When Should Epidural or Intrathecal Medications and Pumps Be Considered for Pain Management?

Introduction and Scope of the Problem

Most patients can achieve satisfactory pain control and tolerable side effects with the standard WHO Three-Step Analgesic Pain Ladder, which increases medication potency and dosages until pain relief is achieved. However, systemic pain medications may not be effective for some patients regardless of route, because of unacceptable side effects like sedation or delirium, or refractory pain despite dose escalation. The number of patients who do not achieve satisfactory pain control varies from 10% to 20% and is likely dependent on who inquires about the patient’s pain, the patient’s expectations, and the level of attention paid to medication side effects. For those who are prescribed a pain regimen that follows the WHO recommendations and do not find relief, the question remains as to what approaches can be used. For some patients, pain relief using peripheral nerve blocks may be an option, but for others, there may be a benefit from neuraxial (intrathecal or epidural) administration of medication. For this group of patients, intrathecal (IT) and epidural catheter infusions may be a viable option, but they should be considered based on current evidence. The use of epidural (alongside the epidural sac, with diffusion across the dura into the spinal fluid) and IT (intrathecal, with the catheter within the subarachnoid space and medication delivered directly to the cerebral spinal fluid) therapy can be a significant help to patients with refractory pain and/or unsatisfactory side effects. These treatments may result in improved pain control, decreased systemic toxicities of the analgesic medications, and possibly prolonged survival. IT medication delivery has been shown to be effective for end-of-life care, cancer pain, and nonmalignant pain. Advantages of IT medication administration include lower doses of medications and fewer catheter migration issues.

Consider the following case, which illustrates the benefit of these systems. L.G. was a 48-year-old with progressively worsening pain in their lower back and left pelvis resulting from metastatic adenocarcinoma of unknown primary origin that was growing in the left psoas muscle. Sustained-release oxycodone 360 mg daily plus ketamine 50 mg orally every 6 hours did not control the pain but did induce somnolence. A trial of methadone 120 mg daily plus oxycodone 140 mg every 4 hours also failed to produce adequate analgesia, especially in terms of pain with movement. An epidural trial (placing an epidural for testing of medication effect) was successful, defined as at least a 50% reduction in pain scores, with 7 mg per hour of preservative-free morphine and 7 mL per hour of 0.25% bupivacaine. The patient’s functional ability also improved. An IT pump was placed with morphine, bupivacaine, and baclofen. After several weeks, clonidine was added to the IT pump in place of the bupivacaine, providing excellent pain relief, and an epidural pump with 0.25% bupivacaine was added to target new vertebral erosion pain. Their pain remained well controlled, until they died a few weeks later comfortably at home with hospice.

This chapter reviews the indications and data on the effectiveness of epidural and IT medication therapy; however, discussion of the implantation or management of these pumps is beyond the scope of this text.

Relevant Pathophysiology

Epidural and IT pain medications target nerve conduction pathways in the spinal cord. For example, IT opioids reduce the release of presynaptic neurotransmitters and inhibit pain impulse transmission by making the nerve membranes in the postsynaptic neurons in the dorsal horn more negative, thus preventing depolarization.

Two main reasons account for the success of this treatment compared to oral, intravenous, or transdermal treatments: the ability to give different classes of drugs for which there is no enteral equivalent and the ability to escalate drugs with fewer side effects. The ability to give different and more effective drugs is one of the key advantages of IT treatment. The local anesthetics are the best example of this therapy; their primary mechanism of action is to prevent nerve conduction (achieve neuronal blockade) by blocking sodium channels, and no effective oral equivalent exists. Table 13.1 lists the main differences between conventional treatments and epidural and intraspinal treatments.

Another advantage of epidural and IT drug delivery is the ability to escalate doses of opioids with fewer side effects and toxicities compared to systemic dosing. These opioids can act directly on opioid receptors in the spinal cord, making 1 mg of IT morphine equivalent to about 300 mg of oral morphine. Conversion ratios of medications from oral or intravenous routes to epidural and IT doses have been recommended by consensus; the commonly accepted conversion ratios are listed in Table 13.2 . Of note, no clinical trials have been conducted comparing the effectiveness of conversion ratios for infused versus oral, IT, and epidural medications, so the ratios currently in use are based on expert consensus. Therefore the clinician should proceed cautiously when converting oral to IT doses and the reverse, because the ratio in some individuals has been demonstrated to be as low as 12:1 as opposed to the more commonly accepted consensus ratio of 300:1.

Summary of Evidence Regarding Treatment Recommendations