Patofisiologi

Cardiopulmonary Cerebral Resuscitation Basics For Life Support

Rita A. Sutjahjo
Lab/SMF Anestesiologi FK. Unair / RSUD Dr. Soetomo Surabaya

Hypoventilation / apnea Low blood flow / cardiac arrest

neuron

ISCHEMIA
Reperfusion CPCR Reoxygenation Good Result
INJURY

Instructional Objective

To understand the pathophysiologic mechanism of post resuscitation syndroma

To define the ultimate potentials & limitations

of resuscitation

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 hypotension PaO2 < 50 - severe hypoxaemia

Determinan kerusakan sel karena anoksia Sel otak Sel miokard 50 % Myosit rusak

Waktu 5 menit 15 menit

Fungsi pompa jantung dapat kembali

Sekelompok sel neurom area tertentu di otak rusak

Gangguan human mentation

S S

Energy deficit

Glutamate excitotoxicity Intracellular accumulation of Ca2+, Acidosis

Oxidative stress Activated NO synthesis Cytokine imbalance Local inflammation, microcirculation derangement

Apoptosis, Trophic dysfunction

Ischemia Minutes
Hours Days

12

24

Time after ischemia onset

Temporal development of processes inducing focal ischemic brain damage

Post-Resuscitation Syndrome

Safar P, 1981

Safar P, 1993

Reperfusion - Reoxygenation Stage I II : No reflow : Transient hyperemia (Acidosis Vasodilation)

5 - 10

III

: Hypoperfusion

30 - 60 48 - 72 hrs

IV

: Evolution

Hypothetical events in the brain following total circulatory arrest

Safar P, 1981

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 preoxidation Cell membrane damage Intracellular Ca overload S

Cascade of early biochemical events occurring during an ischaemic episode

Baillieres Clinical Anaesthesiology-Vo.10.No.3 September 1996

Decreased CBF

Tissue ATP falls

Failure of energy-dependent processes

Glutamate release

Neuronal depolarization

Sodium influx Potassium efflux Calcium influx

Stimulates NMDA receptors

Opens VSCCs

Cell swelling

Calcium entry

Activating of phospholipases, calpains, gene expression etc

Pathway for events linking cerebral ischemia-reperfusion to cellular injury

Role of Glutamate in Excitotoxic Neuroral Injury

VOCC G L U T A M A T E Depolarization
AMPA
Na+ Ca2+

Ca2+/CAM kinase PKC

Free radical production Lipid peroxidation DNA damage Energy depletion

(a)

NMDA

Na+ Ca2+ PLC

cAMP cGMP

NO synthase PLA2
Ca2+ stores

Cell death

m G GLU

Calpains

O2 supply < O2 demand synthesis ATP ATP stores sodium pumps Na+ influx K+ efflux Membrane depolarization Opening of coltage-sensitive Ca2+ channels Release of glutamate

Cell Injury occurred during ischemia reperfusion

Glutamate A mediator of neuronal damage during ischemia

Opening of NMDA receptorcontrolled Ca2+ channels Massive influx of Ca2+ Activation of proteases

Activation of phospholipases Hydrolysis of membrane phosphollipids FFA

Amitochondrial accumulation Uncoupling of oxidative phosphorylation Free radicals Vascular damage

arachidonic acid

prostaglandins

Irreversible cell membrane damage

Lipid peroxidation

Components Contribute To Ultimate Cell Damage

Ischemic component Severity Duration

Re - Perfusion component
Biochemical changes

Cell death

Cell Injury

Reversible injury

Reperfusion component

No injury No injury Treatment window Beyond treatment

TIME

Out come after CPCR Pre insult derangement Duration & type of primary insult Post oxygention syndroma

Clinical Conditions That Are Accompanied By Oxidant Stress*

Target Organs Lung Clinical Conditions Acute respiratory distress syndrome Asthma Reperfusion pulmonary edema Acid aspiration Pulmonary oxygen toxicity Comments The lung is vulnerable to oxidant injury from the airways (e.g. high inspired O2) and from the microcirculation (e.g.WBC sequestration). Protection from O2 is aided by high levels of glutahione and vitamin C in the epithelial lining of the lower airways. Oxidants most likely play a role in the stunned myocardium associated with reperfusion injury

Heart

Acute myocardial infarction Reperfusion injury due to : Angioplasty Cardioplegia Coronary occlusion Thrombolysis Stroke Traumatic brain injury Postresuscitation injury Spinal cord injury

Nervous system

Lipid peroxidation is a prominent form of oxidant injury in the brain and spinal cord. Steroids that inhibit lipid peroxidation are being evaluated for nervous systems injury

..clinical conditions that are accompanied by oxidant stress

Target Organs Gastroinstestinal tract Kidney Clinical Conditions Drug-indused mucosal injury Intestinal ischemia Peptic ulcer disease Acute renal failure due to Aminoglycosides Ischemia Myoglobinuria Cardiopulmonary bypass Multiple organ dysfunction syndrome Multisystem trauma Postresuscitation injury Septic shock Thermal injury Comments The gut is susceptible to reperfusion injury, possibly due to the abundance of xanthine dehydrogenase (a source of O2 during ischemia) in the bowel wall Hydrogen peroxide and iron may have important roles in oxidant injury involving the kidneys. Inflamation is a common source of oxidant production in these conditions Nitric oxide may promote hypotension in septic shock. Agents that inhibit nitric oxide production are being evaluated in septic shock (Ann Phamacother 1995;29;36-46).

Multiple organs

* Includes only conditions that are prevalent in ICU patients

Improved outcome depend on,

1. By stander CPR response time <

2. Early advanced cardiac life support restoration of spontaneous circulation 3. Intensive care Preventing secondary neurologic insult

Extra cranial homeostasis

Myocardial Blood Flow

100
75 % 50 25 0 0/58 <15 15-20 CPP, mm Hg Coronary perfusion pressure (CPP) during closed-chest resuscitation in out-of-hospital victims of cardiac arrest. Paradis NA, 1990 >20 Out-of-Hospital Cardiac Arrest 100 Pts 10/23

14/19

Mean PETCO2 during closed-chest resuscitation in 35 human victims of cardiac arrest. Sanders AB, 1989

Data base > 800 victim (Cardiac arrest in BRCT I & II, Peter Safar)

1. Long duration of arrest & resuscitation effort outcome

poor neurologic

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 S

5. Steroid improved neurologic outcome after cardiac arrest

Cardio Pulmonary Cerebral Resuscitation When not to start Terminal stage of incurable disease When in doubt CPR A s/d F Prolonged life support ? When to stop Based on cardiac death (Heart cannot be restarted despite max effort at leas 30 minute) Brain death certified After 24 hr. extracerebral organ stabilization

Drugs block reperfusion injury Calcium entry blockers

Excitatory amino acid neurotransmitter antagonists

Free radical scavengers

Antagonists to the arachidonic acid cascade

Steroid (inhibit lipid peroxidation of cell membranes) ?

Clinical criteria for brain death certification

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)

Absent cortical function

Unresponsiveness to painfull stimuli No 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

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

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