Randomized Clinical Trial of Antioxidant Therapy Patients with Septic Shock and Organ Dysfunction in the ICU: SOFA Score Reduction by Improvement of the Enzymatic and Non-Enzymatic Antioxidant System

Alfredo Aisa-Álvarez; Israel Pérez-Torres; Verónica Guarner-Lans; Linaloe Manzano-Pech; Randall Cruz-Soto; Ricardo Márquez-Velasco; Sergio Casarez-Alvarado; Juvenal Franco-Granillo; Marcela Elizabeth Núñez-Martínez; María Elena Soto

doi:10.3390/cells12091330

Randomized Clinical Trial of Antioxidant Therapy Patients with Septic Shock and Organ Dysfunction in the ICU: SOFA Score Reduction by Improvement of the Enzymatic and Non-Enzymatic Antioxidant System

Cells. 2023 May 6;12(9):1330. doi: 10.3390/cells12091330.

Affiliations

¹ Critical Care Department, American British Cowdray (ABC) Medical Center, I.A.P. ABC Sur 136 No. 116 Col. Las Américas, México City 01120, Mexico.
² UNAM Master's and Doctoral Program in Medical, Dental and Health Sciences UNAM, México. Av. Universidad 3000, Coyoacán, México City 04510, Mexico.
³ Cardiovascular Biomedicine Department, Instituto Nacional de Cardiología Ignacio Chávez, Juan Badiano 1, Sección XVI, Tlalpan, México City 14080, Mexico.
⁴ Physiology Department, Instituto Nacional de Cardiología Ignacio Chávez, Juan Badiano 1, Sección XVI, Tlalpan, México City 14080, Mexico.
⁵ Immunology Department, Instituto Nacional de Cardiología Ignacio Chávez, Juan Badiano 1, Sección XVI, Tlalpan, México City 14080, Mexico.
⁶ Central Laboratory Department, ABC Hospital Observatory, Sur 136 No. 116 Col. Las Américas, México City 01120, Mexico.
⁷ Department of the Cardiovascular, Division of the American British Cowdray Medical Center, Sur 136 No. 116 Col. Las Américas, México City 01120, Mexico.

Abstract

Background and aim: Here, we assess the effect of adjuvant antioxidant therapies in septic shock patients with organ dysfunction and their effect on the enzymatic and non-enzymatic antioxidant systems.

Methods: Randomized clinical trial run between 2018 and 2022. One hundred and thirty-one patients with septic shock were included in five groups with 25, 27, 24, 26 and 29 patients each. Group 1 received vitamin C (Vit C), Group 2 vitamin E (Vit E), Group 3 n-acetylcysteine (NAC), Group 4 melatonin (MT) and group 5 no treatment. All antioxidants were administered orally or through a nasogastric tube for 5 days as an adjuvant to standard therapy.

Results: All patients had multiple organ failure (MOF) and low Vit C levels. Vit C therapy decreased CRP, PCT and NO₃^-/NO₂^- but increased Vit C levels. The SOFA score decreased with MT in 75%, Vit C 63% and NAC 50% vs. controls 33% (p = 0.0001, p = 0.03 and p = 0.001 respectively). MT diminished lipid peroxidation (LPO) (p = 0.01) and improved total antioxidant capacity (TAC) (p = 0.04). Vit E increased thiol levels (p = 0.02) and tended to decrease LPO (p = 0.06). Selenium levels were decreased in the control group (p = 0.04).

Conclusions: Antioxidants used as an adjuvant therapy in the standard treatment of septic shock decrease MOF and oxidative stress markers. They increase the TAC and thiols, and maintain selenium levels.

Trial registration: ClinicalTrials.gov NCT03557229.

Keywords: N-acetylcysteine; Vitamin C; Vitamin E; antioxidants; melatonin; multiple organ failure.

Publication types

Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Antioxidants / therapeutic use
Ascorbic Acid / therapeutic use
Humans
Intensive Care Units
Melatonin*
Multiple Organ Failure / drug therapy
Organ Dysfunction Scores
Selenium*
Shock, Septic* / drug therapy
Vitamin E / therapeutic use
Vitamins

Substances

Antioxidants
Selenium
Vitamin E
Ascorbic Acid
Melatonin
Vitamins

Associated data

ClinicalTrials.gov/NCT03557229

Grants and funding

This work was supported by funds, Institute National of Cardiology, Ignacio Chávez., and Centro Medico ABC Observatory.