Thiamine in septic shock patients with alcohol abuse

硫胺素在酗酒脓毒症休克患者中的应用

• 批准号: 9769598
• 负责人: Michael William Donnino
• 金额: $ 8.75万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9769598
• 关键词: Acidosis; Adult Respiratory Distress Syndrome; Alcohol abuse; Alcohol dependence; Area; Awareness; Cardiovascular system; Cell Respiration; Cessation of life; Citric Acid Cycle; Clinical; Complication; Critical Illness; Data; Data Analyses; Databases; Disease; Epidemiology; European; Gastrointestinal tract structure; Glucose; Guidelines; Health; Health care facility; Heart failure; High Cardiac Output; High Prevalence; Home environment; Hospital Mortality; Hospitals; ICD-9; Impairment; Incidence; Intake; Intensive Care Units; Intervention; Intestinal Absorption; Intravenous; Investigation; Knowledge; Lead; Legal patent; Life; Literature; Mechanical ventilation; Metabolic; Metabolic acidosis; Metabolism; Morbidity - disease rate; Neurologic; Neuroprotective Agents; Nutritional; Outcome; Patients; Pattern; Physicians; Population; Prevention; Proxy; Pyruvate; Risk; Role; Sepsis; Septic Shock; Testing; Thiamine; Thiamine Deficiency; Time; Treatment Protocols; United States; Wernicke Encephalopathy; Wernicke-Korsakoff Syndrome; Work; alcohol use disorder; alpha ketoglutarate; base; cardiovascular collapse; cofactor; data registry; improved outcome; mitochondrial metabolism; mortality; mortality risk; off-patent; prevent; prospective; pyruvate dehydrogenase; randomized trial; septic; septic patients; standard of care

Abstract Alcohol use disorders (AUDs) have been associated with both an increased incidence and worsened outcomes in sepsis. Thiamine (Vitamin B1) deficiency is common in patients with AUDs and can lead to devastating sequela, including neurological, metabolic, and cardiovascular complications. European guidelines recommend parenteral thiamine for the prevention of neurologic complications in hospitalized patients with known AUDs, however there is little focus on cardiovascular complications or the potential for death. Objective data is lacking as to whether patients with AUDs and sepsis are at increased risk of death without the provision of thiamine. In the present proposal, we seek to characterize practice patterns surrounding thiamine administration amongst patents with septic shock and concomitant AUD. Moreover, we hypothesize that septic patients with AUDs who do not receive intravenous thiamine will have increased hospital mortality when compared with patients who do receive thiamine. We support this with the following preliminary data: 1) Patients with AUDs are well-known to have thiamine deficiency, 2) Patients with thiamine deficiency disorders develop profound life-threatening acidosis that is rapidly responsive to thiamine, 3) Single-center data shows a surprisingly high number of septic shock patients with AUDs not receiving thiamine, 4) There is a high incidence of thiamine deficiency in septic shock patients independent of AUDs, and 5) A prospective randomized trial illustrated that the administration of thiamine reduces mortality in patients with sepsis and thiamine deficiency. For this study, we will leverage a large data registry containing information from over 480 health-care facilities across the Unites States. Specifically, we will investigate the proportion of patients with AUD who are admitted to the intensive care unit with septic shock and do/do not receive thiamine. Further, clinical outcomes in patients who received thiamine will be compared to those who did not receive thiamine, using a time-dependent propensity based analysis with risk set matching. If our hypotheses are proven true, we anticipate that this study will lead to a shift in management of septic patients with AUDs with an increased focus on early thiamine administration. As AUDs are common in septic populations and are effectively a proxy for thiamine deficiency, demonstrating improved outcomes from thiamine administration may spark the widespread provision of thiamine to the larger septic population. Finally, the epidemiology of untreated thiamine deficiency amongst septic patients with AUD and its potential effects on hospital outcomes represents an unexplored avenue of investigation.

抽象的 酒精使用障碍（AUD）与发病率增加和结果恶化有关 在败血症中。硫胺素（维生素B1）缺乏症在AUD患者中很常见，可能导致毁灭性 后遗症，包括神经，代谢和心血管并发症。欧洲准则建议 肠胃外硫胺素预防已知aud的住院患者的神经系统并发症， 但是，几乎没有关注心血管并发症或死亡的潜力。缺乏客观数据 至于没有提供硫胺素的情况，患有AUD和败血症的患者是否有死亡风险增加。在 目前的提议，我们试图表征围绕硫胺素管理的实践模式 具有化粪池冲击和随之而来的AUD的专利。此外，我们假设化粪池患有auds的患者 与这样做的患者相比 收到硫胺素。我们使用以下初步数据来支持这一点：1）AUD的患者众所周知 患有硫胺素缺乏，2）硫胺素缺乏障碍患者会导致严重威胁生命 对硫胺素迅速反应的酸性病，3）单中心数据显示出令人惊讶的化粪池数量 auds不接受硫胺素的休克患者，4）化粪池中硫胺素缺乏症的发病率很高 休克患者独立于AUD，5）一项前瞻性随机试验说明了给药 硫胺素降低了败血症和硫胺素缺乏患者的死亡率。对于这项研究，我们将利用 大型数据注册表包含来自整个国家的480多个医疗机构的信息。 具体来说，我们将调查被接受重症监护病房的AUD患者的比例 带有化粪池冲击，做/不接受硫胺素。此外，接受硫胺素的患者的临床结果 将使用基于时间倾向的分析将未接受硫胺素的人进行比较 风险设置匹配。如果我们的假设被证明是正确的，我们预计这项研究将导致转变 对auds的化粪池患者的管理，重点是早期硫胺素给药。作为音频 在化粪池种群中很常见，实际上是硫胺素缺乏症的代理，证明了改善 Thiamine Administration的结果可能会引发硫胺素的广泛提供给更大的化粪池 人口。最后，在AUD及其ITS的化粪池患者中未经治疗的硫胺素缺乏症的流行病学 对医院结局的潜在影响代表了未开发的调查大道。