John C Oakley

With the discovery that opioid drugs administered into the subarachnoid space could access spinal cord receptor sites and produce effective analgesia in malignant and nonmalignant pain syndromes, implanted drug delivery systems became a standard intervention for pain management. In 1979 Wang and colleagues reported that the use of morphine in cancer-related pain at doses of 0.5 to 1.0 mg resulted in excellent pain relief for 8 to 30 hours.1 Yaksh documented the physiological basis of the pain relief produced by intraspinal administration of opioids as the modulation of inhibitory mechanisms occurring at the spinal cord.2

It is known that opioids produce a marked inhibition of the evoked discharge of spinal cord nociceptive neurons, correlating with an elevation in the pain threshold of animals.3 This effect is not associated, at analgesic levels, with alterations in primary sensory modalities such as touch, or in autonomic changes or changes in voluntary motor function. Analgesic effects of these drugs are dose dependent and stereo-specific. Opioid effects are antagonized by naloxone and have a highly regular structure-activity relationship. This suggests that their primary site of action is on spinal cord receptors. High levels of opioid binding have been found in the substantia gelatinosa, where the majority of the small primary afferent fibers terminate. The local action of morphine in the substantia gelatinosa inhibits the discharge of nociceptive neurons, resulting in the inhibition of pain transmission.2-4

The numerous external methods of accessing the intrathecal space for drug administration include epidural catheters relying on trans-dural absorption, tunneled externalized intrathecal catheters, and internalized ports requiring percutaneous access. These methods are acceptable for short-term treatment. However, their vulnerability to infection, as well as economic considerations, preclude serious consideration for long-term use (>3 months).5,6

Coombs and Poletti and their coworkers were the first to describe the use of an implanted reservoir that, with repeated compression, delivered a bolus of medication into the epidural space.7,8 Percutaneous injection of a subcutaneously implanted infusion port connected to a spinal catheter was also described.9 Bolus dosing in this manner was demonstrated to result in rapid drug tolerance in primates and fell out of favor.10 These external techniques also called for highly skilled personnel and demanded monitoring on an outpatient basis. Infusion ports were connected to external infusion pumps but suffered from an increased risk of infection and patient discomfort.11

Strato-Infusaid Corporation (now Arrow International) developed and manufactured a constant flow rate pump for the delivery of in-travascular, and occasionally intrathecal, chemotherapeutic agents. A constant flow rate device (Figure 15.1) is a hollow titanium shell separated into two chambers by a metal bellows. In one chamber, a two-phase (gas and liquid) charging fluid (Freon) is permanently sealed between the bellows and the outside wall of the cylinder. The other chamber is the drug reservoir, which is filled percutaneously via a self-sealing septum.

As the reservoir is filled, the charging chamber is compressed and the charging fluid returns to a liquid state. As the fluid is warmed to body temperature, it converts to a vapor at a reasonably calculable rate, exerting pressure on the drug chamber. This pressure then forces the infusate through an outlet filter and a flow-restricting capillary tube assembly. The infusate then enters a silicon rubber delivery tube and exits the pump. The final result is a constant flow of medication if the surrounding temperature and pressure remain constant. These systems are reliable and simple; they are limited in their longevity only by the lifetime of the self-sealing septum, which must be punctured for refills. The systems are subject to variable flow rates with altitude, as in mountain travel or on airplanes (increased flow), and most commonly elevated temperatures such as fever or a hot tub (increased flow). An inconvenience of these systems is the need to drain the reservoir and existing drug waste to add a more or less concentrated drug when the prescription is altered.

The early efficacy and safety of intraspinally administered medication was established by constant flow rate systems.7,9,1218 Several constant flow rate systems are commercially available; they are used when a stable dosing regimen is determined or when there are drug compatibility concerns with other systems. Medtronic and Arrow International in the United States, and Tricumed and Medtronic in Europe currently offer such systems.

In 1988 the Medtronic Corporation introduced an externally programmable, fully implantable pump in response to the demand for the ability to change a drug prescription without the need to physically re-

Isomed Pomp
Figure 15.1. Isomed factory preset constant flow rate during infusion pump. (Used with permission, Medtronic, Inc.)

Implanted Drug Delivery Systems 275

Drug Delivery Pump
Figure 15.2. Synchromed programmable drug infusion pump. (Used with permission, Medtronic, Inc.)

move the drug from the pump and replace a new drug or concentration. This device was originally released for the treatment of cancer-related pain in the late 1980s and became commercially available for pain of all types in 1991, after 7 years of clinical trials. This device is an implantable, programmable, battery-powered pump that stores and delivers medication according to instructions delivered by an external programmer (Figure 15.2).

Like constant flow rate pumps, the programmable pump is filled through a self-sealing septum into a drug reservoir. A bellows configuration allows the drug reservoir to collapse as drug exists the chamber and to expand as the chamber fills. The programmable pump consists of a battery module, an electronic module for programming and pump control, and a peristaltic pump motor that pulls infusate from the reservoir by compressing internal tubing. The rate of drug delivery is determined by the turning rate of the pump motor, which is controlled by the programming of the microprocessor in the electronic module. A telemetry unit allows communication with an external programming unit (Figure 15.3), allowing troubleshooting and adjustments. An internal 0.22 ^m retention filter filters out bacteria and other contaminants. Medication passes through the pump tubing by action of the peristaltic pump, exits the pump through the catheter port, and flows through an extension catheter to the intraspinal catheter and to the epidural or intrathecal space.

The programming unit is essentially a laptop computer, printer, and a programming wand, as illustrated in Figure 15.3. The programming wand establishes a two-way radiofrequency link with the implanted pump. The programmer transmits interrogation and programming signals to the pump and receives information from the pump. This capability has established the implantable, programmable pump as the ideal approach for patients with chronic pain.

Medtronic Intrathecal Pump
Figure 15.3. Synchromed programmer. (Used with permission, Medtronic, Inc.)

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Responses

  • mewael
    What type of medication is used in the medtronic drug pump?
    7 years ago

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