SYNERGISTIC EFFECT OF E5, IMIPENEM, AND VOLUME SUPPORT DURING FULMINANT INTRAABDOMINAL SEPSIS IN RATS

The protective effect of volume support, imipenem, and the anti-endoto xin antibody E5 given as mono- or combination therapy was studied in f ulminant intraabdominal sepsis in rats. Mortality, blood levels of bac teria, endotoxin, tumor necrosis factor (TNF), and lactate, and packed cell volume were measured. AU monotherapy regimens improved survival, and protection decreased with delayed intervention. Volume support pr evented dehydration and lactate accumulation but had no effect on leve ls of bacteria, endotoxin, or TNF. Imipenem killed bacteria and releas ed endotoxin, and lactacidosis was reduced. E5 reduced endotoxin, TNF, and lactate but not bacteremia. The imipenem-induced increase in plas ma endotoxin was abolished by E5. When E5 was added to a regimen of vo lume support plus imipenem 6 h after induction, it gave an extra impro vement of survival, but this synergism disappeared when intervention w as delayed 4 h more. The primary effect of E5 was a reduction in plasm a endotoxin level.