Vasopressin And Norepinephrine In Septic Shock

败血性休克中的加压素和去甲肾上腺素

• 批准号: 6683817
• 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/6683817
• 关键词: blood pressure; cardiac output; combination chemotherapy; disease /disorder model; dogs; microorganism disease chemotherapy; 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.

本临床研究的目的是探讨加压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增压剂，是最常用的临床药物，可以逆转感染性休克患者的致命性低血压。一种新的治疗脓毒症的方法是使用加压素来治疗与脓毒症相关的低血压。一些小规模的研究检查了加压素和去甲肾上腺素的联合应用，并表明它们联合使用可能会降低败血症患者对去甲肾上腺素的需求。大剂量的加压素或去甲肾上腺素都可能导致负面结果，包括终末器官灌注量减少和心输出量减少。相信联合应用这两种药物会减少血管收缩相关的器官损伤，提高存活率。然而，还没有临床或动物研究检验去甲肾上腺素、加压素或两者合用对存活率、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。尤其令人担忧的是，其中一些血管升压剂完全有可能可以改善血压，但对存活率产生不利影响。在这种脓毒症模型中，血管升压剂L-NMMA升高了血压，但恶化了预后。不幸的是，这些结果在患有感染性休克的人类身上得到了证实。此前，在一项先导性研究中，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，但不会对存活率产生负面影响。这项研究将研究加压素和去甲肾上腺素在犬脓毒症模型中单独和联合使用的作用。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、心输出量和存活率的影响。