Ernst Hanisch Klinik für Allgemein-, Viszeral- und Endokrine Chirurgie Asklepios Klinik Langen HERFARTH, Editorial Chirurg 1995 „Die Frustration des Chirurgen, die entsteht, wenn er mitansehen muß, wie eine kleine Anastomoseninsuffizienz einen mühsam angestrebten Erfolg zunichte machen kann, verlangt nach intensiver chirurgischer Forschung“ Epidemiologie des Septischen Schocks: MEDAN - Datenbank 2003
Patienten N= 382 Alter [Jahre] 66,0 Liegedauer [Tage] 18,6 Respirator [Tage] 13 Letalität [%] 49 Wenzel R. N Engl J Med 2002;347:966-967 Inflammatory Responses to Sepsis
Russell J. N Engl J Med 2006;355:1699-1713
The Response to Pathogens, Involving "Cross-Talk" among Many Immune Cells, Including Macrophages, Dendritic Cells, and CD4 T Cells
Hotchkiss R and Karl I. N Engl J Med 2003;348:138-150
Feature: Septic Shock -finding the way through the maze
„Most clinicians can recognize septic shock, but
if you ask them, you get a hundred definitions“
Lancet 354, Nr. 9195, December 11th 1999
Definition: SEPSIS „Eine Sepsis liegt dann vor, wenn sich innerhalb des Körpers ein Herd gebildet hat, von dem kontinuierlich oder periodisch pathogene Bakterien in den Blutkreislauf gelangen und zwar derart, daß durch diese Invasion subjektive und objektive Krankheitserscheinungen ausgelöst werden“
Peritonitis-Behandlung Kirschner‘sche Postulate 50.Tagung der Deutschen Gesellschaft für Chirurgie 1926
• Verstopfung der Infektionsquelle
• Beseitigung des Exsudates • Behandlung der Bauchhöhle mit Desinfektionsmitteln • Ableitung des Exsudates • Nachbehandlung Diffuse Peritonitis Eckpfeiler der Therapie • Chirurgische Intervention ohne Verzögerung • Herdsanierung, ausgedehnte intraop Spülung • Kontinuierliche postop Lavage, Offenes Abdomen, geplante Relap (Etappenlavage), Relap on demand
• CAVE: Adominelles Kompartment
British Journal of Surgery 2002, 89, 1516-1524 Comparison of On-Demand vs Planned Relaparotomy Strategy in Patients With Severe Peritonitis A Randomized Trial Oddeke van Ruler, MD et al JAMA, August 22/29, 2007—Vol 298, No. 8 865 Letalität und Morbidität On-Demand Planned P
Letalität 32/112 (29) 41/113 (36) .22
Morbidität 32/80 (40) 32/72 (44) .58
Unterstützende Behandlung
• Antiinfektiöse Maßnahmen • Volumentherapie • Katecholamintherapie Volumentherapie • Sofortige und adäquate Volumensubstitution entscheidender Schritt • Zielkriterium: Kardiale Füllungsdrucke • Keine Evidenz, daß kolloidale den kristalloiden Lösungen überlegen sind • Albumin nicht von Vorteil Katecholamintherapie • Norepinephrin Katecholamin der 1.Wahl • Adrenalin: sehr zurückhaltender Einsatz • Dobutamin: wenn CI erniedrigt
• Taskforce ACCM/SCCM 1999
New directions • Niedriges Tidalvolumen (ALI/ARDS) • Early goal-directed therapy • Aktiviertes Protein C (Xigris) • IgM angereichertes polyvalentes Immunglogulin (Pentaglobin) • Niedrig-dosierte Corticosteroide • Enge Kontrolle des Blutzuckers New directions: Niedriges Tidalvolumen (ALI/ARDS) The ARDSNetwork, NEnglJMed 2000,342:1301-1308
6ml/kg 12 ml/kg Letalität 30 % 40 % New directions: Early goal directed therapy Rivers E et al; NEnglJMed 2001,345:1368-1377
ZVD >8-12mmHg Kristalloide/Kolloide
MAP >65mmHg Vasoaktive Substanzen
Urinproduktion >0,5ml/kg/h
ScvO2 >70% SaO2>93%;Hkt>30%
CI New directions: EGDT-Letalität Standard EGDT (n=133) (n=130) Alle Pat. 46,5 % 30,5 % Schwere Sepsis 30 % 14,9% Sept. Schock 56,8% 42,3 % 28 Tage 49,2 % 33,3 % 60 Tage 56,9% 44,3 % New directions: Aktiviertes Protein C (Xigris) - PROWESS; Bernard et al, NEnglJMed 2001,344,699-709
Placebo (n=840) Xigris(n=850)
No surgery 72,6% 73,5%
Site of infection LUNG 53,6% 53,6%
ABDOMEN 19,9% 20%
URINARY 10,2% 10%
TRACT OTHER 16,3% 16,4% New directions: Aktiviertes Protein C (Xigris) Letalität
Placebo 31,3%
Xigris 24,8%
ARR 6,5(95%CI 2,2-10,7)
Surviving Sepsis — Practice Guidelines, Marketing Campaigns, and Eli Lilly Peter Q. Eichacker, M.D., Charles Natanson, M.D., and Robert L. Danner, M.D. n engl j med 355;16 october 19, 2006 Timeline of Controlled Trials of rhAPC, Regulatory Actions, Yearly Sales, and the Marketing Initiative by Eli Lilly
Eichacker P et al. N Engl J Med 2006;355:1640-1642
Conclusion
In our systematic review, we have shown that
antithrombin III seems ineffective in any population of critically ill patients regarding mortality and it even increases the risk of bleeding events.
Its use in critically ill patients cannot be recommended
based on the available evidence nor in patients without adjuvant heparin, but it may be relevant to explore this further in future trials. Management of Sepsis • …I agree that surgical patients who have single-organ dysfunction are at increased risk for death when they are treated with activated proteinC and therefore should not receive this treatment.
• James A Russel, NEnglJMed 356;11,
March 15, 2007
• Intensive Insulin Therapy and Pentastarch Resuscitation in Severe Sepsis Frank M. Brunkhorst, et al
N Engl J Med 2008;358:125-39
New directions: Enge Kontrolle des Blutzuckers (<110mg%) LETALITÄT van den Berghe et al, NEnglJMed 2001,345,1359- 1367 Konventionelle Insulin Therapie Therapie N=783 N=765 Alle Patienten 10,9% 7,2%
>5 Tage ICU 26,3% 16,8%
New directions: Niedrig dosierte Corticosteroide Annane et al, JAMA 2002, 288:862-871
Placebo Corticosteroide
Letalität 61 % 55 % (28 Tage) Immunologic Response of Three Hypothetical Patients with Sepsis
Hotchkiss R and Karl I. N Engl J Med 2003;348:138-150
Cochrane Review The Cochrane Library, update 2003 (the Cochr ane Library, Issue 1, 2003. Oxford: Update Software)
Intravenous immunoglobulin for treating sepsis and septic shock
Increase of Survival following Therapy
Relative Risk 0.48 Factor 2.1 Pentaglobin® n = 1 94
Relative Risk 0.64 Factor 1.56 IVIG or Pe nta globin® n = 492
Relative Risk 0.73 Factor 1.37 IVIG n = 2 98
Relative Risk 0.93 Factor 1.07
Ant i-Zytokin MABs n = 43 18
Relative Risk 0.97 Factor 1.03
Ant i-Endot oxin MAB n = 28 26 Sepsis: Time to reconsider the concept Jean Carlet, MD; Jonathan Cohen, MD; Thierry Calandra, MD, PhD; Steven M. Opal, MD; Henry Masur, MD
Crit Care Med 2008 Vol. 36, No. 3, 964
The organ in which infection takes place is also of paramount importance.
For example, it is known that defense mechanisms in the
lung and in the peritoneum are quite dissimilar, leading to differential effects of compounds aimed at manipulating the same inflammatory network Another issue is perhaps more difficult to address. If taken to its logical conclusion, clinical trials would need to be carried out in a much more precisely and narrowly defined population.
This represents a real challenge to the pharmaceutical industry
because of the potential (or perceived) limitation to the market. Interestingly,this does not seem to be the case in oncology, and several companieshave now started to take tentative steps in this direction in the field of severe infection.
Patient entry into studies of sepsis using a broad definition is indeed
more readily accrued, but the advantage of rapid accrual is outweighed by the disadvantage of treating a very heterogeneous group of patients. Special Article Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008
R. Phillip Dellinger, MD; Mitchell M. Levy, MD; Jean M. Carlet, MD; Julian Bion, MD; Margaret M. Parker, MD; Roman Jaeschke, MD; Konrad Reinhart, MD; Derek C. Angus, MD, MPH; Christian Brun-Buisson, MD; Richard Beale, MD; Thierry Calandra, MD, PhD; Jean-Francois Dhainaut, MD; Herwig Gerlach, MD; Maurene Harvey, RN; John J. Marini, MD; John Marshall, MD; Marco Ranieri, MD; Graham Ramsay, MD; Jonathan Sevransky, MD; B. Taylor Thompson, MD; Sean Townsend, MD; Jeffrey S. Vender, MD; Janice L. Zimmerman, MD; Jean-Louis Vincent, MD, PhD; for the International Surviving Sepsis Campaign Guidelines Committee
