Thiamine v placebo to improve oxygen consumption after in-hospital cardiac arrest

硫胺素与安慰剂对比改善院内心脏骤停后的耗氧量

• 批准号: 10393885
• 负责人: Katherine M Berg
• 金额: $ 6.9万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10393885
• 关键词: Back; Blinded; Blood Circulation; Cardiac; Cardiac Surgery procedures; Cause of Death; Cell Respiration; Cells; Citric Acid Cycle; Critical Illness; Data; Death Rate; Defect; Enrollment; Enzymes; Failure; Functional disorder; Heart Arrest; Hospitals; Hour; Impairment; Intervention; Lead; Literature; Measures; Multiple Organ Failure; Outcome; Oxygen; Oxygen Consumption; Patients; Phase; Physiologic pulse; Placebos; Randomized; Research; Resuscitation; Sepsis; Septic Shock; Shock; Syndrome; Testing; Thiamine; Thiamine Deficiency; United States; heart preservation; improved; improved outcome; indexing; mortality; placebo controlled trial; primary outcome; pyruvate dehydrogenase; secondary outcome

Over 200,000 people suffer an in-hospital cardiac arrest (IHCA) each year in the United States, and over 80% of those will die. In spite of this extremely high mortality, relatively few trials have been done to investigate treatments to improve outcomes after IHCA. In patients who achieve return of spontaneous circulation (ROSC), the most common cause of death is shock and multi- organ failure. The post-arrest syndrome has been likened to sepsis/septic shock, and both conditions appear to be characterized by impaired oxygen extraction in many patients. This may contribute to increased lactate, failure to clear lactate, and decreased oxygen consumption (VO2), all of which are associated with higher mortality in both sepsis and post-cardiac arrest. We have also found that pyruvate dehydrogenase (PDH), an enzyme required for the Krebs Cycle, is low in sepsis and after cardiac arrest, and that lower levels are associated with higher mortality in sepsis. All of these indicators suggest a dysfunction in aerobic metabolism, and an intervention that could rectify this defect could lead to lower lactate values, increased VO2 and potentially better outcomes. Thiamine, a co-factor of PDH, is also required for aerobic metabolism. We have found that thiamine deficiency is common in septic shock and after cardiac arrest, and that thiamine levels are inversely associated with lactate levels in septic shock and other forms of critical illness. We have also found that thiamine administration lowers lactate and improves survival in thiamine deficient septic shock patients, is associated with a rise in VO2 in critically ill patients with preserved cardiac index (regardless of thiamine level), and appears to increase PDH activity after major cardiac surgery. We therefore hypothesize that thiamine will increase VO2, increase PDH activity and decrease lactate after IHCA. We propose a phase II randomized, blinded, placebo-controlled trial in 60 patients who obtain sustained ROSC after in-hospital cardiac arrest and have preserved cardiac index to test this hypothesis. All enrolled patients will be randomized to either thiamine 200mg or placebo every 12 hours for 24 hours. We will record VO2 and cardiac index data continuously for 24 hours, and will check PDH quantity and activity and lactate at 0, 12 and 24 hours. The primary outcome will be the change in VO2, and the secondary outcomes will be change in PDH activity and lactate. We anticipate that VO2 and PDH activity will rise while lactate will decrease in patients who receive thiamine as compared to placebo. Prior research on VO2 after cardiac arrest is extremely limited, and as such we believe our data will be a significant contribution to the literature on cardiac arrest and the post-arrest syndrome, even if our study results are not positive.

在美国，每年有超过20万人遭受院内心脏骤停（IHCA）， 超过80%的人会死去尽管死亡率极高，但相对较少的试验 研究了改善IHCA后结局的治疗方法。在达到以下标准的患者中 自主循环恢复（ROSC），最常见的死亡原因是休克和多 器官衰竭停搏后综合征被比作脓毒症/脓毒性休克， 在许多患者中，病症的特征似乎是氧提取受损。这可能 导致乳酸盐增加、乳酸盐清除失败和耗氧量降低 (VO2)所有这些都与败血症和心脏骤停后的较高死亡率相关。 我们还发现，丙酮酸脱氢酶（PDH），一种克雷布斯所需的酶， 在败血症和心脏骤停后， 败血症死亡率。所有这些指标都表明有氧代谢功能障碍， 可以纠正这种缺陷的干预可能导致乳酸值降低，VO 2增加， 可能会有更好的结果。硫胺素，PDH的辅因子，也是有氧代谢所必需的。 新陈代谢.我们已经发现，硫胺素缺乏症是常见的感染性休克和 心脏骤停，硫胺素水平与脓毒症患者的乳酸水平呈负相关， 休克和其他形式的严重疾病。我们还发现，硫胺素的管理， 在硫胺素缺乏的感染性休克患者中， 心脏指数正常的危重患者的VO 2升高（不考虑硫胺素水平）， 并且似乎在大心脏手术后增加PDH活性。因此，我们假设， 硫胺素可增加IHCA后VO 2，增加PDH活性，减少乳酸。我们提出 一项在60名患者中进行的II期随机、设盲、安慰剂对照试验， 住院心脏骤停后的ROSC，并保留了心脏指数来验证这一假设。 所有入组的患者将随机接受硫胺素200 mg或安慰剂，每12小时一次， 24小时我们将连续24小时记录VO 2和心脏指数数据，并将检查 在0、12和24小时的PDH量和活性以及乳酸。主要结果将是 VO 2的变化，次要结局将是PDH活性和乳酸的变化。我们 预计VO 2和PDH活性将上升，而乳酸将下降， 与安慰剂相比，硫胺素。先前对心脏骤停后VO 2的研究非常 有限，因此，我们相信我们的数据将是对文献的重大贡献。 心脏骤停和心脏骤停后综合征，即使我们的研究结果不是积极的。

项目成果

Ascorbic acid, corticosteroids, and thiamine in sepsis: a review of the biologic rationale and the present state of clinical evaluation.

• DOI: 10.1186/s13054-018-2217-4
• 发表时间: 2018-10-29
• 期刊: Critical care (London, England)
• 作者: Moskowitz A;Andersen LW;Huang DT;Berg KM;Grossestreuer AV;Marik PE;Sherwin RL;Hou PC;Becker LB;Cocchi MN;Doshi P;Gong J;Sen A;Donnino MW
• 通讯作者: Donnino MW

The limitations of evidence: increasing data and increasing doubt in the treatment of cardiac arrest.

证据的局限性：心脏骤停治疗中的数据不断增加，质疑不断增加。

• DOI: 10.1097/mcc.0000000000000765
• 发表时间: 2020
• 期刊: Current opinion in critical care
• 影响因子: 3.3
• 作者: Berg,KatherineM

Acute respiratory compromise on hospital wards: association between recent ICU discharge and outcome.

• DOI: 10.1016/j.resuscitation.2019.09.002
• 发表时间: 2019-11
• 期刊: Resuscitation
• 影响因子: 6.5
• 作者: K. Berg;M. Donnino;L. Andersen;A. Moskowitz;A. Grossestreuer

A Trigger and Response System for Preventing Cardiac Arrest in the ICU.

• DOI: 10.1097/cce.0000000000000557
• 发表时间: 2021-10
• 期刊: Critical care explorations
• 作者: Moskowitz A;Berg KM;Cocchi MN;Grossestreuer AV;Issa M;Balaji L;Chase M;Yang JX;Sarge J;O'Donoghue S;Sarge T;Donnino MW
• 通讯作者: Donnino MW

Finding a window: Timing of cardiac ultrasound acquisition during cardiac arrest.

寻找窗口：心脏骤停期间心脏超声采集的时间。

• DOI: 10.1016/j.resuscitation.2018.01.014
• 发表时间: 2018
• 期刊: Resuscitation
• 影响因子: 6.5
• 作者: Berg,KatherineM