THERAPEUTIC HYPOTHERMIA FOR POSTRESUSCITATION SYNDROME AND LACTATE

LEVELS

Sule AKIN, Assoc.Prof, MDBaskent University School of Medicine

Anestehsiology and Critical Care DepartmentAdana - TURKEY

2nd World Congress on BIOMARKERS & CLINICAL RESEARCH Baltimore, Maryland , USA. – 13 September 2011

THERAPEUTIC HYPOTHERMIA FOR POSTRESUSCITATION SYNDROME AND LACTATE

LEVELS

Sule AKIN, Assoc.Prof, MDBaskent University School of Medicine

Anestehsiology and Critical Care DepartmentAdana - TURKEY

HYPOTHERMIA

• Body Temperature < 35 C

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• Herat Failure• Postoperative tachicardia• ARDS

Airway

Breathe

Circulate

Drugs

E.C.G.

Fluids

Gauge

Hypothermia

Intensive Care

1961

TH - MECHANISMSHİPOTERMİ

Metabolic rate

1 C CMRO2 6 %

Oxygen consumption

Glutamate release

Calcium shifts

Mitocondrial disfunction

Free oxygen

radicals

Exotoxicity

Inflmmation

cascade

CELL DEATH

BBB Impairment

Brain EdemaNeurol Clin 2008;22:487-506

Anesthesia and Analgesia 1959 38(6);423- 428

N Engl J Med 2002 Feb 21;346(8):557-63Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia.Bernard SA, Gray TW, Buist MD, Jones BM, Silvester W, Guttridge G, Smith K.

N Engl J Med 2002 Feb 21;346(8):549-56Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest.Hypothermia after Cardiac Arrest Study Group (HACA).

Resuscitation 2001 Dec;51(3):275-81Mild hypothermia induced by a helmet device: a clinical feasibility study.Hachimi-Idrissi S, Corne L, Ebinger G, Michotte Y, Huyghens L.

CHAIN OF SURVIVAL

“Chain of Survival Concept”

Circulation 83: 1832-1847, 1991Resuscitation 46: 29-71, 2000

CHAIN OF SURVIVAL

Out-of-hospital CPR, VF First 6 hours, 32-34 C

For 12-24 hours

CHAIN OF SURVIVAL

European Resuscitation Council Guidelines for Resuscitation 2010 Section 1. Executive summaryJerry P. Nolana, Jasmeet Soarb, David A. Zidemanc, Dominique Biarentd, Leo L. Bossaerte, Charles Deakinf, Rudolph W. Kosterg, Jonathan Wyllieh, Bernd Böttigeri, on behalf of the ERC Guidelines Writing Group1Therapeutic HypothermiaThere is good evidence supporting the use of induced hypothermia in comatose survivors of out-of-hospital cardiac arrest caused by VF. One randomised trial704 and a pseudorandomised trial669 demonstrated improved neurological outcome at hospital discharge or at 6 months in comatose patients after out-of-hospital VF cardiac arrest. Cooling was initiated within minutes to hours after ROSC and a temperature range of 32–34 ◦C was maintained for 12–24 h. Two studies with historical control groups showed improvement in neurological outcome after therapeutic hypothermia for comatose survivors of VF cardiac arrest.705–707 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

TH – TO WHOM WE CAN’T APPLY?• Awake patients

• Myoclonus, status epilepticus

• Severe coagulopathy and active bleeding

• Haemodynamic instability

• Resistant arrhythmia

• Septic shock

• Delayed cases ( >12 hours)

• Suspicious intracranial hemorrhage

• Pregnancy

TH – ADVERSE EFFECTS

CARDIVASCULAR HEMATOLOGIC IMMUNOLOGIC METABOLIC

- Arrhythmia -Platelet dysfunction

-Coagulopathy

-Neutrophil dysfunction

- Infection

-Hypocalemia

-Hyperglisemia

-İleus

- Pancreatitis

• Increases due to cooling duration and intensity

POSTRESUSCITATION

SYNDROME (PRS)

POST CARDIAC ARREST

SYNDROME

SYSTEMIC INFLAMMATORY RESPONSE SYNDROME (SIRS)

PRS

Cardiac arrest

ROSC (+)25%

ROSC (-) 75 %

Recovery 7%

PRS18%

Alive 3%

Dead15%

ROSC: Return Of Sontaneous Circulation

İSKEMİ

Blockage Muscle

Blood flow

ischemia

O2

Ca+2Necrosis

Apoptosis

Cell Death

Necrosis

Apoptosis

Cell Death

Inflammation

REPERFUSION

Clot DissolutionFlow Restoration

Oxidative Stress

Mitochondrial Resp. ChainNAD(P)H OxidasesNitric Oxide Synthesas

O2- , H2O2-, OH-, NO, ONO O-

O2

Mitokondri

İskemi

EkstrasellülerCa +2

Mitokondri

Hasar verici ajan

Endoplazmik retikulum

Artmış sitozolik Ca +2

ATPaz Fosfolipaz Proteaz Endonükleaz

ATP’de azalma

Fosfolipidlerde azalma

Membran ve sitoskletal

proteinlerde parçalanma

Nükleus kromatin

hasarı

Membran hasarı

PRS- TREATMENT STRATEGIES

PRS- TREATMENT STRATEGIES

Trombocyte activation(Trombosis + Vasoconstruction)

Metabolism Changes(ATP lost)

Tissue injury

REPERFUSION (REOXYGENATION)

PAF+TTB4

Free radicals

Lipid peroxydation Endotel injury Chemotacytic factors

Neutrophil accumulationDegredation of

membrane integrity

Fagocytosis

Leucocyte

plug O2

radicals Ischemia

NO Adhesion molecules

Compleman activation

PGI2 TXA2 LTB4

Cytokines IL-1 IL-6

Vasoconstruction, thrombocyte aggregation, neutrophil chemotaxis

Ischemia/Reperfusion Injury

GLUCOSE

PyruvateOxygen (-)(anaerobic)

Oxygen (-)(anaerobic)

Acetyl CoA

CO2 + H2OOxygen (+)(aerobic)

PFK

LDHPDH

2 Lactate2 Etanol + H2O

KREB’S Cycle

2 ATP

36 ATP

GLUCOSE

PyruvateOxygen (-)(anaerobic)

Oxygen (-)(anaerobic)

Acetyl CoA

CO2 + H2OOxygen (+)(aerobic)

PFK

LDHPDH

2 Lactate2 Etanol + H2O

2 ATP

36 ATP

THERAPEUTIC HYPOTHERMIA FOR POSTRESUSCITATION SYNDROME AND LACTATE

LEVELS

Sule AKIN, Assoc.Prof, MDBaskent University School of Medicine

Anestehsiology and Critical Care DepartmentAdana - TURKEY