Effect of low-dose glucocorticoid on corticosteroid insufficient patients with acute exacerbation of chronic obstructive pulmonary disease

doi:10.5847/wjem.j.1920-8642.2015.01.006

Abstract

Abstract:

BACKGROUND: This study aimed to investigate the prevalence rate of critical illness-related corticosteroid insufficiency (CIRCI) and the effect of low-dose glucocorticoid on prognosis of CIRCI in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD).
METHODS: Since January 2010 to December 2012, 385 patients, who met the criteria of AECOPD, were enrolled in the Intensive Care Unit (ICU) of the First People's Hospital and Municipal Central Hospital of Xiangtan City. The AECOPD patients complicated with CIRCI screened by an adrenalcorticotrophic hormone test within 12 hours after admission to ICU were divided into a treatment group (n=32) and a control group (n=31) for a prospective, randomized and controlled clinical trial. Hydrocortisone (150 mg/d) or normal saline was injected intravenously for 7 days. The patients were followed up for 28 days after injection. The endpoint included 28-day survival time, non-shock time, ICU stay and the period of non-mechanical ventilation. The markers of inflammation C-reactive protein, tumor necrosis factor-α, interleukin 6 and procalcitonin were measured at baseline and 7 days after treatment. The variables were analyzed by Student's t test, the non-parametric statistical test, the Chi-square test or the Kaplan-Meier method with SPSS18.0 statistic software. A P value <0.05 was considered statistically significant.
RESULTS: Totally 63 patients were diagnosed with CIRCI by an adrenalcorticotrophic hormone test and the prevalence rate was 16.4%. The shock rate of the AECOPD patients complicated with CIRCI was higher than that of the AECOPD patients without CIRCI (23.8% vs. 8.7%, P<0.01). Kaplan-Meier analysis revealed that the 28-day survival time of the treatment group was obviously longer than that of the control group (P<0.05). Compared with the control group, shock-free days within 28 days was longer in the treatment group (18.2±9.5 vs. 25.8±4.1, P<0.05). Treatment with low-dose glucocorticoid obviously decreased the markers of infection and inflammation (P<0.01), such as C-reactive protein (13.2±5.5 mg/L vs. 8.3±3.1 mg/L for the control group; 13.5±5.9 mg/L vs. 5.1±2.3 mg/L for the treatment group), tumor necrosis factor-α (26.1±16.2 μg/L vs. 17.5±11.7 μg/L for the control group; 25.0±14.8 μg/L vs. 10.4±7.8 μg/L for the treatment group) and procalcitonin (3.88 μg/L vs. 2.03 μg/L for the control group; 3.77 μg/L vs. 1.26 μg/L for the treatment group). Furthermore, the markers in the treatment group decreased more obviously than those in the control group (P<0.01).
CONCLUSION: The prevalence rate of CIRCI was higher in the patients with AECOPD in the department of critical medicine, and low-dose glucocorticoid treatment for one week reduced the 28-day mortality, shock time and markers of infection and inflammation.

Key words: Chronic obstructive pulmonary disease, Acute exacerbation, Glucocorticoid, Critical illness, Corticosteroid insufficiency, Prevalence rate, Prognosis, Inflammation

Wei-ping Sun, Guang-xiong Yuan, Yan-juan Hu, Li-zhen Liao, Lin Fu. Effect of low-dose glucocorticoid on corticosteroid insufficient patients with acute exacerbation of chronic obstructive pulmonary disease[J]. World Journal of Emergency Medicine, 2015, 6(1): 34-39.

Figures/Tables 4

Table 1

Figure 1.

Table 2

Table 3

References 16

1	Marik PE, Pastores SM, Annane D, Meduri GU, Sprung CL, Arlt W, 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. Crit Care Med 2008; 36:1937-1949. pmid: 18496365
2	Annane D, Sébille V, Charpentier C, Bollaert PE, François B, Korach JM, et al. Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA 2002; 288:862-871. pmid: 12186604
3	Liu L, Li J, Huang YZ, Liu SQ, Yang CS, Guo FM, et al. The effect of stress dose glucocorticoid on patients with acute respiratory distress syndrome combined with critical illness-related corticosteroid insufficiency. Zhonghua Nei Ke Za Zhi 2012; 51:599-603. pmid: 23158856
4	Schuetz P, Christ-Crain M, Schild U, Süess E, Facompre M, Baty F, et al. Effect of a 14-day course of systemic corticosteroids on the hypothalamic-pituitary-adrenal-axis in patients with acute exacerbation of chronic obstructive pulmonary disease. BMC Pulm Med 2008; 8:1-8.
5	Zhang YC, Zhang SJ, Teng GL, Tian GL, Xu L, Cao RF, et al. Adrenal insufficiency evaluation by using low-dose ACTH stimulation test in critical illness children. Zhonghua Er Ke Za Zhi 2012,21:472-477.
6	Chen YC, Lin YH, Chen SH, Chen YC, Chou LF, Chen TJ, et al. Epidemiology of adrenal insufficiency: a nationwide study of hospitalizations in Taiwan from 1996 to 2008. J Chin Med Assoc 2013; 76:140-145.
7	Niewoehner DE, Erbland ML, Deupree RH, Collins D, Gross NJ, Light RW, et al. Effect of systemic glucocorticoids on exacerbations of chronic obstructive pulmonary disease. Department of Veterans Affairs Cooperative Study Group. N Engl J Med 1999; 340:1941-1947. pmid: 10379017
8	Vondracek SF, Hemstreet BA. Is there an optimal corticosteroid regimen for the management of an acute exacerbation of chronic obstructive pulmonary disease? Pharmacotherapy 2006; 26:522-532. pmid: 16553512
9	He J, Hou XY. The potential contributions of traditional Chinese medicine to emergency medicine. World J Emerg Med 2013; 4:92-97. pmid: 25215100
10	Huang CJ, Lin HC. Association between adrenal insufficiency and ventilator weaning. Am J Respir Crit Care Med 2006; 173:276-280. pmid: 16272449
11	Sprung CL, Annane D, Keh D, Moreno R, Singer M, Freivogel K, et al. Hydrocortisone therapy for patients with septic shock. N Engl J Med 2008; 358:111-124. pmid: 18184957
12	Thomas Z, Fraser GL. An update on the diagnosis of adrenal insufficiency and the use of corticotherapy in critical illness. Ann Pharmacother 2007; 41:1456-1465. pmid: 17698896
13	Xie J, Yang XY, Shi JD, Deng XQ, Long W. A new inflammation marker of chronic obstructive pulmonary disease-adiponectin. World J Emerg Med 2010; 1:190-195. pmid: 25214966
14	Liu ZH, Zhang XR, Hu XY, Cheng MY, Xu JY, Du YC. Effect of glucocorticoid on MIP-1α and NF-κb expressing in the lung of rats undergoing mechanical ventilation with a high tidal volume. World J Emerg Med 2011; 2:66-69. pmid: 25214986
15	Arafah BM. Hypothalamic pituitary adrenal function during critical illness: limitations of current assessment methods. J Clin Endocrinol Metab 2006; 91:3725-3745. doi: 10.1210/jc.2006-0674 pmid: 16882746
16	Seam N, Meduri GU, Wang H, Nylen ES, Sun J, Schultz MJ, et al. Effects of methylprednisolone infusion on markers of inflammation, coagulation, and angiogenesis in early acute respiratory distress syndrome. Crit Care Med 2012; 40:495-501. pmid: 21983371

Baseline data	Patients with CIRCI	Patients without CIRCI
Cases (male/female)	63 (50/13)	322 (255/67)
Age (year)	72.3±16.8^#	58.2±18.9
Shock incidence	23.8%^#	8.7%
PaO₂ (mmHg)	65.7±11.8^*	75.6±12.3
PaCO₂ (mmHg)	47.1±13.4	42.5±11.4
Base excess (mmol/L)	2.5 (-7.5, 8.6)	2.0 (-8.2, 7.9)
pH	7.43±0.18	7.40±0.21
APACHE II (scores)	17.0±4.8	14.3±4.0
CPIS (scores)	4.8±1.8	4.0±1.2
CAPS score (score)	29.8±7.8	25.5±6.5
CRP (mg/L)	13.4±5.3	12.1±4.5
IL-6 (μg/L)	13.6±7.2	14.5±9.1
TNF-α (μg/L)	25.3±15.7	23.1±14.0
PCT (μg/L)	3.85 (0.25, 8.3)	3.25 (0.18, 7.1)
White blood cells (×10⁹/L)	14.1±5.4	14.7±6.0
Platelet (×10⁹/L)	168±109	159±114
Lactic acid (mmol/L)	3.2 (1.3, 4.6)^*	2.5 (1.1, 4.0)

Parameters	Control group	Treatment group
Cases (male/female)	31 (25/6)	32 (25/7)
Age (years)	71.8±15.9	72.7±17.2
Prevalence baseline shock	7/31	8/32
28-day non-mechanical ventilation time (days)	18.3±6.2	20.5±5.1
28-day shock incidence	11/31	8/32
28-day non-shock time (days)	18.2±9.5	25.8±4.1^*
28-day duration of ICU stay (days)	12.8±6.1	10.5±5.3

Parameters	Control group		Treatment group
Parameters	Before	After	Before	After
PaO₂ (mmHg)	65.3±11.3	80.4±12.5^*	65.9±12.2	82.5±11.8^*
PaCO₂ (mmHg)	47.4±12.8	40.3±11.5^*	46.6±12.6	37.8±13.7^*
BE (mmol/L)	2.5 (-7.1, 8.5)	1.3 (-5.7, 6.8)	2.5 (-7.8, 8.8)	1.5 (-4.1, 6.5)
pH	7.44±0.20	7.39±0.12	7.43±0.17	7.40±0.15
APACHE II	16.7±4.5	12.3±3.2^*	17.2±4.7	10.1±2.9^*
CPIS score	4.8±1.9	3.1±0.8^*	4.6±1.8	3.0±1.2^*
CAPS score	30.1±6.7	20.3±5.4^*	29.2±7.0	22.0±5.8^*
WBC (×10⁹/L)	14.3±6.2	8.3±4.7^#	14.0±5.5	11.9±3.5
Platelet (×10⁹/L)	165±105	158±96	170±112	161±103
CRP (mg/L)	13.2±5.5	8.3±3.1^#	13.5±5.9	5.1±2.3^#Δ
IL-6 (μg/L)	13.7±7.5	11.4±5.6	13.1±6.9	8.3±3.2^#Δ
TNF-α (μg/L)	26.1±16.2	17.5±9.7^#	25.0±14.8	10.4±7.8^#▲
PCT (μg/L)	3.88 (0.25, 8.5)	2.03 (0.15, 5.1)^#	3.77 (0.21, 8.0)	1.26 (0.10, 3.2)^#▲
Lactic acid (mmol/L)	3.4 (1.2, 4.8)	2.8 (0.8, 3.6)	3.2 (1.0, 4.5)	2.7 (1.0, 4.6)

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