An Overview on Intraspinal Drug Delivery and Implantable Pain Pumps

By Dr. Adam J. Carinci

08/20/2009: Intraspinal drug delivery is used to treat chronic intractable pain conditions when more conservative measures, including oral medications and injections, have failed to provide adequate pain relief. Intraspinal drug delivery involves the infusion of either opioids, adjuvant drugs (local anesthetics, GABA agonists, α2-agonists, etc) or both into the intrathecal space that surrounds the spinal cord. Since the medications are delivered directly to the intrathecal space via an implanted, programmable infusion pump, this mode of treatment is referred to as intrathecal drug delivery (ITDD).

ITDD is used to treat a variety of intractable pain conditions including both chronic cancer pain and a host of non-cancer related pain syndromes. Based on survey data from 2005 of physicians with experience in implanting ITDD pumps, 79% of intrathecal pumps were placed for non-cancer pain.1 More recently, however, anecdotal evidence suggests that this trend is reversing, with pain physicians now tending to reserve ITDD for cancer-related pain as opposed to noncancer pain. The reasons for this potential trend reversal include concerns in non-cancer pain regarding cost, efficacy, functional improvement, and side effects.

At present, only morphine and ziconotide (an N-type voltage-sensitive calcium channel blocker) are FDA approved for intrathecal drug delivery for chronic pain. There are, however, many more agents that are used by physicians to provide analgesia for chronic pain via the intraspinal route. These include:

• Opioids - i.e., hydromorphone, fentanyl, and methadone
• Local anesthetics - i.e., bupivicaine and ropivacaine
• α2-agonists - i.e., clonidine
• GABA agonists - i.e., baclofen and midazolam
• NMDA antagonists - i.e., ketamine
• Other agents - i.e., ketorolac, gabapentin, and neostigmine

Most often, morphine is used as the primary agent or in combination with one of the above agents. There are few if any studies comparing the efficacy of the above medications relative to one another.

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ITDD is not a benign procedure and complications can arise from both the surgical implantation as well as from the intraspinal medications. Some of these complications include:

Postoperative issues:

• CSF leaks
• Hematoma formation
• Infection
• Medication related side effects:
• Nausea and vomiting
• Sedation
• Pruritis
• Urinary retention
• Sexual dysfunction
• Endocrine abnormalities
• Neurological deficits secondary to spinal cord compression from catheter-tip granuloma formation is one of the most feared complications. These granulomas appear to be related to high dose intrathecal opioids. For these reasons, consideration of potential ITDD should not be taken lightly.

Prospective studies looking at the efficacy of intrathecal drug delivery are limited. Overall, these studies suggest that ITDD can provide significant pain relief with fewer side effects when compared to standard medical analgesic regimens. Most patients experience an improved quality of life, consume less oral opioid analgesics, and have some improved functionality following implantation. Some patients are able to return to work, though this appears to be the exception rather than the rule. Regarding cancer related pain, one study found improved survival among patients in the ITDD group compared to the standard medical analgesic control group; 54% alive at six months versus 37% in the standard control group.1

Although randomized controlled studies on ITDD are few, available evidence suggests that the technique benefits patients with chronic, intractable cancer and non-cancer related pain syndromes. ITDD has been shown to be effective among many types of pain, including neuropathic, nociceptive, and cancer related pain. The decision to pursue ITDD must be done on a patient-by-patient basis, evaluating each patient’s unique needs and carefully weighting the pros and cons of treatment vs. conservative therapy.

Reference:
1. Ahmed, S. Intrathecal Drug Delivery for Chronic Pain Management. In: Translational Pain Research, Volume 1. Editor: Mao, Jianren. Nova Science Publishers, Inc. 2006.