title: Neuropathological findings after continuous intrathecal administration of S(+)-ketamine for the management of neuropathic cancer pain.
abstract: Questions have been raised about the potential neurotoxicity of the neuraxial use of ketamine although ketamine and its active enantiomer S(+)-ketamine have been used intrathecally and epidurally (caudally) for the management of perioperative pain and in a variety of chronic pain syndromes. Clinical experience following neuraxial administration of S(+)-ketamine has been documented without reference to local central nervous system toxicity following this approach. In addition, there are no preclinical safety data regarding stability, compatibility, and neurotoxicity on intrathecal use of single S(+)-ketamine or combinations of S(+)-ketamine, morphine, bupivacaine, and clonidine. In the present case, the continuous intrathecal administration of S(+)-ketamine, in combination with morphine, bupivacaine, and clonidine resulted in adequate pain relief in a patient suffering from intractable neuropathic cancer pain. However, postmortem observation of the spinal cord and nerve roots revealed severe histological abnormalities including central chromatolysis, nerve cell shrinkage, neuronophagia, microglial upregulation, and gliosis. Based on our results, neuraxial administration of S (+)-ketamine cannot be recommended for clinical practise before a systematic study of toxicology of neuraxial S(+)-ketamine in animals or humans has been performed.
authors.affiliation: Department of Anesthesiology Academic Medical Center, University of Amsterdam P.O. Box 22700, 1100 DE Amsterdam, The Netherlands. j.h.vranken@amc.uva.nl
authors.forename: J H
authors.initials: JH
authors.lastname: Vranken
authors.forename: D
authors.initials: D
authors.lastname: Troost
authors.forename: J T
authors.initials: JT
authors.lastname: Wegener
authors.forename: M R
authors.initials: MR
authors.lastname: Kruis
authors.forename: M H
authors.initials: MH
authors.lastname: van der Vegt
mesh_terms: D000700:Analgesics / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007649:Ketamine / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications*; D010146:Pain / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D011180:Postmortem Changes; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology
chemical_list: D000700:Analgesics; D007649:Ketamine