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

Coquerel, David; Sainsily, Xavier; Dumont, L; Sarret, Philippe; Marsault, Éric; Auger‐Messier, Mannix; Lesur, Olivier

doi:10.1186/s13054-018-1942-z

Cited by 19 publications

(17 citation statements)

References 59 publications

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“…NE has been the frontline treatment since the SSC guidelines were first published in 2004, but it is still not perfect. This adrenergic agent causes increased oxidative stress and has harmful biological effects on the inflammatory response and cell energy metabolisms [ 40 ]. In this respect, the concept of “decatecholaminization,” defining as a partially or completely alternative to catecholamines rather than look for the best catecholamine, emerged in the last decade in fear of catecholamine exposure, resulting in a requirement of non-adrenergic receptors like VP, TP, selepressin, and AT-II [ 41 – 43 ], and then began a fight against mortality between adrenergic and non-adrenergic vasopressor agents.…”

Section: Discussionmentioning

confidence: 99%

Non-catecholamine vasopressors in the treatment of adult patients with septic shock—evidence from meta-analysis and trial sequential analysis of randomized clinical trials

et al. 2020

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Background Norepinephrine (NE) has currently been the first-choice vasopressor in treating septic shock despite generally insufficient for patients with refractory septic shock. The aim of this update meta-analysis was to assess the safety and efficacy of a combination of non-catecholamine vasopressors (vasopressin/pituitrin/terlipressin/selepressin/angiotensin II) and NE versus NE in managing adult septic shock patients. Methods We conducted this study of literatures published from the inception to April 30, 2020, using PubMed, Embase, and the Cochrane Library databases without language restriction. Randomized controlled trials comparing NE with non-catecholamine vasopressors among adult septic shock patients were included in this meta-analysis. Pooled effects of relative risk (RR) or standard mean difference (SMD) and corresponding 95% confidence interval (CI) were calculated using a random-effects model. Results Twenty-three studies covering 4380 participants were finally enrolled. The combined analysis of non-catecholamine vasopressors resulted in a nonsignificant reduction in 90-day/ICU/hospital mortality except for a decreased in 28-day mortality (n = 4217; RR, 0.92; 95% CI 0.86–0.99; P = 0.02). This favorable result was subsequently verified by the subgroup analyses of low risk of bias studies (RR = 0.91, 95% CI = 0.84 to 0.98; P = 0.02) and catecholamine-resistant refractory shock patients group (RR, 0.84; 95% CI = 0.70–1.00; P = 0.048). The pooled analysis of non-catecholamine vasopressors showed a 14% higher success rate of shock reversal at 6 h, a 29% decreased risk of continuous renal replacement therapy, but a 51% increased risk of hyponatremia and a 2.43 times higher risk of digital ischemia. Besides, the pooled data showed that non-catecholamine vasopressors decreased heart rate (HR) (SMD, − 0.43; 95% CI − 0.66 – − 0.19; P < 0.001), serum creatinine (− 0.15; 95% CI − 0.29 – − 0.01; P = 0.04), and the length of mechanical ventilation (MV) (− 0.19; 95% CI − 0.31 – − 0.07; P < 0.01, but there was no significant difference in other parameters. Conclusions Current pooled results suggest that the addition of NE to non-catecholamine vasopressors was associated with a marginally significant reduction in 28-day mortality. Moreover, they were able to shorten the length of MV, improved renal function, decreased HR, and increased the 6-h shock reversal success rate at the expense of increased the risk of hyponatremia and digital ischemia.

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Section: Discussionmentioning

confidence: 99%

Non-catecholamine vasopressors in the treatment of adult patients with septic shock—evidence from meta-analysis and trial sequential analysis of randomized clinical trials

et al. 2020

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“…ventriculoarterial recoupling, decongestion), as well as potentially advantageous ancillary effects on kidney function and cellular-protective actions, levosimendan is both a therapeutic resource and experimental tool for investigating this new approach. 161,[177][178][179][180][181][182][183][184] Developments in these areas, although already pioneered by promising exploratory studies will, inevitably, require well-designed and properly powered RCTs. [151][152][153]185,186 Central to future investigations will be the identification of robust and relevant endpoints.…”

Section: The Next 20 Years Of Levosimendanmentioning

confidence: 99%

Levosimendan Efficacy and Safety: 20 years of SIMDAX in Clinical Use

Papp¹,

Agostoni²,

Álvarez³

et al. 2020

Cardiac Failure Review

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Levosimendan was first approved for clinic use in 2000, when authorisation was granted by Swedish regulatory authorities for the haemodynamic stabilisation of patients with acutely decompensated chronic heart failure. In the ensuing 20 years, this distinctive inodilator, which enhances cardiac contractility through calcium sensitisation and promotes vasodilatation through the opening of adenosine triphosphate-dependent potassium channels on vascular smooth muscle cells, has been approved in more than 60 jurisdictions, including most of the countries of the European Union and Latin America. Areas of clinical application have expanded considerably and now include cardiogenic shock, takotsubo cardiomyopathy, advanced heart failure, right ventricular failure and pulmonary hypertension, cardiac surgery, critical care and emergency medicine. Levosimendan is currently in active clinical evaluation in the US. Levosimendan in IV formulation is being used as a research tool in the exploration of a wide range of cardiac and non-cardiac disease states. A levosimendan oral form is at present under evaluation in the management of amyotrophic lateral sclerosis. To mark the 20 years since the advent of levosimendan in clinical use, 51 experts from 23 European countries (Austria, Belgium, Croatia, Cyprus, Czech Republic, Estonia, Finland, France, Germany, Greece, Hungary, Italy, the Netherlands, Norway, Poland, Portugal, Russia, Slovenia, Spain, Sweden, Switzerland, UK and Ukraine) contributed to this essay, which evaluates one of the relatively few drugs to have been successfully introduced into the acute heart failure arena in recent times and charts a possible development trajectory for the next 20 years.

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“…Additional evidence of the deleterious impact of apelin disruption and/or antagonism of its receptor is exemplified by the serious adverse reactions sometimes observed using protamine (a submicromolar affinity competitive antagonist of the apelin receptor that reverses heparin anticoagulation), and by the occurrence of sudden rises in pulmonary arterial pressure, sustained hypotension, and impaired cardiac fractional shortening . Apelins can also potentially influence long‐term vascular remodeling by reducing inflammation and fibrosis …”

Section: Role Of Apelin and Its Receptor In Vascular Disease Modelsmentioning

confidence: 99%

The apelinergic system: a perspective on challenges and opportunities in cardiovascular and metabolic disorders

Marsault

Llorens-Cortes

Iturrioz

et al. 2019

Annals of the New York Academy of Sciences

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The apelinergic pathway has been generating increasing interest in the past few years for its potential as a therapeutic target in several conditions associated with the cardiovascular and metabolic systems. Indeed, preclinical and, more recently, clinical evidence both point to this G protein-coupled receptor as a target of interest in the treatment of not only cardiovascular disorders such as heart failure, pulmonary arterial hypertension, atherosclerosis, or septic shock, but also of additional conditions such as water retention/hyponatremic disorders, type 2 diabetes, and preeclampsia. While it is a peculiar system with its two classes of endogenous ligand, the apelins and Elabela, its intricacies are a matter of continuing investigation to finely pinpoint its potential and how it enables crosstalk between the vasculature and organ systems of interest. In this perspective article, we first review the current knowledge on the role of the apelinergic pathway in the above systems, as well as the associated therapeutic indications and existing pharmacological tools. We also offer a perspective on the challenges and potential ahead to advance the apelinergic system as a target for therapeutic intervention in several key areas.

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

Cited by 19 publications

References 59 publications

Non-catecholamine vasopressors in the treatment of adult patients with septic shock—evidence from meta-analysis and trial sequential analysis of randomized clinical trials

Non-catecholamine vasopressors in the treatment of adult patients with septic shock—evidence from meta-analysis and trial sequential analysis of randomized clinical trials

Levosimendan Efficacy and Safety: 20 years of SIMDAX in Clinical Use

The apelinergic system: a perspective on challenges and opportunities in cardiovascular and metabolic disorders

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