-
Nature Reviews. Disease Primers Feb 2020Burn injuries are under-appreciated injuries that are associated with substantial morbidity and mortality. Burn injuries, particularly severe burns, are accompanied by... (Review)
Review
Burn injuries are under-appreciated injuries that are associated with substantial morbidity and mortality. Burn injuries, particularly severe burns, are accompanied by an immune and inflammatory response, metabolic changes and distributive shock that can be challenging to manage and can lead to multiple organ failure. Of great importance is that the injury affects not only the physical health, but also the mental health and quality of life of the patient. Accordingly, patients with burn injury cannot be considered recovered when the wounds have healed; instead, burn injury leads to long-term profound alterations that must be addressed to optimize quality of life. Burn care providers are, therefore, faced with a plethora of challenges including acute and critical care management, long-term care and rehabilitation. The aim of this Primer is not only to give an overview and update about burn care, but also to raise awareness of the ongoing challenges and stigmata associated with burn injuries.
Topics: Burns; Humans; Multiple Organ Failure; Quality of Life; Shock
PubMed: 32054846
DOI: 10.1038/s41572-020-0145-5 -
Gastroenterology May 2019Acute pancreatitis may be associated with both local and systemic complications. Systemic injury manifests in the form of organ failure, which is seen in approximately... (Review)
Review
Acute pancreatitis may be associated with both local and systemic complications. Systemic injury manifests in the form of organ failure, which is seen in approximately 20% of all cases of acute pancreatitis and defines "severe acute pancreatitis." Organ failure typically develops early in the course of acute pancreatitis, but also may develop later due to infected pancreatic necrosis-induced sepsis. Organ failure is the most important determinant of outcome in acute pancreatitis. We review here the current understanding of the risk factors, pathophysiology, timing, impact on outcome, and therapy of organ failure in acute pancreatitis. As we discuss the pathophysiology of severe systemic injury, the distinctions between markers and mediators of severity are highlighted based on evidence supporting their causality in organ failure. Emphasis is placed on clinically relevant end points of organ failure and the mechanisms underlying the pathophysiological perturbations, which offer insight into potential therapeutic targets to treat.
Topics: Acute Disease; Animals; Humans; Multiple Organ Failure; Pancreatitis; Prognosis; Risk Assessment; Risk Factors
PubMed: 30768987
DOI: 10.1053/j.gastro.2018.12.041 -
Anales de Pediatria Oct 2022Perinatal asphyxia is an event with far-reaching consequences that can lead not only to the development of neonatal encephalopathy, but also to multiple organ failure...
Perinatal asphyxia is an event with far-reaching consequences that can lead not only to the development of neonatal encephalopathy, but also to multiple organ failure (MOF). This ailment may result from the redistribution of blood flow, which would preserve the perfusion of vital organs such as the heart, brain and adrenal glands at the expense of other organs. The objective of the study was to determine the incidence and aetiopathogenesis of failure in the organs most frequently involved in neonatal MOF following perinatal asphyxia. We conducted a systematic literature search in the PubMed, Scopus and Cochrane Library databases using the MeSH terms (ischemia AND hypoxia AND multiorgan dysfunction AND neonat*), (asphyxia AND multiorgan dysfunction AND neonat*) and (liver/kidney/digestive OR gastrointestinal/heart injury AND ischemia AND hypoxia AND neonat*). We selected clinical and preclinical studies published after 2000 and excluded case series, letters to the editor, cohort studies without comparison groups and abstracts. In this study, we found that MOF associated with perinatal asphyxia is a frequent phenomenon with a relevant impact on neonatal morbidity and mortality, as it can cause changes not only in the kidney, liver and gastrointestinal tract, but also cardiomyopathy if the ailment is protracted or severe.
Topics: Asphyxia; Asphyxia Neonatorum; Brain; Female; Humans; Hypoxia; Infant, Newborn; Multiple Organ Failure; Pregnancy
PubMed: 36115781
DOI: 10.1016/j.anpede.2022.08.010 -
Pediatrics Jan 2022Prior criteria for organ dysfunction in critically ill children were based mainly on expert opinion. We convened the Pediatric Organ Dysfunction Information Update...
Prior criteria for organ dysfunction in critically ill children were based mainly on expert opinion. We convened the Pediatric Organ Dysfunction Information Update Mandate (PODIUM) expert panel to summarize data characterizing single and multiple organ dysfunction and to derive contemporary criteria for pediatric organ dysfunction. The panel was composed of 88 members representing 47 institutions and 7 countries. We conducted systematic reviews of the literature to derive evidence-based criteria for single organ dysfunction for neurologic, cardiovascular, respiratory, gastrointestinal, acute liver, renal, hematologic, coagulation, endocrine, endothelial, and immune system dysfunction. We searched PubMed and Embase from January 1992 to January 2020. Study identification was accomplished using a combination of medical subject headings terms and keywords related to concepts of pediatric organ dysfunction. Electronic searches were performed by medical librarians. Studies were eligible for inclusion if the authors reported original data collected in critically ill children; evaluated performance characteristics of scoring tools or clinical assessments for organ dysfunction; and assessed a patient-centered, clinically meaningful outcome. Data were abstracted from each included study into an electronic data extraction form. Risk of bias was assessed using the Quality in Prognosis Studies tool. Consensus was achieved for a final set of 43 criteria for pediatric organ dysfunction through iterative voting and discussion. Although the PODIUM criteria for organ dysfunction were limited by available evidence and will require validation, they provide a contemporary foundation for researchers to identify and study single and multiple organ dysfunction in critically ill children.
Topics: Child; Critical Care; Critical Illness; Evidence-Based Medicine; Humans; Multiple Organ Failure; Organ Dysfunction Scores
PubMed: 34970673
DOI: 10.1542/peds.2021-052888B -
Critical Care Clinics Jan 2018Sepsis-associated organ dysfunction involves multiple responses to inflammation, including endothelial and microvascular dysfunction, immune and autonomic dysregulation,... (Review)
Review
Sepsis-associated organ dysfunction involves multiple responses to inflammation, including endothelial and microvascular dysfunction, immune and autonomic dysregulation, and cellular metabolic reprogramming. The effect of targeting these mechanistic pathways on short- and long-term outcomes depends highly on the timing of therapeutic intervention. Furthermore, there is a need to understand the adaptive or maladaptive character of these mechanisms, to discover phase-specific biomarkers to guide therapy, and to conceptualize these mechanisms in terms of resistance and tolerance.
Topics: Humans; Multiple Organ Failure; Sepsis
PubMed: 29149942
DOI: 10.1016/j.ccc.2017.08.003 -
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 -
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 -
American Journal of Kidney Diseases :... Dec 2018Acute kidney injury (AKI) is common in critically ill patients and is associated with increased morbidity and mortality. Dysfunction of other organs is an important... (Review)
Review
Acute kidney injury (AKI) is common in critically ill patients and is associated with increased morbidity and mortality. Dysfunction of other organs is an important cause of poor outcomes from AKI. Ample clinical and epidemiologic data show that AKI is associated with distant organ dysfunction in lung, heart, brain, and liver. Recent advancements in basic and clinical research have demonstrated physiologic and molecular mechanisms of distant organ interactions in AKI, including leukocyte activation and infiltration, generation of soluble factors such as inflammatory cytokines/chemokines, and endothelial injury. Oxidative stress and production of reactive oxygen species, as well as dysregulation of cell death in distant organs, are also important mechanism of AKI-induced distant organ dysfunction. This review updates recent clinical and experimental findings on organ crosstalk in AKI and highlights potential molecular mechanisms and therapeutic targets to improve clinical outcomes during AKI.
Topics: Acute Kidney Injury; Brain; Cause of Death; Comorbidity; Critical Illness; Female; Humans; Kidney; Liver; Lung; Male; Multiple Organ Failure; Prognosis; Survival Analysis
PubMed: 29866457
DOI: 10.1053/j.ajkd.2018.03.028 -
United European Gastroenterology Journal Mar 2021
Topics: Disease Progression; Humans; Multiple Organ Failure; Pancreatitis; Risk Factors
PubMed: 33871927
DOI: 10.1002/ueg2.12056 -
Shock (Augusta, Ga.) May 2016There is currently no effective treatment for multiorgan failure following shock other than supportive care. A better understanding of the pathogenesis of these sequelae... (Review)
Review
There is currently no effective treatment for multiorgan failure following shock other than supportive care. A better understanding of the pathogenesis of these sequelae to shock is required. The intestine plays a central role in multiorgan failure. It was previously suggested that bacteria and their toxins are responsible for the organ failure seen in circulatory shock, but clinical trials in septic patients have not confirmed this hypothesis. Instead, we review here evidence that the digestive enzymes, synthesized in the pancreas and discharged into the small intestine as requirement for normal digestion, may play a role in multiorgan failure. These powerful enzymes are nonspecific, highly concentrated, and fully activated in the lumen of the intestine. During normal digestion they are compartmentalized in the lumen of the intestine by the mucosal epithelial barrier. However, if this barrier becomes permeable, e.g. in an ischemic state, the digestive enzymes escape into the wall of the intestine. They digest tissues in the mucosa and generate small molecular weight cytotoxic fragments such as unbound free fatty acids. Digestive enzymes may also escape into the systemic circulation and activate other degrading proteases. These proteases have the ability to clip the ectodomain of surface receptors and compromise their function, for example cleaving the insulin receptor causing insulin resistance. The combination of digestive enzymes and cytotoxic fragments leaking into the central circulation causes cell and organ dysfunction, and ultimately may lead to complete organ failure and death. We summarize current evidence suggesting that enteral blockade of digestive enzymes inside the lumen of the intestine may serve to reduce acute cell and organ damage and improve survival in experimental shock.
Topics: Animals; Enzymes; Humans; Insulin Resistance; Multiple Organ Failure; Pancreas; Peptide Hydrolases; Shock
PubMed: 26717111
DOI: 10.1097/SHK.0000000000000544