Long-Term Intrathecal Infusion of Drug Combinations for Chronic Back and Leg Pain

Abstract

Continuous intrathecal infusion of analgesic drugs by implantable pumps is recognized as an established treatment option for patients with chronic pain resistant to oral or parenteral medication. Polyanalgesia, the simultaneous use of more than one intrathecal analgesic drug, is practiced relatively often, but there are only a few published clinical studies on intrathecal polyanalgesia for chronic nonmalignant pain. This pilot study represents a long-term evaluation of a treatment regimen consisting of intrathecal morphine admixed with bupivacaine, clonidine, or midazolam in patients with chronic nonmalignant back and leg pain due to degenerative lumbar spinal disease. Twenty-six adult patients have been treated by intrathecal programmable pump-controlled infusion of analgesic drugs and followed for up to 3.5 years (27 +/- 11 months). Combination of morphine with a second drug was used in 10 cases, morphine with 2 additional drugs in 12 cases, and morphine with 3 additional drugs in 4 cases. Mean daily doses at 24 months after pump implantation were 6.2 +/- 2.8 mg for morphine, 2.5 +/- 1.5 mg for bupivacaine, 0.06 +/- 0.03 mg for clonidine, and 0.8 +/- 0.4 mg for midazolam. Nineteen patients reported excellent or good long-term treatment results, 6 patients had sufficient results, and only 1 patient complained of poor therapeutic efficacy. No long-term clinical side effects of intrathecal polyanalgesia were noted. Mean morphine dose had to be increased from 1.2 mg at baseline to 5.1 mg at 24 months due to tolerance development and disease progression. This experience suggests that intrathecal polyanalgesia employing morphine combined with additional nonopioid drugs can have a favorable analgesic efficacy in patients with complex chronic pain of spinal origin, and lacks major drug-related complications.

Programmable Intrathecal Opioid Delivery Systems for Chronic Noncancer Pain: A Systematic Review of Effectiveness and Complications

“…In another study, pain ratings remained fairly stable from 6 to 24 months. 87 Pain ratings were also stable from 6 to 12 months in a study that did not include follow-up beyond 12 months. 85 Three articles reported follow-up ''success rates'' of IDDS in terms of the number of patients who continued to use their pump and had Z50% reduction in pain.…”

A Systematic Review of Pharmacologic Treatments of Pain After Spinal Cord Injury

“…58 The antinociceptive effects of clonidine are thought to be mediated via inhibitory interaction with pre-and post-synaptic primary afferent nociceptive projections in the dorsal horn, 59 and possibly by inhibition of substance P release. 60,61 Clonidine is a central acting alpha-2 agonist; Ackerman et al 59 have demonstrated that selective alpha-2 adrenergic antagonists (e.g. Yohimbine) can reverse clonidine-induced analgesia.…”

Intrathecal drug therapy for long-term pain management

“…[32][33][34][35][36] Long-term results indicate that tolerance to morphine alone can develop over time, leading to the need for dosage escalation. 34,[37][38][39] If the patient does not respond to morphine, hydromorphone or fentanyl may be necessary. 18,25 Continuously infused intrathecal hydromorphone is distributed similarly to morphine in the CSF.…”

“…36 The combination of morphine and clonidine has shown some efficacy with neuropathic pain but limited utility with other chronic pain conditions. 36,37 Siddall et al 35 conducted a double-blind, randomized, controlled trial in 15 patients with neuropathic pain secondary to spinal cord injury to determine the effectiveness of intrathecal morphine, clonidine, or combined treatment compared with that of intrathecal saline injections. The reduction of pain with either morphine or clonidine alone did not statistically differ from the relief obtained after saline administration.…”