Medications in Intrathecal Pumps

  • Grant H. Chen


Intrathecal (IT) pumps are a critical part of cancer pain treatment. While there are currently three medications (morphine, ziconotide, and baclofen) approved by the Food and Drug Administration (FDA) for intrathecal drug use, there are other medications that can help provide pain relief. The location and characteristics of the pain should always be used in determining which drug(s) to use. Side effects and interaction of IT drugs with other medications should also be investigated prior to initiation of treatment. Starting and adjustment doses can be effectively titrated based on the individual patient’s needs.


Intrathecal pump Opioid Morphine Bupivacaine Ziconotide Hydromorphone Fentanyl Sufentanil Clonidine Dexmedetomidine 


  1. 1.
    Bottros MM, Christo PJ. Current perspectives on intrathecal drug delivery. J Pain Res. 2014;7:615–26.PubMedPubMedCentralGoogle Scholar
  2. 2.
    Wang JK, Nauss LA, Thomas JE. Pain relief by intrathecally applied morphine in man. Anesthesiology. 1979;50(2):149–51.PubMedCrossRefGoogle Scholar
  3. 3.
    Deer TR, Prager J, Levy R, et al. Polyanalgesic consensus conference 2012: recommendations for the management of pain by intrathecal (intraspinal) drug delivery: report of an interdisciplinary expert panel. Neuromodulation. 2012;15(5):436–64.PubMedCrossRefGoogle Scholar
  4. 4.
    Hassenbusch SJ, Pillay PK, Magdinec M, et al. Constant infusion of morphine for intractable cancer pain using an implanted pump. J Neurosurg. 1990;73(3):405–9.PubMedCrossRefGoogle Scholar
  5. 5.
    Atli A, Theodore BR, Turk DC, et al. Intrathecal opioid therapy for chronic nonmalignant pain: a retrospective cohort study with 3-year follow-up. Pain Med. 2010;11(7):1010–6.PubMedCrossRefGoogle Scholar
  6. 6.
    Reig E, Abejon D. Continuous morphine infusion: a retrospective study of efficacy, safety, and demographic variables. Neuromodulation. 2009;12(2):122–9.PubMedCrossRefGoogle Scholar
  7. 7.
    Smith TJ, Staats PS, Deer T, et al. Randomized clinical trial of an implantable drug delivery system compared with comprehensive medical management for refractory cancer pain: impact on pain, drug-related toxicity, and survival. J Clin Oncol. 2002;20(19):4040–9.PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Rauck RL, Cherry D, Boyer MF, et al. Long-term intrathecal opioid therapy with a patient-activated, implanted delivery system for the treatment of refractory cancer pain. J Pain. 2003;4(8):441–7.PubMedCrossRefGoogle Scholar
  9. 9.
    Sjöberg M, Appelgren L, Einarsson S, et al. Long-term intrathecal morphine and bupivacaine in “refractory” cancer pain. I. Results from the first series of 52 patients. Acta Anaesthesiol Scand. 1991;35(1):30–43.PubMedCrossRefGoogle Scholar
  10. 10.
    Sjöberg M, Nitescu P, Appelgren L, et al. Long-term intrathecal morphine and bupivacaine in patients with refractory cancer pain. Results from a morphine: bupivacaine dose regimen of 0.5:4.75 mg/ml. Anesthesiology. 1994;80(2):284–97.PubMedCrossRefGoogle Scholar
  11. 11.
    Mitchell A, McGhie J, Owen M, et al. Audit of intrathecal drug delivery for patients with difficult-to-control cancer pain shows a sustained reduction in pain severity scores over a 6-month period. Palliat Med. 2015;29(6):554–63.PubMedCrossRefGoogle Scholar
  12. 12.
    Mercadante S, Intravala G, Villari P, et al. Intrathecal treatment in cancer patients unresponsive to multiple trials of systemic opioids. Clin J Pain. 2007;23(9):793–8.PubMedCrossRefGoogle Scholar
  13. 13.
    Yaksh TL, Onofrio BM. Retrospective consideration of the doses of morphine given intrathecally by chronic infusion in 163 patients by 19 physicians. Pain. 1987;31(2):211–23.PubMedCrossRefGoogle Scholar
  14. 14.
    Chaney MA. Side effects of intrathecal and epidural opioids. Can J Anaesth. 1995;42:891–903.PubMedCrossRefGoogle Scholar
  15. 15.
    Ruan X. Drug-related side effects of long-term intrathecal morphine therapy. Pain Physician. 2007;10(2):357–66.PubMedGoogle Scholar
  16. 16.
    Malhotra VT, Root J, Kesselbrenner J, et al. Intrathecal pain pump infusions for intractable cancer pain: an algorithm for dosing without a neuraxial trial. Anesth Analg. 2013;116(6):1364–70.PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Veizi E, Tornero-Bold M, Hayek SM. Resolution of intrathecal hydromorphone or morphine-induced peripheral edema by opioid rotation to fentanyl: a case series. Pain Pract. 2016;16(6):E94–8.PubMedCrossRefGoogle Scholar
  18. 18.
    Olivera B, Gray WR, Zikus R, et al. Peptide neurotoxins from fish-hunting cone snails. Science. 1985;230(4732):1338–43.PubMedCrossRefGoogle Scholar
  19. 19.
    Bowersox SS, Gadbois T, Singh T, et al. Selective N-type neuronal voltage-sensitive calcium channel blocker, SNX-111, produces spinal antinociception in rat models of acute, persistent and neuropathic pain. J Pharmacol Exp Ther. 1996;279:1243–9.PubMedGoogle Scholar
  20. 20.
    Alicino I, Giglio M, Manca F, et al. Intrathecal combination of ziconotide and morphine for refractory cancer pain: a rapidly acting and effective choice. Pain. 2012;153(1):245–9.PubMedCrossRefGoogle Scholar
  21. 21.
    Staats PS, Yearwood T, Charapata SG, et al. Intrathecal ziconotide in the treatment of refractory pain in patients with cancer or AIDS: a randomized controlled trial. JAMA. 2004;291(1):63–70.PubMedCrossRefGoogle Scholar
  22. 22.
    Prilat. Ziconotide intrathecal infusion. [prescribing information]. San Diego: Jazz Pharmaceuticals, Inc.; 2016.Google Scholar
  23. 23.
    Maier C, Cockel HH, Gruhn K, et al. Increased risk of suicide under intrathecal ziconotide treatment? – a warning. Pain. 2011;152(1):235–7.PubMedCrossRefGoogle Scholar
  24. 24.
    Malmberg AB, Yaksh TL. Effect of continuous intrathecal infusion of omega-conopeptides, N-type calcium-channel blockers, on behavior and antinociception in the formalin and hot-plate tests in rats. Pain. 1995;60(1):83–90.PubMedCrossRefGoogle Scholar
  25. 25.
    Prialt (ziconotide) Solution, Intrathecal Infusion [package insert]. Palo Alto: Jazz Pharmaceuticals, Inc.; 2013.Google Scholar
  26. 26.
    Fishman S, Ballantyne J, Rathmell JP, Bonica JJ. Bonica’s management of pain. 4th ed. Baltimore: Lippincott, Williams & Wilkins; 2010.Google Scholar
  27. 27.
    Gulati A, Puttanniah V, Hung J, et al. Considerations for evaluating the use of intrathecal drug delivery in the oncologic patient. Curr Pain Headache Rep. 2014;18(2):391.PubMedCrossRefGoogle Scholar
  28. 28.
    Sloan PA. Neuraxial pain relief for intractable cancer pain. Curr Pain Headache Rep. 2007;11(4):238–9.CrossRefGoogle Scholar
  29. 29.
    Graf BM, Abraham I, Eberbach N, et al. Differences in cardiotoxicity of bupivacaine and ropivacaine are the result of physicochemical and stereoselective properties. Anesthesiology. 2002;96(6):1427–34.PubMedCrossRefGoogle Scholar
  30. 30.
    Eisenach JC, DuPen S, Dubois M, et al. Epidural clonidine analgesia for intractable cancer pain. Pain. 1995;61:391–9.PubMedCrossRefGoogle Scholar
  31. 31.
    Klimscha W, Tong C, Eisenach JC. Intrathecal α2-adrenergic agonists stimulate acetylcholine and norepinephrine release from the spinal cord dorsal horn in sheep. An in vivo microdialysis study. Anesthesiology. 1997;87(1):110–6.PubMedCrossRefGoogle Scholar
  32. 32.
    Feng X, Zhang F, Dong R, et al. Intrathecal administration of clonidine attenuates spinal neuroimmune activation in a rat model of neuropathic pain with existing hyperalgesia. Eur J Pharmacol. 2009;614(1–3):38–43.PubMedCrossRefGoogle Scholar
  33. 33.
    Yaksh TL. Pharmacology of spinal adrenergic systems which modulate spinal nociceptive processing. Pharmacol Biochem Behav. 1985;22:845–58.PubMedCrossRefGoogle Scholar
  34. 34.
    Hassenbusch SJ, Gunes S, Wachsman S, et al. Intrathecal clonidine in the treatment of intractable pain: a phase I/II study. Pain Med. 2002;3(2):85–91.PubMedCrossRefGoogle Scholar
  35. 35.
    Hassenbusch SJ, Portenoy RK. Current practices in intraspinal therapy – a survey of clinical trends and decision making. J Pain Symptom Manag. 2000;20(2):S4–11.CrossRefGoogle Scholar
  36. 36.
    Ugur F, Gulcu N, Boyaci A. Intrathecal infusion therapy with dexmedetomidine-supplemented morphine in cancer pain. Acta Anaesthesiol Scand. 2007;51(3):388.PubMedCrossRefGoogle Scholar
  37. 37.
    Konakci S, Adanir T, Yilmax G, et al. The efficacy and neurotoxicity of dexmedetomidine administered via the epidural route. Eur J Anaesthesiol. 2008;25(5):403–9.PubMedCrossRefGoogle Scholar
  38. 38.
    Coffey RJ, Cahil D, Steers W, et al. Intrathecal baclofen for intractable spasticity of spinal origin: results of a long-term multicenter study. J Neurosurg. 1993;78:226–32.PubMedCrossRefGoogle Scholar
  39. 39.
    Albright AL, Gilmartin R, Swift D, et al. Long-term intrathecal baclofen therapy for severe spasticity of cerebral origin. J Neurosurg. 2003;98:291–5.PubMedCrossRefGoogle Scholar
  40. 40.
    Koulousakis A, Kuchta J. Intrathecal antispastic drug application with implantable pumps: results of a 10 year follow-up study. Acta Neurochir Suppl. 2007;97.(Pt 1:181–4.PubMedGoogle Scholar
  41. 41.
    Heetla HW, Staal MJ, Kliphuis C, et al. The incidence and management of tolerance in intrathecal baclofen therapy. Spinal Cord. 2009;47(10):751–6.PubMedCrossRefGoogle Scholar
  42. 42.
    Coffey RJ, Edgar TS, Francisco GE, et al. Abrupt withdrawal from intrathecal baclofen: recognition and management of a potentially life-threatening syndrome. Arch Phys Med Rehabil. 2002;83:735–41.PubMedCrossRefGoogle Scholar
  43. 43.
    Ginsburg GM, Lauder AJ. Progression of scoliosis in patients with spastic quadriplegia after the insertion of an intrathecal baclofen pump. Spine (Phila Pa 1976). 2007;32(24):2745–50.CrossRefGoogle Scholar
  44. 44.
    Yaksh TL, Tozier N, Horais KA, et al. Toxicology profile of N-methyl-D-aspartate antagonists delivered by intrathecal infusion in the canine model. Anesthesiology. 2008;108(5):938–49.PubMedCrossRefGoogle Scholar
  45. 45.
    Wang C, Sadovova N, Fu X, et al. The role of the N-methyl-d-aspartate receptor in ketamine-induced apoptosis in rat forebrain culture. Neuroscience. 2005;132:967–77.PubMedCrossRefGoogle Scholar
  46. 46.
    Vranken JH, Troost D, Wegener JT, et al. Neuropathological findings after continuous intrathecal administration of S(+)-ketamine for the management of neuropathic cancer pain. Pain. 2005;117(1–2):231–5.PubMedCrossRefGoogle Scholar
  47. 47.
    Yang CY, Wong CS, Chang JY, et al. Intrathecal ketamine reduces morphine requirements in patients with terminal cancer pain. Can J Anaesth. 1996;43(4):379–83.PubMedCrossRefGoogle Scholar
  48. 48.
    Osenbach RK. Intrathecal drug delivery in the management of pain. In: Fishman S, Ballantyne J, Rathmell J, editors. Bonica’s management of pain. Philadelphia: Lippencott, Williams, & Wilkins; 2010. p. 1437–57.Google Scholar
  49. 49.
    Pope JE, Deer TR. Intrathecal pharmacology update: novel dosing strategy for intrathecal monotherapy ziconotide on efficacy and sustainability. Neuromodulation. 2015;18(5):414–20.PubMedCrossRefGoogle Scholar
  50. 50.

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Memorial Sloan Kettering Cancer Center, Department of Anesthesiology and Critical Care MedicineNew YorkUSA

Personalised recommendations