Nabil Abouchala, MD, FCCP, FACPConsultant, Pulmonary and Critical Care Medicine
Medical Director, Med-Sug ICU-CKing Faisal Hospital & Research Center
Riyadh, Saudi Arabia
SURVIVING SEPSIS CAMPAIGN:
INTERNATIONAL GUIDELINES FOR
MANAGEMENT OF SEVERE SEPSIS AND SEPTIC SHOCK:
2012A GUIDE TO THE GUIDELINES …
SURVIVING SEPSIS CAMPAIGN: HISTORY OF THE GUIDELINES…
2001
2004
2008 201
2
Crit Care Med 2013; 41:580–637
SURVIVING SEPSIS CAMPAIGN: INTERNATIONAL GUIDELINES FOR MANAGEMENT OF SEVERE SEPSIS AND SEPTIC SHOCK: 2012
1. Initial Resuscitation and Infection Issues 2. Hemodynamic Support and Adjunctive Therapy 3. Other Supportive Therapy of Severe Sepsis4. Special Considerations in Pediatrics
SURVIVING SEPSIS CAMPAIGN: INTERNATIONAL GUIDELINES FOR MANAGEMENT OF SEVERE SEPSIS AND SEPTIC SHOCK: 2012
1. Initial Resuscitation and Infection Issues 2. Hemodynamic Support and Adjunctive Therapy 3. Other Supportive Therapy of Severe Sepsis4. Special Considerations in Pediatrics
A. Initial Resuscitation
B. Screening for Sepsis & Performance Improvement
C. Diagnosis
D. Antimicrobial Therapy
E. Source Control
F. Infection prevention
1. Initial Resuscitation & Infection Issues
• Sepsis BundleA. Initial Resuscitation
• RRT and Use of Sepsis Bundle Protocol
B. Screening for Sepsis & Performance Improvement
• Use of the 1,3 beta-D-glucan assay, mannan and anti-mannan antibody assays
C. Diagnosis
• Use of an echinocandin if candidemia is suspected • Use of low procalcitonin levels or similar biomarkers to
assist the clinician in the discontinuation of empiric antibiotics
D. Antimicrobial Therapy
E. Source Control
• Oral chlorhexidine gluconate (CHG) for prevention of VAPF. Infection prevention
1. Initial Resuscitation & Infection Issues
Serum Lactate MeasuredBlood Culture Obtained Prior to Antibiotic Administration
Broad-Spectrum Antibiotics Administered within 1 Hour of ED Admission
Fluid Resuscitation (30 ML/Kg) for Hypotension or Lactate >4mmol/L
Vasopressors for Ongoing HypotensionMaintain Adequate Central Venous Pressure (CVP ≥ 8)
Maintain Adequate Central Venous Oxygen Saturation (ScvO2 ≥ 70%)Re
susc
itat
ion
Bund
leSEPSIS BUNDLE
Re-measure Serum Lactate
A. Initial Resuscitation
EARLY GOAL-DIRECTED THERAPY IN THE TREATMENT OF SEVERE SEPSIS AND SEPTIC SHOCKTo 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
N Engl J Med, 2001;345:1368-77
#Citing
articles
2469
MORTALITY10-20%
Sudden
Death!
RESULTS Mortality
EGT : 30.5 %Standard: 46.5 %
Absolute Risk Reduction
NNT =
N Engl J Med, 2001;345:1368-77
37 Observational studies showing improved
outcomes with early quantitative resuscitation
between 2001 and 2011
Multicenter trial of 314 patients with severe sepsis in eight Chinese centers (2010). This trial reported a 17.7% absolute reduction
16%
7
FLUID IN SEPTIC SHOCK, HOW MUCH ?
2012: IVF RECOMMENDATION Initial fluid challenge ≥ 1000 mL of
crystalloids or minimum of 30 mL/kg of crystalloids in the 1st 4-6 hours (Strong recommendation; Grade 1C).
Crystalloids is the initial fluid for resuscitation (Strong recommendation; Grade 1A).
Adding albumin to the initial fluid resuscitation (Weak recommendation; Grade 2B).
Against hydroxyethyl starches (hetastarches) with MW >200 dalton (Strong recommendation; Grade 1B).
Timing of Antibiotic Administration
Septic Shock: Timing of Antibiotics
Kumar Crit Care Med 2006
0.0
.20
.40
.60
.80
1.00
% Survival% Total receiving antibiotics
0 - .5 .5 – 1.01 - 2 2 - 3 3-4 4 - 5 5 - 6 6 - 9 9 - 1
212 - 2
424 - 3
6> 36
Percent
Time, hrs
14 ICUs; n = 2,731
Only 50% of patients in Septic Shock received antibiotics w/in 6 hrs.
SURVIVING SEPSIS CAMPAIGN: INTERNATIONAL GUIDELINES FOR MANAGEMENT OF SEVERE SEPSIS AND SEPTIC SHOCK: 2012
1. Initial Resuscitation and Infection Issues 2. Hemodynamic Support and Adjunctive Therapy 3. Other Supportive Therapy of Severe Sepsis4. Special Considerations in Pediatrics
G. Fluid Therapy of Severe Sepsis
H. Vasopressors
I. Inotropic Therapy
J. Corticosteroids
2. Hemodynamic Support and Adjunctive Therapy
WHICH INOTROPES TO USE? Norepinephrine as the first choice
( Grade 1B) Adding or substituting epinephrine when an
additional drug is needed (Strong recommendation; Grade 1B).
Vasopressin 0.03 units/min may be added (Weak recommendation; Grade 2A)
Dopamine only in highly selected patients at very low risk of arrhythmias or low heart rate (Weak recommendation; Grade 2C).
Dobutamine infusion be started or added with low cardiac output) or ongoing signs of hypoperfusion, even after adequate intravascular volume (Strong recommendation; Grade 1C)
NOREPINEPHRINE COMPARED WITH DOPAMINE IN SEVERE SEPSIS SUMMARY OF EVIDENCE
Crit Care Med 2012; 40:725–730
SEPSIS INDUCED VASODILATATION
Lower amount of fluid required to fill the tank
NE
Crit Care Med 2007; 35:1736–1740
Early NE + Fluids
Late NE + Fluids
Fluids
NE
LPS
Adequate fluid resuscitation …
Early administration of norepinephrine aimed at rapidly achieving a sufficient perfusion pressure in severely hypotensive septic-shock (DBP < 40) patients is able to increase cardiac output through an increase in cardiac preload and cardiac contractility
Crit Care Med 2007; 35:64–68
Crit Care Med 2007; 35:64–68
PASSIVE LEG RAISING
PLR mimics fluid challenge
Unlike fluid challenge, no fluid is infused and the effects are reversible
and transient
STROKE VOLUME VARIATIONSVV = SV max – SV min / SV mean
Preload
Stroke Volume
00
Higher PVI = More likely to respond to fluid administration24 %
10 % Lower PVI = Less likely to respond
to fluid administration
PLETH VARIABILITY INDEX (PVI) TO HELP CLINICIANS OPTIMIZE PRELOAD / CARDIAC OUTPUT
Maxime Cannesson, MD, PhD
• Crystalloids = Albumin• Against the use of hydroxyethyl starches• Hemodynamic response based on Dynamic
assessment
G. Fluid Therapy of Severe Sepsis
• Norepinephrine is 1st choice• Epinephrine 2nd
• Dopamine only in highly selected cases • Phenylephrine is not recommended• Low-dose dopamine should not be used for renal
protection
H. Vasopressors
I. Inotropic Therapy
• Not using IV hydrocortisone to treat adult septic shock unless …
• Use Hydrocortisone at 200 mg/day, preferably as IV infusion, to be tapered off
J. Corticosteroids
2. Hemodynamic Support and Adjunctive Therapy
Target MAP ≥ 65 …
SURVIVING SEPSIS CAMPAIGN: INTERNATIONAL GUIDELINES FOR MANAGEMENT OF SEVERE SEPSIS AND SEPTIC SHOCK: 2012
1. Initial Resuscitation and Infection Issues 2. Hemodynamic Support and Adjunctive Therapy 3. Other Supportive Therapy of Severe Sepsis4. Special Considerations in Pediatrics
K. Blood Product Administration Target Hemoglobin (7-9 g/dl) unless …
L. Immunoglobulins: Not recommended
M. Selenium: Not recommendedN. History of Recommendations Regarding Use of Recombinant Activated Protein CO. Mechanical Ventilation of Sepsis-Induced Acute Respiratory Distress Syndrome (ARDS)P. Sedation, Analgesia, and Neuromuscular Blockade in Sepsis
Q. Glucose Control
R. Renal Replacement Therapy
S. Bicarbonate Therapy
T & U. Prophylaxis: Deep Vein Thrombosis and Stress Ulcer
V. Nutrition
W. Setting Goals of Care
3. Other Supportive Therapy of Severe Sepsis
K. Blood Product Administration Target Hemoglobin (7-9 g/dl) unless …
L. Immunoglobulins: Not recommended
M. Selenium: Not recommendedN. History of Recommendations Regarding Use of Recombinant Activated Protein C
R. Renal Replacement Therapy
S. Bicarbonate Therapy
3. Other Supportive Therapy of Severe Sepsis
THE RISE AND FALL OF XIGRIS!
-6.5% +1.2%
K. Blood Product Administration Target Hemoglobin (7-9 g/dl) unless …
L. Immunoglobulins: Not recommended
M. Selenium: Not recommendedN. History of Recommendations Regarding Use of Recombinant Activated Protein CO. Mechanical Ventilation of Sepsis-Induced Acute Respiratory Distress Syndrome (ARDS)P. Sedation, Analgesia, and Neuromuscular Blockade in Sepsis
Q. Glucose Control
R. Renal Replacement Therapy
S. Bicarbonate Therapy
T & U. Prophylaxis: Deep Vein Thrombosis and Stress Ulcer
V. Nutrition
W. Setting Goals of Care
3. Other Supportive Therapy of Severe Sepsis
O. Mechanical Ventilation of Sepsis-Induced (ARDS)
3. Other Supportive Therapy of Severe Sepsis
1. Target a TV of 6 mL/kg predicted body weight (grade 1A vs. 12 mL/kg)2. Plateau pressures be measured in patients with ARDS be ≤30 cm H2O (grade 1B)3. (PEEP) be applied (grade 1B)4. Higher rather than lower levels of PEEP for moderate or severe ARDS (grade 2C)5. Recruitment maneuvers be used with severe refractory hypoxemia (grade 2C)6. Prone positioning be used Pao2/Fio2 ratio ≤ 100 mm (grade 2B)
7. HOB elevated to 30-45 (grade 1B)
8. (NIV) be used in minority of patients in whom the benefits of NIV (grade 2B)
9. Weaning protocol be in place
10. Against the routine use of the pulmonary artery catheter (grade 1A)
11. A conservative rather than liberal fluid strategy (grade 1C)
12. not using beta 2-agonists for treatment of sepsis-induced ARDS (grade 1B)
ARMA Trial
Intervention Control
TV (4-6 ml/Kg)PEEP 8.5
TV (10-12 ml/Kg)
PEEP 8.6
Reducing from 12 to 6 ml/kg VT saved lives
NNT 1214000 Lives Saved/Year
Wet First –Dry later
Approach that combines both adequate initial fluid resuscitation followed by conservative late-fluid management was associated with improved survival
CHEST 2009; 136:102–109
Wet First –Dry later
CHEST 2009; 136:102–109
JAMA. 2010;303(9):865-873
Higher PEEP is better in Moderate to Severe ARDS
(PO2/FiO2 ≤ 200 mmHg)
JAMA. 2010;303(9):865-873
Higher PEEP is better in Moderate to Severe ARDS
(PO2/FiO2 ≤ 200 mmHg)
Death in ICU 6.3 %
NNT 16Days off the MV-5 days JAMA. 2010;303(9):865-873
• (NMBAs) be avoided if possible without ARDS• Short course of NMBA (<48 hours) for early ARDS +
Pao2/Fio2<150 mm Hg
P. Sedation, Analgesia, and Neuromuscular Blockade in Sepsis
Q. Glucose Control
• PPIs rather than H2RA (grade 2D)
T & U. Prophylaxis: Deep Vein Thrombosis and Stress Ulcer
V. Nutrition
3. Other Supportive Therapy of Severe Sepsis
GLUCOSE CONTROL IN ICU-10% +1.5%
ITT- 2001 NICE-SUGAR- 2009
• (NMBAs) be avoided if possible without ARDS• Short course of NMBA (<48 hours) for early ARDS +
Pao2/Fio2<150 mm Hg
P. Sedation, Analgesia, and Neuromuscular Blockade in Sepsis
Q. Glucose Control
• PPIs rather than H2RA (grade 2D)
T & U. Prophylaxis: Deep Vein Thrombosis and Stress Ulcer
V. Nutrition
3. Other Supportive Therapy of Severe Sepsis
Omega/EDEN* studies Objective: dietary
supplementation of Omega-3 FA increase ventilator –free days in patients with ALI/ARDS
Intervention: BID bolus supplementation of omega-3 FA vs isocaloric control
Rice at al. for the NHLBI ARDS Clinical Trials Network JAMA. 2011;306(14):1574-1581
Daily energy intake
Rice at al. for the NHLBI ARDS Clinical Trials Network . JAMA. 2012
Survival and hospital Discharge
Rice at al. for the NHLBI ARDS Clinical Trials Network . JAMA. 2012
• (NMBAs) be avoided if possible without ARDS• Short course of NMBA (<48 hours) for early ARDS +
Pao2/Fio2<150 mm Hg
P. Sedation, Analgesia, and Neuromuscular Blockade in Sepsis
• Target an upper BG 140-180 mg/dL rather than ≤ 110 mg/dL (grade 1A)
Q. Glucose Control
• PPIs rather than H2RA (grade 2D)
T & U. Prophylaxis: Deep Vein Thrombosis and Stress Ulcer
• Avoid mandatory full caloric feeding in the first week but rather suggest low dose feeding (eg, up to 500 calories per day)
• No specific immunomodulating supplementation
V. Nutrition
3. Other Supportive Therapy of Severe Sepsis
TAKE HOME MESSAGE BE Goal Directed:
More and faster fluid No hetastarch Earlier Inotropes Use norepineprine and epinephrine over
dopamine Lactic acid clearance Dynamic SVV is better than CVP
Antimicrobials: Fast <1 hr, consider early antifungals, use
biomarkers to deescalate or stop ARDS:
Wet first, dry later Higher PEEP
Glucose control Not so tight (140-180 mg/dl = 8-10 mmol/l)
Nutrition Underfeed first week No supplement
