Association of Vitamin C, Thiamine, and Hydrocortisone Infusion With Long-term Cognitive, Psychological, and Functional Outcomes in Sepsis Survivors: A Secondary Analysis of the Vitamin C, Thiamine, and Steroids in Sepsis Randomized Clinical Trial.
Association of Vitamin C, Thiamine, and Hydrocortisone Infusion With Long-term Cognitive, Psychological, and Functional Outcomes in Sepsis Survivors: A Secondary Analysis of the Vitamin C, Thiamine, and Steroids in Sepsis Randomized Clinical Trial.
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DOI：
10.1001/jamanetworkopen.2023.0380
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发表时间：
2023-02-01
影响因子：
13.8
通讯作者：
中科院分区：
文献类型：
--
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这项随机临床试验的二次分析报告了脓毒症成人接受抗氧化剂和氢化可的松输注治疗方案 6 个月后的认知表现、创伤后应激障碍和抑郁症风险以及功能状态。早期抗氧化和抗炎治疗是否可以改善脓毒症成人患者的长期认知、心理和功能结果？在这项对 213 名患有呼吸和/或心血管功能障碍的败血症幸存者进行的随机临床试验的二次分析中，与安慰剂相比，早期使用维生素 C、硫胺素和氢化可的松治疗导致许多领域没有改善，即刻记忆评分更差，并且患创伤后应激障碍的几率更高。这项研究的结果表明，抗氧化和抗炎治疗并不能减轻脓毒症幸存者长期认知、心理和功能障碍的发展。脓毒症与长期认知障碍和较差的心理和功能结果有关。潜在的机制包括脑内氧化应激和炎症，但早期抗氧化和抗炎治疗对脓毒症幸存者认知、心理和功能结果的影响知之甚少。描述在维生素 C、硫胺素和类固醇治疗败血症 (VICTAS) 随机临床试验中，干预组和对照组之间观察到的维生素 C、硫胺素和氢化可的松在长期认知、心理和功能结果方面的差异。这项预先指定的二次分析报告了 2018 年 8 月至 2019 年 7 月期间进行的多中心、双盲、安慰剂对照 VICTAS 随机临床试验的 6 个月结果。从美国 43 个重症监护病房招募了存活至出院或第 30 天的脓毒症引起的呼吸和/或心血管功能障碍的成年患者。参与者以 1:1 的比例随机分配到干预组或对照组。通过电话评估随机分组后 6 个月的认知、心理和功能结果，直至 2020 年 1 月。数据分析于 2021 年 2 月至 2022 年 12 月期间进行。干预组每 6 小时静脉注射维生素 C（1.5 g）、盐酸硫胺素（100 mg）和氢化可的松琥珀酸钠（50 mg），持续 96 小时，或直至死亡或出重症监护室。对照组接受匹配的安慰剂。使用一系列标准化工具评估认知表现、创伤后应激障碍和抑郁症风险以及功能状态，这些工具在随机分组后 6 个月的 1 小时电话通话中进行。经过排除、退出和死亡后，最终样本包括 213 名参与者（中位 [IQR] 年龄，57 [47-67] 岁；112 名男性 [52.6%]），他们接受了长期结果评估，并被随机分为干预组 (n = 108) 或对照组 (n = 105)。干预组的即时记忆评分较低（调整后 OR [aOR]，0.49；95% CI，0.26-0.89），患创伤后应激障碍的几率较高（aOR，3.51；95% CI，1.18-10.40），接受心理保健的几率较低（aOR，0.38；95% CI，0.16-0.89）。两组之间在认知、心理和功能结果方面没有发现其他统计学上的显着差异。在脓毒症幸存者中，与接受安慰剂的患者相比，维生素 C、硫胺素和氢化可的松治疗在 6 个月时没有改善或认知、心理和功能结果更差。这些发现挑战了以下假设：危重病期间的抗氧化和抗炎治疗可减轻脓毒症幸存者长期认知、心理和功能障碍的发展。 ClinicalTrials.gov 标识符：NCT03509350
This secondary analysis of a randomized clinical trial reports on the cognitive performance, risk of posttraumatic stress disorder and depression, and functional status 6 months after the administration of a treatment regimen consisting of antioxidants and hydrocortisone infusion in adults with sepsis. Does early antioxidant and anti-inflammatory therapy improve the long-term cognitive, psychological, and functional outcomes in adults with sepsis? In this secondary analysis of a randomized clinical trial involving 213 survivors of sepsis with respiratory and/or cardiovascular dysfunction, early treatment with vitamin C, thiamine, and hydrocortisone resulted in no improvement in many domains, worse immediate memory scores, and higher odds of posttraumatic stress disorder compared with placebo. Findings of this study suggest that antioxidant and anti-inflammatory therapy does not mitigate the development of long-term cognitive, psychological, and functional impairment in sepsis survivors. Sepsis 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. To 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. This 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. The 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. Cognitive 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. After 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. In 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. ClinicalTrials.gov Identifier: NCT03509350
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影响因子：
4.4
作者：
Goldstein RB;Smith SM;Chou SP;Saha TD;Jung J;Zhang H;Pickering RP;Ruan WJ;Huang B;Grant BF
通讯作者：
Grant BF
影响因子：
5.9
作者：
Consoli, David C.;Jesse, Jordan J.;Harrison, Fiona E.
通讯作者：
Harrison, Fiona E.
DOI：
10.1186/1476-9255-11-11
发表时间：
2014
期刊：
Journal of inflammation (London, England)
影响因子：
--
作者：
de Andrade JAA;Gayer CRM;Nogueira NPA;Paes MC;Bastos VLFC;Neto JDCB;Alves SC Jr;Coelho RM;da Cunha MGAT;Gomes RN;Águila MB;Mandarim-de-Lacerda CA;Bozza PT;da Cunha S
通讯作者：
da Cunha S
影响因子：
11.4
作者：
Ferrada, Luciano;Barahona, Maria Jose;Nualart, Francisco
通讯作者：
Nualart, Francisco
影响因子：
120.7
作者：
Fowler, Alpha A., III;Truwit, Jonathon D.;Halquist, Matthew
通讯作者：
Halquist, Matthew