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.

摘要 酒精使用障碍（AUDs）与发病率增加和结局恶化相关 败血症硫胺素（维生素B1）缺乏在AUD患者中很常见，可导致破坏性的 后遗症，包括神经、代谢和心血管并发症。欧洲指南建议 肠外硫胺素用于预防已知AUD住院患者的神经系统并发症， 然而，很少关注心血管并发症或死亡的可能性。缺乏客观数据 是否AUDs和败血症患者在没有硫胺素的情况下死亡风险增加。在 目前建议，我们寻求表征实践模式周围硫胺管理之间 感染性休克伴AUD患者。此外，我们假设患有AUDs的脓毒症患者， 与接受静脉注射硫胺素的患者相比，不接受静脉注射硫胺素的患者住院死亡率增加 接受硫胺素。我们通过以下初步数据支持这一点：1）众所周知，AUD患者 有硫胺素缺乏症，2）硫胺素缺乏症患者发展严重危及生命 对硫胺素反应迅速的酸中毒，3）单中心数据显示， 未接受硫胺素治疗的AUDs休克患者，4）败血症患者中硫胺素缺乏症的发生率较高， 休克患者与AUDs无关，5）一项前瞻性随机试验表明， 硫胺素降低败血症和硫胺素缺乏症患者的死亡率。在本研究中，我们将利用 大型数据注册表包含来自美国480多家医疗机构的信息。 具体来说，我们将调查AUD患者入住重症监护室的比例 感染性休克，并没有/没有接受硫胺素。此外，接受硫胺素治疗的患者的临床结局 将使用基于时间依赖性倾向的分析与未接受硫胺素的患者进行比较 风险匹配。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一个转变， 管理伴有AUDs的脓毒症患者，增加对早期硫胺素给药的关注。以澳元计 在败血症人群中很常见，是硫胺素缺乏症的有效代表， 硫胺素给药的结果可能会引发硫胺素的广泛提供， 人口最后，在患有AUD的脓毒症患者中未治疗的硫胺素缺乏症的流行病学及其 对医院结果的潜在影响是一个未探索的研究途径。