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Çakir MU, Karduz G, Aksu U. Experimental and clinical perspectives on glycocalyx integrity and its relation to acute respiratory distress syndrome. Biochim Biophys Acta Mol Basis Dis 2025; 1871:167745. [PMID: 39987847 DOI: 10.1016/j.bbadis.2025.167745] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2024] [Revised: 02/02/2025] [Accepted: 02/18/2025] [Indexed: 02/25/2025]
Abstract
The development of microcirculation imaging devices has significantly advanced our comprehension of the capillary environment's dynamics. Early research suggested that erythrocytes did not contact the vessel's inner surface due to the Fåhraeus effect, implying the presence of a covering on the endothelial cell surface. Subsequent electron microscopy studies revealed this layer to be a complex part of the vessel wall, now known as the endothelial glycocalyx (EG). The EG is a network of proteoglycans and glycoproteins bound to the endothelial membrane, incorporating soluble molecules from the endothelium and plasma. Over time, studies have elucidated the structure, function, and therapeutic targets of the glycocalyx, underscoring its pivotal role in vascular biology. The presence of cellular extensions of lung tissue cells in both vascular and nonvascular areas demonstrates the pivotal role of the glycocalyx in pulmonary vascular leak, surfactant dysfunction, impaired lung compliance and gas exchange abnormalities, which are hallmarks of acute respiratory distress syndrome (ARDS). It is of the utmost importance to elucidate the mechanisms underlying alveolocapillary glycocalyx degradation to develop efficacious treatments for ARDS, which has a mortality rate of 35 %. An understanding of the glycocalyx's role in vascular integrity provides a foundation for exploring new therapeutic avenues to mitigate lung injury and improve clinical outcomes in ARDS patients.
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Affiliation(s)
- Muzaffer Utku Çakir
- Department of Biology, Faculty of Science, Istanbul University, Istanbul, Türkiye
| | - Gülsüm Karduz
- Department of Biology, Faculty of Science, Istanbul University, Istanbul, Türkiye
| | - Ugur Aksu
- Department of Biology, Faculty of Science, Istanbul University, Istanbul, Türkiye.
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Iizuka Y, Fukano K, Oki S, Sawada I, Miyazawa K, Ono S, Yoshinaga K, Sanui M, Yamaguchi A. Effect of Ascorbic Acid on the Incidence of Postoperative Delirium Among Elderly Patients Undergoing Cardiovascular Surgery: A Pilot Study. J Clin Med Res 2025; 17:145-152. [PMID: 40115841 PMCID: PMC11922629 DOI: 10.14740/jocmr6169] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2024] [Accepted: 02/24/2025] [Indexed: 03/23/2025] Open
Abstract
Background Ascorbic acid is a strong antioxidant that prevents postoperative delirium by inhibiting reactive oxygen species production. This pilot study was designed to investigate the prevalence of postoperative delirium among older patients undergoing cardiovascular surgery, who received perioperative ascorbic acid administration, to estimate an appropriate sample size for further randomized controlled trials. Methods This single-arm prospective interventional study enrolled patients aged > 70 years scheduled to undergo elective cardiovascular surgery using cardiopulmonary bypass. Ascorbic acid (500 mg) was administered intravenously every 6 h for a total of eight times following the induction of general anesthesia. The incidence of postoperative delirium was evaluated until discharge using the Confusion Assessment Method for the Intensive Care Unit. Results Data from 48 patients were analyzed. Of the 48 patients, 16 developed postoperative delirium (33.3%). Patients in the delirium group had more severe heart failure (New York Heart Association Classification), higher European System for Cardiac Operative Risk Evaluation scores, lower intraoperative Bispectral Index, longer duration of cardiopulmonary bypass and surgery, incidence of postoperative cerebral infarction, longer intubation time, and length of intensive care unit stay. Conclusions The incidence of postoperative delirium among older patients undergoing cardiovascular surgery who received ascorbic acid perioperatively (2 g/day for 2 days) was 33%. This incidence was comparable to that observed in a previous observational study, suggesting that ascorbic acid administration may not be effective in preventing the incidence of postoperative delirium.
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Affiliation(s)
- Yusuke Iizuka
- Department of Anesthesiology and Critical Care Medicine, Saitama Medical Center, Jichi Medical University, Saitama City, Saitama 330-8503, Japan
| | - Kentaro Fukano
- Department of Anesthesiology and Critical Care Medicine, Saitama Medical Center, Jichi Medical University, Saitama City, Saitama 330-8503, Japan
| | - Sayaka Oki
- Department of Anesthesiology and Critical Care Medicine, Saitama Medical Center, Jichi Medical University, Saitama City, Saitama 330-8503, Japan
| | - Ikumi Sawada
- Department of Anesthesiology and Critical Care Medicine, Saitama Medical Center, Jichi Medical University, Saitama City, Saitama 330-8503, Japan
| | - Keika Miyazawa
- Department of Anesthesiology and Critical Care Medicine, Saitama Medical Center, Jichi Medical University, Saitama City, Saitama 330-8503, Japan
| | - Shohei Ono
- Department of Anesthesiology and Critical Care Medicine, Saitama Medical Center, Jichi Medical University, Saitama City, Saitama 330-8503, Japan
| | - Koichi Yoshinaga
- Department of Anesthesiology and Critical Care Medicine, Jichi Medical University, Shimotsuke City, Tochigi, Japan
| | - Masamitsu Sanui
- Department of Anesthesiology and Critical Care Medicine, Jichi Medical University, Shimotsuke City, Tochigi, Japan
| | - Atsushi Yamaguchi
- Department of Cardiovascular Surgery, Saitama Medical Center, Jichi Medical University, Saitama City, Saitama, Japan
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Raman S, Gibbons KS, Jayashree M, Lalitha AV, Bellomo R, Blythe R, Buckley D, Butt W, Cho HJ, Cree M, de Souza DC, Erickson S, Festa M, Ganu S, George S, James EJ, Johnson K, Le Marsney R, Lister P, Pham TMT, Singh P, Venkatesh B, Wall R, Long DA, Schlapbach LJ. Resuscitation in Paediatric Septic Shock Using Vitamin C and Hydrocortisone (RESPOND): The RESPOND Randomized Controlled Trial Protocol. Pediatr Crit Care Med 2025; 26:e374-e385. [PMID: 39724024 PMCID: PMC11878590 DOI: 10.1097/pcc.0000000000003674] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2024]
Abstract
OBJECTIVES Pediatric sepsis results in significant morbidity and mortality worldwide. There is an urgent need to investigate adjunctive therapies that can be administered early. We hypothesize that using vitamin C combined with hydrocortisone increases survival free of inotropes/vasopressors support until day 7 compared with standard care. Here we describe the Resuscitation in Paediatric Septic Shock using Vitamin C and Hydrocortisone (RESPOND) trial protocol, which aims to address this hypothesis. DESIGN Randomized, open label, controlled, parallel-group, three-arm trial with integrated economic evaluation. SETTING Nine Australia and New Zealand PICUs, with interest from additional international sites. PATIENTS Children between 7 days and younger than 18 years old who are treated for suspected or confirmed sepsis and receiving inotropes/vasopressors for greater than 1 hour. INTERVENTIONS IV vitamin C (100 mg/kg [maximum 5 g] every 6 hr) and hydrocortisone (1 mg/kg [maximum 50 mg] every 6 hr), or IV hydrocortisone alone (1 mg/kg [maximum 50 mg] every 6 hr) or standard care. MEASUREMENTS AND MAIN RESULTS Three hundred eighty-four children will be randomly assigned to receive the interventions, or standard care in a 1:1:1 ratio with stratification by steroid administration pre-randomization and hospital site. The primary outcome is time alive and free of inotropes/vasopressors, censored at 7 days. Secondary outcomes include 28-day mortality, survival free of organ support, PICU length of stay, quality of life, functional status and neurodevelopmental vulnerability at 6 months post-enrollment, and hospitalization-related costs. Statistical analysis will be based on an intention-to-treat principle. The study has ethical approval (HREC/20/QCHQ/69922, dated December 21, 2020), is registered in the Australian New Zealand Clinical Trials Registry (ACTRN12621000247875), commenced recruitment on December 8, 2021, and is expected to finish recruitment by mid-2026. CONCLUSIONS Dissemination of the results will occur through publication in peer-reviewed journals, presentations at international conferences, and additional consumer-informed pathways.
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Affiliation(s)
- Sainath Raman
- Children’s Intensive Care Research Program, Child Health Research Centre, Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia
- Paediatric Intensive Care Unit, Queensland Children’s Hospital, South Brisbane, QLD, Australia
| | - Kristen S. Gibbons
- Children’s Intensive Care Research Program, Child Health Research Centre, Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia
| | - Muralidharan Jayashree
- Pediatric Critical Care Unit, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - AV Lalitha
- Paediatric Intensive Care Unit, St. John’s Medical College, Bangalore, India
| | - Rinaldo Bellomo
- Austin Health, Melbourne, VIC, Australia
- Intensive Care Unit, The Royal Melbourne Hospital, Parkville, VIC, Australia
- Department of Critical Care, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Parkville, VIC, Australia
- Australian and New Zealand Intensive Care Research Centre, Monash University, Melbourne, VIC, Australia
| | - Robin Blythe
- Centre for Healthcare Transformation, Queensland University of Technology, Brisbane, QLD, Australia
| | - David Buckley
- Paediatric Intensive Care Unit, Starship Children’s Hospital, Auckland, New Zealand
| | - Warwick Butt
- Paediatric Intensive Care Unit, The Royal Children’s Hospital, Melbourne, VIC, Australia
| | - Hwa Jin Cho
- Paediatric Intensive Care Unit, Department of Pediatrics, Chonnam National University Children’s Hospital and Medical school, Gwangju, Korea
| | - Michele Cree
- Department of Pharmacy, Queensland Children’s Hospital, South Brisbane, QLD, Australia
- Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia
| | - Daniela C. de Souza
- Paediatric Intensive Care Unit, Hospital Universitário da Universidade de São Paulo, Sao Paolo, Brazil
| | - Simon Erickson
- Paediatric Intensive Care Unit, Perth Children’s Hospital, Perth, WA, Australia
| | - Marino Festa
- Kids Critical Care Research, Paediatric Intensive Care Unit, Westmead Children’s Hospital, Sydney, NSW, Australia
| | - Subodh Ganu
- Paediatric Intensive Care Unit, Women’s and Children’s Hospital, Adelaide, SA, Australia
| | - Shane George
- Paediatric Critical Care Unit, Gold Coast University Hospital, Gold Coast, QLD, Australia
| | - Ebor Jacob James
- Paediatric Intensive Care Unit, Christian Medical College (CMC), Vellore, India
| | - Kerry Johnson
- Paediatric Intensive Care Unit, Queensland Children’s Hospital, South Brisbane, QLD, Australia
| | - Renate Le Marsney
- Children’s Intensive Care Research Program, Child Health Research Centre, Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia
| | - Paula Lister
- Children’s Intensive Care Research Program, Child Health Research Centre, Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia
- Paediatric Critical Care Unit, Sunshine Coast University Hospital, Sunshine Coast, QLD, Australia
- School of Medicine and Dentistry, Griffith University, Southport, QLD, Australia
| | - Trang M. T. Pham
- Children’s Intensive Care Research Program, Child Health Research Centre, Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia
| | - Puneet Singh
- Paediatric Intensive Care Unit, Sydney Children’s Hospital, Randwick, NSW, Australia
| | - Balasubramanian Venkatesh
- Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia
- The George Institute for Global Health, University of New South Wales, Sydney, NSW, Australia
| | - Renee Wall
- Consumer Representative, Brisbane, QLD, Australia
| | - Debbie A. Long
- Paediatric Intensive Care Unit, Queensland Children’s Hospital, South Brisbane, QLD, Australia
- Centre for Healthcare Transformation, Queensland University of Technology, Brisbane, QLD, Australia
| | - Luregn J. Schlapbach
- Children’s Intensive Care Research Program, Child Health Research Centre, Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia
- Department of Intensive Care and Neonatology, and Children’s Research Center, University Children’s Hospital Zurich, University of Zurich, Zurich, Switzerland
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Sikaria S, Celshia S, Selvamani M, Suresh V, Hussein MA. Electrochemical Detection of Ascorbic Acid by Fe₂O₃ Nanoparticles Modified Glassy Carbon Electrode. Cureus 2024; 16:e64688. [PMID: 39156467 PMCID: PMC11327173 DOI: 10.7759/cureus.64688] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2024] [Accepted: 07/16/2024] [Indexed: 08/20/2024] Open
Abstract
Background The article delineates a strategy for detecting ascorbic acid (AA) through the use of iron oxide (Fe₂O₃) nanoparticles on an electrode. The Fe₂O₃ nanoparticles demonstrated effective electrocatalysis in the oxidation of AA, resulting in increased peak currents. The sensor showcased a wide linear detection range, a low detection limit, and high selectivity towards interferents, making it suitable for accurate AA measurement in food analysis and medical diagnostics applications. This emphasizes the potential of Fe₂O₃ nanoparticle-based sensors for precise AA detection. Aim The primary aim of this research is to develop an electrochemical sensing technique for the identification of ascorbic acid, with the use of Fe₂O₃ nanoparticles as the sensing matrix. Materials and methods The synthesis process involved the utilization of FeCl3.6H2O, ammonia solution, ethanol, and double-distilled water. FeCl3.6H2O was dissolved in ammonia water to produce a brown precipitate for the synthesis of Fe₂O₃ nanoparticles. Subsequently, the brown precipitate underwent hydrothermal treatment at 180 °C, resulting in the formation of a red product. Following centrifugation, washing, and drying steps, Fe₂O₃ nanoparticles were successfully synthesized. These nanoparticles were then utilized to modify the glassy carbon electrode (GCE). Prior to the modification, the GCE underwent polishing and cleaning procedures, after which it was coated with a suspension containing 5 mg of Fe₂O₃ nanoparticles in 10 mL of ethanol. The coated electrode was dried and deemed ready for application in electrochemical sensing. Results The hydrothermal method was employed in this research to synthesize Fe₂O₃ nanoparticles, which were subsequently subjected to a series of experiments to evaluate their electrochemical sensing capabilities. The resulting Fe₂O₃ nanoparticles were determined to possess a high level of purity and a crystalline structure through various analyses, including field emission-scanning electron microscopy (FE-SEM), cyclic voltammetric testing, X-ray diffraction (XRD), energy-dispersive X-ray (EDX) spectroscopy analysis, differential pulse voltammetry (DPV), and the current response of the Fe₂O₃-modified electrode towards ascorbic acid. The morphology of the Fe₂O₃ nanoparticles was observed to be uniform. The synthesized particles successfully fulfilled the study's objective by exhibiting remarkably sensitive and selective sensitivity towards ascorbic acid. Conclusion Our study underscores the potential of utilizing Fe₂O₃ nanoparticle-based electrochemical sensing to detect ascorbic acid, as evidenced by the notably high sensitivity of ascorbic acid towards Fe₂O₃ nanoparticles. The distinctive properties of Fe₂O₃ nanoparticles, which include their large surface area, efficient electron transport, and straightforward manufacturing process, significantly enhance the sensor's performance. Further research is crucial to exploring the wide-ranging applications of the sensor in fields such as food safety, environmental monitoring, and biological diagnostics and to overcome any existing limitations.
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Affiliation(s)
- Sakshi Sikaria
- Department of Physiology, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Science, Saveetha University, Chennai, IND
| | - Sherin Celshia
- Department of Physiology, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Science, Saveetha University, Chennai, IND
| | - Muthamizh Selvamani
- Department of Physiology, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Science, Saveetha University, Chennai, IND
| | - Vasugi Suresh
- Department of Physiology, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Science, Saveetha University, Chennai, IND
| | - Mohammed Asif Hussein
- Department of Physiology, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Science, Saveetha University, Chennai, IND
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Rastegar-Moghaddam SH, Amirahmadi S, Akbarian M, Sharizina M, Beheshti F, Rajabian A, Eshaghi Ghalibaf MH, Azimi M, Mahmoudabady M, Hosseini M. Cardioprotective effect of cedrol in an inflammation systemic model induced by lipopolysaccharide: Biochemical and histological verification. J Cardiovasc Thorac Res 2024; 16:120-128. [PMID: 39253340 PMCID: PMC11380743 DOI: 10.34172/jcvtr.33112] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2024] [Accepted: 06/03/2024] [Indexed: 09/11/2024] Open
Abstract
INTRODUCTION Evidence declared lipopolysaccharide (LPS) initiates inflammatory responses by stimulating the abandon of cytokines, which may perturb organ function. On the other side, it has been suggested Cedrol has potential properties, including anti-inflammatory and anti-oxidative activities. Herein, this study was done to assess the protective effect of Cedrol against LPS-associated heart damage. METHODS Thirty-five rats (200-250 g) were sorted into five groups, including control, LPS, LPS-Cedrol 7.5 mg/kg, LPS-Cedrol 15 mg/kg, and LPS-Cedrol 30 mg/kg groups. Cedrol was administrated through injected intra-peritoneally for two weeks. The heart tissues were removed and malondialdehyde (MDA) as a lipid peroxidation marker, superoxide dismutase (SOD), and catalase (CAT) as antioxidant markers were assessed. Furthermore, the interleukin (IL)-6 level in cardiac tissue was measured and Masson's trichrome methods were employed to appraise cardiac inflammation and fibrosis, respectively. RESULTS Inflammation induced by LPS was significantly accompanied by myocardial fibrosis which was shown by Masson's trichrome staining (P<0.001). In addition, LPS administration enhanced the MDA level while it diminished the activity of anti-oxidant markers such as CAT and SOD (P<0.001 for all cases). In the histological results, Cedrol improved LPS-induced inflammation and cardiac fibrosis (P<0.01 to P<0.001). Cedrol also enhanced CAT and SOD activities, whereas declined MDA level in the cardiac tissue (P<0.01 to P<0.001). CONCLUSION The current findings proposed that the administration of Cedrol exerted a protective role in LPS-associated heart damage by reducing inflammation, cardiac fibrosis, and oxidative stress.
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Affiliation(s)
| | - Sabiheh Amirahmadi
- Psychiatry and Behavioral Sciences Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mahsan Akbarian
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Matin Sharizina
- Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Farimah Beheshti
- Neuroscience Research Center, Torbat Heydariyeh University of Medical Sciences, Torbat Heydariyeh, Iran
- Department of Physiology, School of Medicine, Torbat Heydariyeh University of Medical Sciences, Torbat Heydariyeh, Iran
| | - Arezoo Rajabian
- Neuroscience Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | | | - Mohaddeseh Azimi
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Maryam Mahmoudabady
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Neuroscience Research Center, Torbat Heydariyeh University of Medical Sciences, Torbat Heydariyeh, Iran
| | - Mahmoud Hosseini
- Psychiatry and Behavioral Sciences Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Neuroscience Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
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Cui YN, Tian N, Luo YH, Zhao JJ, Bi CF, Gou Y, Liu J, Feng K, Zhang JF. High-dose Vitamin C injection ameliorates against sepsis-induced myocardial injury by anti-apoptosis, anti-inflammatory and pro-autophagy through regulating MAPK, NF-κB and PI3K/AKT/mTOR signaling pathways in rats. Aging (Albany NY) 2024; 16:6937-6953. [PMID: 38643461 PMCID: PMC11087106 DOI: 10.18632/aging.205735] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2023] [Accepted: 03/13/2024] [Indexed: 04/22/2024]
Abstract
AIMS This study aimed to evaluate the effects of VC on SIMI in rats. METHODS In this study, the survival rate of high dose VC for SIMI was evaluated within 7 days. Rats were randomly assigned to three groups: Sham group, CLP group, and high dose VC (500 mg/kg i.v.) group. The animals in each group were treated with drugs for 1 day, 3 days or 5 days, respectively. Echocardiography, myocardial enzymes and HE were used to detect cardiac function. IL-1β, IL-6, IL-10 and TNF-α) in serum were measured using ELISA kits. Western blot was used to detect proteins related to apoptosis, inflammation, autophagy, MAPK, NF-κB and PI3K/Akt/mTOR signaling pathways. RESULTS High dose VC improved the survival rate of SIMI within 7 days. Echocardiography, HE staining and myocardial enzymes showed that high-dose VC relieved SIMI in rats in a time-dependent manner. And compared with CLP group, high-dose VC decreased the expressions of pro-apoptotic proteins, while increased the expression of anti-apoptotic protein. And compared with CLP group, high dose VC decreased phosphorylation levels of Erk1/2, P38, JNK, NF-κB and IKK α/β in SIMI rats. High dose VC increased the expression of the protein Beclin-1 and LC3-II/LC3-I ratio, whereas decreased the expression of P62 in SIMI rats. Finally, high dose VC attenuated phosphorylation of PI3K, AKT and mTOR compared with the CLP group. SIGNIFICANCE Our results showed that high dose VC has a good protective effect on SIMI after continuous treatment, which may be mediated by inhibiting apoptosis and inflammatory, and promoting autophagy through regulating MAPK, NF-κB and PI3K/AKT/mTOR pathway.
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Affiliation(s)
- Ya-Nan Cui
- Medical Records and Statistics Room, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750000, China
| | - Na Tian
- Department of Emergency Medical, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750000, China
- School of Clinical Medicine, Ningxia Medical University, Yinchuan, Ningxia 750000, China
| | - Yan-Hai Luo
- Department of Pathology, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750000, China
| | - Ji-Jun Zhao
- Department of Emergency Medical, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750000, China
| | - Cheng-Fei Bi
- Department of Emergency Medical, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750000, China
- School of Clinical Medicine, Ningxia Medical University, Yinchuan, Ningxia 750000, China
| | - Yi Gou
- Department of Emergency Medical, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750000, China
- School of Clinical Medicine, Ningxia Medical University, Yinchuan, Ningxia 750000, China
| | - Jia Liu
- Department of Emergency Medical, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750000, China
| | - Ke Feng
- Department of Emergency Medical, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750000, China
| | - Jun-Fei Zhang
- Department of Emergency Medical, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750000, China
- School of Clinical Medicine, Ningxia Medical University, Yinchuan, Ningxia 750000, China
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Yong S, Suping L, Peng Z, Dong L, Qing W. The effects of vitamin C supplementation in the critically ill patients outcomes: A systematic review and meta-analysis of randomized controlled trials. Medicine (Baltimore) 2024; 103:e37420. [PMID: 38518058 PMCID: PMC10956978 DOI: 10.1097/md.0000000000037420] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2023] [Accepted: 02/07/2024] [Indexed: 03/24/2024] Open
Abstract
BACKGROUND Vitamin C has significant anti-inflammatory effects and is particularly important for critically ill patients. However due to inconsistent research findings in critically ill patients in meta-analysis. Therefore, the primary objective of this meta-analysis is to investigate the effects of isolated intravenous supplementation of vitamin C in adults with critical illness by comprehensively incorporating articles from randomized controlled trials. METHODS Articles included searching through PubMed, Embase, Medline, Cochrane Library, and Web of Science up to April 28, 2023, for articles on vitamin C and the critically ill. We calculated pooled standard relative risk (RR), mean difference (MD), and 95% confidence intervals (CIs). And the protocol for the review has been registered on PROSPERO (CRD42023425193). RESULTS There are 2047 critically ill included in 19 articles. Compared with placebo, patients who underwent intravenous vitamin C (IVVC) have reduced duration of vasopressor used (SMD 0.26; CI 0.01-0.51; I2 = 87.0%, P = .044), mechanical ventilation (SMD -0.29; CI -0.55 to -0.03; I2 = 36.8%, P = .031). However, the administration of IVVC had no statistical difference in 28-d mortality (RR 0.95; CI 0.80-1.11; I2 = 12.2%, P = .337), mortality (RR 0.79; CI 0.55-1.12; I2 = 0%, P = .188), fluid intake (SMD -0.02; CI -0.25 to 0.20; I2 = 0%, P = .838), urine output (SMD 0.23; CI -0.03 to 0.49; I2 = 0%, P = .084), ICU days (SMD 0.10; CI -0.03 to 0.22; I2 = 0%, P = .127), hospital stay (SMD 0.10; CI -0.12 to 0.32; I2 = 0%, P = .375), and pneumonia (RR 0.85; CI 0.50-1.44; I2 = 0%, P = .552). CONCLUSION This study comprehensively and systematically evaluated IVVC supplementation in the critically ill through a meta-analysis of RCT. There is no difference except for patients who had reduced duration of vasopressor use and mechanical ventilation by the administration of IVVC. Of course. More scientific and rigorous conclusions can be drawn from multi-center RCT research in the future.
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Affiliation(s)
- Su Yong
- Intensive Care Unit, Pengzhou People’s Hospital, Pengzhou City, Chengdu, Sichuan, China
| | - Liu Suping
- Intensive Care Unit, Pengzhou People’s Hospital, Pengzhou City, Chengdu, Sichuan, China
| | - Zhang Peng
- Department of Gastrointestinal Surgery, Pengzhou People’s Hospital, Pengzhou City, Chengdu, Sichuan, China
| | - Lin Dong
- Department of Urology, Pengzhou People’s Hospital, Pengzhou City, Chengdu, Sichuan, China
| | - Wei Qing
- Intensive Care Unit, Pengzhou People’s Hospital, Pengzhou City, Chengdu, Sichuan, China
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Sahoo DK, Wong D, Patani A, Paital B, Yadav VK, Patel A, Jergens AE. Exploring the role of antioxidants in sepsis-associated oxidative stress: a comprehensive review. Front Cell Infect Microbiol 2024; 14:1348713. [PMID: 38510969 PMCID: PMC10952105 DOI: 10.3389/fcimb.2024.1348713] [Citation(s) in RCA: 21] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2023] [Accepted: 02/15/2024] [Indexed: 03/22/2024] Open
Abstract
Sepsis is a potentially fatal condition characterized by organ dysfunction caused by an imbalanced immune response to infection. Although an increased inflammatory response significantly contributes to the pathogenesis of sepsis, several molecular mechanisms underlying the progression of sepsis are associated with increased cellular reactive oxygen species (ROS) generation and exhausted antioxidant pathways. This review article provides a comprehensive overview of the involvement of ROS in the pathophysiology of sepsis and the potential application of antioxidants with antimicrobial properties as an adjunct to primary therapies (fluid and antibiotic therapies) against sepsis. This article delves into the advantages and disadvantages associated with the utilization of antioxidants in the therapeutic approach to sepsis, which has been explored in a variety of animal models and clinical trials. While the application of antioxidants has been suggested as a potential therapy to suppress the immune response in cases where an intensified inflammatory reaction occurs, the use of multiple antioxidant agents can be beneficial as they can act additively or synergistically on different pathways, thereby enhancing the antioxidant defense. Furthermore, the utilization of immunoadjuvant therapy, specifically in septic patients displaying immunosuppressive tendencies, represents a promising advancement in sepsis therapy.
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Affiliation(s)
- Dipak Kumar Sahoo
- Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA, United States
| | - David Wong
- Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA, United States
| | - Anil Patani
- Department of Biotechnology, Smt. S. S. Patel Nootan Science and Commerce College, Sankalchand Patel University, Gujarat, India
| | - Biswaranjan Paital
- Redox Regulation Laboratory, Department of Zoology, College of Basic Science and Humanities, Odisha University of Agriculture and Technology, Bhubaneswar, India
| | - Virendra Kumar Yadav
- Department of Life Sciences, Hemchandracharya North Gujarat University, Gujarat, India
| | - Ashish Patel
- Department of Life Sciences, Hemchandracharya North Gujarat University, Gujarat, India
| | - Albert E. Jergens
- Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA, United States
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9
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Xia X, Chen K, Chen Y. Change in function and homeostasis of HPA axis: The role of vitamin family. Chem Biol Interact 2024; 391:110899. [PMID: 38325521 DOI: 10.1016/j.cbi.2024.110899] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2023] [Revised: 01/24/2024] [Accepted: 02/04/2024] [Indexed: 02/09/2024]
Abstract
With the improvement of living quality, people pay more and more attention to vitamin supplements. The vitamins in the daily diet can meet the needs of the body. Whether additional vitamin supplementation is necessary still needs to be further explored. Many studies have reported that vitamin deficiency and excessive vitamin supplementation could lead to abnormal development in the body or increase the risk of diseases. Here, we summarize the abnormal levels of vitamins can cause the homeostasis imbalance of hypothalamus-pituitary-adrenal (HPA) axis by affecting its development and function. It can lead to abnormal synthesis and secretion of glucocorticoid in the body, which mediates the occurrence and development of metabolic diseases and psychoneurotic diseases. In addition, vitamin has a strong antioxidant effect, which can eliminate oxygen free radicals. Thereby, vitamins can alter HPA axis function and homeostasis maintenance by combating oxidative stress. This review provides a theoretical basis for clarifying the role of abnormal levels of vitamin in the occurrence and development of multiple diseases and its intervention strategy, and also provides reference value and guiding significance for rational use of vitamins.
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Affiliation(s)
- Xuan Xia
- Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Kaiqi Chen
- Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Yawen Chen
- Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
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10
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Berlin N, Pfaff A, Rozanski EA, Chalifoux NV, Hess RS, Donnino MW, Silverstein DC. Establishment of a reference interval for thiamine concentrations in healthy dogs and evaluation of the prevalence of absolute thiamine deficiency in critically ill dogs with and without sepsis using high-performance liquid chromatography. J Vet Emerg Crit Care (San Antonio) 2024; 34:49-56. [PMID: 37987121 PMCID: PMC11007751 DOI: 10.1111/vec.13341] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2022] [Revised: 07/11/2022] [Accepted: 07/29/2022] [Indexed: 11/22/2023]
Abstract
OBJECTIVE To determine the normal reference interval (RI) for thiamine concentrations in healthy dogs and investigate the prevalence of thiamine deficiency in critically ill dogs with and without sepsis. DESIGN Prospective, observational, multicenter study, conducted between 2019 and 2021. SETTING Two veterinary university teaching hospitals. ANIMALS A total of 109 dogs were enrolled into 3 groups: 40 healthy dogs, 33 dogs with suspected or confirmed sepsis and evidence of tissue hypoperfusion (Doppler blood pressure ≤90 mm Hg or plasma lactate ≥3 mmol/L), and 36 dogs with other critical illnesses and evidence of tissue hypoperfusion. INTERVENTIONS For each dog, CBC, serum biochemistry, plasma lactate concentration, whole-blood thiamine concentration, blood pressure, vital parameters, Acute Patient Physiologic and Laboratory Evaluation (APPLE)fast score, and clinical outcomes were recorded, alongside basic patient parameters and dietary history. Whole-blood thiamine pyrophosphate (TPP) concentrations were measured using high-performance liquid chromatography. MEASUREMENTS AND MAIN RESULTS The RI for whole-blood TPP in healthy dogs was 70.9-135.3 μg/L. Median TPP concentrations were significantly lower in septic dogs compared to healthy controls (P = 0.036). No significant difference in median TPP concentrations was found between septic dogs and nonseptic critically ill dogs, or between healthy dogs and nonseptic critically ill dogs. TPP concentrations were below the normal RI in 27.3% of septic dogs, compared to 19.4% of nonseptic critically ill dogs (P = 0.57). No correlations were found between TPP concentrations and lactate concentrations, age, body condition scores, time since last meal, RBC count, serum alanine aminotransferase, APPLEfast scores, or patient outcomes. CONCLUSIONS TPP concentrations were significantly lower in septic dogs compared to healthy controls, with an absolute thiamine deficiency found in 27.3% of septic dogs. The established TPP RI allows for further investigation of thiamine deficiency in critically ill dogs.
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Affiliation(s)
- Noa Berlin
- Foster Hospital for Small Animals, Cummings School of Veterinary Medicine at Tufts University, North Grafton, MA, USA
- Center for Resuscitation Science, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Alexandra Pfaff
- Foster Hospital for Small Animals, Cummings School of Veterinary Medicine at Tufts University, North Grafton, MA, USA
| | - Elizabeth A Rozanski
- Foster Hospital for Small Animals, Cummings School of Veterinary Medicine at Tufts University, North Grafton, MA, USA
| | - Nolan V Chalifoux
- Matthew J Ryan Veterinary Hospital of the University of Pennsylvania, Philadelphia, PA, USA
| | - Rebecka S Hess
- Matthew J Ryan Veterinary Hospital of the University of Pennsylvania, Philadelphia, PA, USA
| | - Michael W Donnino
- Center for Resuscitation Science, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Deborah C Silverstein
- Matthew J Ryan Veterinary Hospital of the University of Pennsylvania, Philadelphia, PA, USA
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11
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Sun Y, Yang Y, Ye Z, Sun T. HAT therapy for sepsis: A review of the therapeutic rationale and current clinical evaluation status. JOURNAL OF INTENSIVE MEDICINE 2023; 3:320-325. [PMID: 38028642 PMCID: PMC10658041 DOI: 10.1016/j.jointm.2023.04.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/16/2022] [Revised: 04/03/2023] [Accepted: 04/20/2023] [Indexed: 12/01/2023]
Abstract
Vitamin C-based cluster therapy, which involves the combined application of hydrocortisone, vitamin C, and thiamine (HAT), is a recently proposed new treatment option for sepsis on top of conventional treatment. This therapy has a strong theoretical basis, but its clinical efficacy remains inconclusive. This review summarizes the rationale for HAT therapy for sepsis and describes the evaluation of its efficacy in clinical observational studies and randomized controlled trials, with the aim of providing a reference for the future clinical practice application of HAT therapy in sepsis.
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Affiliation(s)
- Yali Sun
- Department of General ICU, The First Affiliated Hospital of Zhengzhou University, Henan Key Laboratory of Critical Care Medicine, Zhengzhou Key Laboratory of Sepsis, Zhengzhou 450052, Henan, China
- Henan Engineering Research Center for Critical Care Medicine, Department of General ICU, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China
| | - Yongfang Yang
- Henan Engineering Research Center for Critical Care Medicine, Department of General ICU, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China
| | - Zhuoyi Ye
- Henan Engineering Research Center for Critical Care Medicine, Department of General ICU, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China
| | - Tongwen Sun
- Department of General ICU, The First Affiliated Hospital of Zhengzhou University, Henan Key Laboratory of Critical Care Medicine, Zhengzhou Key Laboratory of Sepsis, Zhengzhou 450052, Henan, China
- Henan Engineering Research Center for Critical Care Medicine, Department of General ICU, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China
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12
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Yanase F, Spano S, Maeda A, Chaba A, Naorungroj T, Ow CPC, Lankadeva YR, May CN, Betrie AH, Lane DJR, Eastwood GM, Plummer MP, Bellomo R. Mega-dose sodium ascorbate: a pilot, single-dose, physiological effect, double-blind, randomized, controlled trial. Crit Care 2023; 27:371. [PMID: 37828547 PMCID: PMC10571252 DOI: 10.1186/s13054-023-04644-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2023] [Accepted: 09/09/2023] [Indexed: 10/14/2023] Open
Abstract
BACKGROUND Mega-dose sodium ascorbate (NaAscorbate) appears beneficial in experimental sepsis. However, its physiological effects in patients with septic shock are unknown. METHODS We conducted a pilot, single-dose, double-blind, randomized controlled trial. We enrolled patients with septic shock within 24 h of diagnosis. We randomly assigned them to receive a single mega-dose of NaAscorbate (30 g over 1 h followed by 30 g over 5 h) or placebo (vehicle). The primary outcome was the total 24 h urine output (UO) from the beginning of the study treatment. Secondary outcomes included the time course of the progressive cumulative UO, vasopressor dose, and sequential organ failure assessment (SOFA) score. RESULTS We enrolled 30 patients (15 patients in each arm). The mean (95% confidence interval) total 24-h UO was 2056 (1520-2593) ml with placebo and 2948 (2181-3715) ml with NaAscorbate (mean difference 891.5, 95% confidence interval [- 2.1 to 1785.2], P = 0.051). Moreover, the progressive cumulative UO was greater over time on linear mixed modelling with NaAscorbate (P < 0.001). Vasopressor dose and SOFA score changes over time showed faster reductions with NaAscorbate (P < 0.001 and P = 0.042). The sodium level, however, increased more over time with NaAscorbate (P < 0.001). There was no statistical difference in other clinical outcomes. CONCLUSION In patients with septic shock, mega-dose NaAscorbate did not significantly increase cumulative 24-h UO. However, it induced a significantly greater increase in UO and a greater reduction in vasopressor dose and SOFA score over time. One episode of hypernatremia and one of hemolysis were observed in the NaAscorbate group. These findings support further cautious investigation of this novel intervention. Trial registration Australian New Zealand Clinical Trial Registry (ACTRN12620000651987), Date registered June/5/2020.
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Affiliation(s)
- Fumitaka Yanase
- Department of Intensive Care, Austin Hospital, Melbourne, VIC, Australia
- Australian and New Zealand Intensive Care Research Centre (ANZIC-RC), School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia
| | - Sofia Spano
- Department of Intensive Care, Austin Hospital, Melbourne, VIC, Australia
| | - Akinori Maeda
- Department of Intensive Care, Austin Hospital, Melbourne, VIC, Australia
| | - Anis Chaba
- Department of Intensive Care, Austin Hospital, Melbourne, VIC, Australia
| | | | - Connie Pei Chen Ow
- The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Melbourne, VIC, Australia
| | - Yugeesh R Lankadeva
- The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Melbourne, VIC, Australia
- Department of Critical Care, University of Melbourne, Melbourne, Australia
| | - Clive N May
- The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Melbourne, VIC, Australia
- Department of Critical Care, University of Melbourne, Melbourne, Australia
| | - Ashenafi H Betrie
- The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Melbourne, VIC, Australia
| | - Darius J R Lane
- The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Melbourne, VIC, Australia
| | - Glenn M Eastwood
- Department of Intensive Care, Austin Hospital, Melbourne, VIC, Australia
- Australian and New Zealand Intensive Care Research Centre (ANZIC-RC), School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia
| | - Mark P Plummer
- Department of Intensive Care, Royal Adelaide Hospital, Adelaide, Australia
| | - Rinaldo Bellomo
- Department of Intensive Care, Austin Hospital, Melbourne, VIC, Australia.
- Australian and New Zealand Intensive Care Research Centre (ANZIC-RC), School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia.
- Department of Critical Care, University of Melbourne, Melbourne, Australia.
- Data Analytics Research and Evaluation Centre, Austin Hospital, Melbourne, Australia.
- Department of Intensive Care, Royal Melbourne Hospital, Melbourne, Australia.
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13
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Iizuka Y, Yoshinaga K, Takahashi K, Oki S, Chiba Y, Sanui M, Kimura N, Yamaguchi A. Association between Plasma Ascorbic Acid Levels and Postoperative Delirium in Older Patients Undergoing Cardiovascular Surgery: A Prospective Observational Study. J Cardiovasc Dev Dis 2023; 10:293. [PMID: 37504549 PMCID: PMC10380566 DOI: 10.3390/jcdd10070293] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2023] [Revised: 07/01/2023] [Accepted: 07/06/2023] [Indexed: 07/29/2023] Open
Abstract
BACKGROUND The incidence of delirium is high in older patients undergoing cardiovascular surgery with cardiopulmonary bypass (CPB). Intraoperative tissue hypoperfusion and re-reperfusion injury, which generate reactive oxygen species (ROS), are suggested to induce delirium. Ascorbic acid is an excellent antioxidant and may reduce organ damage by inhibiting the production of ROS. This prospective observational study aimed to measure pre- and postoperative plasma ascorbic acid levels and examine their association with delirium. METHODS Patients older than 70 years of age scheduled for elective cardiovascular surgery using CPB were enrolled. From September 2020 to December 2021, we enrolled 100 patients, and the data of 98 patients were analyzed. RESULTS In total, 31 patients developed delirium, while 67 did not. Preoperative plasma ascorbic acid levels did not differ between the non-delirium and delirium groups (6.0 ± 2.2 vs. 5.5 ± 2.4 µg/mL, p = 0.3). Postoperative plasma ascorbic acid levels were significantly different between the groups (2.8 [2.3-3.5] vs. 2.3 [1.6-3.3] µg/mL, p = 0.037). CONCLUSIONS In patients who undergo cardiovascular surgery with CPB, lower postoperative plasma ascorbic acid levels may be associated with the development of delirium.
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Affiliation(s)
- Yusuke Iizuka
- Department of Anesthesiology and Critical Care Medicine, Saitama Medical Center, Jichi Medical University, Saitama 330-8503, Japan
| | - Koichi Yoshinaga
- Department of Anesthesiology and Critical Care Medicine, Saitama Medical Center, Jichi Medical University, Saitama 330-8503, Japan
| | - Kyosuke Takahashi
- Department of Anesthesiology and Critical Care Medicine, Saitama Medical Center, Jichi Medical University, Saitama 330-8503, Japan
| | - Sayaka Oki
- Department of Anesthesiology and Critical Care Medicine, Saitama Medical Center, Jichi Medical University, Saitama 330-8503, Japan
| | - Yoshihiko Chiba
- Department of Anesthesiology and Critical Care Medicine, Saitama Medical Center, Jichi Medical University, Saitama 330-8503, Japan
| | - Masamitsu Sanui
- Department of Anesthesiology and Critical Care Medicine, Saitama Medical Center, Jichi Medical University, Saitama 330-8503, Japan
| | - Naoyuki Kimura
- Department of Cardiovascular Surgery, Saitama Medical Center, Jichi Medical University, Saitama 330-8503, Japan
| | - Atsushi Yamaguchi
- Department of Cardiovascular Surgery, Saitama Medical Center, Jichi Medical University, Saitama 330-8503, Japan
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14
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Suárez-de-la-Rica A, Croes B, Ciudad L, Vallejo I, Mújica J, Díaz-Almirón M, Maseda E. Vitamin C and thiamine for the treatment of refractory septic shock in surgical critically ill patients: a retrospective before-and-after study. REVISTA ESPANOLA DE QUIMIOTERAPIA : PUBLICACION OFICIAL DE LA SOCIEDAD ESPANOLA DE QUIMIOTERAPIA 2023; 36:187-192. [PMID: 36440551 PMCID: PMC10066916 DOI: 10.37201/req/107.2022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/25/2022] [Accepted: 11/02/2022] [Indexed: 11/29/2022]
Abstract
OBJECTIVE This study aimed to evaluate whether early vitamin C and thiamine administration was associated with a lower 28-day and in-hospital mortality in surgical critically ill patients with refractory septic shock. METHODS We performed a retrospective before-and-after study on patients with refractory septic shock. According to local protocol, hydrocortisone is initiated in case of refractory septic shock. In January 2017, the protocol was changed and vitamin C and thiamine were included. Patients who were admitted in 2015-2016 and 2017-2018 were included in the control and treatment groups, respectively. The primary end point was 28-day and in-hospital mortality. Secondary end points were ICU mortality, ICU and hospital length of stay, duration of vasopressors and mechanical ventilation, use of renal replacement therapy (RRT), and the modification in serum procalcitonin and SOFA score during the first 72 h. RESULTS A total of 120 patients were included (58 in the treatment group and 62 in the control group). Log-rank test in Kaplan-Meier curves showed lower 28-day and in-hospital mortality over time in the treatment group (p=0.021 and p=0.035, respectively) but it not reached statistical significance in ICU mortality over time (p=0.100). The need of RRT was less frequent in treatment group (17.2% vs. 37.1%, p=0.024). There were no differences in other secondary outcomes. CONCLUSIONS Intravenous vitamin C and thiamine administration in surgical patients with refractory septic shock may be associated with a lower 28-day and in-hospital mortality. Further prospective studies are needed in refractory septic shock.
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Affiliation(s)
| | | | | | | | | | | | - E Maseda
- Emilio Maseda, Department of Anesthesiology and Surgical Critical Care. Hospital Univer-sitario La Paz. Madrid. Spain.
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15
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Wang J, Song Q, Yang S, Wang H, Meng S, Huang L, Li Q, Xu J, Xie J, Huang Y. Effects of hydrocortisone combined with vitamin C and vitamin B1 versus hydrocortisone alone on microcirculation in septic shock patients: A pilot study. Clin Hemorheol Microcirc 2023:CH221444. [PMID: 36911931 PMCID: PMC10357145 DOI: 10.3233/ch-221444] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/12/2023]
Abstract
OBJECTIVE To investigate the effects of hydrocortisone combined with vitamin C and vitamin B1 versus hydrocortisone on sublingual microcirculation in septic shock patients. METHODS This pilot study enrolled septic shock patients admitted to the ICU of a tertiary teaching hospital from February 2019 to January 2020. We randomly assigned the enrolled patients to the treatment group (hydrocortisone combined with vitamin C and vitamin B1 added to standard care) and the control group (hydrocortisone alone added to standard care) in a 1 : 1 ratio. The primary outcome was perfused small vascular density (sPVD) monitored by a sublingual microcirculation imaging system at 24 hours after treatment. RESULTS Twelve patients in the treatment group and ten in the control group completed the study. The baseline characteristics were comparable between the groups. No statistically significant difference was found in the sPVD between the groups at baseline. The sPVD in the treatment group was significantly higher than that in the control group at 4 hours after treatment (mean difference, 7.042; 95% CI, 2.227-11.857; P = 0.009) and 24 hours after treatment (mean difference, 7.075; 95% CI, 2.390-11.759; P = 0.008). CONCLUSIONS Compared with hydrocortisone, hydrocortisone combined with vitamin C and vitamin B1 significantly improves microcirculation in septic shock patients.
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Affiliation(s)
- Jinlong Wang
- Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Qianwen Song
- Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Shuhe Yang
- Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Haofei Wang
- Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Shanshan Meng
- Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Lili Huang
- Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Qing Li
- Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Jingyuan Xu
- Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Jianfeng Xie
- Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Yingzi Huang
- Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
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16
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Olmsted A, DeSimone A, Lopez-Pastrana J, Becker M. Fetal demise and Wernicke-Korsakoff syndrome in a patient with hyperemesis gravidarum: a case report. J Med Case Rep 2023; 17:32. [PMID: 36726136 PMCID: PMC9893614 DOI: 10.1186/s13256-022-03748-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2022] [Accepted: 12/28/2022] [Indexed: 02/03/2023] Open
Abstract
BACKGROUND Wernicke-Korsakoff syndrome is a neuropsychiatric disorder caused by thiamine deficiency composed of two related disorders accounting for an acute presentation and chronic progression. Hyperemesis gravidarum presents a significant risk factor for Wernicke-Korsakoff syndrome as symptoms may rapidly progress in the setting of pregnancy. We present the first-reported case of hyperemesis-gravidarum-associated Wernicke encephalopathy in a patient in the first half of pregnancy in which a missed diagnosis led to septic shock, fetal demise, and eventual profound Korsakoff syndrome. CASE PRESENTATION We present the case of a 33-year-old primigravid African American woman at 15 weeks gestational age who initially presented at a community emergency department with nausea and vomiting that ultimately progressed to severe hyperemesis-gravidarum-associated Wernicke-Korsakoff syndrome, fetal demise, and septic shock. The patient received a total of 6 weeks of high-dose parenteral thiamine. Magnetic resonance imaging of the head and formal neuropsychological assessment following treatment plateau confirmed the diagnosis of Wernicke-Korsakoff syndrome. CONCLUSIONS The multisystem complications seen in severe thiamine deficiency can delay timely administration of high-dose thiamine, particularly in pregnancy, in which the classic triad of Wernicke-Korsakoff syndrome may not raise clinical suspicion due to rapid progression of neurological sequelae in this population. We advise a low threshold for parenteral thiamine repletion in pregnant women with persistent vomiting as hyperemesis gravidarum-induced severe thiamine deficiency can result in Wernicke-Korsakoff syndrome, sepsis, and fetal demise.
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Affiliation(s)
- Alisa Olmsted
- grid.412726.4Department of Psychiatry and Human Behavior, Thomas Jefferson University Hospital, Philadelphia, PA USA ,grid.280747.e0000 0004 0419 2556Present Address: Stanford University and the Sierra-Pacific Mental Illness Research, Education, and Clinical Center (MIRECC), VA Palo Alto Health Care System, Palo Alto, USA
| | - Andrea DeSimone
- Department of Psychiatry, Bayhealth Medical Center, Dover, DE USA
| | - Jahaira Lopez-Pastrana
- grid.412726.4Department of Psychiatry and Human Behavior, Thomas Jefferson University Hospital, Philadelphia, PA USA
| | - Madeleine Becker
- grid.412726.4Department of Psychiatry and Human Behavior, Thomas Jefferson University Hospital, Philadelphia, PA USA ,grid.412726.4Department of Integrative Medicine and Nutritional Sciences, Thomas Jefferson University Hospital, Philadelphia, USA
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17
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Dvořák Z, Li H, Mani S. Microbial Metabolites as Ligands to Xenobiotic Receptors: Chemical Mimicry as Potential Drugs of the Future. Drug Metab Dispos 2023; 51:219-227. [PMID: 36184080 PMCID: PMC9900867 DOI: 10.1124/dmd.122.000860] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2022] [Revised: 08/28/2022] [Accepted: 09/19/2022] [Indexed: 01/31/2023] Open
Abstract
Xenobiotic receptors, such as the pregnane X receptor, regulate multiple host physiologic pathways including xenobiotic metabolism, certain aspects of cellular metabolism, and innate immunity. These ligand-dependent nuclear factors regulate gene expression via genomic recognition of specific promoters and transcriptional activation of the gene. Natural or endogenous ligands are not commonly associated with this class of receptors; however, since these receptors are expressed in a cell-type specific manner in the liver and intestines, there has been significant recent effort to characterize microbially derived metabolites as ligands for these receptors. In general, these metabolites are thought to be weak micromolar affinity ligands. This journal anniversary minireview focuses on recent efforts to derive potentially nontoxic microbial metabolite chemical mimics that could one day be developed as drugs combating xenobiotic receptor-modifying pathophysiology. The review will include our perspective on the field and recommend certain directions for future research. SIGNIFICANCE STATEMENT: Xenobiotic receptors (XRs) regulate host drug metabolism, cellular metabolism, and immunity. Their presence in host intestines allows them to function not only as xenosensors but also as a response to the complex metabolic environment present in the intestines. Specifically, this review focuses on describing microbial metabolite-XR interactions and the translation of these findings toward discovery of novel chemical mimics as potential drugs of the future for diseases such as inflammatory bowel disease.
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Affiliation(s)
- Zdeněk Dvořák
- Department of Cell Biology and Genetics, Palacký University, Olomouc, Czech Republic (Z.D.); Departments of Medicine (H.L., S.M.), Molecular Pharmacology (S.M.), and Genetics (S.M.), Albert Einstein College of Medicine, Bronx, New York, USA
| | - Hao Li
- Department of Cell Biology and Genetics, Palacký University, Olomouc, Czech Republic (Z.D.); Departments of Medicine (H.L., S.M.), Molecular Pharmacology (S.M.), and Genetics (S.M.), Albert Einstein College of Medicine, Bronx, New York, USA
| | - Sridhar Mani
- Department of Cell Biology and Genetics, Palacký University, Olomouc, Czech Republic (Z.D.); Departments of Medicine (H.L., S.M.), Molecular Pharmacology (S.M.), and Genetics (S.M.), Albert Einstein College of Medicine, Bronx, New York, USA
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18
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Jeon G, Choi H, Park DJ, Nguyen NT, Kim YH, Min J. Melanin Treatment Effect of Vacuoles-Zinc Oxide Nanoparticles Combined with Ascorbic Acid. Mol Biotechnol 2022:10.1007/s12033-022-00608-8. [PMID: 36445610 PMCID: PMC9707414 DOI: 10.1007/s12033-022-00608-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2022] [Accepted: 11/07/2022] [Indexed: 11/30/2022]
Abstract
Currently, ascorbic acid (AA) is widely used as a skin whitening material, but, AA, an unstable hydrophilic molecule, cannot penetrate the skin easily, due to the hydrophobic character of the stratum corneum. Therefore, we conjugated AA with hydrated zinc oxide-an inorganic matrix with positive surface charge, to improve the stability of AA. The metal-conjugated-ascorbic acid (ZnAA) was then combined with yeast vacuole through the vacuolar membrane proteins that relate to metal transportation to create an enhanced vacuole that contained ZnAA. The characteristics of vacuole with ZnAA (ZnAA_Vac) were next examined by various tests that included X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), Field emission scanning electron microscopy (FE-SEM), and energy-dispersive X-ray (EDX) analysis. Furthermore, the ability of ZnAA_Vac to degrade melanin was confirmed in both melanoma cell line B16F10, and the artificial human skin MelanoDerm. The results showed that ZnAA_Vac possessed a higher depigmenting effect than the wild-type vacuole or ascorbic acid by reducing 75% of melanin color. Interestingly, ZnAA_Vac was found to be harmless, and did not cause any cytotoxicity to the cells. Overall, ZnAA_Vac is expected to provide a robust, harmless, and effective whitening agent for the skin.
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Affiliation(s)
- Gyeongchan Jeon
- Graduate School of Semiconductor and Chemical Engineering, Jeonbuk National University, 567 Baekje-Daero, Deokjin-Gu, Jeonju-Si, Jeollabuk-do 54896 Republic of Korea
| | - Hyojin Choi
- Graduate School of Semiconductor and Chemical Engineering, Jeonbuk National University, 567 Baekje-Daero, Deokjin-Gu, Jeonju-Si, Jeollabuk-do 54896 Republic of Korea
| | - Dong-Jun Park
- Department of Surgery, University of California, San Diego, USA
| | - Ngoc-Tu Nguyen
- Center for Ecology and Environmental Toxicology (CEET), Chungbuk National University, 1 Chungdae-Ro, Seowon-Gu, Cheongju, Chungbuk-Do 28644 South Korea
| | - Yang-Hoon Kim
- Center for Ecology and Environmental Toxicology (CEET), Chungbuk National University, 1 Chungdae-Ro, Seowon-Gu, Cheongju, Chungbuk-Do 28644 South Korea
- School of Biological Science, Chungbuk National University, Chungdae-Ro 1, Seowon-Gu, Cheongju, Chungbuk-do 28644 Republic of Korea
| | - Jiho Min
- Graduate School of Semiconductor and Chemical Engineering, Jeonbuk National University, 567 Baekje-Daero, Deokjin-Gu, Jeonju-Si, Jeollabuk-do 54896 Republic of Korea
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Chen CY, Chiu CT, Lee HS, Lai CC. The impact of vitamin C-containing treatment on the mortality of patients with sepsis: a systematic review and meta-analysis of randomized controlled trials. J Infect Public Health 2022; 15:1514-1520. [DOI: 10.1016/j.jiph.2022.11.015] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2022] [Revised: 10/22/2022] [Accepted: 11/13/2022] [Indexed: 11/18/2022] Open
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Plotkin LL, Artamonov VA. Analysis of Efficacy of Ascorbic Acid, Hydrocortisone and Thiamine as a Part Adjuvant Therapy of Sepsis and Septic Shock. MESSENGER OF ANESTHESIOLOGY AND RESUSCITATION 2022. [DOI: 10.21292/2078-5658-2022-19-5-102-110] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/17/2023]
Abstract
The objective: to analyze efficacy of ascorbic acid or its combination with glucocorticoids and thiamine on clinical outcomes in patients with sepsis and septic shock.Subjects and Methods. The literature search was carried out in the database of MEDLINE, Embase, and the Cochrane Library systems. It is limited to published articles from January 1, 2008 to March 1, 2022. The selection criteria were observational studies in patients over 18 years of age with septic shock, if they provide data on the use of ascorbic acid in the form of monotherapy or in combination with hydrocortisone and thiamine.Conclusion. The review includes 18 publications, including 3 meta-analyses on the use of ascorbic acid or its combination with hydrocortisone and thiamine in patients in the adjuvant therapy program for sepsis and septic shock. Clinical efficacy has been proven in 11 studies. However, 7 publications did not show global changes in the outcomes of sepsis and septic shock therapy compared to basic therapy. Currently, there is a need for further research.
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Affiliation(s)
- L. L. Plotkin
- South Ural State Medical University; Chelyabinsk Regional Clinical Hospital
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21
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Madokoro Y, Kamikokuryo C, Niiyama S, Ito T, Hara S, Ichinose H, Kakihana Y. Early ascorbic acid administration prevents vascular endothelial cell damage in septic mice. Front Pharmacol 2022; 13:929448. [PMID: 36278212 PMCID: PMC9582851 DOI: 10.3389/fphar.2022.929448] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2022] [Accepted: 09/21/2022] [Indexed: 11/13/2022] Open
Abstract
Oxidation of BH4, a cofactor of nitric oxide synthase (NOS), produces reactive oxygen species (ROS) through uncoupling of NOS and affects vascular endothelial dysfunction. Ascorbic acid (AsA) inhibits the oxidation of BH4 and reduces ROS. However, the kinetic changes of BH4 in sepsis and its effect on the kinetic changes in AsA administration therapy, as well as the appropriate timing of AsA administration for AsA therapy to be effective, are unclear. Mice with sepsis, induced by cecal ligation and puncture (CLP), were examined for the effect of AsA administration (200 mg/kg) on vascular endothelial cell dysfunction at two administration timings: early group (AsA administered immediately after CLP) and late group (AsA administered 12 h after CLP). Survival rates were compared between the early and late administration groups, and vascular endothelial cell damage, indicated by the dihydrobiopterin/tetrahydrobiopterin ratio, serum syndecan-1, and endothelial nitric oxide synthase, as well as liver damage, were examined. The early group showed significantly improved survival compared to the non-treatment group (p < 0.05), while the late group showed no improved survival compared to the non-treatment group. Compared to the non-treated group, the early AsA group showed less oxidation of BH4 in sepsis. Syndecan1, a marker of vascular endothelial cell damage, was less elevated and organ damage was reduced in the early AsA-treated group. In septic mice, early AsA administration immediately after CLP may protect vascular endothelial cells by inhibiting BH4 oxidation, thereby reducing organ dysfunction and improving survival.
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Affiliation(s)
- Yutaro Madokoro
- Department of Emergency and Intensive Care Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Chinatsu Kamikokuryo
- Department of Emergency and Intensive Care Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Shuhei Niiyama
- Department of Emergency and Intensive Care Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Takashi Ito
- Department of Biomedical Laboratory Sciences, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Satoshi Hara
- School of Life Science and Technology, Tokyo Institute of Technology, Yokohama, Japan
| | - Hiroshi Ichinose
- School of Life Science and Technology, Tokyo Institute of Technology, Yokohama, Japan
| | - Yasuyuki Kakihana
- Department of Emergency and Intensive Care Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
- *Correspondence: Yasuyuki Kakihana,
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Affiliation(s)
| | - Rinaldo Bellomo
- Department of Critical Care, University of Melbourne, Melbourne, Australia.
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Bektaş Uysal H, Yılmaz M, Kurt Ömurlu İ, Demirci B. Protective Efficacy of Thiamine (Vitamin B<sub>1</sub>) Alone on LPS-induced Acute Kidney Injury. MEANDROS MEDICAL AND DENTAL JOURNAL 2022. [DOI: 10.4274/meandros.galenos.2022.70456] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
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Lubis B, Lelo A, Amelia P, Prima A. The Effect of Thiamine, Ascorbic Acid, and the Combination of Them on the Levels of Matrix Metalloproteinase-9 (MMP-9) and Tissue Inhibitor of Matrix Metalloproteinase-1 (TIMP-1) in Sepsis Patients. Infect Drug Resist 2022; 15:5741-5751. [PMID: 36204393 PMCID: PMC9531617 DOI: 10.2147/idr.s378523] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2022] [Accepted: 09/16/2022] [Indexed: 11/23/2022] Open
Abstract
Background Methods Results Conclusion
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Affiliation(s)
- Bastian Lubis
- Department of Anesthesiology and Intensive Care, Faculty of Medicine, Universitas Sumatera Utara, Medan, Indonesia
| | - Aznan Lelo
- Department of Pharmacology and Therapeutics, Universitas Sumatera Utara, Medan, Indonesia
| | - Putri Amelia
- Department of Pediatric, Universitas Sumatera Utara, Medan, Indonesia
- Correspondence: Putri Amelia, Department of Pediatric, Hospital of Haji Adam Malik, Jl. Bunga Lau No. 17, Kemenangan Tani, Kec. Medan Tuntungan, Medan, Sumatera Utara, 20136, Indonesia, Tel +061 8360143, Email
| | - Agus Prima
- Department of Anesthesiology and Intensive Care, Faculty of Medicine, Universitas Sumatera Utara, Medan, Indonesia
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Agarwal A, Basmaji J, Fernando SM, Ge FZ, Xiao Y, Faisal H, Honarmand K, Hylands M, Lau V, Lewis K, Couban R, Lamontagne F, Adhikari NKJ. Parenteral Vitamin C in Patients with Severe Infection: A Systematic Review. NEJM EVIDENCE 2022; 1:EVIDoa2200105. [PMID: 38319815 DOI: 10.1056/evidoa2200105] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND: Inflammation and oxidative damage caused by severe infections may be attenuated by vitamin C. METHODS: We conducted a systematic review of randomized controlled trials (RCTs) of parenteral vitamin C as combined therapy or monotherapy versus no parenteral vitamin C administered to adults hospitalized with severe infection. The primary outcome was mortality. We performed random-effects meta-analyses and assessed certainty in effect estimates. RESULTS: Of 1547 citations, 41 RCTs (n = 4915 patients) were eligible for inclusion. Low-certainty evidence suggested that vitamin C may reduce in-hospital mortality (21 RCTs, 2762 patients; risk ratio, 0.88 [95% confidence interval (CI), 0.73 to 1.06]), 30-day mortality (24 RCTs, 3436 patients; risk ratio, 0.83 [95% CI, 0.71 to 0.98]), and early mortality (before hospital discharge or 30 days; 34 RCTs, 4366 patients; risk ratio, 0.80 [95% CI, 0.68 to 0.93]). Effects were attenuated in sensitivity analyses limited to published blinded trials at low risk-of-bias (in-hospital mortality: risk ratio, 1.07 [95% CI, 0.92 to 1.24], moderate certainty; 30-day mortality: risk ratio, 0.88 [95% CI, 0.71 to 1.10], low certainty; and early mortality: risk ratio, 0.88 [95% CI, 0.73 to 1.06], low certainty). For 90-day mortality, all trials had low risk-of-bias; moderate-certainty evidence suggested harm (five RCTs, 1722 patients; risk ratio, 1.07 [95% CI, 0.94 to 1.21]). Moderate-certainty evidence suggested an increased risk of hypoglycemia (risk ratio, 1.20 [95% CI, 0.69 to 2.08]). Effects on other secondary outcomes were mixed and informed by low-certainty evidence. No credible subgroup effects were observed for mortality related to cointerventions (monotherapy vs. combined therapy), dose, or type of infection (Covid-19 vs. other). CONCLUSIONS: Overall, evidence from RCTs does not establish a survival benefit for vitamin C in patients with severe infection. (PROSPERO number, CRD42020209187.)
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Affiliation(s)
- Arnav Agarwal
- Department of Critical Care Medicine, Sunnybrook Health Sciences Centre, Toronto
- Department of Medicine, Université de Sherbrooke, Sherbrooke, Canada
| | - John Basmaji
- Division of Critical Care, Department of Medicine, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada
| | - Shannon M Fernando
- Division of Critical Care, Department of Medicine, University of Ottawa, Ottawa
- Department of Emergency Medicine, University of Ottawa, Ottawa
| | - Fang Zhou Ge
- Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada
| | - Yingqi Xiao
- Department of Nursing, West China School of Nursing, West China Hospital, Sichuan University, Chengdu, Sichuan, China
- Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada
| | - Haseeb Faisal
- Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada
| | - Kimia Honarmand
- Division of Critical Care, Department of Medicine, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada
| | - Mathieu Hylands
- Department of Critical Care Medicine, Sunnybrook Health Sciences Centre, Toronto
| | - Vincent Lau
- Department of Critical Care, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada
| | - Kimberley Lewis
- Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada
- Department of Medicine, McMaster University, Hamilton, Ontario, Canada
| | - Rachel Couban
- Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada
| | - François Lamontagne
- Department of Medicine, Université de Sherbrooke, Sherbrooke, Canada
- Centre de recherche du CHU de Sherbrooke, Sherbrooke, Canada
| | - Neill K J Adhikari
- Department of Critical Care Medicine, Sunnybrook Health Sciences Centre, Toronto
- Interdepartmental Division of Critical Care Medicine, Institute for Health Policy, Management, and Evaluation, University of Toronto, Toronto
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Thiamine pretreatment improves endotoxemia-related liver injury and cholestatic complications by regulating galactose metabolism and inhibiting macrophage activation. Int Immunopharmacol 2022; 108:108892. [DOI: 10.1016/j.intimp.2022.108892] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2022] [Revised: 05/19/2022] [Accepted: 05/21/2022] [Indexed: 11/05/2022]
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Ascorbic acid along with ciprofloxacin regulates S. aureus induced microglial inflammatory responses and oxidative stress through TLR-2 and glucocorticoid receptor modulation. Inflammopharmacology 2022; 30:1303-1322. [PMID: 35704229 DOI: 10.1007/s10787-022-01012-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2021] [Accepted: 05/13/2022] [Indexed: 11/05/2022]
Abstract
Microglial inflammatory responses play a central role in the pathogenesis of S. aureus induced brain infections. Upon activation, microglia produces free radicals (ROS/RNS) and disrupts the cellular antioxidant defense to combat invading microorganisms. Despite conventional antibiotic or steroid therapy, microglial over-activation could not be controlled. So, an attempt had been taken by using a natural antioxidant ascorbic acid along with ciprofloxacin to regulate microglial over-activation by involving TLR-2 and glucocorticoid receptor (GR) in an in-vitro cell culture-based study. Combinatorial treatment during TLR-2 neutralization effectively reduced the bacterial burden at 60 min compared to the GR blocking condition (p < 0.05). Moreover, the infection-induced H2O2, O2.-, and NO release in microglial cell culture was diminished possibly by enhancing SOD and catalase activities in the same condition (p < 0.05). The arginase activity was markedly increased after TLR-2 blocking in the combinatorial group compared to single treatments (p < 0.05). Experimental results indicated that combinatorial treatment may act through up-regulating GR expression by augmenting endogenous corticosterone levels. However, better bacterial clearance could further suppress the TLR-2 mediated pro-inflammatory NF-κB signaling. From Western blot analysis, it was concluded that ciprofloxacin-ascorbic acid combination in presence of anti-TLR-2 antibody exhibited 81.25% inhibition of TLR-2 expression while the inhibition for GR was 3.57% with respect to the infected group. Therefore, during TLR-2 blockade ascorbic acid combination might be responsible for the restoration of redox balance in microglia via modulating TLR-2/GR interaction. The combination treatment could play a major role in the neuroendocrine-immune regulation of S. aureus induced microglial activation.
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Yuan-Yuan X, Xu CZ, Liang YF, Jin DQ, Ding J, Sheng Y, Zhang L, Deng F. Ascorbic acid and hydrocortisone synergistically inhibit septic organ injury via improving oxidative stress and inhibiting inflammation. Immunopharmacol Immunotoxicol 2022; 44:786-794. [PMID: 35635075 DOI: 10.1080/08923973.2022.2082978] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
BACKGROUND The current study aimed to investigate the effect of the combination of ascorbic acid (AscA) and hydrocortisone (Hyd) on septic organ injury and its potential mechanism. METHOD Sepsis was induced in mice by a single intraperitoneal injection of lipopolysaccharides. RESULTS AscA and Hyd combined showed more effective protection of the injured liver and kidney in septic mice by decreasing ALT, AST, BUN and SCr and ameliorating pathological manifestations than Hyd or AscA alone. AscA showed a mild inhibitory effect on the secretion of proinflammatory cytokines (TNF-α, IL-1β and IL-6). However, Hyd showed a weak regulatory effect on septic oxidative stress markers (MDA, SOD and GSH-Px). However, the combination of AscA and Hyd showed a more powerful inhibitory effect on the septic inflammatory response and oxidative stress than Hyd or AscA alone by decreasing TNF-α, IL-1β and IL-6 and regulating MDA, SOD and GSH. In an in vitro study, cotreatment of RAW 264.7 macrophages with Hyd and AscA sharply reduced reactive oxygen species (ROS) generation and synergistically inhibited TNF-α, IL-1β and IL-6 secretion, which could be abolished by additional stimulation with the ROS donor 3-nitropropionic acid (3-NP). As expected, cotreatment of macrophages with Hyd and AscA synergistically inhibited the activation of p38 MAPK and p-p65, and the effect could be reversed by additional stimulation with 3-NP. CONCLUSIONS AscA and Hyd synergistically protect the kidney and liver from injury by inhibiting the inflammatory response and oxidative stress. The powerful inhibitory effects of AscA on oxidative stress contribute to the synergistic anti-inflammatory action.
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Affiliation(s)
- Xu Yuan-Yuan
- Department of Pediatric Critical Care Medicine, Affiliated Provincial Children's Hospital of Anhui Medical University, Wangjiang East Road No.39, Hefei, 230051, China
| | - Cheng-Zhu Xu
- The Second Clinical Medical College of Anhui Medical University, Meishan Road No.81, Hefei, 230032, China
| | - You-Feng Liang
- Department of Cardiology, The First Affiliated Hospital of Anhui Medical University, Jixi Road No.218, Hefei, 230022, China
| | - Dan-Qun Jin
- Department of Pediatric Critical Care Medicine, Affiliated Provincial Children's Hospital of Anhui Medical University, Wangjiang East Road No.39, Hefei, 230051, China
| | - Jie Ding
- Department of Pediatric Critical Care Medicine, Affiliated Provincial Children's Hospital of Anhui Medical University, Wangjiang East Road No.39, Hefei, 230051, China
| | - Yao Sheng
- Department of Pediatric Critical Care Medicine, Affiliated Provincial Children's Hospital of Anhui Medical University, Wangjiang East Road No.39, Hefei, 230051, China
| | - Le Zhang
- Department of Pediatric Critical Care Medicine, Affiliated Provincial Children's Hospital of Anhui Medical University, Wangjiang East Road No.39, Hefei, 230051, China
| | - Fang Deng
- Department of Pediatric Nephrology, Affiliated Provincial Children's Hospital of Anhui Medical University, Wangjiang East Road No.39, Hefei, 230051, China
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Serum Ascorbic Acid and Thiamine Concentrations in Sepsis: Secondary Analysis of the Swiss Pediatric Sepsis Study. Pediatr Crit Care Med 2022; 23:390-394. [PMID: 35583617 DOI: 10.1097/pcc.0000000000002911] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
OBJECTIVES To determine circulating levels of ascorbic acid (VitC) and thiamine (VitB1) in neonates and children with blood culture-proven sepsis. DESIGN Nested single-center study of neonates and children prospectively included in the Swiss Pediatric Sepsis Study. SETTING One tertiary care academic hospital. PATIENTS Sixty-one neonates and children 0-16 years old. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS VitC and VitB1 were quantified in serum of patients (median age, 10.5 mo; interquartile range [IQR], 0.5-62.1 mo) with blood culture-proven sepsis. Median time between sepsis onset and sampling for measurement of vitamins was 3 days (IQR, 2-4 d). Median serum levels of VitC and VitB1 were 32.4 μmol/L (18.9-53.3 μmol/L) and 22.5 nmol/L (12.6-82 nmol/L); 36% of the patients (22/61) had low VitC and 10% (6/61) had VitC deficiency; and 72% (44/61) had low VitB1 and 13% (8/61) had VitB1 deficiency. Children with low VitC were older (p = 0.007) and had higher C-reactive protein (p = 0.004) compared with children with VitC within the normal range. Children with low VitB1 levels were older (p = 0.0009) and were less frequently receiving enteral or parenteral vitamin supplementation (p = 0.0000003) compared with children with normal VitB1 levels. CONCLUSIONS In this cohort of newborns and children with sepsis, low and deficient VitC and VitB1 levels were frequently observed. Age, systemic inflammation, and vitamin supplementation were associated with vitamin levels during sepsis.
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Wang K, Yin L, Song Y, Zhang M, Lu Y, Wang S. The Use of Hydrocortisone, Ascorbic Acid and Thiamine in Patients with Sepsis and Septic Shock - A Systematic Review. J Pharm Pract 2022:8971900221097193. [PMID: 35465689 DOI: 10.1177/08971900221097193] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Background: Sepsis and septic shock are associated with enormous mortality and health care burden. Since the study of Marik et al suggested mortality benefit, there has been great interest in evaluating the role of hydrocortisone, ascorbic acid and thiamine (HAT therapy) in sepsis and septic shock. Purpose: The objective of this article is to review current literature of using HAT therapy in sepsis and septic shock, and discuss the findings in hospital mortality, change in 72 hr SOFA score, other outcomes, and the study limitations. Research Design: Three databases (PubMed, Embase, and Cochrane) were screened using predefined search terms ascorbic acid, vitamin C, thiamine, vitamin B1, hydrocortisone, sepsis, septic shock. Study Sample: Data extracted from eligible studies include authors, publication year, sample size, study design, intervention, outcome measures and study results. Each study was reviewed critically. Results: Among 11 studies included in this literature review, 3 studies reported HAT therapy was associated with mortality benefit, 1 reported hospital mortality was significantly higher in HAT group and the rest of studies didn't reach statistical significance in mortality analysis. Significant improvement of secondary outcomes, although not consistently, were reported. Conclusions: In conclusion, HAT therapy has demonstrated a good safety profile and potential benefits in management of sepsis and septic shock. Further research is required to confirm these findings.
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Affiliation(s)
- Kunkun Wang
- FMH Pharmacy, 22360Fairbanks Memorial Hospital, Fairbanks, AK, USA
| | - Ling Yin
- Department of Pharmacy, 23067Advent Health Celebration Cancer Institute, Celebration, FL, USA
| | - Yang Song
- Department of Pharmacy, 7814CHI Franciscan Health, Tacoma, WA, USA
| | - Mengqi Zhang
- Department of Pharmacy, 74659Shanghai Jiaotong Universtiy Affiliated with Sixth People's Hospital, Shanghai, China
| | - Yun Lu
- College of Pharmacy, 5532Hennepin Healthcare System, University of Minnesota, Minneapolis, MN, USA
| | - Shan Wang
- Department of Pharmacy, 24998NYU Langone Hospital-Long Island, Mineola, NY, USA
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Almalki WH, Ghoneim MM, Alshehri S, Imam SS, Kazmi I, Gupta G. Sepsis triggered oxidative stress-inflammatory axis: the pathobiology of reprogramming in the normal sleep-wake cycle. Mol Cell Biochem 2022; 477:2203-2211. [PMID: 35451739 DOI: 10.1007/s11010-022-04432-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2022] [Accepted: 03/30/2022] [Indexed: 10/18/2022]
Abstract
In individuals with sepsis-related neurodegenerative illness, sleep and circadian rhythm disturbance are common. The alteration in genomic expression linked with the immune-directed oxidative stress-inflammatory axis is thought to cause these individuals' abnormal sleep. On the other hand, sleep is linked to normal brain activity through common neurotransmitter systems and regulatory mechanisms. Ailments (ranging from cognitive to metabolic abnormalities) are seldom related to aberrant sleep that is made worse by sleep disturbance, which throws off the body's sleep-wake cycle. PubMed/Springer link /Public library of science/ScienceDirect/ Mendeley/Medline and Google Scholar were used to find possibly relevant studies. For the literature search, many keywords were considered, both individually and in combination. 'Sepsis,' 'Epidemiology of sepsis,' 'Sepsis-related hyper inflammation,' 'Relationship of sepsis-associated clock gene expression and relationship of inflammation with the reprogramming of genetic alterations' were some of the key terms utilized in the literature search. Our main objective is to understand better how traumatic infections during sepsis affect CNS processes, particularly sleep, by investigating the pathobiology of circadian reprogramming associated with immune-directed oxidative stress-inflammatory pathway responsive gene expression and sleep-wake behaviour in this study.
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Affiliation(s)
- Waleed Hassan Almalki
- Department of Pharmacology, College of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia.
| | - Mohammed M Ghoneim
- Department of Pharmacy Practice, College of Pharmacy, AlMaarefa University, Ad Diriyah, 13713, Saudi Arabia
| | - Sultan Alshehri
- Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
| | - Syed Sarim Imam
- Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
| | - Imran Kazmi
- Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Gaurav Gupta
- Department of Pharmacology, School of Pharmacy, Suresh Gyan Vihar University, Jagatpura, Jaipur, India.,Department of Pharmacology, Saveetha Dental College, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India.,Uttaranchal Institute of Pharmaceutical Sciences, Uttaranchal University, Dehradun, India
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Del Río-Carbajo L, Nieto-Del Olmo J, Fernández-Ugidos P, Vidal-Cortés P. [Resuscitation strategy for patients with sepsis and septic shock]. Med Intensiva 2022; 46 Suppl 1:60-71. [PMID: 38341261 DOI: 10.1016/j.medine.2022.02.025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2022] [Accepted: 02/11/2022] [Indexed: 02/12/2024]
Abstract
Fluid and vasopressor resuscitation is, along with antimicrobial therapy and control of the focus of infection, a basic issue of the treatment of sepsis and septic shock. There is currently no accepted protocol that we can follow for the resuscitation of these patients and the Surviving Sepsis Campaign proposes controversial measures and without sufficient evidence support to establish firm recommendations. We propose a resuscitation strategy adapted to the situation of each patient: in the patient in whom community sepsis is suspected, we consider that the early administration of 30mL/kg of crystalloids is effective and safe; in the patient with nosocomial sepsis, we must carry out a more in-depth evaluation before initiating aggressive resuscitation. In patients who do not respond to initial resuscitation, it is necessary to increase monitoring level and, depending on the hemodynamic profile, administer more fluids, a second vasopressor or inotropes.
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Affiliation(s)
- L Del Río-Carbajo
- Medicina Intensiva, Complexo Hospitalario Universitario de Ourense. Ourense, España
| | - J Nieto-Del Olmo
- Medicina Intensiva, Complexo Hospitalario Universitario de Ourense. Ourense, España
| | - P Fernández-Ugidos
- Medicina Intensiva, Complexo Hospitalario Universitario de Ourense. Ourense, España
| | - P Vidal-Cortés
- Medicina Intensiva, Complexo Hospitalario Universitario de Ourense. Ourense, España.
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Estrategia integral de reanimación del paciente con sepsis y shock séptico. Med Intensiva 2022. [DOI: 10.1016/j.medin.2022.02.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
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Kory P, Meduri GU, Iglesias J, Varon J, Cadegiani FA, Marik PE. "MATH+" Multi-Modal Hospital Treatment Protocol for COVID-19 Infection: Clinical and Scientific Rationale. J Clin Med Res 2022; 14:53-79. [PMID: 35317360 PMCID: PMC8912998 DOI: 10.14740/jocmr4658] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2022] [Accepted: 02/08/2022] [Indexed: 11/17/2022] Open
Abstract
In December 2019, coronavirus disease 2019 (COVID-19), a severe respiratory illness caused by the new coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China. The greatest impact that COVID-19 had was on intensive care units (ICUs), given that approximately 20% of hospitalized cases developed acute respiratory failure (ARF) requiring ICU admission. Based on the assumption that COVID-19 represented a viral pneumonia and no anti-coronaviral therapy existed, nearly all national and international health care societies recommended "supportive care only" avoiding other therapies outside of randomized controlled trials, with a specific prohibition against the use of corticosteroids in treatment. However, early studies of COVID-19-associated ARF reported inexplicably high mortality rates, with frequent prolonged durations of mechanical ventilation (MV), even from centers expert in such supportive care strategies. These reports led the authors to form a clinical expert panel called the Front-Line COVID-19 Critical Care Alliance (www.flccc.net). The panel collaboratively reviewed the emerging clinical, radiographic, and pathological reports of COVID-19 while initiating multiple discussions among a wide clinical network of front-line clinical ICU experts from initial outbreak areas in China, Italy, and New York. Based on the shared early impressions of "what was working and what wasn't working", the increasing medical journal publications and the rapidly accumulating personal clinical experiences with COVID-19 patients, a treatment protocol was created for the hospitalized patients based on the core therapies of methylprednisolone, ascorbic acid, thiamine, heparin and non-antiviral co-interventions (MATH+). This manuscript reviews the scientific and clinical rationale behind MATH+ based on published in-vitro, pre-clinical, and clinical data in support of each medicine, with a special emphasis of studies supporting their use in the treatment of patients with viral syndromes and COVID-19 specifically.
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Affiliation(s)
- Pierre Kory
- Front Line Critical Care Consortium (FLCCC.org), Washington DC, USA
| | | | - Jose Iglesias
- Jersey Shore University Medical Center, Hackensack School of Medicine at Seton Hall, NJ, USA
| | - Joseph Varon
- University of Texas Health Science Center, Houston, TX, USA
| | | | - Paul E. Marik
- Front Line Critical Care Consortium (FLCCC.org), Washington DC, USA
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Lazzaro A, De Girolamo G, Filippi V, Innocenti GP, Santinelli L, Ceccarelli G, Trecarichi EM, Torti C, Mastroianni CM, d’Ettorre G, Russo A. The Interplay between Host Defense, Infection, and Clinical Status in Septic Patients: A Narrative Review. Int J Mol Sci 2022; 23:ijms23020803. [PMID: 35054993 PMCID: PMC8776148 DOI: 10.3390/ijms23020803] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2021] [Revised: 01/05/2022] [Accepted: 01/09/2022] [Indexed: 01/08/2023] Open
Abstract
Sepsis is a life-threatening condition that arises when the body's response to an infection injures its own tissues and organs. Despite significant morbidity and mortality throughout the world, its pathogenesis and mechanisms are not clearly understood. In this narrative review, we aimed to summarize the recent developments in our understanding of the hallmarks of sepsis pathogenesis (immune and adaptive immune response, the complement system, the endothelial disfunction, and autophagy) and highlight novel laboratory diagnostic approaches. Clinical management is also discussed with pivotal consideration for antimicrobic therapy management in particular settings, such as intensive care unit, altered renal function, obesity, and burn patients.
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Affiliation(s)
- Alessandro Lazzaro
- Department of Public Health and Infectious Diseases, “Sapienza” University of Rome, 00161 Rome, Italy; (A.L.); (G.D.G.); (V.F.); (G.P.I.); (L.S.); (G.C.); (C.M.M.); (G.d.)
| | - Gabriella De Girolamo
- Department of Public Health and Infectious Diseases, “Sapienza” University of Rome, 00161 Rome, Italy; (A.L.); (G.D.G.); (V.F.); (G.P.I.); (L.S.); (G.C.); (C.M.M.); (G.d.)
| | - Valeria Filippi
- Department of Public Health and Infectious Diseases, “Sapienza” University of Rome, 00161 Rome, Italy; (A.L.); (G.D.G.); (V.F.); (G.P.I.); (L.S.); (G.C.); (C.M.M.); (G.d.)
| | - Giuseppe Pietro Innocenti
- Department of Public Health and Infectious Diseases, “Sapienza” University of Rome, 00161 Rome, Italy; (A.L.); (G.D.G.); (V.F.); (G.P.I.); (L.S.); (G.C.); (C.M.M.); (G.d.)
| | - Letizia Santinelli
- Department of Public Health and Infectious Diseases, “Sapienza” University of Rome, 00161 Rome, Italy; (A.L.); (G.D.G.); (V.F.); (G.P.I.); (L.S.); (G.C.); (C.M.M.); (G.d.)
| | - Giancarlo Ceccarelli
- Department of Public Health and Infectious Diseases, “Sapienza” University of Rome, 00161 Rome, Italy; (A.L.); (G.D.G.); (V.F.); (G.P.I.); (L.S.); (G.C.); (C.M.M.); (G.d.)
| | - Enrico Maria Trecarichi
- Infectious and Tropical Disease Unit, Department of Medical and Surgical Sciences, “Magna Graecia” University of Catanzaro, 88100 Catanzaro, Italy; (E.M.T.); (C.T.)
| | - Carlo Torti
- Infectious and Tropical Disease Unit, Department of Medical and Surgical Sciences, “Magna Graecia” University of Catanzaro, 88100 Catanzaro, Italy; (E.M.T.); (C.T.)
| | - Claudio Maria Mastroianni
- Department of Public Health and Infectious Diseases, “Sapienza” University of Rome, 00161 Rome, Italy; (A.L.); (G.D.G.); (V.F.); (G.P.I.); (L.S.); (G.C.); (C.M.M.); (G.d.)
| | - Gabriella d’Ettorre
- Department of Public Health and Infectious Diseases, “Sapienza” University of Rome, 00161 Rome, Italy; (A.L.); (G.D.G.); (V.F.); (G.P.I.); (L.S.); (G.C.); (C.M.M.); (G.d.)
| | - Alessandro Russo
- Infectious and Tropical Disease Unit, Department of Medical and Surgical Sciences, “Magna Graecia” University of Catanzaro, 88100 Catanzaro, Italy; (E.M.T.); (C.T.)
- Correspondence:
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Park JE, Jo YH, Hwang SY, Kim WY, Ryoo SM, Jang DH, Kim T, Kim YJ, Kim S, Cho H, Lee GT, Chung SP, Choi SH, Shin TG, Suh GJ. Biomarker Analysis for Combination Therapy of Vitamin C and Thiamine in Septic Shock: A Post-Hoc Study of the ATESS Trial. Shock 2022; 57:81-87. [PMID: 34482319 DOI: 10.1097/shk.0000000000001850] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
INTRODUCTION We evaluated the effects of vitamin C and thiamine administration on biomarkers in patients with septic shock. METHODS This was a post-hoc analysis of the Ascorbic Acid and Thiamine Effect in Septic Shock (ATESS) trial, a multicenter, double-blind, randomized controlled trial. Patients were randomized to either a treatment group (intravenous vitamin C and thiamine for 48 h) or a control group. Interleukin (IL)-6, IL-10, angiopoietin-II (AP2), and S100β were assessed at baseline and at 72 h. The primary outcomes were the biomarker levels at 72 h, and the secondary outcome was reduction rate. RESULTS Forty-five patients were assigned to the treatment group and 52 were assigned to the control group. Baseline biomarker levels and at 72 h were not significantly different between the treatment and the placebo groups. The reduction rates were not significantly different between the two groups. These outcome variables showed fair diagnostic accuracy for predicting 28-day mortality according to the area under the receiver operating characteristic curve. CONCLUSION Vitamin C and thiamine administration during the early phase of septic shock did not significantly change prognostic biomarker levels of IL-6, IL-10, AP2, and S100β. TRIAL REGISTRATION NCT, ClinicalTrials.gov NCT03756220, ATESS. Registered 28 November 2018, https://clinicaltrials.gov/ct2/show/NCT03756220.
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Affiliation(s)
- Jong Eun Park
- Department of Emergency Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - You Hwan Jo
- Department of Emergency Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
- Department of Emergency Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Sung Yeon Hwang
- Department of Emergency Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Won Young Kim
- Department of Emergency Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Seung Mok Ryoo
- Department of Emergency Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Dong-Hyun Jang
- Department of Emergency Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
- Department of Emergency Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Taegyun Kim
- Department of Emergency Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Youn-Jung Kim
- Department of Emergency Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Seonwoo Kim
- Statistics and Data Center, Samsung Medical Center, Seoul, Korea
| | - Hyun Cho
- Statistics and Data Center, Samsung Medical Center, Seoul, Korea
| | - Gun Tak Lee
- Department of Emergency Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Sung Phil Chung
- Department of Emergency Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Sung-Hyuk Choi
- Department of Emergency Medicine, Guro Hospital, Korea University Medical Center, Seoul, Korea
| | - Tae Gun Shin
- Department of Emergency Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Gil Joon Suh
- Department of Emergency Medicine, Seoul National University College of Medicine, Seoul, Korea
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Na W, Shen H, Li Y, Qu D. Hydrocortisone, ascorbic acid, and thiamine (HAT) for sepsis and septic shock: a meta-analysis with sequential trial analysis. J Intensive Care 2021; 9:75. [PMID: 34922637 PMCID: PMC8684090 DOI: 10.1186/s40560-021-00589-x] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2021] [Accepted: 12/01/2021] [Indexed: 12/25/2022] Open
Abstract
BACKGROUND Sepsis is a primary global health threat and costs a lot, requiring effective and affordable treatments. We performed this meta-analysis to explore the treatment of hydrocortisone, ascorbic acid, and thiamine (HAT) in sepsis and septic shock. METHODS We searched Ovid MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials from inception to August 14, 2021. We included randomized controlled trials (RCTs) that evaluated the HAT treatments in sepsis and septic shock. The primary outcome was the change in SOFA score over the 72 h. The second outcomes were the hospital, and 28-/30-day mortality, the duration of vasopressors, PCT clearance, hospital length of stay (LOS), and ICU LOS. We performed a subgroup analysis and a trial sequential analysis (TSA). The Der Simonian-Laird random-effects models were used to report the pooled risk ratios (RR) or mean difference (MD) with confidence intervals (CI). RESULTS Nine RCTs, enrolling 1427 patients of sepsis and septic shock treated with HAT (717) or only standard care (710), were included. There was a significant difference between the two groups in the change in SOFA score over the first 72 h (MD 0.65, 95% CI 0.30 to 1.00), the duration of vasopressors (MD - 18.16, 95% CI - 25.65 to - 10.68) and the PCT clearance (MD 14.54, 95% CI 0.64 to 28.43). In addition, there was no significant difference in the hospital mortality (RR 1.07, 95% CI 0.85 to 1.34), the 28-/30-day mortality (RR 0.96, 95% CI 0.80 to 1.15), the hospital LOS (MD 0.78, 95% CI - 0.30 to 1.86), and ICU LOS (MD 0.12, 95% CI - 0.53 to 0.78). CONCLUSIONS The HAT combination improves the SOFA score in the first 72 h and reduces the duration of vasopressors in patients with sepsis. Given the minor mean difference of the change in SOFA score, the mortality benefit has not been observed. TRIAL REGISTRATION PROSPERO, CRD42020203166.
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Affiliation(s)
- Weilan Na
- Department of Critical Medicine, Children's Hospital Affiliated to the Capital Institute of Pediatrics, NO.2 Ya Bao Road, Chaoyang District, Beijing, 100020, China
| | - Huili Shen
- Pediatric Intensive Care Unit, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, 100020, China
| | - Yichu Li
- Department of Critical Medicine, Children's Hospital Affiliated to the Capital Institute of Pediatrics, NO.2 Ya Bao Road, Chaoyang District, Beijing, 100020, China
| | - Dong Qu
- Department of Critical Medicine, Children's Hospital Affiliated to the Capital Institute of Pediatrics, NO.2 Ya Bao Road, Chaoyang District, Beijing, 100020, China.
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Yao R, Zhu Y, Yu Y, Li Z, Wang L, Zheng L, Li J, Huang H, Wu G, Zhu F, Xia Z, Ren C, Yao Y. Combination therapy of thiamine, vitamin C and hydrocortisone in treating patients with sepsis and septic shock: a meta-analysis and trial sequential analysis. BURNS & TRAUMA 2021; 9:tkab040. [PMID: 34901285 PMCID: PMC8660008 DOI: 10.1093/burnst/tkab040] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/09/2021] [Revised: 09/12/2021] [Indexed: 12/29/2022]
Abstract
Background The objective of this study was to evaluate the clinical efficacy of thiamine and vitamin C with or without hydrocortisone coadministration on the treatment of sepsis and septic shock. Methods MEDLINE, EMBASE and CENTRAL databases were searched for randomized controlled trials (RCTs) that made a comparative study between the combination therapy of vitamin C and thiamine with or without hydrocortisone and the administration of placebo in patients with sepsis or septic shock. Two reviewers independently performed study selection, data extraction and quality assessment. Both short-term mortality and change in the sequential organ failure assessment (SOFA) score from baseline (delta SOFA) were set as the primary outcomes. Secondary endpoints included intensive care unit (ICU) mortality, new onset of acute kidney injury, total adverse events, ICU and hospital length of stay, duration of vasopressor usage and ventilator-free days. Meanwhile, trial sequential analysis was conducted for primary outcomes. Results Eight RCTs with 1428 patients were included in the current study. The results showed no significant reduction of short-term mortality in sepsis and septic shock patients who received combination therapy of vitamin C and thiamine with or without hydrocortisone compared to those with placebo {risk ratio (RR), 1.02 [95% confidence interval (CI), 0.87 to 1.20], p = 0.81, I2 = 0%; risk difference (RD), 0 [95% CI, −0.04 to 0.05]}. Nevertheless, the combination therapy was associated with significant reduction in SOFA score [mean difference (MD), −0.63, (95% CI, −0.96 to −0.29, p < 0.001, I2 = 0%] and vasopressors duration (MD, −22.11 [95% CI, −30.46 to −13.77], p < 0.001, I2 = 6%). Additionally, there were no statistical differences in the pooled estimate for other outcomes. Conclusions In the current meta-analysis, the combination therapy of vitamin C and thiamine, with or without hydrocortisone had no impact on short-term mortality when compared with placebo, but was associated with significant reduction in SOFA score among patients with sepsis and septic shock.
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Affiliation(s)
- Renqi Yao
- Translational Medicine Research Center, Fourth Medical Center and Medical Innovation Research Division of the Chinese PLA General Hospital, Beijing 100048, China
| | - Yibing Zhu
- Medical Research and Biometrics Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China
| | - Yue Yu
- Department of Cardiothoracic Surgery, Changzheng Hospital, Naval Medical University, Shanghai 200003, China
| | - Zhixuan Li
- International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai 200082, China
| | - Lixue Wang
- Translational Medicine Research Center, Fourth Medical Center and Medical Innovation Research Division of the Chinese PLA General Hospital, Beijing 100048, China
| | - Liyu Zheng
- Translational Medicine Research Center, Fourth Medical Center and Medical Innovation Research Division of the Chinese PLA General Hospital, Beijing 100048, China
| | - Jingyan Li
- Translational Medicine Research Center, Fourth Medical Center and Medical Innovation Research Division of the Chinese PLA General Hospital, Beijing 100048, China
| | - Huibin Huang
- Department of Critical Care Medicine, Beijing Tsinghua Chang Gung Hospital, Beijing 102218, China
| | - Guosheng Wu
- Department of Burn Surgery, the First Affiliated Hospital of Naval Medical University, Shanghai 200433, China
| | - Feng Zhu
- Department of Critical Care Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China
| | - Zhaofan Xia
- Department of Burn Surgery, the First Affiliated Hospital of Naval Medical University, Shanghai 200433, China
| | - Chao Ren
- Translational Medicine Research Center, Fourth Medical Center and Medical Innovation Research Division of the Chinese PLA General Hospital, Beijing 100048, China
| | - Yongming Yao
- Translational Medicine Research Center, Fourth Medical Center and Medical Innovation Research Division of the Chinese PLA General Hospital, Beijing 100048, China
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Winters ME, Hu K, Martinez JP, Mallemat H, Brady WJ. The critical care literature 2020. Am J Emerg Med 2021; 50:683-692. [PMID: 34879487 PMCID: PMC8485063 DOI: 10.1016/j.ajem.2021.09.056] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2021] [Revised: 09/17/2021] [Accepted: 09/21/2021] [Indexed: 12/15/2022] Open
Abstract
Given the dramatic increase in critically ill patients who present to the emergency department for care, along with the persistence of boarding of critically ill patients, it is imperative for the emergency physician to be knowledgeable about recent developments in resuscitation and critical care medicine. This review summarizes important articles published in 2020 that pertain to the resuscitation and care of select critically ill patients. These articles have been selected based on the authors annual review of key critical care, emergency medicine and medicine journals and their opinion of the importance of study findings as it pertains to the care of critically ill ED patients. Several key findings from the studies discussed in this paper include the administration of dexamethasone to patients with COVID-19 infection who require mechanical ventilation or supplemental oxygen, the use of lower levels of positive end-expiratory pressure for patients without acute respiratory distress syndrome, and early initiation of extracorporeal membrane oxygenation for out-of-hospital cardiac arrest patients with refractory ventricular fibrillation if resources are available. Furthermore, the emergency physician should not administer tranexamic acid to patients with acute gastrointestinal bleeding or administer the combination of vitamin C, thiamine, and hydrocortisone for patients with septic shock. Finally, the emergency physician should titrate vasopressor medications to more closely match a patient's chronic perfusion pressure rather than target a mean arterial blood pressure of 65 mmHg for all critically ill patients.
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Affiliation(s)
- Michael E Winters
- Departments of Emergency Medicine and Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
| | - Kami Hu
- Departments of Emergency Medicine and Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA
| | - Joseph P Martinez
- Departments of Emergency Medicine and Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA
| | - Haney Mallemat
- Departments of Critical Care Medicine and Emergency Medicine, Cooper Medical School of Rowan University, Camden, NJ, USA
| | - William J Brady
- Department of Emergency Medicine, University of Virginia School of Medicine, Charlottesville, VA 22908, USA
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Agarwal A, Basmaji J, Fernando SM, Ge FZ, Xiao Y, Faisal H, Honarmand K, Hylands M, Lau VI, Lewis K, Couban R, Lamontagne F, Adhikari NK. Administration of parenteral vitamin C in patients with severe infection: protocol for a systematic review and meta-analysis. JMIR Res Protoc 2021; 11:e33989. [PMID: 34910661 PMCID: PMC8734609 DOI: 10.2196/33989] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2021] [Revised: 11/21/2021] [Accepted: 12/08/2021] [Indexed: 02/06/2023] Open
Abstract
Background Severe infections are characterized by inflammation and oxidative damage. Ascorbic acid (vitamin C) administration may attenuate oxidative damage and, in turn, reduce vascular endothelial injury in pulmonary and systemic vasculature. Objective We aim to describe a protocol for a living systematic review that will evaluate the effectiveness and safety of parenteral vitamin C administration in adults with severe infections, including those with COVID-19. Methods We searched Ovid MEDLINE, Embase, CINAHL, the Centers for Disease Control and Prevention COVID-19 database, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from inception to March 30, 2021, for randomized controlled trials evaluating parenteral vitamin C versus no parenteral vitamin C in hospitalized adults with severe infection. Eligible studies will include at least 1 arm involving any dose of parenteral vitamin C alone or in combination with other cointerventions and at least 1 arm not involving parenteral vitamin C. The primary outcomes of interest will include in-hospital, 30-day, and 90-day mortality. Title and abstract screening, full-text screening, data extraction, and risk of bias evaluation via a modified Risk of Bias 2.0 tool will be conducted independently and in pairs. We will perform random effects modeling for meta-analyses, in which study weights will be generated by using the inverse variance method. We will assess certainty in effect estimates by using the Grading of Recommendations Assessment, Development and Evaluation methodology. Meta-analyses will be updated iteratively as new trial evidence becomes available. Results Among the 1386 citations identified as of March 30, 2021, a total of 17 eligible randomized controlled trials have been identified as of September 2021. We are in the process of updating the search strategy and associated data analyses. Conclusions The results will be of importance to critical care physicians and hospitalists who manage severe infection and COVID-19 in daily practice, and they may directly inform international clinical guidance. Although our systematic review will incorporate the most recent trial evidence, ongoing trials may change our confidence in the estimates of effects, thereby necessitating iterative updates in the form of a living review. Trial Registration PROSPERO CRD42020209187; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=209187 International Registered Report Identifier (IRRID) RR1-10.2196/33989
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Affiliation(s)
- Arnav Agarwal
- Division of General Internal Medicine, Department of Medicine, McMaster University, Hamilton, CA
| | - John Basmaji
- Division of Critical Care, Department of Medicine, Schulich School of Medicine and Dentistry, Western University, London, CA
| | - Shannon M Fernando
- Division of Critical Care, Department of Medicine, University of Ottawa, Ottawa, CA.,Department of Emergency Medicine, University of Ottawa, Ottawa, CA
| | - Fang Zhou Ge
- Michael G. DeGroote School of Medicine, McMaster University, Hamilton, CA
| | - Yingqi Xiao
- Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, CA.,West China School of Nursing/Department of Nursing, West China Hospital, Sichuan University, Chengdu, CN
| | - Haseeb Faisal
- Faculty of Medicine, McMaster University, Hamilton, CA
| | - Kimia Honarmand
- Division of Critical Care, Department of Medicine, Schulich School of Medicine and Dentistry, Western University, London, CA
| | - Mathieu Hylands
- Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, CA
| | - Vincent I Lau
- Department of Critical Care Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, CA
| | | | - Rachel Couban
- Department of Anesthesia, McMaster University, Hamilton, CA
| | - François Lamontagne
- Department of Medicine, Université de Sherbrooke, Sherbrooke, CA.,Centre de recherche du CHU de Sherbrooke, Sherbrooke, CA
| | - Neill Kj Adhikari
- Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, CA.,Department of Critical Care Medicine, Sunnybrook Health Sciences Centre, Room D1.082075 Bayview Avenue, Toronto, CA
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Franco JH, Chen X, Pan ZK. Novel Treatments Targeting the Dysregulated Cell Signaling Pathway during Sepsis. JOURNAL OF CELLULAR SIGNALING 2021; 2:228-234. [PMID: 34988552 PMCID: PMC8725530] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
Previously characterized as a purely immune mediated disease, sepsis is now recognized as a dysregulated multisystem response against a pathogen. Recognition of the infectious agent by pathogen recognition receptors (PRRs) can initiate activation of the NF-κB signaling pathway and promote the secretion of proinflammatory cytokines. During sepsis, the activation of NF-κB is dysregulated and results in cytokine storm, or the pathologic release of cytokines. Current treatments for sepsis rely on broad spectrum antimicrobial medications and fluid replacement therapy, to neutralize the inciting pathogen and maintain adequate blood pressure. The addition of vasopressor therapy is also utilized when sepsis progresses to septic shock, which is defined by treatment resistant hypotension. Even though modern treatment guidelines have improved clinical outcomes, the mortality rate of sepsis and septic shock is still 15-20% and 20-50%, respectively. To reduce mortality, recent sepsis treatment research has focused on investigating novel therapeutics that can attenuate the dysregulated NF-κB signaling pathway. Antioxidants, such as Retinoic acid and Oxytocin, can reduce activation of the NF-κB pathway by neutralizing stimulatory reactive oxygen species (ROS). Likewise, anti-inflammatory agents can also affect the NF-κB pathway by decreasing the secretion of proinflammatory cytokines, such as TNFα and IL-6. Novel anti-inflammatory cytokines, such as IL-37 and IL-38, have recently been characterized and shown to reduce inflammation in mice with bacterial sepsis. Separately, antioxidants and anti-inflammatory cytokines show promise as potential therapies for sepsis, however, a combined therapy including both agents may prove more beneficial in further improving clinical outcomes.
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Affiliation(s)
- Justin H. Franco
- Department of Medical Microbiology and Immunology, University of Toledo College of Medicine and Life Sciences, Toledo, Oh 43614 USA
| | - Xiaohuan Chen
- Department of Medical Microbiology and Immunology, University of Toledo College of Medicine and Life Sciences, Toledo, Oh 43614 USA
| | - Zhixing K. Pan
- Department of Medical Microbiology and Immunology, University of Toledo College of Medicine and Life Sciences, Toledo, Oh 43614 USA
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Krishnan K, Wassermann TB, Tednes P, Bonderski V, Rech MA. Beyond the bundle: Clinical controversies in the management of sepsis in emergency medicine patients. Am J Emerg Med 2021; 51:296-303. [PMID: 34785486 DOI: 10.1016/j.ajem.2021.11.003] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2021] [Revised: 10/29/2021] [Accepted: 11/01/2021] [Indexed: 01/21/2023] Open
Abstract
Sepsis is a condition characterized by life-threatening organ dysfunction caused by a dysregulated host response to infection. The emergency department (ED) serves as a crucial entry point for patients presenting with sepsis. Given the heterogeneous presentation and high mortality rate associated with sepsis and septic shock, several clinical controversies have emerged in the management of sepsis. These include the use of novel therapeutic agents like angiotensin II, hydrocortisone, ascorbic acid, thiamine ("HAT") therapy, and levosimendan, Additionally, controversies with current treatments in vasopressor dosing, and the use of and balanced or unbalanced crystalloid are crucial to consider. The purpose of this review is to discuss clinical controversies in the management of septic patients, including the use of novel medications and dosing strategies, to assist providers in appropriately determining what treatment strategy is best suited for patients.
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Affiliation(s)
- Kavita Krishnan
- Loyola University Chicago, Stritch School of Medicine, Department of Emergency Medicine, Maywood, IL, 60153, United States of America
| | - Travis B Wassermann
- Loyola University Chicago, Stritch School of Medicine, Department of Emergency Medicine, Maywood, IL, 60153, United States of America
| | - Patrick Tednes
- Loyola University Chicago, Stritch School of Medicine, Department of Emergency Medicine, Maywood, IL, 60153, United States of America; Department of Pharmacy, Loyola University Medical Center, Maywood, IL, 60153, United States of America
| | - Veronica Bonderski
- Loyola University Chicago, Stritch School of Medicine, Department of Emergency Medicine, Maywood, IL, 60153, United States of America; Department of Pharmacy, Loyola University Medical Center, Maywood, IL, 60153, United States of America
| | - Megan A Rech
- Loyola University Chicago, Stritch School of Medicine, Department of Emergency Medicine, Maywood, IL, 60153, United States of America; Department of Pharmacy, Loyola University Medical Center, Maywood, IL, 60153, United States of America.
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Klepo L, Ascalic M, Medunjanin D, Copra-Janicijevic A. A new spectrofluorimetric method for the determination of ascorbic acid with bromocresol purple in pharmaceutical samples. SN APPLIED SCIENCES 2021. [DOI: 10.1007/s42452-021-04820-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Abstract
Abstract
Based on the interaction between ascorbic acid and bromocresol purple, a new simple, straightforward, and quick method for the quantification of ascorbic acid is proposed. The procedure is based on the determined quenching effect of ascorbic acid on the natural fluorescence signal of bromocresol purple in the reaction between ascorbic acid and bromocresol purple in phosphate buffer solution (pH 6). The reduction of bromocresol purple fluorescence intensity is detected at 641 nm, while excitation occurs at 318 nm. The linear relationship between the reduced fluorescence intensity of bromocresol purple and the concentration of ascorbic acid is in the range 4.65 × 10–5 to 4.65 × 10–6 mol L−1 (R2 = 0.9964), with the detection limit of 8.77 × 10–7 mol L−1 and quantification limit of 2.35 × 10–5 mol L−1. The findings in this study further show that the new method provides good precision and repeatability, as well as satisfactory recovery values in terms of accuracy. The new method is tested on fifteen samples with different amounts of ascorbic acid and additional components. The effects of interfering components such as citrus bioflavonoids, citric acid, folic acid, paracetamol, calcium, and magnesium carbonate on the intensity of fluorescence of bromocresol purple are also investigated. The effects of interfering components such as citrus bioflavonoids (routine and hesperidin), citric acid, folic acid, paracetamol, calcium, and magnesium carbonate on the intensity of fluorescence of bromocresol purple are also investigated. The results of iodometric titration point out that the new method is effective for the determination of ascorbic acid in pharmaceutical samples.
Article Highlights
A new spectrofluorimetric method for determination of ascorbic acid in pharmaceutical samples using bromocresol purple.
Determination of optimal parameters for ascorbic acid determination in a variety of pharmaceutical samples.
Examination of the influence of additional substances in the pharmaceutical samples on the analysis.
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Schlapbach LJ, de Oliveira CF, Raman S, de Souza D. Metabolic resuscitation in pediatric sepsis: a narrative review. Transl Pediatr 2021; 10:2678-2688. [PMID: 34765493 PMCID: PMC8578751 DOI: 10.21037/tp-21-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2021] [Accepted: 05/27/2021] [Indexed: 12/21/2022] Open
Abstract
Sepsis, defined as infection with associated organ dysfunction, accounts for most childhood deaths due to infection globally. Evidence for the optimal support of children with septic shock refractory to the initial sepsis management bundle remains minimal. There is an urgent need for more effective interventions. Administration of hydrocortisone in children with septic shock might fasten shock resolution, and has been shown to dampen the systemic host immune response, augment adrenergic effects, and support the stress response. Ascorbic acid (vitamin C) is one of the most powerful naturally occurring antioxidants and has beneficial effects on multiple pathways which are severely deranged during septic shock. A regimen combining hydrocortisone, ascorbic acid, and thiamine termed "metabolic resuscitation" or "HAT therapy" has been tested in large trials in critically ill adults with sepsis with conflicting results. Available information on intravenous ascorbic acid indicates an excellent safety profile even at very high doses both in adults and children. Given the pharmacological properties and beneficial effects shown both in vitro and in animal studies, and its safety profile, ascorbic acid either as a single therapy or as part of HAT treatment represents a promising candidate for future pediatric sepsis treatments. While pediatric age groups may be more susceptible to ascorbic acid deficiency during sepsis, there is a lack of high-quality trial data on HAT therapy in this age group. A single centre retrospective study identified potential for mortality benefit in children with septic shock, and the results from a randomized controlled pilot trial are being awaited. It is imperative for pediatric research on ascorbic acid and HAT in children with sepsis to critically investigate key questions related to pharmacology, dosing, timing, feasibility, safety, effects on short- and long-term outcomes, and generalisability in view of the global burden of sepsis.
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Affiliation(s)
- Luregn J Schlapbach
- Child Health Research Centre, The University of Queensland, and Paediatric Intensive Care Unit, Queensland Children's Hospital, Brisbane, QLD, Australia.,Department of Intensive Care and Neonatology, and Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland
| | | | - Sainath Raman
- Child Health Research Centre, The University of Queensland, and Paediatric Intensive Care Unit, Queensland Children's Hospital, Brisbane, QLD, Australia
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Gavelli F, Castello LM, Avanzi GC. Management of sepsis and septic shock in the emergency department. Intern Emerg Med 2021; 16:1649-1661. [PMID: 33890208 PMCID: PMC8354945 DOI: 10.1007/s11739-021-02735-7] [Citation(s) in RCA: 62] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Accepted: 03/30/2021] [Indexed: 12/19/2022]
Abstract
Early management of sepsis and septic shock is crucial for patients' prognosis. As the Emergency Department (ED) is the place where the first medical contact for septic patients is likely to occur, emergency physicians play an essential role in the early phases of patient management, which consists of accurate initial diagnosis, resuscitation, and early antibiotic treatment. Since the issuing of the Surviving Sepsis Campaign guidelines in 2016, several studies have been published on different aspects of sepsis management, adding a substantial amount of new information on the pathophysiology and treatment of sepsis and septic shock. In light of this emerging evidence, the present narrative review provides a comprehensive account of the recent advances in septic patient management in the ED.
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Affiliation(s)
- Francesco Gavelli
- Department of Translational Medicine, Università del Piemonte Orientale UPO, Via Solaroli 17, Novara, Italy.
- Emergency Medicine Department, AOU Maggiore Della Carità, Corso Mazzini 18, Novara, Italy.
| | - Luigi Mario Castello
- Department of Translational Medicine, Università del Piemonte Orientale UPO, Via Solaroli 17, Novara, Italy
- Emergency Medicine Department, AOU Maggiore Della Carità, Corso Mazzini 18, Novara, Italy
| | - Gian Carlo Avanzi
- Department of Translational Medicine, Università del Piemonte Orientale UPO, Via Solaroli 17, Novara, Italy
- Emergency Medicine Department, AOU Maggiore Della Carità, Corso Mazzini 18, Novara, Italy
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Hussein AA, Sabry NA, Abdalla MS, Farid SF. A prospective, randomised clinical study comparing triple therapy regimen to hydrocortisone monotherapy in reducing mortality in septic shock patients. Int J Clin Pract 2021; 75:e14376. [PMID: 34003568 DOI: 10.1111/ijcp.14376] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2021] [Accepted: 05/09/2021] [Indexed: 01/03/2023] Open
Abstract
OBJECTIVES This prospective, comparative and randomised clinical study evaluated the effectiveness of triple therapy regimen (hydrocortisone, thiamine and vitamin C) versus hydrocortisone alone in reducing the mortality rate and preventing progressive organ dysfunction in septic shock patients. METHODS A total of 94 patients were randomly assigned to one of two groups: the first group received hydrocortisone 50 mg/6-h IV for 7 days or till intensive care unit (ICU) discharge, if sooner, followed by tapering. The second group received hydrocortisone 50 mg/6-h IV for 7 days or ICU discharge followed by tapering, vitamin C 1.5 g/6-h IV for 4 days or till ICU discharge and thiamine 200 mg/12-h IV for 4 days or till ICU discharge. RESULTS The triple therapy regimen showed a non-significant reduction in 28-day mortality compared to hydrocortisone alone (17 [36.2%] vs. 21 [44.7%]; P = .4005), but it was significantly lower than the control group regarding shock time and the duration of vasopressor use in days (4.000 [3.000-7.000]; 5.000 [4.000-8.000], [P = .0100]). The patients in the control group were likely to get 0.59 more in SCr level than those in the intervention group by a linear regression model which was significant (P < .05). Also, the number of patients who developed a fever after 216 hours was significantly higher in the control group (P value = .0299). CONCLUSION Vitamin C, thiamine, and hydrocortisone regimen for septic shock management showed non-significant efficacy in decreasing 28-day mortality when compared to hydrocortisone monotherapy. On the other hand, it showed significant efficacy in decreasing the shock time and duration on vasopressors.
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Affiliation(s)
| | - Nirmeen A Sabry
- Clinical pharmacy department, Faculty of Pharmacy, Cairo University, Cairo, Egypt
| | - Maged S Abdalla
- Anaesthesia and Critical Care department, Faculty of Medicine (Kasr-el Ainy), Cairo University, Cairo, Egypt
| | - Samar F Farid
- Department of Clinical Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt
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Jamshidi MR, Zeraati MR, Forouzanfar B, Tahrekhani M, Motamed N. Effects of triple combination of hydrocortisone, thiamine, and Vitamin C on clinical outcome in patients with septic shock: A single-center randomized controlled trial. JOURNAL OF RESEARCH IN MEDICAL SCIENCES : THE OFFICIAL JOURNAL OF ISFAHAN UNIVERSITY OF MEDICAL SCIENCES 2021; 26:47. [PMID: 34484379 PMCID: PMC8383994 DOI: 10.4103/jrms.jrms_593_19] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 01/07/2020] [Revised: 07/30/2020] [Accepted: 01/20/2021] [Indexed: 12/16/2022]
Abstract
BACKGROUND Recent studies suggest that hydrocortisone, Vitamin C, and thiamine alone or in combination may improve the clinical outcomes of patients with septic shock. The aim of this study is the effects of this combination therapy on clinical outcome and sepsis biomarkers in patients with septic shock. MATERIALS AND METHODS Fifty-eight consecutive patients suffering septic shock were randomly assigned into two groups receiving the combination therapy of hydrocortisone (50 mg/6 h, intravenously), Vitamin C (1.5 g/6 h in 100 ml normal saline or DW5%, intravenously), and thiamine (200 mg/12 h in 50 ml normal saline or DW5%, intravenously) or placebo for up to 4 days. RESULTS The decline in procalcitonin, lactate, and leukocyte count 72 h after the initiation of treatment was significantly greater in the intervention as compared to the control group. The intervention group has a significantly lower sequential organ failure assessment score 72 h after treatment (P < 0.001). The mean duration of vasopressor dependency was shorter in the intervention group (P = 0.039). In-hospital death occurred in 10.3% of the patients who received combination therapy and 37.9% in the control group (P = 0.014). CONCLUSION The administration of the triple combination of hydrocortisone, thiamine, and Vitamin C appeared to be effective in improving the clinical outcomes of patients with septic shock and of reducing vasopressor requirements with a significant increase in the rate of improvement of sepsis biomarkers.
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Affiliation(s)
- Mohammad Reza Jamshidi
- Department of Anesthesiology and Critical Care Medcine, Ayatollah Mousavi Hospital, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Mohammad Reza Zeraati
- Department of Anesthesiology and Critical Care Medcine, Ayatollah Mousavi Hospital, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Baharak Forouzanfar
- Department of Anesthesiology and Critical Care Medcine, Ayatollah Mousavi Hospital, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Mehran Tahrekhani
- Department of Nursing Education, Abhar School of Nursing, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Nima Motamed
- Department of Social Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
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