Shock : molecular, cellular, and systemic pathobiological aspects and therapeutic approaches : the official journal the Shock Society, the European Shock Society, the Brazilian Shock Society, the International Federation of Shock Societies
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Randomized Controlled Trial Multicenter Study Clinical Trial
Decreased organ failure in patients with severe SIRS and septic shock treated with the platelet-activating factor antagonist TCV-309: a prospective, multicenter, double-blind, randomized phase II trial. TCV-309 Septic Shock Study Group.
Sepsis and organ failure remain the main cause of death on the ICU. Sepsis is characterized by a severe inflammatory response, in which platelet-activating factor (PAF) is considered to play an important role. This study investigated whether treatment with the PAF-antagonist TCV-309 reduces morbidity and mortality in patients with septic shock. ⋯ Furthermore, the mean APACHE-II score during treatment with TCV-309 was significantly lower and the number of patients recovered from shock after day 14 was significantly higher in the TCV-309 treated patient group (2/32 vs. 9/29, P = 0.01). The number of adverse events was not significantly different between the TCV-309 and placebo treated patients. TCV-309 did not change overall mortality of septic shock, however a substantial reduction in organ dysfunction and morbidity, frequently associated with septic shock was achieved, without significant adverse events.
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Angiotensin II (AngII) is an important vasoconstrictor during hypovolemia. This study focused on the effects of the AngII receptor blocker candesartan on intestinal, hepatic, and renal hemodynamics during severe hypovolemia when administered in preexisting moderate hypovolemia. It was hypothesized that specific AngII receptor blockade might enhance splanchnic perfusion during hypovolemia. ⋯ Arterial acidosis, hypercarbia, and a negative base excess were observed in CTRL animals following retransfusion whereas those parameters were normalised in CAND animals. Administration of candesartan in moderate hypovolemia ameliorated the reduction and consequences of mesenteric and intestinal, but not hepatic perfusion during severe hypovolemia. No adverse effects were observed in the renal circulation.