Loss of intrathecal morphine analgesia in terminal cancer patients is associated with high levels of excitatory amino acids in the CSF (original) (raw)

Abstract

Purpose

To examine excitatory amino acid (EAA) levels in the cerebrospinal fluid (CSF) of patients on long-term morphine treatment for terminal cancer pain relief and to correlate these with morphine’s analgesic effect.

Methods

Fourteen terminal cancer patients suffering severe pain and requiring long-term opioid treatment for pain relief were included. An intrathecal (IT) catheter was implanted at the L3–4/L4–5 level and advanced 10 cm in a cephalad direction. IT morphine injection was started at 100 μg q 12 hr with a daily incremental dose of 50 μg until the effective dose was reached. The CSF was sampled (2 mL) as follows: 1) before the first IT morphine injection, 2) when the effective dose of morphine was reached, 3) when loss of morphine’s analgesic effect at the effective dose (pain visual analogue scale > 5), and 4) after consecutive increases of the morphine dose (50 μg, IT daily) for satisfactory pain relief and up to double the effective dose. The concentrations of glutamate and aspartate in the CSF were determined.

Results

CSF levels of glutamate and aspartate at the effective dose of morphine were lower than the baseline levels and increased when pain intensity increased and when morphine’s analgesic effect was lost.

Conclusion

Long-term IT morphine administration was accompanied by an increase of EAA level in the CSF that was associated with a loss of morphine’s analgesic effect.

Résumé

Objectif

Vérifier les niveaux d’acides aminés excitateurs (AAE) dans le liquide céphalo-rachidien (LCR) de patients en traitement prolongé avec de la morphine pour soulager la douleur d’un cancer terminal et établir une correspondance avec l’effet analgésique de la morphine.

Méthode

Quatorze patients atteints de cancer terminal ressentant de vives douleurs et nécessitant un traitement prolongé avec opioïdes ont été recrutés pour l’étude. Un cathéter intrathécal (IT) a été implanté au niveau de L3–4/L4–5 et poussé de 10 cm en direction céphalique. L’injection de morphine IT a été amorcée avec 100 μg q 12 h et augmentée chaque jour d’une dose progressive de 50 μg jusqu’a l’obtention d’une dose efficace. Le LCR a été échantillonné (2 mL) comme suit : 1) avant la première injection IT de morphine, 2) quand la dose efficace de morphine a été atteinte, 3) au moment de la perte d’effet analgésique de la morphine administrée selon la dose efficace (score > 5 à l’échelle visuelle analogique) et 4) après les augmentations consécutives des doses de morphine (50 )Jg, IT, quotidiennes) nécessaires au soulagement de la douleur et jusqu’au double de la dose efficace. Les concentrations de glutamate et d’aspartate dans le LCR ont été déterminées.

Résultats

Les niveaux de glutamate et d’aspartate dans le LCR pour une dose efficace de morphine ont été plus bas que les niveaux de départ et ont augmenté avec l’intensité de la douleur et avec la perte de l’effet analgésique de la morphine.

Conclusion

Ladministration prolongée de morphine IT s’accompagne d’une hausse du niveau d’AAE dans le LCR, laquelle est associée à une perte de l’effet analgésique de la morphine.

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Authors and Affiliations

  1. Department of Anesthesiology, Tri-Service General Hospital and National Defense Medical Center, #325 Chenggung Road, Section 2, Neihu, 114, Taipei, Taiwan
    Chih-Shung Wong, Yi-Chen Chang, Chun-Chang Yeh, Go-Shine Huang & Chen-Hwan Cherng

Authors

  1. Chih-Shung Wong
  2. Yi-Chen Chang
  3. Chun-Chang Yeh
  4. Go-Shine Huang
  5. Chen-Hwan Cherng

Corresponding author

Correspondence toChih-Shung Wong.

Additional information

This work was supported by grants from the National Defense Medical Center (DOD-92-51) and National Health Research Institute of Taiwan (NHRI-GT-EX90B909). The study was performed at the Department of Anesthesiology, Tri-Service General Hospital and the National Defense Medical Center.

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Wong, CS., Chang, YC., Yeh, CC. et al. Loss of intrathecal morphine analgesia in terminal cancer patients is associated with high levels of excitatory amino acids in the CSF.Can J Anesth 49, 561–565 (2002). https://doi.org/10.1007/BF03017381

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