Inflammatory masses associated with intrathecal drug infusion

A review of preclinical evidence and human data

Tony L. Yaksh, Samuel Hassenbusch, Kim Burchiel, Keith R. Hildebrand, Linda M. Page, Robert J. Coffey

Research output: Contribution to journalArticle

124 Citations (Scopus)

Abstract

Objectives. The phenomenon of inflammatory masses at the tips of intrathecal drug administration catheters was the subject of a recent case-compilation report and a number of animal studies. We sought to synthesize current clinical and preclinical data to formulate hypotheses about the etiology of catheter-tip masses. Methods. We reviewed the published human clinical data, new unpublished clinical data, and the results of preclinical studies in two mammalian species, beagle dogs and sheep. Results. Intrathecal morphine sulfate studies in beagle dogs suggested that the observed inflammatory reaction was dose or concentration dependent. Masses occurred after 28 days in one of three animals at 1.5 mg/day (the lowest morphine dose tested); in two of three animals at 3 and 9 mg/day; and in three of three animals at 12 mg/day. The addition of various amounts of clonidine to 1.5 mg/day of morphine revealed no mass formation when the clonidine dose was >0.25 mg/day. A morphine sulfate study that was performed in sheep using a commercially marketed drug administration system found catheter tip masses in two of three animals that received 12 or 18 mg/day of morphine, the highest doses tested. Human cases have occurred only in pain patients who received intrathecal opioids, alone or mixed with other drugs, or in patients who received investigational agents (such as superoxide dismutase or the partial μ-opioid-receptor agonist, tramadol) that were not labeled for long-term intrathecal use. Discussion/Conclusions. The evidence suggests that the long-term administration of opioids, especially morphine, caused the masses that were observed in humans and in two species of animals. A relationship probably exists between mass formation and intrathecal morphine doses or concentration. Other factors remain to be investigated.

Original languageEnglish (US)
Pages (from-to)300-312
Number of pages13
JournalPain Medicine
Volume3
Issue number4
DOIs
StatePublished - 2002
Externally publishedYes

Fingerprint

Morphine
Pharmaceutical Preparations
Opioid Analgesics
Catheters
Clonidine
Sheep
Dogs
Tramadol
Opioid Receptors
Superoxide Dismutase
Pain

Keywords

  • Complications
  • Granuloma
  • Inflammatory mass
  • Intraspinal catheter
  • Intrathecal
  • Morphine
  • Pain

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Inflammatory masses associated with intrathecal drug infusion : A review of preclinical evidence and human data. / Yaksh, Tony L.; Hassenbusch, Samuel; Burchiel, Kim; Hildebrand, Keith R.; Page, Linda M.; Coffey, Robert J.

In: Pain Medicine, Vol. 3, No. 4, 2002, p. 300-312.

Research output: Contribution to journalArticle

Yaksh, Tony L. ; Hassenbusch, Samuel ; Burchiel, Kim ; Hildebrand, Keith R. ; Page, Linda M. ; Coffey, Robert J. / Inflammatory masses associated with intrathecal drug infusion : A review of preclinical evidence and human data. In: Pain Medicine. 2002 ; Vol. 3, No. 4. pp. 300-312.
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