Aminoglycoside nephrotoxicity in critically iii surgical patients

A clinical method was sought to differentiate aminoglycoside (AG) damage from the renal damage induced by underlying pathophysiology in critically ill surgical patients. One hundred and fourteen such patients were monitored with daily AG blood levels and serum creatinines (Scr); 24-hr urines for creatinine, β₂-microglobulin, AG clearances; and urinary cast count and tissue levels of AG when possible. A two-compartment pharmacokinetic analysis of blood levels was used to characterize the rate and extent of AG tissue accumulation, as this parameter offers a quantitative means of evaluating AG-related nephrotoxicity. In 50% of patients a rise in Scr was noted. In deciding whether this rise was due to renal tubule (RT) damage or glomerular filtration shutdown, we employed tests of RT function such as β₂-microglobulin and cast count to establish tubular damage. The cause of tubular damage was then determined from the pattern of the indices and from the tissue accumulation values. Since not all creatinine rises were AG nephrotoxicity, these drugs should be stopped only in patients with evidence of AG-related RT damage. In contrast, glomerular insufficiency requires only dosage adjustment unless drug-related RT damage also occurs. Employing the criteria above, gentamicin and amikacin were responsible for significantly more AG-related nephrotoxicity than tobramycin (P < 0.05).