was infused repeatedly into the mixing chamber. P was <0.01 for group 5 versus group 6, for group 7 versus group 6, and for adsorption at 150 min versus adsorption at 90 min in the same group. All data are shown as medians (ranges).

FIG. 4.

Cumulative amikacin adsorption (n = 4) by hemofilters with repeated dosing and the circulating concentration in vitro when blood was taken to calculate adsorption (group 8). Data are presented as medians and ranges.