Articles: sepsis.
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The pro-inflammatory cytokines, tumor necrosis factor (TNF) and interleukin-1 (IL-1), are widely assumed to participate in the initial systemic manifestations of sepsis. While the toxicities of excessive cytokine activity have been well described in animal models, clinical evaluations often fail to detect circulating forms of these mediators in critically ill patients. It is now evident that a diverse array of host mechanisms serve to attenuate or block excessive cytokine influences. ⋯ Recombinantly derived forms of these natural cytokine antagonists have proven effective in preventing many of the adverse consequences of sepsis. Prospective clinical trials of these agents are currently underway. While results of such trials are not fully available at present, it is likely that one or more therapies directed against TNF and IL-1 may prove effective in the management of septic shock.
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Journal of anesthesia · Jan 1993
Modification of hepatic protein kinase C with phorbol myristate acetate and staurosporine alters hemodynamics in the perfused rat liver.
Activation of protein kinase C (PKC) has been implicated in the pathogenesis of endotoxicosis and severe sepsis. Since hepatic blood flow and metabolism have been known to be altered in endotoxicosis and sepsis, we studied the hemodynamic effect of PKC modulation with phorbol 12-myristate 13-acetate (PMA) and staurosporine (St) on the perfused rat liver. The liver was isolated from overnight-fasted male Sprague-Dawley rats and placed in a recirculating perfusion apparatus. ⋯ Pretreatment with St significantly attenuated the flow reduction by PMA. St significantly suppressed the flow reductions by 4 x 10(-6) M of prostaglandin E2 and D2. These results suggest that the PKC inside the liver may play an important role in the regulation of hepatic blood flow during endotoxicosis and sepsis.
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Intensive care medicine · Jan 1993
Importance of pre-existing co-morbidities for prognosis of septicemia in critically ill patients.
To determine admission characteristics associated with the outcome of septicemia in critically ill patients and more specifically assess the prognostic value of pre-existing co-morbidities. ⋯ Pre-existing co-morbidities assessed at the admission to the ICU significantly improved the prediction of mortality from septicemia compared to Apache II score alone.
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Sepsis and multiple organ failure are major problems in medical and surgical intensive care units. Critical illness polyneuropathy occurs in 70% of these patients. Difficulty in weaning from the ventilator is an early sign. ⋯ Other effects on muscle are cachectic myopathy and panfascicular muscle fibre necrosis. A variety of combinations of these conditions may affect the same patient. Only well-designed prospective studies will determine the true effect of these medications on the neuromuscular system in septic patients.
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Despite the use of increasingly potent antibiotics and aggressive cardiovascular monitoring and support, Gram-negative bacteremia and ensuing sepsis and septic shock remain a leading cause of morbidity and mortality after surgery and in critically ill patients. In previous years several new agents and techniques have been developed to improve management and outcome of severe Gram-negative infections. A recently introduced treatment is passive immunotherapy by administration of poly- or monoclonal anti-endotoxin antibodies. ⋯ Cytokines such as tumor necrosis factor alpha and interleukin-1 play a pivotal role in sepsis. Experimental studies suggest that specific antagonism of these mediators might offer great perspectives for the treatment of Gram-negative sepsis. An early multi-pharmacological approach aimed at interruption of multiple steps underlying the inflammatory septic cascade will probably constitute the most promising future treatment of severe Gram-negative infectious disease.