Strengths and limitations
acidemia, CKD, alkalosis
ACIDEMIA, RECRUITMENT, ALKALOSIS, SEPTIC SHOCK
Our study has several strengths. It is the first, double-blind, randomized controlled trial to assess the physiological effects of a single mega-dose of NaAscorbate in patients with septic shock. All patients were enrolled within 24 h of onset suggesting that they were in the acute phase of septic shock. We measured the plasma concentration of ascorbate and demonstrated that, in relation to such levels, our treatment profoundly differed from previous trials using vitamin C as a therapy. Finally, we used a preparation which, unlike ascorbic acid-based preparations, has physiological pH levels and, therefore, did not induce acidemia and indeed delivered a mild degree of alkalosis.We acknowledge some limitations. First, we amended the protocol after the first 12 patients. However, this was a pilot feasibility and physiological effect trial, the equivalent of first in man for this intervention in septic shock, and safety was paramount. Second, the recruitment rate was low and profoundly affected by the COVID pandemic. Third, the physiological effects seen are not necessarily due to ascorbate and may simply reflect the impact of a sodium load. In addition, we enrolled patients without CKD and most of the patients received norepinephrine at enrolment, which implies a cardiovascular SOFA score of 3 or more. Thus, the change in vasopressor therapy was responsible for the change in SOFA score. Finally, this trial is a small single-center study and does not have enough power to provide significant information about clinical outcomes.