ANTIBIOTIC PHARMACOKINETICS FOLLOWING FLUID RESUSCITATION FROM TRAUMATIC SHOCK

Objective: To describe the pharmacokinetic profile of aztreonam and va ncomycin hydrochloride in a clinically relevant experimental model of hemorrhagic shock and trauma. Methods: Ten mongrel pigs (mean +/- SD w eight, 26.7 +/- 6.4 kg) were anesthetized with fentanyl citrate and ve ntilated, and an indwelling catheter was placed in the jugular vein. O n day 3, all pigs were subjected to fentanyl administration, ventilati on, soft-tissue injury, and an arterial hemorrhage (mean +/- SD, 40% /- 8%). After a 1-hour shock period, baseline hemodynamics were restor ed by reinfusing shed blood plus twice the shed volume as lactated Rin ger's solution. Aztreonam and vancomycin were infused on day 1, after resuscitation on day 3, and on days 4 and 8. Serial plasma samples wer e collected for 6 hours after treatment, and differences were compared with analysis of variance. Results: Aztreonam clearance initially dec reased 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 va lue. Vancomycin steady-state volume initially increased with trauma (P = .009), but it subsequently decreased by 29% (P < .001) on day 8. Th ese data cannot be explained by changes in plasma volume per se becaus e levels of plasma sodium, potassium, chloride, and calcium were withi n 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 withi n normal reference ranges. Furthermore, our previous work demonstrated that systemic and splanchnic organ oxygen delivery and demand were ne ar normal immediately after fluid resuscitation and for at least 3 day s thereafter; thus, there were probably no major perfusion abnormaliti es in the liver or kidney. Conclusions: For at least 5 days after trau ma, clearance and steady-state volume of aztreonam and vancomycin are altered. These changes suggest that the interval and magnitude of dosi ng should be adjusted, relative to the standard recommended dosages of each antibiotic, to maximize their efficacy. Similar studies should b e done for other antibiotics.