210650767 DPD 3 21Jan Brain Resusitation

8/12/2019 210650767 DPD 3 21Jan Brain Resusitation

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PatofisiologiCardiopulmonary Cerebral Resuscitation

Basics For Life Support

Rita A. Sutjahjo

Lab/SMF AnestesiologiFK. Unair / RSUD Dr. Soetomo

Surabaya


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Hypoventilation / apnea

Low blood flow / cardiac arrest

ISCHEMIA

Reperfusion

Reoxygenation

INJURY

CPCR

neuron

Good Result


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Instructional Objective

To understand the pathophysiologic mechanism

of post resuscitation syndroma

To define the ultimate potentials & limitationsof resuscitation


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Dying Cells

Metabolic changes as result ofDepletion of oxygenDepletion 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

SS


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Energy deficit

Glutamate excitotoxicityIntracellular accumulation

of Ca2+, Acidosis

Oxidative stressActivated NO synthesis

Cytokine imbalanceLocal inflammation, microcirculation

derangement

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 edemavasospasm

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

TissueATPfalls

Failure ofenergy-dependent

processes

Sodium influxPotassium effluxCalcium influx

Cellswelling

Neuronaldepolarization

Glutamaterelease

StimulatesNMDA

receptors

Calcium entry

OpensVSCCs

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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O2supply < O2demand

synthesis ATP

ATP stores

sodium pumps

Na+influxK+efflux

Membrane depolarization

Opening of coltage-sensitiveCa2+channels

Opening of NMDA receptor-controlled Ca2+channels

Release of glutamate

Massive influx of Ca2+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

GlutamateA 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

Cell

Injury


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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 distresssyndromeAsthmaReperfusion pulmonary edemaAcid aspirationPulmonary oxygen toxicity

Acute myocardial infarctionReperfusion injury due to :

AngioplastyCardioplegiaCoronary occlusion

Thrombolysis

StrokeTraumatic brain injuryPostresuscitation injurySpinal cord injury

Comments

The lung is vulnerable to oxidantinjury from the airways (e.g.high inspired O2) and from themicrocirculation (e.g.WBCsequestration).Protection from O2is aided by highlevels of glutahione and vitamin C

in the epithelial lining of the lowerairways.Oxidants most likely play a rolein the stunned myocardiumassociated 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 toAminoglycosidesIschemia

Myoglobinuria

Cardiopulmonary bypassMultiple organ dysfunctionsyndromeMultisystem traumaPostresuscitation injury

Septic shockThermal injury

Comments

The gut is susceptible to reperfusioninjury, possibly due to the abundanceof xanthine dehydrogenase (a source ofO2during 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 neurologic

outcome

2. After restoration of heart beat, high arterial reprefussion

pressure 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 death

(Heart cannot be restarted despite max effort

at 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 ipid perox idat ion o f cel l memb 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 function

Pupils nonreactive and fixed to light

No corneal reflexes

No gag or cough reflexes

No 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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210650767 DPD 3 21Jan Brain Resusitation