Thiamine in Pediatric Sepsis: A Motivating Study.
Thiamine in Pediatric Sepsis: A Motivating Study.
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硫胺素在儿童脓毒症中的作用：一项激动人心的研究。
DOI：
10.1097/pcc.0000000000002084
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发表时间：
2019
期刊：
影响因子：
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通讯作者：
Scott,HaldenF
中科院分区：
文献类型：
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作者：
Scott,HaldenF
儿科败血症仍然是儿童死亡和发病的主要原因（1）。尽管改善儿科败血症早期诊断和复苏的努力取得了一些成功，但仍在继续寻找改善多器官衰竭难治性状态患者结局的治疗方法（2）。一种潜在的治疗方法是硫胺素，其具有生化原理和观察数据，表明其可能是败血症的有用工具。硫胺素是丙酮酸脱氢酶和α-酮戊二酸脱氢酶的辅因子，这两种酶通过糖酵解和柠檬酸循环产生能量（3）。在缺乏硫胺素的情况下，丙酮酸积累并通过转化为乳酸产生能量。尽管组织氧输送减少通常会导致早期高乳酸血症性脓毒性休克，但持续性高乳酸血症，特别是在氧输送优化后，可能代表线粒体能量产生失败（4）。硫胺素依赖性酶的功能有限是可能发生这种情况的一种机制。硫胺素缺乏症存在于10-70%的成人ICU和28%的PICU患者中（5-7）。与单独患有败血症或硫胺素缺乏症的儿童相比，患有败血症和硫胺素缺乏症的儿童死亡几率增加（7）。尽管一项关于硫胺素治疗成人感染性休克的随机对照试验并未显著降低乳酸水平或改善生存率，但硫胺素确实显著改善了35%硫胺素缺乏患者的这些结局（8）。在感染性休克成人中进行的一项前后研究还表明了硫胺素在感染性休克中的潜在益处，其中接受包括硫胺素、维生素C和氢化可的松的方案的患者生存率提高。然而，这项研究无法区分这些疗法中的任何一种是否单独有效，并且受到前后设计的限制（9）。在这种治疗难治性脓毒性休克的前景看好，但儿科人群的前瞻性数据有限的背景下，有必要探索有关儿童脓毒性休克中维生素B1的现有数据。在本期《儿科重症监护医学》中，韦斯等人（10）报告了他们对硫胺素在长期高乳酸血症脓毒性休克儿童中的应用进行的小型回顾性病例对照研究。他们发现，24小时内乳酸水平变化的主要结果在病例组和对照组之间没有显著差异。然而，产生假设的数据出现了，作者在6年中提出了6例病例和9例对照。这些病例是感染性休克和高乳酸血症大于或等于5 mmol/L的儿童，他们接受了硫胺素治疗，目的是逆转高乳酸血症。对照组患者也有感染性休克，乳酸大于或等于5 mmol/L，并在多个适当的人口统计学和严重程度分层上匹配。硫胺素治疗方案各不相同，使用1-5 mg/kg/d，每日1-2次，中位时间为9天（范围，7-30天）。作者发现24小时内乳酸的中位变化无显著差异，病例组降低9.0 mmol/L（5.0-17.0 mmol/L），对照组降低7.2 mmol/L（5.3-9.0 mmol/L）。包括死亡率在内的次要结局没有显示出显著差异。病例中基线前延长的高乳酸血症持续时间较长，为39小时（16.1-64.3），而对照组为3.4小时（0-22.9），这使得硫胺素给药后乳酸水平的快速下降尤为显著。与现有的研究一致，没有观察到与硫胺素给药相关的不良事件，尽管不良事件...
Pediatric sepsis remains a leading cause of death and morbidity in children (1). Although efforts to improve early diagnosis and resuscitation of pediatric sepsis have had some success, the search continues for therapies that improve outcomes for patients in a refractory state of multiple organ failure (2). One potential therapy is thiamine, which has both a biochemical rationale and observational data to suggest it may be a useful tool in sepsis. Thiamine is a cofactor of pyruvate dehydrogenase and α-ketoglutarate dehydrogenase, enzymes in energy production through glycolysis and the citric acid cycle (3). In the absence of thiamine, pyruvate accumulates and produces energy through conversion to lactate. Although decreased oxygen delivery to tissues frequently contributes to early hyperlactatemic septic shock, persistent hyperlactatemia, particularly after oxygen delivery has been optimized, likely represents a failure in mitochondrial energy production (4). Limited function of thiamine-dependent enzymes is one mechanism through which this may occur. Thiamine deficiency is present in 10–70% of adult ICU and 28% of PICU patients (5–7). Children with sepsis and thiamine deficiency together have increased odds of death compared with children with either sepsis or thiamine deficiency alone (7). Although a randomized controlled trial of thiamine treatment in adult septic shock did not significantly lower lactate levels or improve survival, thiamine did significantly improve these outcomes in the 35% of patients who were thiamine deficient (8). The potential benefit of thiamine in septic shock was additionally suggested by a before-and-after study in adults with septic shock, in which patients who received a protocol including thiamine, vitamin C, and hydrocortisone had improved survival. However, this study could not distinguish whether any of these therapies individually had an effect and was subject to the limitations of a before-and-after design (9). In this context of a therapy with promise in refractory septic shock, but limited prospective data in pediatric populations, exploration of existing data about thiamine in pediatric septic shock is warranted. In this issue of Pediatric Critical Care Medicine, Weiss et al (10) report their small retrospective case-control study of the use of thiamine in children with prolonged hyperlactatemic septic shock. They found that the primary outcome of change in lactate level over 24 hours did not significantly differ between cases and controls. However, hypothesisgenerating data emerged.The authors present six cases and nine matched controls over 6 years. The cases were children with septic shock and hyperlactatemia greater than or equal to 5 mmol/L who had been treated with thiamine with a goal of reversing hyperlactatemia. Control patients also had septic shock, lactate greater than or equal to 5 mmol/L, and were matched on multiple appropriate demographic and severity strata. Thiamine treatment regimens varied, using 1–5 mg/kg/d, 1–2 times daily for a median of 9 days (range, 7–30 d). The authors found no significant difference in the median change in lactate over 24 hours, with cases decreasing by 9.0 mmol/L (5.0–17.0 mmol/L) and controls by 7.2 mmol/L (5.3–9.0 mmol/L). Secondary outcomes, including mortality, did not show significant difference. The duration of prolonged hyperlactatemia prior to baseline was longer in cases, 39 hours (16.1–64.3) compared with 3.4 hours (0–22.9) in controls, making the rapid decrease in lactate level after thiamine administration particularly notable. In keeping with existing studies, no adverse events were observed related to thiamine administration, although adverse events were …