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Neurologic and histopathologic evaluation after high-volume intrathecal amitriptyline
Yukari Sudoh1, Sukumar P Desai, Anna E Haderer
1Department of Anesthesiology, Brigham and Women's Hospital, Boston, MA 02115, USA.
Regional Anesthesia and Pain Medicine
|September 17, 2004
Summary
Intrathecal amitriptyline can provide long-acting spinal block at lower doses but causes irreversible nerve damage at higher concentrations. Due to its narrow therapeutic index, intrathecal amitriptyline is not recommended for pain management.
Area of Science:
- Neuroscience
- Pharmacology
- Anesthesiology
Background:
- Amitriptyline is known to reduce pain via various administration routes.
- Intrathecal amitriptyline studies have shown inconsistent results.
- High lipophilicity (logP) of amitriptyline may limit its spread in cerebrospinal fluid.
Purpose of the Study:
- To evaluate spinal block effects of various intrathecal amitriptyline concentrations.
- To assess the safety and efficacy of high-volume intrathecal amitriptyline.
Main Methods:
- Rats received 100 microL of varying amitriptyline hydrochloride concentrations (5–100 mmol/L) or bupivacaine intrathecally.
- Neurologic deficits were assessed via antinociceptive, motor, and proprioceptive responses.
- Spinal cords were examined for histopathologic changes.
Main Results:
- Higher amitriptyline doses (15.9 and 25 mmol/L) produced longer nerve blocks than bupivacaine.
- Lower amitriptyline doses (5 and 10 mmol/L) resulted in only partial nerve block.
- High-dose amitriptyline (50 and 100 mmol/L) led to incomplete recovery and severe axonal/myelin damage.
Conclusions:
- Low-dose, high-volume intrathecal amitriptyline provides prolonged spinal block.
- High-dose intrathecal amitriptyline causes irreversible neurological deficits.
- Intrathecal amitriptyline has a very narrow therapeutic index and is not recommended.