History of Sepsis Bundle in

Management of Septic Shock dedi atila

Early Campaign
 Severe sepsis accounts for 20% of all admissions to intensive care units (ICUs)
 The leading cause of death in non-cardiac ICUs
 Yet comprehensive clinical practice guidelines had not existed
2002

Barcelona
Declaration
The Barcelona Declaration
2002

Barcelona
Declaration

2003

a call to action to reduce

mortality from sepsis
2004
2004

A. Initial resuscitation K. Mechanical ventilation of sepsis-induced

B. Diagnosis acute lung injury (ALI)/acute respiratory
C. Antibiotic therapy distress syndrome (ARDS)
D. Source control L. Sedation, analgesia, and neuromuscular
E. Fluid therapy blockade in sepsis
F. Vasopressors M. Glucose control
G. Inotropic therapy N. Renal replacement
H. Steroids O. Bicarbonate therapy
I. Recombinant activated protein C (rhAPC) P. Deep vein thrombosis prophylaxis
J. Blood product administration Q. Stress ulcer prophylaxis
2004

A. Initial resuscitation

A. I K. Mechanical ventilation of sepsis-induced

B. Diagnosis acute lung injury (ALI)/acute respiratory
C. Antibiotic therapy distress syndrome (ARDS)
D. Source control L. Sedation, analgesia, and neuromuscular
E. Fluid therapy blockade in sepsis
F. Vasopressors M. Glucose control
G. Inotropic therapy N. Renal replacement
H. Steroids O. Bicarbonate therapy
I. Recombinant activated protein C (rhAPC) P. Deep vein thrombosis prophylaxis
J. Blood product administration Q. Stress ulcer prophylaxis
2004

A. Initial resuscitation K. Mechanical ventilation of sepsis-induced

B. Diagnosis acute lung injury (ALI)/acute respiratory
C. Antibiotic therapy distress syndrome (ARDS)
D. Source control L. Sedation, analgesia, and neuromuscular
E. Fluid therapy blockade in sepsis
F. Vasopressors M. Glucose control
G. Inotropic therapy N. Renal replacement
H. Steroids O. Bicarbonate therapy
I. Recombinant activated protein C (rhAPC) P. Deep vein thrombosis prophylaxis
J. Blood product administration Q. Stress ulcer prophylaxis
2004

A. Initial resuscitation K. Mechanical ventilation of sepsis-induced

B. Diagnosis acute lung injury (ALI)/acute respiratory
C. Antibiotic therapy distress syndrome (ARDS)
D. Source control L. Sedation, analgesia, and neuromuscular
E. Fluid therapy blockade in sepsis
F. Vasopressors M. Glucose control
G. Inotropic therapy N. Renal replacement
H. Steroids O. Bicarbonate therapy
I. Recombinant activated protein C (rhAPC) P. Deep vein thrombosis prophylaxis
J. Blood product administration Q. Stress ulcer prophylaxis
Rivers E et al. EARLY GOAL-
DIRECTED THERAPY IN THE
TREATMENT OF SEVERE SEPSIS
AND SEPTIC SHOCK. N Engl J
Med, Vol. 345, No. 19 · November 8,
2001
2005

Sepsis
Bundles

Bundles
“a group of interventions related to a
disease process that, when executed
together, result in better outcomes than
when implemented individually”
 Bundles aim at converting complex guidelines into
meaningful changes in behavior and clinical
outcomes.
 Bundles can help physicians to identify the key
elements of care regarding both the diagnosis and
treatment of patients with septic shock.
The main goals :
◦ to reduce the mortality and to improve patients’
outcomes
◦ to ensure moreconsistent and timely application of
evidence-based care
◦ to ensure reductions in clinical practice variability
2008 Guidelines Revision
2008 Guidelines Revision

I. Management of Severe Sepsis II. Supportive Therapy of Severe Sepsis

A. Initial resuscitation A. Mechanical ventilation of sepsis-induced
B. Diagnosis acute lung injury (ALI)/acute respiratory
C. Antibiotic therapy distress syndrome (ARDS)
D. Source control B. Sedation, analgesia, and neuromuscular
E. Fluid therapy blockade in sepsis
F. Vasopressors C. Glucose control
G. Inotropic therapy D. Renal replacement
H. Steroids E. Bicarbonate therapy
I. Recombinant activated protein C F. Deep vein thrombosis prophylaxis
(rhAPC) G. Stress ulcer prophylaxis (SUP)
J. Blood product administration H. Selective Digestive Tract Decontamination
(SDD)
 2008 Guidelines Revision

I. Management of Severe Sepsis

A. Initial resuscitation II. Supportive Therapy of Severe Sepsis
A. I A. Mechanical ventilation of sepsis-induced
B. Diagnosis acute lung injury (ALI)/acute respiratory
C. Antibiotic therapy distress syndrome (ARDS)
D. Source control B. Sedation, analgesia, and neuromuscular
E. Fluid therapy blockade in sepsis
F. Vasopressors C. Glucose control
G. Inotropic therapy D. Renal replacement
H. Steroids E. Bicarbonate therapy
I. Recombinant activated protein C F. Deep vein thrombosis prophylaxis
(rhAPC) G. Stress ulcer prophylaxis (SUP)
J. Blood product administration H. Selective Digestive Tract Decontamination
(SDD)
2008 Guidelines Revision

I. Management of Severe Sepsis II. Supportive Therapy of Severe Sepsis

A. Initial resuscitation A. Mechanical ventilation of sepsis-induced
B. Diagnosis acute lung injury (ALI)/acute respiratory
C. Antibiotic therapy distress syndrome (ARDS)
D. Source control B. Sedation, analgesia, and neuromuscular
E. Fluid therapy blockade in sepsis
F. Vasopressors C. Glucose control
G. Inotropic therapy D. Renal replacement
H. Steroids E. Bicarbonate therapy
I. Recombinant activated protein C F. Deep vein thrombosis prophylaxis
(rhAPC) G. Stress ulcer prophylaxis (SUP)
J. Blood product administration H. Selective Digestive Tract Decontamination
(SDD)
 2008 Guidelines Revision

I. Management of Severe Sepsis II. Supportive Therapy of Severe Sepsis

A. Initial resuscitation A. Mechanical ventilation of sepsis-induced
B. Diagnosis acute lung injury (ALI)/acute respiratory
C. Antibiotic therapy distress syndrome (ARDS)
D. Source control B. Sedation, analgesia, and neuromuscular
E. Fluid therapy E. F blockade in sepsis
F. Vasopressors C. Glucose control
G. Inotropic therapy D. Renal replacement
H. Steroids E. Bicarbonate therapy
I. Recombinant activated protein C F. Deep vein thrombosis prophylaxis
(rhAPC) G. Stress ulcer prophylaxis (SUP)
J. Blood product administration H. Selective Digestive Tract Decontamination
(SDD)
2012 Guidelines and Bundles Revision
2012 Guidelines and Bundles Revision

Management of Severe Sepsis N. History of recommendations regarding use of

A. Initial resuscitation recombinant activated protein C
B. Screening for sepsis and performance O. Mechanical ventilation of sepsis-induced acute
improvement respiratory distress syndrome
C. Diagnosis P. Sedation, analgesia, and neuromuscular blockade in
D. Antimicrobial therapy sepsis
E. Source control Q. Glucose control
F. Infection prevention R. Renal replacement
G. Fluid therapy of severe sepsis S. Bicarbonate therapy
H. Vasopressors T. Deep vein thrombosis prophylaxis
I. Inotropic therapy U. Stress ulcer prophylaxis
J. Corticosteroids V. Nutrition
K. Blood product administration W. Setting goals of care
L. Immunoglobulins
M. Selenium
2012 Guidelines and Bundles Revision

A. Initial resuscitation

Management of Severe Sepsis N. History of recommendations regarding use of

A. I recombinant activated protein C
B. Screening for sepsis and performance O. Mechanical ventilation of sepsis-induced acute
improvement respiratory distress syndrome
C. Diagnosis P. Sedation, analgesia, and neuromuscular blockade in
D. Antimicrobial therapy sepsis
E. Source control Q. Glucose control
F. Infection prevention R. Renal replacement
G. Fluid therapy of severe sepsis S. Bicarbonate therapy
H. Vasopressors T. Deep vein thrombosis prophylaxis
I. Inotropic therapy U. Stress ulcer prophylaxis
J. Corticosteroids V. Nutrition
K. Blood product administration W. Setting goals of care
L. Immunoglobulins
M. Selenium
2012 Guidelines and Bundles Revision

Management of Severe Sepsis N. History of recommendations regarding use of

A. Initial resuscitation recombinant activated protein C
B. Screening for sepsis and performance O. Mechanical ventilation of sepsis-induced acute
improvement respiratory distress syndrome
C. Diagnosis P. Sedation, analgesia, and neuromuscular blockade in
D. Antimicrobial therapy sepsis
E. Source control Q. Glucose control
F. Infection prevention R. Renal replacement
G. Fluid therapy of severe sepsis S. Bicarbonate therapy
H. Vasopressors T. Deep vein thrombosis prophylaxis
I. Inotropic therapy U. Stress ulcer prophylaxis
J. Corticosteroids V. Nutrition
K. Blood product administration W. Setting goals of care
L. Immunoglobulins
M. Selenium
 2012 Guidelines and Bundles Revision

Management of Severe Sepsis N. History of recommendations regarding use of

A. Initial resuscitation recombinant activated protein C
B. Screening for sepsis and performance O. Mechanical ventilation of sepsis-induced acute
improvement respiratory distress syndrome
G. Fluid therapy of severe sepsis
C. Diagnosis P. Sedation, analgesia, and neuromuscular blockade in
D. Antimicrobial therapy sepsis
E. Source control Q. Glucose control
F. Infection prevention R. Renal replacement
G. Fluid S. Bicarbonate therapy
H. Vasopressors T. Deep vein thrombosis prophylaxis
I. Inotropic therapy U. Stress ulcer prophylaxis
J. Corticosteroids V. Nutrition
K. Blood product administration W. Setting goals of care
L. Immunoglobulins
M. Selenium
March 17, 2015
2016 Guidelines Revision

A. Initial resuscitation K. Blood purification

B. Screening for sepsis and performance L. Anticoagulants
improvement M. Mechanical ventilation
C. Diagnosis N. Sedation and analgesia,
D. Antimicrobial therapy O. Glucose control
E. Source control P. Renal replacement therapy
F. Fluid
F. Fluid therapy
therapy Q. Bicarbonate therapy
G. Vasoactive medications R. veinous thrombembolism prophylaxis
H. Corticosteroids S. Stress ulcer prophylaxis
I. Blood products T. Nutrition
J. Immunoglobulins U. Setting goals of care
2018 Bundles Revision
 The idea of giving large fluid boluses to patients with sepsis is illogical, reflects a poor
understanding of human physiology and is likely harmful.
 The rapid increase in filling pressures may counteract the compensatory mechanism that
occur in shock resulting in cardiovascular collapse.
 Administration of large amounts of crystalloid fluids is unphysiologic and may lead to
fluid accumulation, fluid overload, poly-compartment syndrome and associated
morbidity and mortality
We have waited patiently for years in hope that
the guidelines would improve, but they have not.
The 2018 SSC update appears to have deviated
from evidence-based medicine more than the 2016
version. These recommendations will likely cause
hasty management decisions, inappropriate fluid
administration, and indiscriminate use of broad-
spectrum antibiotics, which are impediments to
providing the best possible care to our septic
patients.
The SSC guidelines have become widely quoted and
supported by researchers, bedside clinicians, and professional
societies. The SSC bundles, derived from the guidelines, have
been tested in multiple international studies in multicultural
environments and in a wide range of hospital types. All the
published studies have demonstrated a clear message:
changing clinical behavior so that sepsis management is
consistent with the guidelines and the bundles is associated
with a statistically significant improvement in survival for
patients with sepsis and septic shock.
first 6 hours :
 initial minimum of 20 ml/kg of
crystalloid
 Apply vasopressors for hypotension
not responding to initial fluid
resuscitation  MAP > 65mmHg
 Achieve central venous pressure
(CVP) of > 8 mm Hg.
 Achieve central venous oxygen
saturation (ScvO2) of > 70%.
first 3 hours : 1 hours :
 Administer 30 ml/kg of crystalloid  Rapid administration of 30 ml/kg
first 6 hours : 2005 of crystalloid
2012
 Apply vasopressors for hypotension 2018
 Apply vasopressors for hypotension
not responding to initial fluid not responding to initial fluid
resuscitation  MAP > 65mmHg resuscitation  MAP > 65mmHg
 Targets for quantitative
resuscitation are CVP of ≥8 mm
Hg,ScvO2 of ≥ 70%, and
normalization of lactate.

There is still pro-con

Timeline of Sepsis Bundles (fluid
resuscitation)
What’s next ?