Guide to Implantable Devices for Intrathecal Therapy
Intrathecal therapy for the management of malignant and nonmalignant pain has undergone a paradigm shift in recent years. Gone are the days of positioning the therapy as a salvage treatment for high-dose opioid patients. With careful selection and vigilance, advanced techniques like intrathecal therapy can be implemented in a manner that greatly improves functionality and pain care.
The intrathecal drug delivery system (IDDS) functions as a platform, much as transdermal and intraveneous formulations, to deliver medication as a pharmacologic therapy. Common aliases for intrathecal therapy include “pain pump” or “morphine pump.” Despite these connotations, the intrathecal-targeted delivery of medications describes the platform itself; it does not define the medication employed. Prior to implantation, a successful trial needs to be performed with at least 50% pain reduction without side effects.
The advantages to opioid intrathecal therapy are numerous, including the ability to deliver medications where they commonly work (ie, the dorsal horn of the spinal cord), increasing potency, and reducing the systemic exposure and dose required to achieve the desired pharmacologic effect, thus reducing side effects.1 Table 1 compares systemic and intrathecal drug delivery systems.
The purpose of this review is to reintroduce the technology, dissect the indications and the risks, comment on the efficacy of the therapy, and provide a few case examples.
The mechanics behind intrathecal therapy are very simple: surgically, a catheter is placed in the intrathecal space and tunneled to an implanted reservoir, where the medication is housed. The reservoir has a mechanism to dose the intrathecal space, based on the volume infused (Figure 1).
Recent work into cerebral spinal fluid (CSF) flow dynamics of the intrathecal space has offered an insight into pharmacokinetic modeling. There is very little bulk CSF flow, but rather discrete regions of mixing, with bidirectional cranio-caudal oscillatory movement, with cardiac and pulmonary motors2-6 producing a relatively non-homogenous fluid.7 Further, animal models suggest that dispersion from the catheter tip within the CSF by slow infusion is limited, dependent on the physiochemical properties of the drug, as well as the rate and volume delivered.8-10 In a pilot study of common volumes of drug delivery by slow infusion typical with intrathecal dosing of 0.48 mL/hour, most staining occurred posteriorly, demonstrated by very little anterior and lateral staining.8 This data suggests that site-specific catheter placement congruent with area of pain within the intrathecal space is important for optimal efficacy.
Employing the current IDDS platforms available—as the rate and volume available for delivery is largely fixed—concentration is typically manipulated. This has led to some challenges with intrathecal therapy for nonmalignant pain, and will be addressed later in the review.
As the medication is depleted from the reservoir, it requires replacement. This necessitates a refill procedure, which is commonly performed in the office. Much of the morbidity and mortality associated with intrathecal therapy centers on iatrogenic causes, specifically around the refill and reprogramming of the device.11 The life of the battery within the reservoir typically lasts 7 to 10 years, and although the mechanics behind the deployment of volume from the reservoir differ based on the manufacturer, the refill procedure is largely the same. Let’s consider them separately.
The Synchromed II by Medtronic (Figure 2), is a pump that has a geared mechanism that is programmable with a variety of infusion strategies. It has the ability to have variable programmable dosing strategies, along with a patient therapy manager, which functions as a patient controlled bolus delivery mechanism much like an inpatient patient controlled analgesia (PCA) system. It is magnetic resonance imaging (MRI) compatible, with the advisory to read the pump before and after the scan, without the need to remove medication from the internal tubing or reservoir. If the pump were to malfunction during an MRI, the therapy would have a motor stall without restarting, with the abrupt withdrawal of the therapy, potentially creating loss of analgesia and withdrawl symptoms.
The Prometra pump by Flowonix (Figure 3) is an implantable, programmable pump. It can be used to deliver a volume at different rates and is refilled percutaneously. The accuracy, efficacy, and safety of the Prometra pump was assessed in clinical trials, demonstrating an accuracy of 97.1%, with a 90% confidence interval of 96.2-98.0%.12,13 The Prometra pump uses a valve-gated dose regulation system, as opposed to the peristaltic pump roller system. Studies have demonstrated improved volume delivery accuracy as compared to the Medtronic Synchromed II.12 The pump is MRI compatible after complete removal of the medication from the reservoir. There currently is no PCA dosing strategy available with the Prometra pump, although it appears to be on the horizon.
Recommendations on drug choice, concentration limits, and starting doses were outlined by the Polyanalgesic Consensus Conference (PACC) latest reiteration in 2012.14 A panel of experts on behalf of the International Neuromodulation Society (INS) convened on intrathecal therapy to promote safety and efficacy. The medication tiers were designed based on nociceptive or neuropathic pain (see Tables 2-4).
To date, only two medications are approved by the FDA to treat chronic pain via intrathecal therapy: morphine (Infumorph) and ziconotide (Prialt). Morphine delivered pharmacodynamically works at the opioid receptors within the dorsal horn, while ziconotide, a non-opioid based medication, antagonizes the N-type calcium channels within the dorsal horn.15-16 Medtronic recently released a statement regarding non-labeled drugs used within the Synchromed II pump, reporting a statistically significantly higher incidence of motor stalls when non-labeled medications—as monotherapy or in combination—are employed.17 Multiple studies have commented on stability of medications within the reservoir, and suggest that the medications as monotherapy or in combination should be replaced routinely every 3 to 4 months.18-23 Combination therapy has been demonstrated to slow dose escalation when initiated at onset of intrathecal therapy.24