The apelinergic system as an alternative to catecholamines in low-output septic shock

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Abstract

Catecholamines, in concert with fluid resuscitation, have long been recommended in the management of septic shock. However, not all patients respond positively and controversy surrounding the efficacy-to-safety profile of catecholamines has emerged, trending toward decatecholaminization. Contextually, it is time to re-examine the “maintaining blood pressure” paradigm by identifying safer and life-saving alternatives. We put in perspective the emerging and growing knowledge on a promising alternative avenue: the apelinergic system. This target exhibits invaluable pleiotropic properties, including inodilator activity, cardio-renal protection, and control of fluid homeostasis. Taken together, its effects are expected to be greatly beneficial for patients in septic shock.

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Most cited references 42

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Benchmarking the incidence and mortality of severe sepsis in the United States.

David F Gaieski, J. Edwards, Michael Kallan … (2013)

In 1992, the first consensus definition of severe sepsis was published. Subsequent epidemiologic estimates were collected using administrative data, but ongoing discrepancies in the definition of severe sepsis produced large differences in estimates. We seek to describe the variations in incidence and mortality of severe sepsis in the United States using four methods of database abstraction. We hypothesized that different methodologies of capturing cases of severe sepsis would result in disparate estimates of incidence and mortality. Using a nationally representative sample, four previously published methods (Angus et al, Martin et al, Dombrovskiy et al, and Wang et al) were used to gather cases of severe sepsis over a 6-year period (2004-2009). In addition, the use of new International Statistical Classification of Diseases, 9th Edition (ICD-9), sepsis codes was compared with previous methods. Annual national incidence and in-hospital mortality of severe sepsis. The average annual incidence varied by as much as 3.5-fold depending on method used and ranged from 894,013 (300/100,000 population) to 3,110,630 (1,031/100,000) using the methods of Dombrovskiy et al and Wang et al, respectively. Average annual increase in the incidence of severe sepsis was similar (13.0% to 13.3%) across all methods. In-hospital mortality ranged from 14.7% to 29.9% using abstraction methods of Wang et al and Dombrovskiy et al. Using all methods, there was a decrease in in-hospital mortality across the 6-year period (35.2% to 25.6% [Dombrovskiy et al] and 17.8% to 12.1% [Wang et al]). Use of ICD-9 sepsis codes more than doubled over the 6-year period (158,722 - 489,632 [995.92 severe sepsis], 131,719 - 303,615 [785.52 septic shock]). There is substantial variability in incidence and mortality of severe sepsis depending on the method of database abstraction used. A uniform, consistent method is needed for use in national registries to facilitate accurate assessment of clinical interventions and outcome comparisons between hospitals and regions.

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Septic shock.

Djillali Annane, Eric Bellissant, Jean-Marc Cavaillon (2005)

Septic shock, the most severe complication of sepsis, is a deadly disease. In recent years, exciting advances have been made in the understanding of its pathophysiology and treatment. Pathogens, via their microbial-associated molecular patterns, trigger sequential intracellular events in immune cells, epithelium, endothelium, and the neuroendocrine system. Proinflammatory mediators that contribute to eradication of invading microorganisms are produced, and anti-inflammatory mediators control this response. The inflammatory response leads to damage to host tissue, and the anti-inflammatory response causes leucocyte reprogramming and changes in immune status. The time-window for interventions is short, and treatment must promptly control the source of infection and restore haemodynamic homoeostasis. Further research is needed to establish which fluids and vasopressors are best. Some patients with septic shock might benefit from drugs such as corticosteroids or activated protein C. Other therapeutic strategies are under investigation, including those that target late proinflammatory mediators, endothelium, or the neuroendocrine system.

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ELABELA: a hormone essential for heart development signals via the apelin receptor.

Bruno Reversade, Xiao-Jing Tian, Lena Ho … (2013)

We report here the discovery and characterization of a gene, ELABELA (ELA), encoding a conserved hormone of 32 amino acids. Present in human embryonic stem cells, ELA is expressed at the onset of zebrafish zygotic transcription and is ubiquitous in the naive ectodermal cells of the embryo. Using zinc-finger-nuclease-mediated gene inactivation in zebrafish, we created an allelic series of ela mutants. ela null embryos have impaired endoderm differentiation potential marked by reduced gata5 and sox17 expression. Loss of Ela causes embryos to develop with a rudimentary heart or no heart at all, surprisingly phenocopying the loss of the apelin receptor (aplnr), which we show serves as Ela's cognate G protein-coupled receptor. Our results reveal the existence of a peptide hormone, ELA, which, together with APLNR, forms an essential signaling axis for early cardiovascular development. Copyright © 2013 Elsevier Inc. All rights reserved.

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Author and article information

Contributors

David Coquerel: david.coquerel@USherbrooke.ca

Xavier Sainsily: xavier.sainsily@USherbrooke.ca

Lauralyne Dumont: lauralyne.dumont@USherbrooke.ca

Philippe Sarret: philippe.sarret@USherbrooke.ca

Éric Marsault: eric.marsault@USherbrooke.ca

Mannix Auger-Messier: mannix.auger-messier@USherbrooke.ca

Olivier Lesur: Olivier.Lesur@USherbrooke.ca

Journal

Journal ID (nlm-ta): Crit Care

Title: Critical Care

Publisher: BioMed Central (London )

ISSN (Print): 1364-8535

ISSN (Electronic): 1466-609X

Publication date (Electronic): 19 January 2018

Publication date PMC-release: 19 January 2018

Publication date Collection: 2018

Volume: 22

Electronic Location Identifier: 10

Affiliations

[1 ]ISNI 0000 0000 9064 6198, GRID grid.86715.3d, Division of Intensive Care Units, Department of Medicine, , Université de Sherbrooke, ; 3001 - 12e Avenue Nord, Sherbrooke, QC J1H 5 N4 Canada

[2 ]ISNI 0000 0000 9064 6198, GRID grid.86715.3d, Division of Cardiology, Department of Medicine, , Université de Sherbrooke, ; Sherbrooke, Québec Canada

[3 ]ISNI 0000 0000 9064 6198, GRID grid.86715.3d, Department of Pharmacology-Physiology, , Université de Sherbrooke, ; Sherbrooke, Québec Canada

[4 ]ISNI 0000 0000 9064 6198, GRID grid.86715.3d, Pharmacology Institute of Sherbrooke, Faculty of Medecine and Health Sciences, Université de Sherbrooke, ; Sherbrooke, Québec Canada

Article

Publisher ID: 1942

DOI: 10.1186/s13054-018-1942-z

PMC ID: 5774146

PubMed ID: 29347994

SO-VID: 551a7034-4b49-4e56-b441-57bc9304f447

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

History

Date received : 7 November 2017

Date accepted : 3 January 2018

Funding

Funded by: FundRef http://dx.doi.org/10.13039/501100000028, Institute of Circulatory and Respiratory Health;

Award ID: 376770

Funded by: Merck-Sharp-Dhome FMSS

Award ID: 2014

Award Recipient : Mannix Auger-Messier

Funded by: CRCHUS2016

Award ID: PAFI

Award Recipient : Olivier Lesur

Funded by: FundRef http://dx.doi.org/10.13039/501100004489, Mitacs;

Award ID: IT05862

Award ID: IT08045

Award Recipient : Philippe Sarret Olivier Lesur

Funded by: FundRef http://dx.doi.org/10.13039/501100002790, Canadian Network for Research and Innovation in Machining Technology, Natural Sciences and Engineering Research Council of Canada;

Award ID: SEP-NSERC (EGP488509-15)

Award Recipient : Mannix Auger-Messier

Custom metadata

ScienceOpen disciplines: Emergency medicine & Trauma

Keywords: apelinergic system,apelin (apj) receptor,biased signaling,decatecholaminization,inodilator,septic shock

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ScienceOpen disciplines: Emergency medicine & Trauma

Keywords: apelinergic system, apelin (apj) receptor, biased signaling, decatecholaminization, inodilator, septic shock

The apelinergic system as an alternative to catecholamines in low-output septic shock

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Abstract

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Irish Journal of Paramedicine

Most cited references 42

Benchmarking the incidence and mortality of severe sepsis in the United States.

Septic shock.

ELABELA: a hormone essential for heart development signals via the apelin receptor.

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