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

The cardiopulmonary support system is an extracorporeal device that allows for rapid cardiopulmonary support of the critically ill patient in the intensive care unit. It provides immediate and complete support of cardiac and pulmonary functions to maintain perfusion to vital organs in patients who are severely physiologically compromised (eg, in cardiogenic shock, adult respiratory distress syndrome or pulmonary edema). Successful cardiopulmonary support requires systemic anticoagulation, percutaneous venous and arterial cannulation and careful monitoring by the critical care team to maintain adequate tissue perfusion and oxygenation. Although patient mortality can occur secondary to bleeding, embolism or sepsis, this technique provides life-sustaining circulatory and respiratory support until definitive treatment can be initiated.
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PMID:Cardiopulmonary support in the intensive care unit. 835 73

We administered teicoplanin as specific antibiotic therapy for nosocomial "ICU specific" infections with methicillin-resistant Staphylococcus aureus and epidermidis (MRSA-MRSE). The above mentioned drug has been given to 20 patients (15 newborns and 5 not-newborns) admitted into intensive care unit during the years 1988, 1989, 1990 with MRSA-MRSE localized and/or systemic infection, affected by severe disease (RDS, pulmonary edema, congenital cardiac disease, cystic fibrosis) undergoing invasive procedures which presented high nosocomial infective risk (tracheal intubation, mechanical ventilation, venous and arterial cannulation, total parenteral nutrition, etc.). Complete recovery from systemic or localized infection (sepsis, low respiratory tract infection, high respiratory tract infection) occurred in 19 out of 20 patients, with a rate of success of 95%. Teicoplanin treatment lasted from a minimum of nine days to a maximum of thirty days. The dose was 5-6 mg/kg/die in one administration for the first three days, then 4 mg/kg/die. The tolerability of teicoplanin has proven satisfactory, since we had no major side effects during treatment and follow up.
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PMID:[Teicoplanin therapy in neonatal and pediatric intensive therapy]. 138 7

The treatment of septic shock remains a major problem in surgical practice. Current research on the pathogenesis of the sepsis syndrome focuses on the effects of the lipopolysaccharide constituents of bacterial endotoxin. Evidence suggests that endotoxin induces a whole-body inflammatory response that in turn mediates organ damage, eventually leading to multiorgan failure. The first organ in which failure is usually apparent is the lung, with the appearance of non-cardiogenic pulmonary oedema as part of the adult respiratory distress syndrome. Inflammatory cells involved in lung injury include neutrophils and macrophages, which release mediators such as elastase, oxygen radicals and cytokines. This review summarizes current experimental work on how endotoxin leads to lung injury, based on its effects in animals and patients. Present knowledge suggests that future treatment of septic shock might involve inhibiting the body's inflammatory response to endotoxin. Possible ways of doing this are discussed.
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PMID:Endotoxin, septic shock and acute lung injury: neutrophils, macrophages and inflammatory mediators. 833 Jan 85

Although tumor necrosis factor-alpha (TNF) is a key mediator in the pathophysiology of sepsis and septic shock, its role in lung microvascular injury is controversial. In isolated blood-perfused rabbit lungs, we studied the microvascular effects of human recombinant TNF by measuring the capillary filtration coefficient (Kf,c) as an index of microvascular leakiness and the arterial and venous resistances and occlusion pressures to define the microvascular pressure profile. At the end of the experiments, the lung wet-to-dry weight ratio (W/D) was determined as an index of edema. TNF increased the pulmonary venous resistance slightly but did not affect Kf,c or W/D. Furthermore, TNF at different doses failed to increase W/D less than or equal to 8 h after in vivo administration. Our data suggest that 1) the pulmonary microvascular response to TNF differs from the systemic response, which is characterized by arteriolar vasodilation, and 2) TNF is insufficient to cause lung edema, both in vivo and in vitro. Thus the development of lung microvascular injury may require the combined action of TNF and other mediators.
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PMID:Tumor necrosis factor-alpha does not cause lung edema in rabbits. 150 65

TNF is a major mediator in the pathogenesis of endotoxic shock, and its inhibition has a protective effect in various animal models of sepsis or endotoxin (lipopolysaccharide, LPS) toxicity. LPS treatment also induces an oxidative damage mediated by increased production of reactive oxygen intermediates. N-Acetylcysteine (NAC) is an antioxidant and a precursor of the synthesis of glutathione (GSH) and was reported to protect against LPS toxicity and LPS-induced pulmonary edema. In this study we investigated the effect of NAC on TNF production and LPS lethality in mice. The results indicated that oral administration of NAC protects against LPS toxicity and inhibits the increase in serum TNF levels in LPS-treated mice. The inhibition was not confined to the released form of TNF, since NAC also inhibited LPS-induced spleen-associated TNF. On the other hand, the inhibitor of GSH synthesis, DL-buthionine-(SR)-sulfoximine (BSO), had the opposite effect of potentiating LPS-induced TNF production, and this was associated with a decrease in liver GSH levels. Repletion of liver GSH with NAC reversed this effect. NAC was also active in inhibiting TNF production and hepatotoxicity in mice treated with LPS in association with a sensitizing dose of Actinomycin D. These data indicate that GSH can be an endogenous modulator of TNF production in vivo. On the other hand, NAC pretreatment did not inhibit other effects of LPS, particularly induction of serum IL-6, spleen IL-1 alpha, and corticosterone, in the same experimental model, suggesting that the observed effect could be specific for TNF.
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PMID:N-acetylcysteine and glutathione as inhibitors of tumor necrosis factor production. 154 68

Gram-negative sepsis has dramatically increased in frequency throughout the twentieth century in the United States. Currently, approximately 200,000 patients develop gram-negative sepsis each year in this country. Of these, about one-quarter develop the adult respiratory distress syndrome (ARDS). Among these critically ill patients, mortality is estimated at 60%-90%. In the complex series of events leading to acute lung injury in gram-negative sepsis, endotoxin is the proximal mediator. Although endotoxin may be capable of causing direct injury to the pulmonary endothelium, its primary role is as a trigger activating inflammatory agents, including complement, neutrophils, and platelets, and inducing the production of cytokines and arachidonic acid metabolites. The end results are impairment of the endothelial barrier, diffusely increased capillary permeability, and adherence of neutrophils to the endothelium with subsequent migration into the tissues. The consequent clinical syndrome is one of acute respiratory distress with pulmonary edema, poorly compliant lungs, and refractory hypoxemia. Endothelial injury often becomes widespread, leading to the failure of multiple organs, including the kidneys, brain, intestine, and liver. Conventional therapy consists of supplemental oxygen, positive end-expiratory pressure, inotropic agents, fluid management, and antibiotics aimed at the offending pathogen. Recent discoveries regarding the mediators of sepsis as well as the expansion of the biotechnological armamentarium have provided clinicians with a plethora of new tools with which to manipulate the host's inflammatory response. The challenge for the next decade will be to ensure the safety, efficacy, and cost-effective use of these expensive but potentially lifesaving immunomodulators, singly or in combination, as adjuvant therapy.
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PMID:Gram-negative sepsis and the adult respiratory distress syndrome. 162 78

Ventilatory depression and apnea are well-known early pulmonary responses of sepsis in infants, yet their underlying mechanisms are not understood. To further elucidate the pathophysiology, we induced Escherichia coli septicemia in piglets and studied the sequential changes in intrapulmonary shunt (QS/QT), physiological dead space (VD/VT), minute ventilation (VE), and blood gases for up to 6 hours of lethal sepsis. Lung lymph was also collected and extravascular lung water (EVLW) was measured. Histology confirmed that interstitial edema developed 1 hour after E. coli infusion. These data suggest that high permeability pulmonary edema and hypoxemia following early intrapulmonary shunt increase may be the causes of septic ventilatory depression.
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PMID:[An experimental study on the pathophysiology of septic ventilatory depression]. 165 Jun 39

The alterations in lung glutamine (GLN) metabolism that occurs in the endotoxin-injured lung were studied in rats and subsequently correlated with flux changes that occur in patients with the adult respiratory distress syndrome (ARDS). Measurements in animals were made at various time-points following the administration of endotoxin, while studies in surgical patients were done in a group of healthy controls, in patients with "early" sepsis who had normal chest x-ray films, and in patients with radiographic and physiologic evidence of ARDS. In healthy control rats, net amounts of GLN are released by the lungs into the systemic circulation. This release rate doubled 30 minutes after intravenous endotoxin (1,580 +/- 320 nmol GLN/100 g BW/min vs. 736 +/- 179 in controls, p less than 0.01) but glutamine synthetase activity was unchanged, suggesting an outpouring of cellular glutamine stores. Two hours after endotoxin treatment, this accelerated fractional release of glutamine by the lungs was no longer detected. By the 12-hour time-point, the lungs reversed to an organ of net glutamine balance (234 +/- 248 nmol/100 g BW/min, p less than 0.05 vs. controls and ENDO30 min) despite a more than two-fold increase in glutamine synthetase activity (p less than 0.01). Simultaneously, lung weights were increased by 21% (p less than 0.01) and histologic examination showed an interstitial infiltrate and pulmonary edema. Similar observations were made in humans; patients with "early" sepsis exhibited a marked increase in lung glutamine release, while patients with ARDS demonstrated glutamine balance across the lungs (4,030 +/- 910 nmol GLN/kg BW/min vs. 637 +/- 496 in ARDS, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Glutamine metabolism by the endotoxin-injured lung. 167 90

We compared the early and late pulmonary effects of human recombinant tumor necrosis factor (TNF) and interleukin 1 (IL-1) challenges in awake dogs with chronic tracheostomies. Serial blood gas analysis, bronchoalveolar lavage (BAL) with cell and protein analysis, intravascular catheter hemodynamics, and radionuclide left ventricular ejection fractions (LVEF) were determined before and after infusion of TNF (60 micrograms/kg body wt, n = 8), IL-1 (1,000 micrograms/kg body wt, n = 6), or heat-inactivated IL-1 (n = 6, controls). Controls given heat-inactivated IL-1 had no changes (P = NS) in any pulmonary parameter throughout the study. Animals given IL-1 had a transient increase (P less than 0.05) in BAL neutrophil concentration 1 day after infusion but no other changes (P = NS) in pulmonary function throughout the study. Animals given TNF had early (0-4 h) decreases (P less than 0.05) in arterial PO2, increases (P less than 0.05) in physiological shunt fraction and alveolar-to-arterial PO2 gradient, and a high mortality rate (50%). In TNF animals, volume challenges at 4 h were associated (P less than 0.05) with death and noncardiogenic pulmonary edema. In TNF survivors, hypoxemia persisted for 2-3 days and was associated with increases (P less than 0.05) in alveolar protein and neutrophil concentration on days 1 and 3, respectively, which in survivors returned to near normal over 6-21 days. Animals challenged with TNF and not IL-1 had reversible depression of LVEF similar in time course to abnormalities in arterial PO2. In this study, TNF (but not IL-1) challenges were lethal and produced acute pulmonary dysfunction sustained over days (reversible in survivors) that was similar to that seen in human septic shock. The ability of TNF to induce pulmonary injury similar to bacterial shock suggests that TNF is a key mediator of sepsis-induced lung injury. Furthermore, because TNF challenge induced both sustained pulmonary and cardiac injury, TNF may be a common pathway for the multiple organ dysfunction that occurs during septic shock.
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PMID:TNF but not IL-1 in dogs causes lethal lung injury and multiple organ dysfunction similar to human sepsis. 176

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


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