perioperative cerebral protection dr. s. parthasarathy md., da., dnb, md (acu), dip. diab.dca, dip....
DESCRIPTION
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 !!TRANSCRIPT
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