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Correspondence  |   July 2004
Intrathecal Morphine and Inflammatory Masses
Author Notes
  • Foothills Regional Pain Center, Seneca, South Carolina.
Article Information
Correspondence
Correspondence   |   July 2004
Intrathecal Morphine and Inflammatory Masses
Anesthesiology 7 2004, Vol.101, 255. doi:
Anesthesiology 7 2004, Vol.101, 255. doi:
To the Editor:—
I read with interest the reports by Yaksh et al.  1 and Gradert et al.  2 in the July 2003 issue of Anesthesiology describing the association of intrathecal analgesia with catheter-associated masses and the accompanying editorial by Follett.3 Both articles describe a clear dose- and/or concentration-dependent relation between commercially prepared preservative-free morphine sulfate and the production of inflammatory masses in opioid-naive sheep and dogs. The authors are to be commended for their scholarly works and timely nature of the conclusions. Such work is of great interest to patients with intractable pain and the physicians and medical vendors who make this effective therapy available to them. It is now clear that high-dose commercially prepared morphine sulfate delivered by continuous infusion causes inflammatory masses and neurologic injury in a high percentage of at-risk research animals, as well as in an unknown percentage of patients receiving this therapy. Most importantly, the time course and frequency of this complication in laboratory animals provides a much needed model for further study and development of effective analgesics with a greater safety profile than the only agent currently approved by the U.S. Food and Drug Administration for use in patients.
Catheter-associated masses have the potential to cause devastating permanent neurologic injury in animal models and patients receiving intrathecal therapy.4,5 It has now been shown that occult lesions may be detected in asymptomatic patients using readily available radiographic screening methods and that noninvasive interventions may be undertaken to reverse or arrest the progression of these masses without additional surgery or catheter explantation.6,7 Termination of drug infusion, initiation of saline infusion, or both in asymptomatic or minimally symptomatic patients have been shown to result in spontaneous regression of lesions without the development of neurologic injury, whereas changing to a different analgesic drug may arrest the progression of lesions without interruption of therapy. Although the treatment of individual patients has been greatly improved by these discoveries, the true prevalence and incidence of this complication in the entire at-risk population of patients receiving intrathecal analgesic therapy must now be determined with a greater degree of certainty and urgency than ever before. I cannot recall a situation in which a serious complication directly attributable to or associated with a medical device or therapy was recognized after introduction without immediate large-scale efforts to define the true incidence, prevalence, and morbidity of that complication in all at-risk patients currently receiving the therapy. This is especially important for that group of asymptomatic patients currently harboring occult inflammatory masses who could be spared serious morbidity through noninvasive means. Medtronic Corporation (Minneapolis, MN) is the largest single vendor of implantable intrathecal drug infusion systems and sponsors much of the research regarding intrathecal therapy, including some of the work cited above. It is disappointing that to date, neither company bulletins nor company-sponsored investigators have endorsed such recommendations for immediate large-scale screening of all patients currently receiving continuous intrathecal opioid analgesia. In addition to issues of informed consent and the time or dose-dependent risk of mass development and neurologic injury, I believe that physicians treating these patients and the medical vendors who produce implantable intrathecal systems will be held accountable by patients, our medical colleagues, and society to endorse conservative recommendations for management and to detect and treat occult catheter-associated masses in at-risk patients before  the development of symptoms. One wonders how long the Food and Drug Administration will allow the continued use of preservative-free morphine sulfate for intrathecal analgesia without a major change in its labeling regarding the risks of catheter-associated masses and greater understanding of the actual degree of risk involved with its widespread clinical use. In the accompanying editorial,3 Dr. Follett appropriately recommends that, “. . . physicians who manage patients receiving intrathecal analgesics must be highly aware of the possible development of intrathecal granulomas and must perform regular surveillance of their patients to detect these masses early, before serious complications arise.” I would take this recommendation a step further. I suggest that all patients currently receiving intrathecal analgesic therapy should be offered initial and periodic follow-up radiographic screening by methods with appropriate sensitivity and specificity to detect occult catheter-associated masses while they can be treated conservatively, before the development of symptoms or neurologic injury.7 The only methods currently shown to have appropriate resolution to reliably detect these lesions are computed tomography with myelography and high-resolution magnetic resonance scanning. Only with an accurate assessment of the risks as well as the benefits of long-term intrathecal analgesic therapy can we confidently and safely provide appropriate medical advocacy and treatment for our patients who benefit from this therapy for the treatment of intractable chronic pain.
Foothills Regional Pain Center, Seneca, South Carolina.
References
Yaksh TL, Horais KA, Tozier NA, Allen JW, Rathbun M, Rossi SS, Sommer C, Meschter C, Richter PJ, Hildebrand KR: Chronically infused intrathecal morphine in dogs. Anesthesiology 2003; 99:174–87Yaksh, TL Horais, KA Tozier, NA Allen, JW Rathbun, M Rossi, SS Sommer, C Meschter, C Richter, PJ Hildebrand, KR
Gradert TL, Baze WB, Satterfield WC, Hildebrand KR, Johansen MJ, Hassenbusch SJ: Safety of chronic intrathecal morphine infusion in a sheep model. Anesthesiology 2003; 99:188–98Gradert, TL Baze, WB Satterfield, WC Hildebrand, KR Johansen, MJ Hassenbusch, SJ
Follett KA: Intrathecal analgesia and catheter-tip inflammatory masses. Anesthesiology 2003; 99:5–6Follett, KA
North RB, Cutchis PT, Epstein JA, Long DM: Spinal cord compression complicating subarachnoid infusion of morphine: Case report and laboratory experience. Neurosurgery 1991; 29:778–84North, RB Cutchis, PT Epstein, JA Long, DM
Coffey RJ and Burchiel K: Inflammatory mass lesions associated with intrathecal drug infusion catheters: Report and observations on 41 patients. Neurosurgery 2002; 50:78–87Coffey, RJ Burchiel, K
Cabbell KL, Taren JA, Sagher O, Spinal cord compression by catheter granulomas in high-dose intrathecal morphine therapy: Case report. Neurosurgery 1998; 42:1176–81Cabbell, KL Taren, JA Sagher, O
McMillan MR, Doud T, Nugent W: Catheter-associated masses in patients receiving intrathecal analgesic therapy. Anesth Analg 2003; 96:186–90McMillan, MR Doud, T Nugent, W