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Critical Care (London, England) Oct 2020Sepsis is characterized by a dysregulated immune response to infection leading to life-threatening organ dysfunction. Sepsis-induced liver injury is recognized as a... (Review)
Review
Sepsis is characterized by a dysregulated immune response to infection leading to life-threatening organ dysfunction. Sepsis-induced liver injury is recognized as a powerful independent predictor of mortality in the intensive care unit. During systemic infections, the liver regulates immune defenses via bacterial clearance, production of acute-phase proteins (APPs) and cytokines, and metabolic adaptation to inflammation. Increased levels of inflammatory cytokines and impaired bacterial clearance and disrupted metabolic products can cause gut microbiota dysbiosis and disruption of the intestinal mucosal barrier. Changes in the gut microbiota play crucial roles in liver injury during sepsis. Bacterial translocation and resulting intestinal inflammation lead to a systemic inflammatory response and acute liver injury. The gut-liver crosstalk is a potential target for therapeutic interventions. This review analyzes the underlying mechanisms for the gut-liver crosstalk in sepsis-induced liver injury.
Topics: Gastrointestinal Microbiome; Gastrointestinal Tract; Humans; Liver; Multiple Organ Failure; Sepsis
PubMed: 33076940
DOI: 10.1186/s13054-020-03327-1 -
American Journal of Health-system... Mar 2022This is the second article in a 2-part series discussing the pathophysiology of sepsis. Part 1 of the series reviewed the immunologic response and overlapping pathways... (Review)
Review
PURPOSE
This is the second article in a 2-part series discussing the pathophysiology of sepsis. Part 1 of the series reviewed the immunologic response and overlapping pathways of inflammation and coagulation that contribute to the widespread organ dysfunction. In this article (part 2), major organ systems and their dysfunction in sepsis are reviewed, with discussion of scoring systems used to identify patterns and abnormal vital signs and laboratory values associated with sepsis.
SUMMARY
Sepsis is a dysregulated host response to infection that produces significant morbidity, and patients with shock due to sepsis have circulatory and cellular and metabolic abnormalities that lead to a higher mortality. Cardiovascular dysfunction produces vasodilation, reduced cardiac output and hypotension/shock requiring fluids, vasopressors, and advanced hemodynamic monitoring. Respiratory dysfunction may require mechanical ventilation and attention to volume status. Renal dysfunction is a frequent manifestation of sepsis. Hematologic dysfunction produces low platelets and either elevation or reduction of leukocytes, so consideration of the neutrophil:lymphocyte ratio may be useful. Procoagulant and antifibrinolytic activity leads to coagulation that is stimulated by inflammation. Hepatic dysfunction manifest as elevated bilirubin is often a late finding in sepsis and may cause reductions in production of essential proteins. Neurologic dysfunction may result from local endothelial injury and systemic inflammation through activity of the vagus nerve.
CONCLUSION
Timely recognition and team response with efficient use of therapies can improve patient outcome, and pharmacists with a complete understanding of the pathophysiologic mechanisms and treatments are valuable members of that team.
Topics: Humans; Hypotension; Multiple Organ Failure; Sepsis; Shock, Septic; Vasoconstrictor Agents
PubMed: 34651652
DOI: 10.1093/ajhp/zxab393 -
The Yale Journal of Biology and Medicine Dec 2019Sepsis is a highly complex and lethal syndrome with highly heterogeneous clinical manifestations that makes it difficult to detect and treat. It is also one of the major... (Review)
Review
Sepsis is a highly complex and lethal syndrome with highly heterogeneous clinical manifestations that makes it difficult to detect and treat. It is also one of the major and most urgent global public health challenges. More than 30 million people are diagnosed with sepsis each year, with 5 million attributable deaths and long-term sequalae among survivors. The current international consensus defines sepsis as a life-threatening organ dysfunction caused by a dysregulated host response to an infection. Over the past decades substantial research has increased the understanding of its pathophysiology. The immune response induces a severe macro and microcirculatory dysfunction that leads to a profound global hypoperfusion, injuring multiple organs. Consequently, patients with sepsis might present dysfunction of virtually any system, regardless of the site of infection. The organs more frequently affected are kidneys, liver, lungs, heart, central nervous system, and hematologic system. This multiple organ failure is the hallmark of sepsis and determines patients' course from infection to recovery or death. There are tools to assess the severity of the disease that can also help to guide treatment, like the Sequential Organ Failure Assessment (SOFA) score. However, sepsis disease process is vastly heterogeneous, which could explain why interventions targeted to directly intervene its mechanisms have shown unsuccessful results and predicting outcomes with accuracy is still elusive. Thus, it is required to implement strong public health strategies and leverage novel technologies in research to improve outcomes and mitigate the burden of sepsis and septic shock worldwide.
Topics: Cost of Illness; Humans; Microcirculation; Multiple Organ Failure; Oxygen; Perfusion; Sepsis
PubMed: 31866778
DOI: No ID Found -
The American Journal of Emergency... Jan 2021Decompensated hypothyroidism, formerly known as myxedema coma, is an endocrine emergency that commonly presents with altered mental status, as well as hypothermia and... (Review)
Review
BACKGROUND
Decompensated hypothyroidism, formerly known as myxedema coma, is an endocrine emergency that commonly presents with altered mental status, as well as hypothermia and depressed vital signs. The condition is often caused by an inciting event, which may lead to significant delays in the diagnosis and management of this disease. Although the incidence is low, this disease is associated with significant morbidity and mortality. Therefore, it is important for emergency clinicians to be aware of this condition.
OBJECTIVE
This narrative review evaluates the emergency medicine diagnosis and management of adult patients with decompensated hypothyroidism.
DISCUSSION
Decompensated hypothyroidism is a severe hypothyroid state associated with multiple organ failure. The diagnosis can be challenging due to similarities with more common diseases and lack of consideration of the diagnosis. Many patients may present with altered sensorium or depressed vital signs. Clinicians should obtain a thyroid stimulating hormone and free thyroxine level when considering the diagnosis. Management involves resuscitation, early steroid supplementation, thyroid hormone replacement, and treatment of the inciting event.
CONCLUSIONS
Decompensated hypothyroidism should be considered in the evaluation of patients with altered sensorium and depressed vital signs so as to not miss this critical diagnosis.
Topics: Coma; Combined Modality Therapy; Diagnosis, Differential; Emergencies; Emergency Medicine; Humans; Hypothyroidism; Multiple Organ Failure; Severity of Illness Index
PubMed: 33039222
DOI: 10.1016/j.ajem.2020.09.062 -
BMJ (Clinical Research Ed.) Oct 2020
Topics: Anti-Bacterial Agents; Blood Culture; Diagnosis, Differential; Disease Progression; Early Diagnosis; Emergency Medical Services; Humans; Infant, Newborn; Meningitis; Multiple Organ Failure; Neonatal Sepsis; Prescription Drug Overuse; Risk Factors; Symptom Assessment
PubMed: 33004379
DOI: 10.1136/bmj.m3672 -
Molecular Medicine Reports Dec 2023Sepsis is a manifestation of the immune and inflammatory response to infection, which may lead to multi‑organ failure. Health care advances have improved outcomes in... (Review)
Review
Sepsis is a manifestation of the immune and inflammatory response to infection, which may lead to multi‑organ failure. Health care advances have improved outcomes in critical illness, but it still remains the leading cause of death. Septic cardiomyopathy is heart dysfunction brought on by sepsis. Septic cardiomyopathy is a common consequence of sepsis and has a mortality rate of up to 70%. There is a lack of understanding of septic cardiomyopathy pathogenesis; knowledge of its pathogenesis and the identification of potential therapeutic targets may reduce the mortality rate of patients with sepsis and lead to clinical improvements. The present review aimed to summarize advances in the pathogenesis of cardiac dysfunction in sepsis, with a focus on mitochondrial dysfunction, metabolic changes and cell death modalities and pathways. The present review summarized diagnostic criteria and outlook for sepsis treatment, with the goal of identifying appropriate treatment methods for this disease.
Topics: Humans; Sepsis; Heart Diseases; Cardiomyopathies; Multiple Organ Failure
PubMed: 37859613
DOI: 10.3892/mmr.2023.13114 -
Blood Dec 2021Multiple organ dysfunction is the most severe outcome of sepsis progression and is highly correlated with a worse prognosis. Excessive neutrophil extracellular traps...
Multiple organ dysfunction is the most severe outcome of sepsis progression and is highly correlated with a worse prognosis. Excessive neutrophil extracellular traps (NETs) are critical players in the development of organ failure during sepsis. Therefore, interventions targeting NET release would likely effectively prevent NET-based organ injury associated with this disease. Herein, we demonstrate that the pore-forming protein gasdermin D (GSDMD) is active in neutrophils from septic humans and mice and plays a crucial role in NET release. Inhibition of GSDMD with disulfiram or genic deletion abrogated NET formation, reducing multiple organ dysfunction and sepsis lethality. Mechanistically, we demonstrate that during sepsis, activation of the caspase-11/GSDMD pathway controls NET release by neutrophils during sepsis. In summary, our findings uncover a novel therapeutic use for disulfiram and suggest that GSDMD is a therapeutic target to improve sepsis treatment.
Topics: Acetaldehyde Dehydrogenase Inhibitors; Adoptive Transfer; Aged; Animals; Cells, Cultured; Disulfiram; Extracellular Traps; Female; Gene Deletion; Humans; Intracellular Signaling Peptides and Proteins; Male; Mice, Inbred C57BL; Middle Aged; Multiple Organ Failure; Phosphate-Binding Proteins; Sepsis; Mice
PubMed: 34407544
DOI: 10.1182/blood.2021011525 -
Biomedicine & Pharmacotherapy =... Dec 2020Severe acute pancreatitis (SAP), a serious inflammatory disease of the pancreas, can easily lead to systemic inflammatory response syndrome (SIRS) and multiple organ... (Review)
Review
Severe acute pancreatitis (SAP), a serious inflammatory disease of the pancreas, can easily lead to systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndromes (MODS). Acute lung injury (ALI) is one of the most serious complications of SAP. However, the specific pathogenesis of SAP-associated ALI is not fully understood. Crosstalk and multi-mechanisms involving pancreatic necrosis, bacteremia, intestinal barrier failure, activation of inflammatory cascades and diffuse alveolar damage is the main reason for the unclear pathological mechanism of SAP-associated ALI. According to previous research on SAP-associated ALI in our laboratory and theories put forward by other scholars, we propose that the complex pattern of SAP-associated ALI is based on the "pancreas-intestine-inflammation/endotoxin-lung (P-I-I/E-L) pathway". In this review, we mainly concentrated on the specific details of the "P-I-I/E-L pathway" and the potential treatments or preventive measures for SAP-associated ALI.
Topics: Acute Lung Injury; Animals; Endotoxins; Humans; Intestines; Multiple Organ Failure; Pancreatitis; Pancreatitis, Acute Necrotizing; Systemic Inflammatory Response Syndrome
PubMed: 33011613
DOI: 10.1016/j.biopha.2020.110770 -
Journal of Intensive Care Medicine Sep 2019Hypovolemic shock exists as a spectrum, with its early stages characterized by subtle pathophysiologic tissue insults and its late stages defined by multi-system organ... (Review)
Review
Hypovolemic shock exists as a spectrum, with its early stages characterized by subtle pathophysiologic tissue insults and its late stages defined by multi-system organ dysfunction. The importance of timely detection of shock is well known, as early interventions improve mortality, while delays render these same interventions ineffective. However, detection is limited by the monitors, parameters, and vital signs that are traditionally used in the intensive care unit (ICU). Many parameters change minimally during the early stages, and when they finally become abnormal, hypovolemic shock has already occurred. The compensatory reserve (CR) is a parameter that represents a new paradigm for assessing physiologic status, as it comprises the sum total of compensatory mechanisms that maintain adequate perfusion to vital organs during hypovolemia. When these mechanisms are overwhelmed, hemodynamic instability and circulatory collapse will follow. Previous studies involving CR measurements demonstrated their utility in detecting central blood volume loss before hemodynamic parameters and vital signs changed. Measurements of the CR have also been used in clinical studies involving patients with traumatic injuries or bleeding, and the results from these studies have been promising. Moreover, these measurements can be made at the bedside, and they provide a real-time assessment of hemodynamic stability. Given the need for rapid diagnostics when treating critically ill patients, CR measurements would complement parameters that are currently being used. Consequently, the purpose of this article is to introduce a conceptual framework where the CR represents a new approach to monitoring critically ill patients. Within this framework, we present evidence to support the notion that the use of the CR could potentially improve the outcomes of ICU patients by alerting intensivists to impending hypovolemic shock before its onset.
Topics: Critical Illness; Early Diagnosis; Early Medical Intervention; Hemodynamic Monitoring; Hemodynamics; Humans; Multiple Organ Failure; Shock; Signal Processing, Computer-Assisted
PubMed: 30068251
DOI: 10.1177/0885066618790537 -
Medizinische Klinik, Intensivmedizin... May 2020The support of failing vital organ function, and the prevention of new injury, has been the primary goal of intensive care since its origins more than six decades ago.... (Review)
Review
The support of failing vital organ function, and the prevention of new injury, has been the primary goal of intensive care since its origins more than six decades ago. A primary focus on specific organ system support has led to the concept that the combined dysfunction of these systems represents a syndrome-the multiple organ dysfunction syndrome or MODS. A variety of tools have been developed to quantify the severity of MODS. This review summarizes the conceptual framework that shapes these, their uses as tools in the care and study of critically ill patients, and the issues that will need to be addressed in future refinements. (This article is freely available.).
Topics: Critical Illness; Humans; Multiple Organ Failure; Syndrome
PubMed: 32077983
DOI: 10.1007/s00063-020-00660-9