Misdirected Sympathy: The Role of Sympatholysis in Sepsis and Septic Shock

2017 ◽  
Vol 33 (2) ◽  
pp. 74-86 ◽  
Author(s):  
Jason A. Ferreira ◽  
Brittany D. Bissell
Keyword(s):  
Septic Shock ◽  
Cardiovascular Effects ◽  
Shock Therapy ◽  
Selective Inhibition ◽  
Sympathetic Tone ◽  
Autonomic Tone ◽  
Prevalent Disease ◽  
Sepsis And Septic Shock ◽  
The Impact

The spectrum of sepsis and septic shock remains a highly prevalent disease state, carrying a high risk of morbidity and mortality. The sympathetic nervous system (SNS) plays an important role in this initial cascade, enabling the host to respond to invading pathogens; however, prolonged activation can become pathological. The potential for unregulated sympathetic tone to become of detriment in patients with sepsis has fueled interest in the role and impact of sympatholysis, the selective inhibition of sympathetic tone. The cornerstone of septic shock therapy for decades has been the supplementation of catecholamines and thus potential further perpetuation of this sympathetic dysregulation. Although the theory of sympatholysis circulates around cardiovascular effects and stroke volume optimization, the impact of augmenting the SNS may extend well beyond this, including the impacts on the immune system, inflammatory cascade, and even gene transcription. Presently, the most robust clinical evidence involves the use of the cardioselective β-blocker esmolol in patients with septic shock with persistent tachycardia secondary to catecholamine use. Evidence is isolated only to animal models with α-agonists. Future evidence stands to elucidate the balance of sympathetic and autonomic tone as well as the potential role of redirecting and maximizing sympathetic activity.

Actual aspects of sepsis and septic shock

2014 ◽  
Vol 5 (2) ◽  
pp. 81-87
Author(s):  
Danila Viktorovich Strukov ◽  
Yuriy Stanislavovich Alexandrovich ◽  
Andrey Glebovich Vasiliev
Keyword(s):  
Septic Shock ◽  
Nitrogen Oxide ◽  
Shock Therapy ◽  
Infection Process ◽  
Nitrogen Oxide Synthase ◽  
Adults And Children ◽  
Contemporary Medicine ◽  
Sepsis And Septic Shock ◽  
Oxide Synthase

He review presents an analysis of up-to-date views on sepsis and septic shock. Results of consenting conferences are given with classification of sepsis in adults and children. Mortality indexes are presented in patients’ group with sepsis. Basic pathogenesis links are examined i.e. bacteriemia, microbe toxemia, endo(auto)toxicosis, systemic destructive vasculitis, growing hypercoagulation transforming into coagulopathia, consumption trombocytopenia with trombohemorrhagic syndrome and severe immunesuppression. Pathogenesis of septic shock is divided into processes developing in various organs and tissues as well as into intracellular ones: such as oxidative stress and mitochondrial insufficiency. The role of pathogen-associated molecular images - patterns is portrayed in the development of generalized acyclic infection process. A scheme of up-to-date septic shock therapy is presented. An important role of nitrogen oxide in the development of stabile hypotonia resistant to vasopressin therapy is proven. The potency of nitrogen oxide to produce free-radical peroxinitrite inducing lipids peroxide oxidation in membranes is reflected. Its ability to react with non-hem iron- and zink- containing proteins is mentioned. Key factors contributing to activation of genes responsible for inducible nitrogen oxide synthase operation are revealed. Extremely severe sepsis and septic shock are believed to be the most serious problem of contemporary medicine thus necessitating to produce new medicines affecting the most drug-resistant links of its pathogenesis. In many a countries trials are continuing to introduce new medicines like nitrogen oxide synthase inhibitors for the treatment of patients with septic shock.

The Role of Histones and Heparin in Sepsis: A Review

2021 ◽  
pp. 088506662199232
Author(s):  
Xiaojuan Zhang ◽  
Xin Li
Keyword(s):  
Septic Shock ◽  
Multiple Organ ◽  
Clinical Settings ◽  
The Past ◽  
Life Saving ◽  
Extracellular Histones ◽  
Sepsis And Septic Shock ◽  
Development And Management ◽  
Made In

Septic shock with multiple organ failure is a devastating situation in clinical settings. Through the past decades, much progress has been made in the management of sepsis and its underlying pathogenesis, but a highly effective therapeutic has not been developed. Recently, macromolecules such as histones have been targeted in the treatment of sepsis. Histones primarily function as chromosomal organizers to pack DNA and regulate its transcription through epigenetic mechanisms. However, a growing body of research has shown that histone family members can also exert cellular toxicity once they relocate from the nucleus into the extracellular space. Heparin, a commonly used anti-coagulant, has been shown to possess life-saving capabilities for septic patients, but the potential interplay between heparin and extracellular histones has not been investigated. In this review, we summarize the pathogenic roles of extracellular histones and the therapeutic roles of heparin in the development and management of sepsis and septic shock.

scholarly journals Maternal Diabetes Mellitus as a Risk Factor for High Blood Pressure in Late Childhood

Hypertension ◽  
2019 ◽  
Vol 73 (1) ◽  
Author(s):  
Joana Oliveira Miranda ◽  
Rui João Cerqueira ◽  
Henrique Barros ◽  
José Carlos Areias
Keyword(s):  
Diabetes Mellitus ◽  
Blood Pressure ◽  
Body Mass ◽  
Cardiovascular Effects ◽  
Maternal Diabetes ◽  
Diabetes Mellitus Group ◽  
The Impact ◽  
Maternal Diabetes Mellitus ◽  
Diabetic Mothers

Intrauterine fetal conditions can have lifelong cardiovascular effects. The impact of maternal diabetes mellitus on children’s cardiovascular profile is not well established. The goal of this study was to explore the association between maternal diabetes mellitus and offspring’s blood pressure (BP) ≤10 years of age. Generation XXI is a prospective birth cohort, which enrolled 8301 mother-offspring pairs, including 586 (7.1%) children of diabetic mothers. The associations between maternal diabetes mellitus and BP at 4, 7, and 10 years of age was modeled using linear regression. A mixed-effects model was built to assess differences in BP variation over time. Path analysis was used to quantify effects of potential mediators. Maternal diabetes mellitus was associated with higher BP in offspring at the age of 10 (systolic: β, 1.48; 95% CI, 0.36–2.59; and diastolic: β, 0.86; 95% CI, 0.05–1.71). This association was independent of maternal perinatal characteristics, and it was mediated by child’s body mass index and, to a lesser extent, by gestational age, type of birth, and birth weight (indirect effect proportion, 73%). No significant differences in BP were found at 4 and 7 years of age. Longitudinal analysis showed an accelerated systolic BP increase on maternal diabetes mellitus group (β, 1.16; 95% CI, 0.03–2.28). These finding were especially relevant in males, suggesting sex differences in the mechanisms of BP prenatal programing. Our results provide further evidence that maternal diabetes mellitus is associated with high BP late in childhood, demonstrating a significant role of child’s body mass in the pathway of this association.

scholarly journals Sepsis Code: dodging mortality in a tertiary hospital

2021 ◽  
Author(s):  
Rosa Méndez ◽  
Angels Figuerola ◽  
Marta Chicot ◽  
Ana Barrios ◽  
Natalia Pascual ◽  
...  
Keyword(s):  
Septic Shock ◽  
Critical Care ◽  
Health Personnel ◽  
Analytical Study ◽  
Statistical Significance ◽  
Tertiary Hospital ◽  
Critical Care Units ◽  
Multidisciplinary Group ◽  
Sepsis And Septic Shock ◽  
The Impact

Background. In the hospital of La Princesa, the “Sepsis Code” (CSP) began in 2015, as a multidisciplinary group that provides health personnel with clinical, analytical and organizational tools, with the aim of the detection and early treatment of patients with sepsis. The objective of this study is to evaluate the impact of CSP implantation on mortality and to determine the variables associated with an increase in it. Material and methods. A retrospective analytical study of patients with CSP alert activation from 2015 to 2018 was conducted. Clinical-epidemiological variables, analytical parameters, and severity factors such as admission to critical care units (UCC) and the need for amines were collected. Statistical significance was established at p < 0.05. Results. We included 1,121 patients. The length of stay was 16 days and 32% required admission to UCC. Mortality showed a statistically significant linear downward trend from 24% in 2015 to 15% in 2018. The predictive mortality variables with statistically significant association were lactate > 2 mmol/L, creatinine > 1.6 mg/dL and the need for amines. Conclusions. The implementation of Sepsis Code decreases the mortality of patients with sepsis and septic shock. The presence of a lactate > 2 mmol/L, creatinine > 1.6 mg/dL and/or the need to administer amines in the first 24 hours, are associated with an increase in mortality in the patient with sepsis.

scholarly journals The impact of duration of organ dysfunction on the outcome of patients with severe sepsis and septic shock

Clinics ◽  
2008 ◽  
Vol 63 (4) ◽  
Author(s):  
Flávio G. R. Freitas ◽  
Reinaldo Salomão ◽  
Nathalia Tereran ◽  
Bruno Franco Mazza ◽  
Murillo Assunção ◽  
...  
Keyword(s):  
Septic Shock ◽  
Severe Sepsis ◽  
Organ Dysfunction ◽  
Sepsis And Septic Shock ◽  
The Impact

NF-κB activation as a pathological mechanism of septic shock and inflammation

2006 ◽  
Vol 290 (4) ◽  
pp. L622-L645 ◽  
Author(s):  
Shu Fang Liu ◽  
Asrar B. Malik
Keyword(s):  
Septic Shock ◽  
Human Subjects ◽  
Myocardial Dysfunction ◽  
Multiple Organ ◽  
Organ Injury ◽  
Pathological Mechanism ◽  
Proinflammatory Gene ◽  
Intensive Investigation ◽  
Sepsis And Septic Shock

The pathophysiology of sepsis and septic shock involves complex cytokine and inflammatory mediator networks. NF-κB activation is a central event leading to the activation of these networks. The role of NF-κB in septic pathophysiology and the signal transduction pathways leading to NF-κB activation during sepsis have been an area of intensive investigation. NF-κB is activated by a variety of pathogens known to cause septic shock syndrome. NF-κB activity is markedly increased in every organ studied, both in animal models of septic shock and in human subjects with sepsis. Greater levels of NF-κB activity are associated with a higher rate of mortality and worse clinical outcome. NF-κB mediates the transcription of exceptional large number of genes, the products of which are known to play important roles in septic pathophysiology. Mice deficient in those NF-κB-dependent genes are resistant to the development of septic shock and to septic lethality. More importantly, blockade of NF-κB pathway corrects septic abnormalities. Inhibition of NF-κB activation restores systemic hypotension, ameliorates septic myocardial dysfunction and vascular derangement, inhibits multiple proinflammatory gene expression, diminishes intravascular coagulation, reduces tissue neutrophil influx, and prevents microvascular endothelial leakage. Inhibition of NF-κB activation prevents multiple organ injury and improves survival in rodent models of septic shock. Thus NF-κB activation plays a central role in the pathophysiology of septic shock.

scholarly journals Interplay between Nox2 Activity and Platelet Activation in Patients with Sepsis and Septic Shock: A Prospective Study

2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Giusy Tiseo ◽  
Elena Cavarretta ◽  
Arianna Forniti ◽  
Cristina Nocella ◽  
Sebastiano Sciarretta ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Septic Shock ◽  
Platelet Aggregation ◽  
Platelet Activation ◽  
Healthy Controls ◽  
Sample Collection ◽  
Oxidative Stress Status ◽  
Sepsis And Septic Shock ◽  
A Prospective Study

Background. Although preclinical studies highlighted the potential role of NADPH oxidase (NOX) in sepsis, only few studies evaluated the oxidative stress in patients with sepsis and septic shock. The objective of the study is to appraise the oxidative stress status and platelet function in patients with sepsis and septic shock compared to healthy controls. Methods and Results. Patients with sepsis or septic shock admitted to the hospital Policlinico Umberto I (Sapienza University, Rome) underwent a blood sample collection within 1 hour from admission. Platelet aggregation, serum thromboxane B2 (TxB2), soluble NOX2-derived peptides (sNox2-dp), and hydrogen peroxide breakdown activity (HBA) were measured and compared to those of healthy volunteers. Overall, 33 patients were enrolled; of these, 20 (60.6%) had sepsis and 13 (39.4%) septic shock. Compared to healthy controls ( n = 10 , age 67.8 ± 3.2 , male 50%), patients with sepsis and septic shock had higher platelet aggregation (49% (IQR 45-55), 60% (55.75-67.25), and 73% (IQR 69-80), respectively, p < 0.001 ), higher serum TxB2 (77.5 (56.5-86.25), 122.5 (114-131.5), and 210 (195-230) pmol/L, respectively, p < 0.001 ), higher sNox2-dp (10 (7.75-12), 19.5 (17.25-21), and 33 (29.5-39) pg/mL, respectively, p < 0.001 ), and lower HBA (75% (67.25-81.5), 50% (45-54.75), and 27% (21.5-32.5), respectively, p < 0.001 ). Although not statistically significant, a trend in higher levels of serum TxB2 and sNox2-dp in patients who died was observed. Conclusions. Patients with septic shock exhibit higher Nox2 activity and platelet activation than patients with sepsis. These insights joined to better knowledge of these mechanisms could guide the identification of future prognostic biomarkers and new therapeutic strategies in the scenario of septic shock.

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