Is 4 MG/KG an adequate loading dose for genta-micin/tobramycin in critically ill surgical patients?

Justin B. Dimick, Todd Dorman, Sandra M. Swoboda, Peter Crompton, Pamela A. Lipsett

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Introduction: Critically ill patients with gram-negative sepsis demonstrate increased volumes of distribution for aminoglycosides (AG), and many do not achieve initial therapeutic levels. We hypothesized that a higher loading dose for AG would increase the proportion of patients who reach therapeutic levels early in therapy when compared with historic controls with 3 mg/kg (1). Methods: This prospective SICU observational study was designed to determine the value of a 4 mg/kg loading dose for tobramycin(T) and gentamicin(G) or 16 mg/kg for amikacin(A )in reaching initial therapeutic serum AG levels (defined as > 8 meg/ml for G and T or > 32 meg/ml for A). The drug was infused over 30 minutes and serum levels obtained one hour (peak) and eight hours post-infusion for pharmacokinetics. Results: Forty seven patients had data available for analysis. Subjects were 58±17 years old, with median APACHE II scores of 14 (range 7 to 28). Baseline serum creatinine levels were 1.6±0.9 mg/dl, with a calculated creatinine clearance of 65±36 ml/min. Pharmacokinetic calculations yielded a 49% increase in the apparent Vd at 0.37±0.12 L/kg. The Kel was 0.13±0.06hr-1 and the t1/2 was 6.8±3.5hrs. The one hour post-infusion aminoglycoside levels were therapeutic in 44 of 47 subjects (94%) vs 50% in historic controls (p<0.001). The median serum level for G and T was 10.5 meg/ml (range 5.6 to 18.3). As suspected, the Kel correlated with the calculated creatinine clearance (R = 0.64; P<0.001) and the APACHE II score correlated with the percent increase in apparent Vd (R = 0.29; P<0.05). Conclusions: The proposed 4mg/kg loading dose achieves initial therapeutic levels in critically ill patients with increased volumes of distribution. The apparent Vd in our population was increased by 49% and correlated with the severity of disease. Due to the variability of pharmacokinetics in these patients, increased loading doses and individualized dosing will achieve optimal AG levels.

Original languageEnglish (US)
Pages (from-to)A93
JournalCritical care medicine
Issue number12 SUPPL.
StatePublished - Dec 1 1999

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine


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