SIRS 2 SIRS SIRS 2001 SCCM ACCP ESICM ATS SIS International Sepsis Definitions Conference SIRS 4 C CRP CRP TNF -α IL -6 6,7 8 CRP SOFA score 6

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1 sepsis severe sepsis / septic shock Schottmuller 1989 Bone sepsis syndrome SCCM ACCP SIRS 3 SIRS 4 SIRS severe sepsis septic shock SIRS / /

2 SIRS 2 SIRS SIRS 2001 SCCM ACCP ESICM ATS SIS International Sepsis Definitions Conference SIRS 4 C CRP CRP TNF -α IL -6 6,7 8 CRP SOFA score 6 infection probability score scd14-st CRP PCT 9,10 / Surviving Sepsis Campaign SSC Surviving Sepsis Campaign Guidelines SSCG SSC SCCM ESCIM International Sepsis Forum SSC 2004 / SSCG SSCG International Guidelines for Management of Severe Sepsis and Septic Shock / SIRS

3 39 1 SSCG2012 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: Crit Care Med. 2013; 41: SSCG SCCM/ESICM/ACCP/ATS/ SIS 1 20 SIRS SIRS SIRS ICU 2000 JANIS ICU ICU sepsis registry

4 40 ICU JANIS ICU 48 ICU SIRS SIRS/ 80 ICU MRSA Angus 1, , , , SOFA score APACHE II T 18

5 41 1 SIRS CARS PAMPs PAMPs Toll TLR NOD NLR PRR PRR IL-1β IL-6 TNF-α DIC T IL-10 SIRS CARS 19 1 EGDT / / early goaldirected therapy EGDT EGDT 3 ICU EGDT EGDT 21,22 SSCG

6 42 2 EGDT Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001; 345: Grade1C Grade1A 11,23 EGDT ProCESS trial EGDT EGDT EGDT / EGDT EGDT ProCESS trial ARISE trial 25 ProMISe trial 26

7 43 SSCG Kumar TNF-α TNF-α TNF-α 28 PRR TLR-4 eritoran 29 SIRS CARS G-CSF fligrastim 30 GM-CSF APACHE ICU 31 PRR LPS ω T PD-1 PD-1 34 CLP PD-1 35 SSC SSC

8 SSCG EGDT / 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. 29: , Bone RC, Fisher CJ Jr, Clemmer TP, Slotman GJ, Metz CA, Balk RA: Sepsis syndrome: a valid clinical entity. Methylprednisolone Severe Sepsis Study Group. Crit Care Med. 17: , Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, et al.: Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest. 101: , Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, et al.: 2001 SCCM/ESICM/ ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med. 31: , Peres Bota D, Mélot C, Lopes Ferreira F, Vincent JL: Infection Probability Score (IPS): A method to help assess the probability of infection in critically ill patients. Crit Care Med. 31: , Ratzinger F, Schuardt M, Eichbichler K, Tsirkinidou I, Bauer M, Haslacher H, et al.: Utility of sepsis biomarkers and the infection probability score to discriminate sepsis and systemic inflammatory response syndrome in standard care patients. PLoS One. 11;8: e82946, Martin GS, Mannino DM, Eaton S, Moss M: The epidemiology of sepsis in the United States from 1979 through N Engl J Med. 348: , Tang BM, Eslick GD, Craig JC, McLean AS: Accuracy of procalcitonin for sepsis diagnosis in critically ill patients: systematic review and metaanalysis. Lancet Infect Dis. 7: , 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. 5;18: 507, Masson S, Caironi P, Spanuth E, Thomae R, Panigada M, Sangiorgi G, et al.: Presepsin (soluble CD14 subtype) and procalcitonin levels for mortality prediction in sepsis: data from the Albumin Italian Outcome Sepsis trial. Crit Care. Jan 7;18: R6, 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: Crit Care Med. 41: , Ogura H, Gando S, Saitoh D, Takeyama N, Kushimoto S, Fujishima S, et al.: Epidemiology of severe sepsis in Japanese intensive care units: aprospective multicenter study. J Infect Chemother. 20: , 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. 34: , Vincent JL, Bihari DJ, Suter PM, Bruining HA, White J, Nicolas-Chanoin MH, et al.: The prevalence of nosocomial infection in intensive care units in Europe. Results of the European Prevalence of Infection in Intensive Care (EPIC) Study. EPIC International Advisory Committee. JAMA. Aug 23-30;274: , go.jp/toukei/list/81-1a.html 17 Sepsis Registry 24: , Wilhelm J, Hettwer S, Schuermann M, Bagger S, Gerhardt F, Mundt S, et al.: Elevated troponin in septic patients in the emergency department: frequency, causes, and prognostic implications. Clin Res Cardiol. 103: , Bone RC: Sir Isaac Newton, sepsis, SIRS, and CARS. Crit Care Med. 24: , Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin

9 45 A, Knoblich B, et al.: Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 345: , Puskarich MA, Marchick MR, Kline JA, Steuerwald MT, Jones AE: One year mortality of patients treated with an emergency department based early goal directed therapy protocol for severe sepsis and septic shock: a before and after study. Crit Care. 13: R167, Sivayoham N, Rhodes A, Jaiganesh T, van Zyl Smit N, Elkhodhair S, Krishnanandan S: Outcomes from implementing early goal-directed therapy for severe sepsis and septic shock: a 4-year observational cohort study. Eur J Emerg Med. 4: , Sepsis Registry 20: , Yealy DM, Kellum JA, Huang DT, Barnato AE, Weissfeld LA, Pike F, et al.: A randomized trial of protocol-based care for early septic shock. N Engl J Med. 370: , ClinicalTrials.gov (http;//clinicaltrials.gov) Identifier: NCT ISRCTN registry. ( Trial number: ISRCTN Kumar A, Roberts D, Wood KE, Light B, Parrillo JE, Sharma S, et al.: Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med. 34: , Bernard GR, Francois B, Mira JP, Vincent JL, Dellinger RP, Russell JA, et al.: Evaluating the efficacy and safety of two doses of the polyclonal anti-tumor necrosis factor-α fragment antibody AZD9773 in adult patients with severe sepsis and/ or septic shock: randomized, double-blind, placebo-controlled phase IIb study*. Crit Care Med. 42: , Opal SM, Laterre PF, Francois B, et al.; ACCESS Study Group. Effect of eritoran, an antagonist of MD2-TLR4, on mortality in patients with severe sepsis: the ACCESS randomized trial. JAMA. 309: , Root RK, Lodato RF, Patrick W, Cade JF, Fotheringham N, Milwee S, et al.: Multicenter, double-blind, placebo-controlled study of the use of filgrastim in patients hospitalized with pneumonia and severe sepsis. Crit Care Med. 31: , Meisel C, Schefold JC, Pschowski R, Baumann T, Hetzger K, Gregor J, et al.: Granulocyte-macrophage colony-stimulating factor to reverse sepsisassociated immunosuppression: a double-blind, randomized, placebo-controlled multicenter trial. Am J Respir Crit Care Med. 180: , Tsutsumi R, Horikawa YT, Kume K, Tanaka K, Kasai A, Kadota T, et al.: Whey Peptide-Based Formulas With ω-3 Fatty Acids Are Protective in LPS-Mediated Sepsis. JPEN J Parenter Enteral Nutr Feb 3. [Epub ahead of print]. 33 Harama D, Koyama K, Mukai M, Shimokawa N, Miyata M, Nakamura Y, et al.: A subcytotoxic dose of subtilase cytotoxin prevents lipopolysaccharide-induced inflammatory responses, depending on its capacity to induce the unfolded protein response. J Immunol. 183: , Huang X, Venet F, Wang YL, Lepape A, Yuan Z, Chen Y, et al.: PD-1 expression by macrophages plays a pathologic role in altering microbial clearance and the innate inflammatory response to sepsis. Proc Natl Acad Sci U S A. 106: , Brahmamdam P, Inoue S, Unsinger J, Chang KC, McDunn JE, Hotchkiss RS: Delayed administration of anti-pd-1 antibody reverses immune dysfunction and improves survival during sepsis. J Leukoc Biol. 88: , Stevenson EK, Rubenstein AR, Radin GT, Wiener RS, Walkey AJ: Two decades of mortality trends among patients with severe sepsis: a comparative meta-analysis. Crit Care Med. 42: , 2014.

164 SDD & SOD SDD E100 mg 80 mg B500 mg 2 E 2 B 48 /59 81 SDD SOD 10 /63 16 RCT RCT 1992 Gastinne 15 ICU 445 SDD E100 mg 80 mg B 10

164 SDD & SOD SDD E100 mg 80 mg B500 mg 2 E 2 B 48 /59 81 SDD SOD 10 /63 16 RCT RCT 1992 Gastinne 15 ICU 445 SDD E100 mg 80 mg B 10 163 特集 SDD & SOD SDD(Selective digestive decontamination),sod(selective oropharynx decontamination), 腸内細菌叢, 耐性菌 Ⅰ はじめに SDD Selective digestive decontamination SOD Selective oropharynx decontamination