Since the publication of the retrospective before and after study by Dr. Marik and colleagues, in which administration of hydrocortisone, intravenous (IV) vitamin C, and thiamine was indicated to provide a survival advantage in septic patients [1], there has been a prevalence of clinical trials of variable quality and subsequent meta-analyses indicating variable outcomes [2]. Unlike previous combination trials, which did not control for corticosteroid use in the control arm, the recently published VITAMINS randomized clinical trial standardized corticosteroid administration in the control arm to determine if IV vitamin C and thiamine could provide an additional survival advantage over hydrocortisone alone [3]. This trial showed no benefit of the combination of hydrocortisone, IV vitamin C, and thiamine in comparison to hydrocortisone alone. Although the accompanying editorial by Dr. Kalil suggested that in light of this finding, IV vitamin C has no place in critical care, limitations of the VITAMINS trial preclude this view. It is well established that septic patients exhibit a high prevalence of vitamin C deficiency, and a recently published clinical trial in JAMA indicated that IV vitamin C may provide a survival advantage in these patients [4]. Since the VITAMINS trial did not include an arm with IV vitamin C monotherapy, this trial does not provide any information as to whether IV vitamin C is of benefit to septic patients in the absence of corticosteroid administration. This trial simply indicated that short-term IV vitamin C administration (mean of 3.4 days) may not be of additional benefit if corticosteroids are being administered to the patients. However, routine corticosteroid administration to septic patients is not a common clinical practice in all intensive care units. Indeed, the VITAMINS trial may in fact indicate redundancy between vitamin C and corticosteroids. Vitamin C is thought to play a role in the stress response as evidenced by its very high concentrations in the adrenal glands and its release in response to ACTH [5]. Furthermore, animals that cannot synthesize vitamin C have significantly elevated cortisol release in response to stress compared with animals that can synthesize vitamin C endogenously (reviewed in [5]). Thus, administration of corticosteroids to septic patients may help compensate for deficient vitamin C concentrations in these patients. Alternatively, in the absence of corticosteroid administration, supplementation of deficient patients with vitamin C may help with their stress response and could potentially provide a survival advantage, particularly in patients with HPA axis dysregulation.

中文翻译：

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维生素 RCT 是否表明皮质类固醇和维生素 C 之间存在潜在冗余？

自 Marik 博士及其同事发表研究前后的回顾性研究以来，表明使用氢化可的松、静脉注射 (IV) 维生素 C 和硫胺素可提高脓毒症患者的生存率 [1]，自不同质量的临床试验的普遍性和随后的荟萃分析表明不同的结果 [2]。与之前的联合试验不控制对照组中皮质类固醇的使用，最近发表的 VITAMINS 随机临床试验对对照组中的皮质类固醇给药进行了标准化，以确定静脉注射维生素 C 和硫胺素是否可以提供比单独使用氢化可的松更多的生存优势 [3] ]。该试验表明，与单独使用氢化可的松相比，氢化可的松、静脉注射维生素 C 和硫胺素的组合没有任何益处。尽管 Kalil 博士随附的社论表明，鉴于这一发现，IV 维生素 C 在重症监护中没有地位，但 VITAMINS 试验的局限性排除了这一观点。众所周知，脓毒症患者维生素 C 缺乏症的患病率很高，最近在 JAMA 上发表的一项临床试验表明，静脉注射维生素 C 可能为这些患者提供生存优势 [4]。由于 VITAMINS 试验不包括静脉注射维生素 C 单一疗法的组，因此该试验没有提供关于静脉注射维生素 C 是否对不使用皮质类固醇的脓毒症患者有益的任何信息。该试验只是表明，如果对患者使用皮质类固醇，短期静脉注射维生素 C（平均 3.4 天）可能不会带来额外的好处。然而，对脓毒症患者进行常规皮质类固醇给药并不是所有重症监护病房的常见临床实践。事实上，维生素试验实际上可能表明维生素 C 和皮质类固醇之间存在冗余。维生素 C 被认为在应激反应中发挥作用，其在肾上腺中的浓度非常高，并且在响应促肾上腺皮质激素时会释放 [5]。此外，与可以内源性合成维生素 C 的动物相比，不能合成维生素 C 的动物在应激反应中的皮质醇释放显着增加（见 [5]）。因此，向脓毒症患者服用皮质类固醇可能有助于弥补这些患者维生素 C 浓度不足的问题。或者，在没有皮质类固醇给药的情况下，