PRagMatic Pediatric Trial of Balanced versus NOrmaL Saline FlUid in Sepsis (PRoMPT BOLUS)

项目摘要 脓毒症是一种医学急症，定义为由于宿主失调而导致的危及生命的器官功能障碍 对感染的反应。感染性休克是最严重的形式，涉及心血管衰竭。超过 每年有75，000名美国儿童和400万名全世界儿童因败血症或感染性休克住院， 年败血症是目前美国最昂贵的住院疾病，对于重症患者来说- 包括儿童-是多器官功能障碍综合征和医院死亡的最常见原因。1，26 世界卫生组织和美国疾病控制和预防中心呼吁， 33因为液体复苏为脓毒症提供了最佳的既定益处， 休克（除抗生素外），一直在努力确定最有效的液体管理 战略尽管取得了进展，幸存脓毒症运动所描述的知识中仍然存在一个关键差距， 哪种晶体液用于感染性休克的初始复苏是最有效和最安全的。 两种类型的晶体用于脓毒症的复苏：0.9%“正常”生理盐水（NS）和平衡液体 （BF）。与NS相比，BF具有良好的生物学和生理学优势，最近的两项成人试验发现 BF降低了主要的肾脏不良事件和死亡率。然而，在缺乏儿科特异性 数据显示，NS复苏仍然是儿科急诊医生的压倒性偏好。我们 因此，提出了PRagMatic小儿败血症平衡与非正常生理盐水试验（PRoMPT BOLUS）研究，一项随机、开放标签、务实的比较有效性试验，旨在测试相对 BF与NS液体复苏在疑似感染性休克患儿中有效性和安全性比较十八 儿科急诊护理应用研究网络（PECARN）的儿科急诊部门将 与加拿大、澳大利亚和新西兰的研究中心合作，招募8,800名疑似败血症的儿童， 冲击.合格患者将通过前瞻性知情同意或适当的 伦理保障，紧急研究的“知情同意例外”。受试者将被随机分配 使用NS或BF进行液体复苏和维持液体，持续24-48小时，并提供其他所有方面的护理 而不是由护理团队自行决定的液体类型。我们的主要结局是在 随机化后30天（MAKE 30），一个以患者为中心的复合终点，包括持续性肾脏 功能障碍、开始透析或死亡。这一结果解决了BF的生物学优势， 与NS相比，保留肾血流和功能。次要结果包括个人 MAKE 30的组成部分、无住院天数、住院时间、90天死亡率和指定的安全事件。 这一务实的审判将为“范式转变”提供必要的明确证据 从0.9%生理盐水到平衡液体复苏在感染性休克儿童中的临床实践。

Project Summary Sepsis is a medical emergency defined as life-threatening organ dysfunction due to a dysregulated host response to infection. Septic shock is the most severe form, involving cardiovascular failure. More than 75,000 children in the US and four million children worldwide are hospitalized with sepsis or septic shock every year. Sepsis is currently the most expensive hospital condition in the US and, for critically ill patients— including children—is the most common cause of multiple organ dysfunction syndrome and hospital death.1,26 The World Health Organization and the US Centers for Disease Control and Prevention have called for optimizing therapies for sepsis.33 Because fluid resuscitation provides the best established benefit for septic shock (other than antibiotics), there has been an effort to identify the most effective fluid administration strategy. Despite progress, a remaining key gap in knowledge delineated by the Surviving Sepsis Campaign is which crystalloid fluid is the most effective and safest to use for initial resuscitation of septic shock. Two types of crystalloids are used for resuscitation in sepsis: 0.9% “normal” saline (NS) and balanced fluids (BF). BF have well-established biologic and physiologic advantages over NS and two recent adult trials found that BF reduced major adverse kidney events and mortality. However, in the absence of pediatric-specific data, NS resuscitation remains the overwhelming preference among pediatric emergency clinicians. We therefore propose the PRagMatic Pediatric Trial of Balanced versus NOrmaL Saline FlUid in Sepsis (PRoMPT BOLUS) study, a randomized, open-label, pragmatic comparative effectiveness trial, to test the relative effectiveness and safety of BF versus NS fluid resuscitation in children with suspected septic shock. Eighteen pediatric emergency departments in the Pediatric Emergency Care Applied Research Network (PECARN) will collaborate with sites in Canada, Australia, and New Zealand to enroll 8,800 children with suspected septic shock. Eligible patients will be enrolled either through prospective informed consent or, after appropriate ethical safeguards, “Exception From Informed Consent” for emergency research. Subjects will be randomized to fluid resuscitation and maintenance fluids with either NS or BF for 24-48 hours, with all aspects of care other than fluid type at the discretion of the care team. Our primary outcome is major adverse kidney events within 30 days from randomization (MAKE30), a patient-centered composite endpoint that includes persistent kidney dysfunction, initiation of dialysis, or death. This outcome addresses the biological advantages of BF to preserve renal blood flow and function compared to NS. Secondary outcomes include the individual components of MAKE30, hospital-free days, length of stay, 90-day mortality, and specified safety events. This pragmatic trial will provide the definitive evidence necessary for a “paradigm shift” to move clinical practice from 0.9% saline to balanced fluid-based resuscitation in children with septic shock.