Levosimendan in septic shock in patients with biochemical evidence of cardiac dysfunction: a subgroup analysis of the LeoPARDS randomised trial

Antcliffe, David; Santhakumaran, Shalini; Orme, Robert; Ward, Josie K; Al-Beidh, Farah; O’Dea, Kieran P.; Perkins, Gavin D.; Singer, Mervyn; McAuley, Daniel F.; Mason, Alexina J.; Cross, Mary; Ashby, Deborah; Gordon, Anthony

doi:10.1007/s00134-019-05731-w

Cited by 34 publications

(28 citation statements)

References 28 publications

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“…Another limitation is the multiple-choice character of our survey, limiting answers to those offered. In addition, studies published after the survey was performed [38,[43][44][45][46] might have altered the answers of the respondents. Nevertheless, after careful analysis of the results of those studies we believe that the experts' recommendation would not have changed significantly.…”

Section: Limitationsmentioning

confidence: 99%

Current use of inotropes in circulatory shock

Scheeren

Bakker

Kaufmann

et al. 2021

Ann. Intensive Care

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Background Treatment decisions on critically ill patients with circulatory shock lack consensus. In an international survey, we aimed to evaluate the indications, current practice, and therapeutic goals of inotrope therapy in the treatment of patients with circulatory shock. Methods From November 2016 to April 2017, an anonymous web-based survey on the use of cardiovascular drugs was accessible to members of the European Society of Intensive Care Medicine (ESICM). A total of 14 questions focused on the profile of respondents, the triggering factors, first-line choice, dosing, timing, targets, additional treatment strategy, and suggested effect of inotropes. In addition, a group of 42 international ESICM experts was asked to formulate recommendations for the use of inotropes based on 11 questions. Results A total of 839 physicians from 82 countries responded. Dobutamine was the first-line inotrope in critically ill patients with acute heart failure for 84% of respondents. Two-thirds of respondents (66%) stated to use inotropes when there were persistent clinical signs of hypoperfusion or persistent hyperlactatemia despite a supposed adequate use of fluids and vasopressors, with (44%) or without (22%) the context of low left ventricular ejection fraction. Nearly half (44%) of respondents stated an adequate cardiac output as target for inotropic treatment. The experts agreed on 11 strong recommendations, all of which were based on excellent (> 90%) or good (81–90%) agreement. Recommendations include the indications for inotropes (septic and cardiogenic shock), the choice of drugs (dobutamine, not dopamine), the triggers (low cardiac output and clinical signs of hypoperfusion) and targets (adequate cardiac output) and stopping criteria (adverse effects and clinical improvement). Conclusion Inotrope use in critically ill patients is quite heterogeneous as self-reported by individual caregivers. Eleven strong recommendations on the indications, choice, triggers and targets for the use of inotropes are given by international experts. Future studies should focus on consistent indications for inotrope use and implementation into a guideline for circulatory shock that encompasses individualized targets and outcomes.

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Section: Limitationsmentioning

confidence: 99%

Current use of inotropes in circulatory shock

Scheeren

Bakker

Kaufmann

et al. 2021

Ann. Intensive Care

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“…Im septischen Schock zeigte eine Levosimendan-Therapie allerdings keinen positiven Einfluss auf das Überleben [45]. Dies bestätigte sich auch in der Subgruppe für Patienten mit Hinweis auf eine kardiale Dysfunktion [46].…”

Section: Merkeunclassified

Diagnose und Therapie des kardiogenen Schocks im akuten Myokardinfarkt

Fichera¹,

Thelemann²,

Fürnau³

2020

Notf.med. up2date

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“…Furthermore, in a sub-group analysis of the LeoPARDS trial, Antcliffe et al used the biomarkers cTnI and NT-proBNP to identify patients with evidence of myocardial injury and dysfunction, respectively. These authors did not observe any benefit from using levosimendan in any subgroup classified by a variety of biomarker cut-off thresholds [73]. No data suggests differences in outcome between dobutamine and levosimendan in septic shock patients.…”

Section: Potential Non-routine (Niche) Indications For Levosimendan (mentioning

confidence: 99%

Levosimendan in the light of the results of the recent randomized controlled trials: an expert opinion paper

et al. 2019

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Despite interesting and unique pharmacological properties, levosimendan has not proven a clear superiority to placebo in the patient populations that have been enrolled in the various recent multicenter randomized controlled trials. However, the pharmacodynamic effects of levosimendan are still considered potentially very useful in a number of specific situations.Patients with decompensated heart failure requiring inotropic support and receiving beta-blockers represent the most widely accepted indication. Repeated infusions of levosimendan are increasingly used to facilitate weaning from dobutamine and avoid prolonged hospitalizations in patients with end-stage heart failure, awaiting heart transplantation or left ventricular assist device implantation. New trials are under way to confirm or refute the potential usefulness of levosimendan to facilitate weaning from veno-arterial ECMO, to treat cardiogenic shock due to left or right ventricular failure because the current evidence is mostly retrospective and requires confirmation with better-designed studies. Takotsubo syndrome may represent an ideal target for this non-adrenergic inotrope, but this statement also relies on expert opinion. There is no benefit from levosimendan in patients with septic shock. The two large trials evaluating the prophylactic administration of levosimendan (pharmacological preconditioning) in cardiac surgical patients with poor left ventricular ejection fraction could not show a significant reduction in their composite endpoints reflecting low cardiac output syndrome with respect to placebo. However, the subgroup of those who underwent isolated CABG appeared to have a reduction in mortality. A new study will be required to confirm this exploratory finding.Levosimendan remains a potentially useful inodilator agent in a number of specific situations due to its unique pharmacological properties. More studies are needed to provide a higher level of proof regarding these indications.

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Levosimendan in septic shock in patients with biochemical evidence of cardiac dysfunction: a subgroup analysis of the LeoPARDS randomised trial

Cited by 34 publications

References 28 publications

Current use of inotropes in circulatory shock

Current use of inotropes in circulatory shock

Diagnose und Therapie des kardiogenen Schocks im akuten Myokardinfarkt

Levosimendan in the light of the results of the recent randomized controlled trials: an expert opinion paper

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