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

The impressive anti-inflammatory effects of the tumor necrosis factor (TNF)alpha blockers etanercept and infliximab have led to their use in multiple inflammatory diseases besides their original indication, rheumatoid arthritis (RA). The well-studied clinical effects of both agents in RA are the reduction of signs and symptoms of joint inflammation as well as the arrest of bone destruction. Infliximab has also been Food and Drug Administration-approved in the treatment of Crohn disease; etanercept is now FDA-approved for juvenile chronic arthritis and psoriatic arthritis. Favorable initial clinical trials have been reported in other rheumatic diseases, including ankylosing spondylitis and adult Still disease. In addition, TNF alpha blockade is being studied in the treatment of uveitis, myelodysplastic syndromes, and graft-versus-host disease. Studies in sepsis and septic shock have identified small subsets of patients that may benefit from TNF alpha blockade, but broader use in septic patients has not improved survival. The TNF alpha blockers have had relatively infrequent serious side effects, especially compared with the immunosuppressive and cytotoxic agents otherwise employed to treat these diseases. Further studies of optimal dosing, combination with other therapies, and long-term benefits and side effects will emerge from future trials.
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PMID:New indications for treatment of chronic inflammation by TNF-alpha blockade. 1258 32

Resuscitation from circulatory and respiratory failure represent mainstays of emergency and critical care management. Importantly, no amount of resuscitative effort will be successful in promoting patient survival if the primary reason for the shock state is not identified and treated, independent of resuscitation. Having said that, aggressive resuscitation to normal functional levels of blood flow and organ perfusion pressure during the first 6 hours following the development of shock improves outcome both in patients with trauma or sepsis. However, clinical studies have demonstrated that restoration of total blood flow to supranormal levels in subjects with established shock that has been present for over 6 hours does not improve survival. Still, some defined clinical targets are essential in these patients as well to prevent further organ injury due to ischemia and its associated inflammatory response. Thus, the rapid restoration of normal hemodynamics by conventional means, including fluid resuscitation and surgical repair, results in a better log term outcome than inadequate or delayed resuscitative efforts. Clear initial targets for resuscitation are a mean arterial pressure > 60 mm Hg, and a cardiac output and O(2) transport to the body adequate enough to prevent tissue hypoperfusion. The level of cardiac output needed to achieve this goal is probably different among subjects and within subjects over time. Indirect signposts of adequate perfusion, such as venous O2 saturation, mentation, urine output and local measures of tissue blood flow are useful in monitoring this response.
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PMID:Targets for resuscitation from shock. 1276 14

Necrotizing fasciitis is a soft tissue infection that causes necrosis of subcutaneous tissue and fascia but usually spares skin and muscle. Management of this condition consists of early diagnosis, broad-spectrum antibiotic coverage, aggressive surgical debridement, wound closure, and intensive supportive care. Mortality estimates reported in the literature have ranged from 20 to 75%. We report the cases of 12 patients treated at the Joseph M. Still Burn Center in Augusta, GA. Because aggressive surgical debridement combined with medical support is required for successful treatment, we recommend that treatment be administered at a burn care center. We performed a retrospective chart review of all patients admitted to our center with a diagnosis of necrotizing fascitis between May 1, 1995, and June 1, 2000. Patients were managed collaboratively by burn surgeons and critical care intensivists in consultation with other appropriate specialists. The mean time from initial diagnosis until transfer to the burn center was 14 days (range, 0-60 d). Complications included pneumonia, heart failure, metabolic abnormalities, anemia, and sepsis. Four (33%) of the 12 patients died, with the primary cause of death being multiorgan failure. Although our sample size is too small to reach statistical significance, the data suggest that early referral to a burn or wound care center improves patient outcome.
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PMID:Experience with necrotizing fasciitis at a burn care center. 1451 81

Bum shock is a complex process involving a series of intertwined physiologic responses to injury that require more rigorous intervention than simply a change in fluid tonicity, fluid composition, or fluid resuscitation volume. Controversy ensues over monitoring techniques and resuscitation goals, in part because the identification of true markers of perfusion is clouded by intradependence of endpoints on other metabolic processes. The persistence of cellular hypoperfusion in patients who have been deemed adequately resuscitated by global indices supports the growing realization that failure of conventional endpoint-monitoring strategies to detect compensated bum shock can lead to significant organ injury from SIRS or MODS. Current endpoints should be interpreted in the aggregate, because none have yet been demonstrated to reflect tissue perfusion status independently and accurately. Numerous technologically advanced endpoints to predict patient outcome, which may be useful in determining futility of treatment or end-of-life decisions, are now available. Still lack-ing, however, is a reliable tool proven to improve outcome that can guide bum shock resuscitation therapies successfully. Exciting new research in tissue oxygenation and perfusion has revealed that damaging mediator cascades and irreversible microvascular changes may preclude complete resolution of bum shock solely through restoration of oxygen delivery. Because bum patients now frequently survive the early resuscitation phase. the focus should be on controlling derangements in oxygen use and correcting occult hypoperfusion to reduce later adverse patient outcomes from SIRS, sepsis, and MODS. Bum-specific research on resuscitation endpoints and monitoring strategies lags behind research in other patient populations. Present standards and monitoring guidelines for bum shock resuscitation should be critically evaluated and based on true, scientifically validated data rather than on observational studies or personal beliefs. Thus the continuing challenge for clinicians and researchers:burn centers must collaborate to perform large, multi-center studies to evaluate critically and to prove resuscitation endpoints and therapies. Future technologies targeted at microcirculatory perfusion and cellular oxygenation offer an exciting promise for less invasive, easily accessible, more accurate endpoints and treatments for bum shock resuscitation.
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PMID:Trends in burn resuscitation: shifting the focus from fluids to adequate endpoint monitoring, edema control, and adjuvant therapies. 1506 15

The acute respiratory distress syndrome (ARDS) is a life-threatening syndrome that may occur in any patient without any predisposition and that is mostly triggered by underlying processes such as sepsis, pneumonia, trauma, multiple transfusions, and pancreatitis. ARDS is defined by (1) acute onset, (2) bilateral infiltrates in chest x-rays, (3) absence of left ventricular failure, and (4) severe arterial hypoxemia with a PaO2/FiO2 ratio less than 200 mmHg. Still, ARDS is feared (mortality 30-40%) and relatively frequent (incidence between 13.5 per 100,000 to 75 per 100,000). Acute lung injury (ALI) describes a similar, but less severe, clinical condition, with PaO2/FiO2 values between 200 and 300 mmHg. Despite ongoing and intensive scientific research in this area, the mechanisms underlying ALI/ARDS are still not completely understood, and until recently, there were no studies demonstrating any beneficial effect of a single treatment modality in ARDS. The recent report that a specific approach to ventilatory support can significantly reduce mortality in ARDS underscores the need for better understanding of the pathophysiological events occurring in this syndrome. This review therefore summarizes the current pathophysiological concepts underlying the evolution of acute hypoxemic respiratory failure and focuses on: (1) possible reasons for the development of ALI/ARDS; (2) cellular and humoral mediator responses leading to a sustained and self-perpetuating inflammation of the lung; (3) consequences with regard to fluid balance, pulmonary perfusion, ventilation, and efficiency of gas exchange; and (4) mechanisms underlying the aggravating complications commonly seen in ARDS, especially ventilator-associated lung injury, ventilator-associated pneumonia, and lung fibrosis.
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PMID:Pathophysiology of acute lung injury. 1608 77

Reactive hemophagocytic syndrome (HS) occurs mainly in the setting of serious infections and lymphomas. HS can occur in the course of 2 active systemic diseases, without simultaneous infection: adult Still disease and systemic lupus erythematosus (SLE). Observations of specific lupus-associated HS are rare, and the long-term outcome of these patients with active SLE is unknown. We retrospectively studied 15 episodes of SLE-associated HS in 12 patients (10 women, 2 men) and noted the long-term outcome. HS occurred at a mean age of 25 years. All patients were febrile with >or=2 cytopenias, and bone marrow aspiration indicated hemophagocytosis. HS revealed SLE in 9 patients and recurred in 3. The main features of SLE-associated HS were a low frequency of hepatosplenomegaly, a high frequency of heart involvement (5 pericarditis, 4 myocarditis requiring transfer to intensive care unit), and a low C-reactive protein level (mean, 15 mg/L). Cutaneous-mucous symptoms of SLE, arthritis, and nephritis were present respectively in 8 (53%), 6 (40%), and 4 (27%) episodes, but symptoms of SLE were absent in 4 episodes at admission. All patients had anti-nuclear antibodies when the HS occurred. Anti-double-stranded DNA antibodies were present in 12 episodes. Treatment was steroids in 14 cases but cyclophosphamide was the only treatment able to control HS in 2 cases. All the cases of SLE-associated HS were controlled by the immunosuppressive regimen. Intravenous immunoglobulins seemed poorly effective. No infectious agent was found. Clinical presentations of the 23 patients with SLE-associated HS described in the literature were reviewed and were similar to those of the current series. The mean follow-up was 88 months (range, 7-240 mo). One patient died at 15 months (sepsis). Among the 5 patients with a follow-up >8 years, 4 always had active disease. During the follow-up of SLE, immunosuppressive drugs were added in 8 patients (cyclophosphamide in 7, azathioprine in 3, mycophenolate mofetil in 2) with significant adverse drug reactions. In the long-term, SLE-associated HS seems to define a severe SLE form with frequent flares, possible HS recurrences, and the need for prolonged immunosuppression.
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PMID:Characteristics and long-term outcome of 15 episodes of systemic lupus erythematosus-associated hemophagocytic syndrome. 1672 Dec 59

Drug-induced hypersensitivity syndrome (DIHS), also called drug rash with eosinophilia and systemic symptoms (DRESS), is a severe reaction usually characterized by fever, rash, and multiorgan failure, occurring 1-8 weeks after drug introduction. It is an immune-mediated reaction involving macrophage and T-lymphocyte activation and cytokine release, although no consensus has been reached as to its etiology. The skin, hematopoietic system, and liver are frequently involved. DIHS can mimic severe sepsis, viral infection, adult-onset Still disease (AOSD), or lymphoproliferation.We describe 24 consecutive patients with DIHS who were hospitalized between September 2004 and March 2008. Criteria for inclusion in this observational study were suspected drug reaction, eosinophilia >or=500/microL and/or atypical lymphocytes, involvement of at least 2 organs (skin being 1 of them), with suggestive chronology and exclusion of other diagnoses. Our cohort of 12 women and 12 men had a median age of 49 years (range, 22-82 yr), and 11 had skin phototype V or VI. Patients with mild or no rash were immunocompromised (7/24)- defined as treatment with prednisone (>or=10 mg/d) and another immunosuppressant drug, or human immunodeficiency virus infection. All patients were febrile (>38 degrees C), 14 had localized or generalized edema, 7 had pharyngitis, 8 had lymphadenopathy, 22 had hepatitis, 4 had nephritis, 2 had noninfectious and nonlithiasic angiocholitis or cholecystitis. Ten patients were hypotensive, 5 of whom had associated laboratory signs and/or imaging findings suggestive of acute myocardial dysfunction. Half of the patients had hemogram abnormalities, including eosinophilia. Nine DIHS patients fulfilled the Fautrel criteria for AOSD diagnosis, including glycosylated ferritin <20% in 4/11, with or without laboratory characteristics of hemophagocytosis. Twenty DIHS episodes occurred during the less sunny months of October to March.We determined 25-hydroxyvitamin D3 (25[OH]D3) levels in 18 patients and found that 9 patients had vitamin D deficiency (<25 nmol/L or <10 microg/L) and 5 had vitamin D insufficiency (25-50 nmol/L). Moreover, 25(OH)D3 levels were inversely correlated with ferritin values. After culprit-drug withdrawal, outcomes were favorable for all patients, including those with cardiac abnormalities under slow tapering of glucocorticoids.We recommend looking for the frequent but underdiagnosed hypersensitivity myocarditis with noninvasive diagnostic tools, such as N-terminal probrain natriuretic peptide, and promptly withdrawing the culprit drug and starting glucocorticoids. Vitamin D deficiency might be a DIHS risk or severity factor, especially for patients with high skin phototype and during the winter. Because DIHS clinical and laboratory patterns share similarities with AOSD and hemophagocytosis, DIHS should be included in their differential diagnoses.
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PMID:Drug-induced hypersensitivity syndrome: clinical and biologic disease patterns in 24 patients. 1944 Jan 16

The inflammation is a response of the organism to damaging factors and leads to the limitation of the tissue destruction. During the inflammatory process, there is stimulation of the immune system as well as other tissue cells. However, sometimes this reaction is excessive and can bring to the sepsis and development of multiorgan insufficiency. Phenomena observed during sepsis influence also, directly or indirectly on the nervous system and cause septic encephalopathy (SE) with consciousness and cognitive functions loss and other neurological symptoms. Often it can lead to persistent brain injuries, and almost always cause changes, which can be manifested later, even many years after the sepsis. It is supposed that in many cases, septic encephalopathy can be the main reason of death during sepsis. Still increasing concern of SE brought to the development of several animal models of this syndrome, which made possible detailed recognition of phenomena accompanying of septic encephalopathy. They include direct administration of endotoxins, or surgical intervention within the abdominal cavity. Every presented experimental model has advantages and weakness, but they make possible the modeling of the inflammatory reaction and multidirectional examining of accompanying phenomena.
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PMID:Sepsis and septic encephalopathy: characteristics and experimental models. 2302 37

Accumulating evidence supports procalcitonin (PCT) as an accurate surrogate biomarker for likelihood and severity of bacterial infections. In community-acquired pneumonia and other respiratory infections, PCT-guided antibiotic therapy algorithms resulted in reduced antibiotic exposure while maintaining a similar or even better level of safety compared with standard care. Reductions in antibiotic use translate into lower treatment costs, decreased risk of side effects and decreased bacterial multiresistance. This is especially important, as acute respiratory infections represent the most frequent reason for antibiotic prescriptions worldwide. Still, there is some controversy about the benefits of PCT measurement in sepsis patients in the intensive care unit and for nonrespiratory infections. Highly sensitive PCT assays are readily available in many hospitals today, and point-of-care assays with high enough sensitivity for antibiotic guidance are expected to be available soon. Herein, the authors provide an overview of recent studies evaluating PCT in different clinical situations and an outlook of currently enrolling or upcoming interventional trials.
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PMID:Streamlining antibiotic therapy with procalcitonin protocols: consensus and controversies. 2354 91

Aggressive dual antiplatelet therapy is associated not only with more bleeding, impaired wound healing, and potentially more solid cancer rates but it also causes higher infection risks including sepsis, and systemic inflammatory response syndrome (SIRS). This may be especially true considering the alarming off-label use of prasugrel. A 65-year-old white male patient with a history of myocardial infarction treated with percutaneous coronary intervention and implantation of 2 bare metal stents, was treated with off-label clopidogrel for 4 years, including a double daily dose (150 mg) for the initial 13 months. Still on clopidogrel, the patient was hospitalized with suspected pneumonia. A diagnostic cardiac catheterization revealed a 60%-70% blockage of the mid left anterior descending, but there was no need for coronary intervention. At discharge, clopidogrel 75 mg/d was switched over to off-label prasugrel 10 mg/d on top of aspirin (81 mg/d). On day 3 after prasugrel was given, a football-sized bruise appeared on the patient's lower right abdomen, but computed tomography results were unremarkable. On day 6 after administration of prasugrel, the patient became dizzy, disoriented, confused, experienced difficulty breathing, severe headache, weakness, intensive petechial rash covering the entire body, and breathing difficulty requiring ventilation. Within 24 hours, the patient was unable to correctly identify his age; his eyes were pale in color to almost colorless and when hearing a sound he would turn his entire head toward the sound and he appeared to be blind. His lungs, liver, and kidneys began to show signs of failure over the next 5-9 days. Sixteen days after the administration of the first prasugrel dose, the patient died of sepsis complicated with SIRS. Aggressive off-label use of clopidogrel (double dose for 13 months, and >4 years overall duration), followed by off-label switchover to the highest daily dose (10 mg) prasugrel may trigger sepsis and fatal SIRS. The mechanism responsible for such harmful association is probably indirect, and involves the weakening of platelet-neutrophil-endothelial crosstalk necessary to combat infections, and/or keep inflammation from spreading.
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PMID:Fatal sepsis and systemic inflammatory response syndrome after off-label prasugrel: a case report. 2366 86


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