Cerebral Protection

1
Cerebral Protection

• British Journal of Anaesthesia 99(1) 10-17
  (2007)
• R3 ???

2
Background

• Cerebral ischemia/hypoxia can occur in a variety
  of perioperative circumstances.
• Outcomes range from sub-clinical neurocognitive
  deficits to catastrophic neurological morbidity
  or death.
• Neuroprotection
• Treatment initiated before onset of ischemia
• Neuroresuscitation
• Treatment begun after the ischemic insult
• Currently available interventions

3
Anesthetics

• Suppress neurotransmission -gt reduce energy
  requirement -gt better to preserve energy balance
  during transient interruption of substrate
  delivery
• Barbiturates
• Overall potency as neuroprotective agents is weak
  in severe ischemic insults
• Optimal protection only when massive doses were
  administered to abolish EEG activities and
  maximal suppression of cerebral metabolic
  rate(CMR)

4
Anesthetics

• Volatile anesthetics
• Protect against both focal and global ischemia
• Transient improvement in global ischemia
• Persistent improvement in focal ischemia
• Suppression of energy requirements
• Inhibition of excitatory neurotransmission
• Potentiation of inhibitory receptors
• Regulation of intracellular calcium response
  during ischemia
• Activation of TREK-1 two-pore-domain K channels
• Isoflurane, sevoflurane largest data
• Desflurane insufficiently studied

5
Anesthetics

• Propofol
• Suppression of CMR
• Free radical scavenging
• Anti-inflammatory properties
• Appears efficacy similar to barbiturates
• Etomidate
• Paradoxically exacerbate ischemic injury
• Cannot use for neuroprotection
• Lidocaine
• Suppress CMR
• Inhibition of apoptosis
• No long-term outcome studies
• Ketamine
• Inhibition of glutamate at NMDA receptor
• Little or no protection against global insult
• Substantial protection against focal insult
• However, no human data

6
Temperature

• Hypothermia
• Reduce CMR in a temperature-dependent fashion
• Mild hypothermia(32-35?) negliable effect on
  CMR
• But, in several studies mild hypothermia produce
  major protection provides scientific basis of
  using off-bypass hypothermia to provide
  meaningful neuroprotection
• Deep hypothermia(18-22?) highly neuroprotective
• In normothermic brain only a few minutes of
  complete global ischemia cause neuronal death
• In deep hypothermia before circulatory arrest
  brain can tolerate over 40 min and completely or
  near-completely recover

7
Temperature

• Traumatic brain injury (TBI)
• In large-scale prospective human trial, cooling
  TBI patients within the first several hours after
  injury failed to improve outcome
• But in later studies, hypothermic group of
  comatose survivors of out-of-hospital cardiac
  arrest had more patients with good outcome than
  normothermic group
• Therefore comatose survivors of out-of-hospital
  cardiac arrest is recommended to undergo cooling
  after restoration of spontaneous circulation
• Some trials reported beneficial effect of
  hypothermia in peripartum neonatal asphyxial
  brain injury either selective head cooling or
  total body cooling

8
Temperature

• Hyperthermia
• In animal studies, spontaneous post-ischemic
  hyperthermia is common and intra-ischemic or
  even delayed post-ischemic hyperthermia
  dramatically worsen outcome
• Advocate frequent temperature monitoring in
  patients with cerebral injuy
• Aggressive treatment of hyperthermia should be
  considered

9
Glucose

• Fundamental substrate for brain energy metabolism
• Deprivation of glucose result in neuronal
  necrosis
• In the absence of oxygen, glucose undergoes
  anaerobic glycolysis resulting in intracellular
  acidosis
• Patients with higher blood glucose concentrations
  have worse outcomes from stroke, TBI, etc.
• More rapid expansion of ischemic lesion in
  hyperglycemic, compared with normoglycemic
  patients
• For all of this reasons, it is rational to
  maintain normoglycemia in all patients at risk
  for ,or recovering from acute brain injury

10
Arterial carbon dioxide partial pressure(PaCO2)

• Cerebral blood flow and PaCO2 are linearly
  related
• Reduction in PaCO2 -gt reduce cerebral blood
  volume -gt offset increase of ICP
• But, hyperventilation-induced vasoconstriction in
  ischemic tissue -gt worsening of perfusion -gt
  markedly increased volume of ischemic tissue
• Clinical trials have found no benefit from
  induced hypocapnia
• Consequently, there ara few data to support use
  of hyperventilation in cerebral resuscitation

11
Arterial oxygen partial pressure

• Reperfusion presents deranged oxygen metabolism
• Formation of reactive oxygen species
• Induce secondary insults
• One retrospective perinatal resuscitation
  analysis worse long-term outcome in children
  when hyperoxemia or hypocapnia was present during
  resuscitation or early recovery
• Rapid normalization of Apgar scores with 40
  oxygen VS 100 oxygen during resuscitation
• Maintain pulse oximeter value 94-96 optimized
  short-term neurological outcome

12
Steroids

• Reduce edema surrounding brain tumors
• Insufficient evidence to define the role of
  steroids in focal ischemic stroke
• Large retrospective analysis no benefit from
  steroid in patients with cardiac arrest
• In animal studies, steroids exacerbate injury
  from global ischemia by increasing plasma glucose
  concentration

13
Conclusion

• Two key advances in the past decade
• Mild hypothermia reduces neurological morbidity
  and mortality with out-of-hospital ventricular
  fibrillation cardiac arrest.
• Efficacy of mild hypothermia depends on the type
  of ischemia could not be shown to be effective
  in trauma and focal ischemia
• Other practices rests on animal studies and weak
  clinical trials
• Recommendations for perioperative ischemic insult