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14 Articles in Volume 18, Issue #2
Ask the Expert: Is there evidence to prescribe cyclobenzaprine long-term?
Challenging the Chronic Pain Personality Profile
Designer Peptide May Prevent Chemo-Induced Neuropathy
Inside the Cancer Pain Research Consortium
Intrathecal Drug Therapy for Cancer-Related Pain
Managing Cancer Pain in an Era of Modern Oncology
Mapping Complex Pain: A Case Study
Medication Overuse Headache: Inaccurate and Overdiagnosed
Pain and Fall Risk in the Elderly
Reporting Quality of Care in Cancer Pain Management
Sharing the Risk: An Update to DEA & Doctors Working Together
The Intensifying Conflict Between Opioid Control and Pain Control
Two Mobile Apps Aim to Target Patient Compliance & Safety
Why Prescribers Need to Adopt Abuse-Deterrent Opioids

Intrathecal Drug Therapy for Cancer-Related Pain

An update on key considerations for oncology and pain practitioners

Overview

Intrathecal drug delivery, or intrathecal therapy (ITT), has been a mainstay for the management of severe pain recalcitrant to systemic pain treatments in the oncology population. While this therapy is well accepted in the literature, there are still barriers to its implementation in patients with cancer. With enhanced education of advanced practice providers in this field, it is hoped that access to the therapy for the management of cancer pain will increase. Herein, the authors discuss general indications and patient selection for ITT, with a discussion on management of the infusion, as well as post-procedure concerns.

Cancer pain remains undertreated, and a significant number of patients with cancer die while suffering from severe untreated pain every year. In addition, it is estimated that at least 1.7 million new cases of cancer were diagnosed in the United States in 2017.1 The number of individuals living beyond a cancer diagnosis reached nearly 14.5 million in 2014 and is expected to rise to almost 19 million by 2024.1

With an increasing survival rate for oncologic patients, the prevalence of cancer pain is also rising. Pain occurs in 67% of patients with metastatic cancer and is the most prevalent symptom of patients presenting to palliative care clinics.2,3 While the vast majority of chronic cancer pain may be managed with pharmacologic therapies, many patients do not achieve adequate analgesia despite the availability of many regimens.4 Treatment of cancer-related pain has shifted toward chronic pain management strategies, especially among cancer survivors. Intrathecal drug delivery may provide an alternate route of administration for analgesics, which may improve pain relief and side effect management.5

Images courtesy Medtronic and FlowonixImages courtesy Medtronic and Flowonix

 

Patient Selection for ITT

As certain cancers are associated with higher incidence of pain, patient selection for ITT is extremely important to establish who may benefit from intrathecal pump placement.

These factors include:

  • patient diagnosis and expected survival time
  • previous opioid history
  • type and location of pain
  • catheter location
  • support system
  • ability to adhere to ITT regimen
  • psychological and cognitive status.

Therefore, before implantation, it is essential to have a clear diagnosis, a comprehensive physical exam and psychological evaluation (this may be voluntary for cancer pain patients). Once it is established that a patient may benefit from ITT, it is essential to receive proper treatment for conditions such as psychiatric disorders and psychosocial issues that could negatively impact treatment outcomes. It may also be helpful for patients with cancer-related pain to undergo counseling to address any existential or spiritual concerns. In addition, all patients should have realistic expectations of ITT on pain relief and understand how it may impact their daily life.2

Typically, ITT is recommended after initial attempts of pain control are not achieved with systemic pain regimens, such as opioid therapy. Intrathecal drug delivery may be considered, if and when, its benefits are consistent with the patient and family’s goals of care. Intrathecal drug delivery involves the infusion of highly concentrated solutions into the intrathecal space. The medication interrupts pain signals to the brain by blocking the transmission (local anesthetic) or facilitating the modulation of the pain signal (opioid) in the spine. When delivered intrathecally, opioids and adjunct analgesics may provide greater pain relief at significantly lower doses with fewer side effects.

Medication Choices

The United States Food and Drug Administration (FDA) approves spinal delivery medications in the same way it approves other medication—that is, after extensive clinical trials demonstrate safety and efficacy. Currently, only three medications have been approved by FDA for use via the intrathecal route: morphine, ziconotide, and baclofen.7 The use of other agents is common among pain practitioners who manage intrathecal pumps, and recommendations from the Polyanalgesic Consensus Conference 2017 of such agents provided guidance on safe practice and patient safety.7 Hydromorphone, fentanyl, and sufentanil are not FDA approved for spinal use, but are commonly used by practitioners for intrathecal infusions.

Side Effects

Despite its relative small dosages compared to oral or parenteral opioids, escalating doses of intrathecal opioids may still lead to undesirable side effects, including pruritus, nausea and vomiting, constipation, respiratory depression, sexual dysfunction, hyperalgesia, urinary retention, and sedation.8 For many patients who are taking high doses of intrathecal opioids and still experience refractory pain, adding a local anesthetic may significantly improve their symptoms, pain scores, activity level, and quality of life.9 Local anesthetics have been used for many years in patients with severe and intractable pain to offer more effective pain control without necessitating very high dosages of opioids. In fact, survey data suggest that almost 20% of intrathecal pump patients received local anesthetics as early as 1996.10

Bupivacaine

Bupivacaine is FDA approved for continuous epidural infusion but is commonly used, intrathecally, in combination with opioids for the treatment of cancer pain. Bupivacaine is a lipophilic sodium channel blocker that preferentially blocks nerve fibers in pain conduction. However, at higher dosages, bupivacaine may also block nerve fibers involved in sensation to light touch and motor function.11 While many researchers have suggested that intrathecal bupivacaine is efficacious when added to opioid medications, to date, there are few guidelines to suggest the safe starting dose of bupivacaine in intrathecal pumps, or the safe rate at which to up-titrate the dosage.12

Doses are typically titrated up or down in accordance to the individual patient, however, there is a gap in the literature in regards to how much and how quickly to titrate. Further studies are needed to elucidate the safe starting dose of bupivacaine, the safe rate of up-titration, and to control for the concurrently used opioids and other adjuvants such as clonidine.

Combinations with Clonidine & Opioids

Drug combinations in spinal infusions are often necessary for effective treatment of neuropathic and mixed pain disorders. The use of other agents is common among pain practitioners who manage intrathecal pumps, and discussions and recommendations for the safety of such agents are included in the Polyanalgesic Consensus Conference.7

Most experienced clinicians are comfortable using two drugs in combination, generally an opioid and bupivacaine or an opioid and clonidine. Both bupivacaine and clonidine may be associated with postural hypotension during initiation. Bupivacaine has also been associated with dose-dependent sensorimotor loss with epidural or intrathecal delivery. In very intractable neuropathic pain situations, one may see both clonidine and bupivacaine used with the opioid in a “three way” infusion. Clonidine and bupivacaine together can be profoundly synergistic for neuropathic pain—so much so that doses used with the combination are almost always less than one would see when using single agent therapy. Oral antihypertensive agents are often discontinued and blood pressure must be carefully monitored when using clonidine and bupivacaine together.

Post-Procedure Care

Potential complications associated with intrathecal pump implantation may be broadly classified as immediate (during the procedure) or later (after the procedure is completed) Hypotension, post-dural puncture headache, bleeding, hematoma, granuloma, and infection all represent potential complications associated with the procedure. Meningitis is the most serious of potential complications. Cancer patients are especially susceptible to infectious complications as they are often immune-compromised, malnourished, and exposed to cytotoxic chemotherapeutic agents. Good surgical techniques and hypervigilance may significantly reduce these risks. The ultimate success of an intrathecal pump further rests in proper patient selection.

Pump Refilling

The vast majority of patients with intrathecal pumps require interrogation and medication refill on a regular basis.7 As with any medical procedure, patient education and consent are required and practitioners refilling the pump are expected to be adequately trained and carefully supervised. Prior to refilling, patients should be assessed for adequacy of analgesia, neurologic function, and any potential infectious and other complications. Medications should be reviewed for proper concentration, volume, and dosing. All intrathecal refill procedures must be performed with sterile technique. Fluoroscopy or ultrasonography may be used as a guide.13

Special precautions are necessary during the refilling process to avoid injecting medication into the catheter access port or into subcutaneous tissues. Inadvertent injection of the drug into subcutaneous tissues may lead to serious injury, opioid withdrawal, underdosing, overdose, and rarely, death. During a refill, pump volume should never be exceeded as overfilling may lead to pump failure and injury of internal pump mechanics.14 Once the pump is refilled, it is interrogated to confirm dose concentration. Necessary dose adjustments may then be made and new reservoir volume is set. In summary, intrathecal pump refill procedure has to be rigorously followed to avoid any potential procedural and post-procedure complications.

Conclusion

In recent years, intrathecal pump therapy has increased in popularity to treat refractory cancer pain.15 It has become more commonly used where conservative forms of pain management have failed to provide substantial pain relief. The benefit of ITT therapy is its direct delivery of medications into cerebrospinal fluid, allowing for smaller doses and fewer systemic side effects. As discussed, patient selection, proper medication management, and meticulous technique are all important factors in achieving successful outcomes. For patients suffering from cancer pain, intrathecal drug delivery may dramatically decrease symptoms and improve quality of life.

Intrathecal drug delivery, or intrathecal therapy (ITT), has been a mainstay for the management of severe pain recalcitrant to systemic pain treatments in the oncology population. While this therapy is well accepted in the literature, there are still barriers to its implementation in patients with cancer. With enhanced education of advanced practice providers in this field, it is hoped that access to the therapy for the management of cancer pain will increase. Herein, the authors discuss general indications and patient selection for ITT, with a discussion on management of the infusion, as well as post-procedure concerns.

Last updated on: April 12, 2019
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Managing Cancer Pain in an Era of Modern Oncology
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