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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

For much of the 20th century, lactate was largely considered a dead-end waste product of glycolysis due to hypoxia, the primary cause of the O2 debt following exercise, a major cause of muscle fatigue, and a key factor in acidosis-induced tissue damage. Since the 1970s, a 'lactate revolution' has occurred. At present, we are in the midst of a lactate shuttle era; the lactate paradigm has shifted. It now appears that increased lactate production and concentration as a result of anoxia or dysoxia are often the exception rather than the rule. Lactic acidosis is being re-evaluated as a factor in muscle fatigue. Lactate is an important intermediate in the process of wound repair and regeneration. The origin of elevated [lactate] in injury and sepsis is being re-investigated. There is essentially unanimous experimental support for a cell-to-cell lactate shuttle, along with mounting evidence for astrocyte-neuron, lactate-alanine, peroxisomal and spermatogenic lactate shuttles. The bulk of the evidence suggests that lactate is an important intermediary in numerous metabolic processes, a particularly mobile fuel for aerobic metabolism, and perhaps a mediator of redox state among various compartments both within and between cells. Lactate can no longer be considered the usual suspect for metabolic 'crimes', but is instead a central player in cellular, regional and whole body metabolism. Overall, the cell-to-cell lactate shuttle has expanded far beyond its initial conception as an explanation for lactate metabolism during muscle contractions and exercise to now subsume all of the other shuttles as a grand description of the role(s) of lactate in numerous metabolic processes and pathways.
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PMID:Lactate metabolism: a new paradigm for the third millennium. 1513 Dec 40

A 3 1/2-year-old boy presented with megaloblastic anemia and recurrent episodes of severe lactic acidosis and coma. At age 4 years, he developed sepsis and died; postmortem examination failed to show any gross abnormality in any tissue. Biochemical analysis of muscle showed decreased activities for all respiratory chain enzymes except complex II. Muscle histochemistry revealed diffuse cytochrome c oxidase deficiency. Southern blot analysis of mitochondrial DNA from muscle, liver, and blood showed a heteroplasmic single mitochindrial DNA deletion of 2.4 kb, which removed the genes for cytochrome c oxidase I and II and the transfer ribonucleic acid genes for serine and aspartic acid. Single large-scale deletions in mitochondrial DNA have been associated with Pearson's syndrome, Kearns-Sayre syndrome, and progressive external ophthalmoplegia. This patient's presentation is unusual and suggests an overlap between Pearson's syndrome and Kearns-Sayre syndrome.
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PMID:Mitochondrial DNA deletion in a child with megaloblastic anemia and recurrent encephalopathy. 1516 90

In August 2003 an exceptional heatwave was recorded in Europe. The authors would like to describe 6 patients for which the intensivist was called as a consultant. All patients had a skin temperature >40 degrees C, central nervous system impairment, severe hyponatremia [124.7 mEq/l+/-5.6 (range 117-130)] and severe metabolic acidosis [BE -6.28 mEq/l+/-3.55 (range -9.5-0), HCO3- 17.75 mEq/l+/-3.25 (range 13.4-21.9)]. All patients had decreased platelet count and coagulation abnormalities. Two patients were hypertensive, 4 hypotensive. The heat stress due to the hot environment is characterized by systemic inflammatory response (as in severe sepsis) and hemodynamic impairment (as in hypovolemic shock). The association between hypovolemia and altered microcirculation leads to cell energy failure with metabolic lactic acidosis. The energy failure may induce structural irreversible damage of mitochondria. It is possible to differentiate, during energy failure, the irreversible or reversible condition by volume loading and vasoactive drugs challenge tests. In fact, if the hemodynamic correction is associated with normalization of SvO2 with disappearance of metabolic acidosis, this suggests hemodynamic impairment with intact mitochondrial function. In contrast, if the hemodynamic improvement with normalization of SvO2 is associated and acidosis persists, this suggests irreversible structural mitochondrial damage. The threshold between reversibility and irreversibility is likely time dependent, as suggested by biochemical consideration and by 2 large randomized studies on hemodynamic treatment. The comparative analysis of these 2 studies suggests that the time of intervention may lead to significant differences in mortality. In these patients time is essential.
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PMID:Heat stress: characteristics, pathophysiology and avoidable mistakes. 1525 73

Carnitine and its congeners may regulate the immune networks, and their influence on functions of immune cells predominantly or exclusively relies on carnitine-dependent energy production from fatty acids. A reduced pool of carnitines has been demonstrated in either serum or tissues, or both, from patients with a wide spectrum of disorders characterized by unregulated or impaired immune responses ranging from sepsis syndrome to systemic sclerosis, infection with human immunodeficiency virus, and chronic fatigue syndrome. Furthermore, experimental studies have consistently reported that the deranged immune responses and the less efficient inflammation towards infectious organisms associated with aging may be enhanced or modulated by treatment with carnitines. There is also evidence that carnitine deprivation could adversely affect the course of the sepsis syndrome, at least in experimental models, and preliminary studies suggest that carnitine deficiency is ultimately implicated in the pathophysiology of endotoxin-mediated multiple organ failure. Several data indicate that carnitine deficiency is a contributing factor to the progression of infection with human immunodeficiency virus, and carnitine therapy in those patients could counteract the unregulated process of lymphocyte apoptosis and improve CD4 counts. Some case reports have suggested the use of carnitine for the treatment of the severe lactic acidosis that complicates in some patients the use of reverse transcriptase inhibitors.
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PMID:Carnitines and its congeners: a metabolic pathway to the regulation of immune response and inflammation. 1559 Oct 10

D-lactate is normally present in the blood of mammals at nanomolar concentrations due to methylglyoxal metabolism; millimolar d-lactate concentrations can arise due to excess gastrointestinal microbial production. Grain overload in ruminants, short-bowel syndrome in humans, and diarrhea in calves can all result in profound D-lactic acidemia, with remarkably similar neurological manifestations. In the past, D-lactate was thought to be excreted mainly in the urine, and metabolized slowly by the enzyme d-alpha-hydroxy acid dehydrogenase. More recent studies reported that mammals have a relatively high capacity for D-lactate metabolism and identified a putative mammalian D-lactate dehydrogenase. A growing body of literature is also emerging describing subclinical elevation of D-lactate as an indicator of sepsis and trauma. This article describes advances in the understanding of D-lactate metabolism, D-lactic acidosis in ruminants and humans, and subclinical elevation of d-lactate.
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PMID:D-lactate in human and ruminant metabolism. 1598 39

Nitric Oxide (NO) plays a controversial role in the pathophysiology of sepsis and septic shock. Its vasodilatory effects are well known, but it also has pro- and antiinflammatory properties, assumes crucial importance in antimicrobial host defense, may act as an oxidant as well as an antioxidant, and is said to be a "vital poison" for the immune and inflammatory network. Large amounts of NO and peroxynitrite are responsible for hypotension, vasoplegia, cellular suffocation, apoptosis, lactic acidosis, and ultimately multiorgan failure. Therefore, NO synthase (NOS) inhibitors were developed to reverse the deleterious effects of NO. Studies using these compounds have not met with uniform success however, and a trial using the nonselective NOS inhibitor N(G)-methyl-l-arginine hydrochloride was terminated prematurely because of increased mortality in the treatment arm despite improved shock resolution. Thus, the issue of NOS inhibition in sepsis remains a matter of debate. Several publications have emphasized the differences concerning clinical applicability of data obtained from unresuscitated, hypodynamic rodent models using a pretreatment approach versus resuscitated, hyperdynamic models in high-order species using posttreatment approaches. Therefore, the present review focuses on clinically relevant large-animal studies of endotoxin or living bacteria-induced, hyperdynamic models of sepsis that integrate standard day-to-day care resuscitative measures.
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PMID:Nitric oxide synthase inhibition in sepsis? Lessons learned from large-animal studies. 1603 66

Despite the commonly accepted indications for hemodialysis and extracorporeal depuritive techniques, some clinicians have come to rely on blood purification for clinical states where the targeted substance for removal differs from uremic waste products. Over the last decade, a number of studies have emerged to help define the application of extracorporeal blood purification (ECBP) to these "nonuremic" indications. This review describes the application of extracorporeal blood purification in clinical states including sepsis, rhabdomyolysis, congestive heart failure, hepatic failure, tumor lysis syndrome, adult respiratory distress syndrome, intravenous contrast exposure, and lactic acidosis. Additional comments are provided to review existing literature on thermoregulation and osmoregulation, including acute brain injury.
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PMID:The current state of nonuremic applications for extracorporeal blood purification. 1619 Nov 78

Sepsis and septic shock continue to contribute to our workload and stimulate our research activities although many fundamental questions remain. Studies reported on here focus on inotrope use and a novel way of predicting inotrope response. Continuing this theme more fundamental work is reported examining the mitochondrial respiratory chain and the effects of sepsis coupled with interesting work on lactic acidosis. Troponin raises its head again and we are still left quizzing over its value in the ICU. Finally we discuss a paper on the outcome of the obese patient on a general ICU. Like sepsis a continuing challenge.
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PMID:Recently published papers: treating sepsis, measuring troponin and managing the obese. 1635 33

The triggering receptor expressed on myeloid cell type 1 (TREM-1) is a cell surface molecule that has been identified on both human and murine polymorphonuclear neutrophils and mature monocytes. The activation of TREM-1 in the presence of microbial components amplifies the inflammatory response and may be responsible for the hyperresponsiveness observed during the initial stage of sepsis. To investigate the effect of the modulation of the TREM-1 pathway during experimental murine sepsis, we used analogue synthetic peptides derived from the extracellular moiety of TREM-1. The TREM-1 ligand was expressed on both peritoneal and peripheral neutrophils during experimental peritonitis in mice. The TREM-1 peptides inhibited the recognition by TREM-1 of its ligand and protected endotoxinic mice from death. In septic rats, the TREM-1 peptides improved the hemodynamic status, attenuated the development of lactic acidosis, modulated the production of such proinflammatory cytokines as tumor necrosis factor alpha and interleukin-1beta, and improved survival. The protective effect of these peptides on arterial pressure could partly be explained by a decreased production of nitric oxide. These data suggest that in vivo modulation of TREM-1 might be a suitable therapeutic tool for the treatment of sepsis.
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PMID:Modulation of the triggering receptor expressed on the myeloid cell type 1 pathway in murine septic shock. 1662 20

Peritoneal dialysis (PD)-associated peritonitis rates have decreased significantly in recent years, especially Staphylococcus epidermidis and Staphylococcus aureus infections. Rates of gram-negative, polymicrobial, and fungal peritonitis have remained steady. The reported mortality of gram-negative and polymicrobial peritonitis varies widely (4%-50%). Most likely, the reason for this variability is that prognosis depends on the underlying etiology more than the specific microorganisms isolated. Gram-negative, polymicrobial, and fungal infection have variable association with documented visceral disease, and the highest mortality occurs in reports with the highest prevalence of intra-abdominal pathology. The odds ratio of death in PD patients with documented abdominal catastrophe and peritonitis is reported to be 20:1 compared with all other causes. Further reductions in PD-associated peritonitis mortality are likely to depend on earlier diagnosis and better management of intra-abdominal pathology. Presentation with hypotension, sepsis, lactic acidosis, and/or elevation of peritoneal fluid amylase should raise immediate concern for "surgical" peritonitis. Suspicion for visceral disease should also be high in patients with gram-negative, polymicrobial, and fungal infection or those who fail to improve rapidly as judged by clinical signs and symptoms, cell counts, and repeat cultures. Nonlocalizing physical examination and negative or nonspecific results of abdominal computed tomography do not rule out serious intra-abdominal disease. Immediate initiation of broad antibiotic coverage including for anaerobic infection is indicated when bowel pathology is suspected. Urgent surgical consultation, with active discussion and participation by the nephrologist, is advisable when visceral pathology is suspected and the patient is unstable or fails to improve rapidly.
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PMID:Diagnosis and management of enteric disease and abdominal catastrophe in peritoneal dialysis patients with peritonitis. 1681 32


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