Changes in gentamicin pharmacokinetic profiles induced by mechanical ventilation

Abstract

The influence of controlled mechanical ventilation (CMV) on the pharmacokinetic profile of gentamicin has been examined in 23 patients after elective open heart surgery. A parallel design was adopted in two groups of patients; 13 patients requiring CMV for at least 32 h after surgery, all of whom were able to breath spontaneously (SB) after 72 h (study group), and 10 patients who required CMV for only a brief period and who showed SB at 32 h postsurgery. Haemodynamic parameters remained stable throughout the study. Apparent volume of distribution (VZ), half-life (t1/2), total clearance (CL), peak (Cmax") and trough (Cmin") plasma levels at steady-state for target levels (6-8 microgram/ml), were measured. In the study group significant differences between CMV and SB conditions were found in VZ (mean 0.36 and 0.25 l/kg). t1/2 (mean 3.63 and 2.90 h) and Cmax" (mean 4.30 and 5.53 microgram/ml) while Cmin" (mean 1.06 microgram.ml-1 and 0.92 microgram.ml-1) did not change significantly. In contrast, the pharmacokinetics in the control group showed no differences. It appears that CMV leads to an increase in gentamicin Vz which accounts for the fall in Cmax" below the therapeutic dose range (less than 5 microgram/ml) recommended for gentamicin. It seems advisable to use a large dose of gentamicin in patients receiving CMV, even before the level is assessed.