title: Neurohistopathological findings after continuous intrathecal administration of morphine or a morphine/bupivacaine mixture in cancer pain patients.
abstract: BACKGROUND
  As the number of terminal cancer patients receiving continuous intrathecal infusion of opioids and local anesthetics for relief of pain increases, we decided to investigate the post-mortem findings of the spinal cord, meninges and nerve roots of patients after continuous intrathecal administration of morphine and combined with bupivacaine.
  
  
  METHODS
  Neurohistopathological findings were obtained from 10 cancer patients [2 men and 8 women, 29-69 (median 52) yrs old] and 4 controls [4 men, 46-75 (median 64) yrs old]. The cancer patients had been treated for a mean of 98 (range 8-452) d with morphine/NaCl 0.9% or morphine/bupivacaine, administered through a polyamide lumbar catheter. Concomitant radiation therapy and chemotherapeutic drugs had been given to 5 and 6 patients, respectively. Cumulative doses of morphine ranged from 22 to 3895 mg, those of bupivacaine from 0 to 3250 mg and of sodium metabisulfite (antioxidant) from 0.6 to 97.4 mg.
  
  
  RESULTS
  No macroscopic abnormalities of the catheter tract, dura, leptomeninges, nerve roots or spinal cord were found. Microscopically, focal foreign body giant cells were seen in 2 cases in the area of the catheter pathway both without any sign of inflammation. In one case treated for 103 d, an intrathecal reaction was found. This consisted of small aggregates of lymphocytes predominantly in the leptomeninges and focally in the cord parenchyma. No abnormalities were found in the other cases when using hematoxylin-eosin and Kluver or Bodian stained specimens, indicating neither myelin nor axonal damage. Microglial reactions were similar in both cancer patients and controls.
  
  
  CONCLUSIONS
  The discrete and limited neurohistopathological findings in both catheter patients and controls suggest that intrathecal infusion of morphine and bupivacaine via a polyamide catheter is devoid of significant neurotoxic effects in cancer patients.
authors.affiliation: Department of Anesthesiology, Academic Hospital Vrije Universiteit, Amsterdam, The Netherlands.
authors.forename: M F
authors.initials: MF
authors.lastname: Wagemans
authors.forename: P
authors.initials: P
authors.lastname: van der Valk
authors.forename: E M
authors.initials: EM
authors.lastname: Spoelder
authors.forename: W W
authors.initials: WW
authors.lastname: Zuurmond
authors.forename: J J
authors.initials: JJ
authors.lastname: de Lange
mesh_terms: D000328:Adult; D000368:Aged; D000701:Analgesics, Opioid / Q000008:administration & dosage*; D000779:Anesthetics, Local / Q000008:administration & dosage*; D002045:Bupivacaine / Q000008:administration & dosage*; D004388:Dura Mater / Q000473:pathology; D005260:Female; D006801:Humans; D007263:Infusions, Parenteral; D007278:Injections, Spinal; D008297:Male; D008578:Meninges / Q000473:pathology*; D008875:Middle Aged; D009020:Morphine / Q000008:administration & dosage*; D009369:Neoplasms / Q000150:complications*; D010148:Intractable Pain / Q000188:drug therapy* / Q000209:etiology; D013116:Spinal Cord / Q000473:pathology*; D013126:Spinal Nerve Roots / Q000473:pathology*
chemical_list: D000701:Analgesics, Opioid; D000779:Anesthetics, Local; D009020:Morphine; D002045:Bupivacaine