Pilot Study of Hemofiltration after Out-of-Hospital Cardiac Arrest

描述(由申请人提供)：这项研究将评估纳入符合条件的患者(PTS)的可行性，以及入选患者从院外心脏骤停(OuchA)复苏后48小时内至少80%接受低容量或高容量血液滤过(HF)的可行性。HF洗涤血液以清除与再灌注损伤(RI)、器官功能障碍和死亡相关的血液炎症因子。背景阻力发生在OuchA后的循环恢复期间。它与促炎细胞因子的大量释放有关。这会导致24小时内的微循环功能障碍。在接下来的三天里，心脏功能得到改善，但血管通透性增加，容易导致神经损伤、多器官功能障碍和死亡。HF是一种去除细胞外液的技术，类似于血液透析。这种细胞外液包括溶质，其中含有在RI期间释放的炎症因子。我们建议评估使用HF技术(Diapact，B Braun Medical Inc.，伯利恒，宾夕法尼亚州伯利恒)在CA复苏后减少RI的可行性。方法设计--个体随机试验。人群-成人OuchA后有任何初始节律的自发循环。排除：不要尝试复苏命令；严重的停搏前神经功能障碍；昏迷的另一个原因；钝性、穿透性或其他损伤；血小板减少或凝血障碍；原位下腔静脉滤器；已知怀孕；血流动力学不稳定；对乙酰氨基酚过敏；事先参加研究。干预--随机分为对照组、低心衰组和高剂量心力衰竭组，持续48小时。对照组和干预组患者应接受必要的静脉输液、血管增压剂或血管扩张剂治疗，以维持中心静脉压在8-12毫米汞柱，平均动脉压在100-120毫米汞之间。同时的干预将包括对昏迷的患者开始和维持治疗性低温。分析-符合条件的入选患者和48小时内至少接受心力衰竭80%的干预患者的比例将以二项式比例汇总。临床措施将进行描述性总结。样本规模-我们预计在12个月的注册期间，将有大约60分符合我们的纳入标准。我们将招收30分(每组10分)。相关性这项试验将证明HF在从OuchA复苏的PTS中是可行的。后续试验的设计将根据这项初步研究的结果进行修改，以测试HF对生存、神经功能和与健康相关的生活质量的影响。与公共卫生相关：大多数最初从心脏骤停复苏的患者无法存活到出院，因为当血流恢复时，细胞释放的循环因子引起炎症。血液滤过从血液中去除这些与器官功能障碍和死亡有关的炎症因子。我们将测试使用血液滤过治疗心脏骤停患者是否可行。

DESCRIPTION (provided by applicant): This study will assess the feasibility of enrolling eligible patients (pts), and of enrolled pts undergoing low-volume or high-volume hemofiltration (HF) for at least 80% of 48 hours among those resuscitated from out-of-hospital cardiac arrest (OOHCA). HF washes the blood to remove the blood inflammatory factors that are associated with reperfusion injury (RI), organ dysfunction and death. Background RI occurs during restoration of circulation after OOHCA. It is associated with substantial release of pro-inflammatory cytokines. This leads to microcirculatory dysfunction within 24 hours. Cardiac function improves but vascular permeability increase over the next three days, predisposing to neurologic injury, multiple organ dysfunction and death. HF is a technique of removing extracellular fluid that is similar to hemodialysis. This extracellular fluid includes the solutes, which contain the inflammatory factors released during RI. We propose to evaluate the feasibility of using HF technology (Diapact, B Braun Medical Inc., Bethlehem, PA) to reduce RI after resuscitation from CA. Methods Design- Individual randomized trial. Population- Adults with spontaneous circulation after OOHCA with any initial rhythm. Excluded: do not attempt resuscitation orders; major pre-arrest neurological dysfunction; another reason to be comatose; blunt, penetrating or other injury; thrombocytopenia or coagulopathy; inferior vena cava filter in situ; known pregnancy; hemodynamic instability; allergy to acetaminophen; prior enrollment in the study. Interventions- randomized to control versus low-HF versus high-volume HF for 48 hours. Control and intervention pts shall receive intravenous fluids, vasopressor or vasodilator treatment as required to maintain a central venous pressure of 8-12 mm Hg and a mean arterial pressure between 100-120 mm Hg. Concurrent intervention will include initiation and maintenance of therapeutic hypothermia in pts who are unconscious. Analyses- The proportion of eligible pts who are enrolled, and of intervention pts who undergo HF for at least 80% of 48 hours will be summarized as binomial proportions. Clinical measures will be summarized descriptively. Sample Size- we anticipate that about 60 pts will meet our inclusion criteria during a 12 month enrollment period. We shall enroll 30 pts (10 per group). Relevance this trial will prove that HF is feasible in pts resuscitated from OOHCA. The design of a subsequent trial to test the effect of HF upon survival, neurologic function and health-related QOL will be modified based on the results of this pilot study. PUBLIC HEALTH RELEVANCE: Most patients initially resuscitated from cardiac arrest do not survive to hospital discharge because of inflammation caused by circulating factors that are released by cells when blood flow is restored. Hemofiltration removes from the blood these inflammatory factors that are associated with organ dysfunction and death. We will test whether it is feasible to use hemofiltration to treat patients who have had cardiac arrest.