Sie sind auf Seite 1von 48

Septischer Schock – Licht am Ende

des therapeutischen Tunnels?

Ernst Hanisch
Klinik für Allgemein-, Viszeral- und
Endokrine Chirurgie
Asklepios Klinik Langen
HERFARTH, Editorial Chirurg
„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
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“

Schottmüller 1914
Definitonen Consensus
Conference ACCP/SCCM 1992

Definition SIRS
Temperatur >38° C oder <36° C

Herzfrequenz >90/min

Tachypnoe >20 Atemzüge/min

oder pCO2<32
Leukozyten >12000 oder <4000
Infectious and Noninfectious Causes of Fever in the Intensive Care Unit

Hotchkiss R and Karl I. N Engl J Med 2003;348:138-150

Definition SEPSIS

Systemic Inflammatory Response to

SIRS und Infektion
• Metabolische Azidose
• Akute Enzephalopathie
• Oligurie (<0,5ml/kg für wenigstens 1h)
• Hypoxämie (paO2/FiO2<280)
• Hypotension (<90mmHg oder Abfall um 40
mmHg vom Ausgangswert)
• Sepsis
• Systolischer Blutdruck <90mmHg oder
Abfall >40mmHg vom Ausgangswert
• Positiv inotrope oder vasoaktive Medikation
zur Korrektur der Hypotension
Therapie des Septischen Schocks

• Definitive Behandlung
• Unterstützende Behandlung

• Round table; Sibbald et al CritCareMed

Erste Priorität

Ubi pus ibi evacua (Celsus)

Kirschner‘sche Postulate 50.Tagung der
Deutschen Gesellschaft für Chirurgie 1926

• Verstopfung der Infektionsquelle

• Beseitigung des Exsudates
• Behandlung der Bauchhöhle mit
• 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
• Sofortige und adäquate
Volumensubstitution entscheidender Schritt
• Zielkriterium: Kardiale Füllungsdrucke
• Keine Evidenz, daß kolloidale den
kristalloiden Lösungen überlegen sind
• Albumin nicht von Vorteil
• 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

6ml/kg 12 ml/kg
Letalität 30 % 40 %
New directions: Early goal directed
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%

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

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%

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
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


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
van den Berghe et al, NEnglJMed 2001,345,1359-
Konventionelle Insulin Therapie
N=783 N=765
Alle Patienten 10,9% 7,2%

>5 Tage ICU 26,3% 16,8%

New directions: Niedrig dosierte
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

Crit Care Med 2008 Vol. 36,

No.1, 296