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

We investigated the pathogenesis of lung injury in sepsis (septic adult respiratory distress syndrome) by focusing on the functional changes of alveolar macrophages (AMs). Sepsis was induced in male WK rats by cecal ligation and puncture. Histological examination of the lungs from this experimental model revealed edematous change at 24 h after the surgery. The protein and endotoxin concentrations in the bronchoalveolar lavage fluid (BALF) increased with time after the surgery. The time course studies of AM function after surgery indicated that AMs from septic rats were activated by endotoxins. Specifically, this was suggested by the finding that AM adherence to and spreading on a plastic dish had increased. On stimulation, these AMs enhanced generation of superoxide anions and increased release of lysosomal enzymes, such as beta-glucuronidase. On the other hand, AMs in sepsis generated much smaller amounts of arachidonate lipoxygenase metabolites, such as leukotriene B4 (LTB4) and 12- and 5-hydroxyeicosatetraenoic acids (HETEs), on stimulation than did AMs from sham rats or untreated rats. However, the concentrations of immunoreactive LTC4 in the BALF of septic rats seemed to be higher than in untreated rats. It is suggested that the AMs of septic rats released lipoxygenase metabolites in alveoli and that these AMs could not be stimulated in vitro. These functional changes in the AMs of septic rats progressed along with the sepsis. These results implicate AMs in the development and progression of septic lung injury by releasing superoxide anions, beta-glucuronidase, and arachidonate metabolites. Furthermore, we speculate that reduced production of LTB4 by septic AMs may increase host susceptibility to severe pulmonary infection during septic ARDS.
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PMID:Characteristics of alveolar macrophages in experimental septic lung. 132 90

Acute respiratory failure in pregnancy is an important cause of maternal and fetal morbidity and mortality. Causes include: ARDS, venous air embolism, beta-adrenergic tocolytic therapy, asthma, thromboembolic disease, pneumothorax, and pneumomediastinum. The most common predisposing diseases for ARDS complicating pregnancy are sepsis, pneumonia, aspiration of gastric contents, and amniotic fluid embolism. Knowledge of normal maternal-fetal physiology and determinants of fetal oxygen delivery (uterine blood flow, placental transfer, fetal circulation) can help sustain normal fetal development, usually without compromising maternal care. The increased microvascular permeability seen in ARDS is likely mediated by neutrophils, proinflammatory mediators (e.g., tumor necrosis factor, interleukin-1, arachidonic acid metabolites) and activation of the complement cascade. Treatment of respiratory failure in pregnancy is largely supportive, including mechanical ventilation, hemodynamic support, nutrition, and prophylaxis against thromboembolism. No specific therapy has as yet been proven effective for ARDS, other than treating the underlying cause. Respiratory failure from status asthmaticus is treated with vigorous bronchodilator therapy, high-dose glucocorticosteroids, magnesium sulfate, and careful ventilator management. Occasionally, more experimental therapies (e.g., isoproterenol infusion, halothane anesthesia) are indicated. Certain strategies can help prevent respiratory failure from aspiration of gastric contents, beta-adrenergic tocolytic therapy, and thromboembolic disease.
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PMID:Acute respiratory failure in pregnancy. 136 44

The most common predisposing factor for development of the adult respiratory distress syndrome is gram-negative sepsis. Our previous studies have shown that a single infusion of Escherichia coli endotoxin into sheep causes early sequestration of lymphocytes in the lungs' microcirculation. In this report, we examined the effects of endotoxin on sheep lymphocyte adherence to sheep pulmonary microvascular endothelial cells in vitro. Endothelial cells were exposed to endotoxin, and subsequent adherence of 51Cr-labeled lymphocytes was measured in a monolayer adhesion assay. Endotoxin enhanced adherence of lymphocytes isolated from blood and caudal mediastinal node (CMN) lymph in a time- and dose-dependent manner. Adherence of CMN lymphocytes increased from a control value of 13.6 +/- 1.6% to 29.9 +/- 3.1% after 4 h of treatment with 1 microgram/ml endotoxin. Both B and T lymphocytes contributed to the increased adherence. Pretreatment of the endothelial cells with cycloheximide revealed that the endotoxin-enhanced adherence was partially dependent upon protein synthesis. Morphologic studies revealed that enhanced adherence was accompanied by a 5-fold increase in migration of lymphocytes between endothelial cells. In contrast to human umbilical vein endothelial cells, antibodies to the known lymphocyte adherence molecules, lymphocyte function-associated antigen (LFA-1), CD-44, and the lymphocyte homing receptor (LECAM-1), were ineffective in blocking adherence to the sheep pulmonary endothelial cells. We conclude that the acute sequestration of lymphocytes in the pulmonary microcirculation of sheep after endotoxin administration is due to increased adhesive properties of the endothelial cells. Our data suggest that this adherence is mediated by as yet undescribed mechanisms that may be unique to pulmonary microvascular endothelium.
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PMID:Endotoxin enhancement of lymphocyte adherence to cultured sheep lung microvascular endothelial cells. 137 87

Under mechanical volume-controlled ventilation, the intensive care patient can develop intrinsic positive end-expiratory pressure (iPEEP); that is, the passive expiration is terminated by the following inspiration before the alveolar pressure comes to its physical equilibrium value. We present a mathematical method to estimate this alveolar dynamic iPEEP breath by breath, without the need of a maneuver. We tested it in paralyzed patients ventilated for adult respiratory distress syndrome after multiple trauma and/or sepsis, and we compared the results obtained with the new mathematical method with those from the occlusion method introduced by Pepe and Marini. The results agreed well (median difference of 0.8 mbar in 201 investigations in 12 patients). However, the mathematically determined values, representing dynamic iPEEP, are systematically slightly smaller than those measured by the occlusion maneuver. A variation of expiratory time suggests that this difference might be due to mechanical time-constant inhomogeneity, viscoelastic processes, or other mechanisms showing time dependence.
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PMID:Intrinsic PEEP monitored in the ventilated ARDS patient with a mathematical method. 139 69

Extracorporeal membrane oxygenation (ECMO) is effective for newborns with pulmonary failure unresponsive to conventional therapy. However, ECMO for the older child and adult has been controversial and not widely utilized. Over 4 years, 24 patients (aged 4 months to 16 years; 11 boys, 13 girls) underwent venoarterial ECMO (duration, 7 to 19 days) for respiratory failure. The diagnoses were: viral pneumonia (7), hydrocarbon aspiration (6), sepsis with adult respiratory distress syndrome (ARDS) (2), bacterial pneumonitis (2), tracheal stenosis (1), bilateral pulmonary contusion (1), diaphragmatic hernia with ARDS (1), ketoacidosis with ARDS (1), pulmonary artery injection of hydrocarbon (1), drowning (1), and epiglottis with barotrauma (1). Pre-ECMO blood gas ranges (and means) were PO2 18 to 65 (46), and PCO2 47 to 112 (65). Nineteen patients received dopamine, dobutamine, or other inotrope for associated cardiac and/or renal failure. Cannulation for ECMO was through neck or groin vessels in 17, and sternotomy in 7. ECMO flow rates were 150 to 250 mL/kg/min, to maintain PO2 greater than 100 and PCO2 less than 40. Nine patients (41%) survived ECMO, with eight long-term survivors, (4 hydrocarbon aspiration or injection, 1 pulmonary contusion, 1 viral pneumonia, 1 ARDS, 1 barotrauma), three of whom have mild neurological deficit. All patients with sternotomy, and 8 of 15 with neck and/or groin cannulation, required 1 to 5 explorations for hemorrhage while on ECMO. All survivors had primarily pulmonary failure; patients with combinations of pulmonary, cardiac, and renal failure did not survive. ECMO can be life-saving in the child with isolated pulmonary failure, but its efficacy in patients with multiorgan failure is uncertain.
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PMID:Prolonged extracorporeal support for nonneonatal respiratory failure. 140 44

Excessive hydrogen peroxide (H2O2) generation appears to contribute to the development of the adult respiratory distress syndrome (ARDS), but H2O2-combatting antioxidant defenses have not been evaluated. We found that serum from septic patients with ARDS scavenged more (p less than 0.05) H2O2 in vitro (82.7 +/- 3.8%) than did serum from septic patients without ARDS (56.9 +/- 3.1%) or control subjects (20.2 +/- 2.4%). Serum from septic patients with ARDS also had more (p less than 0.05) catalase activity (54.9 +/- 10.9 U/ml) than did serum from septic patients without ARDS (28.6 +/- 3.4 U/ml) or control subjects (7.3 +/- 0.8 U/ml). In contrast, serum from septic patients with or without ARDS and control subjects had the same glutathione peroxidase (GPX) activity. Serum H2O2 scavenging activity correlated with serum catalase (r = 0.77) but not GPX (r = 0.33) activity and was inhibitable (greater than 90%) by sodium azide, a catalase inhibitor. Increases in serum catalase activity did not appear to be derived from erythrocytes (RBC) because septic patients with or without ARDS and control subjects had similar RBC hemolysis in response to osmotic stress in vitro and serum haptoglobin concentrations. Serum from septic patients with ARDS also protected endothelial cells against H2O2-mediated damage (34.5 +/- 2.2% 51Cr release) better (p less than 0.05) than serum from septic patients without ARDS (47.3 +/- 7.4%) or control subjects (82.1 +/- 10.2%), but killing of bacteria by neutrophils in vitro was the same in serum from patients and control subjects. Our findings indicate that patients with sepsis and/or ARDS have increased serum catalase activity, which may alter H2O2-dependent processes.
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PMID:Increased serum catalase activity in septic patients with the adult respiratory distress syndrome. 141 29

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

The sequential pulmonary changes occurring in the evolution of adult respiratory distress syndrome (ARDS) were studied in 35 patients by correlative light, scanning, and transmission electron microscopy. The causes of ARDS were diverse, the major ones being sepsis or aspiration. Patient survival ranged from 3 to 51 days. The acute stage in patients surviving 2 to 7 days was characterized by an exudative reaction with a predominance of hyaline membranes. This acute stage merged with and was replaced by a subacute reparative stage in patients surviving 7 to 14 days, which in turn was replaced by a chronic fibroproliferative stage complicated by interstitial pulmonary fibrosis and a deranged acinar architecture. Correlation of findings by scanning electron microscopy with those by light and transmission electron microscopy provided an added dimension to understanding of the evolving stages of ARDS and demonstrated that type 2 pneumocytes contributed to the fibroproliferative stage through organization of hyaline membranes and re-epithelialization of alveoli.
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PMID:Correlative study of adult respiratory distress syndrome by light, scanning, and transmission electron microscopy. 144 81

Acute respiratory failure is still one the main problems in surgical intensive care. Unknown pathophysiological mechanisms permit only symptomatic therapy. Today ventilatory strategies by using PEEP und IRV are established to improve gas exchange and FRC by recruiting collapsed alveoli, decreasing intrapulmonary shunting and returning V/Q matching to normal. Furthermore different studies have shown the effects of supine and lateral decubitus posture in patients with acute respiratory failure. There are only rare reports on using the prone position, which doesn't require two-lung ventilation in difference to lateral position. We have studied 16 patients with acute respiratory failure by using continuous changing between prone and supine position under mechanical ventilation. All were male, aged 41.3 years in the middle and showed an average "Injury Severity Score" of 30 (13-50). 15 were trauma patients with blunt chest trauma in 11 cases. We have used prone position on threatening or manifest ARDS. In all patients we observed an increment of PaO2 during prone position on to 48 mmHg so that FiO2 could be reduced on an average of 0.2 within the first 48 h since changing patient's position. Posture changing depends on blood gas analysis, specifically on decreasing PaO2 after previous increment. Patients remained in prone and supine position at a mean of 6.3 (4.5-20) h and posture changing was proceeded over a period of 15.4 (7-32) days. No problems recording to blood pressure or mechanical ventilation appeared during prone position. 11 of 16 patients survived (68.8%), 5 died of cardiac (2) and multi organic failure (3) in connection with sepsis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Continuously alternating prone and supine positioning in acute lung failure]. 145 88

We determined the generation and metabolism of lipoxygenase products in isolated granulocyte fractions of patients with multiple trauma (n = 9) and compared the results with those of healthy volunteers (n = 8). The supernatants of stimulated cells were analyzed by high-performance liquid chromatography. During the first week after injury a significantly reduced capacity to generate LTB4 and an increased metabolism of LTB4 into omega-oxidated products (20-OH-LTB4 and 20-COOH-LTB4) were observed after stimulation of the granulocytes with Ca ionophore. The depressed leukotriene production could be partly abrogated by the addition of arachidonic acid. These findings are comparable with alterations previously described in severely burned patients with postburn sepsis. Additionally, an elevated production of LTC4 by peripheral granulocyte fractions was observed in two patients suffering from adult respiratory distress syndrome (ARDS) as well as an increased number of eosinophils during the time of lung dysfunction. Analysis of bronchoalveolar lavage in patients with multiple trauma (11 patients with ARDS and 11 patients without ARDS) by a specific radio-immunoassay confirmed an elevated production of cysteinyl-leukotrienes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Leukotriene generation in patients with multiple injuries. 147 18


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