general review on sepsis and early goal directed therapy

1. Sepsis and Early Goal Directed
Therapy : Approach in ED
Faez Baherin
MBBS (Jordan)
ED HTAN Kuala Pilah

2. Outlines
 Introduction
 Definition
 Early Goal Directed Therapy (EGDT) and the
theory behind it
 Component of EGDT
 Conclusion

3. Introduction
 Sepsis continues to be a major cause of mortality
and morbidity throughout the world. The annual
incidence of severe sepsis was approximately 3.0
cases per 1,000 of the population.
 In the United States alone, the incidence of
severe sepsis will see an annual increase of 1.5%
which may be attributable to an increasing ageing
population. (1)
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;29:1303-10.

4. Introduction – cont’
 Malaysia is not immune from the global burden of
sepsis. In 2008, severe sepsis was the second
leading cause of death in the Malaysian Ministry
of Health hospitals. (2)
 To date, there have been no local studies on the
implementation or challenges in applying EGDT
in emergency departments (ED) until 2009 by
UKMMC with a conclusion that EGDT can be
implemented in ED Malaysia with current
resources and expertise.
2. Health Facts 2008. Health Informatics Centre. Planning and Development Division. Ministry of
Health Malaysia [Online]. 2009 May 1

5. Definition by American College of Chest Physicians/Society
of Critical Care Medicine
3. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference, Levy MM et
al., Crit. Care Med. 2003, 31(4): 1250-1256)

6. 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. (4)
4. 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.

7. 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.

8. Theory behind EGDT – cont’
 Damage or impairment of the microvascular network is
increasingly being recognised as having a key role in the
development of organ dysfunction in patients with sepsis via
impaired tissue oxygen transport. (5)
 Thus, although there may be adequate blood flow from the
heart, there is physiological shunting at the level of
microcirculation as a result of impeded flow, so the supply will
be unable to meet oxygen requirements.
 It has been suggested that the benefits of EGDT may relate to
beneficial effects on the microcirculation with adequate
volume resuscitation, vasopressors to maintain MAP and
blood transfusion, inotropes and vasodilators to ensure
adequate global oxygen delivery.
5. Bateman R M, Walley K R. Microvascular resuscitation as a therapeutic goal in severe sepsis. Crit
Care 2005. 9(Suppl 4)S27–S32.S32

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

10. Fluid resuscitation and CVP
Monitoring
 Patients are usually fluid depleted – absolute vs
relative
 Fluid resuscitation can help to reduce the global
tissue hypoxia that is central to the development
of multiorgan dysfunction, by increasing the
cardiac output and improving oxygen delivery to
the tissues (6)
 Continued fluid challenges of 500-1000 ml of
crystalloids or 300-500 ml of colloids over
30minutes and repeated as appropriate.
Haupt M T, Gilbert E M, Carlson R W. Fluid loading increases oxygen consumption in septic
patients with lactic acidosis. Am Rev Respir Dis 1985. 131912–916.916

11. Fluid resuscitation – cont’
 ultimate key to satisfactory fluid resuscitation ?
- clinical, urine output, CVP, peripheral perfusion
 Crystalloid vs colloids ?
- In many recent studies, there’s no apparent
difference between crystalloids and colloid
- no association with hospital/ICU mortality with
type of fluid administered during initial
resuscitation (7)
7. McIntyre LA et al 2007 Canada

12. Fluid resuscitation – cont’
Bottomline :
 Both crystalloids and colloids can be used in the
initial resuscitation of patients with severe sepsis.
The most current Surviving Sepsis Campaign
guidelines recommend giving fluid challenges of
1000ml of crystalloids or 300 – 500ml of colloids
over 30mins to achieve a target CVP of 8mmH2o
or more .(8)(9)
8. Dellinger RP et al. Surviving sepsis campaign: International guidelines for management of severe
sepsis and septic shock 2008. Critical Care Medicine 2008; 36(1); 296-327
9. Powell-Tuck J et al. British consensus guidelines on intravenous fluid therapy for adult surgical patients.
GIFTASUP 2008

13. MAP and vasopressors
 Even after adequate fluid resuscitation many
patients remain hypotensive or have inadequate
tissue perfusion as a result of microvascular
changes, myocardial depression, vasodilatation
and maldistribution of cardiac output (10)
 MAP must be maintained at certain level even
after adequate fluid resuscitation.
 Choice of dopamine vs noradrenaline
10. Beale R J, Hollenberg S M, Vincent J ‐ L. et al Vasopressor and inotropic support in
septic shock: an evidence‐based review. Crit Care Med 2004. 32(Suppl)S455–S465.S465.

14. Dopamine Vs Noradrenaline
 Dopamine has been commonly used as a first-
line therapy for shock at many hospitals for years
 Dopamine has dose related effect-
dopaminergic, beta 1, alpha 1.
 Noradrenaline has effects on alpha 1, weaker
beta 1 effect which is nullified by reflex
bradycardia in response to blood pressure hence
the unchanged overall heart rate

15. Dopamine vs Noradrenaline
11. Xu B, Oziemski P. Dopamine versus noradrenaline in septic shock AMJ 2011, 4, 10, 571-574

16. Dopamine Vs Noradrenaline
 Bottomline
1. There is no significant mortality difference at 28 days in patients
with septic shock treated with dopamine or noradrenaline.
2. Dopamine is associated with more arrhythmic events.
3. Noradrenaline might be preferred over dopamine as
the first line vasopressor to avoid cardiovascular adverse events.
4. The recent SOAP II study challenges the guideline
recommendation that dopamine should be one of two
first line vasopressor agents in septic shock.
11. Xu B, Oziemski P. Dopamine versus noradrenaline in septic shock AMJ 2011, 4, 10, 571-574

17. ScvO2 and blood transfusion
 Scvo2 – central venous oxygen saturation –
reflects tissue perfusion

18. ScvO2 and blood transfusion
 In the instance of the central venous oxygen
saturation (ScvO2) was still below 70% after
adequate fluid and vasopressors, packed red cell
transfusion will be given if the hematocrit <30%.

19. 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)
 A longer duration to antimicrobial therapy was also associated an
increase in incidence of AKI AND AKI was associated with
significantly higher odds of death
 Surviving Sepsis 2008 :
“Begin IV antibiotics as early as possible and always within the first
hour of recognizing severe sepsis and septic shock”
12 . Kumar et al, Intens Care Med 2009

20. Summary

21. Conclusion
 Sepsis, severe sepsis and septic shock are
amongst the leading cause of morbidity and
mortality in Malaysia
 Early recognition of sepsis and activation of
EGDT is crucial to improve the outcome
 Airway maintenance, early administration of
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.

22. Reference
 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
 Xu B, Oziemski P. Dopamine versus noradrenaline in septic shock AMJ 2011
 Dellinger RP et al. Surviving sepsis campaign: International guidelines for
management of severe sepsis and septic shock 2008. Critical Care Medicine
2008
 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions
Conference, Levy MM et al., Crit. Care Med. 2003
 Sarawak Medical Emergency Handbook