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Fundamental questions
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Transcript of Fundamental questions
Fundamental questions
How does the brain damage occur? Can we select at risk patients? What therapies do we have? How do they work? What is the side effect? What is the risk –benefit picture?
CBF & CPP
CBF-50ml/100g/min -750ml/min – 15-20% CO
20-25 ml/100g/min – cerebral impairment
15-20 ml/100g/min - isoelectric EEG
<10 ml/100g/min - irreversible damage
CPP = MAP – ICP : 80-100 –normal
<50 – slowing EEG ,cerebral impairment
25 - 40 – Flat EEG
<25 - irreversible damage
CBF &Variables
CBF depends on, PaCO2 (20-80mmHg)-1-2 ml/100g/min
/mmHg
T- 5-7%change/ 1 change
PaO2 <50 mmHg CBF
0
Cerebral protection -Strategies
Optimize CPP Decrease CMR Block the mediators of cell injury
- at ischemic cascade
- at reperfusion cascade
Protective techniques
Brain Shrinkage Hyperventilation Optimize CPP Appropriate BP
Hypothermia Decrease CMR Burst suppression
Pharmacological protectors -Block the mediators of cell injury
Pharmacological intervention
CMR Reduction Barbiturates: Decreases CMR
Decreases Ca+
Decreases OFR
Na+ channel blockade
Decreases Glucose entry
Decreases refractory ICP
Inverse steal blood flow
Pharmacological intervention
CMR Reduction Propofol, Etomidate Morphine, Fentanil, Sufentanil,
Remifentanil Diazepam, Midazolam Ketamine, Dexmedetomidine Halothane, Enflurane, Isoflurane,
Sevoflurane, Desflurane
Pharmacological intervention
Neuronal injury protectorsA} pre synaptic level- SNX III –Ca+ blocker
B} post synaptic level1.Na+ blocker- All volatile anaesthetic agents -Barbiturates -Lamotrigine - Riluzole -Lubeluzole2. Ca+ blocker -Nimodipine -Nicardipine
3.NMDA antagonists: Competitive blocker-Selfotel Non Competitive blocker-Dizoclypine -Dexromethorphan -ketamine
Pharmacological intervention
4.Glycine site analogues-felbamate, Licostinel
5.NO synthase inhibitors –lifarizine, 7nitroindazole
6.Mg+-Ca+ blockade, NMDA antagonist
7.steroids-anti inflammatory action, ?neuronal protection
-MPS, Tirilazad
8.OFR scavengers- Vit-E, PBN{phenyl derbuyl nitrone},
Tirilazad,Mannitol
9.Cytokinin inhibition-TNF Receptor I, TNF alfa mab
10. Anti adhesion molecule Ab