B. Benjamin

Survival of primates in LD100 septic shock following steroid/antibiotic therapy.

Abstract This study was designed to determine the effect of steroid/antibiotic treatment on the survival of baboons subjected to LD100 Escherichia coli shock. Fourteen baboons (Papio c. cynocephalus), randomly divided into three groups, were anesthetized and administered 2-hr infusions of LD100 viable E. coli. Group A received E. coli alone; Group B was administered E. coli followed by infusions of both gentamicin sulfate (GS) (18 mg/kg) and methylprednisolone sodium succinate (MPSS) (75 mg/kg) during a 12-hr period. Group C was given E. coli plus GS (18 mg/kg) alone. Groups B and C baboons were also given GS intramuscularly, 4.5 mg/kg at 12 hr and twice daily for 3 days. Insensible fluid loss during the intial 12-hr period was replaced by minimal volumes of saline. Fully treated baboons (Group B) received steroid after 0.7 × 1010 organisms/kg body wt had been administered. All fully treated baboons survived; however, all animals of Groups A and C died within 42 hr. Systemic hypotension observed in every baboon within 2 hr was reversed in Group B animals. Hypoglycemia, hypoinsulinemia, anuria, and extensive adrenal pathology were prevented by steroid/antibiotic treatment. Serum creatinine and blood urea nitrogen concentrations increased in all baboons but returned to normal in the fully treated group. Increased survival may have been due in part to augmented antibacterial activity elicited by (a) improved peripheral distribution of the antibiotic and (b) stimulation of the bone marrow by the steroid. Findings demonstrate that the lethal pathophysiology of E. coli-induced shock is effectively prevented by combined steroid and antibiotic therapy.

A morphologic study of live Escherichia coli organism shock in baboons.

Abstract This study was designed to examine the response of the baboon during a 24 hr period following live Escherichia coli organism infusion. Experiments were performed on 10 young adult adolescent baboons. Eight of the baboons received a mean concentration of 1.5 × 10 10 organisms/kg infused during a 30 to 360 min period. Two control baboons received anesthesia and 0.9% sodium chloride solution during the 24 hr period. Heart, lung, liver, and kidney were evaluated with both light and electron microscopy and the morphologic data were interrelated with the physiologic data. The acute lung lesion seen in 2 to 6 hr studies was not found in this prolonged shock model. Both the liver and kidney exhibited dysfunction; these pathophysiologic alterations were accompanied by morphologic changes. Sinusoidal fibrin thrombi and hepatocyte damage were observed in the liver, and were associated with increases in LDH, FLDH, and hypoglycemia. Glomerular fibrin thrombi and tubular epithelial changes of cytoplasmic vacuolization and brush border loss were present in the kidney, and an increase in BUN levels was noted. Our data would indicate that the live E. coli infusion baboon model shows pathologic and physiologic derangements quite similar to those reported in the patient in septic shock.