Resuscitation Of a Patient with Cerebral Ischemia

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Anesthesia Management . Resuscitation of a patient with cerebral Ischemia

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  • Dr.Sudhakar.B, Associate Professor, Dept of Anaesthesia, DrPSIMS & RF, CHINOUTAPALLI.

  • Definition The perfusion of brain insufficient to provide supply of O2 & nutrients needed for maintenance of neuronal integrity and neuronal function

    Normal CMRO2 - 5.5 ml / 100 gm / min Neuronal function utilises 55% - 60% (3.3 ml / 100 gm / min)

    Neuronal integrity utilises 40% - 45% ( 2.2 ml / 100 gm / min)

  • Types ( 1 ) Global Cerebral ischemia - Complete No CBF Seen in cardiac arrest Most vulnerable regions of brain -hippocampus , Cerebral cortex - Incomplete - CBF Seen in hypotension, shock

    ( 2 ) Focal Cerebral ischemia occlusion of a single cerebral artery

  • availability of O2 & glucose ATP depletion Anaerobic metabolism of glucose lactate ischemic damage free radical formation Lipid peroxidation of cell membranes release of excitatory neurotransmitters Neuronal cell death immediate delayed( 24 72 hrs ) NMDA NMDA Influx of Ca+2, Na+ , Cl- , H2O Ca+2 influx Cellular edema phospholipases Cell membrane lysis proteases Cell death Free radical & FFA Cell death

  • Cytosolic Ca+2 due to ATP - Failure of Na+/ K+ ATP ase ion pump intracellular Na+ & Cl- extracellular K+ -Influx of H2O -Cellular edema -Membrane depolarisation -Opening of voltage sensitive Ca+2 channels. ATP -Failure of plasma membrane Ca+2 ATP ase pump Ca+2 pumping out of cell ATP - activity of Ca+2 ATP ase pump in endoplasmic reticulum (which Ca+2 in cytosol & in endoplasmic reticulum NMDA receptor mediated opening of Ca+2 channels Loss of Na+ gradient , an energy source of Na+ Ca+2 exchanger which pumps Ca+2 out

  • Ca+2 phospholipases A,A2,C mitochondrial Ca+2 proteases (calpains) Hydrolysis of membrane mitochondrial dysfunction Phospholipids & damage essential protein FFA release breakdown PG , LT cerebral edema TxA2 platelet aggregation damage ischemia Free radicals lipid peroxidation Mitochondrial & cell membrane damage

  • APOPTOSIS NECROSIS- Milder ischemia - more severe ischemia-Primary form of cell death in penumbra primary form of cell death in the coreOrderly programmed cell death, requires energy - cell disintegration -Can be modulated & reversed - cant be reversed

  • CLINICAL ASPECTS OF ISCHEMIA Most vulnerable part brain

    Loss of consciousness within 15 sec of cardiac arrest

    Brain phosphocreatine to low levels in 1 minute

    ATP , Glucose to low levels in 4 5 minutes

    Critical CBF 18 20 ml /100 gm / minIsoelectric CBF 15 ml / 100 gm / minMetabolic Failure CBF 10 ml / 100 gm / min

    Critical CPP 50 mm Hg

    Critical PaO2 30 -35 mm Hg in healthy awake

  • PATIENTS WHO WOULD BENEFIT FROM CEREBRAL PROTECTION Patients who require resuscitation from cerebral ischemic damage

    ICU patients who have non operative TBI (traumatic brain injury) such as DAI (diffuse axonal injury) with ICP and with cerebral edema and candidates for barbiturate coma

    Patients who have had cardiac arrest with re establishment of circulation

    Neonatal birth asphyxia

    Reyes syndrome and cerebral edema with ICP

    Near drowning victims who have anoxic encephalopathy cerebral edema intracranial hypertension

  • Non hemorrhagic stroke patients who may be candidates for fibrinolytic therapy and rtPA

    Patients who are at risk for cerebral ischemia and reperfusion Injury

    Patients with intracranial volume from tumour, abscess, hematoma, hydrocephalus, chronic cystic fluid collections ICP posted for neurosurgery

    Patients scheduled for intracranial vascular procedures such as cerebral aneurysm coiling or clipping, excision of AVMs & cavernous angioma extracranial vascular procedures such as CEA ( carotid endarterectomy ), superficial temporal artery MCA bypass

    Patients scheduled for clipping / coiling of giant / complex basilar artery aneurysms

  • CPB ( cardio pulmonary bypass patients ) at risk for global ischemia from low flow states focal ischemia from multiple small emboli

    Patients who are at risk for cardio embolic strokes Patients with AF ( atrial fibrillation )

    Patients who are at risk for AF ( > 1 risk factor ) - - CHF ( congestive heart failure ) with EF < 35 % or FS ( fractional shortening ) < 25 - Hypertension - Age 75 years - DM ( diabetes mellitus )

  • CLINICAL CEREBRAL PROTECTIONAvoid hyperthermia

    Avoid hyperglycemia & hypoglycemia AVOID GLUCOSE CONTAINING SOLUTIONS unless the patient is hypoglycaemic or at risk for hypoglycaemia

    Current recommendation is to keep serum glucose < 150 mg / dl

  • Avoid hypoxia & hypercarbia

    Avoid hypotension

    SBP < 90 mm Hg or MAP < 70 mm Hg or CPP < 50 mm Hg

    Prompt correction of acidosis & electrolyte imbalance

    Avoid high hematocrit and hypercoagulated state

    hemodilution to hematocrit of 32% - 34% CBF by

    viscosity & improving O2 delivery

    but excessive hemodilution O2 carrying capacity of blood

  • Normalisation of ICP

    - Head elevation to 30 in neutral position - Mannitol 0.5-1 gm / kg - Furosemide 0.25 0.5 mg / kg diuresis - Limited fluid restriction to maintain normal CVP - Moderate hyperventilation to PaCO2 of 25 30 mm Hg - CSF drainage via ventriculostomy - Barbiturate coma in patients unresponsive to these

  • RECOMBINANT TISSUEPLASMINOGEN ACTIVATORThe only recognised treatment to improve outcome in ischemic stroke

    It should be given to patients within 3 hours of onset of ischemic stroke ( class 1, level of evidence A )

    Recent update says that it can be given in a few subset of patients upto 4.5 hours after onset of symptoms ( class 1, level of evidence B )

  • CRITERIA FOR DETERMINATION OF PATIENTS ELIGIBILITY FOR rtPA

    Diagnosis of ischemic stroke causing measurable neurologic deficit

    The neurological signs shouldnt be minor & isolated and shouldnt be clearing spontaneously

    Symptoms of stroke shouldnt be suggestive of SAH

    Caution in patients who has major deficits

    No history of previous intracranial haemorrhage

  • No arterial puncture at a major non compressible site in previous 7 days

    No major surgery in the previous 14 days

    No gastrointestinal / genitourinary haemorrhage in the previous 21 days

    No myocardial infarction or head trauma or prior stroke in the previous 3 months

    B.P. < 185/110 mm Hg

    Blood glucose > 50 mg/dl

  • No evidence of active bleeding or acute trauma (fracture) on examination

    Not taking an oral anticoagulant or if anti coagulation is taken, INR 1.7 for 3 hours window

    If heparin is taken in the previous 48 hours, normal aPTT is must

    Platelet count > 1,00,000/cc

    No seizures with post ictal residual neurologic deficits

    CT doesnt show multi lobar infarction (hypodensity > 1/3 of cerebral hemisphere)

  • Additional exclusion criteria for patients eligible for rtPA between 3 and 4.5 hours

    Patients older than 80 years

    All patients receiving oral anticoagulants irrespective of INR

    Baseline NIH (National Institute of Health ) Stroke Scale Score > 25 Patients with history of both stroke & diabetes

  • Recommended Regimen for rtPA

    i.v. rtPA 0.9 mg/kg ( maximum dose 90 mg ) over 60 minutes 10% of the dose as bolus over 1 minute

  • Admit the patient to an ICU/ITU/stroke unit for monitoring

    Perform neurologic assessment every 15 minutes during infusion every 30 minutes thereafter for next 6 hours every 60 minutes till 24 hours after treatment

  • Measure the B.P. every 15 minutes for the first 2 hours every 30 minutes for the next 6 hours every 60 minutes till 24 hours after treatment the frequency of B.P. measurements if SBP > 180 mm Hg / DBP > 105 mm Hg give anti hypertensive drugs to maintain B.P. at these levels

  • Discontinue the infusion, if the patient develops severe headache acute hypertension nausea / vomiting and obtain an emergency CT scan

    Delay insertion of nasogastric tubes / indwelling bladder catheters / intra arterial pressure catheters

    Obtain a follow up CT scan at 24 hours before starting to administer anti coagulants or anti platelet drugs

  • HYPOTHERMIA Mild - 32C - 35C Moderate - 26C - 32C Deep - 18C 25C

  • Temperature Coefficient (Q10 )

    The factor by which CMRO2 changes for every 10C change in temperature Q10 between 37C & 27C 2.2-2.4 between 27C & 17C 5 between 17C & 7 C 2.2-2.4

    For each C in body temperature, CMRO2 by 7%

  • Mechanism of neuroprotection in CMRO2 Delayed ischemic / anoxic depolarisationMetabolism downregulationPreservation of ion homeostasis Ca+2 influx excitatory amino acid releasePreservation or reduction of damaging secondary biochemical changesPreservation of protein synthesis & blood brain barrierPrevention of lipid peroxidation in edema formationNeuroprotection of white matterModulation of inflammatory response & apoptotic cell death

  • At present mild hypothermia is recommended only forPost cardiac arrest survivorsNeonatal birth asphyxia which has shown improved survival rates & neurologic outcomes

  • Induced hypothermia after TBI, stroke, CPB, intracranial aneurysm surgery may have beneficial effects for both ICP & neuroprotection, but clinical trials didnt justified its use in these circumstances

    A subset of patients has shown more responsive to therapeutic hypothermia in clinical trials - age < 45 years - severe TBI with GCS 4-7 on admission - ischemic stroke when given with re establishment of cerebral perfusion

  • Deep hypothermic circulatory arrest ( 18C - 25C ) is useful in certain situations - repair of complex congenital heart disease - adult thoracic aortic aneurysm surgeries - giant / complex intracranial aneurysm surgeries

  • Complications of Hypothermia

    1.Cardiovascular complications - myocardial depression - dysrhythmia including ventricular fibrillationhypotension - inadequate tissue perfusion- ischemia

    2.Coagulation

    - thrombocytopenia - fibrinolysis - platelet dysfunction - bleeding3.Metabolism

    - slowed metabolism of anaesthetic agents - neuromuscular blockade - protein catabolism

    4.Shivering

    - O2 consumption - CO2 production - cardiac output - arterial O2 desaturation - hemodynamic instability

  • ANAESTHETICS & ADJUVANT DRUGSIntravenous Anaesthetics

    Barbiturates used for treating cerebral edema that doesnt respond to other approaches

    also indicated for ICP / seizures unresponsive to other treatment

  • TPS

    in CMRO2 upto 55% - 60% CMRO2 more than CBFAlso CBV & ICPpreserves CO2 reactivity

    Inverse Steal Phenomenon

    dosage 3-5 mg/kg every 5-10 min Upto total of 15-20 mg/kg for EEG burst suppression

    Caution avoid hypotension Large doses causes duration of action

  • the extent of cerebral injury in focal ischemia in animal models

    Not shown to improve outcome after global ischemia from cardiac arrest

  • Protective mechanisms

    GABA agonismFree radical scavenging membrane lipid peroxidation & damageNMDA antagonismCa+2 channel blockadeMaintenance of protein synthesis

  • PROPOFOL

    2,6 di iso propyl phenol

    CBF more than CMRO2 (possible direct vasoconstriction) thus ICP

    more hemodynamic suppression than barbiturates So maintain MAP & CPP

    caution while using hyperventilation

    causes minimal interference with electrophysiologic monitoring ( SSEP , MEP , BAEP ) So it is a favourable anaesthetic in neurosurgery

  • ETOMIDATE

    Short acting imidazole

    CMRO2 by 50%,CBF & ICPCO2 reactivity preservedMaintains cardiovascular stability and CPP

    Causes adrenocortical suppression for upto 24 hours by inhibition of 11 hydroxylase

    Also may cause myoclonic activity & seizures

    Experimental studies showed that brain infarct size occurs in some cases

  • BENZODIAZEPINES CMRO2 & CBF but slight in ICPpreserves CO2 reactivity inhibitory GABA neurotransmissionalso has anticonvulsant, amnestic & anxiolytic propertiesCaution for avoiding excessive sedation in patients at risk for ICP due to hypoventilation induced hypercapnia DEXMEDETOMIDINE Sedative, analgesic, anxiolytic, & sympatholyticno respiratory depression MAC for inhalational anestheticsfound to be neuroprotective in animal models of focal ischemiaalso found to CBF without altering CMRO2 ,which is not observed in humans

  • KETAMINE - a phencyclidine derivative - CBF, thus ICP But unchanged or slight in CMRO2 - abolishes autoregulation - a non competitive NMDA receptor antagonist.

    LIDOCAINE - Na+ channel blocker - at low conc. it CMRO2 At higher conc. it causes seizures After pentobarbital induced isoelectric EEG , CMRO2 by another 15%-20% - blunts hemodynamic response & ICP response to intubation - improved neurologic recovery in animals No human trials proved it - 1.5 mg/kg- ischemic damage in animals Inconsistent human studies

  • INHALATIONAL ANESTHETICS Cerebrovasodilators Therefore CBF & thus ICP This is attenuated by prior hyperventilation

    CMRO2 Thus uncouples CBF & CMRO2

    Impairment of autoregulation is seen

    preserves CO2 reactivity

    Ischemic preconditioning Animal models have shown that this is due to proteins formation that damage & repair. - not induced clinically in humans

  • Nitrous oxide CBF, CMRO2 & ICP But this can be attenuated by hypocapnia, prior administration of barbiturates, opioids, benzodiazepines, propofol

    32 times more soluble in blood than N2 , so it diffuses into air containing body cavities and can enlarge an air embolus

    avoided in - Pneumocephalus - Any surgical procedure within 2 weeks of a craniotomy in which N2O was used.

  • ANTICONVULSANT DRUGS Seizures ischemic effects by in CBF, CMRO2 , intracellular Ca+2 during seizure activity

    For seizures Diazepam -2-20 mg Midazolam - 1-5 mg TPS - 25-100 mg Pentobarbital - 100 mg

  • OTHER PHARMACOLOGICAL APPROACHES Calcium channel blockers

    Nimodipine the incidence & severity of vasospasm after aneurysmal SAH By blocking Ca+2 influx into vascular smooth muscle & preventing its hypercontractionoral route only 60 mg every 4 hours for 21 daysCaution against hypotensioni.v. route should not be given because of life threatening adverse events & death

    Nicardipine i.v.form ischemic damage in animal studies but not shown benefit in clinical trials

  • Magnesium

    Ca+2 influx into cells by blocking channels & pathways in addition to blockade of voltage sensitive Ca+2 channelsBlocks neurotransmitter releaseBlocks NMDA receptors non competitively

    Has shown neuroprotection in different models of cerebral ischemiaClinical trials are underway

  • Glutamate receptor antagonists No clinical benefit has been demonstrated in human studies.

    Non competitive NMDA receptor antagonists like - Dizocilpine - Magnesium - Xenon

    Glycine binding site antagonism with - HA-966 - 7- chlorokynurenic acid

    AMPA receptor antagonism with - NBQX ( 2,3 dihydroxy 6-nitro 7-sulfanoyl benzoquinazoline )

  • Sodium channel blocking drugs - Riluzole - Lamotrigine Both es glutamate release during ischemia Clinical trials are underway

    Tirilazad - Lipid soluble 21-amino steroid - Lipid antioxidant free radical formation & lipid peroxidation - Animal studies showed protection only when given before ischemic event - No clinical studies proof

  • sFree radical scavengers - under investigation Superoxide dismutase Deferoxamine Vitamin E Mannitol Glucocorticoids Nitric oxide Erythropoeitin - Produced in brain after hypoxic or ischemic insults - Asialo EPO non hemopoeitic analog blood viscosity that doesnt exacerbate ischemic injury

  • Anaesthesia duration & depthMinimising the duration of time during which patient is deeply anesthetised may neuronal damage by attenuating neuronal apoptosis

    A growing body of evidence indicates that cumulative deep anaesthesia time is an independent predictor of post operative morbidity & mortality in adult patients

  • Thank you