Perioperative cerebral protection Dr. S. Parthasarathy

MD., DA., DNB, MD (Acu), Dip. Diab.DCA, Dip. Software

statistics,Phd (physio)Mahatma Gandhi Medical college and research

institute , puducherry , India

What is it ??

• Neuroprotection • Before the ischemic insult

• Neuro resuscitation – • After the ischemic insult

• Planning an insult = perioperative

After the primary insult

• We have restored perfusion but ??

• apoptosis and inflammation, inhibition of protein synthesis, sustained oxidative stress, and neurogenesis continues !!

• Post ischemic interventions !!

Why should the insult occur ??

Deprivation of oxygen, glucose or both

Some physiology

• CBF = CPP/CVR

• CPP = MAP – ICP • Brain + blood + CSF = same =

MK doctrine

Who needs ??

Indications

1. SOL with or without increased ICP – Neuro surgery

2. Intracranial vascular procedures,

3. extracranial vascular procedures including carotid

endarterectomy (CEA) and superficial temporal

artery to middle cerebral artery (STA-MCA) bypass,

which involve temporary vessel occlusion and the

possibility of focal ischemia.

– for the clipping or coiling of giant or complex

basilar artery aneurysms,

– deep hypothermic circulatory arrest (DHCA).

– Cardiac bypass patients

– Patients who have had a cardiac arrest with

circulation reestablished within 2 hours.

Pharmacological nonpharmacological

Clinical therapies

Nonpharmacological

• Temperature • Hypothermia has been proposed to offer

therapeutic benefit for more than 60 yr• But later put into disuse by studies • But those studies did not induce hypothermia

early • Till further studies , use hypothermia

Hypothermia

• neurosurgical procedures in which the brain is at risk for

ischemic insult, a goal temperature of 35 to 36°C is

reasonable.

• Mild hypothermia (33 to 35°C) may be appropriate in many

patients, even recognizing that there may be no benefit to

this therapy.

• Finally, deep hypothermia (<20°C) is appropriate in any

situation in which a prolonged cardiac arrest is required.

Glucose • No glucose worsens brain injury in the presence of oxygen

• glucose without oxygen is more dangerous ??

• May be due to anaerobic metabolism and intracellular

acidosis

• Hyperglycemia and cerebral ischemia combination deadly

• Maintain normoglycemia

• around 150 – frequent measurement

Hyperventilation

• Hypocapnia can reduce CBF, CBV, and intracranial

pressure (ICP)

• Previously thought useful.

• Probable ischemic insult because of decreased CBF??

• Refractory cerebral edema – may be helpful

• Otherwise not useful

Seizure prophylaxis

• Seizures commonly occur in patients with intracranial pathology.

• Seizure activity is associated with increased neuronal activity, increased CBF and CBV (and consequently increased ICP), and cerebral acidosis

• Prevent and treat seizures aggressively.

Arterial oxygen partial pressure• Normobaric hyperoxia • May be useful in early resuscitation times • But questions ?? • Do you need to remember this picture ??• NO

But- we need to remember this

Pharmacological

Influence of Anesthetics on an Ischemic Brain

• Barbiturates• Propofol• Ketamine• Etomidate• Volatile Anesthetics

What we want ??

• Decrease cerebral metabolism

• Cerebral blood flow increase

• Many agents do !!

Barbiturates

• In humans, thiopental loading has been demonstrated in

a single study to reduce post–cardiopulmonary bypass

neurologic deficits

• Setting of focal ischemia , barbiturates better than in

global ischemia setting

Barbiturates

• anti-oxidant or free radical scavenging actions

• reduce ischaemia induced neurotransmitter release.

• Inhibition of the release of excitatory neurotransmitters

(aspartate, taurine, glutamate & GABA) has been

demonstrated.- (reperfusion)

• Reduce CMRO2 and ICP

Thiopentone

• Loading dose consists of 25 to 50 mg/kg.

followed by an infusion 2 to 10 mg/kg/1hr to give plasma

concentration of 10 to 50 mg/L.

High dose may benefit focal ischemia

There are doses of 3- 5mg /kg doses and barbiturate induced EEG

burst suppression is maintained

Thiopentone

• Low dose in three minutes 1 mg /kg for ICP reduction

• Small bolus dose for short term protection• A dose of 4 mg/kg over 3 minutes• Temporary clamping and focal ischemia• Ten minutes prior start – 24 hours post insult

acceptable • Duration controversial 72 hours !!

Side effects of barbiturates

• Depression of cardiac output & cerebral perfusion pressure,

& even frank cardiovascular collapse in poorly hydrated

patients.

• Depression of respiration – ventilators and ICU ready

• Metabolized by liver – note liver function

• Immune depression and lung infections

• Neuro evaluation ??

High Medium and low

doses

Etomidate

• etomidate produces EEG burst suppression and reduces CMR

for glucose and oxygen.

• Clinically, etomidate decreases CBF, CMRO2 and ICP

• But no hemodynamic compromise

• Steroid suppression is insignificant because we use high dose

steroids BUT ??

• injury-enhancing effect of etomidate has been attributed to its

ability to reduce nitric oxide levels in ischemic brain tissue.

Propofol

• The metabolic changes resulting from propofol

anaesthesia closely resemble the homogenous

depression of CMR caused by barbiturates and

etomidate

• But CVS depression and hypotension and CPP

• Overall !!

• Improved cerebral perfusion and better maintenance

of autoregulation

•

Ketamine ??

• Mechanism of action of ketamine ??

• Some of the neurotransmitters is NMDA

• Hence offer protection • But not much used instead of established

agents ??

Benzodiazepines

No adverse intracranial effects • No adverse cardiopulmonary effects • Decrease CMRO2, CBF and ICP • Anesthetic sparing • Reversal

Anti seizures effect

Inhalational agents

• Isoflurane offers a similar level of metabolic

depression as barbiturates at a concentration less

likely (than barbiturates) to be accompanied by

severe cardiovascular depression or prolonged

recovery

• < 2 MAC

Inhalational agents

• GABA effects • Inhibit ischemia induced calcium influx• Inhibit glutamate induced activation. • Ischemic threshold less than with enflurane or

halothane • Both sevoflurane and desflurane decreased

cerebral insult after focal ischemia

nitrous oxide

• Some forms of cerebral protection may be adversely affected by the presence of nitrous oxide.

• Decreased barbiturate’s efficacy • Nitrous oxide decreases isoflurane’s efficacy as

a neuro protectant

No nitrous oxide

Other agents

Glucocorticoids

• High dose methyl prednisolone ( 30 mg/kg) • Inhibit lipid peroxidation • Possible uses • Spinal injury • Head injury • Cerebral vasospasm • Dangers • Infection, GI bleeding , hyperglycemia

Tirilazad mesylate

• Aminosteroid • Inhibit lipid peroxidation • Decrease vasospasms

• 6 mg /kg in divided doses • SAH and ischemic strokes

Superoxide dismutase• Superoxide anion is generated on reperfusion of post

ischaemic tissues. • It is capable of producing significant biological injury.• Superoxide dismutase (SOD) is a specific scavenger of

superoxide anion. • Because, superoxide dismutase (SOD) has a biological

half-life of only 5 minutes, it has been conjugated with polyethylene glycol (PEG-SOD) for use in humans.

• Head injury use- less vegetative states, less mannitol requirements

Nimodipine

• Calcium influx blocked • Use of nimodipine – prior to surgeries• Brain retraction

• Increases CBF as a vasodilator

Lignocaine

• Prophylactic infusion of lidocaine, substantially improved neuropsychologic outcome at 10 days, 10 weeks, and 6 months after cardiac surgeries

• 1 mg / kg • 240 mg / first hour • 120 mg/ second hour • 60 mg/ 3rd Hour and thereon

Mannitol

• Mannitol can scavenge free radicals & thus reduce tissue damage caused by superoxide radicals.

• 0.25 gm – 1 gm/kg bolus infusions • Cerebral edema decrease and ICP reduction

• Beware of sodium levels and hypovolumia

Miscellaneous drugs

• Alpha2-agonists • Aprotinin • Insulin • Papaverine • Acadesine• Tromethamine • Perflurocarbons

Chemical brain retractor concept

• This concept includes the use of a total IV

anaesthesia technique, mild hypocapnia &

mannitol with strict monitoring & maintenance

of the global cerebral homeostasis

To know ??

• Our ability to protect the brain is limited. By

contrast, our capacity to exacerbate ischemic

brain damage is limitless.

• Emphasis should be placed on maintenance of

physiologic homeostasis rather than on reliance

on pharmacologic agents to protect the brain.

The essence • Mild hypothermia • Maintain PCO2 and glucose • Barbiturates • Any agent • Maintain CPP• Don’t allow seizures

Thank you all