Intrathecal Analgesia: Time to Consider it for Your Patient?

Ziconotide has FDA approval only as monotherapy. But because of its high cost and adverse effect profile, it is mainly used in combination with other IT drugs.²⁷ Ziconotide increases the risk of suicide in patients with a history of depression.²⁸ The prevalence of adverse effects correlates with a higher dose, faster titration rate, and older age.^26,28

Alpha-2 adrenergic agonists. Clonidine is the only alpha-2 agonist with FDA approval for epidural use, with several studies supporting its off-label use in combination with IT therapy.^22,29 In a prospective open-label study evaluating combination IT therapy in patients with failed back surgery syndrome, 73% reported subjective ratings of good or excellent at 2-year follow-up.²² The most common adverse effects were sedation, hypotension, nausea, and dry mouth.

Gamma-aminobutyric acid (GABA) agonists. Baclofen, a GABA agonist with FDA approval for the treatment of spasticity, has been used intrathecally since the mid-1980s.³² Several studies have supported its effectiveness for this purpose.^30,42 Clinical studies have also found IT baclofen to be effective in treating conditions such as complex regional pain syndrome, central pain, and neuropathic pain secondary to failed back surgery syndrome.^31,32 In one randomized double-blind crossover trial, 7 women with complex regional pain syndrome were given bolus injections of baclofen or saline. Those treated with baclofen experienced a reduction in pain and regained function.³¹

In another trial—a double-blind placebo-controlled study of patients with multiple sclerosis and spinal cord injury comparing baclofen with placebo—those treated with baclofen showed significant reductions in dysesthetic and spasm-related pain.³² The most common adverse effects of baclofen are drowsiness, cognitive impairment, weakness, gastrointestinal complaints, and sexual dysfunction.³¹

Which patients and which drugs? An expert consensus

Due to the potential for inconsistent patient management and the use of therapies with anecdotal evidence, the Polyanalgesic Consensus Conference (PACC)—a panel of experts in IT therapy—convened in 2000, 2003, 2007, and 2011 to develop recommendations for IT therapy and an algorithm for drug selection. PACC’s list of chronic conditions for which IT should be considered includes axial low back pain, postherpetic neuralgia, spinal cord injury, spinal stenosis, pancreatitis, osteoporosis, compression fracture, and phantom limb pain, among others.

The algorithm contains separate arms for neuropathic, nociceptive, and mixed pain states. First-line agents for neuropathic pain include morphine, alone or combined with bupivacaine, and ziconotide. For nociceptive pain, morphine, hydromorphone, fentanyl, and ziconotide are all first-line agents; for mixed pain states, the appropriate choice should be based on the clinical scenario.³³

Overseeing IT pain management in primary care

Referring potential candidates for IT therapy to specialists in pain management is just the beginning. While patients typically return to the specialist for pump refills, it is important that they see their primary care physician regularly, as well. Vigilance is required of both the FP and the patient. Any sudden worsening in pain level or acute change in neurologic function must be reported to the pain specialist immediately.

Adverse effects of medications are the most common complications

Kamran and Wright⁴³ performed a retrospective review of their practice’s Intrathecal Drug Delivery Systems database of 122 patients and found that adverse medication effects were most common, accounting for 77% of complications.

Catheter malfunctions were next, at 16%, followed by infections, at 5%.⁴³ In other studies, catheter-related complications were found to have an incidence of 15% to 25%.^44,45 Problems include kinking, breaking, leaking, and migration of the catheter. Advise patients to immediately contact their pain specialist for evaluation if they experience a sudden loss of, or change in, pain control.

Any sudden worsening in pain level or acute change in neurologic function must be reported immediately. Infectious complications, which occur infrequently, are usually limited to superficial wounds, although epidural abscesses and meningitis are possible.⁴⁶ Standard perioperative antibiotic administration helps to minimize the risk of infection. If a patient presents with signs and symptoms of an epidural abscess—back pain, fever, and variable neurologic deficits—emergent initiation of intravenous antibiotics is needed. Magnetic resonance imaging (MRI) with and without gadolinium should be obtained, as well.²²

Spinal damage. Although IT catheters are placed under fluoroscopic guidance, there is a risk of direct injury to the spinal cord; this is more common if the catheter is placed above the level of the conus medullaris. Damage to the spinal cord or exiting spinal nerves will manifest as pain, sensory loss, and/or weakness over a dermatomal distribution.⁴³

Neurologic sequelae, ranging from mild symptoms to paraplegia, can result from the formation of a granuloma at the tip of the spinal catheter. A sudden increase in pain usually occurs prior to neurologic deterioration, thereby allowing for early detection and intervention.⁴⁷ Development of a granuloma appears to be related to the long-term infusion of high-concentration opioids.³⁴ The diagnosis is confirmed by MRI, but physical exam and history are imperative in making the initial diagnosis.