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Prospects for adjuvant therapy with systemic corticosteroids for community-acquired pneumonia: from experiment to clinical practice

https://doi.org/10.18093/0869-0189-2024-34-6-775-787

Abstract

Some patients with severe community-acquired pneumonia develop fatal complications in the form of acute respiratory distress syndrome and/or septic shock despite the timely adequate antibacterial therapy and presumably due to an excessive uncontrolled systemic inflammatory response and inadequate adrenal response to infection due to the critical illness-related corticosteroid insufficiency (CRICI). Therefore, the additional use of systemic corticosteroids can significantly improve the survival of patients with severe community-acquired pneumonia.

Aim. To present the most current preclinical and clinical studies and meta-analyses assessing the effectiveness and safety of the use of systemic corticosteroids for communityacquired pneumonia.

The results of these studies demonstrate that the most optimal regimen for the use of systemic corticosteroids in terms of risk and benefit is early (the first 3 days), low-dose (the dose equivalent of 6 mg/day dexamethasone) short-course (5 – 7 days) therapy with immediate withdrawal of the drugs. This regimen produces the best effect in patients with severe community-acquired pneumonia who require ventilation (invasive or non-invasive) with PEEP ≥ 5 cm H2O or high-flow oxygen therapy with FiO2 ≥ 50% and a PaO2/FiO2 ratio less than 300 and/or vasopressor support.

Conclusion. Currently, the federal clinical guidelines do not recommend the routine use of corticosteroids in adult patients with community-acquired pneumonia, with the exception of patients with refractory septic shock. However, this narrative review presents evidence supporting the use of adjunctive corticosteroid therapy in adult patients with severe community-acquired pneumonia, particularly when complicated by septic shock, acute respiratory distress syndrome, comorbid asthma and/or chronic obstructive pulmonary disease, provided there is no pulmonary suppuration, severe influenza or mycotic infection. Undoubtedly, this is a compelling argument in favor of revising existing domestic clinical guidelines regarding the use of systemic corticosteroids. Thus, further research is needed to identify subgroups of patients who may benefit from or potentially be harmed by corticosteroids. In addition, it is necessary to determine the optimal regimen for the use of corticosteroids in terms of specific drugs, their dose, routes of administration, frequency and duration of therapy, as well as the withdrawal.

About the Authors

Yu. V. Rudakov
Federal State Budgetary Military Educational Institution of Higher Education “Military Medical Academy named after S.M. Kirov” of the Ministry of Defense of the Russian Federation
Russian Federation

Yuri V. Rudakov - Сandidate of Medicine, Associate Professor, 1st Department and Clinic (Advanced Physician Therapy) named after Academician N. S.Molchanov.

Ul. Akademika Lebedeva 6, Saint-Petersburg, 6194044; tel.: (921) 415-45-97


Competing Interests:

The authors did not declare any conflicts of interests



V. V. Salukhov
Federal State Budgetary Military Educational Institution of Higher Education “Military Medical Academy named after S.M. Kirov” of the Ministry of Defense of the Russian Federation
Russian Federation

Vladimir V. Salukhov - Doctor of Medicine, Professor, Head of the 1st Department and Clinic (Advanced Physician Therapy) named after Academician N.S. Molchanov.

Ul. Akademika Lebedeva 6, Saint-Petersburg, 6194044; tel.: (921) 415-45-97


Competing Interests:

The authors did not declare any conflicts of interests



M. A. Kharitonov
Federal State Budgetary Military Educational Institution of Higher Education “Military Medical Academy named after S.M. Kirov” of the Ministry of Defense of the Russian Federation
Russian Federation

Mikhail A. Kharitonov - Doctor of Medicine, Professor, Professor, 1st Department and Clinic (Advanced Physician Therapy) named after Academician N.S. Molchanov.

Ul. Akademika Lebedeva 6, Saint-Petersburg, 6194044; tel.: (921) 415-45-97


Competing Interests:

The authors did not declare any conflicts of interests



N. I. Voloshin
Federal State Budgetary Military Educational Institution of Higher Education “Military Medical Academy named after S.M. Kirov” of the Ministry of Defense of the Russian Federation
Russian Federation

Nikita I. Voloshin - Adjunct, 1st Department and Clinic (Advanced Physician Therapy) named after Academician N.S. Molchanov.

Ul. Akademika Lebedeva 6, Saint-Petersburg, 6194044; tel.: (921) 415-45-97


Competing Interests:

The authors did not declare any conflicts of interests



S. N. Avdeev
Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University)
Russian Federation

Sergey N. Avdeev - Doctor of Medicine, Professor, Academician of Russian Academy of Sciences, Head of the Department of Pulmonology, N.V.Sklifosovsky Institute of Clinical Medicine, Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov First MSMU of the Ministry of Health of the Russian Federation (Sechenov University); Chief Freelance Pulmonologist of the Ministry of Health of the Russian Federation; Director of the National Medical Research Center for Pulmonology.

Ul. Trubetskaya 8, build. 2, Moscow, 119991; tel.: (495) 708-35-76


Competing Interests:

The authors did not declare any conflicts of interests



References

1. Cillóniz C., Cardozo C., García-Vidal C. Epidemiology, pathophysiology, and microbiology of community-acquired pneumonia. Ann. Res. Hosp. 2018; (2): 1. DOI: 10.21037/arh.2017.12.03.

2. Avdeev S.N., Beloborodov V.B., Belotserkovskiy B.Z. et. al. [Severe community-acquired pneumonia in adults. Clinical recommendations from Russian Federation of Anaesthesiologists and Reanimatologists]. Anesteziologiya i reanimatologiya. 2022; (1): 6–35. DOI: 10.17116/anaesthesiology20220116 (in Russian).

3. Minakov A.A., Vakhlevskii V.V., Voloshin N.I. et al. [Modern view on the etiology and immunological aspects of pneumonia] Meditsinskiy sovet. 2023; (4): 141–153. DOI: 10.21518/ms2023-056 (in Russian).

4. Ruiz-Spinelli A., Waterer G., Rello J. Severe community-acquired pneumonia in the post COVID-19 era. Curr. Opin Crit. Care. 2023; 29 (5): 400–406. DOI: 10.1097/MCC.0000000000001083.

5. Battaglini D., Fazzini B., Silva P.L. et. al. Challenges in ARDS definition, management, and identification of effective personalized therapies. Clin. Med. 2023; 12 (4): 1381. DOI: 10.3390/jcm12041381.

6. Buttgereit F., da Silva J.A., Boers M. et. al. Standardised nomenclature for glucocorticoid dosages and glucocorticoid treatment regimens: current questions and tentative answers in rheumatology. Ann. Rheum. Dis. 2002; 61 (8): 718–722. DOI: 10.1136/ard.61.8.718.

7. Pastores S.M., Annane D., Rochwerg B. et al. 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. Crit. Care Med. 2018; 46 (1): 146–148. DOI: 10.1097/CCM.0000000000002737.

8. Czock D., Keller F., Rasche F.M. et al. Pharmacokinetics and pharmacodynamics of systemically administered glucocorticoids. Clin. Pharmacokinet. 2005. 44 (1): 61–98. DOI: 10.2165/00003088-200544010-00003.

9. Williams D.M. Clinical pharmacology of corticosteroids. Respir. Care. 2018; 63 (6): 655–670. DOI: 10.4187/respcare.06314.

10. Yang J.W., Mao B., Tao R.J. Corticosteroids alleviate lipopolysaccharide-induced inflammation and lung injury via inhibiting NLRP3-inflammasome activation. J. Cell. Mol. Med. 2020; 24 (21): 12716–12725. DOI: 10.1111/jcmm.15849.

11. Tu G.W., Shi Y., Zheng Y.J. et al. Glucocorticoid attenuates acute lung injury through induction of type 2 macrophage. J. Transl. Med. 2017; 15 (1): 181. DOI: 10.1186/s12967-017-1284-7.

12. Voloshin N.I., Pugach V.A., Salukhov V.V. et al. [The experimental study of dexamethasone effectiveness in a model of lipopolysaccharide-induced acute lung injury in rats]. Byulleten' sibirskoy meditsiny. 2023; 22 (4): 22-30. DOI: 10.20538/1682-0363-2023-4-22-30 (in Russian).

13. Venkatesh B., Finfer S., Cohen J. et al. Adjunctive glucocorticoid therapy in patients with septic shock. N. Engl. J. Med. 2018; 378 (9): 797–808. DOI: 10.1056/NEJMoa1705835.

14. Kamath S., Hammad Altaq H., Abdo T. Management of sepsis and septic shock: what have we learned in the last two decades? Microorganisms. 2023; 11 (9): 2231. DOI: 10.3390/microorganisms11092231.

15. Lewis S.R., Pritchard M.W., Thomas C.M. et al. Pharmacological agents for adults with acute respiratory distress syndrome. Cochrane Database Syst. Rev. 2019; 7 (7): CD004477. DOI: 10.1002/14651858.cd004477.pub3.

16. Lin P., Zhao Y., Li X. et al. Decreased mortality in acute respiratory distress syndrome patients treated with corticosteroids: an updated meta-analysis of randomized clinical trials with trial sequential analysis. Crit. Care. 2021; 25 (1): 122. DOI: 10.1186/s13054-021-03546-0.

17. Yoshihro S., Taito S., Yatabe T. The influence of steroid type on outcomes in patients with acute respiratory distress syndrome. J. Intensive Care. 2023; 11 (1): 32. DOI: 10.1186/s40560-023-00681-4.

18. He Q., Wang C., Wang Y. et al. Efficacy and safety of glucocorticoids use in patients with COVID-19: a systematic review and network meta-analysis. BMC Infect. Dis. 2023; 23 (1): 896. DOI: 10.1186/s12879-023-08874-w.

19. Saleem N., Kulkarni A., Snow T.A.C. Effect of corticosteroids on mortality and clinical cure in community-acquired pneumonia: a systematic review, meta-analysis, and meta-regression of randomized control trials. Chest. 2023; 163 (3): 484–497. DOI: 10.1016/j.chest.2022.08.2229.

20. Tang Q., Chen Q., Li Y., Wang Z. Association between glucocorticoids and mortality in patients with severe pneumonia: a systematic review and meta-analysis based on randomized controlled trials. Comput. Math. Methods Med. 2022; 2022: 1191205. DOI: 10.1155/2022/1191205.

21. Chen S., Hu C. Effect of corticosteroids on mortality in patients with community-acquired pneumonia. Crit. Care. 2023; 27 (1): 358. DOI: 10.1186/s13054-023-04645-w.

22. Wu J.Y., Tsai Y.W., Hsu W.H. et al. Efficacy and safety of adjunctive corticosteroids in the treatment of severe community-acquired pneumonia: a systematic review and meta-analysis of randomized controlled trials. Crit. Care. 2023; 27 (1): 274. DOI: 10.1186/s13054-023-04561-z.

23. Bradley J., Khurana S., Cavallazzi R. Adjunctive immunomodulation in severe community-acquired pneumonia. J. Bras. Pneumol. 2023; 49 (4): e20230248. DOI: 10.36416/1806-3756/e20230248.

24. Martin-Loeches I., Nagavci B., Torres A. Final approval for corticosteroids in severe CAP? For sure, in septic shock. Crit. Care. 2023; 27 (1): 342. DOI: 10.1186/s13054-023-04613-4.

25. Amratia D.A., Viola H., Ioachimescu O.C. Glucocorticoid therapy in respiratory illness: bench to bedside. J. Investig Med. 2022; 70 (8): 1662–1680. DOI: 10.1136/jim-2021-002161.

26. Vornicu O., Perriens E., Blackman S. et. al. Mortality reduction in severe community-acquired pneumonia: key findings from a large randomized controlled trial and their clinical implications. Ann. Transl. Med 2023; 11 (11): 395. DOI: 10.21037/atm-23-1719.

27. Abdallah M.S., Madi A.F., Rana M.A. The best use of systemic corticosteroids in the intensive care units, review. J. Steroids Horm Sci. 2015; 6 (1): 1000149. DOI: 10.4172/2157-7536.1000149.

28. Mager D.E., Lin S.X., Blum R.A. et al. Dose equivalency evaluation of major corticosteroids: pharmacokinetics and cell trafficking and cortisol dynamics. J. Clin. Pharmacol. 2003; 43 (11): 1216–1227. DOI: 10.1177/0091270003258651.

29. Tanin I.Y., Ivanova L.A., Korol I.V. et al. [Principles of glucocorticosteroid administration in patients with COVID-19]. Vestnik sovremennoy klinicheskoy meditsiny. 2022; 15 (2): 103–109. DOI: 10.20969/VSKM.2022.15(2).103-109 (in Russian).

30. RECOVERY Collaborative Group, Horby P. et al. Dexamethasone in hospitalized patients with COVID‐19. N. Engl. J. Med. 2021; 384: 693–704. DOI: 10.1056/NEJMoa2021436.

31. Rygаrd S.L., Butler E., Granholm A. et al. Low-dose corticosteroids for adult patients with septic shock: a systematic review with meta-analysis and trial sequential analysis. Intensive Care Med. 2018; 44 (7): 1003–1016. DOI: 10.1007/s00134-018-5197-6.

32. Salton F., Confalonieri P., Meduri G.U.et al. Theory and practice of glucocorticoids in COVID-19: getting to the heart of the matter-A critical review and viewpoints. Pharmceuticals (Basel). 2023; 16 (7): 924. DOI: 10.3390/ph16070924.

33. Selye H. A syndrome produced by diverse nocuous agents. 1936. J. Neuropsychiatry Clin. Neurosci. 1998; 10 (2):230 231. DOI: 10.1038/138032a.

34. Russell G., Lightman S. The human stress response. Nat. Rev. Endocrinol. 2019; 15 (9): 525–534. DOI: 10.1038/s41574-019-0228-0.

35. Marik P.E., Pastores S.M., 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. Crit. Care Med. 2008; 36 (6): 1937–1949. DOI: 10.1097/CCM.0b013e31817603ba.

36. Annane D., Pastores S.M., Arlt W. et al. Critical illness-related corticosteroid insufficiency (CIRCI): a narrative review from a multispecialty task force of the Society of Critical Care Medicine (SCCM) and the European Society of Intensive Care Medicine (ESICM). Intensive Care Med. 2017; 43 (12): 1781–1792. DOI: 10.1007/s00134-017-4914-x.

37. Meduri G.U., Chrousos G.P. General adaptation in critical illness: glucocorticoid receptor-alpha master regulator of homeostatic corrections. Front. Endocrinol. (Lausanne). 2020. 11: 161. DOI: 10.3389/fendo.2020.00161.

38. Harris L.K., Crannage A.J. Corticosteroids in community-acquired pneumonia: a review of current literature. J. Pharm. Technol. 2021; 37 (3): 152–160. DOI: 10.1177/8755122521995587.

39. Mueller C., Blum C.A., Trummler M. et.al. Association of adrenal function and disease severity in community-acquired pneumonia. PLoS One. 2014; 9 (6): e99518. DOI: 10.1371/journal.pone.0099518.

40. Beishuizen A., Thijs L.G., Vermes I. Decreased levels of dehydroepiandrosterone sulphate in severe critical illness: a sign of exhausted adrenal reserve? Crit. Care. 2002; 6 (5): 434–438. DOI: 10.1186/cc1530.

41. Draghici S., Nguyen T.M., Sonna L.A. et al. COVID-19: Disease pathways and gene expression changes predict methylprednisolone can improve outcome in severe cases. Bioinformatics. 2021; 37 (17): 2691–2698. DOI: 10.1093/bioinformatics/btab163.

42. Kharitonov M.A., Rudakov Yu.V., Salukhov V.V., Voloshin N.I. [Role of surfactant in the pathogenesis of bronchopulmonary pathology]. Meditsinskiy sovet. 2023; (20): 52–66. DOI: 10.21518/ms2023-340 (in Russian).

43. Young A., Marsh S. Steroid use in critical care. BJA Educ. 2018; 18 (5): 129–134. DOI: 10.1016/j.bjae.2018.01.005.

44. Lansbury L., Rodrigo C., Leonardi-Bee J. et al. Corticosteroids as adjunctive therapy in the treatment of influenza. Cochrane Database Syst. Rev. 2019; 2 (2): Cd010406. DOI: 10.1002/14651858.CD010406.

45. Torres A., Sibila O., Ferrer M. et al. Effect of corticosteroids on treatment failure among hospitalized patients with severe community-acquired pneumonia and high inflammatory response: a randomized clinical trial. JAMA. 2015; 313 (7): 677–686. DOI: 10.1001/jama.2015.88.

46. Martin-Loeches I., Torres A., Nagavci B. et al. ERS/ESICM/ESCMID/ALAT guidelines for the management of severe community-acquired pneumonia. Eur. Respir J. 2023; 61 (4): 2200735. DOI: 10.1183/13993003.00735-2022.

47. Evans L., Rhodes A., Alhazzani W. et al Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021. Intensive Care Med. 2021; 47 (11): 1181–1247. DOI: 10.1007/s00134-021-06506-y.

48. Chaudhuri D., Nei A.M., Rochwerg B. et al. 2024 focused update: guidelines on use of corticosteroids in sepsis, acute respiratory distress syndrome, and community-acquired pneumonia. Crit. Care Med. 2024; 52 (5): e219–233. DOI: 10.1097/CCM.0000000000006172.

49. Cilloniz C., Ferrer M., Liapikou A. et.al. Acute respiratory distress syndrome in mechanically ventilated patients with community-acquired pneumonia. Eur. Respir. J. 2018; 51 (3): 1702215. DOI: 10.1183/13993003.02215-2017.

50. Salukhov V.V., Voloshin N.I., Shperling M.I. [Effectiveness of various regimens of systemic anti-inflammatory therapy with glucocorticoids in the development of acute LPS-induced lung damage in the experiment]. Izvestiya Rossiyskoy Voenno-meditsinskoy akademii. 2022; 41 (2): 111–116. DOI: 10.17816/rmmar104619 (in Russian).

51. Hong S., Jian C., Wang H. Effects of different doses of methylprednisolone therapy on acute respiratory distress syndrome: results from animal and clinical studies. BMC Pulm. Med. 2022; 22 (1): 348. DOI: 10.1186/s12890-022-02148-y.

52. Chaudhuri D., Sasaki K., Karkar A. et al. Corticosteroids in COVID-19 and non-COVID-19 ARDS: a systematic review and meta-analysis. Intensive Care Med. 2021; 47 (5): 521–537. DOI: 10.1007/s00134-021-06394-2

53. Tasaka S., Ohshimo S., Takeuchi M. et al. ARDS clinical practice guideline 2021. J. Intensive Care. 2022; 10 (1): 32. DOI: 10.1186/s40560-022-00615-6.

54. Meduri G.U., Annane D., Confalonieri M. et. al. Pharmacological principles guiding prolonged glucocorticoid treatment in ARDS. Intensive Care Med. 2020; 46 (12): 2284–2296. DOI: 10.1007/s00134-020-06289-8.

55. Vandewalle J., Libert C. Glucocorticoids in sepsis: to be or not to be. Front. Immunol. 2020; 11: 1318. DOI: 10.3389/fimmu.2020.01318.

56. Villar J., Ferrando C., Martínez D. et al Dexamethasone treatment for the acute respiratory distress syndrome: a multicentre, randomised controlled trial. Lancet Respir. Med. 2020; 8: 267–276. DOI: 10.1016/s2213-2600(19)30417-5.

57. Meduri G.U., Headley A.S., Golden E. et al: Effect of prolonged methylprednisolone therapy in unresolving acute respiratory distress syndrome: a randomized controlled trial. JAMA. 1998; 280 (2): 159–165. DOI: 10.1001/jama.280.2.159.

58. Meduri G.U., Golden E., Freire A.X. et al. Methylprednisolone infusion in early severe ARDS: Results of a randomized controlled trial. Chest. 2007; 131 (4): 954–959. DOI: 10.1378/chest.06-2100.

59. Meduri G.U., Shih M.C., Bridges L. et al. Low-dose methylprednisolone treatment in critically ill patients with severe community-acquired pneumonia. Intensive Care Med. 2022; 48 (8): 1009–1023. DOI: 10.1007/s00134-022-06684-3.

60. Dequin P.F., Meziani F., Quenot J.P. et al. Hydrocortisone in severe community-acquired pneumonia. N. Engl. J. Med. 2023; 388 (21): 1931–1941. DOI: 10.1056/NEJMoa2215145.

61. Wu J.Y., Tsai Y.W., Hsu W.H. et al. Efficacy and safety of adjunctive corticosteroids in the treatment of severe community-acquired pneumonia: a systematic review and meta-analysis of randomized controlled trials. Crit. Care. 2023; 27 (1): 274. DOI: 10.1186/s13054-023-04561-z.

62. Metlay J.P., Waterer G.W. Time to treat severe community-acquired pneumonia with steroids? N. Engl. J. Med. 2023; 388 (21): 2001–2002. DOI: 10.1056/NEJMe2302544.

63. Bradley J., Khurana S., Cavallazzi R. Adjunctive immunomodulation in severe community-acquired pneumonia. J. Bras. Pneumol. 2023; 49 (4): e20230248. DOI: 10.36416/1806-3756/e20230248.

64. Pitre T., Abdali D., Chaudhuri D. et al. Corticosteroids in community-acquired bacterial pneumonia: a systematic review, pairwise and dose-response meta-analysis. J. Gen. Intern. Med. 2023; 38 (11): 2593–2606. DOI: 10.1007/s11606-023-08203-6.

65. Gu X., Yang P., Yu L.et al. Glucocorticoids can reduce mortality in patients with severe community-acquired pneumonia: a systematic review and meta-analysis of randomized controlled trials. Research Square. (Version 1). [Preprint. Posted: 2023, Nov. 10]. DOI: 10.21203/rs.3.rs-3576792/v1.


Review

For citations:


Rudakov Yu.V., Salukhov V.V., Kharitonov M.A., Voloshin N.I., Avdeev S.N. Prospects for adjuvant therapy with systemic corticosteroids for community-acquired pneumonia: from experiment to clinical practice. PULMONOLOGIYA. 2024;34(6):775-787. (In Russ.) https://doi.org/10.18093/0869-0189-2024-34-6-775-787

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