糖皮质激素在脓毒症中的应用

1、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 周围抵抗的发生机制肾上腺功能不全以兴奋试验后皮质醇的升幅被削峰为特征临床症状和体征是决定诊断的关键因素快速刺激实验时，皮质醇增加幅度9/若任意时间血皮质醇水平低于 552nmol/L（19.3ug/dl)相对肾上腺功能不全试验后血皮质醇低于 690nmol/L （24.2ug/dl)SymptomsWeaknes

2、s and fatigueAnorexia, nausea, vomitingAbdominal painMyalgia or arthralgiaPostural dizzinessCraving for saltHeadachesMemory impairmentDepressionFindings on physical examinationIncreased pigmentationHypotension (postural)TachycardiaFeverDecreased body hairVitiligoFeatures of hypopituitarismAmenorrhea

3、Intolerance of coldClinical problemsHemodynamic instabilityHyperdynamic (common)Hypodynamic (rare)Ongoing inflammation with no obvious sourceMutiple-organ dysfunctionHypoglycemiaLaboratory 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:

4、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, sep

5、tic 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%), ris

6、e 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反应高死亡率相对肾上腺功能不全和肾上腺功能不全ACTH testpost-corticotropin plasma cortisol levels 18 g/dL2.an increase in p

7、lasma cortisol level 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

8、, 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 hydrocort

9、isone 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 significa

10、ntly different between the groupsJAMA. 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 grou