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Zhang X, Lian C, Shi S, Li J, Wang L, Guo Z, Liu N, Wang H, Hu Y, Du B. The 2-Step Mendelian Randomisation Study Assesses Genetic Causality and Potential Mediators of Periodontal Disease and Atrial Fibrillation. Int Dent J 2025; 75:2093-2103. [PMID: 39988492 DOI: 10.1016/j.identj.2024.12.029] [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: 07/18/2024] [Revised: 12/12/2024] [Accepted: 12/13/2024] [Indexed: 02/25/2025] Open
Abstract
INTRODUCTION AND AIMS This study aims to examine the possible causal link between periodontal diseases and atrial fibrillation (AF), with a focus on the modifiable risk factors that facilitate this connection. METHOD Firstly, bidirectional and multivariable Mendelian Randomisation (MR) analyses were conducted using genome-wide association studies (GWAS) data on periodontal disease (87,497 cases/259,234 controls) from FinnGen and AF (55,114 cases/482,295 controls) from AFGen. Then, a 2-step MR approach was employed to evaluate the mediating role and proportions of 25 candidate factors among the direct causality between periodontal disease and AF. RESULTS Periodontal disease was found to be associated with an increased risk of AF (odds ratio 1.16, 95% CI 1.027-1.314, p = .017), independent of other covariates such as dental caries, pulp, and periapical diseases. Conversely, no causal relationship was detected indicating that AF leads to periodontal disease condition. Furthermore, in the 2-step MR analysis, 5 out of 25 candidate mediators were screened as statistically significant. Ranked by partial mediation proportion, these modifiable mediators included weight (30.3%), IL-17 (17.2%), TNF (14.08%), coronary atherosclerosis (13.4%), and hypertension (11.6%). CONCLUSION Our findings demonstrated the genetic causality between periodontal disease and AF. Maintaining oral hygiene, adopting standardised periodontal therapy, and restricting body weight are critical goals for patients with periodontal disease to mitigate disease progression to AF.
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Affiliation(s)
- Xiaohan Zhang
- Department of Cardiovascular Medicine, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Chengzhong Lian
- Department of Oral Medicine, Shanxi Provincial People's Hospital, Taiyuan, Shanxi, China
| | - Shuqing Shi
- Department of Cardiovascular Medicine, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Jiaran Li
- Department of Cardiovascular Medicine, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Lianxin Wang
- Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, China
| | - Zezhen Guo
- Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, New South Wales, Australia
| | - Naixu Liu
- Department of Pediatrics, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Huan Wang
- Department of Cardiovascular Medicine, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Yuanhui Hu
- Department of Cardiovascular Medicine, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
| | - Bai Du
- Department of Cardiovascular Medicine, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
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2
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Saetang M, Wasinwong W, Oofuvong M, Tanasansutthiporn J, Rattanapittayaporn L, Petsakul S, Duangpakdee P, Rodneam P, Boonthum P, Khunakanan S, Churuangsuk C, Sriwimol W, Chantarokon A, Nuanjun K, Yongsata D. Effect of Combined Vitamin C and Thiamine Therapy on Myocardial and Inflammatory Markers in Cardiac Surgery: A Randomized Controlled Clinical Trial. Nutrients 2025; 17:1006. [PMID: 40290059 PMCID: PMC11944524 DOI: 10.3390/nu17061006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2025] [Revised: 03/07/2025] [Accepted: 03/11/2025] [Indexed: 04/30/2025] Open
Abstract
Background: Oxidative stress and systemic inflammation during cardiac surgery can lead to postoperative complications. Although vitamin C and thiamine (vitamin B1) have individually demonstrated protective effects, their combined effects remain underexplored. This study aimed to evaluate the efficacy of combined vitamin C and B1 therapy versus that of vitamin C alone in reducing inflammatory and cardiac biomarkers and improving postoperative outcomes in patients undergoing cardiac surgery. Methods: In this prospective, double-blind, randomized controlled trial, 64 patients scheduled for elective cardiac surgery at a tertiary care center were randomized to receive either 1000 mg vitamin C or a combination of 1000 mg vitamin C and 100 mg vitamin B1 at four perioperative time points. Primary outcomes included changes in inflammatory biomarkers [C-reactive protein, interleukin-6 (IL-6), and white blood cells], and cardiac biomarkers [creatine kinase-MB, Troponin-I, and lactate dehydrogenase]. Secondary outcomes included hemodynamic parameters and left ventricular function. Results: Compared with vitamin C alone, combined vitamin B1 and vitamin C significantly reduced postoperative cardiac biomarker levels. IL-6 levels were significantly lower immediately in the combined group; however, this effect was not sustained at 24 h post-surgery. Up to 24 h after surgery, no significant differences in hemodynamic stability or left ventricular ejection were observed between the groups. Notably, the combined therapy group demonstrated a lower incidence of postoperative arrhythmias and shorter dobutamine duration within 24 postoperatively. Conclusions: Combined vitamin C and B1 therapy significantly reduced markers of myocardial injury and early inflammatory responses (IL-6) in patients undergoing cardiac surgery, suggesting its potential as a protective agent.
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Affiliation(s)
- Mantana Saetang
- Department of Anesthesiology, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand; (M.S.); (M.O.); (J.T.); (L.R.); (S.P.); (A.C.); (K.N.); (D.Y.)
| | - Wirat Wasinwong
- Department of Anesthesiology, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand; (M.S.); (M.O.); (J.T.); (L.R.); (S.P.); (A.C.); (K.N.); (D.Y.)
| | - Maliwan Oofuvong
- Department of Anesthesiology, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand; (M.S.); (M.O.); (J.T.); (L.R.); (S.P.); (A.C.); (K.N.); (D.Y.)
| | - Jutarat Tanasansutthiporn
- Department of Anesthesiology, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand; (M.S.); (M.O.); (J.T.); (L.R.); (S.P.); (A.C.); (K.N.); (D.Y.)
| | - Laortip Rattanapittayaporn
- Department of Anesthesiology, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand; (M.S.); (M.O.); (J.T.); (L.R.); (S.P.); (A.C.); (K.N.); (D.Y.)
| | - Sutthasinee Petsakul
- Department of Anesthesiology, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand; (M.S.); (M.O.); (J.T.); (L.R.); (S.P.); (A.C.); (K.N.); (D.Y.)
| | - Pongsanae Duangpakdee
- Department of Surgery, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand; (P.D.); (P.R.); (P.B.); (S.K.)
| | - Puripong Rodneam
- Department of Surgery, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand; (P.D.); (P.R.); (P.B.); (S.K.)
| | - Parin Boonthum
- Department of Surgery, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand; (P.D.); (P.R.); (P.B.); (S.K.)
| | - Supphamongkhon Khunakanan
- Department of Surgery, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand; (P.D.); (P.R.); (P.B.); (S.K.)
| | - Chaitong Churuangsuk
- Department of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand;
| | - Wilaiwan Sriwimol
- Department of Pathology, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand;
| | - Amphan Chantarokon
- Department of Anesthesiology, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand; (M.S.); (M.O.); (J.T.); (L.R.); (S.P.); (A.C.); (K.N.); (D.Y.)
| | - Kanjana Nuanjun
- Department of Anesthesiology, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand; (M.S.); (M.O.); (J.T.); (L.R.); (S.P.); (A.C.); (K.N.); (D.Y.)
| | - Dararat Yongsata
- Department of Anesthesiology, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand; (M.S.); (M.O.); (J.T.); (L.R.); (S.P.); (A.C.); (K.N.); (D.Y.)
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3
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Malektojari A, Javidfar Z, Ghazizadeh S, Lahuti S, Shokraei R, Zeinaee M, Badele A, Mirzadeh R, Ashrafi M, Afra F, Ersi MH, Heydari M, Ziaei A, Rezvani Z, Mah J, Zeraatkar D, Abbaszadeh S, Pitre T. Effectiveness of Anti-Inflammatory Agents to Prevent Atrial Fibrillation After Cardiac Surgery: A Systematic Review and Network Meta-Analysis. CJC Open 2025; 7:35-45. [PMID: 39872654 PMCID: PMC11763850 DOI: 10.1016/j.cjco.2024.10.008] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2024] [Accepted: 10/17/2024] [Indexed: 01/30/2025] Open
Abstract
Background Preventing postoperative atrial fibrillation (POAF) as one of the most significant complications of cardiovascular surgeries remains a major clinical challenge. We conducted a systematic review with network meta-analysis of randomized controlled trials, to identify the most effective and safe anti-inflammatory drugs to prevent new-onset POAF. Methods MEDLINE, Embase, Web of Science, and Cochrane Library were searched without language or publication-date restriction on August 8, 2022 (updated on August 8, 2023). We assessed the risk of bias of included trials using the Cochrane risk-of-bias 2.0 tool. We conducted a frequentist random-effects network meta-analysis in R, and we assessed the certainty of evidence using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach. Results A total of 85 trials reported the incidence of new-onset POAF, including 18,981 patients. Use of nonsteroidal anti-inflammatory drugs (relative risk [RR] 0.37 [95% confidence interval [CI] 0.23-0.59]) and statins (RR 0.56 [95% CI 0.45-0.7]) potentially reduced the risk of POAF compared with placebo (both with a moderate certainty level). Use of fish oil in combination with vitamins C and E (RR 0.30 [95% CI 0.13-0.68]) may reduce the risk of POAF, compared with placebo (low level of certainty). Use of colchicine (RR 0.62 [95% CI 0.45- 0.85]), corticosteroids (RR 0.70 [95% CI 0.59-0.82]), and N-acetylcysteine (RR 0.69 [95% CI 0.49- 0.98]) may reduce the risk of POAF (all with a low level of certainty). None of the interventions had a significant effect on mortality rate or risk of serious adverse effects. Conclusions Use of nonsteroidal anti-inflammatory drugs and statins probably are effective in preventing new-onset POAF, with a moderate level of certainty, compared to placebo.
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Affiliation(s)
- Alireza Malektojari
- Cardiovascular Research Center, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
- Evidence Based Medicine Center, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
| | - Zahra Javidfar
- Faculty of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
| | - Sara Ghazizadeh
- Cardiovascular Research Center, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
- Evidence Based Medicine Center, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
| | - Shaghayegh Lahuti
- Faculty of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
| | - Rahele Shokraei
- Infectious and Tropical Diseases Research Center, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
| | - Mohadeseh Zeinaee
- Faculty of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
| | - Amirhosein Badele
- Faculty of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
| | - Raziyeh Mirzadeh
- Faculty of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
| | - Mitra Ashrafi
- Evidence Based Medicine Center, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
| | - Fateme Afra
- Faculty of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
| | - Mohammad Hamed Ersi
- Evidence Based Medicine Center, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
- Faculty of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
| | - Marziyeh Heydari
- Faculty of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
| | - Ava Ziaei
- Evidence Based Medicine Center, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
| | - Zohreh Rezvani
- Xi’an Jiaotong University Health Science Center, Xi’an, Shaanxi, China
| | - Jasmine Mah
- Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada
| | - Dena Zeraatkar
- Department of Health Research Methods Evidence and Impact, McMaster University, Hamilton, Ontario, Canada
- Department of Anesthesiology, McMaster University, Hamilton, Ontario, Canada
| | - Shahin Abbaszadeh
- Cardiovascular Research Center, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
| | - Tyler Pitre
- Division of Respirology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada
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4
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Gawałko M, Middeldorp ME, Saljic A, Penders J, Jespersen T, Albert CM, Marcus GM, Wong CX, Sanders P, Linz D. Diet and risk of atrial fibrillation: a systematic review. Eur Heart J 2024; 45:4259-4274. [PMID: 39288159 DOI: 10.1093/eurheartj/ehae551] [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: 04/16/2024] [Revised: 06/24/2024] [Accepted: 08/13/2024] [Indexed: 09/19/2024] Open
Abstract
Atrial fibrillation (AF) is the most prevalent sustained cardiac arrhythmia. Comprehensive modification of established AF risk factors combined with dietary interventions and breaking deleterious habits has been shown to reduce AF burden and recurrence. Numerous AF risk factors, such as diabetes, obesity or hypertension can be partially related to dietary and lifestyle choices. Therefore, dietary interventions may have potential as a therapeutic approach in AF. Based on available data, current guidelines recommend alcohol abstinence or reduction to decrease AF symptoms, burden, and progression, and do not indicate the need for caffeine abstention to prevent AF episodes (unless it is a trigger for AF symptoms). Uncertainty persists regarding harms or benefits of other dietary factors including chocolate, fish, salt, polyunsaturated and monounsaturated fatty acids, vitamins, and micronutrients. This article provides a systematic review of the association between AF and both dietary patterns and components. Additionally, it discusses potentially related mechanisms and introduces different strategies to assess patients' nutrition patterns, including mobile health solutions and diet indices. Finally, it highlights the gaps in knowledge requiring future investigation.
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Affiliation(s)
- Monika Gawałko
- 1st Department of Cardiology, Medical University of Warsaw, Banacha 1A, 02-097 Warsaw, Poland
- Department of Cardiology, Maastricht University Medical Centre and Cardiovascular Research Institute Maastricht, Universiteitssingel 50, 6229 ER Maastricht, The Netherlands
- Institute of Pharmacology, West German Heart and Vascular Centre, University Duisburg-Essen, Hufelandstraße 55, 45147 Essen, Germany
- Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark
- Centre for Heart Rhythm Disorders, Royal Adelaide Hospital, University of Adelaide, 1 Port Road, SA 5000 Adelaide, Australia
| | - Melissa E Middeldorp
- Centre for Heart Rhythm Disorders, Royal Adelaide Hospital, University of Adelaide, 1 Port Road, SA 5000 Adelaide, Australia
- Department of Cardiology, Smidt Heart Institute, Cedars-Sinai Medical Center, 127 S San Vincente Blvd, AHSP 3100 Los Angeles, CA, USA
- Cardiology Department, University Medical Centre Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands
| | - Arnela Saljic
- Institute of Pharmacology, West German Heart and Vascular Centre, University Duisburg-Essen, Hufelandstraße 55, 45147 Essen, Germany
- Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark
| | - John Penders
- Department of Medical Microbiology, Infectious Diseases and Infection Prevention, School for Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University Medical Centre, Universiteitssingel 40, 6229 ER Maastricht, The Netherlands
| | - Thomas Jespersen
- Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark
| | - Christine M Albert
- Department of Cardiology, Smidt Heart Institute, Cedars-Sinai Medical Center, 127 S San Vincente Blvd, AHSP 3100 Los Angeles, CA, USA
- Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA
| | - Gregory M Marcus
- Division of Cardiology, University of California San Francisco, 505 Parnassus Avenue, San Francisco, CA 94143, USA
| | - Christopher X Wong
- Centre for Heart Rhythm Disorders, Royal Adelaide Hospital, University of Adelaide, 1 Port Road, SA 5000 Adelaide, Australia
- Division of Cardiology, University of California San Francisco, 505 Parnassus Avenue, San Francisco, CA 94143, USA
| | - Prashanthan Sanders
- Centre for Heart Rhythm Disorders, Royal Adelaide Hospital, University of Adelaide, 1 Port Road, SA 5000 Adelaide, Australia
| | - Dominik Linz
- Department of Cardiology, Maastricht University Medical Centre and Cardiovascular Research Institute Maastricht, Universiteitssingel 50, 6229 ER Maastricht, The Netherlands
- Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark
- Department of Cardiology, Radboud University Medical Centre, Geert Grooteplein Zuid 10, 6525 GA Nijmegen, The Netherlands
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5
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Ćurko-Cofek B, Jenko M, Taleska Stupica G, Batičić L, Krsek A, Batinac T, Ljubačev A, Zdravković M, Knežević D, Šoštarič M, Sotošek V. The Crucial Triad: Endothelial Glycocalyx, Oxidative Stress, and Inflammation in Cardiac Surgery-Exploring the Molecular Connections. Int J Mol Sci 2024; 25:10891. [PMID: 39456673 PMCID: PMC11508174 DOI: 10.3390/ijms252010891] [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: 09/11/2024] [Revised: 10/05/2024] [Accepted: 10/08/2024] [Indexed: 10/28/2024] Open
Abstract
Since its introduction, the number of heart surgeries has risen continuously. It is a high-risk procedure, usually involving cardiopulmonary bypass, which is associated with an inflammatory reaction that can lead to perioperative and postoperative organ dysfunction. The extent of complications following cardiac surgery has been the focus of interest for several years because of their impact on patient outcomes. Recently, numerous scientific efforts have been made to uncover the complex mechanisms of interaction between inflammation, oxidative stress, and endothelial dysfunction that occur after cardiac surgery. Numerous factors, such as surgical and anesthetic techniques, hypervolemia and hypovolemia, hypothermia, and various drugs used during cardiac surgery trigger the development of systemic inflammatory response and the release of oxidative species. They affect the endothelium, especially endothelial glycocalyx (EG), a thin surface endothelial layer responsible for vascular hemostasis, its permeability and the interaction between leukocytes and endothelium. This review highlights the current knowledge of the molecular mechanisms involved in endothelial dysfunction, particularly in the degradation of EG. In addition, the major inflammatory events and oxidative stress responses that occur in cardiac surgery, their interaction with EG, and the clinical implications of these events have been summarized and discussed in detail. A better understanding of the complex molecular mechanisms underlying cardiac surgery, leading to endothelial dysfunction, is needed to improve patient management during and after surgery and to develop effective strategies to prevent adverse outcomes that complicate recovery.
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Affiliation(s)
- Božena Ćurko-Cofek
- Department of Physiology, Immunology and Pathophysiology, Faculty of Medicine, University of Rijeka, Braće Branchetta 20, 51000 Rijeka, Croatia
| | - Matej Jenko
- Clinical Department of Anaesthesiology and Surgical Intensive Care, University Medical Centre, Zaloska 7, 1000 Ljubljana, Slovenia; (M.J.); (G.T.S.); (M.Š.)
- Medical Faculty, University of Ljubljana, Vrazov Trg 2, 1000 Ljubljana, Slovenia
| | - Gordana Taleska Stupica
- Clinical Department of Anaesthesiology and Surgical Intensive Care, University Medical Centre, Zaloska 7, 1000 Ljubljana, Slovenia; (M.J.); (G.T.S.); (M.Š.)
| | - Lara Batičić
- Department of Medical Chemistry, Biochemistry and Clinical Chemistry, Faculty of Medicine, University of Rijeka, Braće Branchetta 20, 51000 Rijeka, Croatia;
| | - Antea Krsek
- Faculty of Medicine, University of Rijeka, Braće Branchetta 20, 51000 Rijeka, Croatia;
| | - Tanja Batinac
- Department of Clinical Medical Sciences I, Faculty of Health Studies, University of Rijeka, Viktora Cara Emina 2, 51000 Rijeka, Croatia; (T.B.); (V.S.)
| | - Aleksandra Ljubačev
- Department of Surgery, Faculty of Medicine, University of Rijeka, Braće Branchetta 20, 51000 Rijeka, Croatia;
| | - Marko Zdravković
- Department of Anaesthesiology, Intensive Care and Pain Management, University Medical Centre Maribor, Ljubljanska Ulica 5, 2000 Maribor, Slovenia;
| | - Danijel Knežević
- Department of Anesthesiology, Reanimatology, Emergency and Intensive Care Medicine, University of Rijeka, Braće Branchetta 20, 51000 Rijeka, Croatia;
| | - Maja Šoštarič
- Clinical Department of Anaesthesiology and Surgical Intensive Care, University Medical Centre, Zaloska 7, 1000 Ljubljana, Slovenia; (M.J.); (G.T.S.); (M.Š.)
- Medical Faculty, University of Ljubljana, Vrazov Trg 2, 1000 Ljubljana, Slovenia
| | - Vlatka Sotošek
- Department of Clinical Medical Sciences I, Faculty of Health Studies, University of Rijeka, Viktora Cara Emina 2, 51000 Rijeka, Croatia; (T.B.); (V.S.)
- Department of Anesthesiology, Reanimatology, Emergency and Intensive Care Medicine, University of Rijeka, Braće Branchetta 20, 51000 Rijeka, Croatia;
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6
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Wang C, Sun Z, Zhou W. A commentary on 'Efficacy and safety of vitamin C for atrial fibrillation after cardiac surgery: a meta-analysis with trial sequential analysis of randomized controlled trials'. Int J Surg 2024; 110:4416-4417. [PMID: 38445473 PMCID: PMC11254203 DOI: 10.1097/js9.0000000000001269] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2024] [Accepted: 02/21/2024] [Indexed: 03/07/2024]
Affiliation(s)
- Changzhong Wang
- Graduate School of Tianjin University of Traditional Chinese Medicine
| | - Zijin Sun
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing,People’s Republic of China
| | - Wei Zhou
- The Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China
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7
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Athanasiou A, Charalambous M, Anastasiou T, Aggeli K, Soteriades ES. Preoperative and postoperative administration of vitamin C in cardiac surgery patients - settings, dosages, duration, and clinical outcomes: a narrative review. Ann Med Surg (Lond) 2024; 86:3591-3607. [PMID: 38846824 PMCID: PMC11152825 DOI: 10.1097/ms9.0000000000002112] [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: 01/30/2024] [Accepted: 04/16/2024] [Indexed: 06/09/2024] Open
Abstract
Vitamin C or ascorbic acid is a water-soluble vitamin capable of directly donating electrons to reactive oxygen species, attenuating electrical remodeling, and cardiac dysfunction in patients undergoing cardiac surgery (CS), considered one of the most effective defenses against free radicals in the blood, thus being one of the first antioxidants consumed during oxidative stress. The aim of this review is to assess the effects of perioperative administration of vitamin C in CS patients. A comprehensive literature search was conducted in order to identify prospective cohort studies and/or randomized controlled trials reporting on the perioperative effects of vitamin C among adult patients undergoing CS. Studies published between January 1980 to December 2022 were included in our search, resulting in a total of 31 articles that met all our inclusion criteria. There seems to be a beneficial effect of vitamin C supplementation in arrhythmias such as in postoperative atrial fibrillation, reduction of ICU length of stay, and hospital length of stay, reduction in postoperative ventilation time, in inotropic demand, and in postoperative fatigue. Vitamin C can act as a scavenger of free radicals to decrease the peroxidation of the lipids present in the cell membrane, and to protect the myocardium postoperatively from ischemia/reperfusion injury, thus attenuating oxidative stress and inflammation. It represents a readily available and cost-effective strategy that could improve the outcome of patients undergoing CS, by reducing the risk of serious cardiovascular adverse events, both perioperatively and postoperatively.
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Affiliation(s)
| | | | | | - Konstantina Aggeli
- Department of Cardiology, ‘Hippocrates’ General Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Elpidoforos S. Soteriades
- Healthcare Management Program, School of Economics and Management, Open University of Cyprus, Nicosia, Cyprus
- Department of Environmental Health, Environmental and Occupational Medicine and Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
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8
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Privšek M, Strnad M, Markota A. Addition of Vitamin C Does Not Decrease Neuron-Specific Enolase Levels in Adult Survivors of Cardiac Arrest-Results of a Randomized Trial. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:103. [PMID: 38256364 PMCID: PMC10818462 DOI: 10.3390/medicina60010103] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/10/2023] [Revised: 12/16/2023] [Accepted: 01/03/2024] [Indexed: 01/24/2024]
Abstract
Background and Objectives: Survival with favorable neurologic outcomes after out-of-hospital cardiac arrest (OHCA) remains elusive. Post-cardiac arrest syndrome (PCAS) involves myocardial and neurological injury, ischemia-reperfusion response, and underlying pathology. Neurologic injury is a crucial determinant of survival and functional outcomes, with damage caused by free radicals among the responsible mechanisms. This study explores the feasibility of adding intravenous vitamin C to the treatment of OHCA survivors, aiming to mitigate PCAS. Vitamin C, a nutrient with antioxidative and free radical-scavenging properties, is often depleted in critically ill patients. Materials and Methods: This randomized, double-blinded trial was conducted at a tertiary-level university hospital with adult OHCA survivors. Participants received either standard care or the addition of 1.5 g of intravenous vitamin C every 12 h for eight consecutive doses. Neurologic injury was assessed using neuron-specific enolase (NSE) levels, with additional clinical and laboratory outcomes, such as enhanced neuroprognostication factors, inflammatory markers, and cardiac parameters. Results: NSE levels were non-significantly higher in patients who received vitamin C compared to the placebo group (55.05 µg/L [95% confidence interval (CI) 26.7-124.0] vs. 39.4 µg/L [95% CI 22.6-61.9], p > 0.05). Similarly, a non-significantly greater proportion of patients in the vitamin C group developed myoclonus in the first 72 h. We also observed a non-significantly shorter duration of mechanical ventilation, fewer arrhythmias, and reduced length of stay in the intensive care unit in the group of patients who received vitamin C (p = 0.031). However, caution is warranted in interpretation of our results due to the small number of participants. Conclusions: Our findings suggest that intravenous vitamin C should not be used outside of clinical trials for OHCA survivors. Due to the small sample size and conflicting results, further research is needed to determine the potential role of vitamin C in post-cardiac arrest care.
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Affiliation(s)
- Matevž Privšek
- Emergency Medical Services, Healthcare Centre Dr. Adolf Drolc, Cesta Proletarskih Brigad 21, 2000 Maribor, Slovenia;
| | - Matej Strnad
- Emergency Medical Services, Healthcare Centre Dr. Adolf Drolc, Cesta Proletarskih Brigad 21, 2000 Maribor, Slovenia;
- Emergency Department, University Medical Centre Maribor, Ljubljanska Ulica 5, 2000 Maribor, Slovenia
- Department of Emergency Medicine, Faculty of Medicine, University of Maribor, Taborska Ulica 8, 2000 Maribor, Slovenia
| | - Andrej Markota
- Department of Medical Intensive Care, Clinic of Internal Medicine, University Medical Centre Maribor, 2000 Maribor, Slovenia;
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9
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Al-Subu AM, Long MT, Nelson KL, Amond KL, Lasarev MR, Ferrazzano PA, Lushaj EB, Anagnostopoulos PV. Risk of Hypovitaminosis and Vitamin C Deficiency in Pediatric Patients Undergoing Cardiopulmonary Bypass. Pediatr Cardiol 2023; 44:1487-1494. [PMID: 37498330 DOI: 10.1007/s00246-023-03243-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2023] [Accepted: 07/14/2023] [Indexed: 07/28/2023]
Abstract
Vitamin C levels are known rapidly decrease in adult critical illness. Vitamin C scavenges free radicals, provides critical protection of the endothelial barrier, and improves endothelial responsiveness to catecholamines. Children with congenital heart disease and undergoing cardiac surgery might be at increased risk for low circulating vitamin C levels. A prospective single-center observational study investigated perioperative changes in vitamin C levels in critically ill Children who underwent congenital heart surgery using CPB. Vitamin C serum levels were collected preoperatively and postoperatively (upon admission to the ICU, 24 and 72 h). Linear mixed-effect model was used to estimate mean circulating concentration of vitamin C and to estimate changes in concentration over time. Primary outcome was change in circulating levels of vitamin C before and after CPB. Secondary outcomes were hospital length of stay (LOS), acute kidney injury (AKI), and illness severity. Forty-one patients with a median age of 4.5 [interquartile range (IQR) 2.6-65.6] months at the time of surgery were consented and enrolled. Median CPB duration was 130 [90-175] minutes, and hospital LOS was 9.1 [5.2-19] days. Mean vitamin C levels (μmol/L) before CPB, at PICU admission, 24 h, and 72 h were 82.0 (95% CI 73.4-90.7), 53.4 (95% CI 44.6,62.0), 55.1 (95% CI 46.3,63.8), and 59.2 (95% CI 50.3,68.1), respectively. Upon postoperative admission to the PICU, vitamin C levels decreased by 28.7 (95% CI 20.6-36.8; p < 0.001) μmol/L, whereas levels at 24 and 72 h recovered and did not differ substantially from concentrations reported upon PICU admission (p > 0.15). Changes in vitamin C concentration were not associated with CPB time, STAT mortality category, age, or PIM3. Three patients had post-CPB hypovitaminosis C or vitamin C deficiency. Reduction in vitamin C levels was not associated with hospital LOS (p = 0.673). A 25 μmol/L decrease in vitamin C levels upon PICU admission was associated with developing AKI (aOR = 3.65; 95% CI 1.01-18.0, p = 0.049). Pediatric patients undergoing cardiac surgery with CPB showed decreased vitamin C levels during the immediate postoperative period. Effects of hypovitaminosis C and vitamin C deficiency in this population remain unclear.
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Affiliation(s)
- Awni M Al-Subu
- Division of Pediatric Critical Care Medicine, Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, 600 Highland Ave Rm H6/535, Madison, WI, 53792, USA.
| | - Micah T Long
- Division of Critical Care, Department of Anesthesiology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Kari L Nelson
- Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Kate L Amond
- Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Michael R Lasarev
- Department of Biostatistics and Medical Informatics, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Peter A Ferrazzano
- Division of Pediatric Critical Care Medicine, Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, 600 Highland Ave Rm H6/535, Madison, WI, 53792, USA
| | - Entela B Lushaj
- Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Petros V Anagnostopoulos
- Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
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10
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Xu C, Yi T, Tan S, Xu H, Hu Y, Ma J, Xu J. Association of Oral or Intravenous Vitamin C Supplementation with Mortality: A Systematic Review and Meta-Analysis. Nutrients 2023; 15:1848. [PMID: 37111066 PMCID: PMC10146309 DOI: 10.3390/nu15081848] [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: 03/01/2023] [Revised: 03/21/2023] [Accepted: 04/10/2023] [Indexed: 04/29/2023] Open
Abstract
Mortality is the most clinically serious outcome, and its prevention remains a constant struggle. This study was to assess whether intravenous or oral vitamin C (Vit-C) therapy is related to reduced mortality in adults. Data from Medline, Embase, and the Cochrane Central Register databases were acquired from their inception to 26 October 2022. All randomized controlled trials (RCTs) involving intravenous or oral Vit-C against a placebo or no therapy for mortality were selected. The primary outcome was all-cause mortality. Secondary outcomes were sepsis, COVID-19, cardiac surgery, noncardiac surgery, cancer, and other mortalities. Forty-four trials with 26540 participants were selected. Although a substantial statistical difference was observed in all-cause mortality between the control and the Vit-C-supplemented groups (p = 0.009, RR 0.87, 95% CI 0.78 to 0.97, I2 = 36%), the result was not validated by sequential trial analysis. In the subgroup analysis, mortality was markedly reduced in Vit-C trials with the sepsis patients (p = 0.005, RR 0.74, 95% CI 0.59 to 0.91, I2 = 47%), and this result was confirmed by trial sequential analysis. In addition, a substantial statistical difference was revealed in COVID-19 patient mortality between the Vit-C monotherapy and the control groups (p = 0.03, RR 0.84, 95% CI 0.72 to 0.98, I2 = 0%). However, the trial sequential analysis suggested the need for more trials to confirm its efficacy. Overall, Vit-C monotherapy does decrease the risk of death by sepsis by 26%. To confirm Vit-C is associated with reduced COVID-19 mortality, additional clinical random control trials are required.
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Affiliation(s)
- Chongxi Xu
- Department of Neurosurgery, West China Hospital, Sichuan University, No. 37, Guoxue Alley, Wuhou District, Chengdu 610000, China
| | - Tong Yi
- Department of Neurology, The Second People’s Hospital of Deyang City, No. 340 Minjiang West Road, Deyang 618000, China
| | - Siwen Tan
- Outpatient Department, West China Hospital, Sichuan University, No. 37, Guoxue Alley, Wuhou District, Chengdu 610000, China
| | - Hui Xu
- Department of Neurosurgery, The Second People’s Hospital of Liangshan Yi, Autonomous Prefecture, Liangshan 615000, China
| | - Yu Hu
- Department of Neurosurgery, West China Hospital, Sichuan University, No. 37, Guoxue Alley, Wuhou District, Chengdu 610000, China
| | - Junpeng Ma
- Department of Neurosurgery, West China Hospital, Sichuan University, No. 37, Guoxue Alley, Wuhou District, Chengdu 610000, China
| | - Jianguo Xu
- Department of Neurosurgery, West China Hospital, Sichuan University, No. 37, Guoxue Alley, Wuhou District, Chengdu 610000, China
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11
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Dresen E, Lee ZY, Hill A, Notz Q, Patel JJ, Stoppe C. History of scurvy and use of vitamin C in critical illness: A narrative review. Nutr Clin Pract 2023; 38:46-54. [PMID: 36156315 DOI: 10.1002/ncp.10914] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2022] [Revised: 08/01/2022] [Accepted: 08/28/2022] [Indexed: 01/11/2023] Open
Abstract
In 1747, an important milestone in the history of clinical research was set, as the Scottish surgeon James Lind conducted the first randomized controlled trial. Lind was interested in scurvy, a severe vitamin C deficiency which caused the death of thousands of British seamen. He found that a dietary intervention with oranges and lemons, which are rich in vitamin C by nature, was effective to recover from scurvy. Because of its antioxidative properties and involvement in many biochemical processes, the essential micronutrient vitamin C plays a key role in the human biology. Moreover, the use of vitamin C in critical illness-a condition also resulting in death of thousands in the 21st century-has gained increasing interest, as it may restore vascular responsiveness to vasoactive agents, ameliorate microcirculatory blood flow, preserve endothelial barriers, augment bacterial defense, and prevent apoptosis. Because of its redox potential and powerful antioxidant capacity, vitamin C represents an inexpensive and safe antioxidant, with the potential to modify the inflammatory cascade and improve clinical outcomes of critically ill patients. This narrative review aims to update and provide an overview on the role of vitamin C in the human biology and in critically ill patients, and to summarize current evidence on the use of vitamin C in diverse populations of critically ill patients, in specific focusing on patients with sepsis and coronavirus disease 2019.
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Affiliation(s)
- Ellen Dresen
- Department of Anaesthesiology, Intensive Care, Emergency, and Pain Medicine, University Hospital Wuerzburg, Wuerzburg, Germany
| | - Zheng-Yii Lee
- Department of Anaesthesiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Aileen Hill
- Department of Anesthesiology and Intensive Care Medicine, University Hospital RWTH Aachen, Aachen, Germany
| | - Quirin Notz
- Department of Anaesthesiology, Intensive Care, Emergency, and Pain Medicine, University Hospital Wuerzburg, Wuerzburg, Germany
| | - Jayshil J Patel
- Division of Pulmonary and Critical Care Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
| | - Christian Stoppe
- Department of Anaesthesiology, Intensive Care, Emergency, and Pain Medicine, University Hospital Wuerzburg, Wuerzburg, Germany
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12
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Hill A, Starchl C, Dresen E, Stoppe C, Amrein K. An update of the effects of vitamins D and C in critical illness. Front Med (Lausanne) 2023; 9:1083760. [PMID: 36726354 PMCID: PMC9885715 DOI: 10.3389/fmed.2022.1083760] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2022] [Accepted: 12/20/2022] [Indexed: 01/12/2023] Open
Abstract
Many critically ill patients are vitamin D and vitamin C deficient and the current international guidelines state that hypovitaminoses should be compensated. However, uncertainty about optimal dosage, timing and indication exists in clinical routine, mainly due to the conflicting evidence. This narrative review discusses both micronutrients with regards to pathophysiology, clinical evidence of benefits, potential risks, and guideline recommendations. Evidence generated from the most recent clinical trials are summarized and discussed. In addition, pragmatic tips for the application of these vitamins in the clinical routine are given. The supplementations of vitamin D and C represent cost-effective and simple interventions with excellent safety profiles. Regarding vitamin D, critically ill individuals require a loading dose to improve 25(OH)D levels within a few days, followed by a daily or weekly maintenance dose, usually higher doses than healthy individuals are needed. For vitamin C, dosages of 100-200 mg/d are recommended for patients receiving parenteral nutrition, but needs may be as high as 2-3 g/d in acutely ill patients.
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Affiliation(s)
- Aileen Hill
- Department of Anesthesiology, University Hospital RWTH Aachen, Aachen, Germany,Department of Intensive and Intermediate Care, University Hospital RWTH Aachen, Aachen, Germany,*Correspondence: Aileen Hill,
| | - Christina Starchl
- Klinische Abteilung für Endokrinologie und Diabetologie, Klinik für Innere Medizin, Medizinische Universität Graz, Graz, Austria
| | - Ellen Dresen
- Department of Anaesthesiology, Intensive Care, Emergency, and Pain Medicine, University Hospital Würzburg, Würzburg, Germany
| | - Christian Stoppe
- Department of Anaesthesiology, Intensive Care, Emergency, and Pain Medicine, University Hospital Würzburg, Würzburg, Germany,Department of Cardiac Anesthesiology and Intensive Care Medicine, Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Karin Amrein
- Klinische Abteilung für Endokrinologie und Diabetologie, Klinik für Innere Medizin, Medizinische Universität Graz, Graz, Austria,Karin Amrein,
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13
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Tai YH, Wu HL, Chu YH, Huang CH, Ho ST, Lin TC, Lu CC. Vitamin C supplementation attenuates oxidative stress and improves erythrocyte deformability in cardiac surgery with cardiopulmonary bypass. CHINESE J PHYSIOL 2022; 65:241-249. [PMID: 36308079 DOI: 10.4103/0304-4920.358234] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/16/2023] Open
Abstract
Cardiopulmonary bypass (CPB) depletes endogenous Vitamin C and generates oxidative stress in cardiac surgery. This study aimed to clarify whether Vitamin C supplementation reduces oxidant production and improves erythrocyte deformability in cardiac surgery with CPB. In a randomized and controlled design, 30 eligible patients undergoing cardiac surgery with hypothermic CPB were equally assigned to the Vitamin C group and control group. Subjects of the Vitamin C group and control group received an intravenous infusion of Vitamin C 20 mg·kg-1 and a placebo during rewarming period of CPB, respectively. We measured the plasma level of reactive oxygen species (ROS) and phosphorylation levels of non-muscle myosin IIA (NMIIA) in erythrocyte membrane, as an index of erythrocyte deformability, before and after CPB. Vitamin C supplementation attenuated the surge in plasma ROS after CPB, mean 1.661 ± standard deviation 0.801 folds in the Vitamin C group and 2.743 ± 1.802 in the control group. The tyrosine phosphorylation level of NMIIA after CPB was upregulated in the Vitamin C group compared to the control group, 2.159 ± 0.887 folds and 1.384 ± 0.445 (P = 0.0237). In addition, the phosphorylation of vasodilator-stimulated phosphoprotein (VASP) and focal adhesion kinase (FAK) in erythrocytes was concurrently enhanced in the Vitamin C group after CPB. The phosphorylation level of endothelial nitric oxide synthase in erythrocytes was significantly increased in the Vitamin C group (1.734 ± 0.371 folds) compared to control group (1.102 ± 0.249; P = 0.0061). Patients receiving Vitamin C had lower intraoperative blood loss and higher systemic vascular resistance after CPB compared to controls. Vitamin C supplementation attenuates oxidative stress and improves erythrocyte deformability via VASP/FAK signaling pathway in erythrocytes during CPB.
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Affiliation(s)
- Ying-Hsuan Tai
- Department of Anesthesiology, Shuang Ho Hospital, Taipei Medical University, New Taipei City; Department of Anesthesiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Hsiang-Ling Wu
- Department of Anesthesiology, Taipei Veterans General Hospital; School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - You-Hsiang Chu
- Department of Anesthesiology, Taipei Veterans General Hospital; Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan
| | - Cheng-Hsiung Huang
- School of Medicine, National Yang Ming Chiao Tung University; Division of Cardiovascular Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Shung-Tai Ho
- Department of Anesthesiology, Tri-Service General Hospital, National Defense Medical Center, Taipei; Department of Anesthesiology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Tso-Chou Lin
- Department of Anesthesiology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Chih-Cherng Lu
- Department of Anesthesiology, Taipei Veterans General Hospital; Graduate Institute of Life Sciences; Institute of Aerospace Medicine, National Defense Medical Center, Taipei, Taiwan
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14
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Berger MM, Shenkin A, Schweinlin A, Amrein K, Augsburger M, Biesalski HK, Bischoff SC, Casaer MP, Gundogan K, Lepp HL, de Man AME, Muscogiuri G, Pietka M, Pironi L, Rezzi S, Cuerda C. ESPEN micronutrient guideline. Clin Nutr 2022; 41:1357-1424. [PMID: 35365361 DOI: 10.1016/j.clnu.2022.02.015] [Citation(s) in RCA: 287] [Impact Index Per Article: 95.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2022] [Accepted: 02/16/2022] [Indexed: 11/19/2022]
Abstract
BACKGROUND Trace elements and vitamins, named together micronutrients (MNs), are essential for human metabolism. Recent research has shown the importance of MNs in common pathologies, with significant deficiencies impacting the outcome. OBJECTIVE This guideline aims to provide information for daily clinical nutrition practice regarding assessment of MN status, monitoring, and prescription. It proposes a consensus terminology, since many words are used imprecisely, resulting in confusion. This is particularly true for the words "deficiency", "repletion", "complement", and "supplement". METHODS The expert group attempted to apply the 2015 standard operating procedures (SOP) for ESPEN which focuses on disease. However, this approach could not be applied due to the multiple diseases requiring clinical nutrition resulting in one text for each MN, rather than for diseases. An extensive search of the literature was conducted in the databases Medline, PubMed, Cochrane, Google Scholar, and CINAHL. The search focused on physiological data, historical evidence (published before PubMed release in 1996), and observational and/or randomized trials. For each MN, the main functions, optimal analytical methods, impact of inflammation, potential toxicity, and provision during enteral or parenteral nutrition were addressed. The SOP wording was applied for strength of recommendations. RESULTS There was a limited number of interventional trials, preventing meta-analysis and leading to a low level of evidence. The recommendations underwent a consensus process, which resulted in a percentage of agreement (%): strong consensus required of >90% of votes. Altogether the guideline proposes sets of recommendations for 26 MNs, resulting in 170 single recommendations. Critical MNs were identified with deficiencies being present in numerous acute and chronic diseases. Monitoring and management strategies are proposed. CONCLUSION This guideline should enable addressing suboptimal and deficient status of a bundle of MNs in at-risk diseases. In particular, it offers practical advice on MN provision and monitoring during nutritional support.
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Affiliation(s)
- Mette M Berger
- Department of Adult Intensive Care, Lausanne University Hospital (CHUV), Lausanne, Switzerland.
| | - Alan Shenkin
- Institute of Aging and Chronic Disease, University of Liverpool, Liverpool, UK.
| | - Anna Schweinlin
- Institute of Nutritional Medicine, University of Hohenheim, Stuttgart, Germany.
| | - Karin Amrein
- Medical University of Graz, Department of Internal Medicine, Division of Endocrinology and Diabetology, Austria.
| | - Marc Augsburger
- University Centre of Legal Medicine Lausanne-Geneva, Lausanne University Hospital and University of Lausanne, Geneva University Hospital and University of Geneva, Lausanne-Geneva, Switzerland.
| | | | - Stephan C Bischoff
- Institute of Nutritional Medicine, University of Hohenheim, Stuttgart, Germany.
| | - Michael P Casaer
- KU Leuven, Department of Cellular and Molecular Medicine, Laboratory of Intensive Care Medicine, Leuven, Belgium.
| | - Kursat Gundogan
- Division of Intensive Care Medicine, Department of Internal Medicine, Erciyes University School of Medicine, Kayseri, Turkey.
| | | | - Angélique M E de Man
- Department of Intensive Care Medicine, Research VUmc Intensive Care (REVIVE), Amsterdam Cardiovascular Science (ACS), Amsterdam Infection and Immunity Institute (AI&II), Amsterdam Medical Data Science (AMDS), Amsterdam UMC, Location VUmc, Vrije Universiteit Amsterdam, De Boelelaan 1117, 1081 HV, Amsterdam, the Netherlands.
| | - Giovanna Muscogiuri
- Dipartimento di Medicina Clinica e Chirurgia, Sezione di Endocrinologia, Università di Napoli (Federico II), Naples, Italy; United Nations Educational, Scientific and Cultural Organization (UNESCO) Chair for Health Education and Sustainable Development, Federico II, University, Naples, Italy.
| | - Magdalena Pietka
- Pharmacy Department, Stanley Dudrick's Memorial Hospital, Skawina, Poland.
| | - Loris Pironi
- Alma Mater Studiorum - University of Bologna, Department of Medical and Surgical Sciences, Italy; IRCCS Azienda Ospedaliero-Universitaria di Bologna, Centre for Chronic Intestinal Failure - Clinical Nutrition and Metabolism Unit, Italy.
| | - Serge Rezzi
- Swiss Nutrition and Health Foundation (SNHf), Epalinges, Switzerland.
| | - Cristina Cuerda
- Departamento de Medicina, Universidad Complutense de Madrid, Nutrition Unit, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
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15
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Hemilä H, Chalker E. Vitamin C and the risk of atrial fibrillation: Mendelian randomization study may be misleading. Clin Nutr 2022; 41:1446-1447. [DOI: 10.1016/j.clnu.2022.04.029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2022] [Accepted: 04/26/2022] [Indexed: 11/03/2022]
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16
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Borges L, Gennari-Felipe M, Dias BB, Hatanaka E. Melatonin, Zinc, and Vitamin C: Potential Adjuvant Treatment for COVID-19 Patients. Front Nutr 2022; 8:821824. [PMID: 35155533 PMCID: PMC8826215 DOI: 10.3389/fnut.2021.821824] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2021] [Accepted: 12/27/2021] [Indexed: 12/14/2022] Open
Abstract
The use of nutraceutical approaches may regulate the immune system, performing a potential strategy to contain the worst outcomes of COVID-19. We reviewed the current evidence surrounding nutritional/nutraceutical approaches for the therapy in patients with COVID-19. We searched the PubMed database to report randomized controlled trials (RCTs) and observational research that used melatonin, zinc, or vitamin C supplementation as an intervention for COVID-19 treatment. To date, we found only three concluded studies that assessed zinc supplementation and melatonin therapy in patients with COVID-19, but with inconclusive data, relatively small sample size, and early termination of the trial. On the other hand, vitamin C therapy appears to reduce hyperinflammation and improve the oxygen support status of patients with COVID-19. However, a large part of this research involves pilot trials, and there are still conflicting data regarding mortality rate, mechanical ventilation, and duration of symptoms of patients with COVID-19. Melatonin, zinc, and vitamin C supplementation should be investigated further on the nutritional status-immune response, and data from ongoing trials are needed to understand these molecules as a therapy strategy in patients COVID-19.
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Affiliation(s)
- Leandro Borges
- Interdisciplinary Program of Health Sciences, Cruzeiro Do Sul University, São Paulo, Brazil
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17
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Ngo L, Duc T, Van BV, Hoang K, Tien Le D, Nguyen HC, Nguyen TT, Freedman B, Lowres N. Incidence of New Onset Atrial Fibrillation After Cardiovascular Surgery in Vietnam: Results From A Novel Screening Strategy. J Atr Fibrillation 2021; 14:20200503. [PMID: 34950376 DOI: 10.4022/jafib.20200503] [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: 04/08/2021] [Revised: 05/11/2021] [Accepted: 05/22/2021] [Indexed: 11/10/2022]
Abstract
Objective To examine the incidence of atrial fibrillation (AF) newly developed after cardiovascular surgery in Vietnam, its associated risk factors, and postoperative complications. We also sought to evaluate the feasibility of a novel screening strategy for post-operative AF (POAF) using the combination of two portable devices. Methods Single-centre, prospective cohort study at the Cardiovascular Centre, E Hospital, Hanoi, Vietnam. All patients aged≥18 years, undergoing cardiovascular surgery and in sinus rhythm preoperatively were eligible. The primary outcome was occurrence of new-onset POAF detected by hand-held single-lead electrocardiography (ECG) or a sphygmomanometer with AF-detection algorithm. Multivariate logistic regression was used to identify risk factors of developing post-operative AF. Feasibility was evaluated by compliance to the protocol and semi-structured interviews. Results 112 patients were enrolled between 2018-2019: mean age 52.9±12.2 years; 50.9% female;92.0% (n=103) valve surgery; 9.8% (n=11)coronary surgery. New-onset POAF developed in 49patients (43.8%) with median time to onset 1.27days (IQR 0.96 -2.00 days). Age≥65 years was the only significant risk factor for the development of POAF(OR 3.78, 95% CI 1.16-12.34).The median thromboembolism risk scores (CHA2DS2-VASc score) were comparable among patients with and without POAF (1.0 vs. 1.0, p=0.104). The occurrence of POAF was associated with higher rates of postoperative complications (24.5% vs. 3.2%, p<0.001). Both doctors and nurses found this screening strategy feasible to be implemented long-term with the main difficulties being the instructions on both devices were in English, and an increase in workload. Conclusions In this single-centre study, new-onset POAF occurred in 43.8% of patients who underwent cardiovascular surgery. This novel POAF screening strategy was feasible in a low resource setting, and its implementation could be improved by providing continuous training and translation to local language.
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Affiliation(s)
- Linh Ngo
- Faculty of Medicine, The University of Queensland, Queensland, Australia.,Department of Cardiovascular and Thoracic Surgery, Cardiovascular Centre, E Hospital, Hanoi, Vietnam.,Department of Cardiology, The Prince Charles Hospital, Queensland, Australia
| | - Thinh Duc
- Department of Cardiovascular and Thoracic Surgery, Cardiovascular Centre, E Hospital, Hanoi, Vietnam
| | - Ba Vu Van
- Department of Cardiovascular and Thoracic Surgery, Cardiovascular Centre, E Hospital, Hanoi, Vietnam
| | - KienTrung Hoang
- Department of Cardiovascular and Thoracic Surgery, Cardiovascular Centre, E Hospital, Hanoi, Vietnam
| | - Dzung Tien Le
- Department of Cardiovascular and Thoracic Surgery, Cardiovascular Centre, E Hospital, Hanoi, Vietnam
| | - Huu Cong Nguyen
- Department of Cardiovascular and Thoracic Surgery, Cardiovascular Centre, E Hospital, Hanoi, Vietnam
| | - Thuy Tran Nguyen
- Department of Cardiovascular and Thoracic Surgery, Cardiovascular Centre, E Hospital, Hanoi, Vietnam
| | - Ben Freedman
- Heart Research Institute, Charles Perkins Centre, The University of Sydney, New South Wales, Australia
| | - Nicole Lowres
- Heart Research Institute, Charles Perkins Centre, The University of Sydney, New South Wales, Australia
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18
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Mauerhofer C, Grumet L, Schemmer P, Leber B, Stiegler P. Combating Ischemia-Reperfusion Injury with Micronutrients and Natural Compounds during Solid Organ Transplantation: Data of Clinical Trials and Lessons of Preclinical Findings. Int J Mol Sci 2021; 22:10675. [PMID: 34639016 PMCID: PMC8508760 DOI: 10.3390/ijms221910675] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2021] [Revised: 09/22/2021] [Accepted: 09/26/2021] [Indexed: 02/07/2023] Open
Abstract
Although extended donor criteria grafts bear a higher risk of complications such as graft dysfunction, the exceeding demand requires to extent the pool of potential donors. The risk of complications is highly associated with ischemia-reperfusion injury, a condition characterized by high loads of oxidative stress exceeding antioxidative defense mechanisms. The antioxidative properties, along with other beneficial effects like anti-inflammatory, antiapoptotic or antiarrhythmic effects of several micronutrients and natural compounds, have recently emerged increasing research interest resulting in various preclinical and clinical studies. Preclinical studies reported about ameliorated oxidative stress and inflammatory status, resulting in improved graft survival. Although the majority of clinical studies confirmed these results, reporting about improved recovery and superior organ function, others failed to do so. Yet, only a limited number of micronutrients and natural compounds have been investigated in a (large) clinical trial. Despite some ambiguous clinical results and modest clinical data availability, the vast majority of convincing animal and in vitro data, along with low cost and easy availability, encourage the conductance of future clinical trials. These should implement insights gained from animal data.
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Affiliation(s)
- Christina Mauerhofer
- Department of Science and Product Development, pro medico HandelsGmbH, Liebenauer Tangente 6, 8041 Graz, Austria; (C.M.); (L.G.)
| | - Lukas Grumet
- Department of Science and Product Development, pro medico HandelsGmbH, Liebenauer Tangente 6, 8041 Graz, Austria; (C.M.); (L.G.)
| | - Peter Schemmer
- Division of Transplant Surgery, Department of Surgery, Medical University, 8036 Graz, Austria; (P.S.); (B.L.)
| | - Bettina Leber
- Division of Transplant Surgery, Department of Surgery, Medical University, 8036 Graz, Austria; (P.S.); (B.L.)
| | - Philipp Stiegler
- Division of Transplant Surgery, Department of Surgery, Medical University, 8036 Graz, Austria; (P.S.); (B.L.)
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Agarwal A, Hager DN, Sevransky JE. Any Role of High-Dose Vitamin C for Septic Shock in 2021? Semin Respir Crit Care Med 2021; 42:672-682. [PMID: 34544184 DOI: 10.1055/s-0041-1733986] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
While the use of vitamin C as a therapeutic agent has been investigated since the 1950s, there has been substantial recent interest in the role of vitamin C supplementation in critical illness and particularly, sepsis and septic shock. Humans cannot synthesize vitamin C and rely on exogenous intake to maintain a plasma concentration of approximately 70 to 80 μmol/L. Vitamin C, in healthy humans, is involved with antioxidant function, wound healing, endothelial function, and catecholamine synthesis. Its function in the human body informs the theoretical basis for why vitamin C supplementation may be beneficial in sepsis/septic shock.Critically ill patients can be vitamin C deficient due to low dietary intake, increased metabolic demands, inefficient recycling of vitamin C metabolites, and loss due to renal replacement therapy. Intravenous supplementation is required to achieve supraphysiologic serum levels of vitamin C. While some clinical studies of intravenous vitamin C supplementation in sepsis have shown improvements in secondary outcome measures, none of the randomized clinical trials have shown differences between vitamin C supplementation and standard of care and/or placebo in the primary outcome measures of the trials. There are some ongoing studies of high-dose vitamin C administration in patients with sepsis and coronavirus disease 2019; the majority of evidence so far does not support the routine supplementation of vitamin C in patients with sepsis or septic shock.
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Affiliation(s)
- Ankita Agarwal
- Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, Emory University, Atlanta, Georgia
| | - David N Hager
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University, Baltimore, Maryland
| | - Jonathan E Sevransky
- Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, Emory University, Atlanta, Georgia.,Emory Critical Care Center, Emory University, Atlanta, Georgia
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20
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Chen L, Sun X, Wang Z, Lu Y, Chen M, He Y, Xu H, Zheng L. The impact of plasma vitamin C levels on the risk of cardiovascular diseases and Alzheimer's disease: A Mendelian randomization study. Clin Nutr 2021; 40:5327-5334. [PMID: 34537655 DOI: 10.1016/j.clnu.2021.08.020] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2020] [Revised: 06/23/2021] [Accepted: 08/25/2021] [Indexed: 01/07/2023]
Abstract
BACKGROUND & AIMS Previous observational studies have reported associations between plasma vitamin C levels, and cardiovascular diseases (CVDs) and Alzheimer's disease (AD); however, no conclusive results have been obtained. We conducted a Mendelian randomization (MR) study to investigate the causality of vitamin C on the risk of nine CVDs [including coronary artery disease (CAD), myocardial infarction (MI), atrial fibrillation (AF), heart failure (HF), stroke, ischemic stroke (IS), and IS subtypes] and Alzheimer's disease. METHODS Eleven single-nucleotide polymorphisms (SNPs) identified in a recent genome-wide meta-analysis (N = 52,018) were used as the instrumental variables for plasma vitamin C levels. The summary-level data for CVDs and AD were extracted from consortia and genome-wide association studies (GWAS). We performed MR analyses using the fixed-effects inverse-variance-weighted (IVW) method, weighted median, and MR-Egger approaches. RESULTS This MR study found suggestive evidence that genetic liability to higher vitamin C levels was associated with a lower risk of cardioembolic stroke [odds ratio (OR, presented per 1 standard deviation increase in plasma vitamin C levels) = 0.773; 95% confidence interval (CI), 0.623-0.959; P = 0.020] and AD (OR = 0.968; 95% CI, 0.946-0.991; P = 0.007) using the fixed-effects IVW method. Sensitivity analysis yielded directionally similar results. A null-association was observed between vitamin C and the other CVDs. CONCLUSION Our MR study provided suggestive evidence that higher vitamin C levels were casually associated with a decreased risk of cardioembolic stroke and AD. No evidence was observed to suggest that vitamin C affected the risk of CAD, MI, AF, HF, stroke, IS, large artery stroke, or small vessel stroke. However, well-designed studies are warranted to confirm these results and determine the underlying mechanisms of the causal links.
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Affiliation(s)
- Lu Chen
- Department of Cardiology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310003, China.
| | - Xingang Sun
- Department of Cardiology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310003, China.
| | - Zhen Wang
- Department of Cardiology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310003, China.
| | - Yunlong Lu
- Department of Cardiology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310003, China.
| | - Miao Chen
- Department of Cardiology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310003, China.
| | - Yuxian He
- Department of Cardiology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310003, China.
| | - Hongfei Xu
- Department of Cardiothoracic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310003, China.
| | - Liangrong Zheng
- Department of Cardiology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310003, China.
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Rodrigo R, González-Montero J, Sotomayor CG. Novel Combined Antioxidant Strategy against Hypertension, Acute Myocardial Infarction and Postoperative Atrial Fibrillation. Biomedicines 2021; 9:620. [PMID: 34070760 PMCID: PMC8228412 DOI: 10.3390/biomedicines9060620] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2021] [Revised: 05/19/2021] [Accepted: 05/27/2021] [Indexed: 12/28/2022] Open
Abstract
Reactive oxygen species (ROS) play a physiological role in the modulation of several functions of the vascular wall; however, increased ROS have detrimental effects. Hence, oxidative stress has pathophysiological impacts on the control of the vascular tone and cardiac functions. Recent experimental studies reported the involvement of increased ROS in the mechanism of hypertension, as this disorder associates with increased production of pro-oxidants and decreased bioavailability of antioxidants. In addition, increased ROS exposure is found in ischemia-reperfusion, occurring in acute myocardial infarction and cardiac surgery with extracorporeal circulation, among other settings. Although these effects cause major heart damage, at present, there is no available treatment. Therefore, it should be expected that antioxidants counteract the oxidative processes, thereby being suitable against cardiovascular disease. Nevertheless, although numerous experimental studies agree with this notion, interventional trials have provided mixed results. A better knowledge of ROS modulation and their specific interaction with the molecular targets should contribute to the development of novel multitarget antioxidant effective therapeutic strategies. The complex multifactorial nature of hypertension, acute myocardial infarction, and postoperative atrial fibrillation needs a multitarget antioxidant strategy, which may give rise to additive or synergic protective effects to achieve optimal cardioprotection.
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Affiliation(s)
- Ramón Rodrigo
- Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, CP 8380453 Santiago, Chile;
| | - Jaime González-Montero
- Basic and Clinical Oncology Department, Faculty of Medicine, University of Chile, CP 8380453 Santiago, Chile;
| | - Camilo G. Sotomayor
- Clinical Hospital University of Chile, University of Chile, CP 8380453 Santiago, Chile
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22
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Chuklin S, Chuklin S. Витамин С при критических состояниях: от эксперимента к клинике (часть 2). EMERGENCY MEDICINE 2021; 17:6-13. [DOI: 10.22141/2224-0586.17.1.2021.225708] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/02/2024]
Abstract
Витамин С (аскорбиновая кислота) играет важную физиологическую роль в многочисленных метаболических функциях. Он также является кофактором в синтезе важных веществ, в частности катехоламинов и вазопрессина. Снижение уровня аскорбиновой кислоты отмечено при различных заболеваниях и часто сопровождает тяжелое состояние больного. Целью этой статьи является обзор современных представлений о применении высоких доз витамина С при критических состояниях у хирургических больных. Для поиска литературных источников использовалась база Medline на платформе Pubmed по ключевым словам: витамин С, сепсис, шок, травма, ожоги.
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23
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Zhang J, Rao X, Li Y, Zhu Y, Liu F, Guo G, Luo G, Meng Z, De Backer D, Xiang H, Peng Z. Pilot trial of high-dose vitamin C in critically ill COVID-19 patients. Ann Intensive Care 2021; 11:5. [PMID: 33420963 PMCID: PMC7794643 DOI: 10.1186/s13613-020-00792-3] [Citation(s) in RCA: 161] [Impact Index Per Article: 40.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2020] [Accepted: 12/18/2020] [Indexed: 01/08/2023] Open
Abstract
BACKGROUND Few specific medications have been proven effective for the treatment of patients with severe coronavirus disease 2019 (COVID-19). Here, we tested whether high-dose vitamin C infusion was effective for severe COVID-19. METHODS This randomized, controlled, clinical trial was performed at 3 hospitals in Hubei, China. Patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the ICU were randomly assigned in as 1:1 ratio to either the high-dose intravenous vitamin C (HDIVC) or the placebo. HDIVC group received 12 g of vitamin C/50 ml every 12 h for 7 days at a rate of 12 ml/hour, and the placebo group received bacteriostatic water for injection in the same way within 48 h of arrival to ICU. The primary outcome was invasive mechanical ventilation-free days in 28 days (IMVFD28). Secondary outcomes were 28-day mortality, organ failure (Sequential Organ Failure Assessment (SOFA) score), and inflammation progression (interleukin-6). RESULTS Only 56 critical COVID-19 patients were ultimately recruited due to the early control of the outbreak. There was no difference in IMVFD28 between two groups (26.0 [9.0-28.0] in HDIVC vs 22.0 [8.50-28.0] in control, p = 0.57). HDIVC failed to reduce 28-day mortality (P = 0.27). During the 7-day treatment period, patients in the HDIVC group had a steady rise in the PaO2/FiO2 (day 7: 229 vs. 151 mmHg, 95% CI 33 to 122, P = 0.01), which was not observed in the control group. IL-6 in the HDIVC group was lower than that in the control group (19.42 vs. 158.00; 95% CI -301.72 to -29.79; P = 0.04) on day 7. CONCLUSION This pilot trial showed that HDIVC failed to improve IMVFD28, but might show a potential signal of benefit in oxygenation for critically ill patients with COVID-19 improving PaO2/FiO2 even though.
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Affiliation(s)
- Jing Zhang
- Dept. of Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430071 Hubei China
- Clinical Research Center of Hubei Critical Care Medicine, Wuhan, 430071 Hubei China
| | - Xin Rao
- Dept. of Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430071 Hubei China
- Clinical Research Center of Hubei Critical Care Medicine, Wuhan, 430071 Hubei China
| | - Yiming Li
- Dept. of Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430071 Hubei China
- Clinical Research Center of Hubei Critical Care Medicine, Wuhan, 430071 Hubei China
| | - Yuan Zhu
- Dept. of Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430071 Hubei China
| | - Fang Liu
- Dept. of Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430071 Hubei China
| | - Guangling Guo
- Anti-Aging Medical Center, Taihe Hospital, Huibei University of Medicine, Shiyan, 442000 Hubei China
| | - Guoshi Luo
- Department of Pulmonary and Critical Care Medicine, Taihe Hospital, Huibei University of Medicine, Shiyan, 442000 Hubei China
| | - Zhongji Meng
- Department of Infectious Diseases, Taihe Hospital, Huibei University of Medicine, Shiyan, 442000 Hubei China
| | - Daniel De Backer
- Department of Intensive Care, CHIREC Hospitals, Université Libre de Bruxelles, Brussels, Belgium
| | - Hui Xiang
- Dept. of Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430071 Hubei China
- Clinical Research Center of Hubei Critical Care Medicine, Wuhan, 430071 Hubei China
| | - Zhiyong Peng
- Dept. of Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430071 Hubei China
- Clinical Research Center of Hubei Critical Care Medicine, Wuhan, 430071 Hubei China
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24
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Mukherjee R. Commentary: We don't need no postop AF… All in all it's just another (β)-block in the wall. JTCVS OPEN 2020; 3:88-90. [PMID: 36003868 PMCID: PMC9390644 DOI: 10.1016/j.xjon.2020.08.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/24/2020] [Revised: 07/24/2020] [Accepted: 08/04/2020] [Indexed: 11/28/2022]
Affiliation(s)
- Rupak Mukherjee
- Division of Cardiothoracic Surgery, Department of Surgery, Medical University of South Carolina, Charleston, SC
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25
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Khan SA, Bhattacharjee S, Ghani MOA, Walden R, Chen QM. Vitamin C for Cardiac Protection during Percutaneous Coronary Intervention: A Systematic Review of Randomized Controlled Trials. Nutrients 2020; 12:E2199. [PMID: 32718091 PMCID: PMC7468730 DOI: 10.3390/nu12082199] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2020] [Revised: 07/17/2020] [Accepted: 07/21/2020] [Indexed: 12/28/2022] Open
Abstract
Percutaneous coronary intervention (PCI) is the preferred treatment for acute coronary syndrome (ACS) secondary to atherosclerotic coronary artery disease. This nonsurgical procedure is also used for selective patients with stable angina. Although the procedure is essential for restoring blood flow, reperfusion can increase oxidative stress as a side effect. We address whether intravenous infusion of vitamin C (VC) prior to PCI provides a benefit for cardioprotection. A total of eight randomized controlled trials (RCT) reported in the literature were selected from 371 publications through systematic literature searches in six electronic databases. The data of VC effect on cardiac injury biomarkers and cardiac function were extracted from these trials adding up to a total of 1185 patients. VC administration reduced cardiac injury as measured by troponin and CK-MB elevations, along with increased antioxidant reservoir, reduced reactive oxygen species (ROS) and decreased inflammatory markers. Improvement of the left ventricular ejection fraction (LVEF) and telediastolic left ventricular volume (TLVV) showed a trend but inconclusive association with VC. Intravenous infusion of VC before PCI may serve as an effective method for cardioprotection against reperfusion injury.
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Affiliation(s)
- Sher Ali Khan
- Department of Pharmacy Practice and Science, College of Pharmacy, University of Arizona, 1295 N. Martin Ave, Tucson, AZ 85721, USA; (S.A.K.); (S.B.)
| | - Sandipan Bhattacharjee
- Department of Pharmacy Practice and Science, College of Pharmacy, University of Arizona, 1295 N. Martin Ave, Tucson, AZ 85721, USA; (S.A.K.); (S.B.)
| | | | - Rachel Walden
- Annette and Irwin Eskind Family Biomedical Library, Jean & Alexander Heard Libraries, Vanderbilt University, Nashville, TN 37203, USA;
| | - Qin M. Chen
- Department of Pharmacy Practice and Science, College of Pharmacy, University of Arizona, 1295 N. Martin Ave, Tucson, AZ 85721, USA; (S.A.K.); (S.B.)
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26
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Honore PM, Spapen HD, Marik P, Boer W, Oudemans-van Straaten H. Dosing vitamin C in critically ill patients with special attention to renal replacement therapy: a narrative review. Ann Intensive Care 2020; 10:23. [PMID: 32052229 PMCID: PMC7016079 DOI: 10.1186/s13613-020-0640-6] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2019] [Accepted: 02/06/2020] [Indexed: 01/02/2023] Open
Abstract
RATIONALE/METHODS The primary aim of the present contribution is to find a literature-based agreement on dose adjustments of vitamin C in critically ill patients undergoing renal replacement therapy (RRT). AVAILABLE DATA/STUDY RESULTS Critical illness is frequently accompanied by severe vitamin C deficiency. High-dose supplementation beneficially affects clinical outcome in small cohorts of patients with sepsis, burn injury, and trauma. There are no specific data on clinical outcomes in patients receiving renal replacement therapy (RRT). Vitamin C plasma concentrations in patients on RRT are comparable to critically ill patients not receiving RRT. Vitamin C is cleared from the circulation during RRT at a rate dependent on the plasma concentration, dose and duration of RRT. Sieving coefficient is about 1. While the dose of RRT is lower than normal renal function, tubular reabsorption is absent. Sparse evidence suggests that vitamin C dosing during continuous RRT should not exceed the dose administered to critically ill patients not receiving continuous RRT. Low plasma concentrations are expected during prolonged RRT because of persistent extracorporeal removal, absent renal reabsorption and enhanced metabolic loss due to circuit-induced oxidative stress. A dosage of twice 1 g vitamin C daily may be necessary to achieve normal plasma concentrations during RRT, but more studies are needed. There is no available evidence that high doses of vitamin C administered over a short period can induce oxalate stones or has pro-oxidant effects. CONCLUSIONS Supplementing vitamin C 1 g twice daily to critically ill patients has a solid pathophysiological rationale and a good safety profile. Patients on RRT probably need similar doses as critically ill patients not receiving RRT. Intravenous vitamin C in a dose of 2 g/day may be necessary to achieve normal plasma concentrations during RRT. However, data on dose adjustment of vitamin C during intermittent or chronic RRT are sparse and require more thorough pharmacokinetic and dose-response studies.
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Affiliation(s)
- Patrick M. Honore
- ICU Dept, Centre Hospitalier Universitaire Brugmann/Brugmann University Hospîtal, Place Van Gehuchtenplein, 4, 1020 Brussels, Belgium
| | - Herbert D. Spapen
- Development, Ageing & Pathology Research Department, Vrije Universiteit Brussel, Brussels, Belgium
| | - Paul Marik
- Division of Pulmonary and Critical Care Medicine, Eastern Virginia Medical School, 825 Fairfax Av, Suite 410, Norfolk, VA 23507 USA
| | - Willem Boer
- Dept. of Anesthesiology, Intensive Care Medicine, Emergency Medicine & Pain Medicine, Ziekenhuis Oost-Limburg Genk, Genk, Belgium
| | - Heleen Oudemans-van Straaten
- Department of Intensive Care Medicine, Amsterdam UMC, Vrije Universiteit Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands
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Hill A, Borgs C, Fitzner C, Stoppe C. Perioperative Vitamin C and E levels in Cardiac Surgery Patients and Their Clinical Significance. Nutrients 2019; 11:E2157. [PMID: 31505814 PMCID: PMC6769782 DOI: 10.3390/nu11092157] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2019] [Revised: 08/27/2019] [Accepted: 08/29/2019] [Indexed: 12/25/2022] Open
Abstract
BACKGROUND Oxidative stress contributes to organ dysfunction after cardiac surgery and still represents a major problem. Antioxidants, such as vitamins C and E might be organ protective. METHODS The primary objective of this prospective observational study was the description to evaluate the perioperative vitamin C and E levels in 56 patients undergoing cardiac surgery with the use of cardiopulmonary bypass. The association of vitamin C with inflammatory reaction, oxidative stress, organ dysfunctions, and clinical outcomes were evaluated in an explorative approach. RESULTS Vitamin C levels decreased significantly from 6.5 (3.5-11.5) mg/L before surgery to 2.8 (2.0-3.9) mg/L 48 h after surgery (p < 0.0001). Fifty-six percent of patients had a suboptimal vitamin C status even before surgery. In protein-denaturized probes, significantly higher vitamin C concentrations were detected (p = 0.0008). Vitamin E levels decreased significantly from preoperative level 11.6 (9.5-13.2) mg/L to 7.1 (5.5-7.4) mg/L, (p = 0.0002) at the end of cardiopulmonary bypass, remained low during the first day on ICU and recovered to 8.2 (7.1-9.3) mg/L 48 h after surgery. No patient was vitamin E deficient before surgery. Analysis showed no statistically significant association of vitamin C with inflammation, oxidative stress or organ dysfunction levels in patients with previously suboptimal vitamin C status or patients with a perioperative decrease of ≥50% vitamin C after surgery. Patients with higher vitamin C levels had a shorter ICU stay than those who were vitamin C depleted, which was not statistically significant (72 versus 135 h, p = 0.1990). CONCLUSION Vitamin C and E levels significantly declined intraoperatively and remained significantly reduced low for 2 days after cardiac surgery. The influence of reduced serum levels on the inflammatory reaction and clinical outcome of the patients remain unclear in this small observational study and need to be investigated further. Given vitamin C´s pleiotropic role in the human defense mechanisms, further trials are encouraged to evaluate the clinical significance of Vitamin C in cardiac surgery patients.
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Affiliation(s)
- Aileen Hill
- Department of Intensive Care Medicine, Medical Faculty RWTH Aachen University Hospital, D-52074 Aachen, Germany.
- Department of Anesthesiology, Medical Faculty RWTH Aachen University Hospital, D-52074 Aachen, Germany.
- 3CARE-Cardiovascular Critical Care & Anesthesia Evaluation and Research, RWTH-Aachen University, D-52074 Aachen, Germany.
| | - Christina Borgs
- Department of Intensive Care Medicine, Medical Faculty RWTH Aachen University Hospital, D-52074 Aachen, Germany.
- Department of Anesthesiology, Medical Faculty RWTH Aachen University Hospital, D-52074 Aachen, Germany.
| | - Christina Fitzner
- Department of Anesthesiology, Medical Faculty RWTH Aachen University Hospital, D-52074 Aachen, Germany.
- 3CARE-Cardiovascular Critical Care & Anesthesia Evaluation and Research, RWTH-Aachen University, D-52074 Aachen, Germany.
| | - Christian Stoppe
- Department of Intensive Care Medicine, Medical Faculty RWTH Aachen University Hospital, D-52074 Aachen, Germany.
- 3CARE-Cardiovascular Critical Care & Anesthesia Evaluation and Research, RWTH-Aachen University, D-52074 Aachen, Germany.
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28
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Effects of Vitamin C on Organ Function in Cardiac Surgery Patients: A Systematic Review and Meta-Analysis. Nutrients 2019; 11:nu11092103. [PMID: 31487905 PMCID: PMC6769534 DOI: 10.3390/nu11092103] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2019] [Revised: 08/27/2019] [Accepted: 08/29/2019] [Indexed: 12/18/2022] Open
Abstract
Background: Cardiac surgery is associated with oxidative stress and systemic inflammation, which both contribute to postoperative organ dysfunction. Vitamin C is a pleiotropic, antioxidant, and potentially organ-protective micronutrient. Past clinical trials and meta-analyses have focused predominantly on occurrence of postoperative atrial fibrillation. Therefore, we investigated the influence of perioperative vitamin C administration on clinically relevant parameters closer related to the patient’s recovery, especially organ function, and overall outcomes after cardiac surgery. Methods: Randomized controlled trials (RCTs) comparing perioperative vitamin C administration versus placebo or standard of care in adult patients undergoing cardiac surgery were identified through systematic searches in Pubmed, EMBASE, and CENTRAL on 23 November 2018. Published and unpublished data were included. Assessed outcomes include organ function after cardiac surgery, adverse events, in-hospital mortality, intensive care unit, and hospital length-of-stay. Data was pooled only when appropriate. Results: A total of 19 RCTs with 2008 patients were included in this meta-analysis. Vitamin C significantly decreased the incidence of atrial fibrillation (p = 0.008), ventilation time (p < 0.00001), ICU length-of-stay (p = 0.004), and hospital length-of-stay (p < 0.0001). However, on average, vitamin C had no significant effects on in-hospital mortality (p = 0.76), or on the incidence of stroke (p = 0.82). High statistical heterogeneity was observed in most analyses. Conclusions: Vitamin C impacts clinically and economically important outcomes, such as ICU and hospital length-of-stay, duration of mechanical ventilation and lowers the incidence of atrial fibrillation. Due to missing reports on organ dysfunction, this meta-analysis cannot answer the question, if vitamin C can improve single- or multiorgan function after cardiac surgery.
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29
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Elke G, Hartl WH, Kreymann KG, Adolph M, Felbinger TW, Graf T, de Heer G, Heller AR, Kampa U, Mayer K, Muhl E, Niemann B, Rümelin A, Steiner S, Stoppe C, Weimann A, Bischoff SC. Clinical Nutrition in Critical Care Medicine - Guideline of the German Society for Nutritional Medicine (DGEM). Clin Nutr ESPEN 2019; 33:220-275. [PMID: 31451265 DOI: 10.1016/j.clnesp.2019.05.002] [Citation(s) in RCA: 64] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2019] [Accepted: 05/03/2019] [Indexed: 02/07/2023]
Abstract
PURPOSE Enteral and parenteral nutrition of adult critically ill patients varies in terms of the route of nutrient delivery, the amount and composition of macro- and micronutrients, and the choice of specific, immune-modulating substrates. Variations of clinical nutrition may affect clinical outcomes. The present guideline provides clinicians with updated consensus-based recommendations for clinical nutrition in adult critically ill patients who suffer from at least one acute organ dysfunction requiring specific drug therapy and/or a mechanical support device (e.g., mechanical ventilation) to maintain organ function. METHODS The former guidelines of the German Society for Nutritional Medicine (DGEM) were updated according to the current instructions of the Association of the Scientific Medical Societies in Germany (AWMF) valid for a S2k-guideline. According to the S2k-guideline classification, no systematic review of the available evidence was required to make recommendations, which, therefore, do not state evidence- or recommendation grades. Nevertheless, we considered and commented the evidence from randomized-controlled trials, meta-analyses and observational studies with adequate sample size and high methodological quality (until May 2018) as well as from currently valid guidelines of other societies. The liability of each recommendation was described linguistically. Each recommendation was finally validated and consented through a Delphi process. RESULTS In the introduction the guideline describes a) the pathophysiological consequences of critical illness possibly affecting metabolism and nutrition of critically ill patients, b) potential definitions for different disease phases during the course of illness, and c) methodological shortcomings of clinical trials on nutrition. Then, we make 69 consented recommendations for essential, practice-relevant elements of clinical nutrition in critically ill patients. Among others, recommendations include the assessment of nutrition status, the indication for clinical nutrition, the timing and route of nutrient delivery, and the amount and composition of substrates (macro- and micronutrients); furthermore, we discuss distinctive aspects of nutrition therapy in obese critically ill patients and those treated with extracorporeal support devices. CONCLUSION The current guideline provides clinicians with up-to-date recommendations for enteral and parenteral nutrition of adult critically ill patients who suffer from at least one acute organ dysfunction requiring specific drug therapy and/or a mechanical support device (e.g., mechanical ventilation) to maintain organ function. The period of validity of the guideline is approximately fixed at five years (2018-2023).
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Affiliation(s)
- Gunnar Elke
- Department of Anesthesiology and Intensive Care Medicine, University Medical Center Schleswig-Holstein, Campus Kiel, Arnold-Heller-Str. 3, Haus 12, 24105, Kiel, Germany.
| | - Wolfgang H Hartl
- Department of Surgery, University School of Medicine, Grosshadern Campus, Ludwig-Maximilian University, Marchioninistr. 15, 81377 Munich, Germany.
| | | | - Michael Adolph
- University Department of Anesthesiology and Intensive Care Medicine, University Hospital Tübingen, Hoppe-Seyler-Straße 3, 72076, Tübingen, Germany.
| | - Thomas W Felbinger
- Department of Anesthesiology, Critical Care and Pain Medicine, Neuperlach and Harlaching Medical Center, The Munich Municipal Hospitals Ltd, Oskar-Maria-Graf-Ring 51, 81737, Munich, Germany.
| | - Tobias Graf
- Medical Clinic II, University Heart Center Lübeck, University Medical Center Schleswig-Holstein, Campus Lübeck, Ratzeburger Allee 160, 23538, Lübeck, Germany.
| | - Geraldine de Heer
- Center for Anesthesiology and Intensive Care Medicine, Clinic for Intensive Care Medicine, University Hospital Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.
| | - Axel R Heller
- Clinic for Anesthesiology and Surgical Intensive Care Medicine, University of Augsburg, Stenglinstrasse 2, 86156, Augsburg, Germany.
| | - Ulrich Kampa
- Clinic for Anesthesiology, Lutheran Hospital Hattingen, Bredenscheider Strasse 54, 45525, Hattingen, Germany.
| | - Konstantin Mayer
- Department of Internal Medicine, Justus-Liebig University Giessen, University of Giessen and Marburg Lung Center, Klinikstr. 36, 35392, Gießen, Germany.
| | - Elke Muhl
- Eichhörnchenweg 7, 23627, Gross Grönau, Germany.
| | - Bernd Niemann
- Department of Adult and Pediatric Cardiovascular Surgery, Giessen University Hospital, Rudolf-Buchheim-Str. 7, 35392, Gießen, Germany.
| | - Andreas Rümelin
- Clinic for Anesthesia and Surgical Intensive Care Medicine, HELIOS St. Elisabeth Hospital Bad Kissingen, Kissinger Straße 150, 97688, Bad Kissingen, Germany.
| | - Stephan Steiner
- Department of Cardiology, Pneumology and Intensive Care Medicine, St Vincenz Hospital Limburg, Auf dem Schafsberg, 65549, Limburg, Germany.
| | - Christian Stoppe
- Department of Intensive Care Medicine and Intermediate Care, RWTH Aachen University, Pauwelsstr. 30, 52074, Aachen, Germany.
| | - Arved Weimann
- Department of General, Visceral and Oncological Surgery, Klinikum St. Georg, Delitzscher Straße 141, 04129, Leipzig, Germany.
| | - Stephan C Bischoff
- Department for Nutritional Medicine, University of Hohenheim, Fruwirthstr. 12, 70599, Stuttgart, Germany.
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30
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Abstract
Purpose of Review An overview of recent literature regarding pathophysiology, risk factors, prophylaxis, and treatment of new-onset atrial fibrillation (AF) in post-cardiac surgical patients. Recent Findings AF is the most frequent adverse event after cardiac surgery with significant associated morbidity, mortality, and financial cost. Its causes are multifactorial, and models to stratify patients into risk categories are progressing but a consistent, evidence-based system has not yet been developed. Pharmacologic and surgical interventions to prevent and treat this complication have been an area of ongoing research and recent societal guidelines reflect this. Summary Inconsistencies remain surrounding how to best identify higher-risk AF patients, which interventions should be used to prevent and treat AF, and which patient groups should receive these interventions. The evidence for these available strategies and their place in contemporary guidelines are summarized.
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31
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Hemilä H. Errors in a meta-analysis on vitamin C and post-operative atrial fibrillation. Int J Surg 2019; 64:66. [PMID: 30831247 DOI: 10.1016/j.ijsu.2019.01.025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2018] [Accepted: 01/02/2019] [Indexed: 10/27/2022]
Affiliation(s)
- Harri Hemilä
- Department of Public Health, POB 20 University of Helsinki, Tukholmankatu 8 B, FI-00014, Helsinki, Finland.
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32
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Marik PE. Hydrocortisone, Ascorbic Acid and Thiamine (HAT Therapy) for the Treatment of Sepsis. Focus on Ascorbic Acid. Nutrients 2018; 10:nu10111762. [PMID: 30441816 PMCID: PMC6265973 DOI: 10.3390/nu10111762] [Citation(s) in RCA: 74] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2018] [Revised: 10/30/2018] [Accepted: 11/08/2018] [Indexed: 12/21/2022] Open
Abstract
Sepsis is a devastating disease that carries an enormous toll in terms of human suffering and lives lost. Over 100 novel pharmacologic agents that targeted specific molecules or pathways have failed to improve the outcome of sepsis. Preliminary data suggests that the combination of Hydrocortisone, Ascorbic Acid and Thiamine (HAT therapy) may reduce organ failure and mortality in patients with sepsis and septic shock. HAT therapy is based on the concept that a combination of readily available, safe and cheap agents, which target multiple components of the host’s response to an infectious agent, will synergistically restore the dysregulated immune response and thereby prevent organ failure and death. This paper reviews the rationale for HAT therapy with a focus on vitamin C.
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Affiliation(s)
- Paul E Marik
- Division of Pulmonary and Critical Care Medicine, Eastern Virginia Medical School, Norfolk, VA 23507, USA.
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33
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Nabzdyk CS, Bittner EA. Vitamin C in the critically ill - indications and controversies. World J Crit Care Med 2018; 7:52-61. [PMID: 30370227 PMCID: PMC6201324 DOI: 10.5492/wjccm.v7.i5.52] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2018] [Revised: 08/04/2018] [Accepted: 08/21/2018] [Indexed: 02/06/2023] Open
Abstract
Ascorbic acid (vitamin C) elicits pleiotropic effects in the body. Among its functions, it serves as a potent anti-oxidant, a co-factor in collagen and catecholamine synthesis, and a modulator of immune cell biology. Furthermore, an increasing body of evidence suggests that high-dose vitamin C administration improves hemodynamics, end-organ function, and may improve survival in critically ill patients. This article reviews studies that evaluate vitamin C in pre-clinical models and clinical trials with respect to its therapeutic potential.
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Affiliation(s)
- Christoph S Nabzdyk
- Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, United States
| | - Edward A Bittner
- Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, United States
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34
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Voskoboinik A, Prabhu S, Sugumar H, Kistler PM. Effect of Dietary Factors on Cardiac Rhythm. Am J Cardiol 2018; 122:1265-1271. [PMID: 30075892 DOI: 10.1016/j.amjcard.2018.06.019] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2018] [Revised: 06/15/2018] [Accepted: 06/25/2018] [Indexed: 11/19/2022]
Abstract
The interaction between arrhythmias and certain lifestyle factors such as obesity and alcohol consumption is well-established. There is significant public and professional interest in the role of various diets, vitamins, and minerals in cardiovascular health. However, many widely held beliefs are not supported by the literature. There is limited evidence for routine magnesium and omega-3 poly-unsaturated fatty acids supplementation, while coffee, tea, nuts, antioxidant vitamins, and even chocolate may have some antiarrhythmic properties. Saturated fat, added salt, and excessive energy drink consumption appear to be harmful for patients with rhythm disorders. However most recommendations are based on observation studies, and this remains a fertile area for further research.
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Affiliation(s)
- Aleksandr Voskoboinik
- Alfred Heart Centre, Alfred Hospital, Melbourne, Victoria, Australia; Baker Heart and Diabetes Research Institute, Melbourne, Victoria, Australia
| | - Sandeep Prabhu
- Alfred Heart Centre, Alfred Hospital, Melbourne, Victoria, Australia; Baker Heart and Diabetes Research Institute, Melbourne, Victoria, Australia
| | - Hariharan Sugumar
- Alfred Heart Centre, Alfred Hospital, Melbourne, Victoria, Australia; Baker Heart and Diabetes Research Institute, Melbourne, Victoria, Australia
| | - Peter M Kistler
- Alfred Heart Centre, Alfred Hospital, Melbourne, Victoria, Australia; Baker Heart and Diabetes Research Institute, Melbourne, Victoria, Australia; University of Melbourne, Parkville, Victoria, Australia.
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35
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Ngo THL, Vu VB, Nguyen CH, Le TD, Hoang TK, Freedman B, Lowres N. Identification of new-onset atrial fibrillation after cardiac surgery in Vietnam. A feasibility study of a novel screening strategy in a limited-resource setting: study protocol. BMJ Open 2018; 8:e020800. [PMID: 30181182 PMCID: PMC6129042 DOI: 10.1136/bmjopen-2017-020800] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
Abstract
INTRODUCTION Atrial fibrillation (AF) developing after cardiac surgery is the most common postoperative complication with an incidence up to 50%. The presence of postoperative AF is associated with significant morbidity, mortality and economic burden. However, in Vietnam, data on AF postcardiac surgery are limited, in part due to a shortage of screening equipment. This project aims to identify the incidence, risk factors and postoperative complications of new-onset postoperative AF after cardiac surgery, and the feasibility of introducing a novel screening strategy using the combination of two portable devices to detect AF. METHODS AND ANALYSIS This is a feasibility study examining patients who are (1) ≥18 years old; (2) undergoing coronary artery bypass graft and/or valve surgery and (3) in normal sinus rhythm prior to their operation. Patients with congenital heart disease, a prior history of AF or those who require a pacemaker after surgery will be excluded. All patients will be followed up for the duration of their hospitalisation. The screening strategy will include monitoring the continuous ECG tracing in the intensive care unit, and if AF is suspected, a 30 s lead-1 ECG will be recorded using the smartphone-based AliveCor Kardia Mobile. On the postoperative wards, blood pressure will be measured three times daily using a modified blood pressure device (Microlife BP200 Afib): and if AF is suspected a 30 s ECG will be recorded using the AliveCor Kardia Mobile. A 12-lead ECG may be ordered subsequently if clinically indicated. The primary outcome is the incidence of postoperative AF. Secondary outcomes include establishing the risk factors and complications associated with postoperative AF; and the barriers and facilitators of the screening strategy. ETHICS AND DISSEMINATION Ethics approval was granted by Scientific Board of Cardiovascular Centre, E Hospital on 28 September, 2017. Study results will be disseminated through local and international conferences and peer-reviewed publications.
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Affiliation(s)
| | - Van Ba Vu
- Cardiovascular Centre, E Hospital, Hanoi, Vietnam
| | | | - Tien Dung Le
- Cardiovascular Centre, E Hospital, Hanoi, Vietnam
| | | | - Ben Freedman
- Heart Research Institute, and Charles Perkins Centre, University of Sydney, Sydney, Australia
| | - Nicole Lowres
- Heart Research Institute, and Charles Perkins Centre, University of Sydney, Sydney, Australia
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36
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Efird JT, Jindal C, Kiser AC, Akhter SA, Crane PB, Kypson AP, Sverdlov AL, Davies SW, Kindell LC, Anderson EJ. Increased risk of atrial fibrillation among patients undergoing coronary artery bypass graft surgery while receiving nitrates and antiplatelet agents. J Int Med Res 2018; 46:3183-3194. [PMID: 29808744 PMCID: PMC6134635 DOI: 10.1177/0300060518773934] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2017] [Accepted: 04/09/2018] [Indexed: 01/13/2023] Open
Abstract
Background Postoperative atrial fibrillation (POAF) is a frequent complication of coronary artery bypass graft (CABG) surgery. This arrhythmia occurs more frequently among patients who receive perioperative inotropic therapy (PINOT). Administration of nitrates with antiplatelet agents reduces the conversion rate of cyclic guanosine monophosphate to guanosine monophosphate. This process is associated with increased concentrations of free radicals, catecholamines, and blood plasma volume. We hypothesized that patients undergoing CABG surgery who receive PINOT may be more susceptible to POAF when nitrates are administered with antiplatelet agents. Methods Clinical records were examined from a prospectively maintained cohort of 4,124 patients undergoing primary isolated CABG surgery to identify POAF-associated factors. Results POAF risk was increased among patients receiving PINOT, and the greatest effect was observed when nitrates were administered with antiplatelet therapy. Adjustment for comorbidities did not substantively change the study results. Conclusions Administration of nitrates with certain antiplatelet agents was associated with an increased POAF risk among patients undergoing CABG surgery. Additional studies are needed to determine whether preventive strategies such as administration of antioxidants will reduce this risk.
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Affiliation(s)
- Jimmy T. Efird
- Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, University of Newcastle, Newcastle, NSW, Australia
| | - Charulata Jindal
- Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, University of Newcastle, Newcastle, NSW, Australia
| | - Andy C. Kiser
- Department of Cardiovascular Sciences, Brody School of Medicine, Greenville, NC, USA
| | - Shahab A. Akhter
- Department of Cardiovascular Sciences, Brody School of Medicine, Greenville, NC, USA
| | - Patricia B. Crane
- Office of the Dean, College of Nursing, East Carolina University, Greenville, NC, USA
| | - Alan P. Kypson
- Cardiac Surgical Specialists, REX Health Care, University of North Carolina, Raleigh, NC, USA
| | - Aaron L. Sverdlov
- Priority Clinical Centre for Cardiovascular Health, School of Medicine and Public Health, University of Newcastle, Newcastle, NSW, Australia
| | - Stephen W. Davies
- Department of Surgery, University of Virginia School of Medicine, Charlottesville, VA, USA
| | - Linda C. Kindell
- Department of Cardiovascular Sciences, Brody School of Medicine, Greenville, NC, USA
| | - Ethan J. Anderson
- Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, Fraternal Order of Eagles Diabetes Research Center, University of Iowa, Iowa City, IA, USA
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37
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Hill A, Wendt S, Benstoem C, Neubauer C, Meybohm P, Langlois P, Adhikari NK, Heyland DK, Stoppe C. Vitamin C to Improve Organ Dysfunction in Cardiac Surgery Patients-Review and Pragmatic Approach. Nutrients 2018; 10:nu10080974. [PMID: 30060468 PMCID: PMC6115862 DOI: 10.3390/nu10080974] [Citation(s) in RCA: 39] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2018] [Revised: 07/22/2018] [Accepted: 07/25/2018] [Indexed: 12/15/2022] Open
Abstract
The pleiotropic biochemical and antioxidant functions of vitamin C have sparked recent interest in its application in intensive care. Vitamin C protects important organ systems (cardiovascular, neurologic and renal systems) during inflammation and oxidative stress. It also influences coagulation and inflammation; its application might prevent organ damage. The current evidence of vitamin C's effect on pathophysiological reactions during various acute stress events (such as sepsis, shock, trauma, burn and ischemia-reperfusion injury) questions whether the application of vitamin C might be especially beneficial for cardiac surgery patients who are routinely exposed to ischemia/reperfusion and subsequent inflammation, systematically affecting different organ systems. This review covers current knowledge about the role of vitamin C in cardiac surgery patients with focus on its influence on organ dysfunctions. The relationships between vitamin C and clinical health outcomes are reviewed with special emphasis on its application in cardiac surgery. Additionally, this review pragmatically discusses evidence on the administration of vitamin C in every day clinical practice, tackling the issues of safety, monitoring, dosage, and appropriate application strategy.
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Affiliation(s)
- Aileen Hill
- Department of Intensive Care Medicine, University Hospital RWTH, D-52074 Aachen, Germany.
- Department of Anesthesiology, University Hospital RWTH, D-52074 Aachen, Germany.
- 3CARE-Cardiovascular Critical Care & Anesthesia Evaluation and Research, D-52074 Aachen, Germany.
| | - Sebastian Wendt
- 3CARE-Cardiovascular Critical Care & Anesthesia Evaluation and Research, D-52074 Aachen, Germany.
- Department of Thoracic, Cardiac and Vascular Surgery, University Hospital RWTH, D-52074 Aachen, Germany.
| | - Carina Benstoem
- Department of Intensive Care Medicine, University Hospital RWTH, D-52074 Aachen, Germany.
- 3CARE-Cardiovascular Critical Care & Anesthesia Evaluation and Research, D-52074 Aachen, Germany.
| | - Christina Neubauer
- Department of Intensive Care Medicine, University Hospital RWTH, D-52074 Aachen, Germany.
- 3CARE-Cardiovascular Critical Care & Anesthesia Evaluation and Research, D-52074 Aachen, Germany.
| | - Patrick Meybohm
- Department of Anesthesiology and Intensive Care, University Hospital Frankfurt, D-60590 Frankfurt, Germany.
| | - Pascal Langlois
- Department of Anesthesiology and Reanimation, Faculty of Médecine and Health Sciences, Sherbrooke University Hospital, Sherbrooke, Québec, QC J1H 5N4, Canada.
| | - Neill Kj Adhikari
- Department of Critical Care Medicine, Sunnybrook Health Sciences Centre, Interdepartmental Division of Critical Care Medicine, University of Toronto; Toronto, ON M4N 3M5, Canada.
| | - Daren K Heyland
- Clinical Evaluation Research Unit, Kingston General Hospital, Kingston, ON K7L 2V7, Canada.
| | - Christian Stoppe
- Department of Intensive Care Medicine, University Hospital RWTH, D-52074 Aachen, Germany.
- 3CARE-Cardiovascular Critical Care & Anesthesia Evaluation and Research, D-52074 Aachen, Germany.
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38
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Boriani G, Fauchier L, Aguinaga L, Beattie JM, Blomstrom Lundqvist C, Cohen A, Dan GA, Genovesi S, Israel C, Joung B, Kalarus Z, Lampert R, Malavasi VL, Mansourati J, Mont L, Potpara T, Thornton A, Lip GYH, Gorenek B, Marin F, Dagres N, Ozcan EE, Lenarczyk R, Crijns HJ, Guo Y, Proietti M, Sticherling C, Huang D, Daubert JP, Pokorney SD, Cabrera Ortega M, Chin A. European Heart Rhythm Association (EHRA) consensus document on management of arrhythmias and cardiac electronic devices in the critically ill and post-surgery patient, endorsed by Heart Rhythm Society (HRS), Asia Pacific Heart Rhythm Society (APHRS), Cardiac Arrhythmia Society of Southern Africa (CASSA), and Latin American Heart Rhythm Society (LAHRS). Europace 2018; 21:7-8. [DOI: 10.1093/europace/euy110] [Citation(s) in RCA: 68] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2018] [Accepted: 04/26/2018] [Indexed: 02/05/2023] Open
Affiliation(s)
- Giuseppe Boriani
- Cardiology Division, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Policlinico di Modena, Modena, Italy
| | - Laurent Fauchier
- Centre Hospitalier Universitaire Trousseau et Université François Rabelais, Tours, France
| | | | - James M Beattie
- Cicely Saunders Institute, King’s College London, London, UK
| | | | | | - Gheorghe-Andrei Dan
- Cardiology Department, University of Medicine and Pharmacy “Carol Davila”, Colentina University Hospital, Bucharest, Romania
| | - Simonetta Genovesi
- Department of Medicine and Surgery, University of Milano-Bicocca, Milano and Nephrology Unit, San Gerardo Hospital, Monza, Italy
| | - Carsten Israel
- Evangelisches Krankenhaus Bielefeld GmbH, Bielefeld, Germany
| | - Boyoung Joung
- Cardiology Division, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Zbigniew Kalarus
- SMDZ in Zabrze, Medical University of Silesia, Katowice; Department of Cardiology, Silesian Center for Heart Diseases, Zabrze, Poland
| | | | - Vincenzo L Malavasi
- Cardiology Division, Department of Nephrologic, Cardiac, Vascular Diseases, Azienda ospedaliero-Universitaria di Modena, Modena, Italy
| | - Jacques Mansourati
- University Hospital of Brest and University of Western Brittany, Brest, France
| | - Lluis Mont
- Arrhythmia Section, Cardiovascular Clínical Institute, Hospital Clinic, Universitat Barcelona, Barcelona, Spain
| | - Tatjana Potpara
- School of Medicine, Belgrade University, Belgrade, Serbia
- Cardiology Clinic, Clinical Centre of Serbia, Belgrade, Serbia
| | | | - Gregory Y H Lip
- Institute of Cardiovascular Sciences, University of Birmingham, UK
- Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
| | | | | | | | | | - Radosław Lenarczyk
- Department of Cardiology, Congenital Heart Disease and Electrotherapy, Silesian Center for Heart Diseases, Zabrze, Poland
| | - Harry J Crijns
- Cardiology Maastricht UMC+ and Cardiovascular Research Institute Maastricht, Netherlands
| | - Yutao Guo
- Chinese PLA General Hospital, Beijing, People’s Republic of China
| | - Marco Proietti
- Institute of Cardiovascular Sciences, University of Birmingham, UK
- Department of Internal Medicine and Medical Specialties, Sapienza-University of Rome, Rome, Italy
| | | | - Dejia Huang
- Cardiology Division, Department of Medicine, West China Hospital, Sichuan University, Chengdu, People's Republic of China
| | | | - Sean D Pokorney
- Electrophysiology Section, Division of Cardiology, Duke University, Durham, NC, USA
| | - Michel Cabrera Ortega
- Department of Arrhythmia and Cardiac Pacing, Cardiocentro Pediatrico William Soler, Boyeros, La Havana Cuba
| | - Ashley Chin
- Department of Medicine, Groote Schuur Hospital, University of Cape Town, South Africa
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39
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Shi R, Li ZH, Chen D, Wu QC, Zhou XL, Tie HT. Sole and combined vitamin C supplementation can prevent postoperative atrial fibrillation after cardiac surgery: A systematic review and meta-analysis of randomized controlled trials. Clin Cardiol 2018; 41:871-878. [PMID: 29603289 DOI: 10.1002/clc.22951] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2018] [Revised: 03/15/2018] [Accepted: 03/25/2018] [Indexed: 12/28/2022] Open
Abstract
We undertook a systematic review and meta-analysis to evaluate the effect of vitamin C supplementation (vitamin C solely or as adjunct to other therapy) on prevention of postoperative atrial fibrillation (POAF) in patients after cardiac surgery. PubMed, Embase, Web of Science, and Cochrane Library were systematically searched to identify randomized controlled trials assessing the effect of vitamin C supplementation in adult patients undergoing cardiac surgery, and the meta-analysis was performed with a random-effects model. Thirteen trials involving 1956 patients were included. Pooling estimate showed a significantly reduced incidence of POAF (relative risk [RR]: 0.68, 95% confidence interval [CI]: 0.54 to 0.87, P = 0.002) both in vitamin C alone (RR: 0.75, 95% CI: 0.63 to 0.90, P = 0.002) and as an adjunct to other therapy (RR: 0.32, 95% CI: 0.20 to 0.53, P < 0.001). The results remain stable and robust in subgroup and sensitivity analyses, and trial sequential analysis also confirmed that the evidence was sufficient and conclusive. Additionally, vitamin C could significantly decrease intensive care unit length of stay (weighted mean difference: -0.24 days, 95% CI: -0.45 to -0.03, P = 0.023), hospital length of stay (weighted mean difference: -0.95 days, 95% CI: -1.64 to -0.26, P = 0.007), and risk of adverse events (RR: 0.45, 95% CI: 0.21 to 0.96, P = 0.039). Use of vitamin C alone and as adjunct to other therapy can prevent POAF in patients undergoing cardiac surgery and should be recommended for patients receiving cardiac surgery for prevention of POAF.
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Affiliation(s)
- Rui Shi
- Department of Cardiothoracic Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.,Department of Cardiology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Zhen-Han Li
- Department of Metabolism and Endocrinology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
| | - Dan Chen
- Department of Cardiothoracic Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Qing-Chen Wu
- Department of Cardiothoracic Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Xiao-Li Zhou
- Department of Cardiology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Hong-Tao Tie
- Department of Cardiothoracic Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China
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40
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Spoelstra-de Man AME, Elbers PWG, Oudemans-van Straaten HM. Making sense of early high-dose intravenous vitamin C in ischemia/reperfusion injury. CRITICAL CARE : THE OFFICIAL JOURNAL OF THE CRITICAL CARE FORUM 2018; 22:70. [PMID: 29558975 PMCID: PMC5861638 DOI: 10.1186/s13054-018-1996-y] [Citation(s) in RCA: 78] [Impact Index Per Article: 11.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2018. Other selected articles can be found online at https://www.biomedcentral.com/collections/annualupdate2018. Further information about the Annual Update in Intensive Care and Emergency Medicine is available from http://www.springer.com/series/8901.
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Affiliation(s)
- Angelique M E Spoelstra-de Man
- VU University Medical Center Amsterdam, Department of Intensive Care Medicine, Amsterdam Cardiovascular Sciences, Amsterdam Infection and Immunity Institute, Amsterdam, Netherlands.
| | - Paul W G Elbers
- VU University Medical Center Amsterdam, Department of Intensive Care Medicine, Amsterdam Cardiovascular Sciences, Amsterdam Infection and Immunity Institute, Amsterdam, Netherlands
| | - Heleen M Oudemans-van Straaten
- VU University Medical Center Amsterdam, Department of Intensive Care Medicine, Amsterdam Cardiovascular Sciences, Amsterdam Infection and Immunity Institute, Amsterdam, Netherlands
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41
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Ramanathan N, Tan E, Loh LJ, Soh BS, Yap WN. Tocotrienol is a cardioprotective agent against ageing-associated cardiovascular disease and its associated morbidities. Nutr Metab (Lond) 2018; 15:6. [PMID: 29387138 PMCID: PMC5775572 DOI: 10.1186/s12986-018-0244-4] [Citation(s) in RCA: 50] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2017] [Accepted: 01/15/2018] [Indexed: 02/07/2023] Open
Abstract
Ageing is a nonmodifiable risk factor that is linked to increased likelihood of cardiovascular morbidities. Whilst many pharmacological interventions currently exist to treat many of these disorders such as statins for hypercholesterolemia or beta-blockers for hypertension, the elderly appear to present a greater likelihood of suffering non-related side effects such as increased risk of developing new onset type 2 diabetes (NODM). In some cases, lower efficacy in the elderly have also been reported. Alternative forms of treatment have been sought to address these issues, and there has been a growing interest in looking at herbal remedies or plant-based natural compounds. Oxidative stress and inflammation are implicated in the manifestation of ageing-related cardiovascular disease. Thus, it is natural that a compound that possesses both antioxidative and anti-inflammatory bioactivities would be considered. This review article examines the potential of tocotrienols, a class of Vitamin E compounds with proven superior antioxidative and anti-inflammatory activity compared to tocopherols (the other class of Vitamin E compounds), in ameliorating ageing-related cardiovascular diseases and its associated morbidities. In particular, the potential of tocotrienols in improving inflammaging, dyslipidemia and mitochondrial dysfunction in ageing-related cardiovascular diseases are discussed.
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Affiliation(s)
- Nardev Ramanathan
- Department of R&D, Davos Life Science Pte Ltd, 3 Biopolis Drive, #04-19, Davos, 138623 Singapore
- Department of R&D, Level 8, Menara KLK 1,Jalan Pju 7/6,Mutiara Damansara, 47810, 47800 Petaling Jaya, Selangor Malaysia
| | - Esther Tan
- Disease Modeling and Therapeutics Laboratory, Institute of Molecular and Cell Biology, 61 Biopolis Drive Proteos, Singapore, 138673 Singapore
| | - Li Jun Loh
- Disease Modeling and Therapeutics Laboratory, Institute of Molecular and Cell Biology, 61 Biopolis Drive Proteos, Singapore, 138673 Singapore
| | - Boon Seng Soh
- Disease Modeling and Therapeutics Laboratory, Institute of Molecular and Cell Biology, 61 Biopolis Drive Proteos, Singapore, 138673 Singapore
- Department of Biological Sciences, National University of Singapore, Singapore, 117543 Singapore
- Key Laboratory for Major Obstetric Diseases of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150 China
| | - Wei Ney Yap
- Department of R&D, Davos Life Science Pte Ltd, 3 Biopolis Drive, #04-19, Davos, 138623 Singapore
- Department of R&D, Level 8, Menara KLK 1,Jalan Pju 7/6,Mutiara Damansara, 47810, 47800 Petaling Jaya, Selangor Malaysia
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42
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Vitamins, Amino Acids and Drugs and Formulations Used in Nutrition. SIDE EFFECTS OF DRUGS ANNUAL 2017. [DOI: 10.1016/bs.seda.2017.06.012] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
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