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Intensive Care Medicine
Erschienen in:

13.05.2022 | Original

Low-dose methylprednisolone treatment in critically ill patients with severe community-acquired pneumonia

verfasst von: G. Umberto Meduri, Mei-Chiung Shih, Lisa Bridges, Thomas J. Martin, Ali El-Solh, Nitin Seam, Anne Davis-Karim, Reba Umberger, Antonio Anzueto, Peruvemba Sriram, Charlie Lan, Marcos I. Restrepo, Juan J. Guardiola, Teresa Buck, David P. Johnson, Anthony Suffredini, W. Andrew Bell, Julia Lin, Lan Zhao, Lauren Uyeda, Lori Nielsen, Grant D. Huang, the ESCAPe Study Group

Erschienen in: Intensive Care Medicine | Ausgabe 8/2022

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Abstract

Purpose

Severe community-acquired pneumonia (CAP) requiring intensive care unit admission is associated with significant acute and long-term morbidity and mortality. We hypothesized that downregulation of systemic and pulmonary inflammation with prolonged low-dose methylprednisolone treatment would accelerate pneumonia resolution and improve clinical outcomes.

Methods

This double-blind, randomized, placebo-controlled clinical trial recruited adult patients within 72–96 h of hospital presentation. Patients were randomized in 1:1 ratio; an intravenous 40 mg loading bolus was followed by 40 mg/day through day 7 and progressive tapering during the 20-day treatment course. Randomization was stratified by site and need for mechanical ventilation (MV) at the time of randomization. Outcomes included a primary endpoint of 60-day all-cause mortality and secondary endpoints of morbidity and mortality up to 1 year of follow-up.

Results

Between January 2012 and April 2016, 586 patients from 42 Veterans Affairs Medical Centers were randomized, short of the 1420 target sample size because of low recruitment. 584 patients were included in the analysis. There was no significant difference in 60-day mortality between the methylprednisolone and placebo arms (16% vs. 18%; adjusted odds ratio 0.90, 95% CI 0.57–1.40). There were no significant differences in secondary outcomes or complications.

Conclusions

In patients with severe CAP, prolonged low-dose methylprednisolone treatment did not significantly reduce 60-day mortality. Treatment was not associated with increased complications.
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Literatur
1.
Mayr FB, Yende S, Angus DC (2014) Epidemiology of severe sepsis. Virulence 5:4–11CrossRef
2.
Kang C-I, Song J-H, Kim SH, Chung DR, Peck KR, Thamlikitkul V, Wang H, So TM-K, Hsueh P-R, Yasin RM (2013) Risk factors and pathogenic significance of bacteremic pneumonia in adult patients with community-acquired pneumococcal pneumonia. J Infect 66:34–40CrossRef
3.
Cillóniz C, Polverino E, Ewig S, Aliberti S, Gabarrús A, Menéndez R, Mensa J, Blasi F, Torres A (2013) Impact of age and comorbidity on cause and outcome in community-acquired pneumonia. Chest 144:999–1007CrossRef
4.
Hsu JL, Siroka AM, Smith MW, Holodniy M, Meduri GU (2011) One-year outcomes of community-acquired and healthcare-associated pneumonia in the Veterans Affairs Healthcare System. Int J Infect Dis 15:e382-387CrossRef
5.
Musher DM, Montoya R, Wanahita A (2004) Diagnostic value of microscopic examination of Gram-stained sputum and sputum cultures in patients with bacteremic pneumococcal pneumonia. Clin Infect Dis 39:165–169CrossRef
6.
Corrales-Medina VF, Musher DM (2011) Immunomodulatory agents in the treatment of community-acquired pneumonia: a systematic review. J Infect 63:187–199CrossRef
7.
Iwashyna TJ, Ely EW, Smith DM, Langa KM (2010) Long-term cognitive impairment and functional disability among survivors of severe sepsis. JAMA, J Am Med Assoc 304:1787–1794CrossRef
8.
Wang HE, Szychowski JM, Griffin R, Safford MM, Shapiro NI, Howard G (2014) Long-term mortality after community-acquired sepsis: a longitudinal population-based cohort study. BMJ Open 4:e004283CrossRef
9.
Confalonieri M, Meduri GU (2011) Glucocorticoid treatment in community-acquired pneumonia. Lancet 377:1982–1984CrossRef
10.
Yende S, Kellum JA, Talisa VB, Palmer OMP, Chang C-CH, Filbin MR, Shapiro NI, Hou PC, Venkat A, LoVecchio F (2019) Long-term host immune response trajectories among hospitalized patients with sepsis. JAMA Netw Open 2:e198686–e198686CrossRef
11.
Siemieniuk RA, Meade MO, Alonso-Coello P, Briel M, Evaniew N, Prasad M, Alexander PE, Fei Y, Vandvik PO, Loeb M, Guyatt GH (2015) Corticosteroid therapy for patients hospitalized with community-acquired pneumonia: a systematic review and meta-analysis. Ann Intern Med 163:519–528CrossRef
12.
Briel M, Spoorenberg SM, Snijders D, Torres A, Fernandez-Serrano S, Meduri GU, Gabarrús A, Blum CA, Confalonieri M, Kasenda B (2017) Corticosteroids in patients hospitalized with community-acquired pneumonia: systematic review and individual patient data metaanalysis. Clin Infect Dis 66:346–354CrossRef
13.
Meduri GU, Chrousos GP (2020) General adaptation in critical illness: glucocorticoid receptor-alpha master regulator of homeostatic corrections. Front Endocrinol (Lausanne) 11
14.
Nawab Q, Golden E, Confalonieri M, Umberger R, Meduri G (2011) Corticosteroid treatment in severe community-acquired pneumonia: duration of treatment affects control of systemic inflammation and clinical improvement. Intensive Care Med 37:1153–1554CrossRef
15.
Mandell LA, Wunderink RG, Anzueto A, Bartlett JG, Campbell GD, Dean NC, Dowell SF, File TM Jr, Musher DM, Niederman MS, Torres A, Whitney CG (2007) Infectious diseases society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis 44(Suppl 2):S27-72CrossRef
16.
Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, Reinhart K, Angus DC, Brun-Buisson C, Beale R, Calandra T, Dhainaut JF, Gerlach H, Harvey M, Marini JJ, Marshall J, Ranieri M, Ramsay G, Sevransky J, Thompson BT, Townsend S, Vender JS, Zimmerman JL, Vincent JL (2008) Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Intensive Care Med 34:17–60CrossRef
17.
Ferreira FL, Bota DP, Bross A, Melot C, Vincent JL (2001) Serial evaluation of the SOFA score to predict outcome in critically ill patients. JAMA 286:1754–1758CrossRef
18.
Kazis LE, Selim AJ, Rogers W, Ren XS, Lee A, Miller D, Veterans RAND 12 item Health Survey (VR-12): a white paper summary
19.
Selim AJ, Rogers W, Fleishman JA, Qian SX, Fincke BG, Rothendler JA, Kazis LE (2009) Updated US population standard for the Veterans RAND 12-item Health Survey (VR-12). Qual Life Res 18:43–52CrossRef
20.
Lawton MP, Brody EM (1969) Assessment of older people: self-maintaining and instrumental activities of daily living. Gerontologist 9:179–186CrossRef
21.
Katz S, Ford AB, Moskowitz RW, Jackson BA, Jaffe MW (1963) Studies of illness in the aged. The Index of Adl: a standardized measure of biological and psychosocial function. JAMA 185:914–919CrossRef
22.
Lai TL, Shih M-C (2004) Power, sample size and adaptation considerations in the design of group sequential clinical trials. Biometrika 91:507–528CrossRef
23.
Fine MJ, Auble TE, Yealy DM, Hanusa BH, Weissfeld LA, Singer DE, Coley CM, Marrie TJ, Kapoor WN (1997) A prediction rule to identify low-risk patients with community-acquired pneumonia. N Engl J Med 336:243–250CrossRef
24.
Moreno RP, Metnitz PG, Almeida E, Jordan B, Bauer P, Campos RA, Iapichino G, Edbrooke D, Capuzzo M, Le Gall JR (2005) SAPS 3–from evaluation of the patient to evaluation of the intensive care unit. Part 2: development of a prognostic model for hospital mortality at ICU admission. Intensive Care Med 31:1345–1355CrossRef
25.
Zhao L, Tian L, Uno H, Solomon SD, Pfeffer MA, Schindler JS, Wei LJ (2012) Utilizing the integrated difference of two survival functions to quantify the treatment contrast for designing, monitoring, and analyzing a comparative clinical study. Clin Trials 9:570–577CrossRef
26.
Pastores SM, Annane D, Rochwerg B (2018) Guidelines for the diagnosis and management of critical illness-related corticosteroid insufficiency (CIRCI) in critically ill patients (part II): Society of Critical Care Medicine (SCCM) and European Society of Intensive Care Medicine (ESICM) 2017. Intensive Care Med 44:474–477CrossRef
27.
Briel M, Spoorenberg SMC, Snijders D, Torres A, Fernandez-Serrano S, Meduri GU, Gabarrus A, Blum CA, Confalonieri M, Kasenda B, Siemieniuk RAC, Boersma W, Bos WJW, Christ-Crain M, Ovidius Study G, Capisce Study G, Group SS (2018) Corticosteroids in patients hospitalized with community-acquired pneumonia: systematic review and individual patient data metaanalysis. Clin Infect Dis 66:346–354CrossRef
28.
Coelho LM, Salluh JI, Soares M, Bozza FA, Verdeal JC, Castro-Faria-Neto HC, Lapa-e-Silva JR, Bozza PT, Povoa P (2012) Patterns of c-reactive protein RATIO response in severe community-acquired pneumonia: a cohort study. Crit Care 16:R53CrossRef
29.
Monedero P, Gea A, Castro P, Candela-Toha AM, Hernandez-Sanz ML, Arruti E, Villar J, Ferrando C, Network C-SI (2021) Early corticosteroids are associated with lower mortality in critically ill patients with COVID-19: a cohort study. Crit Care 25:2CrossRef
30.
Meduri GU, Annane D, Confalonieri M, Chrousos GP, Rochwerg B, Busby A, Ruaro B, Meibohm B (2020) Pharmacological principles guiding prolonged glucocorticoid treatment in ARDS. Intensive Care Med 46:2284–2296CrossRef
31.
Torres A, Sibila O, Ferrer M, Polverino E, Menendez R, Mensa J, Gabarrus A, Sellares J, Restrepo MI, Anzueto A, Niederman MS, Agusti C (2015) Effect of corticosteroids on treatment failure among hospitalized patients with severe community-acquired pneumonia and high inflammatory response: a randomized clinical trial. JAMA 313:677–686CrossRef
32.
Rodriguez JM, Monsalves-Alvarez M, Henriquez S, Llanos MN, Troncoso R (2016) Glucocorticoid resistance in chronic diseases. Steroids 115:182–192CrossRef
33.
Cangemi R, Falcone M, Taliani G, Calvieri C, Tiseo G, Romiti GF, Bertazzoni G, Farcomeni A, Violi F, Group SS (2019) Corticosteroid use and incident myocardial infarction in adults hospitalized for community-acquired pneumonia. Ann Am Thorac Soc 16:91–98CrossRef
34.
Annane D, Pastores S, Rochwerg B, Arlt W, Balk R, Beishuizen A, Briegel J, Carcillo J, Christ-Crain M, Cooper M (2017) Guidelines for the diagnosis and management of critical illness-related corticosteroid insufficiency (CIRCI) in critically ill patients (part I): Society of Critical Care Medicine (SCCM) and European Society of Intensive Care Medicine (ESICM) 2017. Crit Care Med 45:2078–2088CrossRef
35.
Odeyemi YE, Herasevich S, Chalmers SJ, Barreto EF, Frank RD, Gajic OO, Yadav H (2020) Biomarker-concordant steroid use in critically ill patients with pneumonia. Mayo Clin Proc Innov Qual Outcomes 4:649–656CrossRef
36.
Li J, Liao X, Zhou Y, Wang L, Yang H, Zhang W, Zhang Z, Kang Y (2021) Comparison of associations between glucocorticoids treatment and mortality in COVID-19 patients and SARS patients: a systematic review and meta-analysis. Shock 56:215–228CrossRef
37.
Recovery Collaborative Group, Horby P, Lim WS, Emberson JR, Mafham M, Bell JL, Linsell L, Staplin N, Brightling C, Ustianowski A, Elmahi E, Prudon B, Green C, Felton T, Chadwick D, Rege K, Fegan C, Chappell LC, Faust SN, Jaki T, Jeffery K, Montgomery A, Rowan K, Juszczak E, Baillie JK, Haynes R, Landray MJ (2021) Dexamethasone in hospitalized patients with COVID-19. N Engl J Med 384:693–704CrossRef
38.
World Health Organization (2020) Corticosteroids for COVID-19: living guidance, 2 September 2020. In: Book corticosteroids for COVID-19: living guidance, 2 September 2020. World Health Organization, City
39.
Villar J, Ferrando C, Martinez D, Ambros A, Munoz T, Soler JA, Aguilar G, Alba F, Gonzalez-Higueras E, Conesa LA, Martin-Rodriguez C, Diaz-Dominguez FJ, Serna-Grande P, Rivas R, Ferreres J, Belda J, Capilla L, Tallet A, Anon JM, Fernandez RL, Gonzalez-Martin JM, Dexamethasone in AN (2020) Dexamethasone treatment for the acute respiratory distress syndrome: a multicentre, randomised controlled trial. Lancet Respir Med 8:267–276CrossRef
40.
Yates CR, Vysokanov A, Mukherjee A, Ludden TM, Tolley EA, Meduri GU, Dalton JT (2001) Time-variant increase in methylprednisolone clearance in patients with acute respiratory distress syndrome: a population pharmocokinetic study. J Clin Pharmacol 41:1–10CrossRef
41.
Chriguer RS, Elias LLK, da Silva Jr IM, Vieira JGH, Moreira AC, de Castro M (2005) Glucocorticoid sensitivity in young healthy individuals: in vitro and in vivo studies. J Clin Endocrinol Metab 90:5978–5984CrossRef
Metadaten
Titel
Low-dose methylprednisolone treatment in critically ill patients with severe community-acquired pneumonia
verfasst von
G. Umberto Meduri
Mei-Chiung Shih
Lisa Bridges
Thomas J. Martin
Ali El-Solh
Nitin Seam
Anne Davis-Karim
Reba Umberger
Antonio Anzueto
Peruvemba Sriram
Charlie Lan
Marcos I. Restrepo
Juan J. Guardiola
Teresa Buck
David P. Johnson
Anthony Suffredini
W. Andrew Bell
Julia Lin
Lan Zhao
Lauren Uyeda
Lori Nielsen
Grant D. Huang
the ESCAPe Study Group
Publikationsdatum
13.05.2022
Verlag
Springer Berlin Heidelberg
Erschienen in
Intensive Care Medicine / Ausgabe 8/2022
Print ISSN: 0342-4642
Elektronische ISSN: 1432-1238
DOI
https://doi.org/10.1007/s00134-022-06684-3

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