Appropriateness of a 4 mg/kg gentamicin or tobramycin loading dose in post-operative septic shock patients

To determine the frequency with which early adequate peak serum concentrations (6-12 mg/ litre) can be achieved following a 4 mg/kg loading dose of gentamicin or tobramycin in post-operative septic shock patients.

Eleven post-operative septic shock patients were grouped into (i) a control group (n=7) who received the conventional gentamicin or tobramycin dosing regimen of 2 mg/kg loading dose followed by a maintenance dose of approximately 1.5mg/kg (peak and trough levels were measured after the third dose), and (ii) a study group (n = 4) who received a tobramycin or gentamicin 4 mg/kg loading dose, followed by 30 min, 3 h and 16 h serum drug level measurements. Pharmacokinetic parameters were calculated using a one-compartmental model. Differences in both groups were determined using Student's t-test.

Pharmacokinetic parameters in both groups showed no statistically significant difference. The dose from which peak levels were drawn was significantly higher in the study group (4 mg/kg vs. 1.66 mg/kg; P = 0.001), which also resulted in higher but adequate peak serum concentrations (8.9+/-2.2 vs. 4.8+/-1.8 mg/litre). In the study group, linear regression analysis showed significant relationships between dose and peak concentrations and volume of distribution and peak concentrations (r = 0.96, P= 0.01 and r= -0.96, P= 0.01, respectively).

One hundred per cent of the post-operative septic shock patients achieved target peak serum concentrations (mean 8.9+/-2.2 mg/litre) following a 4 mg/kg tobramycin or gentamicin loading dose. An expanded Vd (0.46+/-0.13 litres/kg) was also observed.