대한임상검사과학회지 (Korean Journal of Clinical Laboratory Science)

  • 제53권4호
  • /
  • Pages.309-316
  • /
  • 2021
  • /
  • 1738-3544(pISSN)
  • /
  • 2288-1662(eISSN)
대한임상검사과학회 (Korean Society for Clinical Laboratory Science)
권호 표지
DOI QR코드

DOI QR Code

패혈증의 진단 및 예후예측

Diagnosis and Prognosis of Sepsis

  • 박창은 (남서울대학교 임상병리학과.분자진단연구소)
  • Park, Chang-Eun (Department of Biomedical Laboratory Science, Molecular Diagnostics Research Institute, Namseoul University)
  • 투고 : 2021.11.28
  • 심사 : 2021.12.06
  • 발행 : 2021.12.31
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

패혈증은 감염원에 의한 생리학적 반응으로 장기의 기능을 손상시켜 조기에 치료하지 않으면 사망에 이르게 하는 기전을 유발한다. 이에 높은 감도, 특이도, 신속 정확도를 가진 바이오마커는 병원균의 미생물학적 검증에 필요한 제한성과 경과 시간을 감안할 때 패혈증을 비감염성 전신성 염증 반응 증후군(SIRS)과 구별하는 것이 획기적일 것으로 판단된다. 또한 항생제를 사용하기 전에 정확한 감염 진단이 중요하고 임상적으로 요구된다. 해당하는 후보물질인 프로칼시토닌, 젖산, C-반응성 단백질, 사이토카인, 프로아드레노매듈린(ProADM)이 진단에 활용된다. 급성 호흡기 감염 환자에서 프로칼시토닌으로 유도되는 항생제 치료는 항생제 노출과 항생제 부작용을 효과적으로 감소시키면서 사망률을 개선한다. 입원환자에 있어서 패혈증 선별검사에 대한 근거 마련은 제한적이다. 임상의사, 연구원 및 건강검진 의사의 전문가 집단은 일반 입원 환자의 패혈증 인식에 대한 스크리닝 도구, 향후 연구 또는 정책을 시행할 때 새로운 바이오마커의 발견과 한계점을 고려해야 한다. 바이오마커 사용은 항상 임상 평가와 상관관계가 있어야 하지만 소아 패혈증에서도 특히 바이오마커의 사용은 기대된다. 따라서 바이오마커의 활용에 있어서 특정된 전염증성 사이토카인 및 단백질 수준이 상승하는 것에 대해 패혈증의 초기 단계에서 사망률을 예측하는 것에 대해 향상된 진단법을 제공할 수 있다.

Sepsis is a physiological response to a source of infection that triggers mechanisms that compromise organ function, leading to death if not treated early. Biomarkers with high sensitivity, specificity, speed, and accuracy that could differentiate sepsis from non-infectious systemic inflammatory response syndrome (SIRS) could bring about a revolution in sepsis treatment. Given the limitations and time required for microbial verification of pathogens, the accurate diagnosis of infection before employing antibiotic therapy is important and clinically necessary. Procalcitonin (PCT), lactate, C-reactive protein (CRP), cytokines, and proadrenomedullin (ProADM) are the common biomarkers used for diagnosis. The procalcitonin (PCT)-guided antibiotic treatment in patients with acute respiratory infections effectively reduces antibiotic exposure and side effects while improving survival rates. The evidence regarding sepsis screening in hospitalized patients is limited. Clinicians, researchers, and healthcare decision-makers should consider these findings and limitations when implementing screening tools, future research, or policy on sepsis recognition in hospitalized patients. The use of biomarkers in pediatric sepsis is promising, although such use should always be correlated with clinical evaluation. Biomarkers may also improve the prediction of mortality, especially in the early phase of sepsis, when the levels of certain pro-inflammatory cytokines and proteins are elevated.

키워드

과제정보

Funding for this paper was provided by Namseoul University year 2021.

참고문헌

  1. Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med. 2001;29:1303-1310. https://doi.org/10.1097/00003246-200107000-00002
  2. Lawrence KL, Kollef MH. Antimicrobial stewardship in the intensive care unit: advances and obstacles. Am J Respir Crit Care Med. 2009;179:434-438. https://doi.org/10.1164/rccm.200809-1394CP
  3. Kutz A, Briel M, Christ-Crain M, Stolz D, Bouadma L, Wolff M, et al. Prognostic value of procalcitonin in respiratory tract infections across clinical settings. Crit Care. 2015;19:74. https://doi.org/10.1186/s13054-015-0792-1
  4. Schuetz P, Birkhahn R, Sherwin R, Jones AE, Singer A, Kline JA, et al. Serial procalcitonin predicts mortality in severe sepsis patients: results from the multicenter procalcitonin monitoring sepsis (MOSES) study. Crit Care Med. 2017;45:781-789. https://doi.org/10.1097/CCM.0000000000002321
  5. Seymour CW, Liu VX, Iwashyna TJ, Brunkhorst FM, Rea TD, Scherag A, et al. Assessment of clinical criteria for sepsis: for the third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA. 2016;315:762-774. https://doi.org/10.1001/jama.2016.0288
  6. Kitanovski L, Jazbec J, Hojker S, Derganc M. Diagnostic accuracy of lipopolysaccharide-binding protein for predicting bacteremia/clinical sepsis in children with febrile neutropenia: comparison with interleukin-6, procalcitonin and C-reactive protein. Support Care Cancer. 2014;22:269-277. https://doi.org/10.1007/s00520-013-1978-1
  7. Amland RC, Hahn-Cover KE. Clinical decision support for early recognition of sepsis. Am J Med Qual. 2016;31:103-110. https://doi.org/10.1177/1062860614557636
  8. Gyang E, Shieh L, Forsey L, Maggio P. A nurse-driven screening tool for the early identification of sepsis in an intermediate care unit setting. J Hosp Med 2015;10:97-103. https://doi.org/10.1002/jhm.2291
  9. Schuetz P, Wirz Y, Sager R, Christ-Crain M, Stolz D, Tamm M, Effect of procalcitonin-guided antibiotic treatment on mortality in acute respiratory infections: a patient level meta-analysis. Lancet Infect Dis. 2018;18:95-107. https://doi.org/10.1016/S1473-3099(17)30592-3
  10. Levy MM, Rhodes A, Phillips GS, Townsend SR, Schorr CA, Beale R, et al. Surviving sepsis campaign: association between performance metrics and outcomes in a 7.5-year study. Crit Care Med. 2015;43:3-12. https://doi.org/10.1097/CCM.0000000000000723
  11. Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, et al. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med. 2013;41:580-637. https://doi.org/10.1097/CCM.0b013e31827e83af
  12. Liu S, Hou Y, Cui H. Clinical values of the early detection of serum procalcitonin, C-reactive protein and white blood cells for neonates with infectious diseases. Pak J Med Sci. 2016;32:1326-1329. https://doi.org/10.12669/pjms.326.11395
  13. Povoa P, Coelho L, Almeida E, Fernandes A, Mealha R, Moreira P, et al. Early identification of intensive care unit-acquired infections with daily monitoring of c-reactive protein: a prospective observational study. Crit Care. 2006;10:R63. https://doi.org/10.1186/cc4892
  14. Kellum JA, Kong L, Fink MP, Weissfeld LA, Yealy DM, Pinsky MR, et al. Understanding the inflammatory cytokine response in pneumonia and sepsis: results of the genetic and inflammatory markers of sepsis (GenIMS) study. Arch Intern Med. 2007;167:1655-1663. https://doi.org/10.1001/archinte.167.15.1655
  15. Calfee CS, Thompson BT, Parsons PE, Ware LB, Matthay MA, Wong HR. Plasma interleukin-8 is not an effective risk stratification tool for adults with vasopressor-dependent septic shock. Crit Care Med. 2010;38:1436-1441. https://doi.org/10.1097/CCM.0b013e3181de42ad
  16. Prucha M, Bellingan G, Zazula R. Sepsis biomarkers. Clin Chim Acta. 2015;440:97-103. https://doi.org/10.1016/j.cca.2014.11.012
  17. Schuetz P, Aujesky D, Muller C, Muller B. Biomarker-guided personalised emergency medicine for all-hope for another hype? Swiss Med Wkly. 2015;145:w14079. https://doi.org/10.4414/smw.2015.14079
  18. Kelly BJ, Lautenbach E, Nachamkin I, Coffin SE, Gerber JS, Fuchs BD, et al. Combined biomarkers discriminate a low likelihood of bacterial infection among surgical intensive care unit patients with suspected sepsis. Diagn Microbiol Infect Dis. 2016;85:109-115. https://doi.org/10.1016/j.diagmicrobio.2016.01.003
  19. Shapiro NI, Trzeciak S, Hollander JE, Birkhahn R, Otero R, Osborn TM, et al. A prospective, multicenter derivation of a biomarker panel to assess risk of organ dysfunction, shock, and death in emergency department patients with suspected sepsis. Crit Care Med. 2009;37:96-104. https://doi.org/10.1097/CCM.0b013e318192fd9d
  20. Andersen LW, Mackenhauer J, Roberts JC, Berg KM, Cocchi MN, Donnino MW. Etiology and therapeutic approach to elevated lactate levels. Mayo Clin Proc. 2013;88:1127-1140. https://doi.org/10.1016/j.mayocp.2013.06.012
  21. Wong HR, Salisbury S, Xiao Q, Cvijanovich NZ, Hall M, Allen GL, et al. The pediatric sepsis biomarker risk model. Crit Care. 2012;16:R174. https://doi.org/10.1186/cc11652
  22. Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, et al. The third international consensus definitions for sepsis and septic shock (sepsis-3). JAMA. 2016; 315:801-810. https://doi.org/10.1001/jama.2016.0287
  23. Weber GF, Chousterman BG, He S, Fenn AM, Nairz M, Anzai A, et al. Interleukin-3 amplifies acute inflammation and is a potential therapeutic target in sepsis. Science. 2015;347:1260-1265. https://doi.org/10.1126/science.aaa4268
  24. O'Callaghan DJ, O'Dea KP, Scott AJ, Takata M, Gordon AC. Monocyte tumor necrosis factor-alpha-converting enzyme catalytic activity and substrate shedding in sepsis and noninfectious systemic inflammation. Crit Care Med. 2015;43:1375-1385. https://doi.org/10.1097/CCM.0000000000000992
  25. Read CB, Kuijper JL, Hjorth SA, Heipel MD, Tang X, Fleetwood AJ, et al. Cutting edge: identification of neutrophil PGLYRP1 as a ligand for TREM-1. J Immunol. 2015;194:1417-1421. https://doi.org/10.4049/jimmunol.1402303
  26. Motal MC, Klaus DA, Lebherz-Eichinger D, Tudor B, Hamp T, Wiegele M, et al. Increased plasma vaspin concentration in patients with sepsis: an exploratory examination. Biochem Med (Zagreb). 2015;25:90-96. https://doi.org/10.11613/BM.2015.011
  27. Wang K, Bhandari V, Giuliano JS Jr, O Hern CS, Shattuck MD, Kirby M. Angiopoietin-1, angiopoietin-2 and bicarbonate as diagnostic biomarkers in children with severe sepsis. PLoS One. 2014;9:e108461 https://doi.org/10.1371/journal.pone.0108461
  28. Benz F, Roy S, Trautwein C, Roderburg C, Luedde T. Circulating microRNAs as biomarkers for sepsis. Int J Mol Sci. 2016;17:78. https://doi.org/10.3390/ijms17010078
  29. Kumar S, Tripathy S, Jyoti A, Singh SG. Recent advances in biosensors for diagnosis and detection of sepsis: a comprehensive review. Biosens Bioelectron. 2019;124-125:205-215. https://doi.org/10.1016/j.bios.2018.10.034
  30. Stryjewski GR, Nylen ES, Bell MJ, Snider RH, Becker KL, Wu A, et al. Interleukin-6, interleukin-8, and a rapid and sensitive assay for calcitonin precursors for the determination of bacterial sepsis in febrile neutropenic children. Pediatric Crit Care Med. 2005; 6:129-135. https://doi.org/10.1097/01.PCC.0000149317.15274.48
  31. Bozza FA, Salluh JI, Japiassu AM, Soares M, Assis EF, Gomes RN, et al. Cytokine profiles as markers of disease severity in sepsis: a multiplex analysis. Crit Care. 2007;11:R49 https://doi.org/10.1186/cc5783
  32. Tsujimoto H, Ono S, Majima T, Kawarabayashi N, Takayama E, Kinoshita M, et al. Neutrophil elastase, MIP-2, and TLR-4 expression during human and experimental sepsis. Shock. 2005; 23:39-44. https://doi.org/10.1097/01.shk.0000145936.31967.d7
  33. Vaschetto R, Nicola S, Olivieri C, Boggio E, Piccolella F, Mesturini R, et al. Serum levels of osteopontin are increased in SIRS and sepsis. Intensive Care Med. 2008;34:2176-2184. https://doi.org/10.1007/s00134-008-1268-4
  34. Mikolajczyk TP, Nosalski R, Szczepaniak P, Budzyn K, Osmenda G, Skiba D. et al. Role of chemokine RANTES in the regulation of perivascular inflammation, T-cell accumulation, and vascular dysfunction in hypertension. FASEB J. 2016;30:1987-1999. https://doi.org/10.1096/fj.201500088R
  35. Wright SW, Lovelace-Macon L, Hantrakun V, Rudd KE, Teparrukkul P, Kosamo S, et al. sTREM-1 predicts mortality in hospitalized patients with infection in a tropical, middle-income country. BMC Med. 2020;18:159. https://doi.org/10.1186/s12916-020-01627-5
  36. Behnes M, Bertsch T, Lepiorz D, Lang S, Trinkmann F, Brueckmann M, et al. Diagnostic and prognostic utility of soluble CD 14 subtype (presepsin) for severe sepsis and septic shock during the first week of intensive care treatment. Crit Care. 2014;18:507. https://doi.org/10.1186/s13054-014-0507-z
  37. Mansur A, von Gruben L, Popov AF, Steinau M, Bergmann I, Ross D, et al. The regulatory toll-like receptor 4 genetic polymorphism rs11536889 is associated with renal, coagulation and hepatic organ failure in sepsis patients. J Transl Med. 2014;12:177. https://doi.org/10.1186/1479-5876-12-177
  38. Sinha M, Jupe J, Mack H, Coleman TP, Lawrence SM, Fraley SI. Emerging technologies for molecular diagnosis of sepsis. Clin Microbiol Rev. 2018;31:e00089-17. https://doi.org/10.1128/CMR.00089-17
  39. Bloos F, Trips E, Nierhaus A, Briegel J, Heyland DK, Jaschinski U, et al. Effect of sodium selenite administration and procalcitonin-guided therapy on mortality in patients with severe sepsis or septic shock: a randomized clinical trial. JAMA Intern Med. 2016;176:1266-1276. https://doi.org/10.1001/jamainternmed.2016.2514
  40. Vincent JL, Sakr Y, Sprung CL, Ranieri VM, Reinhart K, Gerlach H, et al. Sepsis in European intensive care units: results of the SOAP study. Crit Care Med. 2006;34:344-353. https://doi.org/10.1097/01.ccm.0000194725.48928.3a