Cerebral Protection

1. Cerebral Protection British Journal of Anaesthesia 99(1): 10-17 (2007) R3 이동현

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 -> reduce energy requirement -> 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 -> reduce cerebral blood volume -> offset increase of ICP • But, hyperventilation-induced vasoconstriction in ischemic tissue -> worsening of perfusion -> 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