The Surviving Sepsis Campaign

A Critical Analysis
Andrew A. Quartin, M.D., M.P.H. Professor of Clinical Medicine Division of Pulmonary and Critical Care University of Miami Miller School of Medicine Miami, Florida

 First released in 2004, updated in 2008 2nd revision published in February 2013
Simultaneous release in Critical Care Medicine and Intensive Care Medicine

68 experts, 58 pages, 88 recommendations

Surviving Sepsis Campaign

Improving Survival
0.30 0.25 0.20 0.15 0.10 0.05 0.00 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012

Sepsis Mortality Rate

Surviving Sepsis Campaign

Oops Wrong Time Period!
0.30 0.25 0.20 0.15 0.10 0.05 0.00 1983 1984 1985 1986 1987 1988 1989 1990 1991 1992

Sepsis Mortality Rate

Martin, NEJM 2003

Surviving Sepsis Campaign

Start With Appropriate Skepticism
When you see this . . .

Mortality by quarter at 165 sites after implementing SSC protocols

Levy, Crit Care Med 2010

Surviving Sepsis Campaign

Start With Appropriate Skepticism
When you see this . . . Remember this . . .

Mortality by quarter at 165 sites after implementing SSC protocols

Levy, Crit Care Med 2010

Trends in sepsis mortality in the U.S. over 20 years before SSC

Martin, NEJM 2003

Surviving Sepsis Campaign

Applying a Little Skepticism

Mortality by quarter at 165 sites after implementing SSC protocols

Only the most enthusiastic sites would have 7-8 quarters of data
Levy, Crit Care Med 2010

Surviving Sepsis Campaign (2004)

Strength of Recommendations
Grade A
Supported by at least 2 large randomized trials with clearcut results

Grade B
Supported by 1 large randomized trial with clearcut results

Grade C
Supported by small randomized trials with uncertain results

Grade D
Supported by at least one non-randomized study using contemporaneous controls

Grade E
Even less case series, use of historical controls, expert opinion

Surviving Sepsis Campaign (2004)

Recommendations and Evidence Grades
Grade A
Vent Weaning SBT Protocol DVT Drug Prophylaxis No High Dose Steroids No Supranormal O2 Delivery Goal PUD Prophylaxis For All Patients

Grade B
EGDT Basic Goals MAP65, CVP 8-12 EGDT SCVO270% Goal (Hct to 30%, dobutamine) Do Not Use Renal Dose Dopamine rhAPC for Patients At High Risk of Death Transfuse at Hgb 7 g/dL If Not Hypoperfusing EPO Not Recommended Antithrombin Not Recommended

Grade C
Low-Dose Steroid If On Pressors Semirecumbent Body Position Crystalloids or Colloids Okay High PCO2 Okay if Needed for Low Vt No Bicarbonate For pH>7.15 Sedation Intermittent or Daily Wake Sedation Protocol With Goal

Grade D
Cultures Before Antibiotics Antibiotics to Cover Suspect Bugs Norepi or Dopamine As 1st Line Pressor Glucose <150

Grade E
26 Really Weakly Supported Recommendations

Renal Replacment IHD or CRRT Okay ALI Ventilation Low Vt/Pplat Strategy

Surviving Sepsis Campaign (2004)

Recommendations and Evidence Grades
Grade A Grade B Grade C Grade D Grade E

EGDT SCVO270% Goal (Hct to 30%, dobutamine)

No Supranormal O2 Delivery Goal

Surviving Sepsis Campaign (2004)

Recommendations and Evidence Grades
Grade A Grade B Grade C Grade D Grade E

EGDT SCVO270% Goal (Hct to 30%, dobutamine)

No Supranormal O2 Delivery Goal

How does one achieve Supranormal O2 Delivery? Transfuse PRBCs Dobutamine

Surviving Sepsis Campaign (2004)

Recommendations and Evidence Grades
Grade A Grade B Grade C Grade D Grade E

EGDT SCVO270% Goal (Hct to 30%, dobutamine)

No Supranormal O2 Delivery Goal

Conflict!

How does one achieve Supranormal O2 Delivery? Transfuse PRBCs Dobutamine

Surviving Sepsis Campaign (2004)

Recommendations and Evidence Grades
Grade A
Vent Weaning SBT Protocol DVT Drug Prophylaxis No High Dose Steroids No Supranormal O2 Delivery Goal PUD Prophylaxis For All Patients

Grade B
EGDT Basic Goals MAP65, CVP 8-12 EGDT SCVO270% Goal (Hct to 30%, dobutamine) Do Not Use Renal Dose Dopamine rhAPC for Patients At High Risk of Death Transfuse at Hgb 7 g/dL If Not Hypoperfusing EPO Not Recommended Antithrombin Not Recommended

Grade C
Low-Dose Steroid If On Pressors Semirecumbent Body Position Crystalloids or Colloids Okay High PCO2 Okay if Needed for Low Vt No Bicarbonate For pH>7.15 Sedation Intermittent or Daily Wake Sedation Protocol With Goal

Grade D
Cultures Before Antibiotics Antibiotics to Cover Suspect Bugs Norepi or Dopamine As 1st Line Pressor Glucose <150

Grade E
26 Really Weakly Supported Recommendations

Renal Replacment IHD or CRRT Okay ALI Ventilation Low Vt/Pplat Strategy

Surviving Sepsis Campaign (2004)

Positive Recommendations To Do Something
Recommendations and Evidence Grades
Grade A
Vent Weaning SBT Protocol DVT Drug Prophylaxis

Grade B
EGDT Basic Goals MAP65, CVP 8-12 EGDT SCVO270% Goal (Hct to 30%, dobutamine)

Grade C
Low-Dose Steroid If On Pressors Semirecumbent Body Position

Grade D
Cultures Before Antibiotics Antibiotics to Cover Suspect Bugs Norepi or Dopamine As 1st Line Pressor

Grade E
20 Really Weakly Supported Recommendations

rhAPC for Patients At High Risk of Death PUD Prophylaxis For All Patients

Glucose <150

Sedation Intermittent or Daily Wake Sedation Protocol With Goal ALI Ventilation Low Vt/Pplat Strategy

Surviving Sepsis Campaign (2004)

Sepsis Specific Positive Recommendations
Recommendations and Evidence Grades
Grade A Grade B
EGDT Basic Goals MAP65, CVP 8-12 EGDT SCVO270% Goal (Hct to 30%, dobutamine)

Grade C
Low-Dose Steroid If On Pressors

Grade D
Cultures Before Antibiotics Antibiotics to Cover Suspect Bugs Norepi or Dopamine As 1st Line Pressor

Grade E
11 Really Weakly Supported Recommendations

rhAPC for Patients At High Risk of Death

Surviving Sepsis Campaign

Revised Grading for 2008 and 2012
A numeric score for strength of recommendation
1: 2: Strongly recommended, thought very likely to improve outcome We recommend . . . Weakly recommended, less confident that benefits exceed risks We suggest . . .

A letter score for quality of evidence

A: High B: Moderate C: Low D: Very Low Some play in this Randomized trials usually graded A, but may be downgraded for concerns over reporting bias, limitations in implementation, etc. Observational studies are usually graded C, but may be upgraded if the magnitude of effect is particularly large

A score of UG (ungraded) added for 2012

Surviving Sepsis Campaign Evolution

EGDT and Resuscitation
2004
Basic Goals MAP65, CVP 8-12 1C

2008
Start resuscitation before ICU if BP low or lactate high Goals: MAP65, CVP 8-10*, and UO0.5 mL/kg/hr *12-15 recommended on vent If SCVO2<70% or SVO2<65%: Consider more fluids Transfuse to Hct 30% Dobutamine Crystalloids and Colloids Both Acceptable Bolus Volume 1 L Reduce Fluids if Filling Pressures Increase Without Hemodynamic Improvement 1B 1B 1C 2C 1C

2012
Goals: MAP65, CVP 8-10*, UO0.5 mL/kg/hr, and SCVO270% or SVO265% Target normalized lactate if initially abnormal

1C

2C

SCVO270% Goal (Hct to 30%, dobutamine)

2C

Crystalloids and Colloids Both Acceptable 500-1000 mL Boluses Repeat If Good Effect

1B 1D

Crystalloids Preferred No Hydroxyethyl Starches Bolus Volume 1 L Bolus Total 30 mL/kg Albumin When Given Lots of Crystalloid

1D A B C D E

Surviving Sepsis Campaign Evolution

EGDT and Resuscitation
2004
Basic Goals MAP65, CVP 8-12 1C

2008
Start resuscitation before ICU if BP low or lactate high Goals: MAP65, CVP 8-10*, and UO0.5 mL/kg/hr *12-15 recommended on vent If SCVO2<70% or SVO2<65%: Consider more fluids Transfuse to Hct 30% Dobutamine Crystalloids and Colloids Both Acceptable Bolus Volume 1 L Reduce Fluids if Filling Pressures Increase Without Hemodynamic Improvement 1B 1B 1C 2C 1C

2012
Goals: MAP65, CVP 8-10*, UO0.5 mL/kg/hr, and SCVO270% or SVO265% Target normalized lactate if initially abnormal

1C

2C

SCVO270% Goal (Hct to 30%, dobutamine)

2C

No Method Given
Crystalloids Preferred No Hydroxyethyl Starches Bolus Volume 1 L Bolus Total 30 mL/kg Albumin When Given Lots of Crystalloid

Crystalloids and Colloids Both Acceptable 500-1000 mL Boluses Repeat If Good Effect

1B 1D

1D A B C D E

Surviving Sepsis Campaign Evolution

Activated Protein C (Xigris)
2004 2008
rhAPC for Patients At High Risk of Death 2B APACHE 25 Or Multiple Organ Failures

2012

rhAPC for Patients At High Risk of Death Do Not Use rhAPC for Patients At Low Risk of Death 1A APACHE < 20 And 0-1 Organ Failures

Drug Off Market

Surviving Sepsis Campaign Evolution

Activated Protein C (Xigris)
2004 2008
rhAPC for Patients At High Risk of Death 2B APACHE 25 Or Multiple Organ Failures

2012

rhAPC for Patients At High Risk of Death rhAPC NOT for Patients At Low Risk of Death 1A APACHE < 20 And 0-1 Organ Failures

Drug Off Market

What evidence came out between the 2004 and 2008 guidelines to downgrade the quality of the original PROWESS trial of rhAPC?
A B C D E

Surviving Sepsis Campaign Evolution

Corticosteroids
2004
No High Dose Steroids Low-Dose Steroid If Pressor Dependent 1A

2008
No High Dose Steroids

2012

2C 2B

Consider Low-Dose Steroid If Vasopressor Dependent If Steroid Used, Hydrocortisone Preferred Do Not Treat Sepsis With Steroids if Not Shock Do Not Use ACTH Response Wean Steroids Only When Off Pressors Add Fludrocortisone to Hydrocortisone

2C 2D

Only Use Steroid If Fluids and Pressors Ineffective Use Continuous Infusion Hydrocortisone (200 mg/day) Do Not Treat Sepsis With Steroids if Not Shock Do Not Use ACTH Response Wean Steroids Only When Off Pressors

Do Not Treat Sepsis With Steroids if Not Shock Stop Steroid if ACTH Response Intact Wean Steroid Dose as Pressor Dose Declines Add Fludrocortisone To Hydrocortisone A B C D E

1D 2B 2D

1D 2B 2D

2C

Surviving Sepsis Campaign Evolution

Corticosteroids
2004
No High Dose Steroids Low-Dose Steroid If Pressor Dependent 1A

2008
No High Dose Steroids

2012

2C 2B

Consider Low-Dose Steroid If Vasopressor Dependent If Steroid Used, Hydrocortisone Preferred

2C 2D

Only Use Steroid If Fluids and Pressors Ineffective Use Continuous Infusion Hydrocortisone (200 mg/day)

Do Not Treat Sepsis With Steroids if Not Shock Stop Steroid if ACTH Response Intact Wean Steroid Dose as Pressor Dose Declines Add Fludrocortisone To Hydrocortisone A B C D E

Do Not Treat Sepsis With Do Not Treat Sepsis With 1D Reduced to Salvage 1D Therapy Corticosteroids Steroids if Not Shock Steroids if Not Shock 2B 2D Do Not Use ACTH Response Wean Steroids Only When Off Pressors Add Fludrocortisone to Hydrocortisone 2B 2D Do Not Use ACTH Response Wean Steroids Only When Off Pressors

2C