COVID-19 ve persistent inflamasyon, immünsüpresyon ve katabolizma sendromu

Amaç: Çoklu organ yetmezliği (MOF), yoğun bakım takibi gerektiren ve mortalitesi yüksek bir hastalık grubudur. MOF’lu hastalar MOF’un başlangıcında hemen kaybedilmez ise; ya hızla immünolojik homeostaz durumuna geri döner veya immünolojik disfonksiyon devam ederek kronik kritik hastalığa (KKH) dönüşebilirler. İşte bu grup hastaların bir kısmı, persistent inflamasyon, immünsüpresyon ve katabolizma sendromu (PICS) ile karakterize edilen KKH'den muzdariptir. Biz bu çalışma ile yoğun bakım ünitemizdeki PICS olgularını, mortalite üzerine etkilerini ve biyobelirteçlerini değerlendirmeyi amaçladık. Gereç ve Yöntem: Bu çalışma SARS-CoV-2 nedeniyle akut solunum sıkıntısı sendromu (ARDS) tanısı alan ve yoğun bakım ünitesinde izlenen 190 hastayı içeren retrospektif, gözlemsel bir çalışmadır. Hastaların laboratuvar verileri ve vücut kitle indeksleri (BMI) yoğun bakıma kabulünün 1. günü ile 21. günü karşılaştırılmıştır. Ayrıca hastalar yoğun bakım ünitesinde kalış gün sayısı, CRP, albumin, prealbumin, lenfosit ve BMI verileri kullanılarak PICS açısından değerlendirildi. Bulgular: Hastaların 21. gününde ki laboratuvar değerleri aşağıdaki gibi olup, 1. günde ki değerlerle karşılaştırıldığında istatiksel olarak anlamlı sonuçlar elde edildi. Albumin 2.56±0.57 g/L, prealbumin 9±15 g/L, d-dimer 4.41±4.70 (interquartile range (IQR): 2.53-4,76) µgFEU/mL, fibrinojen 497±189,35 mg/dl, hemoglobin 10.15±1.82 g/dL, lökosit 13.94±8.12 (IQR: 12.34-7.69) 109/L, immatür granülosit 1.16±2.13 (IQR: 0.46-1) 109/L ve BMI’leri 26.92±3.27 (IQR: 26.7-4,8) idi. Yine bu hastalarda lenfosit 0.92±0.80 (IQR: 0.71-0.74) 109/L, CRP 101.42±99,96 mg/L ve trombosit değerleri 214.24±128.08 109/L idi. 28 günlük periyotta 120 (63.8%), 90 günlük periyotta ise 132 (69.5%) hastanın vefat ettiği belirlendi. Sonuç: PICS yoğun bakım hastalarında mortalite ve morbiditeyi etkileyen önemli bir sendromdur. İmmatür granülosit bu grup hastada kullanılabilecek bir diğer biyobelirteç olabilir. PICS ile ilgili çalışmaların eksikliği nedeniyle, PICS'in patogenezini ve yönetimini anlamanın erken bir aşamasındayız ve bu nedenle konuyla ilgili daha kapsamlı araştırmalara ihtiyacımız bulunmaktadır.

Anahtar Kelimeler:

Persistent İnflamasyon, immünsüpresyon, katabolizma sendromu, PICS, covid-19

COVID-19 and persistent inflammation, immunosuppression and catabolism syndrome

Purpose: Multiple organ failure (MOF) is a disease group that necessitates intensive care monitoring and carries a significant mortality rate. If these individuals are not dead as a result of early MOF, they will either quickly restore immunological balance or their immunological dysfunction may persist, resulting in chronic critical illness (CCI). Some of these patients have CCI, which is characterized by chronic inflammation, immunosuppression, and the syndrome of catabolism (PICS). With this study, we aimed to evaluate PICS cases in our intensive care unit, their effects on mortality, and their biomarkers. Materials and Methods: This is a retrospective, observational study involving 190 patients diagnosed with acute respiratory distress syndrome (ARDS) due to SARS-CoV-2 and followed up in the ICU. Patients' laboratory data and body mass index (BMI) were compared between the first and twenty-first days of ICU admission. In addition, the patients were evaluated according to PICS utilizing the number of days they spent in the ICU, CRP, albumin, prealbumin, lymphocytes, and BMI data. Results: The laboratory values of the patients on the 21st day were as follows, and the results obtained were statistically significant when compared with the values on the 1st day. Albumin 2.56±0.57 g/L, prealbumin 9±15 g/L, d-dimer 4.41±4.70 (interquartile range (IQR): 2.53-4.76) µgFEU/mL, fibrinogen 497±189,35 mg/dl, hemoglobin 10.15±1.82 g/dL, leukocytes 13.94±8.12 (IQR: 12.34-7.69) 109/L, immature granulocyte 1.16±2.13 (IQR: 0.46-1)109/L and BMI of 26.92±3.27 (IQR: 26.7-4.8). Again in these patients, lymphocyte values were 0.92±0.80 (IQR: 0.71-0.74)109/L, CRP was 101.42±99,96 mg/L, and platelet values were 214.24±128.08 109/L. Conclusion: PICS is a significant condition affecting mortality and morbidity in critical care patients. In this group of patients, immature granulocytes may also serve as a useful biomarker. Due to the lack of studies regarding PICS, we are in the premature phase of understanding the pathogenesis and management of PICS and therefore need more comprehensive research regarding the topic.

Keywords:

Persistent inflammation, immunosuppression, catabolism syndrome, PICS, covid-19,

PDF

___

Stortz JA, Mira JC, Raymond SL, Loftus TJ, Ozrazgat-Baslanti T, Wang Z et al. Benchmarking clinical outcomes and the immunocatabolic phenotype of chronic critical illness after sepsis in surgical intensive care unit patients. J Trauma Acute Care Surg. 2018;84:342-49.
Loftus TJ, Mira JC, Ozrazgat-Baslanti T, Ghita GL, Wang Z, Stortz JA et al. Sepsis and critical illness research center investigators: protocols and standard operating procedures for a prospective cohort study of sepsis in critically ill surgical patients. BMJ Open. 2017;7:1-7.
Mira JC, Cuschieri J, Ozrazgat-Baslanti T, Wang Z, Ghita GL, Loftus TJ et al. The Epidemiology of chronic critical illness after severe traumatic injury at two level-one trauma centers. Crit Care Med. 2017;45:1989-1996.
Gentile LF, Cuenca AG, Efron PA, Ang D, Bihorac A, McKinley BA et al. Persistent inflammation and immunosuppression: a common syndrome and new horizon for surgical intensive care. J Trauma Acute Care Surg. 2012;72:1491-501.
Zhang J, Luo W, Miao C, Zhong J. Hypercatabolism and anti-catabolic therapies in the persistent inflammation, immunosuppression, and catabolism syndrome. Front Nutr. 2022:13:941097.
Rosenthal MD, Bala T, Wang Z, Loftus T, Moore F. Chronic critical illness patients fail to respond to current evidence-based intensive care nutrition secondarily to persistent inflammation, immunosuppression, and catabolic syndrome. JPEN J Parenter Enter Nutr. 2020;44:1237–1249.
ARDS definition task force. Acute respiratory distress syndrome: the Berlin definition. JAMA 2012;307:2526–33.
Mira JC, Brakenridge SC, Moldawer LL, Moore FA: Persistent inflammation, immunosuppression and catabolism syndrome. Crit Care Clin. 2017;29:245-58.
Ding RY, Qiu JN, Liu BY, Li XX, Sun YN, Liang YJ et al. A retrospective clinical study of sixty-three cases with persistent inflammation immunosuppression and catabolism syndrome. 2016:1;55:941-4.
Stortz JA, Murphy TJ, Raymond SL, Mira JC, Ungaro R, Dirain ML et al. Evidence for persistent immune suppression in patients who develop chronic critical illness after sepsis. Shock. 2018;49:249-58.
Bano G, Trevisan C, Carraro S, Solmi M, Luchini C, Stubbs B et al. Inflammation and sarcopenia: A systematic review and meta-analysis. Maturitas. 2017;96:10-15.
Reintam Blaser A, Malbrain ML, Starkopf J, Fruhwald S, Jakob SM, De Waele J et al. Gastrointestinal function in intensive care patients: terminology, definitions and management. Recommendations of the ESICM working group on abdominal problems. Intensive Care Med. 2012;38:384-94.
Manz MG, Boettcher S. Emergency granulopoiesis. Nat Rev Immunol. 2014;14:302-14.
Kalaitzakis E. Gastrointestinal dysfunction in liver cirrhosis. World J Gastroenterol. 2014;28:14686-95.
Chapple LAS, Plummer MP, Chapman MJ: Gut dysfunction in the ICU: diagnosis and management. Curr Opin Crit Care. 2021;29:141-6.
Hawkins RB, Raymond SL, Stortz JA, Horiguchi H, Brakenridge SC, Gardner A et al. Chronic critical illness and the persistent inflammation, immunosuppression, and catabolism syndrome. Front Immunol. 2018;9:1511.
Hesselink L, Hoepelman RJ, Spijkerman R, de Groot MCH, van Wessem KJP, Koenderman L et al. Persistent inflammation, immunosuppression and catabolism syndrome (PICS) after polytrauma: A rare syndrome with major consequences. J Clin Med. 2020;9:191.
Darden DB, Brakenridge SC, Efron PA, Ghita GL, Fenner BP, Kelly LS et al. Biomarker evidence of the persistent inflammation, immunosuppression and catabolism syndrome (PICS) in chronic critical illness (CCI) after surgical sepsis. Ann Surg. 2021;274:664-73.
Rosenthal MD, Kamel AY, Rosenthal CM, Brakenridge S, Croft CA, Moore FA. Chronic critical illness: application of what we know. Nutr Clin Pract. 2018;33:39-45.
Chao T, Porter C, Herndon DN, Siopi A, Ideker H, Mlcak RP et al. Propranolol and oxandrolone therapy accelerated muscle recovery in burned children. Med Sci Sports Exerc. 2018;50:427-35.
Herndon DN, Voigt CD, Capek KD, Wurzer P, Guillory A, Kline A et al. Reversal of growth arrest with the combined administration of oxandrolone and propranolol in severely burned children. Ann Surg. 2016;264:421-8.
Herndon DN, Rodriguez NA, Diaz EC, Hegde S, Jennings K, Mlcak RP et al. Long-term propranolol use in severely burned pediatric patients: a randomized controlled study. Ann Surg. 2012;256:402-11.