L-carnitine: Searching for New Therapeutic Strategy for Sepsis Management

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Abstract

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In this review, we discussed the biological targets of carnitine, its effects on immune function, and how L-carnitine supplementation may help critically ill patients. L-carnitine is a potent antioxidant. L-carnitine depletion has been observed in prolonged intensive care unit (ICU) stays, while L-carnitine supplementation has beneficial effects in health promotion and regulation of immunity. It is essential for the uptake of fatty acids into mitochondria. By inhibiting the ubiquitin-proteasome system, down-regulating the apelin receptor in cardiac tissue, and reducing β-oxidation of fatty acid, carnitine may decrease vasopressor requirement in septic shock and improve clinical outcomes of this group of patients. We also reviewed animal and clinical studies that have been recruited for evaluating the beneficial effects of L-carnitine in the management of sepsis/ septic shock. Additional clinical data are required to evaluate the optimal daily dose and duration of L-carnitine supplementation.

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Global, regional, and national sepsis incidence and mortality, 1990–2017: analysis for the Global Burden of Disease Study

Kristina Rudd, Sarah Charlotte Johnson, Kareha M Agesa … (2020)

Summary Background Sepsis is life-threatening organ dysfunction due to a dysregulated host response to infection. It is considered a major cause of health loss, but data for the global burden of sepsis are limited. As a syndrome caused by underlying infection, sepsis is not part of standard Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) estimates. Accurate estimates are important to inform and monitor health policy interventions, allocation of resources, and clinical treatment initiatives. We estimated the global, regional, and national incidence of sepsis and mortality from this disorder using data from GBD 2017. Methods We used multiple cause-of-death data from 109 million individual death records to calculate mortality related to sepsis among each of the 282 underlying causes of death in GBD 2017. The percentage of sepsis-related deaths by underlying GBD cause in each location worldwide was modelled using mixed-effects linear regression. Sepsis-related mortality for each age group, sex, location, GBD cause, and year (1990–2017) was estimated by applying modelled cause-specific fractions to GBD 2017 cause-of-death estimates. We used data for 8·7 million individual hospital records to calculate in-hospital sepsis-associated case-fatality, stratified by underlying GBD cause. In-hospital sepsis-associated case-fatality was modelled for each location using linear regression, and sepsis incidence was estimated by applying modelled case-fatality to sepsis-related mortality estimates. Findings In 2017, an estimated 48·9 million (95% uncertainty interval [UI] 38·9–62·9) incident cases of sepsis were recorded worldwide and 11·0 million (10·1–12·0) sepsis-related deaths were reported, representing 19·7% (18·2–21·4) of all global deaths. Age-standardised sepsis incidence fell by 37·0% (95% UI 11·8–54·5) and mortality decreased by 52·8% (47·7–57·5) from 1990 to 2017. Sepsis incidence and mortality varied substantially across regions, with the highest burden in sub-Saharan Africa, Oceania, south Asia, east Asia, and southeast Asia. Interpretation Despite declining age-standardised incidence and mortality, sepsis remains a major cause of health loss worldwide and has an especially high health-related burden in sub-Saharan Africa. Funding The Bill & Melinda Gates Foundation, the National Institutes of Health, the University of Pittsburgh, the British Columbia Children's Hospital Foundation, the Wellcome Trust, and the Fleming Fund.

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Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016.

Andrew Rhodes, Laura E Evans, Waleed Alhazzani … (2017)

To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012".

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Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care.

Derek C Angus, Walter Linde-Zwirble, Jeffrey Lidicker … (2001)

To determine the incidence, cost, and outcome of severe sepsis in the United States. Observational cohort study. All nonfederal hospitals (n = 847) in seven U.S. states. All patients (n = 192,980) meeting criteria for severe sepsis based on the International Classification of Diseases, Ninth Revision, Clinical Modification. None. We linked all 1995 state hospital discharge records (n = 6,621,559) from seven large states with population and hospital data from the U.S. Census, the Centers for Disease Control, the Health Care Financing Administration, and the American Hospital Association. We defined severe sepsis as documented infection and acute organ dysfunction using criteria based on the International Classification of Diseases, Ninth Revision, Clinical Modification. We validated these criteria against prospective clinical and physiologic criteria in a subset of five hospitals. We generated national age- and gender-adjusted estimates of incidence, cost, and outcome. We identified 192,980 cases, yielding national estimates of 751,000 cases (3.0 cases per 1,000 population and 2.26 cases per 100 hospital discharges), of whom 383,000 (51.1%) received intensive care and an additional 130,000 (17.3%) were ventilated in an intermediate care unit or cared for in a coronary care unit. Incidence increased >100-fold with age (0.2/1,000 in children to 26.2/1,000 in those >85 yrs old). Mortality was 28.6%, or 215,000 deaths nationally, and also increased with age, from 10% in children to 38.4% in those >85 yrs old. Women had lower age-specific incidence and mortality, but the difference in mortality was explained by differences in underlying disease and the site of infection. The average costs per case were $22,100, with annual total costs of $16.7 billion nationally. Costs were higher in infants, nonsurvivors, intensive care unit patients, surgical patients, and patients with more organ failure. The incidence was projected to increase by 1.5% per annum. Severe sepsis is a common, expensive, and frequently fatal condition, with as many deaths annually as those from acute myocardial infarction. It is especially common in the elderly and is likely to increase substantially as the U.S. population ages.

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Contributors

Adeleh Sahebnasagh: (View ORCID Profile)

Fatemeh Saghafi: (View ORCID Profile)

Journal

Title: Current Medicinal Chemistry

Abbreviated Title: CMC

Publisher: Bentham Science Publishers Ltd.

ISSN (Print): 09298673

Publication date Created: June 2022

Publication date (Print): June 2022

Volume: 29

Issue: 18

Pages: 3300-3323

Affiliations

[1 ]Clinical Research Center, Department of Internal Medicine, School of Medicine, North Khorasan University of Medical Sciences, Bojnurd, Iran

[2 ]Department of Clinical Pharmacy, Medical Toxicology and Drug Abuse Research Center (MTDRC), School of Pharmacy, Birjand University of Medical Sciences, Birjand, Iran

[3 ]Department of Internal Medicine, Golestan University of Medical Sciences, Gorgan, Iran

[4 ]Department of Pathobiology and Laboratory Sciences, School of Medicine, North Khorasan University of Medical Sciences, Bojnurd, Iran

[5 ]Pharmacognosy Research Laboratories and Herbal Analysis Services, School of Science, University of Greenwich, Central Avenue, Chatham-Maritime, Kent ME4 4TB, United Kingdom

[6 ]Student Research Committee, School of Pharmacy, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

[7 ]Department of Clinical Pharmacy, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

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DOI: 10.2174/0929867328666211117092345

SO-VID: b785b8e3-1136-4cab-bb9d-61da612ad62b

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L-carnitine: Searching for New Therapeutic Strategy for Sepsis Management

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Most cited references 173

Global, regional, and national sepsis incidence and mortality, 1990–2017: analysis for the Global Burden of Disease Study

Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016.

Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care.

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