Ketamine in Brain Injury by Toby Jeffcote
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Historically, when it came to brain injury, ketamine had a bad rap. Much of that dogma was dispelled in the last decade, and ketamine is now frequently used as an induction agent in acute brain injury, especially traumatic brain injury, due to it’s favorable effects on haemodynamics. However a new application of ketamine is now being explored - whether ketamine may be able to reduce secondary brain injury.
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Ketamine in Brain Injury by Toby Jeffcote
- 2. Toby Jeffcote 22 March 2023 Ketamine in acute brain injury New tricks for an old dog?
- 3. What is the evidence for sedation in brain injury? Ketamine sedation in acute brain injury
- 4. Ketamine sedation in acute brain injury
- 5. Limited evidence Ketamine sedation in acute brain injury
- 6. Ketamine sedation in acute brain injury
- 7. • Sedative and analgesic • Racemic mix or enantiomer • Rapid distribution large Vd • Context sensitive half time 50 minutes at 8 hrs • Accumulates in renal/hepatic failure • Cystitis • Contra-indicated in unstable angina Ketamine - pharmacokinetics Ketamine Ketamine sedation in acute brain injury
- 8. Potential benefits of Ketamine Ketamine sedation in acute brain injury
- 9. Potential benefits of Ketamine • Sedative and analgesic sparing • Alternative mechanism of action to GABA agonists • Cardiovascular stability from infusion and bolus • Potential for amelioration of excitotoxic secondary brain injury Ketamine sedation in acute brain injury
- 10. • NMDA receptor • Glutamate/depolarisation mediated opening • Ca2+ influx - cell death signalling Excitotoxic neuronal injury Ketamine sedation in acute brain injury
- 11. • Repeated waves of Glutamate mediated mass depolarisation of cortical tissue • Occur abundantly in TBI/SAH/Ischaemic and Haemorrhagic stroke • Associated with poor outcome in TBI • Release high volumes of Glutamate - ?vehicle of excitotoxic brain injury • Cause tissue stress, vasoconstriction, local hypoglycaemia Cortical Spreading Depolarisation Dreier J (2011) The role of spreading depression, spreading depolarisation and spreading ischaemia in neurological disease. Nature Medicine Vol. 17 (4) 439-447
- 12. Cortical spreading ischaemia Ketamine sedation in acute brain injury
- 13. Ketamine and CSD
- 14. Why is Ketamine not in widespread use? Ketamine sedation in acute brain injury
- 16. Does Ketamine increase ICP?
- 18. • Ketamine sole anaesthetic agent in healthy volunteers • PET scans • Regional increase cerebral blood flow and net increase • Regional increase CMRO2 - nil net increase • Regional increase in GMR - nil net increase Ketamine and cerebral haemo-dynamics Ketamine sedation in acute brain injury
- 19. Ketamine sedation in acute brain injury
- 20. Does Ketamine raise ICP? Ketamine sedation in acute brain injury
- 22. Are NMDA antagonists safe in brain injury? Ketamine sedation in acute brain injury
- 23. • Multiple studies in late 1990’s early 2000’s - novel agents e.g. MK-801 • Mixed results • Methodological issues • Animal studies - paradoxical excitotoxicity, blocking Glutamate mediated repair • Concurrent GABA agonists NMDA antagonists in acute neurological injury Ketamine sedation in acute brain injury
- 24. Ketamine sedation in acute brain injury
- 26. Does Ketamine increase delirium? Ketamine sedation in acute brain injury
- 28. Where to from here?
- 29. Ketamine in Brain Injury (KIBI) • Pilot feasibility study - 1mg/kg/hr, safety efficacy, feasibility, ICP, auto regulation • Multi-centre feasibility study • Larger trial of sedatives in TBI and SAH