-
Lancet (London, England) Jul 2002Levosimendan, a novel calcium sensitiser, improves myocardial contractility without causing an increase in myocardial oxygen demand. We compared the effects of... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
BACKGROUND
Levosimendan, a novel calcium sensitiser, improves myocardial contractility without causing an increase in myocardial oxygen demand. We compared the effects of levosimendan and dobutamine on haemodynamic performance and clinical outcome in patients with low-output heart failure.
METHODS
Patients were recruited into a multicentre, randomised, double-blind, double-dummy, parallel-group trial. Under continuous haemodynamic monitoring, an initial loading dose of levosimendan of 24 microg/kg was infused over 10 min, followed by a continuous infusion of 0.1 microg kg(-1) min(-1) for 24 h. Dobutamine was infused for 24 h at an initial dose of 5 microg kg(-1) min(-1) without a loading dose. The infusion rate was doubled if the response was inadequate at 2h. The primary endpoint was the proportion of patients with haemodynamic improvement (defined as an increase of 30% or more in cardiac output and a decrease of 25% or more in pulmonary-capillary wedge pressure) at 24 h. Analyses were by intention to treat.
FINDINGS
103 patients were assigned levosimendan and 100 dobutamine. The primary haemodynamic endpoint was achieved in 29 (28%) levosimendan-group patients and 15 (15%) in the dobutamine group (hazard ratio 1.9 [95% CI 1.1-3.3]; p=0.022). At 180 days, 27 (26%) levosimendan-group patients had died, compared with 38 (38%) in the dobutamine group (0.57 [0.34-0.95]; p=0.029).
INTERPRETATION
In patients with severe, low-output heart failure, levosimendan improved haemodynamic performance more effectively than dobutamine. This benefit was accompanied by lower mortality in the levosimendan group than in the dobutamine group for up to 180 days.
Topics: Cardiac Output, Low; Cardiotonic Agents; Dobutamine; Double-Blind Method; Female; Hemodynamics; Humans; Hydrazones; Male; Middle Aged; Pyridazines; Simendan; Treatment Outcome
PubMed: 12133653
DOI: 10.1016/s0140-6736(02)09455-2 -
Pharmacotherapy 1989Dobutamine is a commonly used positive inotrope for the short-term management of heart failure. It is commercially available as a 50:50 mixture of two isomers with... (Review)
Review
Dobutamine is a commonly used positive inotrope for the short-term management of heart failure. It is commercially available as a 50:50 mixture of two isomers with unique effects on alpha- and beta adrenergic receptors. In dosages of 2-15 micrograms/kg/minute, dobutamine has been shown to increase cardiac output (mainly through stroke volume), reduce systemic vascular resistance, lower central venous and pulmonary artery wedge pressures, improve renal blood flow, and relieve signs and symptoms of congestive heart failure. At higher dosages it can increase heart rate and induce arrhythmias. Recent evidence indicates that effects of dobutamine last long after the drug has been eliminated from the plasma, and some work has been done on ambulatory use of this agent. Dobutamine has been used successfully in several circumstances, such as after cardiac surgery, in patients with myocardial infarction, and in various shock states. An understanding of the pathophysiology of the underlying disorder is important in deciding which catecholamine to use. With this in mind, monotherapy or combination therapy with inodilators such as dobutamine, or inopressors like dopamine will follow logically.
Topics: Cardiac Output, Low; Cardiac Surgical Procedures; Dobutamine; Humans; Myocardial Infarction; Shock
PubMed: 2671957
DOI: 10.1002/j.1875-9114.1989.tb04133.x -
The American Journal of the Medical... Oct 1987Dobutamine is a sympathomimetic amine that was designed as an inotropic agent for use in congestive heart failure. Clinically, dobutamine increases cardiac output by... (Review)
Review
Dobutamine is a sympathomimetic amine that was designed as an inotropic agent for use in congestive heart failure. Clinically, dobutamine increases cardiac output by selectively augmenting stroke volume, and this is associated with a decrease in total peripheral vascular resistance that is mediated, in part, by reflex withdrawal of sympathetic tone to the vasculature. This hemodynamic profile of dobutamine makes the drug of value in the management of low output cardiac failure. The inotropic activity of dobutamine has previously been attributed to selective stimulation of myocardial beta 1-adrenoceptors. However, recent studies from a number of laboratories indicate that the mechanism of action of dobutamine is substantially more complex. Dobutamine has the capacity to stimulate beta 1-, beta 2-, and alpha 1-adrenoceptors in the cardiovascular system at doses that approximate those used clinically. It has recently been suggested that the inotropic activity of dobutamine results from combined beta 1- and alpha 1-adrenoceptor stimulation in the myocardium, and that this activity could explain, at least in part, the inotropic selectivity of the compound. Furthermore, in the vasculature, the beta 2-adrenoceptor-mediated vasodilatory effect of dobutamine is exactly offset by the alpha 1-adrenoceptor-mediated vasoconstrictor activity, such that net changes in blood pressure are minimal following the administration of dobutamine. It is concluded, therefore, that the hemodynamic profile of dobutamine in patients with congestive heart failure is derived from a unique and complex series of interactions with alpha- and beta-adrenoceptors in the cardiovascular system.
Topics: Dobutamine; Heart Failure; Hemodynamics; Humans; Myocardial Contraction
PubMed: 3310640
DOI: 10.1097/00000441-198710000-00005 -
PloS One 2014Although dobutamine is widely used in neonatal clinical practice, the evidence for its use in this specific population is not clear. We conducted a systematic review of... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Although dobutamine is widely used in neonatal clinical practice, the evidence for its use in this specific population is not clear. We conducted a systematic review of the use of dobutamine in juvenile animals to determine whether the evidence from juvenile animal experiments with dobutamine supported the design of clinical trials in neonatal/paediatric population.
METHODS
Studies were identified by searching MEDLINE (1946-2012) and EMBASE (1974-2012). Articles retrieved were independently reviewed by three authors and only those concerning efficacy and safety of the drug in juvenile animals were included. Only original articles published in English and Spanish were included.
RESULTS
Following our literature search, 265 articles were retrieved and 24 studies were included in the review: 17 focused on neonatal models and 7 on young animal models. Although the aims and design of these studies, as well as the doses and ages analysed, were quite heterogeneous, the majority of authors agree that dobutamine infusion improves cardiac output in a dose dependent manner. Moreover, the cardiovascular effects of dobutamine are influenced by postnatal age, as well as by the dose used and the duration of the therapy. There is inadequate information about the effects of dobutamine on cerebral perfusion to draw conclusions.
CONCLUSION
There is enough preclinical evidence to ensure that dobutamine improves cardiac output, however to better understand its effects in peripheral organs, such as the brain, more specific and well designed studies are required to provide additional data to support the design of clinical trials in a paediatric population.
Topics: Adrenergic beta-1 Receptor Agonists; Age Factors; Animals; Animals, Newborn; Cardiotonic Agents; Cardiovascular System; Dobutamine; Drug Evaluation, Preclinical; Humans; Models, Animal
PubMed: 24755688
DOI: 10.1371/journal.pone.0095644 -
Annales de L'anesthesiologie Francaise 1981
Review
Topics: Animals; Catecholamines; Chemical Phenomena; Chemistry, Physical; Dobutamine; Drug Interactions; Hemodynamics; Humans; Receptors, Adrenergic
PubMed: 6124192
DOI: No ID Found -
Pediatric Cardiology Jan 2016Since its discovery in 1975 dobutamine has been used off-label for treating hemodynamic insufficiency in newborns and children. We present a structured literature review... (Review)
Review
Since its discovery in 1975 dobutamine has been used off-label for treating hemodynamic insufficiency in newborns and children. We present a structured literature review of pharmacokinetic and pharmacodynamic data for dobutamine in the pediatric population. Structured searches were conducted to identify relevant articles according to pre-defined inclusion criteria. Where possible, results for the pharmacodynamic and pharmacokinetic effect of dobutamine were reported as pooled data. Forty-six papers met the inclusion criteria. With regard to pharmacodynamic data a number of studies reported significant increases in a number of clinical parameters such as heart rate, blood pressure, cardiac output across a wide range of pediatric populations. With regard to pharmacokinetic data studies reported that the infusion rate was positively correlated to plasma dobutamine concentration. There was great variability with regard to dobutamine clearance between individuals and as to whether it followed first- or zero-order elimination kinetics. While the pharmacodynamic effects of dobutamine appear to reflect the pharmacological profile of the drug, the pharmacokinetic data are difficult to interpret due to inhomogeneity between study populations ages, comorbidities, dobutamine dosages and methodologies. High-quality prospective pharmacokinetic and pharmacodynamic data especially in newborns are urgently required prior to a large randomized study.
Topics: Blood Pressure; Cardiac Output; Child; Dobutamine; Dose-Response Relationship, Drug; Heart Rate; Humans; Hypotension; Infant; Infant, Newborn; Sympathomimetics
PubMed: 26346024
DOI: 10.1007/s00246-015-1263-9 -
Neonatal Network : NN Oct 1994
Topics: Dobutamine; Hemodynamics; Humans; Infant, Newborn; Neonatal Nursing
PubMed: 7862069
DOI: No ID Found -
American Journal of Cardiovascular... Dec 2015Inotropes and natriuretic peptides are essential components of current therapeutic options for acute decompensated heart failure (ADHF). This systematic review examines... (Meta-Analysis)
Meta-Analysis Review
Dobutamine Therapy is Associated with Worse Clinical Outcomes Compared with Nesiritide Therapy for Acute Decompensated Heart Failure: A Systematic Review and Meta-Analysis.
BACKGROUND
Inotropes and natriuretic peptides are essential components of current therapeutic options for acute decompensated heart failure (ADHF). This systematic review examines the therapeutic effectiveness of dobutamine and brain natriuretic peptide, nesiritide, in reducing mortality and readmission rates for ADHF treatment.
METHODS
Published studies related to dobutamine and nesiritide therapy in ADHF were identified via an exhaustive search of scientific literature databases. The identified studies, published between 2002 and 2012, were carefully screened based on our predefined inclusion criteria. Selected studies were pooled, and odds ratios (ORs) and 95% confidence intervals (95% CI) for each outcome were calculated. Subgroup analysis was conducted to assess the influence of ethnicity on the study outcome.
RESULTS
Seven cohort studies were selected for this meta-analysis. These seven studies included 959 ADHF patients who underwent nesiritide treatment and 1748 ADHF patients who received dobutamine therapy. Our meta-analysis revealed a significantly lower survival rate in dobutamine-treated patients compared with nesiritide-treated patients (OR 0.48, 95% CI 0.36-0.63, P < 0.001). Additionally, a markedly higher readmission rate was associated with dobutamine treatment compared with nesiritide treatment (OR 0.52, 95% CI 0.36-0.73, P < 0.001). A stratified analysis based on ethnicity revealed a significantly lower survival in dobutamine-treated ADHF patients in Caucasian and mixed populations compared with nesiritide treatment (Caucasian: OR 0.60, 95% CI 0.38-0.94, P = 0.024; Mixed: OR 0.38, 95% CI 0.26-0.56, P < 0.001). However, a similar association was not detected in Asian populations (P = 0.738). Further, dobutamine-treated ADHF patients displayed higher readmission rates than did nesiritide-treated patients in both Caucasian and mixed-race populations (all P < 0.05).
CONCLUSIONS
Our study suggests that dobutamine therapy is associated with poorer outcomes, with higher in-hospital mortality rates and increased readmission rates compared with nesiritide therapy in ADHF patients. Thus, current treatment strategies need to be redesigned for better outcomes.
Topics: Acute Disease; Cardiotonic Agents; Cohort Studies; Dobutamine; Heart Failure; Hospital Mortality; Humans; Natriuretic Peptide, Brain; Patient Readmission; Survival Analysis
PubMed: 26123415
DOI: 10.1007/s40256-015-0134-3 -
Revista Brasileira de Terapia Intensiva 2017Dobutamine is the inotrope most commonly used in septic shock patients to increase cardiac output and correct hypoperfusion. Although some experimental and clinical... (Review)
Review
Dobutamine is the inotrope most commonly used in septic shock patients to increase cardiac output and correct hypoperfusion. Although some experimental and clinical studies have shown that dobutamine can improve systemic and regional hemodynamics, other research has found that its effects are heterogenous and unpredictable. In this review, we analyze the pharmacodynamic properties of dobutamine and its physiologic effects. Our goal is to show that the effects of dobutamine might differ between healthy subjects, in experimental and clinical cardiac failure, in animal models and in patients with septic shock. We discuss evidence supporting the claim that dobutamine, in septic shock, frequently behaves as a chronotropic and vasodilatory drug, without evidence of inotropic action. Since the side effects are very common, and the therapeutic benefits are unclear, we suggest that dobutamine should be used cautiously in septic shock. Before a definitive therapeutic decision, the efficacy and tolerance of dobutamine should be assessed during a brief time with close monitoring of its positive and negative side effects.
Topics: Animals; Cardiac Output; Cardiotonic Agents; Dobutamine; Drug Monitoring; Hemodynamics; Humans; Shock, Septic
PubMed: 29340539
DOI: 10.5935/0103-507X.20170068 -
The New England Journal of Medicine Jan 1979
Comparative Study Review
Topics: Animals; Cardiac Output; Catecholamines; Dobutamine; Heart Failure; Humans; Myocardial Contraction; Myocardial Infarction; Sympathomimetics
PubMed: 362214
DOI: 10.1056/NEJM197901043000105