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Critical Care
Published in: Critical Care 1/2017

Open Access 01-12-2017 | Research

Time-dependent association of glucocorticoids with adverse outcome in community-acquired pneumonia: a 6-year prospective cohort study

Authors: Manuela Nickler, Manuel Ottiger, Christian Steuer, Alexander Kutz, Mirjam Christ-Crain, Werner Zimmerli, Robert Thomann, Claus Hoess, Christoph Henzen, Luca Bernasconi, Andreas Huber, Beat Mueller, Philipp Schuetz, for the ProHOSP Study Group

Published in: Critical Care | Issue 1/2017

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Abstract

Background

The hypothalamic-pituitary-adrenal stress axis plays a crucial role in community-acquired pneumonia (CAP), with high cortisol being associated with disease severity and corticosteroid treatment resulting in earlier time to recovery. Our aim in the present study was to compare different glucocorticoid hormones, including cortisol, 11-deoxycortisol, cortisone, and corticosterone, regarding their association with short- and long-term adverse outcomes in a well-defined CAP cohort.

Methods

We prospectively followed 285 patients with CAP from a previous Swiss multicenter trial for a median of 6.1 years and measured different admission glucocorticoid serum levels by liquid chromatography coupled with tandem mass spectrometry. We used adjusted Cox regression models to investigate associations between admission hormone levels and all-cause mortality at different time points.

Results

Mortality was 5.3% after 30 days and increased to 47.3% after 6 years. High admission cortisol was associated with adverse outcome after 30 days (adjusted OR 3.85, 95% CI 1.10–13.49, p = 0.035). In the long term (i.e.,), however, high admission cortisol was associated with better survival (adjusted HR after 3 years 0.53, 95% CI 0.32–0.89, p = 0.017; adjusted HR after 6 years 0.57, 95% CI 0.36–0.90, p = 0.015). Compared with 11-deoxycortisol, cortisone, and corticosterone, cortisol showed the highest association with mortality.

Conclusions

Among different glucocorticoid hormones, cortisol showed the highest association with mortality in CAP. Whereas a more pronounced glucocorticoid stress response on hospital admission was associated with higher short-term adverse outcome, long-term outcome was favorable in these patients. These data should support the correct interpretation of glucocorticoid blood data.
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Literature
1.
Chrousos GP. The hypothalamic-pituitary-adrenal axis and immune-mediated inflammation. N Engl J Med. 1995;332(20):1351–62.CrossRefPubMed
2.
Nylen ES, Müller B. Endocrine changes in critical illness. J Intensive Care Med. 2004;19(2):67–82.CrossRefPubMed
3.
Müller B. Endocrine aspects of critical illness. Ann Endocrinol (Paris). 2007;68(4):290–8.CrossRef
4.
Schuetz P, Müller B. The hypothalamic-pituitary-adrenal axis in critical illness. Endocrinol Metab Clin North Am. 2006;35(4):823–38.CrossRefPubMed
5.
Van den Berghe G, de Zegher F, Bouillon R. Clinical review 95: acute and prolonged critical illness as different neuroendocrine paradigms. J Clin Endocrinol Metab. 1998;83(6):1827–34.PubMed
6.
Marik PE, Kiminyo K, Zaloga GP. Adrenal insufficiency in critically ill patients with human immunodeficiency virus. Crit Care Med. 2002;30(6):1267–73.CrossRefPubMed
7.
Jurney TH, Cockrell Jr JL, Lindberg JS, Lamiell JM, Wade CE. Spectrum of serum cortisol response to ACTH in ICU patients: correlation with degree of illness and mortality. Chest. 1987;92(2):292–5.CrossRefPubMed
8.
Span LF, Hermus AR, Bartelink AK, Hoitsma AJ, Gimbrere JS, Smals AG, et al. Adrenocortical function: an indicator of severity of disease and survival in chronic critically ill patients. Intensive Care Med. 1992;18(2):93–6.CrossRefPubMed
9.
Annane D, Sebille V, Troche G, Raphael JC, Gajdos P, Bellissant E. A 3-level prognostic classification in septic shock based on cortisol levels and cortisol response to corticotropin. JAMA. 2000;283(8):1038–45.CrossRefPubMed
10.
Sam S, Corbridge TC, Mokhlesi B, Comellas AP, Molitch ME. Cortisol levels and mortality in severe sepsis. Clin Endocrinol (Oxf). 2004;60(1):29–35.CrossRef
11.
Burchard K. A review of the adrenal cortex and severe inflammation: quest of the “eucorticoid” state. J Trauma. 2001;51(4):800–14.CrossRefPubMed
12.
Schein RM, Sprung CL, Marcial E, Napolitano L, Chernow B. Plasma cortisol levels in patients with septic shock. Crit Care Med. 1990;18(3):259–63.CrossRefPubMed
13.
Arlt W, Hammer F, Sanning P, Butcher SK, Lord JM, Allolio B, et al. Dissociation of serum dehydroepiandrosterone and dehydroepiandrosterone sulfate in septic shock. J Clin Endocrinol Metab. 2006;91(7):2548–54.CrossRefPubMed
14.
Feng JY, Liu KT, Abraham E, Chen CY, Tsai PY, Chen YC, et al. Serum estradiol levels predict survival and acute kidney injury in patients with septic shock - a prospective study. PLoS One. 2014;9(6):e97967.CrossRefPubMedPubMedCentral
15.
Kung HC, Hoyert DL, Xu J, Murphy SL. Deaths: final data for 2005. Natl Vital Stat Rep. 2008;56(10):1–120.PubMed
16.
17.
18.
Santos-Gallego CG, Badimon JJ. The sum of two evils: pneumonia and myocardial infarction: is platelet activation the missing link? J Am Coll Cardiol. 2014;64(18):1926–8.CrossRefPubMed
19.
Santos-Gallego CG, Badimon JJ. Cardiac complications after community-acquired pneumonia. Am J Cardiol. 2016;117(2):310.CrossRefPubMed
20.
Christ-Crain M, Stolz D, Jutla S, Couppis O, Müller C, Bingisser R, et al. Free and total cortisol levels as predictors of severity and outcome in community-acquired pneumonia. Am J Respir Crit Care Med. 2007;176(9):913–20.CrossRefPubMed
21.
Kolditz M, Hoffken G, Martus P, Rohde G, Schutte H, Bals R, et al. Serum cortisol predicts death and critical disease independently of CRB-65 score in community-acquired pneumonia: a prospective observational cohort study. BMC Infect Dis. 2012;12:90.CrossRefPubMedPubMedCentral
22.
Mueller C, Blum CA, Trummler M, Stolz D, Bingisser R, Mueller C, et al. Association of adrenal function and disease severity in community-acquired pneumonia. PLoS One. 2014;9(6):e99518.CrossRefPubMedPubMedCentral
23.
Kolditz M, Halank M, Schulte-Hubbert B, Hoffken G. Adrenal function is related to prognosis in moderate community-acquired pneumonia. Eur Respir J. 2010;36(3):615–21.CrossRefPubMed
24.
Salluh JI, Bozza FA, Soares M, Verdeal JC, Castro-Faria-Neto HC, Lapa e Silva JR, Bozza PT. Adrenal response in severe community-acquired pneumonia: impact on outcomes and disease severity. Chest. 2008;134(5):947–54.CrossRefPubMed
25.
Nickler M, Ottiger M, Steuer C, Huber A, Anderson JB, Müller B, et al. Systematic review regarding metabolic profiling for improved pathophysiological understanding of disease and outcome prediction in respiratory infections. Respir Res. 2015;16:125.CrossRefPubMedPubMedCentral
26.
Schuetz P, Christ-Crain M, Thomann R, Falconnier C, Wolbers M, Widmer I, et al. Effect of procalcitonin-based guidelines vs standard guidelines on antibiotic use in lower respiratory tract infections: the ProHOSP randomized controlled trial. JAMA. 2009;302(10):1059–66.CrossRefPubMed
27.
Schuetz P, Christ-Crain M, Wolbers M, Schild U, Thomann R, Falconnier C, et al. Procalcitonin guided antibiotic therapy and hospitalization in patients with lower respiratory tract infections: a prospective, multicenter, randomized controlled trial. BMC Health Serv Res. 2007;7:102.CrossRefPubMedPubMedCentral
28.
29.
Niederman MS, Mandell LA, Anzueto A, Bass JB, Broughton WA, Campbell GD, et al. Guidelines for the management of adults with community-acquired pneumonia: diagnosis, assessment of severity, antimicrobial therapy, and prevention. Am J Respir Crit Care Med. 2001;163(7):1730–54.CrossRefPubMed
30.
Woodhead M, Blasi F, Ewig S, Huchon G, Ieven M, Ortqvist A, et al. Guidelines for the management of adult lower respiratory tract infections. Eur Respir J. 2005;26(6):1138–80.CrossRefPubMed
31.
Schuetz P, Christ-Crain M, Albrich W, Zimmerli W, Mueller B, ProHOSP Study Group. Guidance of antibiotic therapy with procalcitonin in lower respiratory tract infections: insights into the ProHOSP study. Virulence. 2010;1(2):88-92. doi:10.4161/viru.1.2.10488.CrossRefPubMed
32.
Fine MJ, Auble TE, Yealy DM, Hanusa BH, Weissfeld LA, Singer DE, et al. A prediction rule to identify low-risk patients with community-acquired pneumonia. N Engl J Med. 1997;336(4):243–50.CrossRefPubMed
33.
Grolimund E, Kutz A, Marlowe RJ, Vogeli A, Alan M, Christ-Crain M, et al. Long-term prognosis in COPD exacerbation: role of biomarkers, clinical variables and exacerbation type. COPD. 2015;12(3):295–305.CrossRefPubMed
34.
Alan M, Grolimund E, Kutz A, Christ-Crain M, Thomann R, Falconnier C, et al. Clinical risk scores and blood biomarkers as predictors of long-term outcome in patients with community-acquired pneumonia: a 6-year prospective follow-up study. J Intern Med. 2015;278(2):174–84.CrossRefPubMed
35.
Blum CA, Nigro N, Briel M, Schuetz P, Ullmer E, Suter-Widmer I, et al. Adjunct prednisone therapy for patients with community-acquired pneumonia: a multicentre, double-blind, randomised, placebo-controlled trial. Lancet. 2015;385(9977):1511–8.CrossRefPubMed
36.
Arafah BM. Hypothalamic pituitary adrenal function during critical illness: limitations of current assessment methods. J Clin Endocrinol Metab. 2006;91(10):3725–45.CrossRefPubMed
37.
Beishuizen A, Thijs LG. Endotoxin and the hypothalamo-pituitary-adrenal (HPA) axis. J Endotoxin Res. 2003;9(1):3–24.PubMed
38.
Guertler C, Wirz B, Christ-Crain M, Zimmerli W, Mueller B, Schuetz P. Inflammatory responses predict long-term mortality risk in community-acquired pneumonia. Eur Respir J. 2011;37(6):1439–46.CrossRefPubMed
39.
Mortensen EM, Kapoor WN, Chang CC, Fine MJ. Assessment of mortality after long-term follow-up of patients with community-acquired pneumonia. Clin Infect Dis. 2003;37(12):1617–24.CrossRefPubMed
40.
Almirall J, Bolibar I, Toran P, Pera G, Boquet X, Balanzo X, et al. Contribution of C-reactive protein to the diagnosis and assessment of severity of community-acquired pneumonia. Chest. 2004;125(4):1335–42.CrossRefPubMed
41.
Menendez R, Martinez R, Reyes S, Mensa J, Polverino E, Filella X, et al. Stability in community-acquired pneumonia: one step forward with markers? Thorax. 2009;64(11):987–92.CrossRefPubMed
42.
Seligman R, Meisner M, Lisboa TC, Hertz FT, Filippin TB, Fachel JM, et al. Decreases in procalcitonin and C-reactive protein are strong predictors of survival in ventilator-associated pneumonia. Crit Care. 2006;10(5):R125.CrossRefPubMedPubMedCentral
43.
Mortensen EM. Potential causes of increased long-term mortality after pneumonia. Eur Respir J. 2011;37(6):1306–7.CrossRefPubMed
44.
Steuer C, Schütz P, Bernasconi L, Huber AR. Simultaneous determination of phosphatidylcholine-derived quaternary ammonium compounds by a LC-MS/MS method in human blood plasma, serum and urine samples. J Chromatogr B Analyt Technol Biomed Life Sci. 2016;1008:206–11.CrossRefPubMed
45.
Tenori L, Oakman C, Claudino WM, Bernini P, Cappadona S, Nepi S, et al. Exploration of serum metabolomic profiles and outcomes in women with metastatic breast cancer: a pilot study. Mol Oncol. 2012;6(4):437–44.CrossRefPubMed
46.
Van den Berghe GH. Acute and prolonged critical illness are two distinct neuroendocrine paradigms. Verh K Acad Geneeskd Belg. 1998;60(6):487–520.PubMed
47.
Bartanusz V, Corneille MG, Sordo S, Gildea M, Michalek JE, Nair PV, et al. Diurnal salivary cortisol measurement in the neurosurgical-surgical intensive care unit in critically ill acute trauma patients. J Clin Neurosci. 2014;21(12):2150–4.CrossRefPubMed
Metadata
Title
Time-dependent association of glucocorticoids with adverse outcome in community-acquired pneumonia: a 6-year prospective cohort study
Authors
Manuela Nickler
Manuel Ottiger
Christian Steuer
Alexander Kutz
Mirjam Christ-Crain
Werner Zimmerli
Robert Thomann
Claus Hoess
Christoph Henzen
Luca Bernasconi
Andreas Huber
Beat Mueller
Philipp Schuetz
for the ProHOSP Study Group
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Critical Care / Issue 1/2017
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/s13054-017-1656-7

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