Implantable Spinal Drug Delivery System Placement

Overview

Intrathecal morphine and other opioids are now widely used as useful adjuncts in the treatment of acute and chronic pain, and a number of agents show promise as analgesic agents with spinal selectivity. Continuous delivery of analgesic agents at the spinal level can be carried out using percutaneous epidural or intrathecal catheters, but vulnerability to infection and the cost of external systems typically limit them to short-term use (<6 weeks). Reliable implanted drug delivery systems are now available that make long-term delivery of medications to the intrathecal space feasible. These systems are comprised of a drug reservoir/pump implanted within the subcutaneous tissue of the abdominal wall, which is refilled periodically through an access port. The pump may be a fixed-rate, constant flow device or a variable-rate pump that can be programmed using a wireless radiofrequency transmitter similar to those used for implanted cardiac pacemakers.

Anatomy

The intrathecal catheter is placed directly within the cerebrospinal fluid (CSF) of the lumbar cistern by advancing a needle between vertebral laminae at the L2/L3 level or below. Direct delivery of the opioid at the spinal level corresponding to the dermatome(s) in which the patient is experiencing pain may improve analgesia, particularly when local anesthetics or lipophilic opioids (e.g., fentanyl or sufentanil) are used. Thus, some practitioners have advocated threading the catheter cephalad to the appropriate dermatome. In more recent years, reports of inflammatory mass formation surrounding the catheter tip of some chronic indwelling intrathecal catheters have appeared. These inflammatory masses often presented with gradual neurologic deterioration caused by spinal cord compression. Some experts recommend that implanted intrathecal catheters be placed only within the lumbar cistern below the conus medullaris (approximately below L2), where the appearance of an inflammatory mass is less likely to directly impinge on the spinal cord.

Patient Selection

Patient selection for intraspinal pain therapy is empiric and remains the subject of debate. In general, intrathecal drug delivery is reserved for patients with severe pain that does not respond to conservative treatment. In patients with cancer-related pain, most will have ongoing pain despite appropriate oral opioid therapy, or they may have developed intolerable side effects related to these medications. A randomized controlled trial (RCT) comparing maximal medical therapy with intrathecal drug delivery for cancer-related pain demonstrated improved pain control and reduction in opioid-related side effects in those who received intrathecal pain therapy. Intrathecal drug delivery has also been widely used for noncancer pain, particularly for the treatment of chronic low back pain. The use of this therapy in noncancer pain has not been subject to controlled trials. Recommendations from a 2010 consensus panel regarding key considerations for selection and implantation of patients with noncancer pain for intrathecal therapy are shown in Table 15-1.

Once a patient is selected for intrathecal therapy, a trial is carried out. Most physicians now conduct trials by placing a temporary, percutaneous intrathecal catheter and infusing the analgesic agent over several days to judge the effectiveness of this therapy before a permanent system is implanted. Some carry out the trial of intrathecal therapy using a single dose or by using a continuous epidural infusion. The most common analgesic agent used for spinal delivery is morphine; this remains the only opioid approved by the U.S. Food and Drug Administration for intrathecal use.

Level of Evidence

Quality of Evidence and Grading of Recommendation

Grade of Recommendation/ Description	Benefit vs. Risk and Burdens	Methodological Quality of Supporting Evidence	Implications
RECOMMENDATION: Intrathecal drug delivery. Intrathecal infusion of opioid, opioid and adjuvant analgesic combinations, or ziconotide may be used in selected patients with persistent, cancer-related pain unresponsive to more conservative treatments. Shared decision making regarding intrathecal infusion should include a specific discussion of potential complications. Neuraxial opioid trials should be performed before considering permanent implantation of intrathecal drug delivery systems.
2B/weak recommendation, moderate- quality evidence	Benefits closely balanced with risks and burden	II-1: RCTs with important limitations (inconsistent results, methodologic flaws, indirect, or imprecise) or exceptionally strong evidence from observational studies	Weak recommendation, best action may differ depending on circumstances or patients’ or societal values
RECOMMENDATION: Intrathecal drug delivery. Intrathecal infusion of opioid, opioid and adjuvant analgesic combinations, or ziconotide may be used in selected patients with persistent, noncancer pain unresponsive to more conservative treatments. Shared decision making regarding intrathecal infusion should include a specific discussion of potential complications. Neuraxial opioid trials should be performed before considering permanent implantation of intrathecal drug delivery systems.
2C/weak recommendation, low-quality or very low-quality evidence	Uncertainty in the estimates of benefits, risks, and burden; benefits, risk, and burden may be closely balanced	II-2: Observational studies or case series	Very weak recommendations; other alternatives may be equally reasonable

The use of intrathecal drug infusions of opioids, opioids in combination with other agents (commonly bupivacaine or clonidine), and ziconotide have all undergone extensive testing, most of which is observational and unblinded in nature. The use of intrathecal morphine has been compared with maximum medical therapy in the treatment of patients with advanced cancer and shown to provide comparable pain relief with significantly fewer opioid-related adverse effects, including sedation and fatigue. Intrathecal ziconotide has been compared with placebo in the treatment of patients with advanced illness and shown to provide marginally superior pain reduction with almost universal appearance of adverse effects, most common among them are vertigo and other central nervous system symptoms. The use of implanted drug delivery systems carries significant risk, including pump malfunction, device-related infection, and catheter-tip granuloma formation. In addition, recent population studies point to an increased risk of death in those receiving intrathecal infusions; errors in programming and misplacement of the drug into the subcutaneous pocket during refill have been proposed as possible causative factors. The risks of therapy must be closely weighed against the benefits when considering the use of long-term intrathecal drug delivery, and attempts to use more conservative means of treatment should be exhausted before using this approach.

Expert recommendations regarding the use of intrathecal drug delivery are mixed. The American Pain Society Low Back Pain Guideline Panel published a report in 2009, concluding, “There is insufficient evidence to adequately evaluate benefits of…intrathecal therapy with opioids or other medications for nonradicular low back pain.” The American Society of Anesthesiologists Task Force on Chronic Pain Management published a 2010 Practice Guideline, offering the following recommendations: “Ziconotide infusion may be used in the treatment of a select subset of patients with refractory chronic pain.” and “Intrathecal opioid injection or infusion may be used for patients with neuropathic pain. Shared decision making regarding intrathecal opioid injection or infusion should include a specific discussion of potential complications. Neuraxial opioid trials should be performed before considering permanent implantation of intrathecal drug delivery systems.” Neither group considered the use of this therapy for cancer-related pain.

Two recent guidelines were prepared by a multidisciplinary panel of experts in the use of intrathecal drug delivery; one of the guidelines reviews the evidence regarding the use of intrathecal drug delivery for patients with cancer pain (Deer, 2011) and the other for patients with noncancer pain (Deer, 2010). The final panel recommendations were similar for both patient groups: “The consensus panel unanimously agrees that appropriate patient selection is vital to achieving successful outcomes with chronic IT analgesic therapy; however, specific patient selection indications for implantation with an IT drug delivery system are not supported by rigorous, literature-based scientific data. The ultimate determination to proceed with IT therapy requires resolution of two
principal overlapping decisions—who to implant and when to implant the patient with an internalized device. Although it is challenging to ascertain optimal timing for the initiation of IT therapy, various indicators may signal that a patient is ‘ready’ for this aggressive form of treatment. To optimize clinical practice in the absence of evidence-based guidance or validated tools for chronic IT analgesic therapy patient selection, the panel has assembled a set of arbitrary, multidisciplinary issues that merit consideration during individualized risk-versus-benefit evaluations.” The list issues proposed by this consensus panel are shown in Table 15-1. While this is directed at selecting appropriate patients with noncancer pain for treatment with intrathecal drug delivery, the considerations are similar in those with cancer-related pain.

Table 15-1 Key Considerations for Selection and Implantation of Patients with Noncancer Pain for Intrathecal Therapy

Contraindications for Immediate Trial/Implant	Indications to Proceed with Trial/Implant
Immunocompromised patients at high risk for infection or patients presenting with an active infection Patients presenting with severe psychological conditions, including untreated significant addiction; active psychosis with delusional/hallucinatory components; major uncontrolled depression/anxiety; active suicidal or homicidal behavior; serious cognitive deficits; or severe sleep disturbances Current or anticipated lack of insurance coverage or means to pay out of pocket for both surgical implantation and ongoing medication refills/reprogramming Inability to comply with medication refill schedule due to geographic limitations	An appropriate diagnosis of the patients’ pain has been established Chronic pain results in significant interference with activities of daily living, including ability to work, and overall quality of life Preexisting medical comorbidities are well controlled and appropriate disease-specific guidelines are followed pre- and postimplantation Patients presenting without any severe or uncontrolled psychological conditions Patients have tried and failed to achieve sufficient analgesia with less invasive therapies Patients in whom oral opioid therapy is contraindicated, for example, a patient who has difficulties managing his or her medications, an individual with certain comorbid conditions in which oral opioids have the potential for severe adverse effects
Reproduced with permission from Deer TR, Smith HS, Cousins M, et al. Consensus guidelines for the selection and implantation of patients with noncancer pain for intrathecal drug delivery. Pain Physician. 2010;13:E175-E213.

Intrathecal drug delivery is an invasive and expensive treatment modality that carries significant risk. The available evidence for long-term efficacy is modest and the risks associated with treatment are significant. The available expert opinion from different consensus groups offers imprecise guidance, highlighting the empiric nature of patient selection. The final recommendations put forth in the table above represents a composite of the available recommendations discussed in this section.

Positioning

Before the procedure, discuss with the patient the location of the pocket for the intrathecal pump. Most devices are large, and the only region suitable for placement is the left or right lower quadrants of the abdomen. Once the site is determined, mark the proposed skin incision with a permanent marker while the patient is in the sitting position. The position of the pocket on the abdominal wall is deceptively difficult to determine once the patient is lying on his or her side. If the location is not marked, the pocket is often placed too far lateral within the abdominal wall. Implantation of an intrathecal drug delivery system is a minor surgical procedure that is carried out in the operating room using aseptic precautions, including skin preparation, sterile draping, and the use of full surgical attire (Fig. 15-1). The procedure can be conducted under either local anesthesia or general anesthesia using dedicated anesthesia personnel. Performing the initial spinal catheter placement under general anesthesia carries concerns about neural injury that are similar to performing any neuraxial technique under general anesthesia. The patient is positioned on a radiolucent table in the lateral decubitus position with the patient’s side for the pump pocket nondependent (see Fig. 15-1). The arms are extended at the shoulders and secured in position so they are well away from the surgical field. The skin is prepared, and sterile drapes are applied. The radiographic C-arm is then positioned across the lumbar region to provide a cross-table anterior-posterior (AP) view of the lumbar spine. Care must be taken to ensure that the x-ray view is not rotated by observing that the spinous processes are in the midline, halfway between the vertebral pedicles (Fig. 15-2).