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Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Brain dysfunction is a severe complication of sepsis with an incidence ranging from 9% to 71% that is associated with increased morbidity and mortality. Its diagnosis relies mainly on neurologic examination with clinical manifestations ranging from confusion to coma. An electroencephalogram, somatosensory evoked potentials, and measurement of plasma S-100b protein and neuron-specific enolase can be useful for the detection of brain dysfunction. Brain MRI can identify brain lesions such as cerebral infarction, posterior reversible encephalopathy syndrome, and leukoencephalopathy. The mechanism of sepsis-associated encephalopathy involves inflammatory and non-inflammatory processes that affect endothelial cells, glial cells, and neurons and induce blood-brain barrier breakdown, derangements of intracellular metabolism, and cell death. Specific treatments for sepsis-associated encephalopathy need to be developed. Currently, treatment is mainly the management of sepsis.
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PMID:The encephalopathy in sepsis. 1824 79

Treatment of severe sepsis and septic shock often focuses on resolving immediate life-threatening problems related to infection (source control, antibiotics) and providing circulatory, ventilatory and other organ support. Neurologic complications, such as sepsis-associated encephalopathy, frequently occur in septic patients and are associated with higher mortality and long-term complications. As case fatalities and overall mortality continue to decline, long-term cognitive problems are becoming more common among survivors. Although the aetiology of septic encephalopathy has not been clearly established, systemic inflammation appears to play a key role in altering both the blood-brain barrier permeability and amplifying the inflammatory response. Several new therapies are now aimed at reducing systemic inflammation. These may eventually play a role in reducing neurologic complications related to the acute pathophysiology of sepsis and may be able to reduce early cerebral dysfunction with the goal of reducing long-term neurologic complications. Coupled plasma filtration adsorption is an extracorporeal therapy aimed at the non-specific removal of cytokines and mediators involved in systemic inflammation and immune suppression by the use of plasma filtration coupled to an adsorbent resin cartridge with high affinity for many cytokines and mediators. Several cytokines that are removed by coupled plasma filtration adsorption have also been implicated in blood-brain barrier permeability, leucocyte recruitment and amplification of the inflammatory response. Current studies are ongoing to determine whether treatments such as coupled plasma filtration adsorption may also be beneficial in reducing long-term neurologic complications.
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PMID:Therapeutic approaches to reduce systemic inflammation in septic-associated neurologic complications. 1828 9

Cerebral dysfunction and injury in the ICU presents as focal neurologic deficits, seizures, coma, and delirium. These syndromes may result from a primary brain insult, such as stroke or trauma, but commonly are a complication of a systemic insult, such as cardiac arrest, hypoxemia, sepsis, metabolic derangements, and pharmacologic exposures. Many survivors of critical illness have cognitive impairment, which is believed to underlie the poor long-term functional status and quality of life observed in many critical illness survivors. Although progress has been made in characterizing the epidemiology of cerebral dysfunction in the ICU, more research is needed to elucidate underlying mechanisms that might represent targets for therapeutic intervention.
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PMID:Types of brain dysfunction in critical illness. 1851 22

The mechanisms responsible to the development of brain dysfunction during sepsis are not well understood. The objective of this study is to evaluate mitochondrial respiratory chain and creatine kinase activities in the brain after cecal ligation and perforation (CLP) in rats. We performed a prospective, controlled experiment in male Wistar rats. Rats were subjected to CLP (sepsis group) with saline resuscitation (at 50mL/kg immediately and 12h after cecal ligation and perforation) or sham operation (control group). Several times (0, 6, 12, 24, 48 and 96h) after CLP six rats were killed by decapitation, and brain structures (cerebellum, hippocampus, striatum and cortex) were isolated. Mitochondrial respiratory chain and creatine kinase activity were then measured. It was observed that animals submitted to CLP presented decreased mitochondrial respiratory chain activity in complex I, but not in complex II, III and IV, 24, 48 and 96h in all analyzed structures. Activity of succinate dehydrogenase was decreased in 48 and 96h in all analyzed structures. Creatine kinase activity increased after CLP in cerebellum, hippocampus and cortex (after 0h) and striatum (after 6h). Sepsis associated brain injury may include dysfunction in the mitochondrial respiratory chain activity.
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PMID:Mitochondrial respiratory chain and creatine kinase activities in rat brain after sepsis induced by cecal ligation and perforation. 1865 32

The pathogenesis of sepsis associated encephalopathy (SAE) is not yet clear: the blood-brain barrier (BBB) disruption has been indicated among the possible causative mechanisms. S100B, a calcium binding protein, originates in the central nervous system but it can be also produced by extra-cerebral sources; it is passively released from damaged glial cells and neurons; it has limited passage through the BBB. We aimed to demonstrate BBB damage as part of the pathogenesis of SAE by cerebral spinal fluid (CSF) and serum S100B measurements and by magnetic resonance imaging (MRI). This paper describes four septic patients in whom SAE was clinically evident, who underwent MRI and S100B measurement. We have not found any evidence of CSF-S100B increase. Serum S100B increase was found in three out of four patients. MRI did not identify images attributable to BBB disruption but vasogenic edema, probably caused by an alteration of autoregulation, was diagnosed. S100B does not increase in CSF of septic patients; S100B increase in serum may be due to extracerebral sources and does not prove any injury of BBB. MRI can exclude other cerebral pathologies causing brain dysfunction but is not specific of SAE. BBB damage may be numbered among the contributors of SAE, which aetiology is certainly multifactorial: an interplay between the toxic mediators involved in sepsis and the indirect effects of hyperthermia, hypossia and hypoperfusion.
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PMID:Sepsis associated encephalopathy studied by MRI and cerebral spinal fluid S100B measurement. 1913 30

The intimate mechanisms of sepsis-induced delirium are unknown. Among the potential contributing factors, the breakdown of the blood-brain barrier is considered a key determinant of brain dysfunction. The complement activation is paramount to an appropriate activation of the central nervous system during stress. C3a and C5a have been extensively studied and may be involved in sepsis-induced delirium. Here we discuss the pro and con for inhibiting C5a to attenuate brain damage during sepsis. In particular, we discuss the hypothesis that C5a increased blood-brain barrier permeability amy ease the brain to mount an appropriate response to sepsis. Thus, blockade of C5a may be detrimental, resulting in an attenuated response of the stress system.
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PMID:Sepsis-associated delirium: the pro and con of C5a blockade. 1919 77

Oxidative stress has drawn a lot of attention in the past few decades, since it has been reported to participate in the mechanism of many diseases. Therefore, it seemed to be a good rationale to aim oxidative stress on therapeutic research. Sepsis is a complex systemic syndrome characterized by an imbalance between pro- and anti-inflammatory responses to a pathogen; its pathophysiology is a dynamic process which involves components of the immune system, the coagulation pathway, parenchymal cells, and the endocrine and metabolic pathways. It is well characterized that oxidative stress plays a crucial role in sepsis development, but the relation between central nervous system dysfunction and oxidative stress during sepsis is not well understood. Thus, we here summarize the current knowledge on the role of free radicals in the development of brain dysfunction in sepsis focusing on oxidative damage and the redox control of brain inflammatory pathways.
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PMID:Oxidative mechanisms of brain dysfunction during sepsis. 1968 Aug 6

The inflammatory and immune responses evoked in sepsis may create not only an acute brain dysfunction, which occurs in the majority of septic patients, but also long-term deficits such as memory impairment. In this context, we evaluated depressive-like parameters in sepsis survivor rats. For this purpose, male Wistar rats, weighing 300-350 g, underwent cecal ligation and perforation (CLP) (sepsis group) followed by "basic support", or were sham-operated (control group). After 3 days of the sepsis procedure, the animals were treated with imipramine at 10 mg/kg or saline during 14 days (days 3-17). The consumption of sweet food was measured for 7 days (days 10-17) and the body weight was measured before CLP, 10, and 17 days after CLP. Seventeen days after sepsis (immediately after sweet food consumption measurement), the animals were anesthetized and blood was withdrawn for the analyses of corticosterone and adrenocorticotropic hormone (ACTH) levels, and immediately killed by decapitation. The adrenal gland and hippocampus were immediately isolated and weighed, and the hippocampus was utilized for determining brain-derived neurotrophic factor (BDNF) levels. It was observed that animals subjected to CLP presented decreased sucrose intake. Septic rats did not increase body weight and presented an increase in the weight of adrenal gland. Both corticosterone and ACTH levels were increased, while hippocampus weight and BDNF levels in the hippocampus decreased. The treatment with imipramine reversed all the parameters described above. Our results supported the hypothesis that rats that survive sepsis show depressive-like behavior, alterations in the hypothalamus-pituitary-adrenal axis, and decreased BDNF levels in the hippocampus.
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PMID:Depressive-like parameters in sepsis survivor rats. 1970 13

We report on two children with sepsis-associated encephalopathy. They presented with fulminant neurological damage on clinical, neuroimaging, and neurophysiological findings. At onset, both went into deep coma after status epilepticus, resulting in near brain death. Both patients showed diffuse brain edema on CT and severe brain dysfunction on electroencephalography within a day of onset. Brain magnetic resonance (MR) imaging of one patient on day 2 showed restricted diffusion in the basal ganglia and the subcortical white matter of the frontal and occipital lobes. Brain edema aggravated and lasted for a few months despite a variety of treatments. MR imaging in the chronic phase revealed cracking lesions extending to the cerebral white matter, the cerebellum, and the brainstem. MR angiography showed diminished intracranial major arteries. These serial neuroradiological findings suggested severe brain damage resulting from fulminant elevation of intracranial pressure, which mimicked "brain death" or "respirator brain".
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PMID:Fulminant sepsis-associated encephalopathy in two children: serial neuroimaging findings and clinical course. 2013 72

Sepsis and septic shock are the commonest causes of death in the intensive care units. Although recent research have improved our understanding of the progress and pathophysiology of sepsis and septic shock, underlying mechanisms in sepsis-associated encephalopathy is still poorly understood. The incidence of sepsis-associated encephalopathy has been reported to vary from 8% to 70% of septic patients. We aimed at investigating the brain's electrical activity using somatosensory-evoked potentials and electrocorticographical recordings in cecal ligation and puncture rat model of sepsis. Significant decrease in mean arterial pressure, increase in heart rate, deteriorated neurological reflexes together with positive blood cultures results, thrombocytopenia and increased blood lactate levels suggesting the successful induction of sepsis in the present study. Elongated latencies and increased amplitudes were observed in somatosensory recordings of septic group, while electrocorticograms revealed slight decrease in median and spectral edge frequencies amplitudes and significantly increased delta activities in 50% of the septic rats. These results would suggest that the studies based on the investigation of the sepsis-associated encephalopathy in animal models needs to be combined with the electrophysiological confirmations of the brain dysfunction following the induction of sepsis.
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PMID:Alterations in the brain electrical activity in a rat model of sepsis-associated encephalopathy. 2067 56


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