Acute and Critical Care

Original Article

Immunology
Patterns of inflammatory immune responses in patients with septic shock receiving vitamin C, hydrocortisone, and thiamine: clustering analysis in Korea: Seung-Hun You, Oh Joo Kweon, Sun-Young Jung, Moon Seong Baek, Won-Young Kim; Acute Crit Care. 2023;38(3):286-297. Published online August 21, 2023; DOI: https://doi.org/10.4266/acc.2023.00507

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Background
Sepsis is characterized by heterogeneous immune responses that may evolve during the course of illness. This study identified inflammatory immune responses in septic patients receiving vitamin C, hydrocortisone, and thiamine.
Methods
This was a single-center, post-hoc analysis of 95 patients with septic shock who received the vitamin C protocol. Blood samples were drawn on days 1–2, 3–4, and 6–8 after shock onset. Group-based multi-trajectory modeling was used to identify immune trajectory groups.
Results
The median age was 78 years (interquartile range, 70–84 years), and 56% were male. Clustering analysis identified group 1 (n=41), which was characterized by lower interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-10 levels, and these levels remained stationary or mildly increased until day 7. Conversely, group 2 (n=54) expressed initially higher IL-6, TNF-α, and IL-10 levels that decreased rapidly by day 4. There was a nonsignificant increase in lymphocyte count and a decrease in C-reactive protein level until day 7 in group 2. The intensive care unit mortality rate was significantly lower in group 2 (39.0% vs. 18.5%, P=0.03). Group 2 also had a significantly higher decrease in the mean (standard deviation) vasopressor dose (norepinephrine equivalent: –0.09±0.16 μg/kg/min vs. –0.23±0.31 μg/kg/min, P<0.001) and Sequential Organ Failure Assessment score (0±5 vs. –4±3, P=0.002) between days 1 and 4.
Conclusions
There may be different subphenotypes in septic patients receiving the vitamin C protocol.

Citations

Citations to this article as recorded by

Micronutrients as therapy in critical illness
Christian Stoppe, Ellen Dresen, Angelique de Man
Current Opinion in Critical Care.2024; 30(2): 178. CrossRef

Review Article

Meta-analysis
The efficacy of vitamin C, thiamine, and corticosteroid therapy in adult sepsis patients: a systematic review and meta-analysis: Manoj Kumar Reddy Somagutta, Maria Kezia Lourdes Pormento, Muhammad Adnan Khan, Alaa Hamdan, Namrata Hange, Manish KC, Sukrut Pagad, Molly Sanjay Jain, Sivasthikka Lingarajah, Vishal Sharma, Jaspreet Kaur, Bernard Emuze, Erkan Batti, Obumneme Jude Iloeje; Acute Crit Care. 2021;36(3):185-200. Published online June 30, 2021; DOI: https://doi.org/10.4266/acc.2021.00108

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Abstract PDF Supplementary Material

Previous studies have suggested favorable outcomes of hydrocortisone, ascorbic acid (vitamin C), and thiamine (HAT) therapy in patients with sepsis. However, similar results have not been duplicated in sequential studies. This meta-analysis aimed to reevaluate the value of HAT treatment in patients with sepsis. Electronic databases were searched up until October 2020 for any studies that compared the effect of HAT versus non-HAT use in patients with sepsis. Data from 15 studies (eight randomized controlled trials [RCTs] and seven cohort studies) involving 67,349 patients were included. The results from the RCTs show no significant benefit of triple therapy on hospital mortality (risk ratio [RR], 0.99; P=0.92; I²=0%); intensive care unit (ICU) mortality (RR, 0.77; P=0.20; I²=58%); ICU length of stay (weighted mean difference [WMD], 0.11; P=0.86; I² =37%) or hospital length of stay (WMD: 0.57; P=0.49; I²=17%), and renal replacement therapy (RR, 0.64; P=0.44; I²=39%). The delta Sequential Organ Failure Assessment (SOFA) score favored treatment after a sensitivity analysis (WMD, –0.72; P=0.01; I²=32%). However, a significant effect was noted for the duration of vasopressor use (WMD, –25.49; P<0.001; I²=46%). The results from cohort studies have also shown no significant benefit of HAT therapy on hospital mortality, ICU mortality, ICU length of stay, length of hospital stay, the delta SOFA score, the use of renal replacement therapy, or vasopressor duration. HAT therapy significantly reduced the duration of vasopressor use and improved the SOFA score but appeared not to have significant benefits in other outcomes for patients with sepsis. Further RCTs can help understand its benefit exclusively.

Citations

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Effect of intravenous vitamin C on adult septic patients: a systematic review and meta-analysis
Huoyan Liang, Qingqing Mu, Wenju Sun, Liming Liu, Simin Qiu, Zili Xu, Yuqing Cui, Yan Yan, Tongwen Sun
Frontiers in Nutrition.2023;[Epub] CrossRef
Insights Into Thiamine Supplementation in Patients With Septic Shock
Nara Aline Costa, Amanda Gomes Pereira, Clara Sandra Araujo Sugizaki, Nayane Maria Vieira, Leonardo Rufino Garcia, Sérgio Alberto Rupp de Paiva, Leonardo Antonio Mamede Zornoff, Paula Schmidt Azevedo, Bertha Furlan Polegato, Marcos Ferreira Minicucci
Frontiers in Medicine.2022;[Epub] CrossRef
Vitamin C-induced Hemolysis: Meta-summary and Review of Literature
Deven Juneja, Ravi Jain
Indian Journal of Critical Care Medicine.2022; 26(2): 224. CrossRef
Is it time to reconsider the administration of thiamine alone or in combination with vitamin C in critically ill patients? A meta-analysis of clinical trial studies
Nafiseh Shokri-mashhadi, Ali Aliyari, Zahra Hajhashemy, Saeed Saadat, Mohammad Hossein Rouhani
Journal of Intensive Care.2022;[Epub] CrossRef
Parenteral Vitamin C in Patients with Severe Infection: A Systematic Review
Arnav Agarwal, John Basmaji, Shannon M. Fernando, Fang Zhou Ge, Yingqi Xiao, Haseeb Faisal, Kimia Honarmand, Mathieu Hylands, Vincent Lau, Kimberley Lewis, Rachel Couban, François Lamontagne, Neill K. J. Adhikari
NEJM Evidence.2022;[Epub] CrossRef
Unanswered questions on the use of hydrocortisone, ascorbic acid, and thiamine therapy in sepsis and septic shock
David Ragoonanan, Nicolas Tran, Veeshal Modi, Paige Morgan Nickelsen
American Journal of Health-System Pharmacy.2022; 79(19): 1626. CrossRef
Impacts of Corticosteroid Therapy at Acute Stage of Hospital-Onset Clostridioides difficile Infections
Ching-Chi Lee, Jen-Chieh Lee, Chun-Wei Chiu, Pei-Jane Tsai, Wen-Chien Ko, Yuan-Pin Hung
Infection and Drug Resistance.2022; Volume 15: 5387. CrossRef
The impact of vitamin C-containing treatment on the mortality of patients with sepsis: A systematic review and meta-analysis of randomized controlled trials
Ching-Yi Chen, Chien-Tung Chiu, Ho-Sheng Lee, Chih-Cheng Lai
Journal of Infection and Public Health.2022; 15(12): 1514. CrossRef
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Deven Juneja, Anish Gupta, Sahil Kataria, Omender Singh
World Journal of Virology.2022; 11(5): 300. CrossRef
Current role of high dose vitamin C in sepsis management: A concise review
Deven Juneja, Prashant Nasa, Ravi Jain
World Journal of Critical Care Medicine.2022; 11(6): 349. CrossRef
HYDROCORTISONE, ASCORBIC ACID, AND THIAMINE THERAPY DECREASE RENAL OXIDATIVE STRESS AND ACUTE KIDNEY INJURY IN MURINE SEPSIS
John Kim, Allan Stolarski, Qiuyang Zhang, Katherine Wee, Daniel Remick
Shock.2022; 58(5): 426. CrossRef
Early administration of Vitamin C in patients with sepsis or septic shock in emergency departments: A multicenter, double blinded, randomized controlled trial: The C-EASIE trial protocol
Stefanie Vandervelden, Lina Wauters, Jan Breuls, Steffen Fieuws, Philippe Vanhove, Ives Hubloue, Magali Bartiaux, Jacques Creteur, François Stifkens, Koen Monsieurs, Didier Desruelles, Elisa Panada
PLOS ONE.2021; 16(11): e0259699. CrossRef
Hydrocortisone, ascorbic acid, and thiamine (HAT) for sepsis and septic shock: a meta-analysis with sequential trial analysis
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Journal of Intensive Care.2021;[Epub] CrossRef

Case Reports

Experiences of Wet Beriberi and Wernicke's Encephalopathy Caused by Thiamine Deficiency in Critically Ill Patients: Ji Young Jang, Hongjin Shim, Jae Gil Lee; Korean J Crit Care Med. 2013;28(2):156-159.; DOI: https://doi.org/10.4266/kjccm.2013.28.2.156

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Abstract PDF

Wet beriberi and Wernicke's encephalopathy (WE) are caused by thiamine deficiency and are potentially lethal and serious diseases. Thiamine deficiency occurs mainly due to poor oral intake or inadequate provision of thiamine in enteral or parenteral nutrition therapy. We report cases of wet beriberi and WE that developed after surgery in a surgical intensive care unit. The first patient, who was diagnosed with wet beriberi, underwent right total mastectomy and radical subtotal gastrectomy, simultaneously. The second was diagnosed with irreversible WE, respectively, due to long-term malnutrition. In both cases, intravenous replacement of thiamine was initiated after the admission to the surgical intensive care unit. However, comatose mentality of the second patient did not improve. As a result, we conclude that, if a patient's clinical feature is suspected to be thiamine deficiency, prompt intravenous thiamine replacement is needed.

Citations

Citations to this article as recorded by

A Critical Case of Wernicke's Encephalopathy Induced by Hyperemesis Gravidarum
Byung Ju Kang, Min Gu Kim, Jwa Hoon Kim, Mingee Lee, Sang-Beom Jeon, Ha Il Kim, Jin Won Huh
The Korean Journal of Critical Care Medicine.2015; 30(2): 128. CrossRef

A Case of Wernicke's Encephalopathy in a Postoperative Patient with Parenteral Nutrition and Temporary Oral Feeding: A Case Report: Hannah Lee, Eun Hye Lee, Sang Chul Lee, Hee Pyoung Park; Korean J Crit Care Med. 2010;25(3):186-189.; DOI: https://doi.org/10.4266/kjccm.2010.25.3.186

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23 Download
2 Crossref

Abstract PDF

Wernicke's encephalopathy is an acute neurological disorder, caused by thiamine deficiency, which is clinically characterized by a triad of ophthalmoplegia, ataxia and disturbances of consciousness. Most frequently, the encephalopathy is a consequence of chronic alcoholism, but it may occur in other forms of malnutrition or malabsorption, such as in prolonged parenteral nutrition without the addition of thiamine, total gastrectomy, gastrojejunostomy, severe anorexia or hyperemesis gravidarum. Thiamine requirement increases during critical illness and in chronically depleted patients, and its supplementation may influence the outcome of the disease. We report a case of a 73-year-old man, who presented with recurred colon cancer, who was affected by Wernicke's encephalopathy while undergoing oral feeding and parenteral nutrition. This case suggests that we should be more aware of potential thiamine deficiency in critically ill patients, even those undergoing parenteral nutrition and temporary oral feeding.

Citations

Citations to this article as recorded by

Two Cases of Wernicke's Encephalopathy That Developed during Total Parenteral Nutrition in Colon Cancer Patients Treated with 5-Fluorouracil-based Chemotherapy
Kyung Pyo Cho, Jae Sung Lee, Ji Seok Seong, Yong Moon Woo, Young Jun Cho, Beom Jin Jeong, Jee Hoon Sohn, Su-Jung Kim
The Korean Journal of Gastroenterology.2014; 64(3): 158. CrossRef
Experiences of Wet Beriberi and Wernicke's Encephalopathy Caused by Thiamine Deficiency in Critically Ill Patients
Ji Young Jang, Hongjin Shim, Jae Gil Lee
Korean Journal of Critical Care Medicine.2013; 28(2): 156. CrossRef

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