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Current Problems in Cardiology Aug 2023This study aims to evaluate the difference between dobutamine and milrinone in patients presenting with acute decompensated heart failure (AHF). Inotropes are indicated... (Meta-Analysis)
Meta-Analysis Review
This study aims to evaluate the difference between dobutamine and milrinone in patients presenting with acute decompensated heart failure (AHF). Inotropes are indicated for treating AHF, especially in patients with concomitant hypoperfusion indicative of cardiogenic shock. However, previous studies have not identified the optimal inotrope. We sought to compare outcomes associated with milrinone versus dobutamine in patients with AHF. A systematic literature search was performed to identify relevant trials from inception to August 2021. Our primary outcome of interest was mortality. Analysis was sub-categorized according to subpopulation, including AHF, AHF with cardiogenic shock (AHF-shock), AHF with a bridge to transplantation, and AHF with destination therapy. Summary effects were calculated using a fixed-effects model as risk ratio or mean difference with 95% confidence intervals for all the clinical endpoints. Ten studies, including one randomized controlled trial with 21,106 patients, were included in the analysis (4918 patients were in the Milrinone group, while 15188 were in the Dobutamine group). Milrinone was associated with a lower risk of mortality in patients with AHF (relative risk 0.87; confidence interval :0.79-0.97; P < 0.05, heterogeneity I² = 0%) with event rates of 9.4% vs 9.8% (number needed to treat of 250). Milrinone was also associated with improved mortality with relative risk 0.76 (0.79-0.95; P < 0.05) in patients with AHF with destination therapy. There was a non-significant trend towards improved mortality in AHF-shock patients. However, AHF with a bridge to transplantation patients had a non-significant trend towards improved mortality with dobutamine. There was no difference between the 2 strategies for the outcomes of acute kidney injury, initiation of renal replacement therapy, mechanical ventilation, arrhythmias, symptomatic hypotension, and length of hospital stay in the overall population. Intensive care unit length of hospital stay was lower in AHF-shock patients in the milrinone group, whereas dobutamine was associated with a lower length of intensive care unit stay in AHF patients. The cumulative data comparing milrinone with dobutamine indicate an overall marginal benefit of milrinone compared to dobutamine in the totality of patients with AFH with or without cardiogenic shock, and whether or not they are bridged to transplantation or destination assist device. More appropriately powered prospective studies are needed to identify a conclusive benefit of one inotrope over another.
Topics: Humans; Dobutamine; Milrinone; Shock, Cardiogenic; Cardiotonic Agents; Retrospective Studies; Heart Failure; Randomized Controlled Trials as Topic
PubMed: 35545181
DOI: 10.1016/j.cpcardiol.2022.101245 -
The Cochrane Database of Systematic... Nov 2020Cardiogenic shock (CS) and low cardiac output syndrome (LCOS) are potentially life-threatening complications of acute myocardial infarction (AMI), heart failure (HF) or... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Cardiogenic shock (CS) and low cardiac output syndrome (LCOS) are potentially life-threatening complications of acute myocardial infarction (AMI), heart failure (HF) or cardiac surgery. While there is solid evidence for the treatment of other cardiovascular diseases of acute onset, treatment strategies in haemodynamic instability due to CS and LCOS remains less robustly supported by the given scientific literature. Therefore, we have analysed the current body of evidence for the treatment of CS or LCOS with inotropic and/or vasodilating agents. This is the second update of a Cochrane review originally published in 2014.
OBJECTIVES
Assessment of efficacy and safety of cardiac care with positive inotropic agents and vasodilator agents in CS or LCOS due to AMI, HF or after cardiac surgery.
SEARCH METHODS
We conducted a search in CENTRAL, MEDLINE, Embase and CPCI-S Web of Science in October 2019. We also searched four registers of ongoing trials and scanned reference lists and contacted experts in the field to obtain further information. No language restrictions were applied.
SELECTION CRITERIA
Randomised controlled trials (RCTs) enrolling patients with AMI, HF or cardiac surgery complicated by CS or LCOS.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures according to Cochrane standards.
MAIN RESULTS
We identified 19 eligible studies including 2385 individuals (mean or median age range 56 to 73 years) and three ongoing studies. We categorised studies into 11 comparisons, all against standard cardiac care and additional other drugs or placebo. These comparisons investigated the efficacy of levosimendan versus dobutamine, enoximone or placebo; enoximone versus dobutamine, piroximone or epinephrine-nitroglycerine; epinephrine versus norepinephrine or norepinephrine-dobutamine; dopexamine versus dopamine; milrinone versus dobutamine and dopamine-milrinone versus dopamine-dobutamine. All trials were published in peer-reviewed journals, and analyses were done by the intention-to-treat (ITT) principle. Eighteen of 19 trials were small with only a few included participants. An acknowledgement of funding by the pharmaceutical industry or missing conflict of interest statements occurred in nine of 19 trials. In general, confidence in the results of analysed studies was reduced due to relevant study limitations (risk of bias), imprecision or indirectness. Domains of concern, which showed a high risk in more than 50% of included studies, encompassed performance bias (blinding of participants and personnel) and bias affecting the quality of evidence on adverse events. All comparisons revealed uncertainty on the effect of inotropic/vasodilating drugs on all-cause mortality with a low to very low quality of evidence. In detail, the findings were: levosimendan versus dobutamine (short-term mortality: RR 0.60, 95% CI 0.36 to 1.03; participants = 1701; low-quality evidence; long-term mortality: RR 0.84, 95% CI 0.63 to 1.13; participants = 1591; low-quality evidence); levosimendan versus placebo (short-term mortality: no data available; long-term mortality: RR 0.55, 95% CI 0.16 to 1.90; participants = 55; very low-quality evidence); levosimendan versus enoximone (short-term mortality: RR 0.50, 0.22 to 1.14; participants = 32; very low-quality evidence; long-term mortality: no data available); epinephrine versus norepinephrine-dobutamine (short-term mortality: RR 1.25; 95% CI 0.41 to 3.77; participants = 30; very low-quality evidence; long-term mortality: no data available); dopexamine versus dopamine (short-term mortality: no deaths in either intervention arm; participants = 70; very low-quality evidence; long-term mortality: no data available); enoximone versus dobutamine (short-term mortality RR 0.21; 95% CI 0.01 to 4.11; participants = 27; very low-quality evidence; long-term mortality: no data available); epinephrine versus norepinephrine (short-term mortality: RR 1.81, 0.89 to 3.68; participants = 57; very low-quality evidence; long-term mortality: no data available); and dopamine-milrinone versus dopamine-dobutamine (short-term mortality: RR 1.0, 95% CI 0.34 to 2.93; participants = 20; very low-quality evidence; long-term mortality: no data available). No information regarding all-cause mortality were available for the comparisons milrinone versus dobutamine, enoximone versus piroximone and enoximone versus epinephrine-nitroglycerine.
AUTHORS' CONCLUSIONS
At present, there are no convincing data supporting any specific inotropic or vasodilating therapy to reduce mortality in haemodynamically unstable patients with CS or LCOS. Considering the limited evidence derived from the present data due to a high risk of bias and imprecision, it should be emphasised that there is an unmet need for large-scale, well-designed randomised trials on this topic to close the gap between daily practice in critical care of cardiovascular patients and the available evidence. In light of the uncertainties in the field, partially due to the underlying methodological flaws in existing studies, future RCTs should be carefully designed to potentially overcome given limitations and ultimately define the role of inotropic agents and vasodilator strategies in CS and LCOS.
Topics: Aged; Cardiac Output, Low; Cardiotonic Agents; Cause of Death; Dobutamine; Enoximone; Epinephrine; Humans; Hydrazones; Middle Aged; Myocardial Infarction; Nitric Oxide; Placebos; Pyridazines; Randomized Controlled Trials as Topic; Shock, Cardiogenic; Simendan; Vasodilator Agents
PubMed: 33152122
DOI: 10.1002/14651858.CD009669.pub4 -
Shock (Augusta, Ga.) Dec 2023Background: Septic shock is a distributive shock with decreased systemic vascular resistance and MAP. Septic shock contributes to the most common causes of death in the... (Meta-Analysis)
Meta-Analysis
Background: Septic shock is a distributive shock with decreased systemic vascular resistance and MAP. Septic shock contributes to the most common causes of death in the intensive care unit (ICU). Current guidelines recommend the use of norepinephrine as the first-line vasopressor, whereas adrenergic agonists and vasopressin analogs are also commonly used by physicians. To date, very few studies have synthetically compared the effects of multiple types of vasoactive medications. The aim of this study was to systemically evaluate the efficacy of vasoactive agents both individually and in combination to treat septic shock. Methods: The PubMed, MEDLINE, Embase, Web of Science, and Cochrane Central Register for Controlled Trials (CENTRAL) were searched up to May 12, 2022, to identify relevant randomized controlled trials. A network meta-analysis was performed to evaluate the effect of different types of vasopressors. The primary outcome was 28-day all-cause mortality. The secondary outcome was the ICU length of stay. Adverse events are defined as any undesirable outcomes, including myocardial infarction, cardiac arrhythmia, peripheral ischemia, or stroke and cerebrovascular events. Findings: Thirty-three randomized controlled trials comprising 4,966 patients and assessing 8 types of vasoactive treatments were included in the network meta-analysis. The surface under the cumulative ranking curve provided a ranking of vasoactive medications in terms of 28-day all-cause mortality from most effective to least effective: norepinephrine plus dobutamine, epinephrine, vasopressin, terlipressin, norepinephrine, norepinephrine plus vasopressin, dopamine, and dobutamine. Dopamine was associated with a significantly shorter ICU stay than norepinephrine, terlipressin, and vasopressin, whereas other vasoactive medications showed no definite difference in ICU length of stay. Regarding adverse events, norepinephrine was associated with the highest incidences of myocardial infarction and peripheral ischemia. Dopamine was associated with the highest incidence of cardiac arrhythmia. Epinephrine and terlipressin were associated with the highest incidences of myocardial infarction and peripheral ischemia. Interpretation: The results of this network meta-analysis suggest that norepinephrine plus dobutamine is associated with a lower risk of 28-day mortality in septic shock patients than other vasoactive medications, and the use of dopamine is associated with a higher risk of 28-day mortality due to septic shock than norepinephrine, terlipressin, and vasopressin.
Topics: Humans; Shock, Septic; Dopamine; Terlipressin; Dobutamine; Network Meta-Analysis; Vasoconstrictor Agents; Epinephrine; Norepinephrine; Vasopressins; Arrhythmias, Cardiac; Ischemia; Myocardial Infarction
PubMed: 37548686
DOI: 10.1097/SHK.0000000000002193 -
Frontiers in Pharmacology 2022Erythrocytes and their breakdown products in the subarachnoid space (SAS) are the main contributors to the pathogenesis of subarachnoid hemorrhage (SAH). Dobutamine is...
Erythrocytes and their breakdown products in the subarachnoid space (SAS) are the main contributors to the pathogenesis of subarachnoid hemorrhage (SAH). Dobutamine is a potent β-adrenoreceptor agonist that can increase cardiac output, thus improving blood perfusion and arterial pulsation in the brain. In this study, we investigated whether the administration of dobutamine promoted the clearance of red blood cells (RBCs) and their degraded products meningeal lymphatic vessels (mLVs), thus alleviating neurological deficits in the early stage post-SAH. Experimental SAH was induced by injecting autologous arterial blood into the prechiasmatic cistern in male C57BL/6 mice. Evans blue was injected into the cisterna magna, and dobutamine was administered by inserting a femoral venous catheter. RBCs in the deep cervical lymphatic nodes (dCLNs) were evaluated by hematoxylin-eosin staining, and the hemoglobin content in dCLNs was detected by Drabkin's reagent. The accumulation of RBCs in the dura mater was examined by immunofluorescence staining, neuronal death was evaluated by Nissl staining, and apoptotic cell death was evaluated by TUNEL staining. The Morris water maze test was used to examine the cognitive function of mice after SAH. RBCs appeared in dCLNs as early as 3 h post-SAH, and the hemoglobin in dCLNs peaked at 12 h after SAH. Dobutamine significantly promoted cerebrospinal fluid (CSF) drainage from the SAS to dCLNs and obviously reduced the RBC residue in mLVs, leading to a decrease in neuronal death and an improvement in cognitive function after SAH. Dobutamine administration significantly promoted RBC drainage from cerebrospinal fluid in the SAS mLVs into dCLNs, ultimately relieving neuronal death and improving cognitive function.
PubMed: 36703738
DOI: 10.3389/fphar.2022.1061457 -
Clinics in Perinatology Sep 2020Primary function of cardiovascular system is to meet body's metabolic demands. The aim of inotrope therapy is to minimise adverse impact of cardiovascular compromise.... (Review)
Review
Primary function of cardiovascular system is to meet body's metabolic demands. The aim of inotrope therapy is to minimise adverse impact of cardiovascular compromise. Current use of inotropes is primarily guided by the pathophysiology of cardiovascular compromise and anticipated actions of inotropes. Lack of significant reduction in morbidity and mortality associated with cardiovascular compromise despite inotrope use, highlights major gaps in our understanding of circulatory targets, thresholds and choices of inotrope therapy. Thus far, prevention of cardiovascular compromise remains the most effective strategy to optimize outcomes. Studies of alternative design are needed for further advancement in cardiovascular therapy in neonates.
Topics: Cardiac Output; Cardiotonic Agents; Dobutamine; Dopamine; Echocardiography; Epinephrine; Heart; Humans; Hypotension; Infant, Newborn; Lactic Acid; Milrinone; Norepinephrine; Perfusion Index; Skin; Spectroscopy, Near-Infrared; Ultrasonography; Urination; Vasopressins
PubMed: 32713449
DOI: 10.1016/j.clp.2020.05.010 -
Current Cardiology Reports Jan 2021Myocardial viability is an important pathophysiologic concept which may have significant clinical impact in patients with left ventricular dysfunction due to ischemic... (Review)
Review
PURPOSE OF REVIEW
Myocardial viability is an important pathophysiologic concept which may have significant clinical impact in patients with left ventricular dysfunction due to ischemic heart disease. Understanding the imaging modalities used to assess viability, and the clinical implication of their findings, is critical for clinical decision-making in this population.
RECENT FINDINGS
The ability of dobutamine echocardiography, single-photon emission computed tomography, positron emission tomography, and cardiac magnetic resonance imaging to predict functional recovery following revascularization is well-established. Despite different advantages and disadvantages for each imaging modality, each modality has demonstrated reasonable performance characteristics in identifying viable myocardium. Recent data, however, has called into question whether this functional recovery leads to improved clinical outcomes. Although the assessment of viability can be used to aid in clinical decision-making prior to revascularization, its broad application to all patients is limited by a lack of data confirming improvement in clinical outcomes. Thus, viability assessments may be best applied to select patients (such as those with increased surgical risk) and integrated with clinical, laboratory, and imaging data to guide clinical care. Future research efforts should be aimed at establishing the impact of viability on clinical outcomes.
Topics: Echocardiography; Heart; Humans; Magnetic Resonance Imaging; Myocardial Ischemia; Myocardial Revascularization; Myocardium; Tomography, Emission-Computed, Single-Photon; Ventricular Dysfunction, Left
PubMed: 33398512
DOI: 10.1007/s11886-020-01433-8 -
Biomolecules Nov 2022Sympathomimetic agents are a group of chemical compounds that are able to activate the sympathetic nervous system either directly via adrenergic receptors or indirectly... (Review)
Review
Sympathomimetic agents are a group of chemical compounds that are able to activate the sympathetic nervous system either directly via adrenergic receptors or indirectly by increasing endogenous catecholamine levels or mimicking their intracellular signaling pathways. Compounds from this group, both used therapeutically or abused, comprise endogenous catecholamines (such as adrenaline and noradrenaline), synthetic amines (e.g., isoproterenol and dobutamine), trace amines (e.g., tyramine, tryptamine, histamine and octopamine), illicit drugs (e.g., ephedrine, cathinone, and cocaine), or even caffeine and synephrine. In addition to the effects triggered by stimulation of the sympathetic system, the discovery of trace amine associated receptors (TAARs) in humans brought new insights about their sympathomimetic pharmacology and toxicology. Although synthetic sympathomimetic agents are mostly seen as toxic, natural sympathomimetic agents are considered more complacently in the terms of safety in the vision of the lay public. Here, we aim to discuss the pharmacological and mainly toxicological aspects related to sympathomimetic natural agents, in particular of trace amines, compounds derived from plants like ephedra and khat, and finally cocaine. The main purpose of this review is to give a scientific and updated view of those agents and serve as a reminder on the safety issues of natural sympathomimetic agents most used in the community.
Topics: Humans; Sympathomimetics; Norepinephrine; Tyramine; Amines; Cocaine
PubMed: 36551221
DOI: 10.3390/biom12121793 -
Journal of Nuclear Cardiology :... Feb 2021
Topics: Dipyridamole; Dobutamine; Humans; Positron-Emission Tomography; Rubidium Radioisotopes; Tomography, X-Ray Computed; Vasodilator Agents
PubMed: 32968970
DOI: 10.1007/s12350-020-02309-8 -
Critical Care Explorations Sep 2023Inotropic support is commonly used in patients with cardiogenic shock (CS). High-quality data guiding the use of dobutamine or milrinone among this patient population is... (Review)
Review
OBJECTIVES
Inotropic support is commonly used in patients with cardiogenic shock (CS). High-quality data guiding the use of dobutamine or milrinone among this patient population is limited. We compared the efficacy and safety of these two inotropes among patients with low cardiac output states (LCOS) or CS.
DATA SOURCES
MEDLINE, Embase, and Cochrane Central Register of Controlled Trials were searched up to February 1, 2023, using key terms and index headings related to LCOS or CS and inotropes.
DATA EXTRACTION
Two independent reviewers included studies that compared dobutamine to milrinone on all-cause in-hospital mortality, length of ICU stay, length of hospital stay, and significant arrhythmias in hospitalized patients.
DATA SYNTHESIS
A total of eleven studies with 21,084 patients were included in the meta-analysis. Only two randomized controlled trials were identified. The primary outcome, all-cause mortality, favored milrinone in observational studies only (odds ratio [OR] 1.19 (95% CI, 1.02-1.39; = 0.02). In-hospital length of stay (LOS) was reduced with dobutamine in observational studies only (mean difference -1.85 d; 95% CI -3.62 to -0.09; = 0.04). There was no difference in the prevalence of significant arrhythmias or in ICU LOS.
CONCLUSIONS
Only limited data exists supporting the use of one inotropic agent over another exists. Dobutamine may be associated with a shorter hospital LOS; however, there is also a potential for increased all-cause mortality. Larger randomized studies sufficiently powered to detect a difference in these outcomes are required to confirm these findings.
PubMed: 37649849
DOI: 10.1097/CCE.0000000000000962