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Objectives
Epidemiology of Sepsis
Review Guidelines for Resuscitationx: ac a e, cu ures,
Tx: EGDT, timing/choice of abx, activated
o e
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Epidemiology
In the U.S. Annually:Inci ence of e sis 50 000
160,000 (~20%) are surgical patients
30-40% mortalit des ite abx and source control
~250,000 deaths per year
Cost $17 Billion
Barie, Am J Surg 2004; 188:212-220
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Epidemiology
Compared to medical septic pts, surgical pts:LO + a s
Cost +$10,000
-
Cost 5x higher
Angus, Crit Care Med 2001; 29:1303
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Importance of Severe Sepsis:
Comparison With Other Major Diseases
300
Sepsis
or a y o evere
Sepsis
200
250
00,000
200,000
250,000
r
100
150
Cases/1
100,000
150,000
D
eaths/Ye
0
50
AIDS*Colon Breast CHF Severe0
50,000
* SevereAMIBreast
National Center for Health Statistics, 2001. American Cancer Society, 2001. *American HeartAssociation. 2000. Angus DC et al. Crit Care Med. 2001 (In Press).
Cancer Sepsis SepsisCancer
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Determinants of Mortality
Source control is most vital factor -
Appropriate IV abx in 1 hr
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Definitions
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Systemic Inflammatory Response
Syndrome (SIRS)
Inflammatory response that includes 2 or more
Temp > 38C or < 36 C
RR > 20/min or PaCO2 < 32 mmHg
, ,
Sepsis : SIRS + Infection
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Severe Sepsis
Sepsis with end-organ dysfunctionOli ria
Increase Creatinine
Elevated Lactate
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Definition Summary
SIRS: HR > 90, RR > 20, 12 < WBC < 4,38 < tem
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Pathophysiology
Distributive shock stateaso ilation of arterioles lo R lo BP
Compensate with tachycardia and elevated CO/CI
Pre-ca illar A-V shunts
Low BP bypass capillary resistance beds
Elevated SVO2 Elevated lactate
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Pathophysiology
Classic physiologic derangements mostassociated with LPS
Can be associated with exotoxin from gram
Least associated with fungemia (atypical
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Diagnosing the Septic Pt
Combine clinical exam and labs/imagingEl erl
Cant mount a fever or leukocytosis
Ability to develop bandemia preserved
Immunosuppressed/steroids
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Diagnosing Sepsis
Lab tests: CBC, Chem, CULTURES,lactate SVO2
SVO2 is a measure of O2 extraction (NL 70%)
UNDER-RESUSCITATED se tic ts have a
LOW SVO2
RESUSCITATED septic pts have a HIGH SVO2
Lactate is a measure of the severity of sepsis
Lactate > 4 that does not correct in 6 hrs is bad
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Treatment
Based on Early Goal Directed Therapy , ,
of iv abx
Minimal role for steroids
Surviving Sepsis Campaign: International
guidelines for management of severe sepsis and
septic shock, 2008. Critical Care Med
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=
9% Surgical
u ures
Rivers, NEJM2001; 345:1368
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Treatment
Start with 1-4 liter bolus of saline or LREle ate lactate is not a contrain ication to LR
Pressor if needed to temporize while fluids are
runnin or if unres onsive to fluids alone
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Treatment Fluid Choice
Colloid (Hespan) Starch polymer that cannot cross cap endothelium in non-inflammed state
Mild anti-platelet effects after 1.5-2 liters/dayoss e a verse e ec on rena unc on
Albumin (SAFE Trial)*
Possibly worse in trauma, esp TBI
*NEJM 2004; 350:2247
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Treatment Choice of Fluids
FFP We recommend FFPnot
be used tocorrect laborator clottin abnormalities in
the absence of bleeding or planned
o eration*
Surviving sepsis campaign 2008
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18
16
18
20
12
14
8
66
8
FFP N=380
0
2
4o =
Total FFPTransfused
No FFPTransfused
Sarani Critical Care Med 2008; 36:1114
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OR 95% CI P value
Age 0.994 0.98-1.005 0.27
FFP 1.039 1.013-1.067
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-
MAP > 65 mm Hg, HR < 100 bpmUOP > 0.5 cc/kg/hr
SVO2 70% or more
CVP > 10-15 Higher if known cardiomegaly or intubated
TTE showing cardiac filling
following boluses (concept of volume-responsiveness)
T V
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Treatment - Vasopressors
- 1 2 1
Dopamine 1-5 mcg/kg/min 6-10 mcg/kg/min >10 mcg/kg/min
-
Phenylephrine
(Neosynephrine)
1-300mc /min
+++
Norepinephrine
(Levophed)
1-20 mc /min
+ ++++
Epinephrine
(Gods Pressor)
1-10 mc /min
++++ +++ ++++
Dobutamine (1-10
mcg/kg/min)
+++ ++
Milrinone 0.125- +++ +++
0.5 mcg/kg/min)
Potency + scale is from 1-4
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Treatment
Blood TransfusionRi ers trial transf se for H < 10 if O2
remained low after IVF and after MAP > 65
Role for re-em tive transfusion?
e.g. Hg 10-11 with elevated lactate/shock
Time to replete 2,3 DPG, good colloid resuscitant
Immunosuppressive
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O2 Delivery in Sepsis
Author, Year,
Journal
Population Findings
Dietrich 1990 CritCare Med
N= 32, MICU,se tic RCT
Hg 810.5, nochan e in PAOP
CI, lactate, SVO2
Lorente 1993 Crit N=16, MICU, DobutamineCare Med septic, RCT increases SVO2
but RBC does not
Fernandes 2001
Crit Care
N=15, MICU,
septic, RCT
RBC does not
change gastric
tonometry orlactate
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Consider U/S if too unstable to travel
e s e percutaneous ntervent ons ra ns
Conditions with 100% mortality if notoperated on quickly
Nec fasciitis, non-sealed perforated viscus
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Treatment IV Abx
Mortality increases 7% for every hour delayin antibiotic administration*
)
Minute
Time
eps sBundle at
HUP
unr se*Kumar A. Crit Care Med 2006; 34:
1589-96
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-
Recommended only for shock refractory to pressors
Annane multicenter, European, RCT Pts with vasopressor-resistant hypotension
mprove mor a y r se n cor so o ow ng was9mcg/dL and if baseline cortisol < 21
CORTICUS lar er, Euro ean, RCT All pts with septic shock (regardless of vasopressor response)
No difference in mortality but vasopressor sparing effect with
ACTH stim could not predict who was steroid deficient
Annane 2002; 288:862Insert CORTICUS Reference
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Treatment - Xigris
Activated protein CAnticoa lant inhibits Factors an III
Stop microthrombi formation and prevent end-organ
loss?
Endothelial cell stabilizer (anti-inflammatory)
Stop excessive production of cytokines and
apoptos s
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PROWESS - Limitations
Never replicated
Entr criteria chan ed in the middle of the stud
Study terminated early
Dru a roved for use in a ost-hoc derived
subgroup (APACHE II > 25 or high risk of death
as determined by intensivist)
Higher APACHE II mortality in the control arm
than anticipated