1. For an appropriate candidate for intrathecal drug delivery, what kind of protocol is typically followed for a screening test?

There are a number of viable options to choose from when conducting a screening test for intrathecal drug delivery. The specific protocol that is selected depends on the physician's preference but may be influenced by the requirements of insurers or hospital protocol.

The screening test can be performed epidurally or intrathecally.
A screening dose can be administered as a bolus dose or continuous flow through a percutaneous catheter (that may be tunneled). The length of the screening test can vary.
The screening test can be performed on an inpatient or outpatient basis. The patient's pathology and the goals of treatment often influence the type of screening protocol. For example, a cancer patient might be considered for a short trial, perhaps even a single shot, whereas a patient in whom improved function is a major goal of therapy might warrant a prolonged trial with objective assessment. Epidural fibrosis or metastases would argue for intrathecal rather than an epidural trial. If reduction of side effects from oral opiates is the goal of therapy, a trial of sufficient length with a (probably intrathecal) dose that approximates that which will need to be delivered by the intrathecal drug delivery system is indicated. Some practitioners feel that certain settings, such as outpatient trials, are safer when done with epidural catheters.

Regardless of the selected screening test protocol, trained staff must closely monitor the patient and appropriate equipment should be available in case of an overdose. The screening dose will depend on the patient's regimen of pain medications. Converting the current oral or parenteral opioid dose to an intrathecal dose is an acceptable starting point for opioid-tolerant patients.

2. During a screening test for intrathecal drug delivery for chronic nonmalignant pain, what are the relative merits of using functionality/achievement of Activities of Daily Living (ADLs) in addition to pain scores as a measure of success?

The value of a functional assessment depends on the specific patient and the goals of therapy. Functional assessments provide more objective evidence of the response to a screening test than can be obtained by patient self-report of pain and can facilitate appropriate patient selection for intrathecal drug delivery. Placebo responses may complicate interpretation of screening test results. Some patients may overstate their pain relief during a screening test
out of concern that they might be denied the therapy. Some patients have pain relief without accompanying functional improvement such that a satisfactory long-term outcome will not be achieved (depending upon the goals of the therapy). Functional assessments clarify some of these confounding factors. However, functional assessment adds a layer of complexity to the evaluation. Additional time and personnel may be required, the length of the screening test may need to be extended to have adequate time to assess responses, and additional expense may be incurred. No data are available to indicate that functional assessments improve long-term outcomes, but functional assessments may facilitate realistic outcomes expectations and promote good long-term outcomes.

3. Is an MRI/CT of the spine routinely requested before implantation of an intrathecal drug delivery system for cancer pain?

Radiographic imaging of the spinal column with MRI/CT is prudent to assess canal patency whenever spinal canal compromise is suspected. It is not necessary for every patient with cancer-related pain to undergo spine imaging. However, it is appropriate for those patients with known or suspected metastatic bone disease. Radiographic imaging of the spinal
column is also appropriate in patients who may have spinal canal compromise from other causes (e.g., previous spine trauma, advanced degenerative disease of the spine).

4. Can an intrathecal catheter be implanted immediately after a successful screening test of epidural/intrathecal narcotics or should you wait days to weeks to watch for possible infection?

Implantation of a permanent intrathecal catheter can be performed with relatively little risk of infection immediately after a single bolus screening test. Implantation of a permanent catheter immediately after a screening test with a percutaneous catheter may be performed safely in most instances, especially if the screening test is relatively short (less than 3-5 days duration) and if contamination of the catheter site is believed to be unlikely. A permanent catheter should not be implanted until the intended implant site is completely free of evidence of infection (which may require days to several weeks, depending upon the degree of inflammation at the implant site). This is of particular concern if:

The screening test is greater than 5-7 days duration.
The possibility exists that the percutaneous catheter was contaminated.
Evidence of inflammation or infection is present at the temporary catheter site.
Ideally, the percutaneous screening catheter should be placed at a spinal level different from where the permanent catheter is to be inserted to minimize the chance of cross-contamination.

5. Do you need to use fluoroscopy when placing the intrathecal catheter?

Many physicians recommend that fluoroscopy be used during insertion of intrathecal catheters: difficult placement of the 15-gauge introducer at an acceptable angle and level cannot always be predicted preoperatively. Fluoroscopy facilitates placement. Return of cerebrospinal fluid (CSF) serves as evidence that a catheter is in the intrathecal space but provides no information about catheter tip location. Catheter tip placement through the neural foramina is also possible with poor delivery of drug and possible nerve root irritation. A badly coiled or misplaced catheter may allow CSF flow in the position of the patient in theatre but is subject to obstruction once the patient flexes and extends. These would not be evident without fluoroscopy. Once the catheter is placed contrast can be injected intraoperatively to assess for obstruction to CSF flow.

At this time, only morphine and baclofen are approved for intrathecal use-both diffuse readily throughout CSF and catheter tip location does not seem to be a critical issue. However, many physicians recommend that the catheter tip be positioned in the thoracic region. Without radiographic guidance, a catheter may end up in the lumbar area in spite of efforts to direct it rostrally. Catheter tip location might become more important as new intrathecal agents are developed, some of which might act at the level of the spinal dorsal horn and which might require infusion at specific spinal segmental levels. Some physicians recommend that the tip of the catheter be placed at the approximate spinal level of incoming nociceptive pain signals to ensure drug delivery at these locations along the spinal cord. Fluoroscopy facilitates placement of the catheter at the appropriate level in such cases.

1. What are the options for pump refill if it is not done in a clinic?

Pump refills are typically performed in a clinic or other suitable medical setting (e.g., hospital). Some patients may be unable to travel to the clinic of the physician who typically refills their pumps (e.g., if travel distances are great and/or the patient is too ill to travel). These patients can usually have their pumps refilled in their homes by properly trained visiting nurses or in the clinic of a nearby physician who is familiar with the intrathecal drug infusion system. Refill of the SynchroMed pump requires that a physician programmer be available to interrogate and program the pump

2. For patients with nonmalignant pain, "drug holidays" may be used to address drug tolerance. How often and at what point should they be implemented?

A patient who has had progressively increasing dose requirements and no longer receives sufficient symptom relief may benefit from a "drug holiday." A careful history taking may reveal that the pain is much worse with certain, predictable patterns or at certain times of the day.
In this case, delivering more medicine at these times (complex continuous programming)
may allow better control without increasing the overall daily dose. The role of the drug holiday approach in the management of patients receiving intrathecal analgesic infusions has not been established.

The specific timing of drug holidays varies with the individual patient and the managing physician but can be considered:

When the patient is receiving the maximum dose of medication that s/he and the physician
are comfortable delivering intrathecally, or If further dose increases are limited by the delivery rate of the infusion system. In general, holidays of several days to several weeks have been described, but the time necessary for reversal of tolerance is unknown. In addition, the patient may require management of their withdrawal symptoms during the initial drug holiday period. Close monitoring for signs of withdrawal must be observed during the time that the patient is being weaned off the intrathecal opiates, especially if substantial doses are in use.

Before implementing a drug holiday, any potential explanation for perceived increased tolerance must be thoroughly considered. The following can all mimic a tolerance syndrome:

Progression of existing disease (e.g., worsening metastases, fractures)
Appearance of a new disease process that may be remediable (e.g., a new herniated disc)
Technical problems (e.g., catheter leaks)

3. Under what conditions should an implanted drug delivery system be removed?

An implanted drug delivery system should be removed if it becomes infected (e.g., meningitis, epidural abscess, pocket infection, catheter track infection). It may also be explanted if the patient requests removal, for example, when an acceptable therapeutic response cannot be achieved. In this instance, it is recommended that a psychological evaluation be performed before explantation, perhaps even before and after weaning off the narcotics. In addition, consideration should be given to placing saline in the pump and continuing a low-rate infusion for several weeks-at least a month-to provide the patient sufficient opportunity to be certain that s/he wants the system removed.

In the case of a deceased patient, disable the alarm and remove the pump before cremation.

4. What are the factors that may lead to dose escalation?

There are many reasons for escalating dose requirements, frequently referred to as "tolerance." True physiological/pharmacological tolerance may occur (i.e., alterations in drug receptors within the central nervous system). Drug diffusion through spinal fluid and into the spinal cord may become impaired (e.g., arachnoid scarring or cyst, granuloma, or inflammatory mass formation at the catheter tip). Increasing dose requirements can also signal changes in the patient's pain disorder. The underlying disease for which the patient is receiving therapy may progress (e.g., cancer, osteoarthritis), new pain disorders may arise, and/or changes in psychosocial factors may exacerbate the pain disorder. Some patients, once having achieved a degree of pain relief, increase their level of activity and work up to their level of pain tolerance. Outcomes expectations may be unrealistic, leading patients to request increasing amounts of medication to achieve the degree of pain relief they hope for. The delivery system may malfunction (e.g., pump malfunction, catheter obstruction, migration, or break). Each of these possibilities should be considered when an individual has progressively increasing dose requirements with insufficient pain relief.

For information on contraindications, warnings, precautions and adverse events, see Important Safety Information and Risks for intrathecal drug delivery.

1. What types of complication can occur at the tip of the catheter of an intrathecal drug delivery system placed a few years earlier?

Epidural abscess formation at the tip of a catheter placed several years earlier is extremely rare. Should such an infection occur, consideration should be given to the possibility that it is coincidental, unrelated to placement of the catheter. The patient should be carefully evaluated for the primary source of the infection. A granuloma or inflammatory mass may form at the catheter tip (see note below).

The formation of a granuloma or inflammatory mass is more likely than epidural abscess to occur after several years, and should be suspected in any individual with an implanted drug delivery system who has the onset of symptoms and signs of spinal cord or cauda equina compression. However, granuloma or inflammatory mass formation may occur at any time,
as the aetiology for their formation has not been established.

Note: In rare instances, the development of an inflammatory mass at the tip of the implanted catheter may occur. This can result in progressive clinical signs that bear monitoring. These signs include a progressive change in the character, quality, or intensity of pain; an increase
in the level and degree of pain despite dose escalation; sensory changes (i.e., numbness, tingling, burning); hyperesthesia and/or hyperalgesia. Presentations that require immediate evaluation include bowel and/or bladder dysfunction, myelopathy, conus syndrome, gait disturbances or difficulty ambulating, paraparesis or paralysis, or sensory loss.