2nd world congress on biomarker's and clinical research

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

THERAPEUTIC

HYPOTHERMIA

LACTATE

LEVELS

POST

RESUSCITATION

SYNDROME

THERAPEUTIC

HYPOTHERMIA

LACTATE

LEVELS

POST

RESUSCITATION

SYNDROME

POST

RESUSCITATION

SYNDROME (PRS)

POST

CARDIAC ARREST

SYNDROME

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)

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

Severe Global

IschemiaReperfusion

Multiple

Organ

Failure

SYSTEMIC INFLAMMATORY

RESPONSE SYNDROME (SIRS)

PRS

ISCHEMIA

Blockage Muscle

Blood

flow

ischemia

O2

Ca+2

Necrosis

Apoptosis

Cell Death

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

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

• Ischemia and reperfusion syndrome

• Inflammatory response

• Coagulopathy

• Circulatory failure

• Adrenal dysfunction

Current Opinion in Crit Care. 2004

ut

Systemic Ischemia

and

Reperfusion

Cardiovascular

and

Neurologic

Dysfunction

MODS

CONCLUSION

SIRS

Death Recovery

PRS-MODS

61%

23%

10%3%

3%

Proceedings of the ATS 2007;4:A792

BRAIN INJURY DUE TO PRS

Causes:

- Limited tolerence to ischemia

- Specific response to reperfusion

OUT -OF-

HOSPITAL

CPR

23%

IN-

HOSPITAL

CPR

68%

Totally

Awakeness

Cognitive

Dysfunction

Vegetative

State

Cortical/

Spinal

Stroke

Seizure/

Myoclonus

Coma

Brain

Death

CLINICS

WHAT WILL WE DO

AFTER THE CRISIS

(CPR) ENDS?

POST CPR

INTENSIVE CARE

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

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

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

Hyperthermia

Hypotension

Hypocapnia

Hypercapnia

Hypoxemia

Hypothermia

THERAPEUTIC

HYPOTHERMIA

LACTATE

LEVELS

POST

RESUSCITATION

SYNDROME

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

THERAPEUTIC HYPOTHERMIA

(TH)

Low Blood Flow

Tissue Ischemia

THERAPEUTIC

HYPOTHERMIA

TH INDICATIONS IN CLINICS

• Cardiopulmonary Resuscitation

• Traumatic Brain Injury

• Cerebral Infarct

• Encephalitis / Bacterial Menengitis

• Hepatic Encephalopathy

• Heart Failure

• Postoperative tachicardia

• ARDS

P

E

T

E

R

S

A

F

A

R

Airway

Breathe

Circulate

Drugs

E.C.G.

Fluids

Gauge

Hypothermia

Intensive Care

1961

Anesthesia and Analgesia

1959 38(6);423- 428

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

THE CHAIN OF SURVIVAL

Resuscitation 2005: 67S1;3-6

Circulation 2005: 112; 206-211

Out-of-hospital CPR, VF

First 6 hours, 32-34 C

For 12-24 hours

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

POST

RESUSCITATION

SYNDROME

LACTATE

LEVELS

THERAPEUTIC

HYPOTHERMIA

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

GLUCOSE

Pyruvate

Oxygen (-)

(anaerobic)

Oxygen (-)

(anaerobic)

Acetyl CoA

CO2 + H

2O

Oxygen (+)

(aerobic)

PFK

LDHPDH

2 Lactate2 Ethanol + H2O

2 ATP

36 ATP

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

TH

Peripheral

vasoconstruction

Low blood

flow

Low oxygen

supply

BLOOD

LACTATE

LEVELS

MY

CLINIC’S

EXPERIENCE

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?

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

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

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)

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

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

22/08/2011 02/09/2011

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)

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

AT THE END OF THE WORDS…

THE TEAM OF CPR AND PRS

GETS UP ON STAGE…

“I’m afraid you’ll have to go back down.

You’ve been resuscitated….”

Blood Lactate Analyzer