cardiovascular-agents and Sepsis

The obesity pandemic now affects hundreds of millions of people worldwide. As obesity rates continue to increase, emergency physicians are called on with increasing frequency to resuscitate obese patients. This article discusses important anatomic, physiologic, and practical challenges imposed by obesity on resuscitative care. Impacts on hemodynamic monitoring, airway and ventilator management, and pharmacologic therapy are discussed. Finally, several important clinical scenarios (trauma, cardiac arrest, and sepsis), in which alterations to standard treatments may benefit obese patients, are highlighted.

Topics: Airway Management; Analgesics; Anti-Bacterial Agents; Body Composition; Cardiovascular Agents; Cardiovascular Diseases; Dose-Response Relationship, Drug; Emergency Service, Hospital; Heart Arrest; Humans; Hypnotics and Sedatives; Lung Volume Measurements; Obesity; Oxygen Consumption; Pharmacokinetics; Positive-Pressure Respiration; Resuscitation; Sepsis; Wounds and Injuries

New-onset atrial fibrillation (NOAF) is common and associated with increased morbidity and mortality. However, its clinical importance and management in critically ill patients are not well described. The aim of this scoping review is to assess the epidemiology and management strategies of NOAF during critical illness.. The review was conducted in accordance with the PRISMA extension for scoping reviews. We searched PubMed, EMBASE and the Cochrane Library for studies assessing the incidence, outcome and management strategies of NOAF in adult critically ill patients. The quality of evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach.. A total of 99 studies were included, of which 79 were observational and 20 were interventional. The incidence of NOAF varied from 1.7% to 43.9% with considerable inter-population variation (very low quality of evidence). Commonly identified risk factors for NOAF included higher age, cardiovascular comorbidities and sepsis. The occurrence of NOAF was associated with adverse outcomes, including stroke, prolonged length of stay and mortality (very low quality of evidence). We found limited data on the optimal management strategy with no evidence for firm benefit or harm for any intervention (very low/low quality of evidence).. The definition and incidence of NOAF in critically ill patients varied considerably and many risk factors were identified. NOAF seemed to be associated with adverse outcomes, but data were very limited and current management strategies are not evidence-based.

Topics: Age Factors; Atrial Fibrillation; Cardiovascular Agents; Cardiovascular Diseases; Comorbidity; Critical Illness; Electrocardiography; Hematologic Tests; Hospitalization; Humans; Incidence; Length of Stay; Risk Factors; Sepsis; Severity of Illness Index; Sex Factors; Stroke

Sepsis-induced cardiogenic shock is a lethal condition and the management of it is challenging. Cardiogenic shock in the septic patient involves myocardial systolic and diastolic dysfunction. The limited ability of the ventricles to contract effectively results in a decrease in oxygen delivery to the organs and tissues. Supportive therapy is provided to patients with sepsis and no specific drug can reverse the myocardial dysfunction. Rapid diagnosis, prompt antibiotic therapy, cautious protocol-driven fluid resuscitation and vasoactive agents, control of infectious source, and expeditious coronary artery revascularization is recommended to achieve a positive outcome.

Topics: Anti-Bacterial Agents; Cardiovascular Agents; Critical Care Nursing; Early Diagnosis; Evidence-Based Medicine; Fluid Therapy; Humans; Sepsis; Shock, Cardiogenic

Acute cardiogenic pulmonary edema and cardiogenic shock are two of the main forms of presentation of acute heart failure. Both entities are serious, with high mortality, and require early diagnosis and prompt and aggressive management. Acute pulmonary edema is due to the passage of fluid through the alveolarcapillary membrane and is usually the result of an acute cardiac episode. Correct evaluation and clinical identification of the process is essential in the management of acute pulmonary edema. The initial aim of treatment is to ensure hemodynamic stability and to correct hypoxemia. Other measures that can be used are vasodilators such as nitroglycerin, loop diuretics and, in specific instances, opioids. Cardiogenic shock is characterized by sustained hypoperfusion, pulmonary wedge pressure > 18 mmHg and a cardiac index < 2.2l/min/m(2). The process typically presents with hypotension (systolic blood pressure < 90 mmHg or a decrease in mean arterial pressure > 30 mmHg) and absent or reduced diuresis (< 0.5 ml/kg/h). The most common cause is left ventricular failure due to acute myocardial infarction. Treatment consists of general measures to reverse acidosis and hypoxemia, as well as the use of vasopressors and inotropic drugs. Early coronary revascularization has been demonstrated to improve survival in shock associated with ischaemic heart disease.

Topics: Acute Disease; Cardiovascular Agents; Combined Modality Therapy; Diagnosis, Differential; Diuresis; Heart Failure; Humans; Hypotension; Hypoxia; Myocardial Infarction; Myocardial Revascularization; Narcotics; Oxygen Inhalation Therapy; Pulmonary Edema; Respiration, Artificial; Sepsis; Shock; Shock, Cardiogenic; Sodium Potassium Chloride Symporter Inhibitors; Vasoconstrictor Agents; Vasodilator Agents; Ventricular Dysfunction, Left

About 50% of patients with sepsis show myocardial involvement characterized by biventricular enlargement, reduced contractility and diastolic dysfunction. This increases the risk of death and leads to an extremely poor prognosis in the case of severe sepsis or septic shock, with full recovery of cardiac function seen in survivors at 7-10 days. The pathogenesis of myocardial dysfunction has long been investigated and, although it is still not fully understood, seems not to be due to reduced coronary flow, but to circulating substances released by pathogens (e.g. endotoxins) and host immuno-inflammatory responses (e.g. cytokines and mechanisms related to nitric oxide). First-line therapy is causal and consists of antibiotics plus the surgical excision of the infectious focus; in the presence of severe sepsis or septic shock, it is also necessary to promptly start circulatory and multiorgan support treatment. This review describes current knowledge concerning the instrumental and clinical characteristics, pathophysiology, prognosis and therapy of myocardial dysfunction during sepsis, and briefly considers possible future therapeutic perspectives.

Topics: Anti-Bacterial Agents; Biomarkers; Cardiomyopathies; Cardiovascular Agents; Combined Modality Therapy; Complement C5a; Counterpulsation; Cytokines; Endothelins; Endotoxins; Humans; Immunotherapy; Mitochondria, Heart; Myocardial Contraction; Nitric Oxide; Prognosis; Sepsis; Toll-Like Receptor 4

Sepsis remains a major cause of death in intensive care units. Despite an intense research, a new drug that is effective in reducing mortality in sepsis is still awaited.. The literature was analyzed with Pubmed() during the 2008 - 2009 period. If required, seminal articles published before 2008 were cited. Clinical trials focusing on 'sepsis' were first assessed. Next, relevant experimental data in this field were reported.. The goal of the review is to determine the role for new licensed antibiotics, to give an insight into the conflict on adjuvant therapies and to disclose new experimental concepts.. New licensed antibiotics will offer the opportunity to refine the treatment choices. Direct hemoperfusion using polymyxin B-immobilized fiber column may be an option in sepsis due to Gram-negative bacilli. Among non-antibiotic drugs, new ongoing studies will clarify the role of drotrecogin alfa (activated) and low dose hydrocortisone. The modulation of monocytic human leukocyte antigen-DR seems the most prominent treatment. The use of cardiovascular drugs requires well-conducted clinical trials. The regulation of high mobility group box 1, adenosine blockade or correction of the impaired energy production is still at the experimental level.

Topics: Animals; Anti-Infective Agents; Cardiovascular Agents; Drug Delivery Systems; Drug Resistance, Bacterial; Drugs, Investigational; Granulocyte-Macrophage Colony-Stimulating Factor; Hemoperfusion; Humans; Hydrocortisone; Polymyxin B; Protein C; Recombinant Proteins; Sepsis; Signal Transduction

To present the recent findings obtained in clinical and experimental studies examining microcirculatory alterations in sepsis, their link to mitochondrial dysfunction, and current knowledge regarding the impact of these alterations on the outcome of septic patients.. Interlinked by a mutual cascade effect and driven by the host-pathogen interaction, microcirculatory and mitochondrial functions are impaired during sepsis. Mitochondrial respiration seems to evolve during the course of sepsis, demonstrating a change from reversible to irreversible inhibition. The spatiotemporal heterogeneity of microcirculatory and mitochondrial dysfunction suggests that these processes may be compartmentalized. Although a causal relationship between mitochondrial and microcirculatory dysfunction and organ failure in sepsis is supported by an increasing number of studies, adaptive processes have also emerged as part of microcirculatory and mitochondrial alterations. Treatments for improving or preserving microcirculatory, mitochondrial function, or both seem to yield a better outcome in patients.. Even though there is evidence that microcirculatory and mitochondrial dysfunction plays a role in the development of sepsis-induced organ failure, their interaction and respective contribution to the disease remains poorly understood. Future research is necessary to better define such relationships in order to identify therapeutic targets and refine treatment strategies.

Topics: Capillary Permeability; Cardiovascular Agents; Cytochromes c; Erythropoietin; Humans; Microcirculation; Mitochondria; Mitochondrial Diseases; Poly Adenosine Diphosphate Ribose; Recombinant Proteins; Sepsis

Statins are pluripotent agents exhibiting multiple non-lipid-lowering actions. Besides their established role in the management of hypercholesterolemia, statins may also have beneficial actions in other pathological conditions, namely: a) osteoporosis and osteoporosis-related bone fractures, b) cancer, c) solid organ transplantation, d) cerebrovascular events (transient ischemic attack and stroke episodes), e) various neurological disorders, such as Alzheimer's disease, Parkinson's disease and multiple sclerosis, f) cardiac arrhythmias and heart failure, g) renal diseases, h) rheumatoid arthritis, i) autoimmune diseases, j) sepsis, and k) allergic asthma. We reviewed the literature searching for studies that support or oppose the use of statins in each proposed indication. In some of these emerging indications, a role for statin treatment is more firmly set; for others, current evidence is more controversial. Future trials may reveal more convincing evidence that will make statin use necessary in the therapeutic management of several diseases.

Topics: Animals; Anti-Asthmatic Agents; Antineoplastic Agents; Antirheumatic Agents; Arthritis, Rheumatoid; Asthma; Autoimmune Diseases; Bone Density Conservation Agents; Cardiovascular Agents; Cerebrovascular Disorders; Heart Diseases; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Kidney Diseases; Neoplasms; Nervous System Diseases; Neuroprotective Agents; Organ Transplantation; Osteoporosis; Sepsis

Severe sepsis and septic shock are as common and lethal as other acute life-threatening conditions that emergency physicians routinely confront such as acute myocardial infarction, stroke, and trauma. Recent studies have led to a better understanding of the pathogenic mechanisms and the development of new or newly applied therapies. These therapies place early and aggressive management of severe sepsis and septic shock as integral to improving outcome. This independent review of the literature examines the recent pathogenic, diagnostic, and therapeutic advances in severe sepsis and septic shock for adults, with particular relevance to emergency practice. Recommendations are provided for therapies that have been shown to improve outcomes, including early goal-directed therapy, early and appropriate antimicrobials, source control, recombinant human activated protein C, corticosteroids, and low tidal volume mechanical ventilation.

Topics: Adrenal Cortex Hormones; Algorithms; Anti-Bacterial Agents; Cardiovascular Agents; Drug Therapy, Combination; Humans; Practice Guidelines as Topic; Protein C; Recombinant Proteins; Respiration, Artificial; Sepsis; Shock, Septic

Topics: Adjuvants, Immunologic; Cardiovascular Agents; Fluid Therapy; Humans; Infection Control; Intensive Care Units; Respiration, Artificial; Resuscitation; Sepsis; Shock, Septic

Topics: Adrenal Cortex Hormones; Cardiovascular Agents; Hemofiltration; Hemoglobins; Humans; Hypertonic Solutions; Plasma Substitutes; Sepsis; Terminology as Topic

Adequate volume loading may be the most important step in the treatment of patients with septic shock. Techniques allowing us to achieve and tightly control volume loading and regional perfusion are considered to be helpful. An elevated oxygen delivery may be beneficial in some patients but the increase of oxygen delivery should be guided by the measurement of parameters assessing global and regional oxygenation. Forcing an increase in oxygen delivery by the use of very high dosages of catecholamines can be harmful. Vasopressors should be used for achieving an adequate perfusion pressure. For norepinephrine, no negative effects on regional perfusion have been demonstrated. Epinephrine and dopamine should be avoided because they seem to redistribute blood flow away from the splanchnic region. There are no convincing data yet to support the routine use of low dose dopamine or dopexamine in patients with sepsis. Neither low dose dopamine nor dopexamine has been proven to prevent renal failure in septic patients. Furthermore, there is evidence that low dose dopamine may reduce mucosal perfusion in the gut in some patients. There is some suggestion that dopexamine can improve splanchnic perfusion but since these effects remain somewhat controversial, there is no reason for a general recommendation for dopexamine in septic patients.

Topics: Cardiovascular Agents; Fluid Therapy; Humans; Sepsis

Distributive shock is defined as circulatory insufficiency induced by excessive dilatation of the peripheral vasculature or maldistribution of cardiac output. Septicemia, systemic inflammatory response syndrome, anaphylaxis, injuries to the central nervous system, and drug intoxication are causative factors of shock. Circulatory derangements induced by bacterial infection have been divided into hyperdynamic and hypodynamic shock. Administration of inotropic drugs, vasopressors, and/or vasodilators are primary treatments in this type of shock. Continuous infusion of norepinephrine to maintain blood pressure or administration of inoptropes such as dopamine or dobutamine are recommended to improve tissue perfusion. High-dose intravenous epinephrine is required to reestablish cardiac function, followed by continuous infusion of norepinephrine in severe anaphylactic shock. Vasoconstrictors such as norepinephrine, vasopressin, or amaminone are administered to maintain vascular tone in shock caused by nerve damage or drug overdose.

Topics: Anaphylaxis; Brain Injuries; Cardiovascular Agents; Dopamine; Epinephrine; Humans; Norepinephrine; Sepsis; Shock; Spinal Cord Injuries; Vascular Resistance

In all respects, the child with fulminant meningococcemia presents a formidable challenge to those who care for him/her. Only with prompt recognition of the disease and immediate institution of intensive treatment can the likelihood of survival be improved and morbidity minimized.

Topics: Anti-Bacterial Agents; Cardiovascular Agents; Child; Child, Preschool; Chloramphenicol; Humans; Infant; Meningococcal Infections; Naloxone; Penicillin G; Plasmapheresis; Prognosis; Sepsis; Steroids

Dexrazoxane administration prior to short infusion doxorubicin prevents anthracycline-related heart damage. Since delivery of doxorubicin by 96-h continuous intravenous infusion also reduces cardiac injury, we studied delivering dexrazoxane and doxorubicin concomitantly by prolonged intravenous infusion.. Patients with advanced malignancies received tandem cycles of concurrent 96-h infusions of dexrazoxane 500 mg/m2 and doxorubicin 165 mg/m2, and 24 h after completion of chemotherapy, granulocyte-colony stimulating factor (5 microg/kg) and oral levofloxacin (500 mg) were administered daily until the white blood cell count reached 10,000 microl(-1). Plasma samples were analyzed for dexrazoxane and doxorubicin concentrations.. Ten patients were enrolled; eight patients had measurable disease. Two partial responses were observed in patients with soft-tissue sarcoma. The median number of days of granulocytopenia (<500 microl(-1)) was nine and of platelet count <20,000 microl(-1) was seven. Six patients received a single cycle because of progression (one), stable disease (four), or reversible, asymptomatic 10% decrease in cardiac ejection fraction (two). Principal grade 3/4 toxicities included hypotension (two), anorexia (four), stomatitis (four), typhlitis (two), and febrile neutropenia (seven), with documented infection (three). One death from neutropenic sepsis occurred. Dexrazoxane levels ranged from 1270 to 2800 nM, and doxorubicin levels ranged from 59.1 to 106.9 nM.. These results suggest that tandem cycles of concurrent 96-h infusions of dexrazoxane and high-dose doxorubicin can be administered with minimal cardiac toxicity, and have activity in patients with recurrent sarcomas. However, significant non-cardiac toxicities indicate that the cardiac sparing potential of this approach would be maximized at lower dose levels of doxorubicin.

Topics: Adult; Antibiotics, Antineoplastic; Cardiovascular Agents; Doxorubicin; Drug Administration Schedule; Drug Therapy, Combination; Female; Granulocyte Colony-Stimulating Factor; Heart Failure; Humans; Infusions, Intravenous; Levofloxacin; Male; Middle Aged; Neoplasms; Neutropenia; Ofloxacin; Razoxane; Sarcoma; Sepsis; Treatment Outcome

Left ventricular assist device (LVAD) failure and malfunction rates are critical gauges for establishing LVADs as a long-term therapy for end-stage heart failure patients. These device performance measures, however, have been inadequately characterized in the bridge-to-transplantation literature.. REMATCH is a randomized trial that compares optimal medical management with LVAD implantation for patients with end-stage heart failure. An independent committee adjudicated patient outcomes. The primary endpoint--survival--was analyzed by intention to treat using the log-rank statistic. Frequency of event occurrence was analyzed by Poisson regression. The time to first event was analyzed by the product limit method. Device performance was disaggregated into confirmed malfunctions and system failures. The latter were events in which patients could not be rescued with backup circulatory support measures.. The 1-year survival rate was 52% (95% confidence limit [CL]; 40%-63%) for LVAD patients versus 28% (95% CL; 17%-39%) for medical patients and the 2-year survival rate was 29% (95% CL; 19%-40%) for LVAD patients versus 13% (95% CL; 5%-22%) for medical patients. System failure was 0.13 per patient per year and the confirmed LVAD malfunction rate was 0.90. Freedom from device replacement was 87% at 1 year and 37% at 2 years.. Despite the observed rates of device malfunction and replacement, LVAD implantation confers clinically significant improvement with regard to survival as compared with medical management. Device modifications and innovations for infection management exhibit great promise of improving device performance in the near future.

Topics: Aged; Cardiovascular Agents; Cause of Death; Female; Heart Failure; Heart-Assist Devices; Hemorrhage; Humans; Male; Middle Aged; Poisson Distribution; Prosthesis Failure; Sepsis; Stroke; Survival Rate

Goal-directed therapy has been used for severe sepsis and septic shock in the intensive care unit. This approach involves adjustments of cardiac preload, afterload, and contractility to balance oxygen delivery with oxygen demand. The purpose of this study was to evaluate the efficacy of early goal-directed therapy before admission to the intensive care unit.. We randomly assigned patients who arrived at an urban emergency department with severe sepsis or septic shock to receive either six hours of early goal-directed therapy or standard therapy (as a control) before admission to the intensive care unit. Clinicians who subsequently assumed the care of the patients were blinded to the treatment assignment. In-hospital mortality (the primary efficacy outcome), end points with respect to resuscitation, and Acute Physiology and Chronic Health Evaluation (APACHE II) scores were obtained serially for 72 hours and compared between the study groups.. Of the 263 enrolled patients, 130 were randomly assigned to early goal-directed therapy and 133 to standard therapy; there were no significant differences between the groups with respect to base-line characteristics. In-hospital mortality was 30.5 percent in the group assigned to early goal-directed therapy, as compared with 46.5 percent in the group assigned to standard therapy (P = 0.009). During the interval from 7 to 72 hours, the patients assigned to early goal-directed therapy had a significantly higher mean (+/-SD) central venous oxygen saturation (70.4+/-10.7 percent vs. 65.3+/-11.4 percent), a lower lactate concentration (3.0+/-4.4 vs. 3.9+/-4.4 mmol per liter), a lower base deficit (2.0+/-6.6 vs. 5.1+/-6.7 mmol per liter), and a higher pH (7.40+/-0.12 vs. 7.36+/-0.12) than the patients assigned to standard therapy (P < or = 0.02 for all comparisons). During the same period, mean APACHE II scores were significantly lower, indicating less severe organ dysfunction, in the patients assigned to early goal-directed therapy than in those assigned to standard therapy (13.0+/-6.3 vs. 15.9+/-6.4, P < 0.001).. Early goal-directed therapy provides significant benefits with respect to outcome in patients with severe sepsis and septic shock.

Topics: Aged; Algorithms; APACHE; Blood Pressure; Cardiovascular Agents; Emergency Service, Hospital; Erythrocyte Transfusion; Female; Fluid Therapy; Health Resources; Hemodynamics; Hospital Mortality; Hospitals, Urban; Humans; Male; Middle Aged; Monitoring, Physiologic; Oxygen; Prospective Studies; Sepsis; Shock, Septic; Single-Blind Method; Systemic Inflammatory Response Syndrome; Treatment Outcome

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. As such, circulating cytokines and danger- and pathogen-associated molecular patterns (such as endotoxins) are recognized as central in the pathogenesis of sepsis and organ dysfunction. Removing these compounds by extracorporeal blood filtration, commonly considered blood purification, may improve the septic patients' condition. This study aimed to assess the vaso-inotropic support evolution over time in pediatric patients with vasoplegic shock treated with oXiris©.. All patients aged below 18 years admitted at the Paris Saclay University Quaternary Pediatric Intensive Care Unit with vasoplegic shock and acute kidney injury and treated with oXiris© between October 2017 and January 2020 were included. The vaso-inotropic score and the 28-day mortality were assessed. Improvement under treatment was defined as a 50% decrease in the vaso-inotropic score following 24 h of oXiris© therapy.. Eleven pediatric patients aged 2-15 years and weighing 11-60 kg were admitted with vasoplegic shock and acute kidney injury. They received thirteen sessions of oXiris© therapy for septic shock (N = 7) and liver failure (N = 6). Eight patients did not improve their condition during the session, and five ultimately died (37.5% survival). Five patients improved, decreasing their inotropic support by >50% in 24 h. Among them, four survived (80%).. Hemofiltration and extracorporeal blood purification with oXiris© can be used in pediatric patients with vasoplegic shock with rapid improvement in hemodynamics in selected patients.

Topics: Acute Kidney Injury; Adolescent; Cardiovascular Agents; Child; Child, Preschool; Critical Illness; Humans; Multiple Organ Failure; Sepsis; Shock, Septic

Tachycardia is a hallmark of sepsis. An elevated heart rate could impair ventricular filling and increase myocardial oxygen demand. β-Blockers and ivabradine (a selective inhibitor of If channels in the sinoatrial node) are both able to control sinus tachycardia, with the latter drug being devoid of negative inotropic effect. This work aimed at assessing the hemodynamic effects of ivabradine as compared with a β-blocker (atenolol) during murine peritonitis.. Ivabradine (3 μg/g), atenolol (3 μg/g), or placebo was administered intraperitoneally 2 h after induction of peritonitis (cecal ligation and puncture) in male C57BL6 mice. The authors used invasive (left ventricular catheterization) and noninvasive (transthoracic echocardiography) monitoring to assess hemodynamics 20 h after surgery, including heart rate, blood pressure, left ventricular systolic, and diastolic function (n = 10 mice/group). The authors also assessed overall mortality 30 and 60 h after surgery in a distinct subset of animals (n = 20 mice/group). Descriptive data are presented as median (25th to 75th percentile).. As compared with placebo (601 beats/min [547 to 612]), ivabradine (447 beats/min [430 to 496]) and atenolol (482 beats/min [412 to 505]) blunted sepsis-induced tachycardia assessed by transthoracic echocardiography in awake animals (P < 0.001 and P = 0.004, respectively). Unlike ivabradine, atenolol reduced cardiac output, systolic blood pressure, and left ventricular systolic function (as assessed by ejection fraction, maximal left ventricular pressure rise, and anterior wall strain rate) as compared with septic mice receiving placebo. There was no difference in survival 60 h after sepsis induction with ivabradine (6 of 20, 30%) or atenolol (7 of 20, 35%), as compared with placebo (5 of 20, 25%; P = 0.224).. Heart rate control could be similarly achieved by ivabradine or atenolol, with preservation of blood pressure, cardiac output, and left ventricular systolic function with the former drug.

Topics: Adrenergic beta-Antagonists; Animals; Cardiovascular Agents; Heart Rate; Ivabradine; Male; Mice; Mice, Inbred C57BL; Random Allocation; Sepsis

Experimental data suggest that ivabradine, an inhibitor of the pacemaker current in sinoatrial node, exerts beneficial effects on endothelial cell function, but it is unclear if this drug could prevent microcirculatory dysfunction in septic subjects, improving tissue perfusion and reducing organ failure. Therefore, this study was designed to characterize the microcirculatory effects of ivabradine on a murine model of abdominal sepsis using intravital videomicroscopy.. Twenty-eight golden Syrian hamsters were allocated in four groups: sham-operated animals, nontreated septic animals, septic animals treated with saline, and septic animals treated with ivabradine (2.0 mg/kg intravenous bolus + 0.5 mg · kg · h). The primary endpoint was the effect of ivabradine on the microcirculation of skinfold chamber preparations, assessed by changes in microvascular reactivity and rheologic variables, and the secondary endpoint was its effects on organ function, evaluated by differences in arterial blood pressure, motor activity score, arterial blood gases, and hematologic and biochemical parameters among groups.. Compared with septic animals treated with saline, those treated with ivabradine had greater functional capillary density (90 ± 4% of baseline values vs. 71 ± 16%; P < 0.001), erythrocyte velocity in capillaries (87 ± 11% of baseline values vs. 62 ± 14%; P < 0.001), and arteriolar diameter (99 ± 4% of baseline values vs. 91 ± 7%; P = 0.041) at the end of the experiment. Besides that, ivabradine-treated animals had less renal, hepatic, and neurologic dysfunction.. Ivabradine was effective in reducing microvascular derangements evoked by experimental sepsis, which was accompanied by less organ dysfunction. These results suggest that ivabradine yields beneficial effects on the microcirculation of septic animals.

Topics: Animals; Benzazepines; Cardiovascular Agents; Cricetinae; Disease Models, Animal; Ivabradine; Male; Mesocricetus; Microcirculation; Sepsis

Topics: Aged; Arrhythmias, Cardiac; Benzazepines; Cardiovascular Agents; Humans; Ivabradine; Male; Middle Aged; Multiple Organ Failure; Pilot Projects; Sepsis; Treatment Outcome

Toll-like receptors (TLRs) play a role in the pathophysiology of sepsis and multiple organ failure. This study examined the effect of CpG oligodeoxynucleotide (CpG-ODN), the TLR9 ligand, on polymicrobial sepsis-induced cardiac dysfunction.. Male C57BL/6 mice were treated with CpG-ODN, control CpG-ODN (control-ODN), or inhibitory CpG-ODN (iCpG-ODN) 1 hour prior to cecal ligation and puncture (CLP)-induced sepsis. Mice that underwent sham surgery served as sham controls. Cardiac function was examined by echocardiography before and 6 hours after CLP.. Cardiac function was significantly decreased 6 hours after CLP. CpG-ODN prevented CLP-induced cardiac dysfunction, as evidenced by maintenance of the ejection fraction and fractional shortening. Control-ODN or iCpG-ODN did not alter CLP-induced cardiac dysfunction. CpG-ODN significantly attenuated CLP-induced myocardial apoptosis and increased myocardial Akt and extracellular-signal-related kinase (ERK) phosphorylation levels following CLP. In vitro experiments demonstrated that CpG-ODN promotes an association between TLR9 and Ras, resulting in Akt and ERK phosphorylation. Inhibition of phosphoinositide 3-kinase (PI3K) by Ly294002 or inhibition of ERK by U0126 in vivo abolished CpG-ODN attenuation of CLP-induced cardiac dysfunction.. CpG-ODN prevents CLP-induced cardiac dysfunction, in part through activation of PI3K/Akt and ERK signaling. Modulation of TLR9 could be an effective approach for treatment of cardiovascular dysfunction in patients with sepsis or septic shock.

Topics: Animals; Cardiovascular Agents; Echocardiography; Heart; Heart Failure; Male; Mice; Mice, Inbred C57BL; Oligodeoxyribonucleotides; Sepsis; Treatment Outcome

Cardiac dysfunction occurs commonly in sepsis. Impaired mitochondrial function is a potential cause of sepsis-associated myocardial depression. Cytochrome oxidase (COX), the terminal oxidase of the electron transport chain, is inhibited in the septic heart. Glutamine (GLN) increases Krebs cycle intermediates and supports oxidative phosphorylation. Exogenous GLN has been shown to restore myocardial adenosine triphosphate levels and cardiac function following ischemia-reperfusion injury. The authors hypothesize that exogenous GLN will abrogate sepsis-induced myocardial COX inhibition and improve sepsis-associated myocardial depression.. Under general anesthesia, male Sprague-Dawley rats underwent cecal ligation and double puncture (CLP) or sham operation. At the time of operation, rats underwent intraperitoneal injection of either GLN (0.75 g/kg) or an equal volume of saline. Twenty-four hours after the procedure, animals were killed, cardiac ventricles harvested, and mitochondria isolated. Steady-state COX kinetic activity was measured and normalized to citrate synthase activity. Steady-state levels of COX subunit I protein were determined with immunoblot analysis. Cardiac function was assessed using an isolated rat heart preparation. Five animals per group were evaluated. Significance was determined with analysis of variance and post hoc Tukey test.. CLP significantly decreased myocardial COX activity, oxygen consumption, left ventricular pressure (LVP), and pressure developed during isovolumic contraction (+dP/dt) and relaxation (-dP/dt). GLN restored COX activity to sham levels, significantly increased myocardial oxygen extraction and consumption, increased LVP toward sham values, and increased ±dP/dt by >30% following CLP.. The beneficial effects of GLN therapy during sepsis may be in part due to restoration of oxidative phosphorylation and abrogation of sepsis-associated myocardial depression.

Topics: Animals; Blood Pressure; Cardiovascular Agents; Disease Models, Animal; Electron Transport Complex IV; Glutamine; Heart; Heart Ventricles; Male; Muscle Contraction; Myocardium; Oxygen Consumption; Rats; Rats, Sprague-Dawley; Sepsis

Several cases of inverted Takotsubo cardiomyopathy--a variant form with hyperdynamic left ventricular apex and akinesia of the left ventricular base and mid-portion--have been reported recently, especially in association with cerebrovascular accidents and catecholamine cardiomyopathies. Herein, we describe 2 cases of inverted Takotsubo cardiomyopathy: one that occurred in a middle-aged woman who had a septic condition, and another in a young woman who was in the postpartal state. Such cases have not been reported previously.

Topics: Adult; Anti-Bacterial Agents; Cardiovascular Agents; Coronary Angiography; Drug Therapy, Combination; Echocardiography; Female; Hemodynamics; Humans; Intra-Aortic Balloon Pumping; Postpartum Period; Pregnancy; Puerperal Disorders; Sepsis; Takotsubo Cardiomyopathy; Treatment Outcome

To audit current UK practice of the management of severe sepsis in children against the 2002 American College of Critical Care Medicine/Pediatric Advanced Life Support (ACCM-PALS) guideline.. Prospective observational study.. 17 UK paediatric intensive care units (PICUs) and two UK PICU transport services.. 200 children accepted for PICU admission within 12 h of arrival in hospital, whether or not successfully transported to a PICU, with a discharge diagnosis of sepsis or suspected sepsis.. Medical interventions, physiological and laboratory data to determine the presence or absence of shock, inter-hospital transfer times, predicted mortality (using the Paediatric Index of Mortality, version 2 (PIM2) scoring system) and observed mortality.. 34/200 (17%) children died following referral. Although children defined as being in shock received significantly more fluid (p<0.001) than those who were not in shock, overall fluid and inotrope management suggested by the 2002 ACCM-PALS guideline was not followed in 62% of shocked children. Binary logistic regression analysis demonstrated that the odds ratio for death, if shock was present at PICU admission, was 3.8 (95% CI 1.4 to 10.2, p = 0.008).. The presence of shock at PICU admission is associated with an increased risk of death. Despite clear consensus guidelines for the emergency management of children with severe sepsis and septic shock, most children received inadequate fluid resuscitation and inotropic support in the crucial few hours following presentation.

Topics: Cardiovascular Agents; Child, Preschool; Critical Care; Emergency Treatment; Female; Fluid Therapy; Guideline Adherence; Humans; Infant; Intensive Care Units, Pediatric; Male; Medical Audit; Practice Guidelines as Topic; Prospective Studies; Sepsis; Time Factors; Treatment Outcome; United Kingdom

Preload parameters in postresuscitation phase are not sufficiently sensitive to guide fluid therapy in critically ill patients. We analyzed modifications in the fluid therapy and vasoactive drugs of critically ill patients that were produced by inclusion of extravascular lung water (EVLW) data in the treatment protocol and evaluated the short-term response.. This observational and prospective study included consecutive patients with hypotension or hypoxemia, comparing the therapeutic plan for fluid and vasoactive drug treatment between before and after knowing the EVLW value.. We studied 42 patients. After knowing the EVLW, 52.4% (n = 22) of initial therapeutic plans were changed, modifying fluid therapy in all of these cases and vasoactive therapy in 22% of them. EVLW value was 13.91 +/- 5.62 in patients with change of therapeutic plan versus 10 +/- 4.52 in those with no change (p < 0.05). No differences were found in preload parameters as a function of change/no change. The most frequent decision change (n = 13) was to fluid reduction plus diuretic administration, and patients with this modification had significantly (p < 0.05) higher EVLW values compared with the remaining patients with a change in fluid therapy. Out of the 22 patients with a modified therapeutic decision, the therapy proved effective in 18 patients. Quantification of EVLW in patients who can be considered euvolemic induces important modifications in fluid and vasoactive therapy. These changes generally resulted in a lower volume loading and a positive outcome for the patient.

Topics: Analysis of Variance; Cardiovascular Agents; Chi-Square Distribution; Critical Illness; Extravascular Lung Water; Female; Fluid Therapy; Hemodynamics; Humans; Hypotension; Hypoxia; Indicator Dilution Techniques; Male; Prospective Studies; Respiration, Artificial; Respiratory Distress Syndrome; Sepsis

Topics: Anti-Bacterial Agents; Cardiovascular Agents; Clinical Protocols; Critical Care; Drug Therapy, Combination; Evidence-Based Medicine; Guideline Adherence; Humans; International Cooperation; Practice Guidelines as Topic; Sepsis; Shock, Septic

Patent ductus arteriosus (PDA), especially PDA with sepsis, has been reported as a risk factor for feed intolerance in preterm neonates. In this study, the start to full feeds interval was found to be longest in preterm neonates (

Topics: Age Factors; Analysis of Variance; Cardiovascular Agents; Ductus Arteriosus, Patent; Enteral Nutrition; Enterocolitis, Necrotizing; Female; Humans; Indomethacin; Infant, Newborn; Infant, Premature, Diseases; Male; Prognosis; Risk Factors; Sepsis

The landmark Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure (REMATCH) trial first demonstrated that implantation of left ventricular assist devices (LVADs) as destination therapy (DT) can provide survival superior to any known medical treatment in patients with end-stage heart failure who are ineligible for transplantation. In the present study, we describe outcomes of DT in the post-REMATCH era in the United States.. The present study included 280 patients who underwent HeartMate XVE LVAD implantation between November 2001 and December 2005. A preoperative risk score for in-hospital mortality after LVAD implantation was established in 222 patients with complete data. All patients were followed up until death or December 2006. The 1-year survival after LVAD implantation was 56%. The in-hospital mortality after LVAD surgery was 27%. The main causes of death included sepsis, right heart failure, and multiorgan failure. The most important determinants of in-hospital mortality were poor nutrition, hematological abnormalities, markers of end-organ or right ventricular dysfunction, and lack of inotropic support. Stratification of DT candidates into low (n=65), medium (n=111), high (n=28), and very high (n=18) risk on the basis of the risk score calculated from these predictors corresponded with 1-year survival rates of 81%, 62%, 28%, and 11%, respectively.. Appropriate selection of candidates and timing of LVAD implantation are critical for improved outcomes of DT. Patients with advanced heart failure who are referred for DT before major complications of heart failure develop have the best chance of achieving an excellent 1-year survival with LVAD therapy.

Topics: Aged; Cardiovascular Agents; Cause of Death; Equipment Failure; Female; Follow-Up Studies; Heart Failure; Heart Transplantation; Heart-Assist Devices; Hematologic Diseases; Hospital Mortality; Hospitalization; Humans; Kaplan-Meier Estimate; Logistic Models; Male; Malnutrition; Middle Aged; Multiple Organ Failure; Quality of Life; Registries; Retrospective Studies; Risk; Sepsis; Survival Analysis; Survival Rate; Treatment Outcome; United States; Ventricular Dysfunction, Right

Topics: Aged; Cardiovascular Agents; Equipment Failure; Heart Failure; Heart Transplantation; Heart-Assist Devices; Hospitalization; Humans; Middle Aged; Postoperative Complications; Quality of Life; Randomized Controlled Trials as Topic; Sepsis; Survival Rate; Treatment Outcome

A preterm male infant with a patent ductus arteriosus developed neutropenia during treatment with indomethacin. Afterward, the mother described her own history of indomethacin-associated neutropenia. During the recovery from the neutropenia, the infant became septic with bacteremia caused by Enterobacter cloacae. Although indomethacin-related neutropenia has been described in adults, no case in a neonate has been reported. If neutropenia occurs after indomethacin therapy in a neonate, a familial history of indomethacin-associated neutropenia should be sought and the increased risk of infection should be considered.

Topics: Cardiovascular Agents; Ductus Arteriosus, Patent; Enterobacter cloacae; Enterobacteriaceae Infections; Humans; Indomethacin; Infant, Newborn; Infant, Premature; Male; Neutropenia; Sepsis

We present a consensus report from the SFAR/SLRF (Société Française d'Anesthésie et de Réanimation/Société de Réanimation de Langue Française) Consensus Conference, held on 13 October 2005 in Paris, France. The consensus report made recommendations on five topics relevant to the treatment of circulatory failure in sepsis and its underlying rationale. These topics are as follows: therapeutic goals of haemodynamic support in sepsis; goals of fluid resuscitation (including transfusion); role of inotropes and vasoactive drugs; role of other treatments; and treatment strategy. This report is reproduced from a translation of the original in Annales Francaises of Anesthésie and Réanimation.

Topics: Cardiovascular Agents; Critical Care; Disease Management; France; Hemodynamics; Humans; Paris; Sepsis; Societies, Medical

Topics: Cardiovascular Agents; Fluid Therapy; Humans; Sepsis; Shock, Septic

We have previously shown that in vitro myocardial performance is impaired in rats during the hyperdynamic, hypermetabolic phase of sepsis. Although the heart in the resting animal generated an elevated cardiac output, the isolated, perfused heart showed a depressed ventricular function curve. In the present studies, interventions to improve contractile function (increased perfusate calcium concentration or perfusion with ouabain) or to decrease calcium availability to the myofibrils (verapamil and tetracaine) were investigated using the isolated perfused working heart. These studies showed that increasing or decreasing calcium concentration in the perfusion medium had little effect on ventricular performance in the septic group, whereas ouabain enhanced performance by approximately 25%. Addition of verapamil at a dose that caused a minimal decrease in myocardial work (cardiac output X peak systolic pressure) in control hearts showed a 20-25% increase in work in the experimental hearts. Increased levels of verapamil caused a greater depression in myocardial performance in the control hearts than in the hearts from septic rats. Thus, it appears that a multifaceted defect may be present in these hearts with a derangement that can be slightly improved with either ouabain or verapamil. Since neither intervention could completely reverse the myocardial dysfunction in hyperdynamic sepsis, it appears that the defect may be due to other factors in addition to calcium availability for contraction.

Topics: Animals; Blood Pressure; Calcium; Cardiac Output; Cardiovascular Agents; Heart; In Vitro Techniques; Male; Myocardial Contraction; Ouabain; Rats; Rats, Inbred Strains; Sepsis; Tetracaine; Verapamil

Topics: Adrenal Cortex Hormones; Anti-Bacterial Agents; Cardiovascular Agents; Gram-Negative Aerobic Bacteria; Gram-Negative Anaerobic Bacteria; Humans; Infusions, Parenteral; Sepsis; Shock, Septic

Topics: Bacterial Infections; Cardiovascular Agents; Ergot Alkaloids; Female; Pre-Eclampsia; Pregnancy; Sepsis; Toxemia

Topics: Bacterial Infections; Cardiovascular Agents; Ergot Alkaloids; Female; Pre-Eclampsia; Pregnancy; Sepsis; Toxemia