Vitamin C and thiamine for sepsis: time to go back to fundamental principles
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EDITORIAL
Vitamin C and thiamine for sepsis: time to go back to fundamental principles Tomoko Fujii1,2* , Robert Fowler3 and Jean‑Louis Vincent4 © 2020 Springer-Verlag GmbH Germany, part of Springer Nature
Vitamin C plays a vital role in human physiology. For decades, intriguing research has highlighted the possibility of acute effects of vitamin C deficiency in patients with sepsis [1]. Vitamin C is a mediator of endothelial function through its co-factor role with many enzymes (including one that catalyses the conversion of dopamine to noradrenaline). Vitamin C also works as an antioxidant by scavenging free radicals (Fig. 1). In animal models of sepsis, exogenous vitamin C increases perfused capillary density and arteriolar vasoconstrictor responsiveness, implying its possible role in treating vasoplegic status in sepsis [2]. The synergistic effect of hydrocortisone and vitamin C has also been suggested as vitamin C helps to reduce oxidised glucocorticoid receptors, and glucocorticoids induce the expression of a vitamin C transporter [2]. Thiamine, which is a coenzyme for the oxidation of pyruvate to acetyl-CoA in the Krebs cycle, is also depleted in some patients with sepsis [3]. Thus, thiamine has been suggested as another treatment option for sepsis. The combination of vitamin C, thiamine, and hydrocortisone has recently been advocated as a treatment for patients with septic shock, largely based upon a singlecentre before-after study [4]. This suggestion has provoked substantial global debate on incorporation into clinical practice ahead of assessing the balance of benefits and harms in valid clinical trials that comprise a contemporaneous control group with potentially confounding factors balanced between study arms. In this issue of Intensive Care Medicine, results from the ATESS trial, a double-blind RCT of vitamin C and *Correspondence: tofujii‑[email protected] 1 Intensive Care Unit, Jikei University Hospital, 3‑19‑18, Nishi‑Shimbashi, Minato‑ku, Tokyo 105‑8461, Japan Full author information is available at the end of the article
thiamine for septic shock are reported [5]. The trial was conducted in four emergency departments in South Korea. The trial was designed to assess the effect of intravenous vitamin C (50 mg/kg, max 3 g/dose, every 12 h) and thiamine (200 mg, every 12 h) for 48 h compared with placebo on organ dysfunction. A sample size of 116 was calculated to have 80% power to detect a difference of 1.5 points in the change of SOFA score at 72 h of enrolment. Subsequently, 111 of 116 randomised patients were included in the analysis. There was no difference in delta SOFA score [median of differences, 0 (− 2–1), p = 0.96]. None of the secondary outcomes, including mortality, vasopressor dependency, need for mechanical ventilation or renal replacement therapy, and inflammatory biomarkers, indicated a beneficial effect of the intervention. The allocation sequence and randomisation were concealed appropriately, and the major co-intervention with hydrocortisone was well-balanced between the group
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