Progress of critical illness-related corticosteroid insufficiency

doi:10.3877/cma.j.issn.2096-1537.2017.03.013

Abstract

Abstract:

Despite considerable advances in diagnosis and treatment of the critical illness-related corticosteroid insufficiency (CIRCI), it is still common and related to high morbidity and mortality in critically ill patients. It is difficult for the clinicians to identify those patients who suffer from the disease due to the lack of diagnostic gold standard. Furthermore, CIRCI does not draw enough attention by clinicians because there is lack of high-quality clinical randomized controlled study evidence to support the clinical intervention. In this article, we will summarize the findings of previous studies about the epidemiological evidence, mechanism, diagnosis and treatment of CIRCI, aiming to help further researches in understanding of CIRCI at a more comprehensive level.

Key words: Critical care medicine, Relative adrenal insufficiency, Hypothalamic-pituitary-adrenal axis

Jing Ma, Wei Zhang. Progress of critical illness-related corticosteroid insufficiency[J]. Chinese Journal of Critical Care & Intensive Care Medicine(Electronic Edition), 2017, 03(03): 220-225.

/ / Recommend

Add to citation manager EndNote|Ris|BibTeX

URL: https://icu.cma-cmc.com.cn/EN/10.3877/cma.j.issn.2096-1537.2017.03.013

https://icu.cma-cmc.com.cn/EN/Y2017/V03/I03/220

Figures/Tables 2

References 49

1	Kwon YS, Kang E, Suh GY, et al. A prospective study on the incidence and predictive factors of relative adrenal insufficiency in Korean critically-ill patients[J]. J Korean Med Sci, 2009, 24(4): 668-673.
2	Yang Y, Liu L, Jiang D, et al. Critical illness-related corticosteroid insufficiency after multiple traumas: a multicenter, prospective cohort study[J]. J Trauma Acute Care Surg, 2014, 76(6): 1390-1396.
3	Venkatesh B, Cohen J, Cooper M. Ten false beliefs about cortisol in critically ill patients[J]. Intens Care Med, 2015, 41(10): 1817-1819.
4	Kozyra EF, Wax RS, Burry LD. Can 1 microg of cosyntropin be used to evaluate adrenal insufficiency in critically ill patients? [J]. Ann Pharmacother, 2005, 39(4): 691-698.
5	Annane D, Sebille V, Troche G, et al. A 3-level prognostic classification in septic shock based on cortisol levels and cortisol response to corticotropin[J]. JAMA, 2000, 283(8): 1038-1045.
6	Marik PE. Mechanisms and clinical consequences of critical illness associated adrenal insufficiency[J]. Curr Opin Crit Care, 2007, 13(4): 363-369.
7	Rothwell PM, Udwadia ZF, Lawler PG. Cortisol response to corticotropin and survival in septic shock[J]. Lancet, 1991, 337(8741):582-583.
8	Marik PE, Pastores SM, Annane D, et al. Recommendations for the diagnosis and management of corticosteroid insufficiency in critically ill adult patients: consensus statements from an international task force by the American College of Critical Care Medicine[J]. Crit Care Med, 2008, 36(6): 1937-1949.
9	Bhatia R, Muraskas J, Janusek LW, et al. Measurement of the glucocorticoid receptor: relevance to the diagnosis of critical illness-related corticosteroid insufficiency in children[J]. J Crit Care, 2014, 29(4):691 e1-5.
10	Charmandari E. Primary generalized glucocorticoid resistance and hypersensitivity: the end-organ involvement in the stress response[J]. Sci Signal, 2012, 5(244): 5.
11	Silverman MN, Sternberg EM. Glucocorticoid regulation of inflammation and its functional correlates: from HPA axis to glucocorticoid receptor dysfunction[J]. Ann N Y Acad Sci, 2012, 1261: 55-63.
12	Barquist E, Kirton O. Adrenal insufficiency in the surgical intensive care unit patient[J]. J Trauma, 1997, 42(1): 27-31.
13	Rivers EP, Gaspari M, Saad GA, et al. Adrenal insufficiency in high-risk surgical ICU patients[J]. Chest, 2001, 119(3): 889-896.
14	Zaloga GP, Marik P. Hypothalamic-pituitary-adrenal insufficiency[J]. Crit Care Clin, 2001, 17(1): 25-41.
15	Annane D, Sebille V, Charpentier C, et al. Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock[J]. JAMA, 2002, 288(7): 862-871.
16	Pene F, Hyvernat H, Mallet V, et al. Prognostic value of relative adrenal insufficiency after out-of-hospital cardiac arrest[J]. Intens Care Med, 2005, 31(5): 627-633.
17	Salluh JI, Verdeal JC, Mello GW, et al. Cortisol levels in patients with severe community- acquired pneumonia[J]. Intens Care Med, 2006, 32(4): 595-598.
18	Bornstein SR, Briegel J. A new role for glucocorticoids in septic shock: balancing the immune response[J]. Am J Respir Crit Care Med, 2003, 167(4): 485-486.
19	Galon J, Franchimont D, Hiroi N, et al. Gene profiling reveals unknown enhancing and suppressive actions of glucocorticoids on immune cells[J]. FASEB J, 2002, 16(1): 61-71.
20	Lamberts SW, Bruining HA, De Jong FH. Corticosteroid therapy in severe illness[J]. N Engl J Med, 1997, 337(18): 1285-1292.
21	Shenker Y, Skatrud JB. Adrenal insufficiency in critically ill patients[J]. Am J Respir Crit Care Med, 2001, 163(7): 1520-1523.
22	Cooper MS, Stewart PM. Corticosteroid insufficiency in acutely ill patients[J]. N Engl J Med, 2003, 348(8): 727-734.
23	Boonen E, Vervenne H, Meersseman P, et al. Reduced cortisol metabolism during critical illness[J]. N Engl J Med, 2013, 368(16): 1477-1488.
24	Beishuizen A, Thijs LG, Vermes I. Patterns of corticosteroid-binding globulin and the free cortisol index during septic shock and multitrauma[J]. Intens Care Med, 2001, 27(10):1584-1591.
25	Rothwell PM, Lawler PG. Prediction of outcome in intensive care patients using endocrine parameters[J]. Crit Care Med, 1995, 23(1): 78-83.
26	Michie HR, Manogue KR, Spriggs DR, et al. Detection of circulating tumor necrosis factor after endotoxin administration[J]. N Engl J Med, 1988, 318(23): 1481-1486.
27	Breder CD, Dinarello CA, Saper CB. Interleukin-1 immunoreactive innervation of the human hypothalamus[J]. Science, 1988, 240(4850): 321-324.
28	Erturk E, Jaffe CA, Barkan AL. Evaluation of the integrity of the hypothalamic- pituitary-adrenal axis by insulin hypoglycemia test[J]. J Clin Endocrinol Metab, 1998, 83(7): 2350-2354.
29	Hamrahian AH, Oseni TS, Arafah BM. Measurements of serum free cortisol in critically ill patients[J]. N Engl J Med, 2004, 350(16): 1629-1638.
30	Park YJ, Park KS, Kim JH, et al. Reproducibility of the cortisol response to stimulation with the low dose (1 microg) of ACTH[J]. Clin Endocrinol, 1999, 51(2): 153-158.
31	Dickstein G, Shechner C, Nicholson WE, et al. Adrenocorticotropin stimulation test: effects of basal cortisol level, time of day, and suggested new sensitive low dose test[J]. J Clin Endocrinol Metab, 1991, 72(4): 773-778.
32	Levy-Shraga Y, Pinhas-Hamiel O. Critical illness-related corticosteroid insufficiency in children[J]. Horm Res Paediatr, 2013, 80(5): 309-317.
33	Moraes RB, Czepielewski MA, Friedman G, et al. Diagnosis of adrenal failure in critically ill patients[J]. Arq Bras Endocrinol Metabol, 2011, 55(5): 295-302.
34	Mello RC, Sad EF, Andrade BC, et al. Serum and salivary cortisol in the diagnosis of adrenal insufficiency and as a predictor of the outcome in patients with severe sepsis[J]. Arq Bras Endocrinol Metabol, 2011, 55(7): 455-459.
35	Polito A, Aboab J, Annane D. Adrenal insufficiency in sepsis[J]. Rev Bras Ter Intensiva, 2006, 18(1): 86-94.
36	Annane D, Maxime V, Ibrahim F, et al. Diagnosis of adrenal insufficiency in severe sepsis and septic shock[J]. Am J Respir Crit Care Med, 2006, 174(12): 1319-1326.
37	Selye H. A syndrome produced by diverse nocuous agents[J]. J Neuropsychiatry Clin Neurosci, 1998, 10(2): 230-231.
38	Schneider AJ, Voerman HJ. Abrupt hemodynamic improvement in late septic shock with physiological doses of glucocorticoids[J]. Intens Care Med, 1991, 17(7): 436-437.
39	Dellinger RP, Levy MM, Carlet JM, et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008[J]. Intens Care Med, 2008, 34(1): 17-60.
40	Beigel J, Eichacker P. Hydrocortisone and fludrocortisone improved 28-day survival in septic shock and adrenal insufficiency[J]. ACP J Club, 2003, 138(2): 44.
41	Eisen LA. Epoetin alfa in critically ill patients[J]. N Engl J Med, 2007, 357(24): 2516.
42	Sprung CL, Annane D, Keh D, et al. Hydrocortisone therapy for patients with septic shock[J]. N Engl J Med, 2008, 358(2): 111-124.
43	Annane D, Bellissant E, Bollaert PE, et al. Corticosteroids in the treatment of severe sepsis and septic shock in adults: a systematic review[J]. JAMA, 2009, 301(22): 2362-2375.
44	Minneci PC, Deans KJ, Eichacker PQ, et al. The effects of steroids during sepsis depend on dose and severity of illness: an updated meta-analysis[J]. Clin Microbiol Infect, 2009, 15(4): 308-318.
45	Minneci PC, Deans KJ, Natanson C. Corticosteroid therapy for severe sepsis and septic shock[J]. JAMA, 2009, 302(15): 1643.
46	Boonen E, Bornstein SR, Van den Berghe G. New insights into the controversy of adrenal function during critical illness[J]. Lancet Diabetes Endocrinol, 2015, 3(10): 805-815.
47	Dellinger RP, Levy MM, Rhodes A, et al. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012[J]. Crit Care Med, 2013, 41(2): 580-637.
48	Venkatesh B, Myburgh J, Finfer S, et al. The ADRENAL study protocol: adjunctive corticosteroid treatment in critically ill patients with septic shock[J]. Crit Care Resusc, 2013, 15(2):83-88.
49	Bornstein SR, Allolio B, Arlt W, et al. Diagnosis and Treatment of Primary Adrenal Insufficiency: an Endocrine Society Clinical Practice Guideline[J]. J Clin Endocrinol Metab, 2016, 101(2): 364-389.

作者	国别	时间	研究对象	研究期限	例数	发病人群	发病率（%）
Barquist等^[12]	美国	1997年	SICU	9个月	不详	外伤和外科患者	0.66
						住院时间>14 d	6
						住院时间>14 d且年龄>55岁	11
Rivers等^[13]	美国	2001年	SICU	不详	104	年龄>55岁的术后出现血管收缩剂依赖型低血压者	32.7
Zaloga等^[14]	美国	2001年	ICU	综述		危重症患者	30~40
						脓毒性休克	60
Annane等^[15]	法国	2002年	ICU	1995—1999年	300	脓毒症休克	76.5
Pene等^[16]	法国	2005年	MICU	不详	64	64例心脏停搏后复苏	52
Salluh等^[17]	比利时	2006年	M-SICU	2003—2005年	40	40例社区获得性重症肺炎、败血症休克患者	65
Salluh等^[17]	比利时	2006年	M-SICU	2003—2005年	40	40例社区获得性重症肺炎、败血症休克患者	63

作者	国别	时间	研究对象	研究期限	例数	发病人群	发病率（%）
Barquist等^[12]	美国	1997年	SICU	9个月	不详	外伤和外科患者	0.66
						住院时间>14 d	6
						住院时间>14 d且年龄>55岁	11
Rivers等^[13]	美国	2001年	SICU	不详	104	年龄>55岁的术后出现血管收缩剂依赖型低血压者	32.7
Zaloga等^[14]	美国	2001年	ICU	综述		危重症患者	30~40
						脓毒性休克	60
Annane等^[15]	法国	2002年	ICU	1995—1999年	300	脓毒症休克	76.5
Pene等^[16]	法国	2005年	MICU	不详	64	64例心脏停搏后复苏	52
Salluh等^[17]	比利时	2006年	M-SICU	2003—2005年	40	40例社区获得性重症肺炎、败血症休克患者	65
Salluh等^[17]	比利时	2006年	M-SICU	2003—2005年	40	40例社区获得性重症肺炎、败血症休克患者	63

实验方法	取值范围	诊断效能
总皮质醇水平^[28]	<10 μg/dL	特异度为100%，阳性预测值为0.93，敏感度仅为19%
游离皮质醇水平^[29]	<2.0 μg/dL	尤其对于白蛋白<25g/L的危重症患者动态监测其浓度可减少不必要糖皮质激素治疗
标准ACTH兴奋试验（250 μg）^[30,31]	正常昼夜波动节律消失	容易得出假阴性结果^[32]，为避免假性异常结果，试验最好在清晨进行
小剂量ACTH兴奋试验（1 μg）^[32]	20 min或30 min后正常皮质醇反应的标准多变：17~22.5 μg/dL	敏感度较低（62%~69%），操作复杂，未在临床上广泛应用，2008年SCCM仍推荐^[8]采用250 μg标准ACTH快速兴奋试验
清晨唾液皮质醇浓度^[33,34]	>5.8 ng/mL	可排除肾上腺皮质功能减退症
	<1.8 ng/mL	肾上腺皮质功能减退症的可能性较大，故可用于筛查肾上腺皮质功能减退症
美替拉酮刺激试验^[35,36]	缺乏高质量证据	临床上尚未普及

实验方法	取值范围	诊断效能
总皮质醇水平^[28]	<10 μg/dL	特异度为100%，阳性预测值为0.93，敏感度仅为19%
游离皮质醇水平^[29]	<2.0 μg/dL	尤其对于白蛋白<25g/L的危重症患者动态监测其浓度可减少不必要糖皮质激素治疗
标准ACTH兴奋试验（250 μg）^[30,31]	正常昼夜波动节律消失	容易得出假阴性结果^[32]，为避免假性异常结果，试验最好在清晨进行
小剂量ACTH兴奋试验（1 μg）^[32]	20 min或30 min后正常皮质醇反应的标准多变：17~22.5 μg/dL	敏感度较低（62%~69%），操作复杂，未在临床上广泛应用，2008年SCCM仍推荐^[8]采用250 μg标准ACTH快速兴奋试验
清晨唾液皮质醇浓度^[33,34]	>5.8 ng/mL	可排除肾上腺皮质功能减退症
	<1.8 ng/mL	肾上腺皮质功能减退症的可能性较大，故可用于筛查肾上腺皮质功能减退症
美替拉酮刺激试验^[35,36]	缺乏高质量证据	临床上尚未普及

[1]	Wen Zhang, Chuanwei Li, Gang Liu, Min Chen, Helian Zhang, Qi Li, Yuchao Dong. Clinical characteristics of patients with infectious caused by carbapenem-resistant Klebsiella pneumonia in an intensive care unit [J]. Chinese Journal of Lung Diseases(Electronic Edition), 2017, 10(01): 5-9.
[2]	Jingyuan Xu, Bo Xie, Haibo Qiu, Yi Yang. Exploration and practice for integration of political courses into Critical Care Medicine [J]. Chinese Journal of Critical Care & Intensive Care Medicine(Electronic Edition), 2023, 09(03): 265-268.
[3]	Yan Cui, Keliang Xie. Exploration and practice of integrating humanities with ideological and political education in critical care medicine teaching [J]. Chinese Journal of Critical Care & Intensive Care Medicine(Electronic Edition), 2023, 09(02): 205-209.
[4]	Fei Yang, Shaohua Wang, Zhuang Chen, Hui Shi, Yun Long. Clinical outcomes of heart dysfunction treated by extracorporeal membrane oxygenation (ECMO): a meta-analysis [J]. Chinese Journal of Critical Care & Intensive Care Medicine(Electronic Edition), 2021, 07(04): 347-354.
[5]	Wenyan Xiao, Yu Liu, Zongqing Lu, Gan Tao, Jin Zhang, Yang Zhang, Tianfeng Hua, Min Yang. Progress in septic cardiomyopathy from 2000 to 2020: analysis based on knowledge visualization [J]. Chinese Journal of Critical Care & Intensive Care Medicine(Electronic Edition), 2021, 07(04): 331-338.
[6]	Qianyi Zhan, Zhihui Zhang, Qing Zang, Yang Chen, Shiyi Wu, Ruize Zhu, Jiana Chen, Hongzhen Wu, Xinyi Zhou, Shuchang Weng, Yongbo Huang, Chun Yang, Xiaoqing Liu, Yimin Li. Investigation and strategic study on clinical medical students' knowledge of critical care medicine [J]. Chinese Journal of Critical Care & Intensive Care Medicine(Electronic Edition), 2021, 07(03): 241-245.
[7]	Xiang Zhou, Longxiang Su, Hao Wang, Dongkai Li, Huan Chen, Meili Duan, Jian Liu, Bin Ouyang, Bingyu Qin, Hongliang Wang, Xue Wang, Lei Xu, Xiangyou Yu, Feihu Zhou, Jiao Liu, Lina Zhang, Yun Long. Infrastructure and willingness survey for big data research of critical care medicine in 2019 [J]. Chinese Journal of Critical Care & Intensive Care Medicine(Electronic Edition), 2020, 06(04): 411-417.
[8]	Yibing Zhu, Xiuming Xi. The impact of current clinical research methodology on randomized controlled studies [J]. Chinese Journal of Critical Care & Intensive Care Medicine(Electronic Edition), 2020, 06(04): 365-369.
[9]	Wei Huang. Significance of negative clinical trials in the field of Critical Care Medicine [J]. Chinese Journal of Critical Care & Intensive Care Medicine(Electronic Edition), 2018, 04(02): 128-130.
[10]	Chang Liu, Yan Kang. How to evaluate and select sedatives and analgesics considering their cardiovascular and respiratory effects? [J]. Chinese Journal of Critical Care & Intensive Care Medicine(Electronic Edition), 2017, 03(04): 291-295.
[11]	Lixia Liu, Zhenjie Hu. Fluid overload and acute kidney injury: cause or consequence [J]. Chinese Journal of Critical Care & Intensive Care Medicine(Electronic Edition), 2017, 03(01): 73-77.
[12]	Xiangdong Guan, Ye Zhang. The Status of continuous blood purification technology in intensive care unit [J]. Chinese Journal of Critical Care & Intensive Care Medicine(Electronic Edition), 2017, 03(01): 2-4.
[13]	Chunting Wang, Man Chen, Kaijiang Yu, Linlin Zhang, Haibo Qiu, Yi Yang, Xiangdong Guan, Duning Zhu, Tongwa Cao, Dechang Chen, Renhua Sun, Jing Yan, Rongguo Yu, Jiandong Lin, Bao Liu, Xiandi He, Kejian Qian, Critical Care Medicine Branch of Chinese Medical Association. Current status of critical care medicine in Eastern China [J]. Chinese Journal of Critical Care & Intensive Care Medicine(Electronic Edition), 2016, 02(01): 43-49.
[14]	Jianxin Zhou. Severe brain injury: pathophysiology and treatment [J]. Chinese Journal of Critical Care & Intensive Care Medicine(Electronic Edition), 2015, 01(01): 48-52.
[15]	Maimaiti Zuolamu·, Mikerensha. Correlation analysis of between gastroesophageal reflux and ventilator associated pneumonia in patients with mechanical ventilation in ICU [J]. Chinese Journal of Gastroesophageal Reflux Disease(Electronic Edition), 2018, 05(04): 157-159.

Please choose a citation manager

Content to export