-
The Cochrane Database of Systematic... Jan 2018Cardiogenic shock (CS) and low cardiac output syndrome (LCOS) as complications of acute myocardial infarction (AMI), heart failure (HF) or cardiac surgery are... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cardiogenic shock (CS) and low cardiac output syndrome (LCOS) as complications of acute myocardial infarction (AMI), heart failure (HF) or cardiac surgery are life-threatening conditions. While there is a broad body of evidence for the treatment of people with acute coronary syndrome under stable haemodynamic conditions, the treatment strategies for people who become haemodynamically unstable or develop CS remain less clear. We have therefore summarised here the evidence on the treatment of people with CS or LCOS with different inotropic agents and vasodilative drugs. This is the first update of a Cochrane review originally published in 2014.
OBJECTIVES
To assess efficacy and safety of cardiac care with positive inotropic agents and vasodilator strategies in people with CS or LCOS due to AMI, HF or cardiac surgery.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase and CPCI-S Web of Science in June 2017. 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 in people with myocardial infarction, heart failure or cardiac surgery complicated by cardiogenic shock or LCOS.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane.
MAIN RESULTS
We identified 13 eligible studies with 2001 participants (mean or median age range 58 to 73 years) and two ongoing studies. We categorised studies into eight comparisons, all against cardiac care and additional other active drugs or placebo. These comparisons investigated the efficacy of levosimendan versus dobutamine, enoximone or placebo, epinephrine versus norepinephrine-dobutamine, amrinone versus dobutamine, dopexamine versus dopamine, enoximone versus dopamine and nitric oxide versus placebo.All trials were published in peer-reviewed journals, and analysis was done by the intention-to-treat (ITT) principle. Twelve of 13 trials were small with few included participants. Acknowledgement of funding by the pharmaceutical industry or missing conflict of interest statements emerged in five of 13 trials. In general, confidence in the results of analysed studies was reduced due to serious study limitations, very serious imprecision or indirectness. Domains of concern, which show a high risk of more than 50%, include performance bias (blinding of participants and personnel) and bias affecting the quality of evidence on adverse events.Levosimendan may reduce short-term mortality compared to a therapy with dobutamine (RR 0.60, 95% CI 0.37 to 0.95; 6 studies; 1776 participants; low-quality evidence; NNT: 16 (patients with moderate risk), NNT: 5 (patients with CS)). This initial short-term survival benefit with levosimendan vs. dobutamine is not confirmed on long-term follow up. There is uncertainty (due to lack of statistical power) as to the effect of levosimendan compared to therapy with placebo (RR 0.48, 95% CI 0.12 to 1.94; 2 studies; 55 participants, very low-quality evidence) or enoximone (RR 0.50, 95% CI 0.22 to 1.14; 1 study; 32 participants, very low-quality evidence).All comparisons comparing other positive inotropic, inodilative or vasodilative drugs presented uncertainty on their effect on short-term mortality with very low-quality evidence and based on only one RCT. These single studies compared epinephrine with norepinephrine-dobutamine (RR 1.25, 95% CI 0.41 to 3.77; 30 participants), amrinone with dobutamine (RR 0.33, 95% CI 0.04 to 2.85; 30 participants), dopexamine with dopamine (no in-hospital deaths from 70 participants), enoximone with dobutamine (two deaths from 40 participants) and nitric oxide with placebo (one death from three participants).
AUTHORS' CONCLUSIONS
Apart from low quality of evidence data suggesting a short-term mortality benefit of levosimendan compared with dobutamine, at present there are no robust and convincing data to support a distinct inotropic or vasodilator drug-based therapy as a superior solution to reduce mortality in haemodynamically unstable people with cardiogenic shock or LCOS.Considering the limited evidence derived from the present data due to a generally high risk of bias and imprecision, it should be emphasised that there remains a great need for large, well-designed randomised trials on this topic to close the gap between daily practice in critical care medicine and the available evidence. It seems to be useful to apply the concept of 'early goal-directed therapy' in cardiogenic shock and LCOS with early haemodynamic stabilisation within predefined timelines. Future clinical trials should therefore investigate whether such a therapeutic concept would influence survival rates much more than looking for the 'best' drug for haemodynamic support.
Topics: Aged; Cardiac Output, Low; Cardiotonic Agents; Cause of Death; Dobutamine; Enoximone; Humans; Hydrazones; Middle Aged; Myocardial Infarction; Nitric Oxide; Pyridazines; Randomized Controlled Trials as Topic; Shock, Cardiogenic; Simendan; Vasodilator Agents
PubMed: 29376560
DOI: 10.1002/14651858.CD009669.pub3 -
Journal of Healthcare Engineering 2020(1) To conduct a network meta-analysis of clinical drugs used for cardiogenic shock and (2) provide evidence for the selection of medication for the treatment of this... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
(1) To conduct a network meta-analysis of clinical drugs used for cardiogenic shock and (2) provide evidence for the selection of medication for the treatment of this condition.
METHODS
PubMed, EMBASE, Cochrane library, China HowNet (CNKI), Wanfang database, and Weipu database were searched using keywords Dopamine, Dobutamine, Epinephrine, Adrenaline, Norepinephrine, Noradrenaline, Milrinone, Natriuretic peptide, Recombinant human brain natriuretic peptide, Levosimendan, Cardiac shock, and Cardiogenic shock. We select literature according to prespecified inclusion and exclusion criteria and record data such as drug type, mortality, and adverse reactions.
RESULTS
Twenty-eight of 1387 articles met inclusion criteria, comprising 1806 patients who suffered from cardiogenic shock. Dopamine, dobutamine, epinephrine, norepinephrine, milrinone, recombinant human brain natriuretic peptide, and levosimendan were all commonly used in the treatment of cardiogenic shock. Milrinone was most effective at reducing mortality and had the lowest incidence of adverse reactions.
CONCLUSION
This network meta-analysis demonstrated that milrinone was the most effective medication at reducing mortality and adverse events in patients suffering from cardiogenic shock.
Topics: Aged; Disease Progression; Dobutamine; Dopamine; Epinephrine; Female; Hemodynamics; Humans; Male; Middle Aged; Milrinone; Natriuretic Peptide, Brain; Network Meta-Analysis; Norepinephrine; Patient Safety; Recombinant Proteins; Shock, Cardiogenic; Simendan; Treatment Outcome
PubMed: 32802302
DOI: 10.1155/2020/8862256 -
Frontiers in Nutrition 2021Anaerobic glycolysis is the process by which glucose is broken down into pyruvate and lactate and is the primary metabolic pathway in sepsis. The pyruvate dehydrogenase... (Review)
Review
Anaerobic glycolysis is the process by which glucose is broken down into pyruvate and lactate and is the primary metabolic pathway in sepsis. The pyruvate dehydrogenase complex (PDHC) is a multienzyme complex that serves as a critical hub in energy metabolism. Under aerobic conditions, pyruvate translocates to mitochondria, where it is oxidized into acetyl-CoA through the activation of PDHC, thereby accelerating aerobic oxidation. Both phosphorylation and acetylation affect PDHC activity and, consequently, the regulation of energy metabolism. The mechanisms underlying the protective effects of PDHC in sepsis involve the regulation on the balance of lactate, the release of inflammatory mediators, the remodeling of tricarboxylic acid (TCA) cycle, as well as on the improvement of lipid and energy metabolism. Therapeutic drugs that target PDHC activation for sepsis treatment include dichloroacetate, thiamine, amrinone, TNF-binding protein, and ciprofloxacin. In this review, we summarize the recent findings regarding the metabolic regulation of PDHC in sepsis and the therapies targeting PDHC for the treatment of this condition.
PubMed: 34970577
DOI: 10.3389/fnut.2021.783164 -
Anesthesiology Aug 2023Conflicting evidence exists regarding the risks and benefits of inotropic therapies during cardiac surgery, and the extent of variation in clinical practice remains... (Observational Study)
Observational Study
BACKGROUND
Conflicting evidence exists regarding the risks and benefits of inotropic therapies during cardiac surgery, and the extent of variation in clinical practice remains understudied. Therefore, the authors sought to quantify patient-, anesthesiologist-, and hospital-related contributions to variation in inotrope use.
METHODS
In this observational study, nonemergent adult cardiac surgeries using cardiopulmonary bypass were reviewed across a multicenter cohort of academic and community hospitals from 2014 to 2019. Patients who were moribund, receiving mechanical circulatory support, or receiving preoperative or home inotropes were excluded. The primary outcome was an inotrope infusion (epinephrine, dobutamine, milrinone, dopamine) administered for greater than 60 consecutive min intraoperatively or ongoing upon transport from the operating room. Institution-, clinician-, and patient-level variance components were studied.
RESULTS
Among 51,085 cases across 611 attending anesthesiologists and 29 hospitals, 27,033 (52.9%) cases received at least one intraoperative inotrope, including 21,796 (42.7%) epinephrine, 6,360 (12.4%) milrinone, 2,000 (3.9%) dobutamine, and 602 (1.2%) dopamine (non-mutually exclusive). Variation in inotrope use was 22.6% attributable to the institution, 6.8% attributable to the primary attending anesthesiologist, and 70.6% attributable to the patient. The adjusted median odds ratio for the same patient receiving inotropes was 1.73 between 2 randomly selected clinicians and 3.55 between 2 randomly selected institutions. Factors most strongly associated with increased likelihood of inotrope use were institutional medical school affiliation (adjusted odds ratio, 6.2; 95% CI, 1.39 to 27.8), heart failure (adjusted odds ratio, 2.60; 95% CI, 2.46 to 2.76), pulmonary circulation disorder (adjusted odds ratio, 1.72; 95% CI, 1.58 to 1.87), loop diuretic home medication (adjusted odds ratio, 1.55; 95% CI, 1.42 to 1.69), Black race (adjusted odds ratio, 1.49; 95% CI, 1.32 to 1.68), and digoxin home medication (adjusted odds ratio, 1.48; 95% CI, 1.18 to 1.86).
CONCLUSIONS
Variation in inotrope use during cardiac surgery is attributable to the institution and to the clinician, in addition to the patient. Variation across institutions and clinicians suggests a need for future quantitative and qualitative research to understand variation in inotrope use affecting outcomes and develop evidence-based, patient-centered inotrope therapies.
Topics: Humans; Male; Female; Adolescent; Adult; Middle Aged; Aged; Aged, 80 and over; Myocardial Contraction; Cardiotonic Agents; Cardiac Surgical Procedures; Epinephrine; Dopamine; Dobutamine; Milrinone; Intraoperative Care
PubMed: 37094103
DOI: 10.1097/ALN.0000000000004593 -
Academic Emergency Medicine : Official... Aug 1997
PubMed: 28776886
DOI: 10.1111/j.1553-2712.1997.tb03803.x -
The Journal of Thoracic and... Nov 2014
Topics: Animals; Cardiotonic Agents; Female; Heart Failure; Milrinone; Myocardial Infarction
PubMed: 25175955
DOI: 10.1016/j.jtcvs.2014.07.034 -
Annals of Cardiac Anaesthesia 2018
Topics: Cardiotonic Agents; Child; Humans; Milrinone; Pulmonary Wedge Pressure
PubMed: 29652274
DOI: 10.4103/aca.ACA_221_17 -
Clinical Cardiology May 2022Advanced heart failure (HF) patients usually poorly tolerate guideline-directed HF medical therapy (GDMT) and suffer high rates of morbidity and mortality. The use of...
BACKGROUND
Advanced heart failure (HF) patients usually poorly tolerate guideline-directed HF medical therapy (GDMT) and suffer high rates of morbidity and mortality. The use of continuous inotropes in the outpatient settings is hampered by previous data showing excess morbidity. We aimed to assess the safety and efficacy of repetitive, intermittent, short-term intravenous milrinone therapy in advanced HF patients with an intention to introduce and up-titrate GDMT and improve functional class.
HYPOTHESIS
Repetitive, intermittent milrinone therapy may assist with the stabilization of advanced HF patients.
METHODS
Advanced HF patients treated with beta-blockers and implanted with defibrillators were initiated with repetitive, intermittent short-term intravenous milrinone therapy at our HF outpatient unit. Patients were prospectively followed with defibrillator interrogation, functional class assessment, B-natriuretic peptide (BNP) levels, and echocardiography parameters.
RESULTS
The cohort included 24 patients with a mean 330 ± 240 days of milrinone therapy exposure. Mean age was 73 ± 6 years with male predominance (96%). Following milrinone therapy, median BNP levels decreased significantly (882 [286-3768] to 631 [278-1378] pg/ml, p = .017) with a significant reduction in the number of patients with New York Heart Association (NYHA) Class III and IV (p = .012, 0.013) and an increase in number of patients on GDMT. Importantly, the number of total sustained ventricular tachycardia events and HF hospitalizations did not change.
CONCLUSIONS
In this small cohort of advanced HF, repetitive, intermittent, short-term milrinone therapy was found to be safe and potentially efficacious.
Topics: Adrenergic beta-Antagonists; Aged; Cardiotonic Agents; Echocardiography; Female; Heart Failure; Humans; Male; Milrinone; Tachycardia, Ventricular
PubMed: 35243658
DOI: 10.1002/clc.23802 -
The Cochrane Database of Systematic... Nov 2010Persistent pulmonary hypertension of the newborn (PPHN) is a clinical syndrome characterized by suboptimal oxygenation as a result of sustained elevation in pulmonary... (Review)
Review
BACKGROUND
Persistent pulmonary hypertension of the newborn (PPHN) is a clinical syndrome characterized by suboptimal oxygenation as a result of sustained elevation in pulmonary vascular resistance after birth. Currently, the therapeutic mainstay for PPHN is optimal lung inflation and selective vasodilatation with inhaled nitric oxide (iNO). However, iNO is not available in all countries and not all infants will respond to iNO. Milrinone is a phosphodiesterase III inhibitor which induces pulmonary vasodilatation by its actions through a cyclic adenylate monophosphate mediated signaling pathway.
OBJECTIVES
To assess efficacy and safety in infants with PPHN either treated with: milrinone compared with placebo or no treatment; milrinone compared with iNO; milrinone as an adjunct to iNO compared with iNO alone; milrinone compared with potential treatments for PPHN other than iNO.
SEARCH STRATEGY
We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 2, 2010), MEDLINE and EMBASE databases from their inception until January 2010. We searched the reference lists of potentially relevant studies without any language restriction.
SELECTION CRITERIA
Fully published randomized controlled trials (RCTs) and quasi-RCTs comparing milrinone with placebo, iNO or potential treatments other than iNO in neonates with PPHN were included if trials reported any clinical outcome.
DATA COLLECTION AND ANALYSIS
We found no studies meeting the criteria for inclusion in this review.
MAIN RESULTS
We found no studies meeting the criteria for inclusion in this review.
AUTHORS' CONCLUSIONS
The efficacy and safety of milrinone in the treatment of PPHN are not known and its use should be restricted within the context of RCTs. Such studies should address a comparison of milrinone with placebo (in clinical situations where iNO is not available) or, in well resourced countries, should compare milrinone with iNO or as an adjunct to iNO compared with iNO alone.
Topics: Humans; Infant, Newborn; Milrinone; Persistent Fetal Circulation Syndrome; Vasodilator Agents
PubMed: 21069698
DOI: 10.1002/14651858.CD007802.pub2