This PPT is part of a lecture given to second year pharmacy students in a pharmacology & toxicology class.

1. Agents for Traumatic Brain
Injury
Brian J. Piper, Ph.D., M.S.
piperbj@husson.edu
February 15, 2013

2. Objective
• Pharmacy students should be familiar with
different pharmacotherapies used with brain
injury including their:
– mechanisms of action
– relative efficacy
– adverse effects

3. falls motor-vehicle/assaults falls/motor-vehicle
Burns & Hauser (2003) Epilepsia, 44(S10), 2-10.

4. Individual Differences following TBI
apoE4+ (N=27) apoE4- (N=42)
Unconscious for >1 week 77.8% 38.1%*
Dysarthria 63.0% 33.3%*
Overall Function: excellent 3.7% 31.0%*
* p < .05
Friedman et al. (1999). Neurology, 52(2), 244-250.

5. Secondary Injury
• All brain damage does not occur at the
moment of impact (primary injury) but
evolves over the ensuing hours and days
(secondary injury).
• The injured brain is extremely vulnerable to
hypotension, hypoxia, and increased
intracranial pressure which are causes of
secondary injury.

6. ↓ Blood Pressure: Tx-Dopamine
• MOA: D1 > α1
• Effects: ↑ systolic bp

7. Intra-Cranial Pressure
• There is only one way out of the intracranial vault, the
opening at the base of the skull: foramen magnum

8. ↑ Intracranial Pressure: Tx-Mannitol
• History: sugar derivative of mannose-1961
• Frequency: majority of trauma centers
• Effect:
– immediate ↓ ICP; withdrawal ↑ ICP
– renal failure
Grande & Romner (2012). J Neurosurg, 24(4), 407-412.

9. Mannitol versus Hypertonic Saline
->
Vialet et al. (2003). Critical Care Medicine, 36, 795-800.

10. Mannitol versus Hypertonic Saline
Vialet et al. (2003). Critical Care Medicine, 36, 795-800.

11. ↑ Intracranial Pressure: Tx-
Barbiturates
• Indications:
– ↑ ICP refractory to other treatments
• Frequency: minority of trauma centers
• Rationale:
– ↓ neuron activity ↓ metabolic demands
– ↓ free radical formation
• Effect:
– immediate ↓ ICP; hypotension (25%)
Roberts & Sydenham (2012). Cochrane Database of Systematic Reviews, 10.1002/14651858.CD000033.pub2.

12. Absence of evidence ≠
Evidence of absence
• “There is insufficient reliable evidence to
make recommendations on the use of
mannitol in the management of patients with
traumatic brain injury.”
• “There is no evidence that barbiturates
improve outcomes in people with acute brain
injury.”
Wakai et al. (2008). Cochrane Database of Systematic Reviews, 10.1002/14651858.CD001049.pub4.
Roberts & Sydenham (2012). Cochrane Database of Systematic Reviews, 10.1002/14651858.CD000033.pub2.

13. Propofol Factoids

14. Propofol
• Indication: hypnotic (not analgesic)
• MOA:
– GABAA agonist
– NMDA antagonist
– ↓ glutamate release
– ↓ excitotoxicity/antioxidant
• General: consistent, rapid loss (& recovery) of
consciousness, amnesic, excellent safety margin
• Other ingredients: egg phosphatate & edetate
disodium (EDTA)
Example 0:35 to 1:20: http://www.youtube.com/watch?v=kmMFLOXLD-Q
Kotani et al. (2008). CNS Neuroscience & Therapeutics, 10.1111/j.1527-3458.2008.00043.x

15. Propofol Infusion Syndrome
• Combination
– critically ill children + long-term/high-dose propofol
– catecholamines or steroids too
• Symptoms:
– rhabdomyolasis
– renal/cardiac failure
Vasile et al. (2003). Intensive Care Medicine, 29, 1417-1425.

16. Memory
• ------------------------|----------------------------
trauma
• Anterograde Memory: propofol decreases
memory of events that happen post-trauma
• Retrograde Memory: propofol increases
memory of events that occur pre-trauma

17. Passive Avoidance
Day 1: Training
Drug
Day 3: Test
Hauer et al. (2011). Anesthesiology, 114(6), 1380 – 1388.