Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The main clinical characteristics of sepsis and septic shock are derangements of cardiocirculatory and respiratory function. Additionally, profound alterations in metabolic pathways occur leading to hypermetabolism, enhanced energy expenditure, and insulin resistance. The clinical hallmarks are hyperglycemia, hyperlactatemia, and enhanced protein catabolism. These metabolic alterations are even more pronounced during sepsis as a result of cytokine release and subsequent induction of inflammatory pathways. Increased oxygen demands from mitochondrial oxygen utilization and oxygen consumption related to oxygen radical formation may contribute to hypermetabolism. In addition, mitochondrial dysfunction with impaired cellular respiration may be present. Mainstay therapeutic interventions for hemodynamic stabilization are adequate volume resuscitation and vasoactive agents, which, however, have additional impact on metabolic activity. Therefore, beyond hemodynamic effects, specific drug-related metabolic alterations need to be considered for optimal treatment during sepsis. This review gives an overview of the typical metabolic alterations during sepsis and septic shock and highlights the impact of vasoactive therapy on metabolism.
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PMID:Metabolic alterations in sepsis and vasoactive drug-related metabolic effects. 1288 81

Sepsis and septic shock account for substantial morbidity and mortality in the intensive care units. NF-kappaB activation, and elevated concentrations of macrophage migration inhibitory factor (MIF), tumor necrosis factor-a (TNF-alpha), interleukin-1 (IL-1), IL-6, free radicals, inducible nitric oxide (iNO), and stress hyperglycemia are some of the factors that induce systemic inflammatory response and myocardial depression seen in sepsis. Conversely, adenosine, activated protein C, oxidized phospholipids, w-3 fatty acids, and insulin have beneficial effects in sepsis and septic shock. These molecules and in particular insulin have the ability to suppress synthesis of MIF, TNF-alpha, IL-1, IL-6, and free radicals, enhance endothelial NO production, and enhance the production of anti-inflammatory cytokines IL-10, and IL-4. In addition, insulin corrects stress hyperglycemia and improves myocardial function. Thus insulin, adenosine, activated protein C, oxidized phospholipids, and w-fatty acids show anti-inflammatory actions and explain why and how they are useful in sepsis and septic shock and possibly, other inflammatory conditions. Hence, their combined use may be of significant benefit in sepsis and septic shock.
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PMID:Current advances in sepsis and septic shock with particular emphasis on the role of insulin. 1294 44

This review discusses the myocardial protective property of the insulin/glucose-insulin-potassium regimen and the mechanisms involved in this beneficial action. Several recent studies suggest that insulin not only is useful to control hyperglycemia and maintain glucose homeostasis but also may have the unique property to protect the myocardium from reperfusion injury and ischemia and prevent apoptosis of myocardial cells. The insulin/glucose-insulin-potassium (GIK) regimen suppresses the production of tumor necrosis factor-alpha, interleukin-6, macrophage migration inhibitory factor and other pro-inflammatory cytokines, and free radicals; and enhances the synthesis of endothelial nitric oxide and anti-inflammatory cytokines interleukin-4 and interleukin-10. Thus, the insulin/GIK regimen brings about its cardioprotective action. This may also explain why the insulin/GIK regimen is useful in sepsis and septic shock, myocardial recovery in acute myocardial infarction, and critical illness. It is suggested that the infusion of adequate amounts of insulin to patients with acute myocardial infarction, congestive heart failure, cardiogenic shock, and critical illness preserves myocardial integrity and function and ensures rapid recovery. In view of the suppressive action of insulin on the synthesis of proinflammatory cytokines and free radicals, it is possible that the insulin/GIK regimen, when used in a timely and appropriate fashion, may also protect other tissues and organs and facilitate in the recovery of patients who are critically ill.
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PMID:Insulin: an endogenous cardioprotector. 1450 50

NF-kappaB activation, and elevated concentrations of macrophage migration inhibitory factor (MIF), tumor necrosis factor-alpha (TNF-alpha), interleukin-1(IL-1), IL-6, free radicals, inducible nitric oxide (iNO), and stress hyperglycemia occurs in sepsis and this leads to systemic inflammatory response and myocardial depression seen in sepsis and septic shock. Conversely, insulin suppresses production of MIF, TNF-alpha, IL-1, IL-6, and free radicals, enhances endothelial NO generation, and enhances the production of anti-inflammatory cytokines IL-4, and IL-10, corrects stress hyperglycemia and improves myocardial function. This supports my earlier proposal that insulin (with or without glucose and potassium) therapy to maintain euglycemia suppresses the inflammatory response, improves myocardial function, and thus, is of benefit in acute myocardial infarction, sepsis andseptic shock.
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PMID:Insulin in sepsis and septic shock. 1462 Oct 41

Hyperglycemia is a risk marker of morbidity and mortality in acute critical illness, and insulin therapy seems to be beneficial in this patient group. Whether this is true for a population of sepsis patients, as such, has not been investigated in clinical trials, but evidence from in vitro studies and experimental sepsis suggests that this may be the case. The endocrinology of septic patients is characterized by a shift in the balance between insulin and its counter-regulatory hormones favoring the latter. This leads to prominent metabolic derangements composed of high release and low use of glucose, amino acids, and free fatty acids (FFA), resulting in increased blood levels of these substrates. Circulating, proinflammatory mediators further enhance this state of global catabolism. Increased levels of glucose and FFA have distinct effects on inflammatory signaling leading to additional release of proinflammatory mediators and endothelial and neutrophil dysfunction. Insulin has the inherent capability to counteract the metabolic changes observed in septic patients. Concomitantly, insulin therapy may act as a modulator of inflammatory pathways inhibiting the unspecific, inflammatory activation caused by metabolic substrates. Given these properties, insulin could conceivably be serving a dual purpose for the benefit of septic patients.
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PMID:The roles of insulin and hyperglycemia in sepsis pathogenesis. 1465 7

Stress-hyperglycemia and insulin resistance are exceedingly common in critically ill patients, particularly those with sepsis. Multiple pathogenetic mechanisms are responsible for this metabolic syndrome; however, increased release of pro-inflammatory mediators and counter-regulatory hormones may play a pivotal role. Recent data suggests that hyperglycemia may potentiate the pro-inflammatory response while insulin has the opposite effect. Furthermore, emerging evidence suggests that tight glycemic control will improve the outcome of critically ill patients. This paper reviews the pathophysiology of stress hyperglycemia in the critically ill septic patient and outlines a treatment strategy for the management of this disorder.
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PMID:Stress-hyperglycemia, insulin and immunomodulation in sepsis. 1499 Nov 1

A 15-year-old female with short intestine syndrome due to chronic intestinal pseudo-obstruction associated with kidney failure underwent a multivisceral (stomach-duodenum-jejunum-ileum-pancreas-liver) and kidney transplant. She had required parenteral nutrition for the last 5 years, with numerous complications such as sepsis from the central catheter, deep venous thrombosis, severe liver dysfunction, pancytopenia due to bone marrow failure, and severe malnutrition. Surgery lasted 15 hours and was free of complications other than hypothermia, which worsened after revascularization of the grafts. Replacement of 6 units of blood products and crystalloids was required. Biochemical and hemodynamic variables were stable, apart from the development of hypernatremia, hyperglycemia, and lactic acidosis. The anesthetic approach included preoperative assessment of problems related to chronic parenteral nutrition (liver dysfunction, coagulopathy, and restricted venous access), the prevention of hypothermia, correction of electrolyte imbalance and the acid-base status, treatment of reperfusion syndrome, and the replacement of fluids and blood products to maintain circulatory homeostasis and assure sufficient splanchnic perfusion.
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PMID:[Anesthesia for a pediatric multivisceral transplant]. 1507 2

A 59-year-old female was referred to our institute for urinary tract infection with septicemia, thrombocytopenia, and hyperglycemia. Plain abdominal X-ray and computed tomography (CT) showed emphysema at the left renal parenchyma and urinary tract along with the perirenal inflammatory changes. These findings suggested emphysematous pyelonephritis in the early phase of occurrence in a diabetic patient. Transurethral catheterization of the left ureter was immediately performed, and occluded cloudy urine was drained. Ureteral stent was left indwelt transurethrally for easy accession in case of occlusion. E. coli was cultured in drained urine. Administration of antibiotics, insulin, and anti-coagulant was performed, and drained urine became clear in several hours. General condition and laboratory findings were improved normally in a week, and CT did not reveal the emphysematous change of the left renal unit at the 11th hospital day.
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PMID:[A case of emphysematous pyelonephritis successfully treated by transurethral retrograde drainage]. 1523 83

Acute pancreatitis is one of the most catabolic of critical illnesses, and its clinical course is often prolonged. Consequently, the need for interventional nutritional support is great. Because of fears that feeding might exacerbate the tryptic autodigestion and disease process, total parenteral nutrition was used exclusively until recent years, when it was recognized that the complications of hyperglycemia and sepsis outweighed nutritional benefits. In clinical practice, enteral feeding has proven superior because it avoids these complications and maintains gut function, but enteral feeding needs to be given in a form that minimizes pancreatic stimulation. This review discusses the advances in our understanding of the pathophysiology of the disease, the results of recent clinical trials of nutritional support, and the challenges that remain in optimizing nutritional management.
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PMID:Nutritional support in acute pancreatitis. 1524 2

A number of important clinical trials focusing on critically ill patients have been completed in the last few years. These trials have been among the first critical care clinical trials to demonstrate mortality reduction in the critically ill. As in any adaptation of evidence-based medicine, it is essential to closely examine the trials and to determine whether the demonstrated benefits can be translated to the individual patient. In addition to the primary outcome, usually survival benefit, it is also important to examine cost-effectiveness. All of the trials examined in this review were able to demonstrate mortality reduction. Most focused on patients with severe sepsis, because this population has been associated with both frequent mortality and increased hospital costs. Some of the interventions, such as small tidal volume mechanical ventilation in patients with acute lung injury or the administration of low-dose corticosteroids for patients with septic shock, are cost-effective and relatively simple to implement. Others, such as use of activated protein C in patients with severe sepsis or "tight" glycemic control in patients with hyperglycemia, require either significant pharmaceutical expenditure or, possibly, additional health care personnel. Nevertheless, the trials discussed represent significant advances in the field of critical care medicine and should at least be considered for implementation in all intensive care units.
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PMID:Evidence-based management of critically ill patients: analysis and implementation. 1527 40


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