Effect Of Vasopressin And Norepinephrine In Septic shock

加压素和去甲肾上腺素在感染性休克中的作用

• 批准号: 6993967
• 负责人: Steven Solomon
• 金额: --
• 依托单位: CLINICAL CENTER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6993967
• 关键词: blood pressure; cardiac output; cardiovascular disorder chemotherapy; combination chemotherapy; disease /disorder model; dogs; hypotension; medical complication; multiple organ failure; nonhuman therapy evaluation; norepinephrine; septic shock; vasopressins

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. The results of this study suggest that the combination treatment of vasopressin and norepinphrine was more beneficial but due to early mortality further experiments will have to be performed to provide sufficient statistical power.

本临床研究的目的是检查加压素和去甲肾上腺素在治疗感染性休克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药，是临床上最常用的逆转感染性休克患者致死性低血压的药物。血管加压素是治疗脓毒症的一种新方法。一些小型研究对加压素与去甲肾上腺素联合使用进行了研究，结果表明两者联合使用可能会降低脓毒症患者对去甲肾上腺素的需求。高剂量的血管加压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。据信，通过联合这两种药物，将减少血管收缩相关的器官损伤，并提高存活率。然而，没有临床或动物研究已经检查了去甲肾上腺素、血管加压素或其组合对存活率、血压和器官损伤的影响。这部分是由于这种疾病的致命性，在这种情况下，不进行这种治疗是不可能的。特别值得关注的是，这些血管加压药中的一些完全有可能改善血压，但对生存率有不利影响。L-NMMA是一种血管加压药，在这种脓毒症模型中，血压升高，但结局恶化。不幸的是，这些结果在感染性休克患者中得到了证实。以前，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。本研究将检查加压素和去甲肾上腺素单独使用和联合使用在犬模型中治疗脓毒症的作用。我们将首次在脓毒症模型中确定加压素和去甲肾上腺素对血压、心输出量和存活率的影响。 本研究的结果表明，加压素和去甲肾上腺素的联合治疗更有益，但由于早期死亡率，必须进行进一步的实验以提供足够的统计功效。