Review of all studies published in relation to Early Goal Directed therapy starting with Rivers finding to the most recent trials .

1. What Does It Mean that EGDT is Not Better
than Usual Care in Severe Sepsis?

2. 46,
DM,
HTN,
CAD, PTCA,
Dyslipidemia
Progressive
respiratory distress
with fever (38.1) , HR
120, RR 28/min and
SBP 82 mm Hg
9/14/2015 11:30:31 PM 2
WBC 16,000
Plts 130,000
Creat 3.2
K 6.1,
LA 6.4,
HCO3 18,
PO2 60 on 15L/m
SepsisSIRS Severe Sepsis Septic ShockInfection
 A clinical response
arising from a
nonspecific insult,
with 2 of the
following:
 T >38oC or <36oC
 HR >90 beats/min
 RR >20/min
 WBC
>12,000/mm3 or
<4,000/mm3 or
>10% bands
Microorganism
invading
sterile tissue
SIRS with a
presumed
or confirmed
infectious
process
Sepsis with
organ failure
Vascular collapse
Renal
Hemostasis
Lung
LA
Refractory
hypotension

3. 9/14/2015 11:30:31 PM 3
Trauma
BSI
Severe
Sepsis
Shock
Infection SIRS
Sepsis
Burns
46,
DM,
HTN,
CAD, PTCA,
Dyslipidemia
Progressive
respiratory distress
with fever (38.1) , HR
120, RR 28/min and
SBP 82 mm Hg
WBC 16,000
Plts 130,000
Creat 3.2
K 6.1,
LA 6.4,
HCO3 18,
PO2 60 on 15L/m
What is his chance of survival?

4. Retrospective, observational study from 2000 to 2012
N= 101,064 patients with severe sepsis
171 ICUs with various patient case mix in Australia & New Zealand
Hospital outcome (mortality and discharge to home, to other
hospital, or to rehabilitation)
JAMA. 2014;311(13):1308-1316. Published online March 18, 2014

5. 1% / year
1.1-1.9% / year
Declining Sepsis mortality
JAMA. 2014;311(13):1308-1316. Published online March 18, 2014

6. Rate Among Severe Sepsis Patients
Overall and within Subgroups in 2000 -2012
JAMA. 2014;311(13):1308-1316. Published online March 18, 2014
Risk Reduction
50%

7. Declining Sepsis mortality
JAMA. 2014;311(13):1308-1316. Published online March 18, 2014

8. Change in Hospital Outcomes Reported as Odds Ratios
Referenced Against the Year 2000
DC RehabDC Home
JAMA. 2014;311(13):1308-1316. Published online March 18, 2014

9. Resuscitation End Points (Goals)
MAP >65
mm Hg
Urine
Output >0.5
mL/kg/hr
SVcO2
>70%
CVP 8-12
cm H2O
IVC >2 cm
SVV <12%
P(cv-a)CO2 Lactic Acid
↓ing
OPSI
Improve Mortality!

10. Detroit.. The legend..

11. Resuscitation Goals (End Point) in Severe Sepsis
MAP >65
mm Hg
CVP 8-12
cm H2O
SVcO2
>70%
Urine
Output
>0.5
ml/kg/hr
Within 6 hours
Emanuel Rivers et al. N Engl J Med, 2001;345:1368-77
To Examine whether
Early Goal Directed
Therapy (EGDT)
before admission to
the ICU is superior
to standard
hemodynamic
therapy in patients
with sever sepsis
and septic shock

12. JAMA. 2014;311(13):1308-1316. Published online March 18, 2014
Early Goal-directed Therapy in the Treatment of
Severe Sepsis and Septic Shock: EGDT Protocol
N Engl J Med, 2001;345:1368-77
Central line placement
Arterial lie placement
ScvO2
Fluids
Blood
Norepinephrine
Dobutamine

13. 30.5%
46.5%
Mortality
EGDT Standard
EGDT Results
16% Absolute
Risk Reduction
NNT 7
Emanuel Rivers et al. N Engl J Med, 2001;345:1368-77

14. System-based Approaches to sepsis: Early-Goal
Directed Therapy
INCLUSION = Sepsis AND [BP < 90 after fluid OR Lactate > 4]
Control Intervention EGDT
CVP 8-12 Fluids CVP 8-12
MAP > 65 Vasopressors MAP > 65
Transfusions
Dobutamine
ScvO2 > 70%
47% mortality
31% mortality
LOS 4 less days
$13-16,000 savings
Do what you normally do.
We’ll be watching you!
Emanuel Rivers et al. N Engl J Med, 2001;345:1368-77

15. Treatment Administered
Emanuel Rivers et al. N Engl J Med, 2001;345:1368-77

16. Hospital-wide impact of a standardized order set for
the management of bacteremic severe sepsis
After
Before
Thiel, S. W., Asghar, M. F., Micek, S. T., Reichley, R. M., Doherty, J. A., & Kollef, M. H. (2009). Hospital-wide impact of a standardized order set for
the management of bacteremic severe sepsis*. Critical Care Medicine, 37(3), 819–824. doi:10.1097/CCM.0b013e318196206b

17. The Chinese Study
Multicenter trial of 314 patients with severe
sepsis in eight Chinese centers (2010).
24.8%
42.5%
Mortality
EGDT Standard
17.7% absolute
reduction
Zhongguo Wei Zhong Bing Ji Jiu Yi Xue. 2010. Chinese Critical Care Medicine. Jun;22(6):331-4.

18. Summary of Trials
Rivers 2001
RCT
Sebat 2005
Before-After
Nguyen 2007
Complete or Not
Thiel 2009
Before-After
Levy 2011
Before-After
Goals
CVP >8
MAP > 65
ScVO2 >70%
HCT >30
MAP > 70
SaO2 > 92
UOP > 30ml/h
SvO2 > 60
CI > 2.5
ABX in 4 h
CVP > 8, MAP > 65,
ScVO2 > 70%, HCT >
30
Check Lactate
Steroids
Appropriate ABX in 4 h,
CVP > 8, MAP > 65,
ScVO2 > 70%
Early ABX, Blood
Cultures, Appropriate
ABX, CVP > 8, MAP >
65,
SvO2 > 70%
Specific
Interventions
Fluids, Blood, Pressors
ABX, Fluids
Pressors
ABX, Fluids, Blood,
Pressors
ABX, Fluids, Pressors,
Steroids, Xigris, Other
Supportive Care
ABX, Fluids, Pressors,
Steroids, Xigris, Other
Supportive Care
System
Interventions
ED-based Sepsis Team
Screening, Education,
Shock Team, Protocols
Education, In-services,
Protocols
Education, In-services,
Order Set, Protocols
Screening, Education,
Order Sets
Absolute Change in
Mortality -16% -12% -19% -16% -7%

19. Studies Using EGDT and/or Bundled
Care to Treat Sepsis
RIVERS E. CHEST (2010) 136:476 –480

20. Sepsis Guidelines 2012
During the first 6 hrs of resuscitation, the goals of initial resuscitation of sepsis-
induced hypoperfusion should include all of the following as a part of a treatment
protocol (grade 1C):
1. CVP 8-12 mm Hg
2. MAP ≥ 65 mm Hg
3. Urine output ≥ 0.5 mL/kg.hr
4. Scvo2 70% or SVO2 65%

21. Concerns:
The potential risks associated
with individual elements:
•Dobutamine does not improve
microvascular perfusion
•Transfusion to hematocrit of
30% appears harmful
Uncertainty about the external
validity of the original trial
Uncertainty about the
infrastructure and resource
requirements for implementing
EGDT.
ProCESSARISE ProMISe

22. Resuscitation Goals in Severe Sepsis
ProCESS Study ARISE Study
ProMISe Study Your Practice?
Rivers Study

23. N Engl J Med 2014; 370:1683-1693 Online March 18, 2014
31 ED Departments: 2008-2012
N= 1341 Patients
Early septic shock with refractory hypotension:
◦ After 1000 ml of IVF over 30 minutes if SBP < 90 or Lactate > 4
3 groups:
◦ Protocol-based EGDT: CVC + SVO2 + Target HB ≥10
◦ Protocol-based ST: Target HB ≥ 7.5
◦ Usual care
ProCESS

24. March 18, 2014, at NEJM.org.
Protocol based EGDT
Protocol based ST
ProCESS

26. A Randomized Trial of Protocol-Based
Care for Early Septic Shock
ProCESS (60d)
EGDT 21%
PB-ST 18.2%
UC 18.9%
N Engl J Med 2014; 370:1683-1693 Online March 18, 2014

27. October 5, 2008, to April 23, 2014
Prospective, randomized, parallel group trial
51 centers
N= 1600 Patients
2 groups:
◦ Protocol-based EGDT: 796 patients
◦ Usual care: 804 patients
ARISE
N Engl J Med 2014; 371:1496-1506

28. N Engl J Med 2014; 371:1496-1506

29. N Engl J Med 2014; 371:1496-1506

30. ProMISe
Published March 17, 2015 At nejm.Org
From February 16, 2011, to July 24, 2014
Open, multicenter, parallel-group, randomized, controlled tria
56 centers
N= 1260 patients
2 groups:
◦ EGDT: 630 patients
◦ Usual care: 630 patients

31. Published March 17, 2015 At nejm.Org

32. Published March 17, 2015 At nejm.Org

33. EGDT vs UC
ProCESS ARISE ProMISe
EGDT PB-ST UC EGDT UC EGDT UC
20.8 20.6 20.7 15.4 15.8 18.7 18
21% 18% 18.9% 18.6% 18.8% 29.5% 29.2%
APACHE II
Mortality
APCHE II 20 vs 21
46% vs 30%

34. In Conclusions
These studies confirm the most important elements in management of sepsis:
If these essential aspects of care are in place, NO
ADDED VALUE of protocolized measurements of
central hemodynamics and oxygen saturation
Early
Recognition
Early
Administration
of Antibiotics
Early Adequate
Volume
Resuscitation
using Clinical
Parameters
Adequate
Source Control

36. EGDT vs UC
HES vs
Crystalloids
Colloid vs
Crystalloids
Dopamine vs
Norepinephrine
Low vs High Hg
Steroids
High vs Low BP
Intensive vs
Conventional BS
Control
Drotrecogin Alfa
CRRT vs Intermittent
RRT
Intensity of CRRT
Fresh vs Old Blood

37. The University of Michigan