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

There is considerable evidence to implicate aggressive species of oxygen in the pathogenesis of organ dysfunction consequent to sepsis and septic shock. The inflammatory process appears to participate ubiquitously in this setting. A characteristic of inflammation is the involvement of activated neutrophils and their generation of aggressive oxygen species. Such species may both directly injure cells proximal to the oxidant generating cells, and may inactivate any proteolytic mechanisms normally protective against proteolytic injury caused by neutrophil elastase and other proteolytic enzymes released during inflammation. The offending agent in sepsis is most commonly envisioned as bacterial lipopolysaccharide, or endotoxin. Infusion of endotoxin into animals can reproduce much of the pathophysiology of sepsis and septic shock. In addition, administration of endotoxin to cultured cells, particularly endothelial cells, can cause responses consistent with a sequence of events that occurs in intact animals and humans. In both experimental models, it appears that aggressive oxygen species are important actors in the scenario eventuating in cell or organ injury. Of importance, the toxic consequences of these free radicals probably occurs in relatively protected spaces, including microenvironments created by close adherence between inflammatory cells and endothelial cells and the cell interior. For those reasons, the potential for antioxidants as therapy should include consideration of the volume of distribution of such substances. It is probably important that antioxidants access excluded spaces including cell interiors in order to have their maximum effect in this setting. We have studied ina preliminary way the effects of n-acetyl-cysteine, a highly permeable free radical scavenger and anti-oxidant, in patients with established ARDS.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Oxygen radicals--an important mediator of sepsis and septic shock. 179 73

Although the shock syndrome is recognized as a form of "mediator poisoning", a plethora of details is hardly converging into a coherent concept of chronological and molecular order. As a model for organ failure in septic shock, three alternative experimental approaches with a common pathology are presented: When galactosamine-sensitized mice receive either lipopolysaccharide or leukotriene D4 or tumor necrosis factor alpha they develop fulminant hepatitis within few hours with a lethal outcome within one day. Detailed pharmacological intervention studies allow to conclude that endotoxin-induced leukotriene D4 release induces a transient ischemia by the known vasoconstrictive action of this eicosanoid. A following reperfusion/reoxygenation phase gives rise to superoxide formation which inactivates alpha 1 proteinase inhibitor. Thus a serine protease becomes active which is responsible for the processing of a monocytic tumor necrosis factor alpha precursor to be released into the circulation after proteolytic cleavage. By this sequence the final central mediator of shock and sepsis becomes systematically abundant. The concept arising from these studies reconciles previously known findings and provides a link between the role of reactive oxygen species in inflammation, the balance of proteases and antiproteases in the extracellular space and the release of the cytokine tumor necrosis factor in sepsis and shock.
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PMID:Reactive oxygen species, antiproteases, and cytokines in sepsis. 179 93

In 40 intensive care patients, tissue oxygen partial pressure distribution within skeletal muscle was measured in order to estimate peripheral oxygen availability. In septic patients with multiple organ failure (n = 20) mean skeletal muscle pO2 was abnormally high (48.8 +/- 8.5 mmHg, p less than 0.001) in contrast to patients with limited infection without sepsis (28.3 +/- 5.9 mmHg, n = 10). Mean muscle pO2 also discriminated between septic and cardiogenic shock (22.6 +/- 6.9 mmHg, p less than 0.001). The characteristic pattern of oxygen availability in septic patients--but not in patients with limited infection--was high skeletal muscle pO2 high whole body oxygen delivery and low whole body oxygen extraction, which was not influenced by the type of pathogenic agent of sepsis. In our patients in severe stage of sepsis, we did not observe local skeletal muscle hypoxia due to microcirculatory disorder. High mean skeletal muscle pO2 suggested reduced oxygen consumption within tissue rather than reduced oxygen transport to tissue in sepsis.
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PMID:Peripheral oxygen availability within skeletal muscle in sepsis and septic shock: comparison to limited infection and cardiogenic shock. 180 Mar 70

For health, well perfused tissues, oxygen uptake is determined primarily by metabolic need rather than by oxygen supply. Tissue hypoxia supervenes when tissue oxygen tension (PO2) falls below a critical point, and the point where this occurs can be predicted from the systemic oxygen delivery or extraction ratio. A growing body of evidence suggest that tissue oxygen extraction may be impaired in adult respiratory distress syndrome (ARDS) and sepsis. In these syndromes the minimum oxygen delivery needed to maintain a normal oxygen uptake appears to be increased, as tissues become hypoxic despite high levels of delivery. However, controversy surrounds every phase of this observation, from its experimental basis, to potential causes, to its implications for patient care. In this review, we discuss the physiology of oxygen transport, the determinants of tissue oxygenation in normal and pathological states, and the therapeutic implications of oxygen transport.
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PMID:Oxygen delivery to tissues. 180 74

The primary function of the cardio-respiratory system is to meet the oxygen demands of the various organs and tissues and to remove metabolic wastes. The cellular O2 supply in the critically ill patient afflicted with severe infection, sepsis or ARDS is impaired not only by reduced O2 transport to the tissue due to myocardial depression caused by inadequate preloading and depressed contractility, but also by inadequate blood flow at the regional and microcirculatory levels. To obtain adequate tissue oxygenation despite derangements of the microcirculation, it is useful to aim for a hyperdynamic circulatory state that provides a supramaximal O2 transport. The best way to achieve this goal is first to optimize cardiac filling pressures, i.e. to the upper range of normal, and then to improve cardiac output using inotropic support. Only when the arterial pressure remains too low despite these measures is the use of vasopressors indicated.
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PMID:[Oxygen transport and tissue oxygenation in critically ill patients--value of volumes and vasoactive substances]. 181 5

Perioperative circulatory disorders in patients may take the form of a transitory reduction in oxygen transport to the peripheral tissues (pre-shock), manifest circulatory insufficiency in the presence or absence of concomitant heart insufficiency or general congestive heart failure due to the destabilization of an preexisting heart disease. The least problematical stage in this programme of therapy is the treatment of transitory perioperative circulatory insufficiency by manipulation of the oxygen transport system using the following means: comparative volume optimization [according to the central venous pressure (CVP)], positive inotropic support with dobutamine (5-10 micrograms.kg-1.min-1), monitoring of the blood pressure, heart rate and oxygen consumption and, in severe cases, insertion of a Swan-Ganz catheter. In manifest circulatory insufficiency, sepsis or acute congestive heart failure, the Swan-Ganz catheter seems to be obligatory. In such cases, the positive inotropic therapy is based on catecholamines of medium (dobutamine) or high (epinephrine) positive inotropic efficacy, as a normal pattern and functioning of beta-adrenoceptors can be assumed in such cases if there is no history of cardiac insufficiency. The systemic vascular resistance (SVR) is adjusted to 800-1200 n.s.cm-5 to relieve the working capacity of the heart and to maintain sufficient perfusion pressure by means of constrictors (phenylephrine, norepinephrine) or dilators [nifedipine, nitroglycerin or, if necessary, angiotensin-converting-enzyme (ACE) inhibitors].(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Therapeutic concepts in treatment of circulatory and heart failure in surgery]. 181 8

Twenty years have now elapsed since Ashbaugh and Petty first described the syndrome of acute respiratory failure associated with a wide spectrum of clinical conditions. During the past two decades, significant advances have emerged in our understanding of the clinical conditions associated with the syndrome and the pathophysiological changes affecting the alveolar-capillary membrane responsible for the characteristic non-cardiogenic pulmonary edema. Recent data have reaffirmed the notion that mortality rates in ARDS remain in excess of 60 percent, essentially unchanged since the first description of the syndrome, despite all the advances in critical care medicine in the intervening years. The incidence of ARDS has been difficult to establish because of lack of agreement on precise definition criteria. The lack of agreed definition criteria has hampered evaluation of the natural history of the syndrome, its epidemiology and mortality rates, and the efficacy or otherwise of a variety of therapeutic interventions. This review will highlight a recent, clinically appropriate, expanded definition of ARDS. New understandings of the roles of sepsis and multi-system organ failure in mortality associated with ARDS will be discussed. Several mediators, both locally in the lung and in the systemic circulation, have been implicated in the pathophysiology of ARDS. This review will discuss the evidence for and against neutrophils, platelets, cytokines derived from mononuclear cells and macrophages, complement, prostaglandins/leukotrienes, oxygen-derived radicals, and a variety of proteases. Current treatment strategies for ARDS are designed to increase tissue oxygen delivery by increasing arterial oxygen tension and cardiac output while simultaneously attenuating the pulmonary and systemic injury by appropriate pharmacologic and surgical interventions. Recent data advocating pharmacological augmentation of cardiac index and oxygen delivery will be highlighted. The persistently high mortality rates of 60-70 percent in patients with established ARDS have provoked recurring interest in new techniques of providing mechanical ventilation. Most studies have shown, however, that mortality in ARDS patients is attributable mainly to sepsis and multi-system organ failure rather than primarily to respiratory failure. Established and speculative intervention to reduce sepsis and multi-system organ failure associated with ARDS will be featured in the review.
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PMID:Acute respiratory distress syndrome--two decades later. 181 55

Transfusion, either with whole blood or blood components is frequently needed in the neonatal intensive care. Certain aspects are very important to consider. Citrated blood is preferred to heparinized blood. Transfusion must be rational, either with whole blood or blood components. Whole blood is only indicated for repletion of blood volume, exchange transfusion and certain cases in which no blood component needed is available. To improve oxygen carrying capacity, to stop bleeding due to coagulation defect, thrombocytopenic bleeding due to depressed platelets production and to counter gram negative septicemia, blood component is indicated to obtain optimal effects with minimal side effects.
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PMID:Transfusion in the newborn. 184 59

Six patients with end-stage emphysema (age 44 +/- 2 years) underwent double lung transplantation (Tx) from June 1988 through May 1990. All suffered from severe inanition and required oxygen therapy. The ischemic time was 193 +/- 28 minutes. Post-Tx immune suppression was OKT3 (14 days), cyclosporine (trough levels of 150 +/- 25 ng/ml), azathioprine to keep WBC at 3,000 to 5,000/cu mm (1 to 3.0 mg/kg/day) and following OKT3, a tapering prednisone regimen. Two rejection episodes that occurred in two patients on post-Tx day 5 and 10 were treated with bolus doses of methylprednisolone. The mean hospital stay was 32 +/- 7 days (range, 20 to 69 days). Four patients required treatment of cytomegalovirus (CMV) infection: gastritis (+donor, +recipient) in one and CMV pneumonia in two (+donor, -recipient). A fourth (+donor, -recipient) had right-sided Candida empyema six weeks post-Tx, developed CMV and staphylococcal sepsis, and died 64 days post-Tx. One patient required pyloroplasty eight weeks post-Tx and one patient underwent tracheal suture line repair at eight weeks. During a follow-up of 81 patients months (range, 8 to 24 months), one patient had developed Epstein-Barr viral (EBV) induced lymphoproliferative disease in the lung and one patient had developed EBV lymphoma. Three patients are at work, one is continuing rehabilitation, and one is at home. Double lung Tx offers a definitive benefit to patients with emphysema; however, a prolonged postoperative course can be expected. Viral infections remain serious but treatable problems.
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PMID:Treatment of end-stage chronic obstructive pulmonary disease with double lung transplantation. 184 23

Oxygen consumption (VO2) is dependent on oxygen delivery (DO2) in septic shock. Local hypoxia with later secondary organ failure may develop, however, despite an often hyperdynamic circulation. The splanchnic organs seem to be of vital importance in this context. In experiments performed in pigs we compared total body VO2 and DO2 with oxygen consumption and delivery in the gastrointestinal organs and the liver in two different shock states: (1) septic shock induced by peritonitis (n = 6) and (2) hemorrhagic shock (n = 6). Another group of six animals not in shock served as controls. Total, gastrointestinal, and liver DO2 decreased in a similar pattern in both septic and hemorrhagic shock. Gastrointestinal and liver VO2 increased in sepsis, whereas it was unchanged in hemorrhage. In the later phase of sepsis, liver VO2, but not gastrointestinal VO2, again decreased, because liver oxygen extraction was almost total and liver DO2 decreased further. The development of flow-dependent liver hypoxia was reflected in a decrease in liver lactate turnover (increased liver lactate release) during late sepsis. Early hypoxia in the splanchnic region is suggested as a plausible mechanism behind the development of secondary organ failure, especially in sepsis.
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PMID:Splanchnic oxygen consumption in septic and hemorrhagic shock. 189 92


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