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Outline
Definition and pathophysiology of sepsis syndrome Guidelines for management of severe sepsis/septic shock
Sepsis resuscitation bundle Sepsis management bundle
40% total ICU expenditure in Europe Average cost per individual case is approximately $22,000
National Taiwan University Hospital
Septic shock
Acute circulatory failure as persistent arterial hypotension (SBP <90 mmHg, MAP <60, or a reduction in SBP >40 mm Hg from baseline) despite fluid resuscitation
National Taiwan University Hospital
Infection
Severe Sepsis
Increasing inflammation
High risk of infection Infection SIRS plus infection Septic shock
Antibiotics, antitoxins
Endotoxin (LPS)
Trigger
Cytokine Storm
Hyperreactive immune response Hyporeactive immune response, immnoparalysis
Edema Tissue damage Organ failure Phagocytic cell function Susceptibility to infection
Causative agents
Pro-inflammatory cytokines + chemokines ROS production Enzyme release
National Taiwan University Hospital
Fi
s lysi o brin
Homeostasis
National Taiwan University Hospital
Increased PAI-1 Increased TAFI Reduced Protein C (endogenous activated Protein C inhibits PAI-1)
2004
Dellinger RP, Carlet JM, et al. Crit Care Med 2004; 32:858
2008
Dellinger RP, Levy MM, et al. Intensive Care Med 2008; 34:17
National Taiwan University Hospital
Management of Sepsis
Infection control
Antibiotics, source control
Hemodynamic support
Ventilation, vasopressor, infusion, pump
New drug
Activated protein C
National Taiwan University Hospital
http://www.survivingsepsis.org/
National Taiwan University Hospital
Source control
Drainage Debridement Device removal Definitive control
13.4
13.1
13.9
0.95
.34
Retrospective study of a national random sample of 18,209 Medicare patients older than 65 years of age with pneumonia
National Taiwan University Hospital
Houck et al. Arch Intern Med 2004; 164:637-44 Department of Internal Medicine
Adequate
Luna
AlvarezLerma
Rello
Kollef
SanchezNieto
Ruiz
Dupont
Fagon JY, Chastre J. Clin Chest Med 2005; 26:97-104 Department of Internal Medicine
Crystalloid vs Colloid
Crystalloid
Intravascular persistence Poor Hemodynamic stabilization Transient Required infusion volume Risk of tissue edema Enhancement of capillary perfusion Risk of anaphylaxis Plasma colloid osmotic pressure Cost
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Colloid
Good Prolonged Moderate Insignificant Good Low to moderate Maintained Expensive
Vasopressors
Initiate vasopressor if appropriate fluid challenge fails to restore adequate BP and perfusion Either NE or dopamine are first line agents to correct hypotension in septic shock
NE is more potent than DA and may be more effective at reversing hypotension in septic shock Dopamine may cause more tachycardia and more arrhythmogenic
National Taiwan University Hospital
Vasopressors
Low dose DA should NOT be used for renal protection in severe sepsis An arterial catheter should be placed as soon as possible Vasopressin may be considered in shock patients that are refractory to fluid resuscitation and high dose vasopressors
Infusion rate of 0.01-0.04 units/min in adults May decrease stroke volume
National Taiwan University Hospital
Inotropic Therapy
In patients with low cardiac output despite adequate fluid resuscitation, dobutamine may be used to increase cardiac output Epinephrine, phenylephrine, vasopressin should Not be the initial vasopressor It is NOT recommended to increase cardiac index to target an arbitrarily predefined elevated level
No benefit from increasing oxygen delivery to supranormal levels by use of dobutamine
National Taiwan University Hospital
Transfuse PRBC to Hct > 30% and/or Administer dobutamine (max 20 g/kg/min) to goal
River E. N Engl J Med 2001;345:1368.
P = 0.01*
33.3%
Standard Therapy EGDT n=133 n=130 *Key difference was in sudden CV collapse, not MODS
National Taiwan University Hospital
Stress, Cytokines
CS-binding
Intact HPA axis is Crucial for the survival of critical ill patients
Mortality rate of patients with multiple injuries, University hospital of Glasgow, Scotland
1969-1980 22-29% vs. 1981,1982 44% Coincides with the use of Etomidate, a shortacting hypnotic drug (a selective inhibitor of adrenal 11-hydroxylase)
(Ledingham & Watt. Lancet 1983;1:1270)
National Taiwan University Hospital
Prognostic classification in septic shock based on cortisol levels and cortisol response to corticotropin
Baseline cortisol level (g/dL) Good Intermediate Poor 34 34 > 34 > 34 max (g/dL) >9 9 >9 9 28 d mortality (%) 26 67 82
100%
100%
P=0.96
80% 61% 60% 40% 20% 0%
N=36
53%
N=34
Low-dose Steroids
National Taiwan University Hospital
Placebo
(Annane et al. JAMA 2002;288:862)
Steroids
Intravenous corticosteroids are recommended in patients with septic shock who require vasopressor therapy to maintain blood pressure
Administer intravenous hydrocortisone 200-300 mg/day for 7 days in three or four divided doses or by continuous infusion with gradual tapering ACTH stimulation is not recommended routinely done Shown to reduce mortality rate in patients with relative adrenal insufficiency
National Taiwan University Hospital
VT (mL/kg)
10 8 6 4 2 0
1978-1981
1986-1989
1993-1996
2000-2004
Years
National Taiwan University Hospital
Setting PEEP based on FIO2 requirement and thoracopulmonary compliance Consider prone positioning in ARDS when:
Potentially injurious levels of F1O2 or plateau pressure exist and not at high risk from positional changes
National Taiwan University Hospital
% Mortality
30 25 20 15 10 5 0 6 ml/kg 12 ml/kg
Insulin Bolus and Infusion Rate Stop infusion Reduce rate by 0.1-0.5 U/hr No change unless decreased > 20% from previous result; if > 20%, decrease rate 20% Increase rate by 0.1-0.5 U/hr Increase rate by 0.5-1 U/hr Increase rate by 2 U/hr
In-Hospital Mortality
15%
p = 0.01
10.9%
Mortality (%)
10%
8.0% 4.6%
10% 7.2% 5%
n=783 n=765
5%
n=783
n=765
0%
0%
Conventional
Intensive Insulin
ITT group
In-hospital survival (%) Intensive treatment
P=0.40
100 80 60
ICU3 days
Intensive treatment
P=0.02
Conventional treatment
40
Conventional treatment
20 0
100
200
300
400
500
100
200
300
400
500
Hypotension <90 mmHg or MAP<70 mmHg Hypoxia pO2 /FiO2 < 250 Oliguria < 0.5cc/kg for 1h Platelets <80k /D.I.C. or 50% drop Lactic acidosis (level >1.5 X normal) with pH<7.35
Bernard GR. N Engl J Med. 2001;344(10):699-709.
Mortality Rate
40%
Placebo
* as defined by APACHE II 25
Treatment should begin as soon as possible once been identified No absolute contraindication
Dellinger, et. al. Crit Care Med 2004, 32: 858-873.
National Taiwan University Hospital
Department of Internal (Eichacker & Natanson. Intensive Care Med 2007;33:396) Medicine
Closing Remarks
Goal of Surviving Sepsis Campaign Managing sepsis based on evidence Managing sepsis with protocol Sepsis resuscitation & management bundle