1) Sepsis is a systemic inflammatory response to infection that can lead to organ dysfunction. It ranges from sepsis to severe sepsis with organ dysfunction to septic shock with hypotension. 2) Early goal directed therapy aims to optimize oxygen delivery through fluid resuscitation, vasopressors if needed, and blood transfusion to maintain certain goals such as a central venous pressure of 8-12 mmHg and central venous oxygen saturation above 70% within 6 hours. 3) Early goal directed therapy within 6 hours that includes early antibiotics, fluid resuscitation, and maintaining blood pressure and oxygen delivery goals can significantly reduce mortality from sepsis.

1. Sepsis

2. Wat is sepsis?
• Sepsis is een heftige immuunrespons op
bacterien / toxinen in de bloedbaan.
• Gekenmerkt door een systemische
inflammatoire respons, SIRS.
• Bij infecties in het bloed, urine, longen, hart, etc.
• SIRS ook bij operatie en trauma
• Continuum van SIRS – septische shock

3. Wat gebeurt er bij sepsis?
• Sepsis bij circa 2% van de SEH patiënten
• Mortaliteit:
– 33% bij ernstige sepsis
– 59% bij septische shock

4. Systemic Inflammatory Response
Syndrome (SIRS)
Twee of meer criteria:
• Temperatuur >38˚C of <36˚C
• Hartslag >90/min
• Ademhalingsfrequentie > 20/min
• Leuko’s > 12 of < 4

5. Stadia
Stadia sepsis
Sepsis
≥ 2 SIRS-verschijnselen met
verdenking op of aanwijzing voor
infectie.
Ernstige sepsis
sepsis met orgaanfalen zoals
verwardheid, acute oligurie < 0,5
ml/kg, ARDS
Septische shock
sepsis met hypotensie ondanks
adequate volumeresuscitatie (SBP < 90
mmHg of daling > 40 mmHg van
baseline)

7. Types of sepsis
• Sepsis:
– Two or more SIRS criteria, known or suspected infection
• Severe sepsis:
– Sepsis as above
– Organ dysfunction
-Hypotension:
systolic <90 mmHg, MAP <65 mmHg, or a decrease
in 40 mmHg from usual reading
-Lactate > 4mmol/L
-Altered mental status
-Hyperglycemia in the absence of diabetes
-Hypoxemia, O2 < 93%
-UOP <0.5 ml/kg/hr and/or raised urea or creatinine
-Coagulopathy, INR >1.5

8. Types of sepsis
• Septic shock:
– Severe sepsis
– Hypotension or raised lactate that does not improve with adequate
fluid resuscitation
• Multiple organ dysfunction:
– Perfusion is compromised, ischemia and hypoxia of organs
– Cardiovascular-Heart Failure, Neurological- change in LOC,
Pulmonary-ARDS, Renal- Acute Renal Failure, Metabolic-acidosis,
Hepatic- Liver Failure, Hematologic-Disseminated Intravascular
Clotting

10. Wat gebeurt er bij (ernstige) sepsis?
• Lage perifere weerstand door lekkage van capillairen
en vasodilatatie
• Initieel hoge cardiac output tot een kantelpunt
• Inadequate weefselperfusie en weefselhypoxie
• Gestoord zuurstofgebruik
• Anaerobe verbranding en lactaatacidose
• Oligurie
• Verwardheid
• Diffuus intravasale stolling

12. Waarom orgaanfalen?

13. Hoe meten we (ernstige) sepsis?
•
•
•
•
•
•
Verhoogde infectieparameters
Verhoogd lactaatgehalte
Verlaagde veneuze zuurstofsaturatie
Verlaagde bloeddruk
Verlaagde urineproductie
Diverse tekenen van orgaanfalen

15. Hoe ernstig is sepsis?
Incidence of Severe Sepsis
Mortality of Severe Sepsis
250,000
250
200
150
100
200,000
Deaths/Year
Cases/100,000
300
150,000
100,000
50,000
50
0
AIDS* Colon Breast CHF† Severe
Cancer§
Sepsis‡
†National
0
AIDS*
Breast AMI†
Cancer§
Severe
Sepsis‡
Center for Health Statistics, 2001. §American Cancer Society, 2001. *American Heart Association.
2000. ‡Angus DC et al. Crit Care Med. 2001;29(7):1303-1310.

16. Surviving Sepsis Campaign
A global program to:
• Reduce mortality rates
•Improve standards of care
•Secure adequate funding

17. 6 Hour Resuscitation Bundle
• Early Identification
• Early Antibiotics and
Cultures
• Early Goal Directed
Therapy

18. Early Goal Directed Therapy
• Early goal-directed therapy (EGDT) is a
haemodynamic optimization protocol that is
proven to reduce mortality in cases of severe
sepsis/septic shock.
• Early goal-directed therapy (EGDT) was
proposed by Rivers et al in 2001. This protocol
advocates aggressive treatment commencing
in the emergency department to achieve certain
haemodynamic goals.
• This achieved a 16% absolute risk reduction
for in-hospital mortality.
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;345:1368-77.

19. What’s the theory behind Early Goal
Directed Therapy?
In sepsis, circulatory insufficiency (intravascular volume
depletion, peripheral vasodilatation and myocardial
depression), combined with an increased metabolic state could
lead to an imbalance between oxygen demand and delivery,
resulting in anaerobic metabolism and the potential
development of multiple organ dysfunction syndrome.

20. Initial Resuscitation
Goals during first 6 hours:
•
•
•
•
Central venous pressure: 8–12 mm Hg
Mean arterial pressure  65 mm Hg (≈95/50)
Urine output  0.5 mL kg-1/hr-1 (≈40ml)
Central venous (superior vena cava) [SvO2]
saturation  70%
Grade B

21. Components of EGDT
• Fluid resuscitation and CVP monitoring
• MAP maintenance and vasopressors
• ScvO2 monitoring and blood transfusion
+ Intravenous antibiotics administration early

22. Fluid resuscitation and CVP
Monitoring
• Patients are usually fluid depleted – absolute
vs relative
• Fluid resuscitation can help to reduce the
global tissue hypoxia, by increasing the
cardiac output and improving oxygen
delivery to the tissues
• Continued fluid challenges of 500 ml

24. ScvO2
• Scvo2 – central venous oxygen saturation –
reflects tissue perfusion

25. 6 - hour Severe Sepsis/
Septic Shock Bundle
•
•
•
•
• Vasopressors:
Early Detection:
– Hypotension not
– Obtain serum lactate level.
responding to fluid
– Titrate to MAP > 65
Early Blood Cx/Antibiotics:
mmHg.
– within 3 hours of
• Septic shock or lactate > 4
presentation.
mmol/L:
– CVP and ScvO2 measured.
Early EGDT:
– CVP maintained >8 mmHg.
Hypotension (SBP < 90, MAP
– MAP maintain > 65 mmHg.
< 65) or lactate > 4 mmol/L:
– initial fluid bolus 20-40 ml of
• ScvO2<70%with CVP > 8
crystalloid (or colloid equivalent)
mmHg, MAP > 65 mmHg:
per kg of body weight.
– PRBCs if hematocrit < 30%.
– Inotropes.

26. Sepsis Resuscitation Bundle
1.
2.
3.
4.
5.
6.
Measure serum lactate
Blood cultures obtained prior to administration of antibiotic
From time of presentation, broad spectrum antibiotics must be
administered within 3hrs of ED admission, or within 1hr of non-ED
admission
In the event that hypotension and/or serum lactate >4mmol
a) Deliver initial minimum of 20ml/kg of crystalloid or
colloid equivalent.
b) Apply vasopressors for hypotension not responding to
initial fluid resuscitation to maintain a MAP of ≥65mmHg.
Consider insertion of urinary catheter (measure UOP)
If hypotension persists and serum lactate >4mmol despite fluid
resuscitation achieve
a) CVP ≥8mmHg and
b) (ScvO2) of ≥70%.

27. Sepsis in the Emergency Department

28. The Importance of Early Goal-Directed
Therapy for Sepsis Induced Hypoperfusion
NNT to prevent 1 event (death) = 6-8
Mortality (%)
60
50
Standard therapy
EGDT
40
30
20
10
0
In28-day
60-day
hospital
mortality mortality
mortality
Adapted from Table 3, page 1374, with permission from Rivers E, Nguyen B, Havstad S, et al.
(all
Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med
2001; 345:1368-1377
patients)

29. Antibiotics Administration
– Administration of an antimicrobial effective for isolated or suspected
pathogens within the first hour of documented hypotension was associated
with a survival rate of 79.9%
– Each hour of delay in antimicrobial administration over the ensuing 6 hrs
was associated with an average decrease in survival of 7.6%.(12)
–
Surviving Sepsis 2008 :
“Begin IV antibiotics as early as possible and always within the first hour of
recognizing severe sepsis and septic shock”
Kumar et al, Intens Care Med 2009

31. Conclusion
• Sepsis, severe sepsis and septic shock are a
serious cause of morbidity and mortality
• Early recognition of sepsis and activation of
EGDT is crucial to improve the outcome
• Airway maintenance, broad spectrum
antibiotics, fluid resuscitation and blood
pressure maintenance are the components of
EGDT that should be carried out for better
survival chance of the patients.