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/ 3 rd Hour and thereon

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