The Effects Of High Volume Hemofiltration On IL-18 In Plasma Of Patients With Severe Sepsis

Objective: Severe sepsis is still a great challenge in hospitals over the world. The mortality of severe sepsis is very high, although newly medical therapeutics has been developed. Therefore, further study of pathophysiology in the pathogenesis of sepsis still need to be conducted. In recent years, people have been encouraged because several cytokines which might be a special mediation to diagnose and prevent severe sepsis are often detected. IL-18, as a proinflammatory cytokine, can enhances the secretion of TNF-α,IL-1β,IL-8,GM-CSF, and then increases IFN-γ. So IL-18 can be considered as a prognostic factor to severe sepsis. In our study, we hypothesis that downregulating the IL-18 level in the plasma could improve the prognosis of severe sepsis.With the development of continuous blood purification (CBP), more and more scholars consider that CBP should be used to treat sepsis. High volume hemofiltration (HVHF) is one of the modes of CBP, which can reduce all kinds of soluble inflammatory mediators through convection and absorption. HVHF can upregulate or downregulate several inflammatory cytokines, which can block excessive inflammatory response. HVHF could significantly improve unstable hemodynamic disorders, the cardiac function and respiratory function of severe septic patients. Therefore, HVHF is considered to be the most effective method to treat patients with sepsis, septic shock and multiple organ dysfunction syndrome (MODS). In our study, we detected IL-18 level in plasma and ultrafiltrate in order to elucidate whether HVHF could improve the prognosis of the patients with severe sepsis by deducing the excessive IL-18 level in their plasma.Method: Twenty-three patients with severe sepsis and twenty-three healthy volunteers were selected, and the changes of metabolism, circulation, temperature, oxygenation and the concentration of IL-18 were detected.1 Patients with severe sepsis vs healthy volunteers Twenty three patients with severe sepsis include 15 males and 8 females. Twelve healthy volunteers include 8 males and 4 females. Temperature (T), mean arterial pressure (MAP), white blood cell (WBC), C-reactive protein (CRP) and the concentration of IL-18 of them were examinated.2 Survivors vs nonsurvivorsSurvivors group: 18 patients, including 12 males and 6 femalesNonsurvivors group: 3 males and 2 females.Mean APACHE II score of all patients with severe sepsis was 20.13, whose hemofiltration rate was 4L·h^-1 and blood rate was 120～180 ml·min^-1 with renal replacement machine (Hospal PRISMA-TM, Italy). The filter model was M100 (1.0 m2, AN69). The changes of temperature (T), Heart rate (HR), MAP, oxygen index(OI), blood urea nitrogen (BUN), creatinine (Cr),electrolyte and IL-18(plasma and ultrafiltrate) were measured before and after HVHF treatment (0h, 24h, 48h, 72h) to investigate the influence of HVHF and the prognosis. The total HVHF treatment time is 72 hours.Result:1 The temperature, WBC and CRP of the patients with severe sepsis were all higher than that of the healthy volunteers, whereas the MAP was lower than that of the healthy volunteers (p<0.01). The concentration of IL-18 in severe septic patients was significantly higher than that of volunteers (1022.30±960.37 pg/ml vs 87.9±31.7pg/ml,p<0.01).2 After HVHF treatment, the HR, CVP and temperature of all patients were significantly increased, meanwhile their MAP was significantly decreased, and their Oxygen index was significantly increased too (p<0.05). The hemodynamics was stabile. HVHF could significantly improve the cardiac function of severe septic patients and can be applied to the patients who had circulation failure and unstable hemodynamic disorders. Meanwhile HVHF could significantly improve the respiratory function of severe septic patients.3 After HVHF treatment, the BUN, Cr, HCO₃^- in the plasma of the patients with severe sepsis were all significantly decreased (p<0.05) and the value of pH had no significant change (p>0.05).4 The plasma level of IL-18 was placidly decreased after HVHF treatment. The concentration of IL-18 were no significant difference among the four time points (p>0.05). IL-18 can be detected in the ultrafiltrate. The concentration of IL-18 in ultrafiltrate was positively correlated with that in plasma (r=0.75, p<0.01).5 Five patients died and 18 patients survived in 28 days. The actual mortality is 21.7%, but the predicted mortality according to APACHEâ…¡score is 47.5%. So it is concluded that HVHF could significantly improve their prognosis.Conclusion:1 The IL-18 levels in the plasma of severe sepsis patient is significantly higher than that of the healthy volunteers, which shows more IL-18 is produced in severe septic patient.2 HVHF could distinctly improve the cardiac function of the patients with severe sepsis and should be applied to treat septic patients who had circulation failure and unstable hemodynamic. HVHF can significantly alleviate lung injury and improve ventilation and oxygenation, improve the respiratory function of septic patients.3 HVHF could significantly improve the renal function of severe septic patients, rectify the disturbance of electrolytes and keep the balance of acid and base.4 HVHF can effectively remove IL-18 and decline the plasma level of IL-18 through the convection transport. The beneficial effect of HVHF is contribute to downregulate the release of excessive IL-18 and rectify the unbalance of inflammatory cytokines.5 After HVHF treatment, the actual mortality is significantly lower than the predicted mortality .