The impact of anesthetic selection on sepsis outcome and its mechanism

麻醉选择对脓毒症结局的影响及其机制

• 批准号: 9452998
• 负责人: Koichi Yuki
• 金额: $ 35.4万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-01 至 2021-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9452998
• 关键词: 16S ribosomal RNA sequencing; Abdomen; Abdominal Cavity; Address; Affect; Anesthesia procedures; Anesthetics; Award; Bacteria; Binding; CD11a Antigen; Cell Adhesion Molecules; Cells; Cessation of life; Chemotactic Factors; Chronology; Clinical Research; Clinical Trials; Complement; Data; Defect; Functional disorder; Future; General Anesthesia; Grant; Growth; Health Care Costs; Homologous Gene; IL8 gene; Immune; Immune system; Immunoglobulin G; Immunologics; Impairment; In Vitro; Incidence; Infection; Inflammation; Injury; Intercellular adhesion molecule 1; Intravenous Anesthetics; Investigation; Isoflurane; Lead; Leukocyte Adhesion Deficiency; Leukocyte Adhesion Molecules; Leukotriene B4; Lymphocyte Function-Associated Antigen-1; Macrophage-1 Antigen; Mediating; Modeling; Mus; Neutrophil Infiltration; Organ; Outcome; Patients; Phagocytes; Phagocytosis; Pharmaceutical Preparations; Plasma; Procedures; Propofol; Protocols documentation; Provider; Reporting; Research; Respiratory Burst; Role; Sepsis; Signal Transduction; Site; Source; Testing; Tissues; Work; clinically relevant; experimental study; fighting; imaging study; immune function; improved outcome; in vivo; insight; mortality; neutrophil; pediatric patients; public health relevance; recruit; septic; septic patients; sevoflurane

 DESCRIPTION (provided by applicant): The proposed research titled "The impact of anesthetic selection on sepsis outcome and its mechanism" is to study the impact of daily used anesthetic drugs on sepsis pathophysiology. Despite extensive research on sepsis pathophysiology, and initiation of protocol-driven sepsis management worldwide, the mortalities of sepsis continue to be high at around 20-30%. One of the cardinal tenets of sepsis management is infection source control. Patients suffering from sepsis, particularly abdominal sepsis often undergo source control procedures under general anesthesia on an emergent or urgent basis. Pediatric patients often require general anesthesia even for imaging studies to identify the source of infection. Despite the reports of potential effects of anesthetics on immune functions in vitro, there is a paucity of research investigating the in vivo significance and underlying mechanisms. We previously reported that the commonly used anesthetics isoflurane, sevoflurane and propofol differently affected critical adhesion molecules LFA-1 and Mac-1 on immune cells in vitro. In this project we hypothesize that these anesthetics have different impacts on sepsis outcome via their differential effects on LFA-1 and Mac-1. To test this hypothesis, we will perform the study of the three common anesthetic drugs isoflurane, sevoflurane and propofol, using polymicrobial abdominal sepsis model in mice. In Aim 1, we will determine the role of LFA-1 and Mac-1 and the impact of anesthetics in neutrophil recruitment. In Aim 2, we will determine the role of LFA-1 and Mac-1 and the impact of anesthetics in neutrophil bacterial phagocytosis. In Aim 3, we will determine the impact of these anesthetics on outcome, systemic bacterial loads and systemic tissue injury. In addition, we will evaluate if anesthetics affect bacterial profiles and growth directly. The characterization of immunological impact by anesthetics in our proposed study will provide the in- depth insight of anesthetic effects on sepsis pathophysiology and lead anesthesia providers to reconsider how to anesthetize patients suffering from sepsis.

 描述（由适用提供）：拟议的研究标题为“麻醉选择对败血症结果及其机制的影响”是研究日常使用麻醉药物对脓毒症病理生理学的影响。尽管对脓毒症的病理生理学以及方案驱动的败血症管理的倡议进行了广泛的研究，但败血症的死亡率仍然很高，约为20-30％。败血症管理的主要宗旨之一是感染源控制。患有败血症，尤其是腹部败血症的患者在紧急或紧急的基础上经常在全身麻醉下接受源控制程序。小儿患者即使对成像研究也需要全身麻醉才能确定感染的来源。尽管有报道说麻醉药对免疫的潜在影响 在体外的功能，研究了体内意义和潜在机制的研究很少。我们先前曾报道过，通常使用麻醉药异氟烷，七氟醚和建议对临界粘合剂分子LFA-1和MAC-1的影响不同。在这个项目中，我们假设这些麻醉药通过对LFA-1和MAC-1的不同影响对败血症产生不同的影响。为了检验这一假设，我们将使用小鼠中多细胞性腹部败血症模型对三种常见的麻醉药物异氟烷，七氟醚和建议进行研究。在AIM 1中，我们将确定LFA-1和MAC-1的作用以及麻醉药在中性粒细胞募集中的影响。在AIM 2中，我们将确定LFA-1和MAC-1的作用以及麻醉药在中性粒细胞细菌吞噬作用中的影响。在AIM 3中，我们将确定这些麻醉剂对预后，全身细菌负荷和全身组织损伤的影响。此外，我们将评估麻醉药是否影响细菌谱并直接生长。麻醉药在我们提出的研究中对免疫学影响的表征将提供对麻醉对脓毒症病理生理学的影响的深入了解，并促使麻醉提供者重新考虑如何麻醉患者患者。