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

基本信息

批准号：
9250801
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
项目类别：
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/9250801
关键词：
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 Recruitment Activity Reporting Research Respiratory Burst Ribosomal RNA Role Sepsis Signal Transduction Site Source Testing Tissues Work clinically relevant experimental study fighting imaging study immune function improved outcome in vivo insight killings mortality neutrophil pediatric patients public health relevance septic sevoflurane

项目摘要

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（由申请人提供）：尽管对脓毒症病理生理学进行了广泛的研究，并启动了方案，但拟议的题为“麻醉剂选择对脓毒症结果及其机制的影响”的研究旨在研究日常使用的麻醉药物对脓毒症病理生理学的影响。在全球脓毒症管理的推动下，脓毒症的死亡率仍然很高，约为 20-30%。脓毒症管理的主要原则之一是感染源控制，尤其是腹部感染。尽管有报道称麻醉药对免疫有潜在影响，但脓毒症患者通常在紧急或紧急情况下在全身麻醉下接受感染源控制手术。我们之前报道过常用的麻醉剂异氟烷、七氟烷和丙泊酚对体外免疫细胞的关键粘附分子 LFA-1 和 Mac-1 有不同的影响。在这个项目中，我们认为这些麻醉剂通过对 LFA-1 和 Mac-1 的不同作用对脓毒症结局产生不同的影响。为了检验这一假设，我们将对三种常见麻醉药物进行研究。在目标 1 中，我们将确定 LFA-1 和 Mac-1 的作用以及麻醉剂在中性粒细胞募集中的影响。 LFA-1 和 Mac-1 以及麻醉剂对中性粒细胞吞噬作用的影响在目标 3 中，我们将确定这些麻醉剂的影响。此外，我们将评估麻醉剂是否直接影响细菌特征和生长。在我们提出的研究中，麻醉剂对免疫学影响的表征将提供麻醉剂对脓毒症病理生理学影响的深入见解。并引导麻醉人员重新考虑如何对脓毒症患者进行麻醉。