multiple-injury patient, despite the fact that antibiotics are used for a wide array of indications
in these patients. The effects of pathophysiologic changes upon antibiotic therapy will be cited
among studies of critically ill and severely septic patients in the intensive care unit, and not
exclusively in multiple-trauma patients.
Preventive Antibiotics in the Injured Patient
Preventive antibiotics have been used for over 30 years in trauma patients (1). The recognized
principals of preoperative administration of an antibiotic with activity against the likely
pathogens to be encountered have been the hallmark of utilization in this setting. However,
trauma patients have blood loss and large volumes of resuscitation in the period of time
leading up to, and during, the operative intervention. The sequestration of the resuscitation
volume into injured tissue results and the obligatory expansion of the extracellular water
volume all contribute to a vastly expandedVd. Should antibiotic doses be modified in this
clinical setting?
Ericsson et al. (2) studied penetrating abdominal trauma patients with a regimen of
preventive antibiotics that employed clindamycin and amikacin. In a limited number of
preliminary-study patients, they noted that conventional doses of 7.5 mg/kg amikacin given
preoperative resulted in suboptimal peak serum concentrations (13.5 to 18.0m/mL) compared
with effective therapeutic peak concentrations (25 to 28m/mL) at 30 minutes after infusion
when 11 mg/kg of the drug was administered.
The explanation for the lower antibiotic concentrations in the conventional dosing
regimen was found in the largerVdand shortT1/2that were seen in the trauma patients
compared to normal controls. In a study of eight patients that averaged 37 years of age and had
normal creatinine, each received between 6.7 to 11 mg/kg of amikacin. The measuredVdwas
20.9 L compared with the estimated normal of 14.3 L. TheT1/2was measured at 1.9 hours and
the estimated normalT1/2for amikacin was 3.3 hours. Subsequent studies of an additional
28 trauma patients confirmed the impact of the increasedVdand the increased elimination
rates of the drug in adversely affecting preventive antibiotic concentrations (3).
A prospective study examined the wound and intra-abdominal infection rates of
penetrating abdominal trauma patients who received different doses of amikacin (2). The data
are illustrated in Table 2. Significantly, higher doses of amikacin resulted in statistically
reduced infection rates in all patients studied. Subgroup analysis indicated that lower infection
rates were identified in patients with high-volume blood loss and in patients with injury
severity scores>20. No improvement in rates infections was seen in patients when colon injury
was present, indicating that high inocula of surgical site contamination cannot likely be
overcome by preventive antibiotics. This observed uncertainty about antibiotic pharmacoki-
netics in the setting of blood loss and injury has led to some experimental investigation in the
use of continuous infusion of antibiotics as a means to overcome the problem. Another strategy
has been to simply not use potentially toxic agents like the aminoglycosides, but rather choose
Table 2 Differences in Clinical Outcomes of Infection when 7.5 mg/kg of Amikacin is Compared with 10 mg/kg of
Amikacin in Trauma Patients with Penetrating Abdominal Trauma
Patient characteristic 7.5 mg/kg 10 mg/kg P¼ Comment
All patients 21/87 (24%) 5/63 (8%) <0.01 The dose does matter!
No colon injury 12/57 (21%) 1/48 (2%) <0.005 Small inoculum responds well to
preventive drug
Colon injury 9/30 (30%) 4/15 (27%) N.S.a Large inoculum eliminates
effectiveness
Blood loss>6 L 16/43 (37%) 3/27 (11%) <0.02 Loss of antibiotic?
ISSb> 20 11/32 (34%) 1/18 (6%) <0.025 Large dose is necessary for large
injuries.
ISSb< 20 10/55 (18%) 4/45 (9%) N.S.a May have been a type-2 statistical
error
aNot significant.
bInjury severity score.
526 Fry