Transcript Surviving Sepsis Therapy Across the Sepsis Continuum 2008 Guidelines

Surviving Sepsis
2008 Guidelines
Therapy Across the Sepsis Continuum
MAZEN KHERALLAH, MD, FCCP
INFECTIOUS DISEASE AND CRITICAL CARE
MEDICINE
Therapy Across the Sepsis Continuum
Infection
SIRS
Microorganism
invading
sterile tissue
 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
Sepsis
Severe Sepsis Septic Shock
SIRS with a
presumed
or confirmed
infectious
process
Sepsis with
organ failure
Vascular collapse
Renal
Hemostasis
Lung
LA
Refractory
hypotension
Chest 1992;101:1644
Surviving Sepsis Campaign
 Launched in Fall 2002 as a collaborative effort of
European Society of Intensive Care Medicine, the
International Sepsis Forum, and the Society of
Critical Care Medicine
 Goal: reduce sepsis mortality by 25% in the next 5
years
 Guidelines revealed at SCCM in Feb 2004
Critical Care Medicine March 2004 32(3):858-87.
 Website: survivingsepsis.org

THE SEVERE SEPSIS BUNDLES: SSC/IHI
6 Hour Bundle







Measure serum lactate
Blood Cultures prior to antibiotics
Broad spectrum antibiotics within 3
hours of presentation, 1 hour in hospital
Initial fluid resuscitation with 20-40
mL/kg crystalloid (or equivalent
colloid) if hypotensive (SBP < 90
mmHg or MAP < 70) or lactate > 4
mmol/L
Vasopressors
If septic shock or lactate > 4 mmol/L:
 CVP and ScvO2 or SvO2 measured
 CVP maintained 8-12 mm Hg
Inotropes (and/or PRBCs if Hct < 30%)
delivered for ScvO2 <70% or SvO2<65%
if CVP > 8 mmHg
24 Hour Bundle
 Glucose control maintained < 150
mg/dL
 Drotrecogin alfa (activated)
administered in accordance with
hospital guidelines
 Steroids given for septic shock
requiring continued use of
vasopressors for > 6 hours
 Lung protective strategy with
plateau pressures < 30 cm H2O
for mechanically ventilated
patients
http://www.ihi.org
Key Components: Prevent Complications of Critical
Illness
 Prophylaxis for DVT
 Stress ulcer prophylaxis
 Prevention of nosocomial pneumonia by elevation of
head to 45 degrees
 Facilitate extubation by daily interruption of
sedation and early SBT
 Narrowing of antibiotic spectrum when appropriate
SUMMARY: SEPSIS GUIDELINES 2008
Strong Recommendation (1): Recommended
A
B
DVT Prophylaxis
Antibiotics within 1 hr
for Septic Shock
EGDT and Protocolized
Resuscitation
Glycemic Control
Fluid Challenge
Crystalloid = Colloid
BC prior to Abx
PPI PUD Prophylaxis
Source Control
Low VT for ALI
Dopamine or
Norepinephrine
H2 Blocker PUD
Prophylaxis
No Routine Use
of SGC
No Renal Dose
Dopamine
No High Dose
Steroids
HOB >45
Limited Transfusion
No Antithrombin II
No Erythropoietin
Intermittent =
Continuous sedation
Weaning Protocol/SBT
Avoid NMB
C
Limit P plateau <30
cm H2O
PEEP
De-escalation
Antibiotic Therapy
Conservative Fluid in
ALI with no Shock
D
Antibiotics within 1
hr in No septic
Shock Patients
7-10 day Antibiotic
Duration
Consider Limiting
Support
SUMMARY: SEPSIS GUIDELINES 2008
Weak Recommendation (2): Suggested
A
B
C
D
APC in high risk
and non-surgical
PRBCs or
Dobutamine
Wean Steroids
equivalency
of continuous
veno-veno
hemofiltration
or intermittent
hemodialysis
APC for high risk
and surgical
NIV for ALI/ARDS
mild/moderate
hypoxemia
Low dose steroids
for septic shock
ACTH test not to
be done
B/S < 150
Prone Position in
ARDS
Therapy Across the Sepsis Continuum
Infection
SIRS
Sepsis
Severe Sepsis Septic Shock
*
Antibiotics and Source Control
Drainage
Debridement
Device
removal
Resection
Amputation
Chest 2000;118(1):146
Mortality* Associated With Initial Inadequate Therapy in Critically
Ill Patients With Serious Infections in the ICU
Initial adequate
therapy
Alvarez-Lerma,1996
Rello, 1997
Initial inadequate
therapy
Kollef, 1999
Kollef, 1998
Ibrahim, 2000
Luna, 1997
Mortality*
0%
20%
40%
60%
80%
100%
*Mortality refers to crude or infection-related mortality.
Alvarez-Lerma F et al. Intensive Care Med 1996;22:387-394.
Rello J et al. Am J Respir Crit Care Med 1997;156:196-200.
Kollef MH et al. Chest 1999; 115:462-474
Kollef MH et al. Chest 1998;113:412-420.
Ibrahim EH at al. Chest 2000;118:146-155.
Luna CM et al. Chest 1997;111:676-685.
Therapy Across the Sepsis Continuum
Infection
SIRS
Sepsis
Severe Sepsis Septic Shock
 CVP > 8-12 mm Hg
 MAP > 65 mm Hg
 Urine Output > 0.5 ml/kg/hr
 ScvO2 > 70%
 SaO2 > 93%
 Hct > 30%
* Early Goal Directed Therapy
Antibiotics and Source Control
Early Goal-Directed Therapy (EGDT): involves adjustments of cardiac preload, afterload, and contractility to
balance O2 delivery with O2 demand: Fluids, Blood, and Inotropes
Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. NEJM 2001;345:1368.
Early Goal-Directed Therapy Results:
28 Day Mortality
60
50
49.2%
Vascular
Collapse
P = 0.01*
40
Mortality %
33.3%
21% vs 10%
p=0.02
30
MODS
20
22% vs 16%
10
P=0.27
0
Standard Therapy
N=133
EGDT
N=130
*Key difference was in sudden CV collapse, not MODS
NEJM 2001;345:1368-77.
Therapy Across the Sepsis Continuum
Infection
SIRS
Sepsis
Severe Sepsis Septic Shock
Early Goal Directed Therapy
Antibiotics and Source Control
*
Insulin and Tight Glucose Control
Van den Burghe, NEJM 2001;345:1359-1367.
Intensive Insulin Therapy in Critically Ill Patients
Randomization
Conventional
Intensive
Blood glucose level
when insulin infusion
was started
>215 mg/dL
>110 mg/dL
Infusion adjusted to
maintain blood
glucose
180 to 200 mg/dL
(10.0 and 11.1
mmol/L)
80 to 110 mg/dL
(4.4 to 6.1
mmol/L)
39 % Received insulin
99% Received Insulin
van den Berghe G, et al. NEJM 2001;345:1359-1367.
Tight Glucose Control Improved Survival
Van den Burghe, NEJM 2001;345:1359-1367.
Intensive Insulin Therapy in Critically Ill Patients:
Mortality
ICU Mortality was reduced
by 42%
Mortality (%)
15%
p < 0.04 (adjusted)
In-Hospital Mortality was
reduced by 34%
15%
p = 0.01
10.9%
10%
10%
8.0%
7.2%
4.6%
5%
5%
0%
N=783
N=765
Conventional
0%
N=783
N=765
Intensive
Van den Burghe, NEJM 2001;345:1359-1367.
Effect of Intensive Insulin Therapy on Morbidity In MICU
Patients
Van den Berghe, G. et al. N Engl J Med 2006;354:449-461
Tight Glucose Control in the MICU: Effect on Mortality
Van den Berghe, G. et al. N Engl J Med 2006;354:449-461
Therapy Across the Sepsis Continuum
Infection
SIRS
Severe Sepsis Septic Shock
Sepsis
*
Drotrecogin Alpha
Early Goal Directed Therapy
Antibiotics and Source Control
Insulin and Tight Glucose Control
Chest 1992;101:1644
Activated Protein C in Sepsis
Activated Protein C:
 Inactivates clotting
factors
 limiting the
generation of thrombin
 Inhibits production
of inflammatory
cytokines
Endogenous Activated Protein C Modulates Coagulation,
Fibrinolysis, and Inflammation in Severe Sepsis
Activated Protein C
Activated Protein C
 Coagulation
 Inflammation
 Fibrinolysis
Homeostasis
Carvalho AC et al. J Crit Illness. 1994;9:51-75; Kidokoro A et al. Shock. 1996;5:223-8; Vervloet MG et al. Semin Thromb Hemost. 1998;24:33-44.
Results: 28-day All-cause Mortality
35
Primary analysis results
0.005
19.4%
38.1%
2-sided p-value
Adjusted relative risk reduction
Increase in odds of survival
30.8%
30
24.7%
25
6.1% absolute
reduction in
mortality
20
15
10
Placebo
(n - 840)
Drotrecogin
alfa (activated)
(n = 850)
5
0
Adapted from Table 4, page 704, with permission from Bernard GR, Vincent JL, Laterre PF, et al. Efficacy and safety of
recombinant human activated protein C for severe sepsis. N Engl J Med. 2001;344:699-709.
SIGNIFICANTLY
IMPROVED SURVIVAL IN PROWESS
13% Absolute Reduction / p=0.0002 @ 28
days
11% Absolute Reduction / p=0.003 @ 90 days
Subgroup analyses have the potential to mislead due to the absence of an intent to treat, sampling bias, and selection error
DrotAA
Therapy Across the Sepsis Continuum
Infection
SIRS
Sepsis
Severe Sepsis Septic Shock
*
Steroids
Drotrecogin Alpha
Early Goal Directed Therapy
Antibiotics and Source Control
Insulin and Tight Glucose Control
Chest 1992;101:1644
Low Dose Steroid Treatment in Septic Shock:
28 Day Mortality (Non-responders vs. Responders)
Patients with Relative Adrenal
Insuffiency (ACTH Test Nonresponders) (77%)
100%
28-day Mortality
p = 0.04
Patients Without Relative
Adrenal Insufficiency (ACTH
Test Responders) (23%)
100%
80%
63%
60%
40%
53%
N=114
p = 0.96
80%
61%
53%
60%
N=115
40%
20%
20%
0%
0%
Low-dose Steroids
N=36
N=34
Placebo
Annane D, et. al. JAMA 2002;288(7):862.
PREVENT COMPLICATIONS
 Stress ulcer and DVT prophylaxis
 Narrow antibiotic spectrum
 Prevent VAP: 45 degree elevation
 Facilitate early discontinuation of mechanical
ventilation: sedation interruption, early SBT
Therapy Across the Sepsis Continuum
Infection
SIRS
Sepsis
Severe Sepsis Septic Shock
*
Steroids
Drotrecogin Alpha
Early Goal Directed Therapy
Antibiotics and Source Control
Insulin and Tight Glucose Control
Chest 1992;101:1644
THE SEVERE SEPSIS BUNDLES: SSC/IHI
6 Hour Bundle







Measure serum lactate
Blood Cultures prior to antibiotics
Broad spectrum antibiotics within 3
hours of presentation, 1 hour in hospital
Initial fluid resuscitation with 20-40
mL/kg crystalloid (or equivalent
colloid) if hypotensive (SBP < 90
mmHg or MAP < 70) or lactate > 4
mmol/L
Vasopressors
If septic shock or lactate > 4 mmol/L:
 CVP and ScvO2 or SvO2 measured
 CVP maintained 8-12 mm Hg
Inotropes (and/or PRBCs if Hct < 30%)
delivered for ScvO2 <70% or SvO2<65%
if CVP > 8 mmHg
24 Hour Bundle
 Glucose control maintained < 150
mg/dL
 Drotrecogin alfa (activated)
administered in accordance with
hospital guidelines
 Steroids given for septic shock
requiring continued use of
vasopressors for > 6 hours
 Lung protective strategy with
plateau pressures < 30 cm H2O
for mechanically ventilated
patients
http://www.ihi.org
SCCM 2009: Sepsis Management "Bundles" Boost
Guideline Implementation, Reduce Mortality
15,022 Patients
7% Absolute Risk Reduction
19% Relative Risk Reduction
Society of Critical Care Medicine (SCCM) 38th Critical Care Congress. Late breaker. Presented February 2, 2009
Therapy Across the Sepsis Continuum
Infection
SIRS
Sepsis
Severe Sepsis Septic Shock
300 mg hydrocortisone/day for
non-responding septic shock
Drotrecogin Aapha for 2 organ dysfunction or septic
shock with APACHE II >24 and not postop
CVP > 8-12 mm Hg MAP > 65 mm Hg Urine Output > 0.5 ml/kg/hr
ScvO2 > 70% SaO2 > 93% Hct > 30%
1 hour appropriate antibiotics and source control
Blood Sugar Level <150 mg/dl (8.3 mmol/L)
‫‪Critical Care is A Promise‬‬
‫ان هللا يحب العبد اذا عمل عمال أن يتقنه‬
If you are admitted to our ICU with severe
sepsis we will:
Get blood cultures and get lactic acid level ASAP
Start broad spectrum antibiotics within 1 hour
Control the source of infection
Use early goal directed therapy
Start steroid therapy when indicated
Tight control your blood sugar
Use our “Sepsis Bundle” to manage your sepsis
Thank You