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EBioMedicine Dec 2022Management of the patient with sepsis comprises three key branches: control of the underlying infection, haemodynamic stabilization, and modulation of the host response.... (Review)
Review
Management of the patient with sepsis comprises three key branches: control of the underlying infection, haemodynamic stabilization, and modulation of the host response. Each aspect should be considered in all patients and, when relevant, managed at the same time. Infection control is applicable to all patients with sepsis and will include antibiotic therapy and often surgical intervention to remove an infectious source. Haemodynamic support involves fluid administration in all patients and vasoactive agents in patients with associated circulatory shock. Noradrenaline is the first choice vasopressor agent; inotropic agents, usually dobutamine, may be added in case of myocardial depression. No interventions directed at individual components of the host response to sepsis have yet been shown to improve outcomes, but glucocorticoids and vasopressin have a global impact on the response and can thus be considered in this category. A move toward more personalized treatment is needed across all three arms of sepsis management.
Topics: Humans; Shock, Septic; Sepsis; Vasoconstrictor Agents; Hemodynamics; Anti-Bacterial Agents
PubMed: 36470828
DOI: 10.1016/j.ebiom.2022.104318 -
Acute and Critical Care Aug 2019Post-cardiac arrest syndrome is a complex and critical issue in resuscitated patients undergone cardiac arrest. Ischemic-reperfusion injury occurs in multiple organs due... (Review)
Review
Post-cardiac arrest syndrome is a complex and critical issue in resuscitated patients undergone cardiac arrest. Ischemic-reperfusion injury occurs in multiple organs due to the return of spontaneous circulation. Bundle of management practicies are required for post-cardiac arrest care. Early invasive coronary angiography should be considered to identify and treat coronary artery obstructive disease. Vasopressors such as norepinephrine and dobutamine are the first-line treatment for shock. Maintainance of oxyhemoglobin saturation greater than 94% but less than 100% is recommended to avoid fatality. Target temperature therapeutic hypothermia helps to resuscitated patients. Strict temperature control is required and is maintained with the help of cooling devices and monitoring the core temperature. Montorings include electrocardiogram, oxymetry, capnography, and electroencephalography (EEG) along with blood pressue, temprature, and vital signs. Seizure should be treated if EEG shows evidence of seizure or epileptiform activity. Clinical neurologic examination and magnetic resonance imaging are considered to predict neurological outcome. Glycemic control and metabolic management are favorable for a good neurological outcome. Recovery from acute kidney injury is essential for survival and a good neurological outcome.
PubMed: 31723926
DOI: 10.4266/acc.2019.00654 -
European Heart Journal Nov 2019Acute heart failure (HF) and in particular, cardiogenic shock are associated with high morbidity and mortality. A therapeutic dilemma is that the use of positive...
Acute heart failure (HF) and in particular, cardiogenic shock are associated with high morbidity and mortality. A therapeutic dilemma is that the use of positive inotropic agents, such as catecholamines or phosphodiesterase-inhibitors, is associated with increased mortality. Newer drugs, such as levosimendan or omecamtiv mecarbil, target sarcomeres to improve systolic function putatively without elevating intracellular Ca2+. Although meta-analyses of smaller trials suggested that levosimendan is associated with a better outcome than dobutamine, larger comparative trials failed to confirm this observation. For omecamtiv mecarbil, Phase II clinical trials suggest a favourable haemodynamic profile in patients with acute and chronic HF, and a Phase III morbidity/mortality trial in patients with chronic HF has recently begun. Here, we review the pathophysiological basis of systolic dysfunction in patients with HF and the mechanisms through which different inotropic agents improve cardiac function. Since adenosine triphosphate and reactive oxygen species production in mitochondria are intimately linked to the processes of excitation-contraction coupling, we also discuss the impact of inotropic agents on mitochondrial bioenergetics and redox regulation. Therefore, this position paper should help identify novel targets for treatments that could not only safely improve systolic and diastolic function acutely, but potentially also myocardial structure and function over a longer-term.
Topics: Acute Disease; Animals; Antioxidants; Calcium; Cardiotonic Agents; Case-Control Studies; Catecholamines; Clinical Trials as Topic; Diastole; Dobutamine; Dogs; Energy Metabolism; Excitation Contraction Coupling; Heart Failure; Humans; Mitochondria; Models, Animal; Myocardial Contraction; Nitrogen Oxides; Oxidation-Reduction; Phosphodiesterase Inhibitors; Placebos; Receptors, Adrenergic; Sarcomeres; Shock, Cardiogenic; Simendan; Swine; Systole; Urea
PubMed: 30295807
DOI: 10.1093/eurheartj/ehy600 -
Acta Bio-medica : Atenei Parmensis Jul 2022Septic shock is a main cause of morbidity and mortality in neonates. Septic shock evolves from compensated to uncompensated through 3 distinct phases. Prompt diagnosis... (Review)
Review
Septic shock is a main cause of morbidity and mortality in neonates. Septic shock evolves from compensated to uncompensated through 3 distinct phases. Prompt diagnosis is challenging, since neonatal septic shock may overlap with the physiological changes occurring at birth. The outcome of septic shock depends on a prompt recognition of symptoms and a strict adherence to cardiopulmonary resuscitation guidelines. Fluid administration plays a major role in the initial management of septic shock. If there is no response to volume filling, inotropes must be infused within one hour of onset (dopamine, dobutamine, adrenaline). Life-threatening infections require immediate and aggressive empiric use of antimicrobials. In the pediatric age, delay in antibiotic initiation for treating septic shock is associated with poor outcome and increased risk of mortality. There is a gap regarding first line interventions in neonatal septic shock. This review addresses initial interventions in the treatment of neonatal septic shock and discusses currently available evidences., These interventions may allow to improve the outcome if they are promptly carried out.
Topics: Anti-Bacterial Agents; Anti-Infective Agents; Child; Humans; Infant, Newborn; Resuscitation; Shock, Septic
PubMed: 35775767
DOI: 10.23750/abm.v93i3.12577 -
Journal of Intensive Care Medicine Sep 2021Preexisting heart failure (HF) in patients with sepsis is associated with worse clinical outcomes. Core sepsis management includes aggressive volume resuscitation... (Review)
Review
Preexisting heart failure (HF) in patients with sepsis is associated with worse clinical outcomes. Core sepsis management includes aggressive volume resuscitation followed by vasopressors (and potentially inotropes) if fluid is inadequate to restore perfusion; however, large fluid boluses and vasoactive agents are concerning amid the cardiac dysfunction of HF. This review summarizes evidence regarding the influence of HF on sepsis clinical outcomes, pathophysiologic concerns, resuscitation targets, hemodynamic interventions, and adjunct management (ie, antiarrhythmics, positive pressure ventilatory support, and renal replacement therapy) in patients with sepsis and preexisting HF. Patients with sepsis and preexisting HF receive less fluid during resuscitation; however, evidence suggests traditional fluid resuscitation targets do not increase the risk of adverse events in HF patients with sepsis and likely improve outcomes. Norepinephrine remains the most well-supported vasopressor for patients with sepsis with preexisting HF, while dopamine may induce more cardiac adverse events. Dobutamine should be used cautiously given its generally detrimental effects but may have an application when combined with norepinephrine in patients with low cardiac output. Management of chronic HF medications warrants careful consideration for continuation or discontinuation upon development of sepsis, and β-blockers may be appropriate to continue in the absence of acute hemodynamic decompensation. Optimal management of atrial fibrillation may include β-blockers after acute hemodynamic stabilization as they have also shown independent benefits in sepsis. Positive pressure ventilatory support and renal replacement must be carefully monitored for effects on cardiac function when HF is present.
Topics: Fluid Therapy; Heart Failure; Humans; Resuscitation; Sepsis; Shock, Septic; Vasoconstrictor Agents
PubMed: 32495686
DOI: 10.1177/0885066620928299 -
Circulation May 2023Sodium-glucose co-transporter 2 inhibitors (SGLT2i) have emerged as a paramount treatment for patients with heart failure (HF), irrespective of underlying reduced or... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Sodium-glucose co-transporter 2 inhibitors (SGLT2i) have emerged as a paramount treatment for patients with heart failure (HF), irrespective of underlying reduced or preserved ejection fraction. However, a definite cardiac mechanism of action remains elusive. Derangements in myocardial energy metabolism are detectable in all HF phenotypes, and it was proposed that SGLT2i may improve energy production. The authors aimed to investigate whether treatment with empagliflozin leads to changes in myocardial energetics, serum metabolomics, and cardiorespiratory fitness.
METHODS
EMPA-VISION (Assessment of Cardiac Energy Metabolism, Function and Physiology in Patients With Heart Failure Taking Empagliflozin) is a prospective, randomized, double-blind, placebo-controlled, mechanistic trial that enrolled 72 symptomatic patients with chronic HF with reduced ejection fraction (HFrEF; n=36; left ventricular ejection fraction ≤40%; New York Heart Association class ≥II; NT-proBNP [N-terminal pro-B-type natriuretic peptide] ≥125 pg/mL) and HF with preserved ejection fraction (HFpEF; n=36; left ventricular ejection fraction ≥50%; New York Heart Association class ≥II; NT-proBNP ≥125 pg/mL). Patients were stratified into respective cohorts (HFrEF versus HFpEF) and randomly assigned to empagliflozin (10 mg; n=35: 17 HFrEF and 18 HFpEF) or placebo (n=37: 19 HFrEF and 18 HFpEF) once daily for 12 weeks. The primary end point was a change in the cardiac phosphocreatine:ATP ratio (PCr/ATP) from baseline to week 12, determined by phosphorus magnetic resonance spectroscopy at rest and during peak dobutamine stress (65% of age-maximum heart rate). Mass spectrometry on a targeted set of 19 metabolites was performed at baseline and after treatment. Other exploratory end points were investigated.
RESULTS
Empagliflozin treatment did not change cardiac energetics (ie, PCr/ATP) at rest in HFrEF (adjusted mean treatment difference [empagliflozin - placebo], -0.25 [95% CI, -0.58 to 0.09]; =0.14) or HFpEF (adjusted mean treatment difference, -0.16 [95% CI, -0.60 to 0.29]; =0.47]. Likewise, there were no changes in PCr/ATP during dobutamine stress in HFrEF (adjusted mean treatment difference, -0.13 [95% CI, -0.35 to 0.09]; =0.23) or HFpEF (adjusted mean treatment difference, -0.22 [95% CI, -0.66 to 0.23]; =0.32). No changes in serum metabolomics or levels of circulating ketone bodies were observed.
CONCLUSIONS
In patients with either HFrEF or HFpEF, treatment with 10 mg of empagliflozin once daily for 12 weeks did not improve cardiac energetics or change circulating serum metabolites associated with energy metabolism when compared with placebo. Based on our results, it is unlikely that enhancing cardiac energy metabolism mediates the beneficial effects of SGLT2i in HF.
REGISTRATION
URL: https://www.
CLINICALTRIALS
gov; Unique identifier: NCT03332212.
Topics: Humans; Heart Failure; Stroke Volume; Ventricular Function, Left; Prospective Studies; Dobutamine; Energy Metabolism; Adenosine Triphosphate
PubMed: 37070436
DOI: 10.1161/CIRCULATIONAHA.122.062021 -
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