糖皮質(zhì)激素在膿毒血癥中的應(yīng)用課件

21、沒有人陪你走一輩子，所以你要適應(yīng)孤獨(dú)，沒有人會幫你一輩子，所以你要奮斗一生。22、當(dāng)眼淚流盡的時候，留下的應(yīng)該是堅(jiān)強(qiáng)。23、要改變命運(yùn)，首先改變自己。24、勇氣很有理由被當(dāng)作人類德性之首，因?yàn)檫@種德性保證了所有其余的德性。--溫斯頓．丘吉爾。25、梯子的梯階從來不是用來擱腳的，它只是讓人們的腳放上一段時間，以便讓別一只腳能夠再往上登。糖皮質(zhì)激素在膿毒血癥中的應(yīng)用糖皮質(zhì)激素在膿毒血癥中的應(yīng)用21、沒有人陪你走一輩子，所以你要適應(yīng)孤獨(dú)，沒有人會幫你一輩子，所以你要奮斗一生。22、當(dāng)眼淚流盡的時候，留下的應(yīng)該是堅(jiān)強(qiáng)。23、要改變命運(yùn)，首先改變自己。24、勇氣很有理由被當(dāng)作人類德性之首，因?yàn)檫@種德性保證了所有其余的德性。--溫斯頓．丘吉爾。25、梯子的梯階從來不是用來擱腳的，它只是讓人們的腳放上一段時間，以便讓別一只腳能夠再往上登。糖皮質(zhì)激素在膿毒血癥中的應(yīng)用

糖皮質(zhì)激素在膿毒癥中的應(yīng)用浙江省中醫(yī)院ICU雷澍體內(nèi)的作用對應(yīng)激誘發(fā)的反應(yīng)的反饋系統(tǒng)的活化，保證人體在防御機(jī)制方面不反應(yīng)過度相對腎上腺皮質(zhì)功能不全周圍ＧＣ抵抗膿毒癥GC相對不足炎癥反應(yīng)過度循環(huán)衰竭病情加重外源性GC相對腎上腺皮質(zhì)功能不全的發(fā)生機(jī)制ＴＮＦ-α及促皮質(zhì)素抑素抑制腎上腺功能并降低皮質(zhì)醇水平機(jī)體ＡＣＴＨ水平偏低活化的淋巴細(xì)胞產(chǎn)生ＡＣＴＨ片段干擾經(jīng)典ＡＣＴＨ的功能腎上腺皮質(zhì)血液灌注不足周圍ＧＣ抵抗的發(fā)生機(jī)制皮質(zhì)醇向炎癥部位轉(zhuǎn)運(yùn)障礙糖皮質(zhì)激素受體(ＧＲ)數(shù)目減少和親和力下降炎癥部位皮質(zhì)醇濃度調(diào)節(jié)異常如何確定存在相對腎上腺功能不全以ＡＣＴＨ興奮試驗(yàn)后皮質(zhì)醇的升幅被削峰為特征臨床癥狀和體征是決定診斷的關(guān)鍵因素快速ＡＣＴＨ刺激實(shí)驗(yàn)時，皮質(zhì)醇增加幅度<9μｇ/ｄｌ若任意時間血皮質(zhì)醇水平低于552nmol/L（19.3ug/dl)相對腎上腺功能不全ＡＣＴＨ試驗(yàn)后血皮質(zhì)醇低于690nmol/L（24.2ug/dl)FeaturessuggestingcorticosteroidinsufficiencySymptomsWeaknessandfatigueAnorexia,nausea,vomitingAbdominalpainMyalgiaorarthralgiaPosturaldizzinessCravingforsaltHeadachesMemoryimpairmentDepressionFindingsonphysicalexaminationIncreasedpigmentationHypotension(postural)TachycardiaFeverDecreasedbodyhairVitiligoFeaturesofhypopituitarismAmenorrheaIntoleranceofcoldClinicalproblemsHemodynamicinstabilityHyperdynamic(common)Hypodynamic(rare)OngoinginflammationwithnoobvioussourceMutiple-organdysfunctionHypoglycemiaLaboratoryfindingsHyponatremiaHyperkalemiaHypoglycemiaEosinophiliaElevatedthyrotropinlevels相對腎上腺功能不全和周圍ＧＣ抵抗的發(fā)生率相對腎上腺功能不全:基于ＲＡＩ的不同定義,膿毒癥及感染性休克時,其發(fā)生率為6.25%～75%周圍ＧＣ抵抗:?相對腎上腺功能不全Lancet.1991,RothwellPM,septicshock,13/32（41%）,riselessthan250nmol/l(9ug/dl)tocorticotropin

IntensiveCareMed.1994,MoranJL,septicshock,22/33(67%),

riselessthan200nmol/ltocorticotropin

IntensiveCareMed.1995,BouachourG,

septicshock,1/40(2.5%),basalcortisollevelbelow10micrograms/dl;responsetotheACTHstimulationtestbelow18micrograms/dl

ExpClinEndocrinolDiabetes.1997,AygenB,sepsis,16.3%,

riselessthan250nmol/l(9ug/dl)tocorticotropin

JAMA.

2002,DjillaliAnnane,

septicshock,229/299(77%),

riselessthan250nmol/l(9ug/dl)tocorticotropin

相對腎上腺功能不全一項(xiàng)由Annane等完成的189例膿毒性休克患者的隊(duì)列研究證實(shí),相對腎上腺皮質(zhì)功能不全的最佳定義為:快速ＡＣＴＨ刺激實(shí)驗(yàn)時,皮質(zhì)醇增加幅度<9μｇ/ｄｌ。應(yīng)用此概念,嚴(yán)重膿毒癥時相對腎上腺皮質(zhì)功能不全發(fā)生率約50%,28ｄ的死亡率約75%。相對腎上腺功能不全較高的皮質(zhì)醇水平較低的ACTH反應(yīng)高死亡率區(qū)分相對腎上腺功能不全和腎上腺功能不全ACTHtestpost-corticotropinplasmacortisollevels<18μg/dLtrueprimaryorsecondaryadrenalinsufficiency

1.post-corticotropinplasmacortisollevels>18μg/dL2.anincreaseinplasmacortisollevel<9μg/dL

RelativeAdrenalInsufficiency相對腎上腺皮質(zhì)功能不全與ＧＣ抵抗的關(guān)系過度活化的ＨＤＲ炎癥介質(zhì)升高降低皮質(zhì)醇與ＧＲ的親和力炎癥部位皮質(zhì)醇濃度調(diào)節(jié)異常抑制ＣＲＨ和ＡＣＴＨ對垂體和腎上腺皮質(zhì)的刺激作用膿毒癥炎癥反應(yīng)進(jìn)一步失衡相對腎上腺功能不全1994年,Briegel等第1次報道12例外科嚴(yán)重膿毒癥及感染性休克病例,持續(xù)滴注小劑量ＨＣ(10ｍｇ/ｈ)能減輕全身炎癥反應(yīng)綜合征(ＳＩＲＳ),全部病例均獲好轉(zhuǎn)。該劑量與促腎上腺皮質(zhì)激素(ＡＣＴＨ)興奮試驗(yàn)后健康人群皮質(zhì)醇最大理論分泌速率相當(dāng)。其后,至少有8篇英文文獻(xiàn)得出了類似的結(jié)果。并不一致的治療結(jié)果CritCareMed1998,BollaertPE,Prospective,randomized,double-blind,placebo-controlledstudy,Forty-onepatientswithsepticshock,post-corticotropincortisolplasmaconcentrationof>18μg/dL(excludingadrenalinsufficiency)

hydrocortisone(100mgi.v.threetimesdailyfor5days),asignificantimprovementinhemodynamicsandabeneficialeffectonsurvival.Thesebeneficialeffectsdonotappearrelatedtoadrenocorticalinsufficiency

CritCareMed.1999,BriegelJ,

Prospective,randomized,double-blind,single-centerstudy,Fortypatientswithsepticshock,Hydrocortisonewasstartedwithaloadingdoseof100mggivenwithin30minsandfollowedbyacontinuousinfusionof0.18mg/kg/hr.Whensepticshockhadbeenreversed,thedoseofhydrocortisonewasreducedto0.08mg/kg/hr.Thisdosewaskeptconstantfor6days,reducedthetimetocessationofvasopressortherapyinhumansepticshock.Thiswasassociatedwithatrendtoearlierresolutionofsepsis-inducedorgandysfunctions.OverallshockreversalandmortalitywerenotsignificantlydifferentbetweenthegroupsJAMA.

2002,DjillaliAnnane,Placebo-controlled,randomized,double-blind,parallel-grouptrialperformedin19intensivecareunitsinFrance.Threehundredadultpatientswithsepticshock,(50-mgintravenousbolusevery6hours)andfludrocortisone(50-μgtabletoncedaily)for7days,significantlyreducedtheriskofdeathinpatientswithsepticshockandrelativeadrenalinsufficiency,Therewasnosignificantdifferencebetweengroupsinresponders

所有的膿毒性休克患者需要激素嗎patientswhorespondednormallytocorticotropindisplayedatrendforhighermortalitywithhydrocortisonetherapy(61%vs53%

intheplacebogroup).