SpringerLink
Log in

Intrathecal Drug Delivery: Medication Selection

  • Chapter
  • First Online:
Advanced Procedures for Pain Management

  • 1900 Accesses

Abstract

The appropriate selection of medications is key to the accomplishment of symptom control when using an intrathecal drug delivery system (IDDS). Medications must be preservative-free, safe for intrathecal use, and efficacious. For control of chronic pain, a number of intrathecal agents are commonly used, including opioids, the local anesthetic bupivacaine, the peptide ziconotide, and clonidine. Morphine and ziconotide are the only medications approved by the US Food and Drug Administration (FDA) for the intrathecal treatment of chronic pain. Baclofen is the only FDA-approved medication for treatment of spasticity using intrathecal drug delivery (IDD).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Institutional subscriptions

Similar content being viewed by others

References

  1. Veizi IE, Hayek SM, Narouze S, Pope JE, Mekhail N. Combination of intrathecal opioids with bupivacaine attenuates opioid dose escalation in chronic noncancer pain patients. Pain Med. 2011;12:1481–9.

    Article  PubMed  Google Scholar 

  2. Dominguez E, Sahinler B, Bassam D, Day M, Lou L, Racz G, et al. Predictive value of intrathecal narcotic trials for long-term therapy with implantable drug administration systems in chronic non-cancer pain patients. Pain Pract. 2002;2:315–25.

    Article  PubMed  Google Scholar 

  3. Flack SH, Bernards CM. Cerebrospinal fluid and spinal cord distribution of hyperbaric bupivacaine and baclofen during slow intrathecal infusion in pigs. Anesthesiology. 2010;112:165–73.

    Article  CAS  PubMed  Google Scholar 

  4. Mekhail N, Mahboobi R, Farajzadeh Deroee A, Costandi S, Dalton J, et al. Factors that might impact intrathecal drug delivery (IDD) dose escalation: a longitudinal study. Pain Pract. 2014;14:301–8.

    Article  PubMed  Google Scholar 

  5. Coffey RJ, Owens ML, Broste SK, Dubois MY, Ferrante FM, Schultz DM, et al. Medical practice perspective: identification and mitigation of risk factors for mortality associated with intrathecal opioids for non-cancer pain. Pain Med. 2010;11:1001–9.

    Article  PubMed  Google Scholar 

  6. Urman RD. National perioperative outcomes for intrathecal pump, spinal cord stimulator, and peripheral nerve stimulator procedures. Pain Physician. 2015;18:547–54.

    PubMed  Google Scholar 

  7. Smith TJ, Staats PS, Deer T, Stearns LJ, Rauck RL, Boortz-Marx RL, et al. Implantable Drug Delivery Systems Study Group. 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;20:4040–9.

    Article  CAS  PubMed  Google Scholar 

  8. Herz A, Albus K, Metys J, Schubert P, Teschemacher H. On the central sites for the antinociceptive action of morphine and fentanyl. Neuropharmacology. 1970;9:539–51.

    Article  CAS  PubMed  Google Scholar 

  9. Herz A, Teschemacher HJ. Activities and sites of antinociceptive action of morphine-like analgesics and kinetics of distribution following intravenous, intracerebral and intraventricular application. Adv Drug Res. 1971;6:79–119.

    CAS  Google Scholar 

  10. Ummenhofer WC, Arends RH, Shen DD, Bernards CM. Comparative spinal distribution and clearance kinetics of intrathecally administered morphine, fentanyl, alfentanil, and sufentanil. Anesthesiology. 2000;92:739–53.

    Article  CAS  PubMed  Google Scholar 

  11. Deer TR, Pope JE, Hayek S, Bux A, Buchser E, Eldabe S, et al. The polyanalgesic consensus conference (PACC): recommendations on intrathecal drug infusion systems best practices and guidelines. Neuromodulation. 2017. https://doi.org/10.1111/ner.12538.

  12. North RB, Cutchis PN, Epstein JA, Long DM. Spinal cord compression complicating subarachnoid infusion of morphine: case report and laboratory experience. Neurosurgery. 1991;29:778–84.

    Article  CAS  PubMed  Google Scholar 

  13. Coffey RJ, Owens ML, Broste SK, Dubois MY, Ferrante FM, Schultz DM, et al. Mortality associated with implantation and management of intrathecal opioid drug infusion systems to treat noncancer pain. Anesthesiology. 2009;111:881–91.

    Article  PubMed  Google Scholar 

  14. 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:E94–8.

    Article  PubMed  Google Scholar 

  15. Hayek SM, Veizi IE, Narouze SN, Mekhail N. Age-dependent intrathecal opioid escalation in chronic noncancer pain patients. Pain Med. 2011;12:1179–89.

    Article  PubMed  Google Scholar 

  16. Grider JSH, Harned ME, Etscheidt MA. Patient selection and outcomes using a low-dose intrathecal opioid trialing method for chronic nonmalignant pain. Pain Physician. 2011;14:343–51.

    PubMed  Google Scholar 

  17. Hamza M, Doleys D, Wells M, Weisbein J, Hoff J, Martin M, et al. Prospective study of 3-year follow-up of low-dose intrathecal opioids in the management of chronic nonmalignant pain. Pain Med. 2012;13:1304–13.

    Article  PubMed  Google Scholar 

  18. Galica R, Hayek SM, Veizi IE, Lawrence MM, Khalil AA, McEwan MT. sudden intrathecal drug delivery device motor stalls: a case series. Reg Anesth Pain Med. 2016;41:135–9.

    Article  CAS  PubMed  Google Scholar 

  19. Singla A, Stojanovic MP, Chen L, Mao J. A differential diagnosis of hyperalgesia, toxicity, and withdrawal from intrathecal morphine infusion. Anesth Analg. 2007;105:1816–9.

    Article  PubMed  Google Scholar 

  20. Compton P, Athanasos P, Elashoff D. Withdrawal hyperalgesia after acute opioid physical dependence in nonaddicted humans: a preliminary study. J Pain. 2003;4(9):511.

    Article  PubMed  Google Scholar 

  21. Devulder J, Bohyn P, Castille F, De Laat M, Rolly G. A case of uncommon withdrawal symptoms after a short period of spinal morphine administration. Pain. 1996;64:589–91.

    Article  CAS  PubMed  Google Scholar 

  22. Tomycz ND, Ortiz V, McFadden KA, Urgo L, Moossy JJ. Management of symptomatic intrathecal catheter-associated inflammatory masses. Clin Neurol Neurosurg. 2012;114:190–5.

    Article  PubMed  Google Scholar 

  23. Deer TR, Prager J, Levy R, Rathmell J, Buchser E, Burton A, et al. Polyanalgesic consensus conference—2012: consensus on diagnosis, detection, and treatment of catheter-tip granulomas (inflammatory masses). Neuromodulation. 2012;15:483–95.

    Article  PubMed  Google Scholar 

  24. Yaksh TL, Allen JW, Veesart SL, Horais KA, Malkmus SA, Scadeng M, et al. Role of meningeal mast cells in intrathecal morphine-evoked granuloma formation. Anesthesiology. 2013;118:664–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Rhee SM, Choi EJ, Lee PB, Nahm FS. Catheter obstruction of intrathecal drug administration system—a case report. Korean J Pain. 2012;25:47–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Mironer YE, Haasis JC, Chapple I, Brown C, Satterthwaite JR. Efficacy and safety of intrathecal opioids/bupivacaine mixture in chronic nonmalignant pain: a double blind, randomized, crossover, multicenter study by the National Forum of Independent Pain Clinicians (NFIPC). Neuromodulation. 2002;5:208–13.

    Article  PubMed  Google Scholar 

  27. Deer TR, Caraway DL, Kim CK, Dempsey CD, Stewart CD, McNeil KF. Clinical experience with intrathecal bupivacaine in combination with opioid for the treatment of chronic pain related to failed back surgery syndrome and metastatic cancer pain of the spine. Spine J. 2002;2:274–8.

    Article  PubMed  Google Scholar 

  28. Hayek SM, Veizi E, Hanes M. Intrathecal hydromorphone and bupivacaine combination therapy for post-laminectomy syndrome optimized with patient-activated bolus device. Pain Med. 2016;17:561–71.

    Article  PubMed  Google Scholar 

  29. Boswell MV, Iacono RP, Guthkelch AN. Sites of action of subarachnoid lidocaine and tetracaine: observations with evoked potential monitoring during spinal cord stimulator implantation. Reg Anesth. 1992;17:37–42.

    CAS  PubMed  Google Scholar 

  30. Schug SA, Saunders D, Kurowski I, Paech MJ. Neuraxial drug administration: a review of treatment options for anaesthesia and analgesia. CNS Drugs. 2006;20:917–33.

    Article  CAS  PubMed  Google Scholar 

  31. Naguib M, Magboul MM, Samarkandi AH, Attia M. Adverse effects and drug interactions associated with local and regional anaesthesia. Drug Saf. 1998;18:221–50.

    Article  CAS  PubMed  Google Scholar 

  32. Zhong Z, Qulian G, Yuan Z, Wangyuan Z, Zhihua S. Repeated intrathecal administration of ropivacaine causes neurotoxicity in rats. Anaesth Intensive Care. 2009;37:929–36.

    CAS  PubMed  Google Scholar 

  33. Malinovsky JM, Charles F, Baudrimont M, Pereon Y, Le Corre P, Pinaud M, et al. Intrathecal ropivacaine in rabbits: pharmacodynamic and neurotoxicologic study. Anesthesiology. 2002;97:429–35.

    Article  CAS  PubMed  Google Scholar 

  34. Yamashita A, Matsumoto M, Matsumoto S, Itoh M, Kawai K, Sakabe T. A comparison of the neurotoxic effects on the spinal cord of tetracaine, lidocaine, bupivacaine, and ropivacaine administered intrathecally in rabbits. Anesth Analg. 2003;97:512–9.

    Article  CAS  PubMed  Google Scholar 

  35. Liu PL, Feldman HS, Giasi R, Patterson MK, Covino BG. Comparative CNS toxicity of lidocaine, etidocaine, bupivacaine, and tetracaine in awake dogs following rapid intravenous administration. Anesth Analg. 1983;62:375–9.

    Article  CAS  PubMed  Google Scholar 

  36. Morrison SG, Dominguez JJ, Frascarolo P, Reiz S. A comparison of the electrocardiographic cardiotoxic effects of racemic bupivacaine, levobupivacaine, and ropivacaine in anesthetized swine. Anesth Analg. 2000;90:1308–14.

    Article  CAS  PubMed  Google Scholar 

  37. Sjoberg M, Nitescu P, Appelgren L, Curelaru I. 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;80:284–97.

    Article  CAS  PubMed  Google Scholar 

  38. Nitescu P, Dahm P, Appelgren L, Curelaru I. Continuous infusion of opioid and bupivacaine by externalized intrathecal catheters in long-term treatment of “refractory” nonmalignant pain. Clin J Pain. 1998;14:17–28.

    Article  CAS  PubMed  Google Scholar 

  39. Rauck RL, Wallace MS, Leong MS, Minehart M, Webster LR, Charapata SG, et al. A randomized, double-blind, placebo-controlled study of intrathecal ziconotide in adults with severe chronic pain. J Pain Symptom Manag. 2006;31:393–406.

    Article  CAS  Google Scholar 

  40. Staats PS, Yearwood T, Charapata SG, Presley RW, Wallace MS, Byas-Smith M, et al. Intrathecal ziconotide in the treatment of refractory pain in patients with cancer or AIDS: a randomized controlled trial. JAMA. 2004;291:63–70.

    Article  CAS  PubMed  Google Scholar 

  41. Wallace MS, Charapata SG, Fisher R, Byas-Smith M, Staats PS, Mayo M, et al. Intrathecal ziconotide in the treatment of chronic nonmalignant pain: a randomized, double-blind, placebo-controlled clinical trial. Neuromodulation. 2006;9:75–86.

    Article  PubMed  Google Scholar 

  42. Miljanich GP. Ziconotide: neuronal calcium channel blocker for treating severe chronic pain. Curr Med Chem. 2004;11:3029–40.

    Article  CAS  PubMed  Google Scholar 

  43. McGivern JG. Ziconotide: a review of its pharmacology and use in the treatment of pain. Neuropsychiatr Dis Treat. 2007;3:69–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Wermeling D, Drass M, Ellis D, Mayo M, McGuire D, O'Connell D, et al. Pharmacokinetics and pharmacodynamics of intrathecal ziconotide in chronic pain patients. J Clin Pharmacol. 2003;43:624–36.

    Article  CAS  PubMed  Google Scholar 

  45. Wallace MS, Rauck R, Fisher R, Charapata SG, Ellis D, Dissanayake S. Intrathecal ziconotide for severe chronic pain: safety and tolerability results of an open-label, long-term trial. Anesth Analg. 2008;106:628–37.

    Article  CAS  PubMed  Google Scholar 

  46. Hayek SM, Hanes MC, Wang C, Veizi IE. Ziconotide combination intrathecal therapy for noncancer pain is limited secondary to delayed adverse effects: a case series with a 24-month follow-up. Neuromodulation. 2015;18:397–403.

    Article  PubMed  Google Scholar 

  47. Maier C, Gockel HH, Gruhn K, Krumova EK, Edel MA. Increased risk of suicide under intrathecal ziconotide treatment? A warning. Pain. 2011;152:235–7.

    Article  CAS  PubMed  Google Scholar 

  48. Ver Donck A, Collins R, Rauck RL, Nitescu P. An open-label, multicenter study of the safety and efficacy of intrathecal ziconotide for severe chronic pain when delivered via an external pump. Neuromodulation. 2008;11:103–11.

    Article  Google Scholar 

  49. Ackerman LL, Follett KA, Rosenquist RW. Long-term outcomes during treatment of chronic pain with intrathecal clonidine or clonidine/opioid combinations. J Pain Symptom Manag. 2003;26:668–77.

    Article  CAS  Google Scholar 

  50. Feng X, Zhang F, Dong R, Li W, Liu J, Zhao X, et al. Intrathecal administration of clonidine attenuates spinal neuroimmune activation in a rat model of neuropathic pain with existing hyperalgesia. Eur J Pharmacol. 2009;614:38–43.

    Article  CAS  PubMed  Google Scholar 

  51. Naruse T, Ishida T, Ishii R, Tagawa T, Namba K. Relationship between hypotensive effects and plasma concentrations of clonidine in spontaneously hypertensive rats: continuous treatment and sudden termination of clonidine infusion. Gen Pharmacol. 1994;25:1421–5.

    Article  CAS  PubMed  Google Scholar 

  52. Bevacqua BK, Fattouh M, Backonja M. Depression, night terrors, and insomnia associated with long-term intrathecal clonidine therapy. Pain Pract. 2007;7:36–8.

    Article  PubMed  Google Scholar 

  53. Lee HM, Ruggoo V, Graudins A. Intrathecal clonidine pump failure causing acute withdrawal syndrome with ‘stress-induced’ cardiomyopathy. J Med Toxicol. 2016;12:134–8.

    Article  CAS  PubMed  Google Scholar 

  54. Penn RD, Kroin JS. Continuous intrathecal baclofen for severe spasticity. Lancet. 1985;2(8447):125–7.

    Article  CAS  PubMed  Google Scholar 

  55. Hayek SM, Joseph PN, Mekhail NA. Pharmacology of intrathecally administered agents for treatment of spasticity and pain. Semin Pain Med. 2003;1(4):238–53.

    Article  CAS  Google Scholar 

  56. Gracies JM, Nance P, Elovic E, McGuire J, Simpson DM. Traditional pharmacological treatments for spasticity. Part II: general and regional treatments. Muscle Nerve Suppl. 1997;6:S92–120.

    Article  CAS  PubMed  Google Scholar 

  57. Kroin JS, Penn RD. Cerebrospinal fluid pharmacokinetics of lumbar intrathecal baclofen. In: Lakke JP, Delhaas EM, Rutgers AW, editors. Parenteral drug therapy in spasticity and Parkinson’s disease. New York, NY: Parthenon; 1991. p. 73–83.

    Google Scholar 

  58. Hoving MA, van Raak EP, Spincemaille GH, Palmans LJ, Becher JG, Vles JS, Dutch Study Group on Child Spasticity. Efficacy of intrathecal baclofen therapy in children with intractable spastic cerebral palsy: a randomised controlled trial. Eur J Paediatr Neurol. 2009;13:240–6.

    Article  PubMed  Google Scholar 

  59. Hoving MA, van Raak EP, Spincemaille GH, Palmans LJ, Sleypen FA, Vles JS, Dutch Study Group on Child Spasticity. Intrathecal baclofen in children with spastic cerebral palsy: a double-blind, randomized, placebo-controlled, dose-finding study. Dev Med Child Neurol. 2007;49:654–9.

    Article  PubMed  Google Scholar 

  60. Stearns L, Boortz-Marx R, Du Pen S, Friehs G, Gordon M, Halyard M, et al. Intrathecal drug delivery for the management of cancer pain: a multidisciplinary consensus of best clinical practices. J Support Oncol. 2005;3:399–408.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. University at Buffalo Neurosurgery, 180 Park Club Lane, Williamsville, NY, 14221, USA

    Andrea C. Wong

  2. Department of Anesthesiology and Pain Management, University Hospitals Cleveland Medical Center, Cleveland, OH, USA

    Salim M. Hayek

Authors
  1. Andrea C. Wong
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Salim M. Hayek
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Andrea C. Wong .

Editor information

Editors and Affiliations

  1. Lenox Hill Hospital, New York, New York, USA

    Sudhir Diwan

  2. The Center for Pain Relief, Charleston, West Virginia, USA

    Timothy R Deer

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer International Publishing AG, part of Springer Nature

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Wong, A.C., Hayek, S.M. (2018). Intrathecal Drug Delivery: Medication Selection. In: Diwan, S., Deer, T. (eds) Advanced Procedures for Pain Management. Springer, Cham. https://doi.org/10.1007/978-3-319-68841-1_31

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-68841-1_31

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-68839-8

  • Online ISBN: 978-3-319-68841-1

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation