Intractable pruritus during outpatient epidural hydromorphone infusion: A case report and a focused review of the literature

Xiulu Ruan, MD; Li Ma, MD, PhD; J. Patrick Couch, MD; Tao Chen, MD, PhD; Gary W. Bumgarner, PhD

doi:10.5055/jom.2015.0267

Authors

Xiulu Ruan, MD
Li Ma, MD, PhD
J. Patrick Couch, MD
Tao Chen, MD, PhD
Gary W. Bumgarner, PhD

DOI:

https://doi.org/10.5055/jom.2015.0267

Keywords:

opioid-induced pruritus, epidural infusion, peripheral opioid receptor, μ-opioid receptor, -opioid receptor, hydromorphone, oxycodone, methadone

Abstract

Background: Intraspinal drug delivery therapy has been increasingly used in patients with intractable, nonmalignant pain who have failed to respond to conventional treatment or cannot tolerate systemic opioid(s) due to adverse events. By infusing a small dose of an opioid analgesic directly into the cerebrospinal fluid, near opioid receptors, profound spinal analgesia can be obtained. Before the implantation of permanent intraspinal pump, a neuraxial opioid infusion trial is usually conducted to demonstrate the effectiveness of neuraxial opioid for analgesia. Patient-controlled epidural opioid infusion trial, performed in an outpatient setting, is one of the approaches used to conduct such a trial.

Objective: To report a case of severe pruritus observed during the continuous epidural hydromorphone infusion trial and to conduct a focused review of the literature.

Case report: An otherwise healthy 56-year-old lady, with a 4-year history of severe low back pain and bilateral leg pain due to failed back surgery syndrome, was referred to our clinic for intraspinal drug delivery therapy. Following a preimplantation psychological evaluation confirming her candidacy, she consented to an outpatient patient-controlled continuous epidural hydromorphone trial. A tunneled lumbar epidural catheter was placed at L3-L4 with catheter tip advanced to L2 under fluoroscopic guidance. Satisfactory catheter placement was confirmed by epidurogram. The catheter was then tunneled subcutaneously and connected to a Microject™ patient-controlled epidural analgesia (PCEA) pump (Codman, Raynham, MA). The pump was programmed to deliver hydromorphone 0.3 mL/h (0.06 mg, concentration 0.2 mg/mL) at basal rate of 0.3 mL/h, with bolus dose set at 0.2 mL (0.04 mg) and 30-minute lockout interval. The patient was instructed how to operate the infusion pump prior to discharging home. During the infusion trial, she reported satisfactory analgesia (>90 percent pain reduction) and was able to reduce her oral opioid dose by more than 80 percent. However, she developed severe, persistent itching, unresponsive to meticulous epidural infusion titration or various antipruritic treatments. Her pruritus remained severe and unabated until a few hours after the termination of the epidural hydromorphone infusion.

Conclusion: Pruritus may occur and persist during epidural hydromorphone infusion. This report describes severe pruritus in a patient on epidural hydromorphone administration, in the setting of an outpatient infusion trial.

Author Biographies

Xiulu Ruan, MD

Co-Medical Director, Director, Clinical Research, Physicians’ Pain Specialists of Alabama, PC, Mobile, Alabama.

Li Ma, MD, PhD

Associate Director, Physicians’ Weight Loss & Wellness, LLC, Mobile, Alabama

J. Patrick Couch, MD

Co-Medical Director, Physicians’ Pain Specialists of Alabama, PC, Mobile, Alabama

Tao Chen, MD, PhD

Staff Physician, Physicians’ Pain Specialists of Alabama, PC, Mobile, Alabama.

Gary W. Bumgarner, PhD

McWhorter School of Pharmacy, Samford University, Birmingham, Alabama

References

Krames E: Intraspinal analgesia for nonmalignant pain. In Interventional Pain Management. 2nd ed. Philadelphia, PA: WB Saunders Company, 2001: 609-619.

Raphael J, Southall J, Gnanadurai T, et al.: Long-term experience with implanted intrathecal drug administration systems for failed back syndrome and chronic mechanical low back pain. BMC Musculoskelet Disord. 2002; 3(1): 17.

Deer T, Chapple I, Classen A, et al.: Intrathecal drug delivery for treatment of chronic low back pain: Report from the National Outcomes Registry for Low Back Pain. Pain Med. 2004; 5(1): 6-13.

Kumar K, Kelly M, Pirlot T: Continuous intrathecal morphine treatment for chronic pain of nonmalignant etiology: Long-term benefits and efficacy. Surg Neurol. 2001; 55(2): 79-86.

Anderson VC, Burchiel KJ: A prospective study of long-term intrathecal morphine in the management of chronic nonmalignant pain. Neurosurgery. 1999; 44(2): 289-300.

Paice JA, Penn RD, Shott S: Intraspinal morphine for chronic pain: A retrospective, multicenter study. J Pain Symptom Manage. 1996; 11(2): 71-80.

Du Pen SL, Du Pen A: Tunneled epidural catheters: Practical considerations and implantation techniques. In Waldman SD (ed.): Interventional Pain Management. 2nd ed. Philadelphia, PA: WB Saunders; 2001: 627-643.

Paus R, Schmelz M, Bíró T, et al.: Frontiers in pruritus research: Scratching the brain for more effective itch therapy. J Clin Investig. 2006; 116(5): 1174-1186.

Ballantyne JC, Loach AB, Carr DB: Itching after epidural and spinal opiates. Pain. 1988; 33(2): 149-160.

Ganesh A, Maxwell LG: Pathophysiology and management of opioid-induced pruritus. Drugs. 2007; 67(16): 2323-2333.

Scott PV, Fischer H: Spinal opiate analgesia and facial pruritus: A neural theory. Postgrad Med J. 1982; 58(683): 531-535.

Horta ML, Ramos L, Gonçalves ZR: The inhibition of epidural morphine-induced pruritus by epidural droperidol. Anesth Analg. 2000; 90(3): 638-641.

Reich A, Szepietowski J: Opioid-induced pruritus: An update. Clin Exp Dermatol. 2010; 35(1): 2-6.

Gan TJ, Ginsberg B, Glass PS, et al.: Opioid-sparing effects of a low-dose infusion of naloxone in patient-administered morphine sulfate. Anesthesiology. 1997; 87(5): 1075-1081.

Soledad Cepeda M, Alvarez H, Morales O, et al.: Addition of ultralow dose naloxone to postoperative morphine PCA: Unchanged analgesia and opioid requirement but decreased incidence of opioid side effects. Pain. 2004; 107(1): 41-46.

Charuluxananan S, Kyokong O, Somboonviboon W, et al.: Nalbuphine versus ondansetron for prevention of intrathecal morphine-induced pruritus after cesarean delivery. Anesth Analg. 2003; 96(6): 1789-1793.

Gunter J, McAuliffe J, Gregg T, et al.: Continuous epidural butorphanol relieves pruritus associated with epidural morphine infusions in children. Pediatr Anesth. 2000; 10(2): 167-172.

Jeon Y, Hwang J, Kang J, et al.: Effects of epidural naloxone on pruritus induced by epidural morphine: A randomized controlled trial. Int J Obstet Anesth. 2005; 14(1): 22-25.

Maxwell LG, Kaufmann SC, Bitzer S, et al.: The effects of a small-dose naloxone infusion on opioid-induced side effects and analgesia in children and adolescents treated with intravenous patient-controlled analgesia: A double-blind, prospective, randomized, controlled study. Anesth Analg. 2005; 100(4): 953- 958.

Ko M, Song M, Edwards T, et al.: The role of central μ opioid receptors in opioid-induced itch in primates. J Pharmacol Exp Ther. 2004; 310(1): 169-176.

Waxler B, Dadabhoy ZP, Stojiljkovic L, et al.: Primer of postoperative pruritus for anesthesiologists. Anesthesiology. 2005; 103(1): 168-178.

Kumar K, Singh SI: Neuraxial opioid-induced pruritus: An update. J Anaesthesiol Clin Pharmacol. 2013; 29(3): 303.

Rapp SE, Egan KJ, Ross BK, et al.: A multidimensional comparison of morphine and hydromorphone patient-controlled analgesia. Anesth Analg. 1996; 82(5): 1043-1048.

Guedes A, Papich M, Rude E, et al.: Comparison of plasma histamine levels after intravenous administration of hydromorphone and morphine in dogs. J Vet Pharmacol Ther. 2007; 30(6): 516-522.

Yamamoto A, Sugimoto Y: Involvement of peripheral mu opioid receptors in scratching behavior in mice. Eur J Pharmacol. 2010; 649(1): 336-341.

Phan NQ, Bernhard JD, Luger TA, et al.: Antipruritic treatment with systemic μ-opioid receptor antagonists: A review. J Am Acad Dermatol. 2010; 63(4): 680-688.

Wang Y-h, Sun J-f, Tao Y-m, et al.: The role of -opioid receptor activation in mediating antinociception and addiction. Acta Pharmacol Sin. 2010; 31(9): 1065-1070.

Spetea M: Opioid receptors and their ligands in the musculoskeletal system and relevance for pain control. Curr Pharm Des. 2013; 19(42): 7382-7390.

Arendt-Nielsen L, Olesen AE, Staahl C, et al.: Analgesic efficacy of peripheral -opioid receptor agonist CR665 compared to oxycodone in a multi-modal, multi-tissue experimental human pain model: Selective effect on visceral pain. Anesthesiology. 2009; 111(3): 616-624.

Nielsen CK, Ross FB, Lotfipour S, et al.: Oxycodone and morphine have distinctly different pharmacological profiles: Radioligand binding and behavioural studies in two rat models of neuropathic pain. Pain. 2007; 132(3): 289-300.

Lalovic B, Kharasch E, Hoffer C, et al.: Pharmacokinetics and pharmacodynamics of oral oxycodone in healthy human subjects: Role of circulating active metabolites. Clin Pharmacol Ther. 2006; 79(5): 461-479.

Zwisler ST, Enggaard TP, Noehr-Jensen L, et al.: The hypoalgesic effect of oxycodone in human experimental pain models in relation to the CYP2D6 oxidation polymorphism. Basic Clin Pharmacol Toxicol. 2009; 104(4): 335-344.

Volpe DA, Tobin GAM, Mellon RD, et al.: Uniform assessment and ranking of opioid mu receptor binding constants for selected opioid drugs. Regul Toxicol Pharmacol. 2011; 59(3): 385-390.

Klimas R, Witticke D, El Fallah S, et al.: Contribution of oxycodone and its metabolites to the overall analgesic effect after oxycodone administration. Expert Opinion Drug Metab Toxicol. 2013; 9(5): 517-528.

Löfdal KCS, Andersson ML, Gustafsson LL: Cytochrome P450-mediated changes in oxycodone pharmacokinetics/pharmacodynamics and their clinical implications. Drugs. 2013; 73(6): 533-543.

Lorenzini K, Daali Y, Dayer P, et al.: Pharmacokinetic–pharmacodynamics modelling of opioids in healthy human volunteers. A minireview. Basic Clin Pharmacol Toxicol. 2012; 110(3): 219-226.

Staahl C, Upton R, Foster DJ, et al.: Pharmacokinetic-pharmacodynamic modeling of morphine and oxycodone concentrations and analgesic effect in a multimodal experimental pain model. J Clin Pharmacol. 2008; 48(5): 619-631.

Trescot AM, Datta S, Lee M, et al.: Opioid pharmacology. Pain Physician. 2008; 11(2 suppl): S133-S153.

Nalamachu SR: Opioid rotation in clinical practice. Adv Ther. 2012; 29(10): 849-863.

Vissers K, Besse K, Hans G, et al.: Opioid rotation in the management of chronic pain: Where is the evidence? Pain Pract. 2010; 10(2): 85-93.

Davis MP, Walsh D: Methadone for relief of cancer pain: A review of pharmacokinetics, pharmacodynamics, drug interactions and protocols of administration. Support Care Cancer. 2001; 9(2): 73-83.

Eap CB, Buclin T, Baumann P: Interindividual variability of the clinical pharmacokinetics of methadone. Clin Pharmacokinet. 2002; 41(14): 1153-1193.

Foster DJ, Somogyi AA, Bochner F: Methadone N-demethylation in human liver microsomes: Lack of stereoselectivity and involvement of CYP3A4. Br J Clin Pharmacol. 1999; 47(4): 403-412.

Garrido MJ, Trocóniz IF: Methadone: A review of its pharmacokinetic/pharmacodynamic properties. J Pharmacol Toxicol Methods. 1999; 42(2): 61-66.

Blake AD, Bot G, Freeman JC, et al.: Differential opioid agonist regulation of the mouse μ opioid receptor. J Biol Chem. 1997; 272(2): 782-790.

He L, Kim J, Ou C, et al.: Methadone antinociception is dependent on peripheral opioid receptors. J Pain. 2009; 10(4): 369-379.