Association of Vitamin C, Thiamine, and Hydrocortisone Infusion With Long-term Cognitive, Psychological, and Functional Outcomes in Sepsis Survivors
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Published:2023-02-28
Issue:2
Volume:6
Page:e230380
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ISSN:2574-3805
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Container-title:JAMA Network Open
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language:en
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Short-container-title:JAMA Netw Open
Author:
Williams Roberson Shawniqua123, Nwosu Samuel4, Collar Erin M.15, Kiehl Amy L.15, Harrison Fiona E.67, Bastarache Julie57, Wilson Jo Ellen189, Mart Matthew F.159, Sevransky Jonathan E.1011, Ely E. Wesley159, Lindsell Christopher J.4, Jackson James C.159, Nugent Katherine12, Spainhour Christine12, Polito Carmen12, Moore Brooks12, Negrin Lovie12, Khan Akram12, Kea Bory12, Krol Olivia12, Haq Ebaad12, Pinkert Vincent12, Nguyen Kelly12, Brown Samuel M12, Bledsoe Joseph12, Peltan Ithan12, Applegate Darrin12, Armbuster Brent12, Montgomery Quinn12, Brown Katie12, Daw Austin12, Gong Michelle12, Aboodi Michael12, Chen Jen-Ting (Tina)12, Hope Aluko12, Gummadi Swarna12, Lopez Brenda12, Hinson Jeremiah12, Hager David12, Ricketts Erin12, Clare Johnathan12, McBryde Breana12, Clements Casey M.12, Gajic Ognjen12, Kashyap Rahul12, Vanmeter Derek12, Busse Laurence12, McBride Mary12, Ginde Adit12, Moss Marc12, Finck Lani12, Howell Michelle12, McKeehan Jeffrey12, Higgins Carrie12, Barksdale Aaron12, Kalin Dan12, Kruse Derek12, Hilz Katlyn12, Qadir Nida12, Chang Steven Y.12, Beutler Rebecca12, Tam Andrea12, Harris Estelle S.12, Youngquist Scott T.12, Middleton Elizabeth A.12, Davidov Ervin12, Plante Amber12, Belsky Justin12, Siner Jonathan12, Wira Charles12, Brokowski Carolyn12, Steingrub Jay12, Smithline Howard12, Thorton-Thompson Sherell12, Fowler Alpha12, Miller Stephen12, Narron Kyle12, Pusckarich Michael A.12, Prekker Matthew E.12, Hendrickson Audrey12, Quinn James12, Wilson Jennifer12, Levitt Joseph12, Mann Rosen12, Visweswaran Anita12, Gentile Nina12, Marchetti Nathaniel12, Reimer Hannah12, Guirgis Faheem12, Jones Lisa12, Black Lauren12, Henson Morgan12, Meyer Nuala J.12, Greenwood John C.12, Ittner Caroline12, Rivers Emanuel12, Jayaprakash Namita12, Gardner-Gray Jayna12, Hurst Gina12, Pflaum Jacqueline12, Jaehne Anja Kathrin12, Gill Jasreen12, Cook Aaron12, Janz David R12, Vonderhaar Derek12, Romaine Connie12, Wilkerson R. Gentry12, McCurdy Michael T.12, Beach Dana12, Lasko Kyra12, Gill Richard12, Price Katherine12, Dickson Lisa12, Duggal Abhijit12, Mace Sharon E.12, Hite R. Duncan12, Hastings Andrei12, Haukoos Jason12, Dougla Ivor12, Trent Stacy12, Lyle Carolynn12, Cupelo Alicia12, Gravitz Stephanie12, Hiller Terra12, Oakes Judy12, LoVecchio Frank12, Quiroga Pedro12, Danley Shiloh12, Mulrow Mary12, Encinas Amanda12, Goodwin Andrew12, Hall Gregory12, Grady Abigail12, Exline Matthew12, Terndrup Thomas12, Pannu Sonal12, Robart Emily12, Karow Sarah12, Files D. Clark12, Smith Lane12, Gibbs Kevin12, Flores Lori12, Pastores Stephen M.12, Shaz David J.12, Kostelecky Natalie12, Chase Chad12, Wilkins Elizabeth (Liz)12, Gaieski David12, Baram Michael12, Schwegler Daniel12, Renzi Nicole12, Mosier Jarrod M.12, Hypes Cameron12, Salvagio Campbell Elizabeth12, Hooper Michael12, Sill Joshua12, Mitchell Kate12, Hudock Kristin12, Lyons Michael12, Gordner Kari12, Ahmad Yousef12, Studer Autumn12, Davis Jacqueline12, Barrett Matthew12, Nomura Jason12, Knox Jennifer12, Park Pauline12, Co Ivan12, McSparron Jakob12, Hyzy Robert12, McDonough Kelli12, Hanna Sinan12, Self Wesley H.12, Semler Matthew W.12, Hays Margaret12, Bartz Racquel12, Limkakeng Alexander12, Sweeney Katherine12, Woodburn Rachael12, Goyal Munish12, Zaaqoq Akram12, Moriarty Theresa12, Oropello John12, Zhang Ziya12,
Affiliation:
1. Critical Illness, Brain Dysfunction and Survivorship Center, Vanderbilt University Medical Center, Nashville, Tennessee 2. Department of Neurology, Vanderbilt University Medical Center, Nashville, Tennessee 3. Department of Biomedical Engineering, Vanderbilt University, Nashville, Tennessee 4. Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee 5. Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, Tennessee 6. Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee 7. Vanderbilt Brain Institute, Vanderbilt University, Nashville, Tennessee 8. Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, Tennessee 9. Veteran’s Affairs Tennessee Valley Geriatric Research Education Clinical Center, Nashville, Tennessee 10. Division of Pulmonary, Allergy Critical Care and Sleep, Emory University School of Medicine, Atlanta, Georgia 11. Emory Critical Care Center, Emory Healthcare, Atlanta, Georgia 12. for the VICTAS Investigators
Abstract
ImportanceSepsis is associated with long-term cognitive impairment and worse psychological and functional outcomes. Potential mechanisms include intracerebral oxidative stress and inflammation, yet little is known about the effects of early antioxidant and anti-inflammatory therapy on cognitive, psychological, and functional outcomes in sepsis survivors.ObjectiveTo describe observed differences in long-term cognitive, psychological, and functional outcomes of vitamin C, thiamine, and hydrocortisone between the intervention and control groups in the Vitamin C, Thiamine, and Steroids in Sepsis (VICTAS) randomized clinical trial.Design, Setting, and ParticipantsThis prespecified secondary analysis reports the 6-month outcomes of the multicenter, double-blind, placebo-controlled VICTAS randomized clinical trial, which was conducted between August 2018 and July 2019. Adult patients with sepsis-induced respiratory and/or cardiovascular dysfunction who survived to discharge or day 30 were recruited from 43 intensive care units in the US. Participants were randomized 1:1 to either the intervention or control group. Cognitive, psychological, and functional outcomes at 6 months after randomization were assessed via telephone through January 2020. Data analyses were conducted between February 2021 and December 2022.InterventionsThe intervention group received intravenous vitamin C (1.5 g), thiamine hydrochloride (100 mg), and hydrocortisone sodium succinate (50 mg) every 6 hours for 96 hours or until death or intensive care unit discharge. The control group received matching placebo.Main Outcomes and MeasuresCognitive performance, risk of posttraumatic stress disorder and depression, and functional status were assessed using a battery of standardized instruments that were administered during a 1-hour telephone call 6 months after randomization.ResultsAfter exclusions, withdrawals, and deaths, the final sample included 213 participants (median [IQR] age, 57 [47-67] years; 112 males [52.6%]) who underwent long-term outcomes assessment and had been randomized to either the intervention group (n = 108) or control group (n = 105). The intervention group had lower immediate memory scores (adjusted OR [aOR], 0.49; 95% CI, 0.26-0.89), higher odds of posttraumatic stress disorder (aOR, 3.51; 95% CI, 1.18-10.40), and lower odds of receiving mental health care (aOR, 0.38; 95% CI, 0.16-0.89). No other statistically significant differences in cognitive, psychological, and functional outcomes were found between the 2 groups.Conclusions and RelevanceIn survivors of sepsis, treatment with vitamin C, thiamine, and hydrocortisone did not improve or had worse cognitive, psychological, and functional outcomes at 6 months compared with patients who received placebo. These findings challenge the hypothesis that antioxidant and anti-inflammatory therapy during critical illness mitigates the development of long-term cognitive, psychological, and functional impairment in sepsis survivors.Trial RegistrationClinicalTrials.gov Identifier: NCT03509350
Publisher
American Medical Association (AMA)
Cited by
13 articles.
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