糖皮质激素在脓毒症中的应用课件.ppt
糖皮质激素在脓毒症中的应用,浙江省中医院ICU 雷澍,体内的作用,对应激诱发的反应的反馈系统的活化，保证人体在防御机制方面不反应过度,应用的现状,2003年6月，SSC制定了新的脓毒症治疗指南：推荐对脓毒性休克静脉使用小剂量氢化可的松 50mg，q6h，连续7天(C级)；可以同时每日给 予氟氢可的松 50ug，鼻饲(E级)；避免氢化可 的松300mg/d(A级).,应用的新理论依据,伴发相对肾上腺皮质功能不全,周围抵抗,GC相对不足,相对肾上腺皮质功能不全,周围抵抗,脓毒症,GC相对不足,炎症反应过度,循环衰竭,病情加重,外源性GC,相对肾上腺皮质功能不全的发生机制,-及促皮质素抑素抑制肾上腺功能并降低皮质醇水平,机体水平偏低,活化的淋巴细胞产生片段干扰经典的功能,肾上腺皮质血液灌注不足,Features suggesting corticosteroid insufficiency,SymptomsWeakness and fatigueAnorexia,nausea,vomitingAbdominal painMyalgia or arthralgiaPostural dizzinessCraving for saltHeadachesMemory impairmentDepression,Findings on physical examinationIncreased pigmentationHypotension(postural)TachycardiaFeverDecreased body hairVitiligoFeatures of hypopituitarismAmenorrheaIntolerance of cold,Clinical problemsHemodynamic instabilityHyperdynamic(common)Hypodynamic(rare)Ongoing inflammation with no obvious sourceMutiple-organ dysfunctionHypoglycemia,Laboratory findingsHyponatremiaHyperkalemiaHypoglycemiaEosinophiliaElevated thyrotropin levels,相对肾上腺功能不全和周围抵抗的发生率,相对肾上腺功能不全:基于的不同定义,脓毒症及感染性休克时,其发生率为 6.25%75%周围抵抗:?,相对肾上腺功能不全,Lancet.1991,Rothwell PM,septic shock,13/32（41%）,rise less than 250 nmol/l(9ug/dl)to corticotropin,Intensive Care Med.1994,Moran JL,septic shock,22/33(67%),rise less than 200 nmol/l to corticotropin,Intensive Care Med.1995,Bouachour G,septic shock,1/40(2.5%),basal cortisol level below 10 micrograms/dl;response to the ACTH stimulation test below 18 micrograms/dl,Exp Clin Endocrinol Diabetes.1997,Aygen B,sepsis,16.3%,rise less than 250 nmol/l(9ug/dl)to corticotropin,JAMA.2002,Djillali Annane,septic shock,229/299(77%),rise less than 250 nmol/l(9ug/dl)to corticotropin,相对肾上腺功能不全,一项 由Annane 等完成的189例脓毒性休克患者的队列研究证实,相对肾上腺皮质功能不全的最佳定义为:快速刺激实验时,皮质醇增加幅度 9/。应用此概念,严重脓毒症时相对肾上腺皮质功能不全发生率约 50%,28的死亡率约75%。,相对肾上腺功能不全,较高的皮质醇水平,较低的ACTH反应,高死亡率,区分相对肾上腺功能不全和肾上腺功能不全,ACTH test,post-corticotropin plasma cortisol levels 18 g/dL,true primary or secondary adrenal insufficiency,1.post-corticotropin plasma cortisol levels 18 g/dL2.an increase in plasma cortisol level 9 g/dL,Relative Adrenal Insufficiency,相对肾上腺皮质功能不全与抵抗的关系,过度活化的,炎症介质升高,降低皮质醇与的亲和力炎症部位皮质醇浓度调节异常,抑制和对垂体和肾上腺皮质的刺激作用,脓毒症,炎症反应进一步失衡,相对肾上腺功能不全,1994年,Briegel等第1次报道 12例外科严重脓毒症及感染性休克病例,持续滴注小剂量(10/)能减轻全身炎症反应综合征(),全部病例均获好转。该剂量与促肾上腺皮质激素()兴奋试验后健康人群皮质醇最大理论分泌速率相当。其后,至少有 8篇英文文献得出了类似的结果。,并不一致的治疗结果,Crit Care Med 1998,Bollaert PE,Prospective,randomized,double-blind,placebo-controlled study,Forty-one patients with septic shock,post-corticotropin cortisol plasma concentration of 18 g/dL(excluding adrenal insufficiency)hydrocortisone(100 mg i.v.three times daily for 5 days),a significant improvement in hemodynamics and a beneficial effect on survival.These beneficial effects do not appear related to adrenocortical insufficiency,Crit Care Med.1999,Briegel J,Prospective,randomized,double-blind,single-center study,Forty patients with septic shock,Hydrocortisone was started with a loading dose of 100 mg given within 30 mins and followed by a continuous infusion of 0.18 mg/kg/hr.When septic shock had been reversed,the dose of hydrocortisone was reduced to 0.08 mg/kg/hr.This dose was kept constant for 6 days,reduced the time to cessation of vasopressor therapy in human septic shock.This was associated with a trend to earlier resolution of sepsis-induced organ dysfunctions.Overall shock reversal and mortality were not significantly different between the groups,JAMA.2002,Djillali Annane,Placebo-controlled,randomized,double-blind,parallel-group trial performed in 19 intensive care units in France.Three hundred adult patients with septic shock,(50-mg intravenous bolus every 6 hours)and fludrocortisone(50-g tablet once daily)for 7 days,significantly reduced the risk of death in patients with septic shock and relative adrenal insufficiency,There was no significant difference between groups in responders,所有的脓毒性休克患者需要激素吗,patients who responded normally to corticotropin displayed a trend for higher mortality with hydrocortisone therapy(61%vs 53%in the placebo group).,等 待,新的循证医学依据：CORTICUS我们自己的探索,
