DPD-3 21Jan Brain Resusitation

8/12/2019 DPD-3 21Jan Brain Resusitation

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PatofisiologiCardiopulmonary Cerebral Resuscitation

Basics For Life Support

Rita A. Sutjahjo Lab/SMF Anestesiologi

FK. Unair / RSUD Dr. SoetomoSurabaya


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Hypoventilation / apneaLow blood flow / cardiac arrest

ISCHEMIA

Reperfusion

Reoxygenation

INJURY

CPCR

neuron

Good Result


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Instructional Objective

To understand the pathophysiologic mechanismof post resuscitation syndroma

To define the ultimate potentials & limitationsof resuscitation


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Dying Cells

Metabolic changes as result of Depletion of oxygen Depletion of energy substrate

Accumulation of metabolic end products

Point of Threatening Viability

MAP < 60 - severe hypotensionPaO2 < 50 - severe hypoxaemia


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Determinan kerusakan sel karena anoksia Waktu

Sel otak 5 menitSel miokard 15 menit

50 % Myosit rusak

Fungsi pompa jantung dapat kembali

Sekelompok sel neurom area tertentu di otak rusak

Gangguan human mentation

S

S

S


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Energy deficit

Glutamate excitotoxicityIntracellular accumulation

of Ca 2+ , Acidosis

Oxidative stress Activated NO synthesis

Cytokine imbalanceLocal inflammation, microcirculationderangement

Apoptosis, Trophic dysfunction

Hours Days

3 6 12 24 3 7

Time after ischemia onset

IschemiaMinutes

Temporal development of processes inducing focalischemic brain damage


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Safar P, 1981

Post-Resuscitation Syndrome


8/34Safar P, 1993


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Reperfusion - Reoxygenation

Stage I : No reflow

II : Transient hyperemia(Acidosis Vasodilation)

5 - 10

III : Hypoperfusion30 - 60

IV : Evolution48 - 72 hrs


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Hypothetical events in the brain following total circulatory arrest

Safar P, 1981


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Bio Chemical Changes

In Re - Perfusion Injury

Tissue edema vasospasm Red cell sludging

Intracellular edema (Impaired ionic pump) Release of excitatory AA

Free radicals - lipid preoxidationCell membrane damage

Intracellular Ca overload S


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DecreasedCBF

Tissue ATPfalls

Failure ofenergy-dependent

processes

Sodium influxPotassium efflux

Calcium influx

Cellswelling

Neuronaldepolarization

Glutamaterelease

StimulatesNMDAreceptors

Calcium entry

Opens VSCCs

Activating of phospholipases, calpains, gene expression etc

Cascade of early biochemical events occurring during an ischaemic episodeBaillieres Clinical Anaesthesiology -Vo.10.No.3 September 1996


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Pathway for events linking cerebral

ischemia-reperfusion to cellular injury


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cAMPcGMP

Free radicalproduction

Lipidperoxidation

DNAdamage

Energydepletion

Ca2+ /CAMkinase

PKC

NO synthase

PLA 2

Calpains

Depolarization AMPA

NMDA

m

GLUG

PLC

Na+

Na+

(a)

Ca2+

Ca2+

Ca2+

stores

VOCC

Celldeath

GLUT

AM ATE

Role of Glutamate in Excitotoxic Neuroral Injury


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O2 supply < O 2 demand

synthesis ATP

ATP stores

sodium pumps

Na+ influxK + efflux

Membrane depolarization

Opening of coltage-sensitiveCa2+ channels

Opening of NMDA receptor-controlled Ca 2+ channels

Release of glutamate

Massive influx of Ca 2+ Activation of phospholipases Amitochondrial accumulation

Activation of proteasesHydrolysis of membranephosphollipids

FFA arachidonic acid

prostaglandins

Uncoupling of oxidativephosphorylation

Free radicals

Irreversible cell membrane damage

Vascular damage

Lipid peroxidation

Glutamate A mediator of neuronal

damage during ischemia

Cell Injury occurred duringischemia reperfusion


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Components Contribute To

Ultimate Cell Damage

Ischemic component

Severity

Duration

Re - Perfusion component

Biochemical changes


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No injury Treatment window Beyond treatment

Reperfusioncomponent

Cell death

Reversibleinjury

No injury

TIME

C e

l l I n

j u r y


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Out come after CPCR

Pre insult derangement

Duration & type of primary insult

Post oxygention syndroma


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Target Organs

Lung

Heart

Nervoussystem

Clinical Conditions

Acute respiratory distresssyndrome

AsthmaReperfusion pulmonary edema

Acid aspirationPulmonary oxygen toxicity

Acute myocardial infarctionReperfusion injury due to :

AngioplastyCardioplegiaCoronary occlusionThrombolysis

StrokeTraumatic brain injuryPostresuscitation injurySpinal cord injury

Comments

The lung is vulnerable to oxidantinjury from the airways (e.g.high inspired O 2) and from themicrocirculation (e.g.WBCsequestration).Protection from O 2 is aided by highlevels of glutahione and vitamin C

in the epithelial lining of the lowerairways.Oxidants most likely play a rolein the stunned myocardium associated with reperfusion injury

Lipid peroxidation is a prominentform of oxidant injury in thebrain and spinal cord. Steroidsthat inhibit lipid peroxidation are

being evaluated for nervous systemsinjury

Clinical Conditions That Are Accompanied By Oxidant Stress*


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Target Organs

Gastroinstestinaltract

Kidney

Multiple organs

Clinical Conditions

Drug-indused mucosal injuryIntestinal ischemiaPeptic ulcer disease

Acute renal failure due to AminoglycosidesIschemia

Myoglobinuria

Cardiopulmonary bypassMultiple organ dysfunctionsyndromeMultisystem traumaPostresuscitation injurySeptic shockThermal injury

Comments

The gut is susceptible to reperfusioninjury, possibly due to the abundanceof xanthine dehydrogenase (a source ofO2 during ischemia) in the bowel wallHydrogen peroxide and iron may haveimportant roles in oxidant injuryinvolving the kidneys.

Inflamation is a common source ofoxidant production in theseconditionsNitric oxide may promotehypotension in septic shock.

Agents that inhibit nitric oxideproduction are being evaluated inseptic shock (Ann Phamacother1995;29;36-46).

..clinical conditions that are accompanied by oxidant stress

* Includes only conditions that are prevalent in ICU patients


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Improved outcome depend on,

1. By stander CPR response time 800 victim(Cardiac arrest in BRCT I & II, Peter Safar)

1. Long duration of arrest & resuscitation effort poor neurologicoutcome

2. After restoration of heart beat, high arterial reprefussionpressure good cerebral recovery

3. Cardiac arrest without CPR > 5 irreversible brain damage

4. Advanced aged mortality

worse neurologic outcome

5. Steroid improved neurologic outcome after cardiac arrest

S

S

S


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When not to start

Terminal stage of incurable disease

CPR A s/d F

Prolonged life support ?

Based on cardiac d eath (Heart cannot be restarted despite max effortat leas 30 minute)

When in doubt

When to stop

Brain death certified After 24 hr. extracerebral organ stabilization

Cardio Pulmonary Cerebral Resuscitation


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Drugs block reperfusion injury

Calcium entry blockers

Excitatory amino acid neurotransmitter antagonists

Free radical scavengers

Antagonists to the arachidonic acid cascade

Steroid ( inhib i t l ip id perox idat ion o f cel l m emb ranes) ?


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Exclusion of reversible CNS depression Absence of hypothermia

Absence of drugs (e.g. ethanol, barbiburates) Absence of metabolic perturbations that could potentiate CNS depression

(e.g. abnormalities in electrolytes, osmolarity, serum ammonia,creatinine, hypercarbia, hypoxemia)

Clinical criteria for brain death certification

Absent cortical function

Unresponsiveness to painfull stimuliNo spontaneous muscular movements

(in the absence of muscle relaxants)no posturing, shivering, or sezure activity

(in the absence of musle relaxants)

Absent brainstem functionPupils nonreactive and fixed to lightNo corneal reflexesNo gag or cough reflexesNo oculocephalic reflexes

No oculovestibular reflexes


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Organ blood flow measurements utilizing radioactive mecrospheres in a rodentmodel of cardiac arrest. Precordial compression was initiated 4 minutes afterinduction of ventricular fibrillation. Spontaneous circulation was successfully restoredby external transthoracic countershock in 5 of 10 animals after 9 minutes

of ventricular fibrillation.


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Blood flow generated as a function of depth of compression during closed-chestresuscitation in 8 dogs. Cardiac output (CO) is represented as a fraction of thecardiac output generated at a compression depth of 5 cm.


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DPD-3 21Jan Brain Resusitation

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