Neuropathologic lesions and CSF morphine concentrations during chronic continuous intraspinal morphine infusion. A clinical and post-mortem study.
Seven patients with chronic intractable pain due to cancer were given chronic intraspinal narcotic administration (CINA) and subsequently underwent post-mortem examination. All deaths were unrelated to CINA. Two of these patients were found to have clinically unsuspected posterior column degeneration. Both patients had had epidural catheters placed, and one had received prior radiotherapy to ports which included parts of the spinal cord. In retrospect, it is impossible to ascertain whether the degeneration occurred before or after infusion of morphine began. Review of the potential causes for posterior column degeneration suggests that neuropathy associated with malignant disease is more likely the cause of the degeneration rather than intraspinal infusion of morphine. However, continued vigilance at autopsy is recommended. In addition, utilizing a new method for measuring cerebrospinal fluid (CSF) concentrations of morphine via high-pressure liquid chromatography, CSF morphine levels at steady state were measured in 5 patients. These levels were much lower than peak levels previously reported following bolus intraspinal administration. The ability of these measurements to contribute to knowledge of efficacy, toxicity, lumbar-cisternal concentration gradients, and differentiation of tolerance from drug delivery problems is discussed.
Department of Surgery (Anes.)Pharmacology, Dartmouth-Hitchcock Medical Center, Hanover, NH 03755 U.S.A. Department of Pathology Dartmouth-Hitchcock Medical Center, Hanover, NH 03755 U.S.A. Departments of Medicine and Pharmacology, Dartmouth-Hitchcock Medical Center, Hanover, NH 03755 U.S.A.
Dennis W
DW
Coombs
Jonathan D
JD
Fratkin
Frederick A
FA
Meier
David W
DW
Nierenberg
Richard L
RL
Saunders
D000368:Aged; D001344:Autopsy; D002851:Chromatography, High Pressure Liquid; D004824:Epidural Space; D006801:Humans; D008875:Middle Aged; D009020:Morphine / Q000008:administration & dosage / Q000134:cerebrospinal fluid* / Q000627:therapeutic use; D009369:Neoplasms / Q000150:complications; D010148:Intractable Pain / Q000188:drug therapy; D010166:Palliative Care; D013116:Spinal Cord / Q000473:pathology*; D013122:Spinal Diseases / Q000209:etiology / Q000473:pathology
D009020:Morphine