Antibiotic pharmacokinetics following fluid resuscitation from traumatic shock
D. S. McKindley, T. C. Fabian, B. A. Boucher, M. A. Croce and K. G. Proctor
Department of Clinical Pharmacy, University of Tennessee, Memphis, USA.
OBJECTIVE: To describe the pharmacokinetic profile of aztreonam and
vancomycin hydrochloride in a clinically relevant experimental model of
hemorrhagic shock and trauma. METHODS: Ten mongrel pigs (mean +/- SD
weight, 26.7 +/- 6.4 kg) were anesthetized with fentanyl citrate and
ventilated, and an indwelling catheter was placed in the jugular vein. On
day 3, all pigs were subjected to fentanyl administration, ventilation,
soft-tissue injury, and an arterial hemorrhage (mean +/- SD, 40% +/- 8%).
After a 1-hour shock period, baseline hemodynamics were restored by
reinfusing shed blood plus twice the shed volume as lactated Ringer's
solution. Aztreonam and vancomycin were infused on day 1, after
resuscitation on day 3, and on days 4 and 8. Serial plasma samples were
collected for 6 hours after treatment, and differences were compared with
analysis of variance. RESULTS: Aztreonam clearance initially decreased with
trauma, but subsequently increased by 48% (P < .02) by day 8. Aztreonam
steady-state volume decreased by 34% (P = .05, baseline value vs that on
day 8). Vancomycin clearance was increased between 25% and 52% (P <
.001) on days 3, 4, and 8 compared with the baseline value. Vancomycin
steady-state volume initially increased with trauma (P = .009), but it
subsequently decreased by 29% (P < .001) on day 8. These data cannot be
explained by changes in plasma volume per se because levels of plasma
sodium, potassium, chloride, and calcium were within normal reference
ranges at all time points. Neither liver nor renal functions were severely
impaired because levels of serum urea nitrogen, bilirubin, liver enzymes,
creatinine, and plasma proteins were within normal reference ranges.
Furthermore, our previous work demonstrated that systemic and splanchnic
organ oxygen delivery and demand were near normal immediately after fluid
resuscitation and for at least 3 days thereafter; thus, there were probably
no major perfusion abnormalities in the liver or kidney. CONCLUSIONS: For
at least 5 days after trauma, clearance and steady-state volume of
aztreonam and vancomycin are altered. These changes suggest that the
interval and magnitude of dosing should be adjusted, relative to the
standard recommended dosages of each antibiotic, to maximize their
efficacy. Similar studies should be done for other antibiotics.