The effect of vasoactive drugs on mortality in patients with severe sepsis and septic shock. A network meta-analysis of randomized trials

Belletti, Alessandro; Benedetto, Umberto; Biondi‐Zoccai, Giuseppe; Leggieri, Carlo; Silvani, Paolo; Angelini, Gianni; Zangrillo, Alberto; Landoni, Giovanni

doi:10.1016/j.jcrc.2016.08.010

Cited by 64 publications

(34 citation statements)

References 87 publications

(111 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…167 'Decatecholaminisation' of the medical armamentarium is a developing line of practice in the management of critically ill patients. [168][169][170][171][172][173][174][175][176] As an established non-adrenergic vasoactive agent that offers positive cardiovascular effects (e.g. 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.…”

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

View full text Add to dashboard Cite

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.

show abstract

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

View full text Add to dashboard Cite

show abstract

“…Inotropic support is endorsed for restoration of an adequate cardiac output and peripheral oxygen delivery. 48 In the absence of a fully evidence-based alternative, dobutamine remains the suggested first-line inotrope for those goals, despite the observations that: (1) high levels of circulating catecholamines and adrenergic overstimulation contribute to the pathophysiology of SCM 54,76 ; (2) the adrenergic response at the cardiomyocyte level is attenuated by downregulation of β-adrenergic receptors 77,78 ; (3) adrenergic drugs have been associated with worse outcomes in a pooled network meta-analysis 36 ; and (4) esmolol, a β 1 -receptor antagonist, seems to improve the outcome of severe SCM, 78 especially in cases of persistent tachycardia. 79…”

Section: Levosimendan In Septic Shockmentioning

confidence: 99%

Use of Levosimendan in Intensive Care Unit Settings: An Opinion Paper

Herpain

Bouchez

Girardis

et al. 2019

Journal of Cardiovascular Pharmacology

View full text Add to dashboard Cite

Abstract:Levosimendan is an inodilator that promotes cardiac contractility primarily through calcium sensitization of cardiac troponin C and vasodilatation via opening of adenosine triphosphate–sensitive potassium (KATP) channels in vascular smooth muscle cells; the drug also exerts organ-protective effects through a similar effect on mitochondrial KATP channels. This pharmacological profile identifies levosimendan as a drug that may have applications in a wide range of critical illness situations encountered in intensive care unit medicine: hemodynamic support in cardiogenic or septic shock; weaning from mechanical ventilation or from extracorporeal membrane oxygenation; and in the context of cardiorenal syndrome. This review, authored by experts from 9 European countries (Austria, Belgium, Czech republic, Finland, France, Germany, Italy, Sweden, and Switzerland), examines the clinical and experimental data for levosimendan in these situations and concludes that, in most instances, the evidence is encouraging, which is not the case with other cardioactive and vasoactive drugs routinely used in the intensive care unit. The size of the available studies is, however, limited and the data are in need of verification in larger controlled trials. Some proposals are offered for the aims and designs of these additional studies.

show abstract

“…In these trials, the frequency of dobutamine use was significantly higher in the EGDT group than in the standard care group (ProCESS trial 8.0 vs. 1.1%, respectively; p < 0.001; ProMISe trial 8.0 vs. 1.1%, respectively; p < 0.001; and ARISE trial 15.4 vs. 2.6%, respectively; p < 0.0001), but there were no significant differences in the mortality between the groups. Although recent meta-analysis of randomized trials suggested inodilators such as levosimendan and dobutamine might improve the survival in septic patients [ 6 ], most studies comparing inotropes included in this study were small single center studies, and we have to be careful to interpret the results. Furthermore, the biggest randomized controlled trial showed no benefit of levosimendan in mortality or prevention for organ dysfunction in septic patients [ 7 ].…”

Section: Manuscriptmentioning

confidence: 99%

Time to re-think the use of dobutamine in sepsis

Sato

Nasu²

2017

j intensive care

View full text Add to dashboard Cite

Dobutamine is commonly used worldwide and included in the protocol for early goal-directed therapy (EGDT). Since the use of dobutamine in EGDT was reported, it has been considered to be an important component, especially in the treatment of septic patients with myocardial dysfunction. However, it is questionable whether dobutamine improves the mortality of sepsis and septic shock.In three recent randomized controlled trials (ProCESS, ProMISe, and ARISE trials), the frequency of dobutamine use was significantly higher in the EGDT group than in the standard care group, but there were no significant differences in the mortality between the groups. These results suggested that dobutamine use may have been overemphasized despite its insignificant effect on the mortality in septic patients. Further, a propensity score analysis revealed that dobutamine use was associated with higher mortality in patients with septic shock.Although dobutamine leads to an increase in cardiac index, myocardial oxygen demand also increases, thus increasing the risk of myocardial ischemia and tachyarrhythmia. It is well known that the mortality in sepsis complicated with atrial fibrillation (AFib) is worse than that in sepsis without AFib. A propensity score-matched analysis reported that β-blockers were associated with better survival in patients with sepsis complicated with AFib. Further, a randomized controlled trial reported that a short-acting β-blocker improved the survival in patients with septic shock. These studies also indicated the risk of β-stimulation during sepsis.Notably, improvements in surrogate markers, such as CI, do not always indicate improvements in patient-centered outcomes, such as mortality. Conversely, some evidence indicates the worsening of patient-centered outcomes despite improvements in surrogate markers.Thus, available evidence suggests that the benefits of dobutamine in patients with sepsis are unclear, but its use might be harmful rather than beneficial, considering the beneficial effects of β-blockers in sepsis that have been reported in recent clinical studies. From this perspective, we will soon have to rethink regarding dobutamine use in patients with sepsis.

show abstract

The effect of vasoactive drugs on mortality in patients with severe sepsis and septic shock. A network meta-analysis of randomized trials

Abstract: Among several regimens for pharmacological cardiovascular support in septic patients, regimens based on inodilators have the highest probability of improve survival.

Cited by 64 publications

References 87 publications

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

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

Use of Levosimendan in Intensive Care Unit Settings: An Opinion Paper

Time to re-think the use of dobutamine in sepsis

Contact Info

Product

Resources

About