Synergistic effect of E5, imipenem, and volume support during fulminant intraabdominal sepsis in rats

The protective effect of volume support, imipenem, and the anti-endotoxin antibody E5 given as mono- or combination therapy was studied in fulminant intraabdominal sepsis in rats. Mortality, blood levels of bacteria, endotoxin, tumor necrosis factor (TNF), and lactate, and packed cell volume were measured. All monotherapy regimens improved survival, and protection decreased with delayed intervention. Volume support prevented dehydration and lactate accumulation but had no effect on levels of bacteria, endotoxin, or TNF. Imipenem killed bacteria and released endotoxin, and lactacidosis was reduced. E5 reduced endotoxin, TNF, and lactate but not bacteremia. The imipenem-induced increase in plasma endotoxin was abolished by E5. When E5 was added to a regimen of volume support plus imipenem 6 h after induction, it gave an extra improvement of survival, but this synergism disappeared when intervention was delayed 4 h more. The primary effect of E5 was a reduction in plasma endotoxin level.