Aminoglycoside pharmacokinetics: dosage requirements and nephrotoxicity in trauma patients

We evaluated prospectively gentamicin and tobramycin pharmacokinetics in 37 patients with multiple system trauma and seven patients with isolated closed head trauma. The mean apparent volume of distribution (Vd) was 0.38 +/- 0.10 and 0.27 +/- 0.04 L/kg actual body weight (ABW) in patients with multiple trauma and closed head trauma, respectively. The difference in Vd between the two groups of patients was significant (p less than .002). Vd was not predictable on the basis of age, sex, weight, trauma score, or hospital day that therapy was initiated. Mean aminoglycoside clearance (Cl) was 123 +/- 46 ml/min. Neither serum creatinine nor estimated creatinine Cl predicted aminoglycoside Cl with sufficient accuracy to be clinically useful (r = .33 and .67, respectively). The mean daily dose was 6.1 +/- 1.6 mg/kg. The mean peak serum level was 5.8 +/- 1.3 micrograms/ml. Only one patient developed clinically significant renal dysfunction. Our data indicate that a loading dose of gentamicin or tobramycin of 3 mg/kg ABW in patients with multiple trauma and 2.5 mg/kg ABW in patients with isolated head trauma will obtain a mean initial peak serum level of 6.6 micrograms/ml. Although adequate maintenance dosing requires individualization based on pharmacokinetic analyses, large aminoglycoside doses can be used safely in patients with blunt trauma if appropriate monitoring is employed.