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This canine study was designed to evaluate the effects of the intravenous infusion of coliform endotoxin with a simultaneous infusion of prostaglandin D2 (PGD2) on hemodynamics, blood gas, blood chemistry, and some hematologic parameters. The information derived from the present study supports the view that the intravenous administration of PGD2 moderates the effects of endotoxin, with its main beneficial effect being on the renal vascular bed. Treatment with PGD2 did not change the endotoxin-induced hemoconcentration, or the reduction in the platelet and white blood cell counts. However, four of nine animals survived more than 7 days when treated with PGD2, whereas without it only one of nine animals survived the administration of the same dose of endotoxin. Although the mechanism of action is not clear, the correlation between PGD2 infusion and improved renal blood flow warrants further study in endotoxic shock.

A primate model was utilized to study the cardiovascular and coagulation effects of endotoxic shock. The therapeutic effectiveness of drugs such as aspirin and dipyridamole, which diminish platelet aggregation and adherence, were evaluated. From the data, it appears that the kidney is a target organ in endotoxic shock, at least when a bolus injection of endotoxin is administered. The precipitate falls in the renal artery flow (p less than 0.01) and platelet count (p less than 0.01), which occur 3 minutes after the intravenous injection of endotoxin, can be prevented in part by pretreatment with aspirin (40 mg/kg of body weight). The changes in the coagulation profile were of less magnitude, and the fibrin degradation products appeared late in the group pretreated with aspirin as compared to the other groups. The combination of dipyridamole and aspirin was not as effective as aspirin alone in achieving the apparently protective effect. The study suggests that the administration of aspirin to patients with gram-negative infections may be beneficial.

The circulatory effects of dopamine (3,4-dihydroxyphenylethylamine) in baboons with endotoxic shock were studied. A beneficial effect was seen in all cardiovascular parameters studied. Cardiac output was better maintained, and this was primarily due to an increase in the stroke volume. The renal artery flow was improved with a decrease in the renal resistance in the dopamine-treated group when compared with the group receiving endotoxin alone. Arterial pH and PO2 did not show significant changes. A rise in blood lactic acid level and a decrease in arterial PCO2 were consistent findings whether or not the animals received dopamine. This study supports the view that dopamine improves the cardiovascular status of the subhuman primate in endotoxic shock and has implications with regard to the patient with endotoxic shock.

Septic shock in obstetric patients can be prevented by recognition of patients at risk and aggressive intervention in the warm-hypotensive phase. These patients must be monitored closely. Rarely will an obstetrical floor be capable of providing adequate monitoring of these patients; therefore, the patient should be transferred to an intensive care unit. Individualize therapy, but do not procrastinate in the surgical removal of the nidus of infection.

Septic shock may be classified clinically as primary (reversible) or secondary (irreversible). Primary shock is further distinguished as early ("warm-hypotensive") or late ("cold-hypotensive"). Infected abortion, chorioamnionitis, or pyelonephritis of pregnancy calls for appropriate measures directed toward preventing septic shock, including administration of huge doses of antibiotics. If septic shock ensues, extirpation of the nidus of infection becomes a primary consideration. Surgical extirpation should be carried out if possible, and as soon as possible. Besides antibiotics, patients with septic shock may require glucocorticoids, vasomotor drugs, digitalis, and heparin. Careful monitoring is essential.

Septic shock continues to be a serious problem with a mortality ranging from 11% to 82%, depending upon the cause, the time of diagnosis, and the type of treatment. The condition is seen in pregnant patients with postabortal or postpartal endometritis, chorioamnionitis, and pyelonephritis. In gynecology patients it is seen after severe pelvic infection and in immunosuppressed patients with gynecologic cancer. Prompt diagnosis, adequate monitoring and vigorous treatment are essential if deaths are to be reduced. Over the period July 1, 1959, to June 30, 1981, 91 patients were treated for septic shock with a mortality of 18%. Although medical treatment is important, the most important aspect of treatment for most patients is removal of the septic focus.

Infusion of endotoxin in chemically sympathectomized monkeys caused a fall in the mean aortic pressure, but the cardiac output, stroke volume, and central venous pressure were well maintained. Endotoxin-induced tachycardia in monkeys with functional sympathetics was not seen in the sympathectomized animals. Infusion of dopamine improved the hemodynamic and cardiovascular status, probably by causing vasoconstriction of the splenic and hepatic artery where the pooling of blood is believed to occur in endotoxin shock. However, these beneficial effects were not apparent when dopamine was administered in the chemically sympathectomized animal infused with endotoxin. Since chemical sympathectomy did not affect the endotoxin-induced decline in the systolic and mean aortic pressure or the severity of the endotoxin shock, it is suggested that catecholamines may not be the primary initiator or trigger substances in endotoxin shock.

1. Isolated left-atrial strips of guinea-pigs were driven electrically at a constant rate and log-concentration curves were determined for the positive inotropic effect of noradrenaline and tyramine.2. The atrial tissue from endotoxin-treated animals had a reduced sensitivity to noradrenaline and tyramine.3. After endotoxin, the sensitizing effect of cocaine on the response to noradrenaline was normal but accumulation of (3)H-noradrenaline in nerve terminals was markedly reduced.4. Atrial tissue of endotoxin-treated guinea-pigs responded normally to stretch.