A Randomized clinical trial of antioxidant therapy in patients with septic shock. Reference study to propose adjuvant therapy in patients with critical organic damage by COVID-19

Abstract Background: Oxidative stress (OS) participates in the pathophysiology of patients with septic shock having multiple organ failure (MOF), ischemia-reperfusion injury and acute respiratory failure syndrome (ARDS). Antioxidants have been proposed in their therapy.Objective: To evaluate the effect of antioxidant treatment in patients with septic shock with MOF and levels OS after treatment.Research question: Will the administration of specific antioxidant therapy decrease deregulatory factors of oxidative stress and organ failure in patients with septic shock?Study design and Methods: Double-blind, placebo-controlled randomized clinical trial run in 2 ICU in Mexico City between May 2018 and January 2020. The random allocation sequence was generated using computer methods. Patients older than 18 years of either sex, with septic shock were included, were excluded when informed consent could not be obtained, they received chronic or recent use of steroids, statins, or antioxidants or if they had contraindications to the use of antioxidants. All antioxidants were administered by mouth or nasogastric tube during 5 days and were added to standard.Results: 97 patients were included with median age of 66 years. 20 were treated with MT and 18 with Vit C and they showed post-treatment decreased SOFA scores [p=0.007 and p<0.001 respectively]. Also, total antioxidant capacity (TAC) was improved by NAC. All patients had decreased basal levels of Vit C and patients that received Vit C had decreased levels of the NO3−/NO2− (p=0.02) and RCP levels [p=0.045]. Procalcitonin (PCT) levels were reduced by Vit E, [p=0.047], NAC; [p=0.001] and MT [p=0.045]. LPO was reduced in patients that received MT p=0.042 Conclusion: In septic shock, antioxidant therapy associated with standard intensive care unit therapy reduces MOF, the oxidative and inflammatory state. These results could be a reference to use adjuvant antioxidant therapy in patients with septic shock in COVID19.Trial Registration: ClinicalTrials.gov Identifier: NCT 03557229