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David S. McKindley, PharmD; Timothy C. Fabian, MD; Bradley A. Boucher, PharmD; Martin A. Croce, MD; Kenneth G. Proctor, PhD

Arch Surg. 1995;130(12):1321-1329.

Abstract
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.

(Arch Surg. 1995;130:1321-1329)

Author Affiliations
From the Departments of Clinical Pharmacy (Drs McKindley and Boucher), Surgery (Drs Fabian and Croce), and Physiology (Dr Proctor), University of Tennessee, Memphis. Dr McKindley is now with the Department of Pharmacy Practice, University of Rhode Island, Kingston.

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