1/2: An Anesthesia-Centered Bundle to Reduce Postoperative Pulmonary Complications: The PRIME-AIR Study

1/2：以麻醉为中心的捆绑方案，可减少术后肺部并发症：PRIME-AIR 研究

• 批准号: 9896976
• 负责人: Ana Fernandez-Bustamante
• 金额: $ 208.49万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-03-19 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9896976
• 关键词: Abdomen; Address; Adoption; Adult Respiratory Distress Syndrome; American College of Physicians; Anesthesia procedures; Anesthetics; Atelectasis; Attention; Automobile Driving; Bacteria; Biological Markers; Blinded; Cardiac; Caring; Cessation of life; Classification; Clinical; Collaborations; Data; Early Mobilizations; Endothelial Cells; Endothelium; Endotoxins; Epithelial; Epithelial Cells; Epithelium; Functional disorder; Goals; Grant; Health Care Costs; Hospitalization; Incidence; Inflammation; Inflammatory; Injury; Intervention; Lung; Mechanical ventilation; Mechanics; Morbidity - disease rate; Muscle; Neuromuscular Blocking Agents; Operative Surgical Procedures; Outcome; Oxygen; Pain; Paralysed; Patients; Perioperative; Perioperative Care; Plasma; Positive-Pressure Respiration; Postoperative Period; Process; Public Health; Randomized; Randomized Controlled Trials; Recommendation; Research; Resources; Respiratory Diaphragm; Respiratory System; Risk; Role; Severities; Solid; Stretching; Supine Position; Surgical complication; Testing; Trauma; base; biobank; cell injury; clinical practice; experience; inpatient surgery; insight; lung injury; mortality; novel; patient population; personalized management; pragmatic trial; pressure; prevent; primary outcome; prospective; recruit; standard of care; treatment arm; treatment as usual; ventilation

Postoperative pulmonary complications (PPCs) are a major cause of morbidity and mortality in surgical patients. National estimates suggest 1,062,000 PPCs per year, with 46,200 deaths, and 4.8 million additional days of hospitalization. Abdominal surgery is the field with the largest absolute number of PPCs. Our long-term goal is to develop and implement perioperative strategies to eliminate PPCs. Whereas PPCs are as significant and lethal as cardiac complications, research in the field has received much less attention, and strategies to minimize PPCs are regrettably limited. Recently, we and others have suggested a crucial role of anesthesia related interventions such as ventilatory strategies, and administration and reversal of neuromuscular blocking agents in reducing PPCs. These findings are consistent with the beneficial effects of lung protective ventilation during the adult respiratory distress syndrome (ARDS). While surgical patients differ substantially from ARDS patients as most have no or limited lung injury at the start of surgery, intraoperative anesthetic and abdominal surgery interventions result in lung derecruitment and predispose to or produce direct and indirect, potentially multiple-hit, lung injury. Thus, effective anesthetic strategies aiming at early lung protection in this group of patients are greatly needed. Indeed, the current lack of evidence results in wide and unexplained variability in anesthetic practices creating a major public health issue as some practices within usual care appear to be suboptimal and even potentially injurious. We hypothesize that an anesthesia-centered bundle, based on our recent findings and focused on perioperative lung protection, will minimize multiple and synergistic factors responsible for the multiple-hit perioperative pulmonary dysfunction and result in decreased incidence and severity of PPCs. Founded on strong preliminary data, we will leverage a network of US academic centers to study this hypothesis in two aims: Aim 1. To compare the number and severity of PPCs in patients receiving an individualized perioperative anesthesia-centered bundle to those in patients receiving usual anesthetic care during open abdominal surgery. For this, we propose to conduct a prospective multicenter randomized controlled pragmatic trial with a blinded assessor in a total of 750 patients. The bundle will consist of optimal mechanical ventilation comprising individualized positive end-expiratory pressure to maximize respiratory system compliance and minimize driving pressures, individualized use of neuromuscular blocking agents and their reversal, and postoperative lung expansion and early mobilization; Aim 2. To assess the effect of the proposed bundle on plasma levels of lung injury biomarkers. We theorize that our intervention will minimize overinflation and atelectasis reducing plasma levels of biomarkers of lung inflammatory, epithelial, and endothelial injury. Such mechanistic insights will facilitate bundle dissemination and support adoption as it has for lung protective ventilation for ARDS. At the end of this project, we expect to change clinical practice by establishing a new and clinically feasible anesthesia-centered strategy to reduce perioperative lung morbidity.

术后肺部并发症（PPC）是外科手术中发病率和死亡率的主要原因， 患者国家估计数表明，每年有1，062，000例PPC，其中46，200例死亡，另有480万人死亡。 住院天数。腹部手术是PPC绝对数量最多的领域。我们的长期 我们的目标是制定和实施围手术期策略，以消除PPC。尽管PPC与 和致命的心脏并发症，该领域的研究受到的关注要少得多， 令人遗憾的是，减少PPC的数量有限。最近，我们和其他人提出了麻醉的关键作用， 相关的干预措施，如治疗策略，以及神经肌肉阻滞的给药和逆转 降低PPC的药物。这些发现与肺保护性通气的有益作用一致 成人呼吸窘迫综合征（ARDS）。虽然手术患者与ARDS患者有很大不同， 大多数患者在手术开始时没有或只有有限的肺损伤，术中麻醉和腹部手术 外科手术干预导致肺去复张，并使其易于发生或产生直接和间接、潜在 多次撞击肺部受伤因此，有效的麻醉策略，旨在早期肺保护，在这组 患者非常需要。事实上，目前缺乏证据导致广泛和无法解释的变化， 麻醉实践造成了一个重大的公共卫生问题，因为在常规护理中的一些做法似乎是 次优的，甚至可能有害的。我们假设一个以麻醉为中心的束，基于我们的 最近的研究结果，并集中在围手术期肺保护，将尽量减少多重和协同因素 负责多次打击围手术期肺功能障碍，并导致发病率下降， PPC的严重性。基于强大的初步数据，我们将利用美国学术中心网络， 研究这个假设有两个目的：目的1。比较接受以下治疗的患者中PPC的数量和严重程度： 针对接受常规麻醉护理的患者的个性化围手术期麻醉集中包 腹部开放手术中死亡为此，我们建议进行一项前瞻性多中心随机 在总共750名患者中进行的盲法评估者对照实用性试验。该捆绑包将包括最佳的 包括个体化呼气末正压的机械通气， 系统顺应性和最小化驱动压力，个体化使用神经肌肉阻滞剂， 逆转，术后肺扩张和早期活动;目的2。为了评估 建议捆绑肺损伤生物标志物的血浆水平。我们的理论是我们的干预将最小化 过度充气和肺不张降低了肺炎症、上皮和 内皮损伤这种机械的见解将促进捆绑传播和支持采用，因为它 用于肺保护性通气治疗ARDS在这个项目结束时，我们希望通过以下方式改变临床实践： 建立一个新的和临床上可行的麻醉为中心的战略，以减少围手术期肺部发病率。