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.

Recommended β-lactam regimens are inadequate in septic patients treated with continuous renal replacement therapy

“…In such patients, the pharmacokinetics is altered both in terms of distribution (sepsis itself can modify the V d , resuscitation measures and nutritional factors) and of elimination (drains, altered metabolism and clearance changes). The higher V d in the initial phase of sepsis has been previously described in studies on aminoglycosides [32,33] and vancomycin [34]. We recently demonstrated an increased V d and a high variability of serum antibiotic concentrations in ICU patients with severe sepsis and septic shock [14].…”

Comparison of two methods to obtain a desired first isepamicin peak in intensive care patients

“…The influence of mechanical ventilation on the pharmacokinetic of aminoglycoside has been studied in previous study [26]. Ventilation is accompanied by modification of antidiuretic hormone secretion that, in turn, alters the volume of extracellular fluids.…”

Mechanical Ventilation: A Tutorial for Pharmacists

“…Data have shown that mechanical ventilation directly affects the pharmacokinetic profile of many pharmaceutical agents, including gentamicin, midazolam, lidocaine, ofloxacin, levofloxacin, dexmedetomidine, cisatracurium, atracurium, propofol, and midazolam. [42][43][44][45][46][47][48] Although data identify the direct result of positive pressure ventilation on altering pharmacokinetic parameters, clinicians have other therapeutic modalities to minimize the effects of these changes. These therapeutic modalities include volume resuscitation, inotropic and vasopressor support, and ventilator management (e.g., lowering tidal volumes and decreasing PEEP).…”