2nd world congress on biomarker's and clinical research
DESCRIPTION
2nd world congress on biomarker's and clinical research 2011 - baltimore - usa - turkey 13.09.2011TRANSCRIPT
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THERAPEUTIC HYPOTHERMIA
FOR POSTRESUSCITATION
SYNDROME AND LACTATE
LEVELS
Sule AKIN, Assoc.Prof, MD
Baskent University School of Medicine
Anesthesiology and Critical Care Department
Adana - TURKEY
2nd
World Congress on BIOMARKERS & CLINICAL RESEARCH
Baltimore, Maryland , USA. – 13 September 2011
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THERAPEUTIC
HYPOTHERMIA
LACTATE
LEVELS
POST
RESUSCITATION
SYNDROME
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THERAPEUTIC
HYPOTHERMIA
LACTATE
LEVELS
POST
RESUSCITATION
SYNDROME
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POST
RESUSCITATION
SYNDROME (PRS)
POST
CARDIAC ARREST
SYNDROME
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Cardiac
arrest
ROSC (+)
25%
ROSC (-)
75 %
Recovery
7%
PRS
18%
Alive
3%
Dead
15%
ROSC: Return Of Spontaneous Circulation
Estimated ratios of cardiac arrest patients
(< 4 min)
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Resuscitation after cardiac arrest : a 3-phase
time-sensitive model
Weisfeldt ML. JAMA 2002
No Flow Low Flow Post-CPR
ROSCCardiacArrest
CPR
Electrical
phase
0 – 4 min
Circıulatory
phase
4 – 10 min
Metabolic
phase
> 10 min
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Severe Global
IschemiaReperfusion
Multiple
Organ
Failure
SYSTEMIC INFLAMMATORY
RESPONSE SYNDROME (SIRS)
PRS
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ISCHEMIA
Blockage Muscle
Blood
flow
ischemia
O2
Ca+2
Necrosis
Apoptosis
Cell Death
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Ischemia
Mitochondrian
Oxidative phosphorylation
Extracellular
Ca+2
Injurious agent
MitochondrionEndolasmic
reticulum
Injcreased cytosolic Ca+2
ATPase Phospholipase Protease Endonuclease
Decreased
ATP
Decreased
phospholipids
Disruption of
membrane
and cytoskeletal
proteins
Nucleus
chromatin
damage
Membrane damage
Ca+2
Ca+2
Ca+2
Ca+2
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Necrosis
Apoptosis
Cell Death
Inflammation
REPERFUSION
Clot Dissolution
Flow Restoration
Oxidative Stress
Mitochondrial Resp. Chain
NAD(P)H Oxidases
Nitric Oxide Synthesas
O2-, H2O2
-, OH
-, NO, ONO O
-
O2
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• Ischemia and reperfusion syndrome
• Inflammatory response
• Coagulopathy
• Circulatory failure
• Adrenal dysfunction
Current Opinion in Crit Care. 2004
ut
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Systemic Ischemia
and
Reperfusion
Cardiovascular
and
Neurologic
Dysfunction
MODS
CONCLUSION
SIRS
Death Recovery
PRS-MODS
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61%
23%
10%3%
3%
Proceedings of the ATS 2007;4:A792
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BRAIN INJURY DUE TO PRS
Causes:
- Limited tolerence to ischemia
- Specific response to reperfusion
OUT -OF-
HOSPITAL
CPR
23%
IN-
HOSPITAL
CPR
68%
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Totally
Awakeness
Cognitive
Dysfunction
Vegetative
State
Cortical/
Spinal
Stroke
Seizure/
Myoclonus
Coma
Brain
Death
CLINICS
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WHAT WILL WE DO
AFTER THE CRISIS
(CPR) ENDS?
POST CPR
INTENSIVE CARE
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Common intensive care
protocols
Sedation and neuromuscular
blockade
Monitorisation Seizıre control and propylaxis
Early hemodynamic
optimisation
GLUCOSE control
Oxygenation Neuroprotection by drugs
Ventilation Adrenal dysfunction treatment
Circulatory support Renal failure management
Acute Coronary Syndrome
management
Infection control
PRS- TREATMENT STRATEGIES
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Common intensive care
protocols
Sedation and neuromuscular
blockade
Monitorisation Seizıre control and prophylaxis
Early hemodynamic
optimisation
GLUCOSE control
Oxygenation Neuroprotection by drugs
Ventilation Adrenal dysfunction treatment
Circulatory support Renal failure management
Acute Coronary Syndrome
management
Infection control
PRS- TREATMENT STRATEGIES
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THERAPEUTIC HYPOTHERMIA
Common intensive care
protocols
Sedation and neuromuscular
blockade
Monitorisation Seizıre control and propylaxis
Early hemodynamic
optimisation
GLUCOSE control
Oxygenation Neuroprotection by drugs
Ventilation Adrenal dysfunction treatment
Circulatory support Renal failure management
Acute Coronary Syndrome
management
Infection control
PRS- TREATMENT STRATEGIES
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Hyperthermia
Hypotension
Hypocapnia
Hypercapnia
Hypoxemia
Hypothermia
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THERAPEUTIC
HYPOTHERMIA
LACTATE
LEVELS
POST
RESUSCITATION
SYNDROME
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HYPOTHERMIA
• Body Temperature < 35 C (95 F)
MILD
HYPOTHERMIA
32-35 C 90 -95 F
MODERATE
HYPOTHERMIA
28-32 C 82-90 F
SEVERE
HYPOTHERMIA
20-28 C 68-82 F
PROFOUND
HYPOTHERMIA
< 20 C < 68 F
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THERAPEUTIC HYPOTHERMIA
(TH)
Low Blood Flow
Tissue Ischemia
THERAPEUTIC
HYPOTHERMIA
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TH INDICATIONS IN CLINICS
• Cardiopulmonary Resuscitation
• Traumatic Brain Injury
• Cerebral Infarct
• Encephalitis / Bacterial Menengitis
• Hepatic Encephalopathy
• Heart Failure
• Postoperative tachicardia
• ARDS
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P
E
T
E
R
S
A
F
A
R
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Airway
Breathe
Circulate
Drugs
E.C.G.
Fluids
Gauge
Hypothermia
Intensive Care
1961
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Anesthesia and Analgesia
1959 38(6);423- 428
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TH - MECHANISMS
HYPOTHERMIA
Metabolic rate
1 C
CMRO2
6 %
Oxygen
consumption
reperfusion
ischemia
Glutamate
release
Calcium
shifts
Mitocondrial
disfunction
Free oxygen
radicals
Exotoxicity
Inflammation
cascade
CELL DEATH
BBB Impairment
Brain Edema
Neurol Clin 2008;22:487-506
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THE CHAIN OF SURVIVAL
Resuscitation 2005: 67S1;3-6
Circulation 2005: 112; 206-211
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Out-of-hospital CPR, VF
First 6 hours, 32-34 C
For 12-24 hours
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European Resuscitation Council Guidelines for Resuscitation2010 Section 1. Executive summaryJerry P. Nolana, Jasmeet Soarb, David A. Zidemanc, DominiqueBiarentd, Leo L. Bossaerte, Charles Deakinf, Rudolph W. Kosterg, Jonathan Wyllieh, Bernd Böttigeri, on behalf of the ERC Guidelines Writing Group1
Therapeutic HypothermiaThere is good evidence supporting the use of induced hypothermia in comatose survivors of out-of-hospital cardiac arrest caused by VF. One randomised trial and a pseudorandomised trial669demonstrated improved neurological outcome at hospital discharge or at 6 months in comatose patientsafter out-of-hospital VF cardiac arrest. Cooling was initiated within minutes to hours after ROSC and atemperature range of 32–34 ◦C was maintained for 12–24 h. Two studies with historical control groupsshowed improvement in neurological outcome after therapeutic hypothermia for comatose survivors ofVF cardiac arrest. Extrapolation of these data to other cardiac arrests (e.g., other initial rhythms, in-hospital arrests, paediatric patients) seems reasonable but is supported by only lower level data.
Out-of-hospital CPR, In –hospital CPR
VF, PVT, Asistoly, PEA
First 6 hours, 32-34 C
For 12-24 hours
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POST
RESUSCITATION
SYNDROME
LACTATE
LEVELS
THERAPEUTIC
HYPOTHERMIA
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GLUCOSE
Pyruvate
Oxygen (-)
(anaerobic)
Oxygen (-)
(anaerobic)
Acetyl CoA
CO2 + H
2O
Oxygen (+)
(aerobic)
PPK
LDHPDH
2 Lactate2 Ethanol + H2O
KREB’S
Cycle
2 ATP
36 ATP
GLYCOLYSIS
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GLUCOSE
Pyruvate
Oxygen (-)
(anaerobic)
Oxygen (-)
(anaerobic)
Acetyl CoA
CO2 + H
2O
Oxygen (+)
(aerobic)
PFK
LDHPDH
2 Lactate2 Ethanol + H2O
2 ATP
36 ATP
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PRS
Ischemia
Low blood
flow
Low oxygen
supply
Less removal of
lactic acid
/CO2/protons
Reperfusion
Rapidly
removal of
extracellular
protons and
CO2 BLOOD
LACTATE
LEVELS
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TH
Peripheral
vasoconstruction
Low blood
flow
Low oxygen
supply
BLOOD
LACTATE
LEVELS
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MY
CLINIC’S
EXPERIENCE
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MY CLINIC’S EXPERIENCE
• Lactate ;
• Retrospective investigation
• 63 resuscitated patient
• Group I (n=33) ; TH administered patients
for 24 hours (32-35 C)
• Grouıp II (n=30) ; No TH
A predictor of neurologic outcome?
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MY CLINIC’S EXPERIENCE
• Initial cardiac arres t rhythms
• ICU admission times
• Initial and after 24 hours Glasgow Coma
Scales (GCS) and Cerebral Performance
Categories (CPC)
• Lactate
• AST, ALT
• BUN, Creatinine
Levels at
1st, 3rd, 6th, 12th,
18th, 24th hours
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Cerebral Performance Categories
(CPC) Scale
CPC 1 Good cerebral performance: conscious, alert, able to
work, might have mild neurologic or psychologic deficit.
CPC 2 Moderate cerebral disability: conscious, sufficient
cerebral function for independent activities of daily life. Able to
work in sheltered environment.
CPC 3 Severe cerebral disability: conscious, dependent on
others for daily support because of impaired brain function.
Ranges from ambulatory state to severe dementia or paralysis.
CPC 4 Coma or vegetative state: any degree of coma without
the presence of all brain death criteria. Unawareness, even if
appears awake (vegetative state) without interaction with
environment; may have spontaneous eye opening and
sleep/awake cycles. Cerebral unresponsiveness.
CPC 5 Brain death: apnea, areflexia, EEG silence, etc.
Safar P. Brain Failure and Resuscitation
Churchill Livingstone, New York, 1981; 155-184
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MY CLINIC’S EXPERIENCE
Demographical
findings
Comparable
Initial
rhythms
Comparable
Renal and hepatic
functions
Insignificant
differences (p>0.05)
Neurologic outcomes
(GCS CPC)
Better in Group I
(p<0.05)
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MY CLINIC’S EXPERIENCE
DURATION
AFTER CPR
GROUP I
(n=33)
GROUP II
(n=30)
1st
hour 4.8 1.2 4.7 1.2
3rd
hour 4.8 1.0 4.8 1.1
6th
hour 3.9 0.9 4.3 0.9
12th
hour 3.2 0.9 3.6 0.8
18th
hour 2.6 1.0 3.0 1.1
24th
hour 2.1 0.7 2.7 1.1
Blood Lactate Levels
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MY CLINIC’S EXPERIENCE
DURATION
AFTER CPR
GROUP I
(n=33)
GROUP II
(n=30)
1st
hour 4.8 1.2 4.7 1.2
3rd
hour 4.8 1.0 4.8 1.1
6th
hour 3.9 0.9 4.3 0.9
12th
hour 3.2 0.9 3.6 0.8
18th
hour 2.6 1.0 3.0 1.1
24th
hour 2.1 0.7 2.7 1.1
Blood Lactate Levels
MY CLINIC’S EXPERIENCE
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22/08/2011 02/09/2011
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MY CLINIC’S EXPERIENCE
• Significant decrease s in lactate levels on
targeted temperature times (6th hours) were
associated with good outcomes of
neurological status
(CPC 1 and CPC 2)
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SUMMARY
POST RESUSCITATION SYNDROME is a problem caused
by ishemia-reperfusion injury after CPR
Besides “Intensive Care” protocols, THERAEPEUTIC
HYPOTHERMIA is one of the best strategy for PRS
TH does not only improve neurologic outcome but also
helps to cure other organ functions
LACTATE is recommended to follow up as a biomarker
of good neurologic outcome during TH for PRS
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AT THE END OF THE WORDS…
THE TEAM OF CPR AND PRS
GETS UP ON STAGE…
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“I’m afraid you’ll have to go back down.
You’ve been resuscitated….”
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Blood Lactate Analyzer