圍術(shù)期糖皮質(zhì)激素的基礎(chǔ)與臨床課件

1、圍術(shù)期糖皮質(zhì)激素應(yīng)用的基礎(chǔ)與臨床Perioperative Glucocorticoid Application: from Basic Science to Clinical Trials病例報(bào)道：Case Reports病例1：女，82歲，41kg,因摔倒后致右側(cè)人工股骨粗隆區(qū)粉碎性骨折，需擇期行人工股骨頭置換術(shù)；術(shù)前合并T2DM、有高血壓病史多年，不規(guī)則服用降壓藥，腦梗病史十余年，體質(zhì)消瘦，內(nèi)科藥物控制尚可。麻醉方式：全身麻醉氣管內(nèi)插管，誘導(dǎo)與維持平穩(wěn)；手術(shù)進(jìn)展順利，術(shù)中填充人工骨水泥時(shí)出現(xiàn)血壓驟降、心動(dòng)過(guò)速，SPO2下降；給予甲基強(qiáng)的松龍針劑80mg靜注、去氧腎上腺素分次靜注，去甲腎上

2、腺素與腎上腺素泵注，血流動(dòng)力學(xué)仍難以維持穩(wěn)定，全身大面積皮疹漸現(xiàn)?？紤]：極罕見(jiàn)的嚴(yán)重骨水泥過(guò)敏反應(yīng)，合并應(yīng)激功能不全，遂給予氫化可的松150mg快速靜滴后，有創(chuàng)血壓回升至105/50mmHg, HR110次/分，繼續(xù)給予氫化可的松150mg靜滴、大劑量Ad 80ng/kgmin、NE120ng/kgmin泵注，維持MAP55 mmHg；手術(shù)結(jié)束后轉(zhuǎn)ICU；次日清醒，出現(xiàn)急性腎功能衰竭，繼續(xù)抗過(guò)敏、免疫調(diào)節(jié)、強(qiáng)心、利尿、床旁腹膜透析支持等綜合性處理，術(shù)后3d脫機(jī)，繼續(xù)透析、激素支持治療；30d后基本康復(fù)。病例2：成年男性，車(chē)禍后雙下肢大面積撕脫傷清創(chuàng)、多發(fā)性肋骨骨折合并血?dú)庑匦厍婚]式引流術(shù)后，胸

3、椎CT/MRI 示：T8T12壓縮性骨折伴不完全截癱，由外院轉(zhuǎn)至我院。術(shù)前出現(xiàn)神志基本清醒，頭顱CT/MRI未見(jiàn)明顯異常。擬行手術(shù)：俯臥位椎管內(nèi)探查減壓，胸椎壓縮性骨折復(fù)位內(nèi)固定術(shù)。麻醉方式：有創(chuàng)血流動(dòng)力學(xué)監(jiān)測(cè)下靜-吸全麻、慢誘導(dǎo)氣管內(nèi)插管；麻醉誘導(dǎo)與維持均平穩(wěn)，術(shù)中生命體征平穩(wěn)，椎管內(nèi)減壓前給予甲基強(qiáng)的松龍500mg靜注，術(shù)畢轉(zhuǎn)PACU，半小時(shí)內(nèi)拔除氣管內(nèi)導(dǎo)管、生命體征平穩(wěn)，患者平靜合作，轉(zhuǎn)回普通病房，術(shù)后1d病房繼續(xù)靜脈給予甲基強(qiáng)的松龍500mg，出現(xiàn)睡眠倒錯(cuò)，72h后漸出現(xiàn)意識(shí)障礙，注意力與定向力異常表現(xiàn)，請(qǐng)麻醉科會(huì)診：考慮系創(chuàng)傷后應(yīng)激功能紊亂，給予氟哌利多2mg，q6h（用藥24h后停

4、藥），癥狀緩解，拔除胸腔閉式引流，睡眠節(jié)律恢復(fù)至正常?；颊咭恢芎笕?、輪椅平推出院。30d隨訪(fǎng)預(yù)后基本良好，無(wú)麻醉遠(yuǎn)期并發(fā)癥。病例3：女性，83歲，行人工股骨頭置換術(shù)，患者術(shù)前隱瞞病史，術(shù)中發(fā)生嚴(yán)重哮喘持續(xù)狀態(tài)，給予：甲基強(qiáng)的松龍50mg靜注 +氫考150mg靜滴+布地奈德/博利康尼霧化吸入，緩解。問(wèn)題：圍術(shù)期創(chuàng)傷后應(yīng)激功能失調(diào)、生物節(jié)律改變與麻醉安全及危重癥患者的管理原發(fā)性腎上腺皮質(zhì)功能不全危及生命，多種內(nèi)分泌激素不足繼發(fā)性或三發(fā)性腎上腺皮質(zhì)機(jī)能不全，糖皮質(zhì)激素典型缺乏為什么圍術(shù)期會(huì)出現(xiàn)各類(lèi)生物節(jié)律的紊亂現(xiàn)象？流行病學(xué)病因病機(jī)臨床表現(xiàn)疾病診斷 胰島素激發(fā)試驗(yàn)CRH激發(fā)試驗(yàn)麻醉管理一、機(jī)體內(nèi)穩(wěn)

5、態(tài)維持的主要應(yīng)激激素 糖皮質(zhì)激素下丘腦-腺垂體-腎上腺軸：hypothalamic-pituitary-adrenal （HPA）axis糖皮質(zhì)激素-糖皮質(zhì)激素受體：glucocorticoid-activated GR11beta-hydroxysteroid dehydrogenase,11beta-HSD)二、糖皮質(zhì)激素受體的結(jié)構(gòu)三、糖皮質(zhì)激素調(diào)節(jié)的信號(hào)轉(zhuǎn)導(dǎo)途徑Glucocorticoid activation of the membrane-associated GR regulates gap junction intercellular.四、糖皮質(zhì)激素的生物學(xué)功能PTSD & GC

6、五、糖皮質(zhì)激素的藥理學(xué)功能（小結(jié)）調(diào)節(jié)糖、脂肪、和蛋白質(zhì)的生物合成和代謝抑制免疫應(yīng)答抗炎提高機(jī)體對(duì)內(nèi)毒素的耐受力抗毒抗休克刺激骨髓的造血功能提高中樞神經(jīng)系統(tǒng)興奮性 六、圍術(shù)期應(yīng)激性記憶受損與GR應(yīng)激狀態(tài)下，外源性系統(tǒng)給予大劑量糖皮質(zhì)激素?fù)p害記憶的提取與鞏固GC穿越血-腦屏障，影響HPA軸，參與PTSD的形成與發(fā)展七、糖皮質(zhì)激素與急性肺損傷糖皮質(zhì)激素能有效糾正系統(tǒng)性炎癥與部分逆轉(zhuǎn)ALI / ARDS的病理生理紊亂盲目增加糖皮質(zhì)激素用量并不能改善ALI / ARDS的病理生理進(jìn)程Glucocorticoid Treatment in Acute Lung Injury and AcuteRespi

7、ratory Distress SyndromeReview ArticleCritical Care Clinics, Volume 27, Issue 3, July 2011, Pages 589-607Paul E. Marik, G. Umberto Meduri, Patricia R.M. Rocco, Djillali AnnaneExperimental and clinical evidence show a strong association between dysregulated systemic inflammation and progression of ac

8、ute respiratory distress syndrome (ARDS). This article reviews eight controlled studies evaluating corticosteroid treatment initiated before day 14 of ARDS. Available data provide a consistent strong level of evidence for improving outcomes. Treatment was also associated with a markedly reduced risk

9、 of death. This low-cost highly effective therapy is well-known, and has a low-risk profile when secondary prevention measures are implemented. The authors recommend prolonged methylprednisolone at 1 mg/kg/d initially in early ARDS, increasing to 2 mg/kg/d after 7 to 9 days of no improvement.八、糖皮質(zhì)激素

10、全身用藥的利弊抑制下丘腦-垂體-腎上腺素（HPA）軸：腎上腺萎縮腎臟：水鈉潴留代謝：T2DMCNS：行為、認(rèn)知與情緒改變循環(huán)：高血壓、消化：應(yīng)激性潰瘍骨骼肌肉系統(tǒng)：骨折、肌肉萎縮眼科：青光眼、白內(nèi)障ICS1.5mg/d, 同樣引起全身性副作用！主要因素：經(jīng)口服吸收，肝首過(guò)消除！九、圍術(shù)期吸入糖皮質(zhì)激素的可行性早在上世紀(jì)80年代,吸入用布地奈德混懸液（普米克令舒），試用于治療支氣管哮喘等氣道高反應(yīng)性疾??；在口服布地奈德類(lèi)固醇類(lèi)藥物治療不適合時(shí)，吸入普米克令舒與0.9%生理鹽水和特布他林、沙丁胺醇、色甘酸鈉或異丙托溴銨溶液混合吸入使用，取得良好的臨床效應(yīng)；肝功能不全可能會(huì)影響到皮質(zhì)類(lèi)固醇的消除。P

11、roof of concept for next-generation nanoparticle drugs in humans. Chrastina A, Massey KA Schnitzer JE. Overcoming in vivo barriers to targeted nanodelivery. Wiley Interdiscip. Rev. Nanomedicine Nanobiotechnol., 3 (2011), pp. 421437Sheridan C. Proof of concept for next-generation nanoparticle drugs i

12、n humansNat. Biotechnol., 30 (2012), pp. 471473九、圍術(shù)期吸入糖皮質(zhì)激素的可行性十、吸入糖皮質(zhì)激素治療呼吸道炎癥性疾病肺炎哮喘COPD過(guò)敏性鼻炎BackgroundThe incidence of pediatric asthma has increased dramatically over the past few decades, with approximately 5% of American children affected by the disease.ObjectivesTo compare the efficacy and sa

13、fety of once-daily budesonide Turbuhaler with placebo in asthmatic children previously treated with orally inhaled corticosteroids.MethodsThis randomized, double-blind, placebo-controlled, multicenter (17 centers) study included 274 male and female children (aged 6 to 17 years) with a history of ast

14、hma for at least the previous 6 months. Patients received placebo or budesonide Turbuhaler (200 g or 400 g) once daily for 12 weeks. Efficacy variables included mean changes from baseline in forced expiratory volume in 1 second (FEV1), am and pm peak expiratory flow rates (PEFRs), nighttime and dayt

15、ime asthma symptom severity scores, patient discontinuations, use of 2-agonists as breakthrough medication, forced vital capacity (FVC), and midexpiratory flow rate between 25% and 75% of FVC (FEF25%-75%). Safety was evaluated by adverse events, physical examinations, vital signs, and laboratory tes

16、ts.ResultsBaseline characteristics were comparable among treatment groups. Percentage of predicted FEV1 at baseline was 76.6 6.9 for placebo, 77.5 7.1, and 77.0 7.8 for the budesonide Turbuhaler 200 g and 400 g groups, respectively. Significantly (P 0.024) more placebo patients (24%) discontinued tr

17、eatment because of disease deterioration or no improvement than budesonide Turbuhaler 200 g (11%) or 400 g patients (10%). Patients receiving budesonide Turbuhaler experienced significant improvements in FEV1 compared with patients receiving placebo (P 0.015). Significant (P 0.041) improvements over placebo also were observed in am and pm PEFRs, FVC, FEF25%-75%, nighttime and daytime asthma symptoms, and amount of 2-agonist used in both budesonide Turbuhaler groups. Adverse events were generally mi