CRRT在全身感染MODS和SIRS治療中的應用學習教案

1、會計學1CRRT在全身感染在全身感染MODS和和SIRS治療中的治療中的應用應用第1頁/共36頁全身感染（sepsis)第2頁/共36頁第3頁/共36頁第4頁/共36頁第5頁/共36頁第6頁/共36頁第7頁/共36頁第8頁/共36頁局部感染灶激活炎癥細胞內(nèi)皮細胞釋放炎癥介質(zhì)釋放細菌產(chǎn)物單核/巨噬細胞多形核白細胞第9頁/共36頁MicrobesMicrobialproductsResponsivecellsMediatorsEffectGram NegativeBacteriaGrampositive BacteriaFungiCoagulation cascade(factor XII, ti

2、ssue factor)+complement cascade(C5a)+Inflammation(TNF,IL-1,IL-8,MCP-1)+Vessel injury(PLA2,NO)+SEPSIStissue damage and organ failurehypotension and shockPMNMACROPHAGEENDOTHELIAL CELL第10頁/共36頁LPSLBPBP1Gram negative bacteriaCD14LPSUnidentified LPS receptorMacrophageCytokinegenesHDLSignal transduction第1

3、1頁/共36頁第12頁/共36頁第13頁/共36頁第14頁/共36頁High-dose steroids2 phase III trialsNo overall benefit; subgroup withARF worsened by treatmentHA-1A(anti-lipid A Mab)2 phase III trials, small trialNo overall benefit; favorable trendin meningococcemiaE5(anti-lipid A Mab)3 phase III trialsNo overall benefit; improve

4、d organdysfunction in some subgroupsInterkeukin 1-receptorantagonist2 phase trialsNo overall benefitPlatelet activating factorinhibitors1 phase II, 1 phase III trialNo overall benefit; favorable trendwith gram negative sepsisBradykinin antagonistsPhase II, phase III trialsNo overall benefit; favorab

5、le trendwith gram negativeImmunoglobulinsAnti -TNF MabTNF receptor:immunoglobulin constructsL-N-Mono Methyl arginineIbuprofenI phase III trial3 phase III trials2phase trials, 1 phase III1 phase III trial2 phase II, 1 phase IIINo overall benefit; some evidenceof improvement in subgroups ofshock PtsPh

6、ase II-p75 worsened outcomeNo benefitReduction in fever, tachycardia,oxygen consumption, no survivalbenefit抗炎癥介質(zhì)臨床試驗第15頁/共36頁第16頁/共36頁第17頁/共36頁第18頁/共36頁促促炎癥反應炎癥反應抗抗炎癥反應炎癥反應TNF ,IL-1 ,IFN ,LT IL-2,IL8,IL-12,IL-18,LTB4,GM-CSF,Chemokines,MIFIL-1ra, sTNFR, sIL-1RTGF ,IL-4,IL-6,IL-10IL-11,IL13,PGE2,G -CS

7、Fantioxidants,IFN / 第19頁/共36頁內(nèi)環(huán)境穩(wěn)定促炎癥反應抗炎癥反應第20頁/共36頁內(nèi)環(huán)境保持穩(wěn)定促炎癥反應抗炎癥反應第21頁/共36頁促炎癥介質(zhì)過度形成和釋放過度炎癥反應促炎癥反應抗炎癥反應第22頁/共36頁抗炎癥介質(zhì)過度生成與釋放免疫功能抑制促炎癥反應抗炎癥反應第23頁/共36頁促炎反應與抗炎癥反應失衡過度炎癥反應與免疫功能低下并存促炎癥反應抗炎癥反應第24頁/共36頁第25頁/共36頁第26頁/共36頁第27頁/共36頁第28頁/共36頁存活率隨超濾率上升而提高。存活率隨超濾率上升而提高。第29頁/共36頁CRRT血清細胞因子濃度Time TNF-a(pg/ml) IL-1(pg/ml) IL-8(pg/ml) NO(umol/L) 0h1678+789795+170472+149111+43 1h1722+735786+153426+119104+42 2h1570+564754+162430+112115+43 3h1368+447768+154412+154105+46 6h1064+522#*735+183402+122108+42 9h1160+456748+156475+156101+4912h1188+616772+167462+161108+40 # p0.05, 6h vs 0h * p0.01, 6h