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      Evolving concepts of therapy for sepsis and septic shock and the use of hyperpermeable membranes :

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      Current Opinion in Critical Care

      Ovid Technologies (Wolters Kluwer Health)

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          Anti-inflammatory cytokine profile and mortality in febrile patients.

          An anti-inflammatory cytokine profile on whole-blood stimulation in vitro is associated with fatal outcome of meningococcal disease. We investigated whether an anti-inflammatory cytokine profile in the circulation is associated with adverse outcome in other infectious diseases. We enrolled 464 consecutive patients (272 men, 192 women) who presented to hospital with fever (> or = 38.2 degrees C). On admission we measured plasma interleukin 10 (IL-10) and tumour necrosis factor alpha (TNF alpha), and collected clinical and microbiological data on the febrile illness, then followed up all patients for clinical outcome. In at least 399 of the 464 patients fever was caused by infection. 33 patients died after a median hospital stay of 11 days (interquartile range 3-20). Concentrations of IL-10 were significantly higher in non-survivors (median 169 pg/mL [IQR 83-530]) than in survivors (median 88 pg/mL [42-235], p=0.042). When dichotomised around the median, the mortality risk was two times higher in patients who had high concentrations of IL-10 than in those with low concentrations (relative risk 2.39 [95% CI 1.07-5.33]), in patients with low and high concentrations of TNF alpha. In the 406 patients without haemodynamic deterioration in the first 24 h, IL-10 was higher and TNF alpha lower in patients who died than in those who survived. The ratio of IL-10 to TNF alpha was higher in non-survivors (median 6.9 [3.0-21.0]) than in survivors (median 3.9 [2.0-7.0], p=0.040). This ratio was highest in patients who died without underlying disease (median 21.5 [5.0-25.0]). Age, sex, and duration of fever before admission did not explain the differences in IL-10 and TNF alpha. An anti-inflammatory cytokine profile of a high ratio of IL-10 to TNF alpha is associated with fatal outcome in febrile patients with community-acquired infection. Our findings caution against a widespread use of proinflammatory cytokine inhibition in patients with sepsis.
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            Confirmatory interleukin-1 receptor antagonist trial in severe sepsis

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              Cytokine removal and cardiovascular hemodynamics in septic patients with continuous venovenous hemofiltration.

              To determine whether continuous venovenous hemofiltration leads to extraction of tumor necrosis factor alpha (TNF alpha) and cytokines from the circulation of critically ill patients with sepsis and acute renal failure and to quantitate the clearance and the removal rate of these cytokines and their effect on serum cytokine concentrations. Prospective, controlled study in patients with continuous venovenous hemofiltration (24 1/24 h) using a polysulphone membrane in patients with acute renal failure. 33 ventilated patients with acute renal failure of septic (n = 18) and cardiovascular origin (n = 15) were studied. Hemodynamic monitoring and collection of blood and ultrafiltrate samples before and during the first 72 h of continuous hemofiltration. Cardiovascular hemodynamics (Swan-Ganz catheter), Acute Physiology and Chronic Health Evaluation II score, creatinine, electrolytes, and blood urea nitrogen were recorded daily. Cytokines (TNF alpha, TNF alpha-RII, interleukin (IL) 1beta, IL1RA, IL2, IL2R, IL6, IL6R, IL8, IL10) were measured in prefilter blood and in ultrafiltrate immediately preceding and 12, 24, 48, and 72 h after initiating continuous venovenous hemofiltration (CVVH). Septic patients showed elevated cardiovascular values for cardiac output (7.2 +/- 2.1 l/min), cardiac index (4.2 +/- 1.3 l/min per m2), and stroke volume (67 +/- 23 ml) and reduced values for systemic vascular resistance (540 +/- 299 dyn x s x cm(-5)). All hemodynamic values normalized within the first 24 h after initiating CVVH treatment. TNF alpha was 1833 +/- 1217 pg/ml in septic patients and 42.9 +/- 6.3 pg/ml in nonseptic patients (p < 0.05) prior to CVVH. TNF alpha was detected in ultrafiltrate but did not decrease in blood during treatment with CVVH. There was no difference in IL 1beta between septic (3.8 +/- 1.9 pg/ml) and nonseptic patients (1.7 +/- 0.5 pg/ml). No significant elimination of cytokines was achieved in the present study by CVVH treatment. These findings demonstrate that CVVH can remove TNF alpha and special cytokines from the circulation of critically ill patients. Cardiovascular hemodynamics seemed to improve in septic patients after induction of hemofiltration treatment, although there was no evidence that extracorporeal removal of cytokines achieved a reduction in blood levels. The study indicates that low volume continuous hemofiltration with polysulphone membranes in patients with acute renal failure is not able to induce significant removal of cytokines.
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                Author and article information

                Journal
                Current Opinion in Critical Care
                Current Opinion in Critical Care
                Ovid Technologies (Wolters Kluwer Health)
                1070-5295
                2000
                December 2000
                : 6
                : 6
                : 431-436
                Article
                10.1097/00075198-200012000-00011
                f98dde84-2d40-4563-9c26-a443bf42374e
                © 2000

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