Vasopressin And Norepinephrine In Septic Shock

本临床研究的目的是探讨抗利尿激素和去甲肾上腺素在感染性休克治疗中的作用及其对生存的影响。去甲肾上腺素是一种血管加压剂，是临床上最常用的药物，用于逆转感染性休克患者的致命性低血压。一种新的治疗败血症的方法是使用加压素治疗与败血症相关的低血压。小型研究已经检查了加压素与去甲肾上腺素的联合使用，并表明它们一起使用可能降低脓毒症患者对去甲肾上腺素的需求。高剂量的抗利尿激素或去甲肾上腺素可导致负面结果，包括终末器官灌注减少和心输出量减少。相信这两种药物联合使用，会减少血管收缩相关的器官损伤，提高生存率。然而，没有临床或动物研究检验去甲肾上腺素、加压素或联合使用对存活率、血压和器官损伤的影响。这在一定程度上是由于这种疾病的致命性，不进行这种治疗是不可能的。特别值得关注的是，这些血管加压药完全有可能改善血压，但对生存产生不利影响。L-NMMA，一种血管加压剂，在这个脓毒症模型中，血压升高，但结果恶化。不幸的是，这些结果在感染性休克患者中得到了证实。此前，在一项初步研究中，我们确定了单独使用的每种药物的剂量，这些药物会升高血压，但不会对生存率产生不利影响。本研究将探讨抗利尿激素和去甲肾上腺素单独使用和一起使用在治疗犬模型脓毒症中的作用。我们将首次在任何脓毒症模型中确定加压素和去甲肾上腺素对血压、心输出量和生存率的影响。

The purpose of this clinical study is to examine the role of vasopressin and norepinephrine in the treatment of septic shock and their impact on survival. Norepinephrine, a vasopressor, is the most commonly used clinical agent to reverse the lethal hypotension in patients with septic shock. A new therapy for sepsis has been the use of vasopressin to treat the hypotension associated with sepsis. Small studies have examined vasopressin in conjunction with norepinephrine and suggest that their use together may lower norepinephrine requirements in septic patients. High doses of either vasopressin or norepinephrine can lead to negative outcomes including decreased end organ perfusion and decreased cardiac output. It is believed that by combining these two drugs, there will be less vasoconstriction related organ injury and an increased benefit in survival rate. However, no clinical or animal study has examined the effect of norepinephrine, vasopressin or a combination on survival rate, blood pressure and organ injury. This is, in part, due to the lethality of the disease where withholding such therapies would be impossible. Of particular concern is that it is entirely possible that some of these vasopressors can improve blood pressure but adversely affect survival. L-NMMA, a vasopressor, increased blood pressure but worsened outcome in this model of sepsis. Unfortunately these results were confirmed in humans with septic shock. Previously, in a pilot study, we determined doses of each drug used alone that raised blood pressure but did not adversely affect survival rate. This study will examine the role of vasopressin and norepinephrine used alone and together in treating sepsis in the canine model. We will for the first time in any model of sepsis determine the effects of vasopressin and norepinephrine on blood pressure, cardiac output and survival.