Articles: sepsis.
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Prostaglandins Leukot. Essent. Fatty Acids · Feb 1996
Evaluation of the effects of steroids on experimental septic lung injury.
To evaluate the clinical usefulness of steroids for septic lung injury, we investigated the effects of methylprednisolone (MP) on this disorder using an experimental rat model of cecal ligation and puncture (CLP). While 92% of the rats that underwent CLP (CLP rats) died within 30 h, those given high-dose MP (30 mg/kg) just after the operation (CLP + MP rats) survived for a significantly longer period (p < 0.01). Concentrations of endotoxin (ET) in arterial blood were significantly higher in the CLP + MP rats than in the CLP rats, while those in the bronchoalveolar lavage fluid (BALF) were significantly lower. ⋯ The administration of MP did not cause recoveries in the uptake and release of 3H-AA by CLP-AM. Although the survival time of CLP rats was significantly prolonged and the translocation of ET into BALF was reduced by steroid administration, the steroid effects were not explained by those on altered AM function. The upregulated generation of O2- and reduced LTB4 production from CLP-AM were not reversed by the treatment of this drug.
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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.
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Am. J. Respir. Crit. Care Med. · Jan 1996
Comparative Study Clinical Trial Controlled Clinical TrialSkeletal muscle microvascular blood flow and oxygen transport in patients with severe sepsis.
To compare skeletal muscle microvascular blood flow at rest and during reactive hyperemia in septic patients, a prospective, controlled trial was conducted on 16 patients with severe sepsis and a control group of 10 patients free of infection in the intensive care unit of a university hospital. Systemic hemodynamics, whole-body oxygen transport, and skeletal muscle microvascular blood flow at rest and during reactive hyperemia were measured. Reactive hyperemia was produced by arrest of leg blood flow with a pneumatic cuff; on completion of the 3 min ischemic phase the occluding cuff was rapidly deflated to 0. ⋯ Cyclic variation in blood flow (vasomotion) was observed in control subjects but not in septic patients. Skeletal muscle microvascular perfusion is altered in patients with severe sepsis despite normal or elevated whole-body oxygen delivery. These microvascular abnormalities may further compromise tissue nutrient flow and may contribute to the development of organ failure in septic patients.
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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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Scand J Infect Dis Suppl · Jan 1996
ReviewEvidence for antibiotic-mediated endotoxin release as a contributing factor to lethality in experimental gram-negative sepsis.
Endotoxic lipopolysaccharide (LPS) is a major constituent of the outer membrane of the Gram-negative microbe. Following its release from the bacterium, LPS serves as a potent proinflammatory stimulus by interacting with humoral and cellular mediator systems to stimulate production of an array of inflammatory molecules. Cell-wall active antibiotics are known to promote endotoxin release. ⋯ Lethality data correlate well with circulating levels of interleukin-6 (Il-6) in vivo and with induction of Il-6 in ex vivo studies in which anticoagulated mouse blood is incubated with bacteria and antibiotics. Finally, antiendotoxin agents manifest additional levels of protection in vivo under conditions in which antibiotics alone are not protective. Collectively, these results strongly implicate antibiotic-induced endotoxin release as a significant contributing factor in experimental Gram-negative sepsis.