Yoğun Bakımda COVID-19 ve Kortikosteroid Tedavi Protokolleri
Özet
Bu çalışmada, COVID-19 enfeksiyonunun patofizyolojisi ve yoğun bakım hastalarında kortikosteroid kullanımına dair tedavi protokolleri detaylı bir şekilde ele alınmaktadır. SARS-CoV-2 virüsünün ACE 2 reseptörlerine bağlanarak başlattığı süreç, ileri aşamalarda düzensiz sitokin salınımı ve akut ARDS ile sonuçlanan yaygın alveol hasarına yol açmaktadır. Bu hiperinflamasyon fazında, kortikosteroidlerin güçlü antienflamatuar özellikleri sayesinde immun yanıtı baskılayabileceği ve pulmoner hasarı azaltabileceği öngörülmektedir. RECOVERY çalışması ve Dünya Sağlık Örgütü (DSÖ) kriterlerine göre, ek oksijen veya mekanik ventilasyon ihtiyacı olan ciddi ve kritik COVID-19 hastalarında günde 6 mg deksametazon veya eşdeğeri kortikosteroid tedavisinin 28 günlük mortaliteyi ve hastanede kalış süresini anlamlı derecede azalttığı kanıtlanmıştır. Buna karşın, ek oksijen ihtiyacı bulunmayan hafif seyirli vakalarda kortikosteroid kullanımının mortalite üzerinde olumlu bir etkisi saptanmamış, aksine potansiyel yan etkiler nedeniyle önerilmemiştir. Tedavi süresince klinisyenlerin hiperglisemi, sekonder enfeksiyonlar ve fırsatçı mantar enfeksiyonları gibi riskleri yakından takip etmesi hayati önem taşımaktadır. Sonuç olarak, oksijen desteğine ihtiyaç duyan ağır hastalarda standart dozda deksametazon kullanımı güçlü bir şekilde tavsiye edilirken, pulse steroid ve inhale steroid uygulamaları için daha fazla randomize kontrollü araştırmaya gereksinim duyulmaktadır.
In this study, the pathophysiology of COVID-19 infection and corticosteroid treatment protocols in intensive care patients are discussed in detail. The process initiated by the binding of the SARS-CoV-2 virus to ACE 2 receptors leads to irregular cytokine release and widespread alveolar damage resulting in acute ARDS in advanced stages. In this hyperinflammation phase, it is predicted that corticosteroids can suppress the immune response and reduce pulmonary damage due to their strong anti-inflammatory properties. According to the RECOVERY trial and World Health Organization (WHO) criteria, the use of 6 mg daily dexamethasone or equivalent corticosteroid therapy for 7-10 days in severe and critical COVID-19 patients requiring supplemental oxygen or mechanical ventilation has been proven to significantly reduce 28-day mortality and the duration of hospitalization. In contrast, no positive effect of corticosteroid use on mortality was found in mild cases without supplemental oxygen demand, and it is not recommended due to potential side effects. During treatment, it is vital for clinicians to closely monitor risks such as hyperglycemia, secondary infections, and opportunistic fungal infections. In conclusion, while the use of standard-dose dexamethasone is strongly recommended in severe patients requiring oxygen support, more randomized controlled trials are needed for pulse steroid and inhaled steroid administrations.
Referanslar
Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention. JAMA 2020; 323(13): 1239-1242.
Recovery Collaborative Group. Lopinavir–ritonavir in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. Lancet 2020; 396 (24): 1345-1352.
WHO Solidarity Trial Consortium. Repurposed antiviral drugs for Covid-19 - interim WHO Solidarity trial results. N Engl J Med 2021; 384 (6): 497-511
Mason RJ. Pathogenesis of COVID-19 from a cell biology perspective. Eur Respir J. 2020;55(4):2000607. doi:10.1183/13993003.00607-2020
Hoffmann M, Kleine-Weber H, Schroeder S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 2020;181:271–280.e8.
Tang NL, Chan PK, Wong CK, et al. Early enhanced expression of interferon-inducible protein-10 (CXCL-10) and other chemokines predicts adverse outcome in severe acute respiratory syndrome. Clin Chem 2005;51:2333–40.
Xu Z, Shi L, Wang Y, et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med 2020;8:420–422.
Singh SP, Pritam M, Pandey B, Yadav TP. Microstructure, pathophysiology, and potential therapeutics of COVID-19: A comprehensive review. J Med Virol. 2021 Jan;93(1):275-299. doi: 10.1002/jmv.26254.
Teuwen LA, Geldhof V, Pasut A, et al. Author Correction: COVID-19: the vasculature unleashed. Nat Rev Immunol. 2020;1. doi:10.1038/s41577-020-0356- 8
Zaim S, Chong JH, Sankaranarayanan V, et al. COVID-19 and Multiorgan Response. Curr Probl Cardiol. 2020;45(8):100618. doi:10.1016/j.cpcardiol.2020.100618
Buttgereit F, da Silva JA, Boers M, et al. Standardised nomenclature for glucocorticoid dosages and glucocorticoid treatment regimens: current questions and tentative answers in rheumatology. Ann Rheum Dis 2002;61:718-722.
Ronchetti S, Ricci E, Migliorati G, Gentili M, Riccardi C. How glucocorticoids affect the neutrophil life. Int J Mol Sci 2018;19:4090.
Buttgereit F, Straub RH, Wehling M, et al. Glucocorticoids in the treatment of rheumatic diseases: an update on the mechanisms of action. Arthritis Rheum 2004;50:3408-17.
Lee N, Allen Chan KC, Hui DS, et al. Effects of early corticosteroid treatment on plasma SARS-associated Coronavirus RNA concentrations in adult patients. J Clin Virol. 2004;31(4):304-309. doi:10.1016/j.jcv.2004.07.006
Arabi YM, Mandourah Y, Al-Hameed F, et al. Corticosteroid Therapy for Critically Ill Patients with Middle East Respiratory Syndrome. Am J Respir Crit Care Med. 2018;197(6):757-767. doi:10.1164/rccm.201706-1172OC
Villar J, Confalonieri M, Pastores SM, et al. Rationale for Prolonged Corticosteroid Treatment in the Acute Respiratory Distress Syndrome Caused by Coronavirus Disease 2019. Crit Care Explor. 2020;2(4):e0111. doi:10.1097/CCE.0000000000000111
Annane D, Pastores SM, Rochwerg B, et al. 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. 2017;45(12):2078-2088. doi:10.1097/CCM.0000000000002737
Siddiqi HK, Mehra MR. COVID-19 illness in native and immunosuppressed states: A clinical−therapeutic staging proposal. J Heart Lung Transplant. 2020;39(5):405- 7.
2020 https://www.who.int/publications/i/item/WHO-2019-nCoV-Corticosteroids -2020.1
COVID-19 Treatment Guidelines Panel. Coronavirus Disease 2019 (COVID-19) Treatment Guidelines. National Institutes of Health. https://www.covid19treatmentguidelines.nih.gov/
Bai C, Chotirmall SH, Rello J, et al. Updated guidance on the management of COVID-19: from an American Thoracic Society/European Respiratory Society coordinated International Task Force. Eur Respir Rev. 2020;29:200287.
Garg D, Muthu V, Sehgal IS, et al. Coronavirus disease (COVID-19) associated mucormycosis (CAM): case report and systematic review of literature. Mycopathologia. 2021;186(2):289-298.
Moorthy A, Gaikwad R, Krishna S, et al. SARS-CoV-2, uncontrolled diabetes and corticosteroids—an unholy trinity in invasive fungal infections of the maxillofacial region? A retrospective, multi-centric analysis. J Maxillofac Oral Surg. 2021:1-8.
Machado M, Valerio M, Alvarez-Uria A, et al. Invasive pulmonary aspergillosis in the COVID-19 era: An expected new entity. Mycoses. 2021;64(2):132-143.
