Effect of anti-OprF-OprI immunoglobulin on APACHE II score in a porcine two-hit model of hemorrhagic shock/resuscitation and pseudomonas aeruginosa sepsis.

Abstract

BACKGROUND: Up to now, randomized clinical trials of treatment of bacterial sepsis with immunoglobulins show conflicting results. This paper investigates the effect of prophylactic immunization with anti-OprF-OprI antiserum on the APACHE II score in a clinically relevant two-hit model of hemorrhagic shock/resuscitation followed by Pseudomonas aeruginosa sepsis in pigs. METHODS: Twenty-three German Landrace-Hybrid pigs underwent chronic implantation of vascular catheters (internal and external jugular vein, carotic and pulmonary artery), hemorrhagic shock (mean blood loss 40% of estimated blood volume) for 45 min, followed by resuscitation with crystalloid, colloid, and shed blood. Randomization was to a control group (no immunization, n=6), an F-I group (50 mg/kg i.p. anti-OprF-OprI immunoglobulin, n=6), an S group (50 mg/kg i.p. unspecific porcine immunoglobulins, n=6), and a PS group (50 mg/kg i.p. immunoglobulin against the antigens of heat-killed P. aeruginosa, n=5). After at least 18 h for recovery from anesthesia, the pigs underwent a continuous intravenous infusion of P. aeruginosa for 48 h. Thereafter, the animals were monitored for another 48 h and then dissected. RESULTS: The APACHE II score significantly increased from baseline value in all groups during bacterial challenge. However, there were no between-group differences in APACHE II score. In contrast, pigs of the F-I and PS groups showed significant lower lung concentrations of P. aeruginosa (p<0.05 vs. control group) at autopsy. CONCLUSION: These experimental data suggest that under comparable clinical conditions, a prophylactic immunization with anti-OprF-OprI immunoglobulin would not have an overall benefit to patients with P. aeruginosa sepsis.