egdt and septic shock
TRANSCRIPT
Emanuel P. Rivers, MD, MPH, IOM
Vice Chair and Research Director
Senior Staff in Emergency Medicine and Critical Care
Henry Ford Hospital
Clinical Professor, Wayne State University
Detroit, Michigan
Early Goal Directed Therapy inSevere Sepsis and Septic Shock:
Where are we 10 years later
Why Should You Botherwith Early Sepsis Intervention?
Time Sensitive DiseasesChanging the Paradigm of Practice
< 5%
Trauma
7%
Stroke
< 10%
AMI
Acute MyocardialInfarction Mortality - 10%
Liver TransplantMortality - 5%
Trauma Mortality - 5% Cardiac Surgery Mortality - 5%
Septic Shock Mortality– 50-55%
10% of Hospital Admissions – 40% of Hospital Deaths
$100 million in total hospital costs per year
HealthGrades analyzed over 5 million Medicarerecords of patients admitted through the emergencydepartment at 4,907 hospitals from 2006 through2008, to identify the top 5% of the best-performinghospitals in emergency medicine.
InflammationMicrocirculation
Early Goal DirectedHemodynamic Optimization
Organ Dysfunction
Decrease Mortality
Decrease Health Care ResourceConsumption
Early Detection of HighRisk Patients
AppropriateDisposition
ICU
ER
Collaboration is Fun
The Lecture Goals
The First Step:Understanding the Pathogenesis and
Expanding theLandscape of Sepsis
Global TissueHypoxia and
OrganDysfunction
Organism
Multiple OrganDysfunction and
Refractory Hypotension
Diffuse endothelialdisruption and
microcirculation defects
Systemic Inflammationor Inflammatory
Response
Septic Shock
Sepsis: A Complex and Dynamic Landscape
Severe Sepsis
EmergencyDepartment
Intensive CareUnit
Out PatientSetting
At Home orResidence
SepsisSource
Systemic Inflammatory Response Syndrome (SIRS)A clinical response arising from a nonspecific insult,including 2 of the following:
• Temperature ≥38oC or ≤36oC
• HR ≥90 beats/min
• Respirations ≥20/min
• WBC count ≥12,000/mm3 or≤4,000/mm3 or >10% bands
• PaCO2 < 32mmHg
General PracticeFloors
ORand Recovery
• 115 million visits/year.• 2.9% of hospital admits are
severe sepsis and septic shock.– 600,000 admissions per
year through the ED.• ED waiting times (5-6 hours)
approaching 24 hours.
• After ICU Admission:
– > 6 hour total delay forhemodynamic optimization.
– ICU is poor
• Shock mortality rate:
– ICU - 24% to 70%.
McCaig: MMWR, 2001, Angus DC et al. CCM, 2001,
Varon, CCM, 1997, Lundberg, 1998, CCM, Lefrant, 2000*, CCM
• 67 minute delay toICU arrival.#
• 3 fold increase inmortality.
General IPD Floors and Post OpICU
ED
Pre-Hospital
A Systems Approachand A Resuscitation
Golden Hours
Silver Day
Bundles
The Evidence behind theResuscitation Bundle
The Role of Antibiotics
• 2,154 septic shock patients
• Received antibiotics after theonset of recurrent or persistenthypotension
• Each hour of delay over 6 hrswas associated with 7.6%decrease in survival.
The Importance ofSource Control
• 54 y/o high school principlepresents with pyelonephritis,receives antibiotics.
• Radiography
• Remove infected devices
• Early Surgical Intervention
Crit Care Med, 2004
Sepsis is the friend of the elderly……. Greg Henry
Miss World FinalistMariana Bridi da Costa
Age 20, Dies From septic shock
“Doctors diagnosed her with aurinary track infection, her
condition worsened and doctorsthen diagnosed her with kidneystone and urinary tract infection
spread”
“She was hospitalized, requireddialysis and had her hands andfeet amputated in a bid to save
her from a deadly and little-knownillness”
The Diagnosisof Sepsis
is Imperfect
Stephen HalesStephen Hales -- 17331733
Outcome Implication of Not RecognizingA Subtle but Deadly Disease Transition
ER or Ward ICU
MAP ~ SVR X CO
The Physiology ofOxygen Transport:
Defining Tissue Hypoperfusion
250 ml/min
25%
1000 ml/min
SvO2 = 65-75%Hgb x SaO2
+ PaO2 x0.003 =
20 volume %
Cardiac Output5 liters/min.
Global Tissue Hypoxia:A More Sensitive Measure of Shock
OXYGENDEMAND
OXYGENDELIVERY
OXYGENBALANCE
Global TissueHypoxia
OXYGENDEMAND
OXYGENDELIVERY
Lactic Acid> 4 mM/L
70-75%
VO2
• Stress
• Pain
• Hyperthermia
• Shivering
• Work of breathing
DO2
• SaO2/PaO2
• Hgb
• Cardiac Output
- +
ScvO2 SvO2
Pope, Annals of Emerg Med, 2009
619 Patientsreceived EGDT
in 4 centers
Pope, Annals of Emerg Med, 2009
< 70% 70 - 90% > 90%
Risk Stratification or EarlyDetection of High Risk Patients:
The Use of Lactate
Diagnostic and Therapeutic Markers
SvO2
<2mM/L4 mM/L
38- 40%
Diagnostic and Therapeutic Markers
SvO2
4 mM/L
The Implications ofLactate Clearance
-30-20-10
01020304050607080
LactateClearance
%
1 2 3 4
Quartiles of Lactate Clearance
Lactate (ED or ICU Admission – (ED or ICU @ 6 hours)ED or ICU Length of Stay (hrs)
Early LactateClearance
0 12 24 36 48 60 726
3
4
5
6
7
8
9
10
11 No ClearanceIntermediate Clearance
High Clearance
Time (hr) p<0.05
MO
DS
53
42
29
16
0
10
20
30
40
50
60
Mo
rtali
ty(%
)
1 2 3 4
Debaker, 2006
7.73.8Lactate
5.311Central Venous Pressure
48.674ScvO2
51.244.8SAPS II
EGDTJAMA
48.4%34.8%Predicted Mortality
Systemic O2 Delivery (ml/min/m2)
SvO2Lactate
Critical O2 DeliveryThreshold
Sy
stem
icO
2C
onsu
mpti
on
(ml/
min
/m2)
EGDT JAMA
7.73.8Lactate
5.311CVP
48.674ScvO2
51.244.8SAPS
EGDTJAMA
Crit Care, 2009
50% of vasopressor-dependent septic shockpatients do not express lactic acidosis and
have higher mortalities
The Hemodynamic Perturbationsof Early Sepsis
Increased Metabolic Demands:Fever, Tachypnea Hypovolemia,Vasodilation &
Myocardial Depression
Microvascular Alterations:Impaired Tissue Oxygen
Utilization
Inflammatory Mediators Produce Cardiovascular Insufficiency
Cytopathic Tissue Hypoxia
Fink, Crit Care Clin, 2002
SepticShock
Goal Directed
DO2
- PaO2
- Hemoglobin
- Cardiac Output
Cardiac Optimization- Preload (CVP, PCWP, SVV)- Afterload (MAP, SVR)Contractility (SV)
- Heart Rate (BPM)- Coronary Perfusion Pressure
Microcirculation
CNS and Systemic VO2
- Stress
- Pain
- Hyperthermia
- Shivering
- Work of breathing
Endpoints of Resuscitation
Lactate
HappyCell
BaseDeficit
(a-v)CO2
SvO2
pHi
VO2
StO2
Excellence is performing commonthings in uncommon places….
George Washington Carver
Task Force of the American College ofCritical Care Medicine
Practice parameters for hemodynamicsupport of sepsis in adult patients in
sepsis.
Crit Care Med 1999 ;27:639-60
Fluids Vasopressors
Hematocrit of 30%
SvO2
LactateInotropes
Sepsis is a Spectrum of Disease
↑↑NormalVariableImpairment oftissue O2 utilization
↑↓↑VariableMyocardialSuppression
Variable↑Normal↓Compensated andvasodilatory
↑↓↓VariableHypovolemia
LactateScvO2
CVPFTcPPV
MAP
Vasodilators,r-APC
Correct anemiaInotropic Therapy
VasopressorsAdrenal Dysf.
Volume
Treatment andComments
• 62 year presents with sepsis after a prostate biopsy.• He also complains of SIRS, SOB and disorientation.• WBC of 25,000 and Lactate of 9 mM/L• Blood cultures and Antibiotics• 7 liters of fluid
May, 2006
7 liters of fluids in first6 hours and offvasopressors
Before Surgery
Day 2 – Extubated in theRecovery Room
10 liters of fluid in10 hours
Day 3 –Mobilization
93 years old Perforated Ulcer
Levophed – 10 ug/min
Although no difference in mortality at 60 days between the twotreatment groups, patients treated according to a conservativestrategy of fluid management (47 hours after ICU adm) had:
1. Significantly improved lung function and centralnervous system function
2. Decreased need for sedation, mechanicalventilation, and intensive care.
3. A small (0.3 day) increase in the number ofcardiovascular-failure–free days during the first 7 dayswith the liberal strategy.
These salutary effects were achieved without an increase in thefrequency of non-pulmonary organ failure or shock.
0 12 24 36 48 60 723 6
200
250
300
350Standard
EGDT
Hours after start of treatment
PaO
2/F
iO2
Ratio
PaO2/FIO2 Ratio
Sepsis is a Spectrum of Disease
↑↑NormalVariableImpairment oftissue O2 utilization
↑↓↑VariableMyocardialSuppression
Variable↑Normal↓Compensated andvasodilatory
↑↓↓VariableHypovolemia
LactateScvO2CVPMAP
Vasodilators,r-APC
Correct anemiaInotropic Therapy
VasopressorsAdrenal Dysf.
Volume
Treatment andComments
The Choice of a Vasopressor
Hypotensive
Tachycardic Patient
Hypotensive
Bradycardic Patient
Low Doseto High DoseVasopressor
No Vasopressorto High DoseVasopressor
0
20
40
60
NoVasopressor
No Vasopressorto Low DoseVasopressor
Mort
alit
y(%
)
20%
37%
58%54%
What do these individuals havein common?
Adrenal Insufficiency
Design: Randomized, double-blind,
multi-center
Patients: Septic shock
Intervention:
Hydrocortisone (50 mg every six hours)
Fludrocortisone (50 ug once per day)
Main Outcome: 28-day survival innonresponders to CST
Effect of Low Doses of Hydrocortisone andFludrocortisone on Mortality in
Patients with Septic Shock(Annane JAMA 2002)
229 Non-respondersRandomized
115 Treatment &
114 controls
10% decrease in
28-day mortality
17% reduction invasopressors use
Patients Receiving Vasopressors – Septic Shock
No OutcomeBenefit
Now what should I do about steroids?
The Original Trial
• 8 hour time frame
• Minimal steroid use
• 56% mortality
The Corticus Trial
• 72 hour time frame
• Excluded patientstreated – over 50%
• Less severe patients –30 - 40% mortality
• Similar benefit withhigher mortality
14.5% Reductionin Vasopressor
Use if Optimizedwith EGDT
Hold steroid useuntil the patient
has beenresuscitated and
endpoints met(6-8 hours)
Sepsis is a Spectrum of Disease
↑↑NormalVariableImpairment oftissue O2 utilization
↑↓↑ andBNP
VariableMyocardialSuppression
Variable↑Normal↓Compensated andvasodilatory
↑↓↓VariableHypovolemia
LactateScvO2
CVPFTcPPV
MAP
Vasodilators,r-APC
Correct anemiaInotropic Therapy
VasopressorsAdrenal Dysf.
Volume
Treatment andComments
Global TissueHypoxia
InflammatoryMediators
Parillo, JClin.Invest, 1985
Ms. Peterson
• Infected foot – clostridium Perf (anaerobe)
• Lactate of 10 and oliguric
• BNP -3467
• BUN-77 and creatinine 4.3
• CXR
• Ultrasound
Sepsis is a Spectrum of Disease
↑↑ ↑NormalVariableImpairment oftissue O2 utilization
↑↓↑VariableMyocardialSuppression
Variable↑Normal↓Compensated andvasodilatory
↑↓↓VariableHypovolemia
LactateScvO2
CVPFTcPPV
MAP
Vasodilators,r-APC
Correct anemiaInotropic Therapy
VasopressorsAdrenal Dysf.
Volume
Treatment andComments
Venous Hyperoxia in Sepsis
Pope, Annals of Emerg Med, 2009
< 70% 70 - 90% > 90%
Developing a sepsis quality improvement programis not as painful as it appears!
TimelyInterventionsUpon Arrival
24 hourBundle
Recognizingone has aproblem?
6 hourBundle
Early Stagingof IllnessSeverity
DefinitiveCare
ED or ICU?
ImprovedOutcomesAnd Costs
QualityAssurance
CMEandPeer
Uniformity
Understandingthe
Pathogenesis
Early Markers
Epidemiology
Current SepsisManagement
3 Conceptsof
Teams
DocumentationAnd Orders
The Devil is in the Details of a Sepsis Program
Documentation andStandard Operating Procedures
Early Sepsis Intervention SavesHospital Costs
54.336 Billion
183% Increaseover 8 years
20% Reduction in Sepsis Related CostsOr
$10 Billion of the $500 Billion inNational Health Care Savings
Roberta Mooney
Sepsis Coordinator at HFHS
DailyAssessment of
all admittedsepsis patients
Feed back to allclinicians
MonthlyMeetings andReports for allICU’s and ED
EGDT after a DecadeNEJM, 2001
Mo
rtali
ty%
Pre-EGDT Control EGDT
51%46%
30%
November 8, 2001
2009
2008
November, 2009
6125 Before
16-18%Mortality Reduction
0 10 20 30 40 50
Rivers, 2001Gao, 2005
Sebat, 2005Kortgen, 2006Shapiro, 2006
Trzeciak, 2006Micek, 2006
Shu-Min Lin, 2006Qu, 2006
Nguyen, 2007Chen, 2007
Jones, 2007Sebat, 2007
El Sohl, 2007Zubrow, 2008Zambon, 2008
Focth, 2009Moore, 2009
Puskarich, 2009Castellanos-Ortega, 2010
Cardoso, 2010Lefrant, 2010Crowe, 2010
Abstracts (4298 Patients)
Absolute Risk Reduction
5328 Before
0.0 2.5 5.0 7.5 10.0
Abstracts
Publications
Rivers, 2001
Number Need To Treat
1 of every 6Patients
Abstracts and Publications
5125 Before 4328 After
Which component of the sepsisbundle actually works?
The Future of SepsisManagement
What should I target formy next septic patient?
Lactate,Cultures, Antibiotics
Source ControlEGDT, r-APC
Vasopressin
Steroids
Norm GlycemicControl
Tight GlycemicControl