Articles: sepsis.
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Despite recent advances in antibiotic therapy, aggressive operative intervention and intravenous hyperalimentation, sepsis, and multiple organ failure are still reported to contribute to significant morbidity and mortality in the surgical intensive care unit. In light of this, it is essential to determine the mechanism underlying the pathophysiology of sepsis so that better therapeutic interventions can be designed. Experimental studies indicate that murine polymicrobial sepsis induces a marked suppression in both lymphocytic and macrophage function associated with decreased cellular adenosine triphosphate levels and increased Ca2+. ⋯ We have presented evidence of marked changes in the rate of Ao in immune cells after the onset of sepsis. These data suggest the possibility that mediators released in response to septic insult contribute to the observed changes in immune cell function through the induction of Ao. Inasmuch, understanding the contribution of PCD to the pathophysiology of sepsis, should provide a better basis from which to develop more effective therapy for the septic patient.
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Scand J Infect Dis Suppl · Jan 1996
ReviewAntibiotics, cytokines, and endotoxin: a complex and evolving relationship in gram-negative sepsis.
Compelling experimental evidence now exists that antimicrobial agents induce the release of endotoxin from Gram-negative bacteria during the process of bacteriolysis. Different antimicrobial classes, particularly those which act upon the outer membrane of bacteria, vary in the amount of free endotoxin released from Gram-negative organisms. ⋯ Complexities in the host-pathogen interactions during actual infection with Gram-negative bacteria may account for the difficulties in demonstrating this phenomena in vivo. This brief review analyses these interactions and defines clinical settings where antibiotic-induced endotoxin release may prove to be clinically relevant.
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During sepsis, there is release of various endotoxins from microorganisms which more or less activates cascade systems including release of cytokines such as tumor necrosis factor alpha and interleukin 6 and complement components. This causes impairment of vascular integrity and permeability which may progress into septic shock and a disseminated intravascular coagulation which progresses into multiorgan failure, including acute renal failure and subsequent death. Although most endotoxins and cytokines have a molecular size < 50 kD, there is little efficacy in removal of them by hemofiltration filters used for acute dialysis. ⋯ In contrast, these studies showed a survival rate of about 75% by addition of such therapeutic interventions to the conventional intensive care unit treatment. The substitution of the removed plasma products must be considered to include products important for the host defense and coagulation process and to avoid infections, bleeding, or increased coagulation. This type of removal is unselective and probably in the future will include addition of absorption techniques which may add further benefit to the outcome.