Vol. 5 No. 3 June 1990

JoumJ of Pain and symptom&nap~~~t -

169

Steven D. Waldman, MD Pain Consortium of Greater Kansas City, Leawood, Kansas

Abstract Spanal opioidr have dramatically changed the way acute, obstetrical and pain of malignant origin is managed. The development of various implantable narcotic delivery systems has com+nented and facilitated the growth of this treatment modality. By intflacing a@ro#triate patient selection with the unique advantages and disadvantages of each of the six types of implantable narcotic delivery systems, improved results both in terms of pain relief and patient satisfaction can be achieved. J Pain Symptom Manage 1990;5:169- 174.

Analgesics, opioids, anesthetic techniques, spinal opioids, implantable narcotic delivq 5@ns

I&-oduct&m In the late I97Os, a group of cancer patients at the Mayo Clinic underwent spinal administration of morphine in the hope of finding an alternative to neurodestructive procedures for relief of intractable pain of malignant origin. Thii brilliant clinical application by Wang and Nauss’ of the basic research of Yaksh* heralded a new era in the specialty of pain management. This development not only dramatically changed the management of cancer pain but triggered an entirely new way of looking at the route of drug administration. The years since this landmark event have yielded a vast clinical experience with this powerful new modality, which in turn has resulted in the publication of an extensive literature describing the use of spinal opioids in a variety of clinical situati0ns.s As clinicians gained more experience in the use of A&es repint requests to: Stercn D. Waldman, MD, Pain Consortium of Greater Kansas City, 11111 NaPi, Suite 222, Leawood, KS 66211 0 U.S. Cancer Pain Relief Committee, 1990 Published by Elsevier, New York, New York

spinal opioids for the management of cancer pain, they began to apply this modality to nonmalignant acute pain and experiment with the spinal administration of drugs other than opioids. ‘This experimentation has not l>een without its ctitics.4 However, in spite of the controversy, anesthesiologists have successfully adapted this technique to relieve postoperative and other acute pain, obstetric pain, and cancer pain in thousands of patients. In tandem, the development of various implantable drug delivery systems IIDDS) has occurred, and has facilitated this expanded r.ole of spinal drugs in the palliation of pain, and more recently, spasticitY*s-9 In this l.~~~ess, anesthesiologists have substantially increased the visibility of their specialty in the field of pain management.

Table 1 describes the six basic types of IDDS. The type I system, a simple percutaneous cath-

Table I

Spinal Drug Delivery Systems Type 1 Type i4

Percutaneous catheter

epidural or subarachnoid

Percu~neous epidural or subarachnoid catheter_wi& swbcutaneoVs tunneling

Type III Totally implanted epidural or subarachnoid catheter with subcutaneous

injection port

Type IV

Totally implanted epidural or subarachnoid catheter with implanted manually activated pump Type V Totally implanted epidural or subarachnoid catheter with implanted infusion pump Type VI Totally implanted epidural or subarachnoid catheter with implanted programmable infusion pump

plies needed to use the delivery system. Similarly, implanted systems may superimpose financial hardship upon a difficult terminal course. With prior planning, the financial issues can be individualized and resolved.

Be ConsideredPrim to Devke Plucm Issues

to

Appropriate patient selection is crucial if optimal results are to be achieved, both in terms of palliation of pain and degree of patient satisfaction. Factors that must be considered prior to placement of an IDDS are summarized in Table 2.1° These issues will be discussed further.

Preimphantahn Trial. The first responsibility eter analogous to those used for obstetrical pain control is one which anesthesiologists are most familiar with. The type II system is simply a catheter suitable for percutaneous placement and tunneling. The type III system consists of a totally implantable injection port that is attached to a type II tunneled catheter. The type IV system is a totally implantable, mechanically activated pump that is attached to a type II tunneled catheter. The type IV system is in principle a totally implantable patient-controlled analgesia device. The type V system is the totally implantable continuous infusion pump that is connected to a type II tunneled catheter. The type VI system is a totally implantable prograD timable infusion pump attached to a type II tunneled catheter. The programmable feature of the type VI implantable drug delivery system allows a broad spectrum of delivery rates and modes, including occasional bolus injections. Each of these drug delivery systems has its own unique profile of advantages and disadVW.iigCS.*O The pain management specialist must be familiar with the particular merits of each system if optimal selection is to be made. In this time of increasing pressure to control the costs of health care, economic factors must also play a role in the s&ection of an IDDS. The cost of both the intended delivery system and the drugs to be administered through the delivery system must be considered prior to impkmation of an IDDS. A perfectly functioning IDDS is of no value to the patient who is unable to pay for the drugs, special needles, and sup-

to the patient being considered for an IDDS is to make a diagnosis of the pain problem and analyze the appropriateness of the patient’s current analgesic regimen. If the diagnosis and therapy are correct, if the extent of disease is Gefined, and if oncologic and analgesic therapy have been optimized, it is appropriate to proceed to a trial of spinal opioids.‘OJ’ A preimplantation trial of spinal opioids is necessary to determine whether an IDDS can adequately relieve the patient’s pa.in. Not all pain is relieved by spinal opioids. lo An IDDS should never be implanted without first verifying the ability of the spinal drug being considered to relieve the patient’s symptoms adequately on two separate occasions.lg Extensive clinical experience suggests that implantation should not proceed unless the magnitude of relief is >50% of the preinjection intensity with a duration of at least twice the halflife of the agent, that is, 8-12 hr in the case of morphine.’ Failure to provide pain relief during a preimplantation trial may occur for several reasons. Tab& 2

Preimplantation Considerations 1. Results of preimplantation trials of spinal drugs 2. Infection 3. Clotting disorders 4. Behavioral abnormalities 5. Physiologic abnormalities 6. Cost of delivery system ‘7. Cost of drugs, needles, and supplies 8. Evaluation of support system 9. Concurrent therapy 10. Life expectancy

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ImplantableDrug De&q

These include test injections that are not made into the correct place; psychologic reasons such as depression; advanced tolerance to opioids; incorrect dose of spinal drugs; or because a principal component of the patient’s symptoms are not susceptible to spinal application of opioid, for example, some central pains.6J2.Ls If a question remains as to the ability of spinal drugs to provide symptom relief after two trial doses, a placebo injection may help clarify the situation. It is becoming widely accepted that this response to acute administration is highly predictive of the long-term outcome of chronic drug administration. Failure to see a good, long-lasting analgesia under these conditions is cause to reconsider placement of an implantable narcotic delivery system. Unless the efficacy of spinal opioids is clearly demonstrated during the preimplantation trial, the patient could be subjected to the implantation of a delivery system that will fail to achieve the desired results-namely, pain relief. With the exception of electrical stimulation and spinal drugs, few invasive pain therapies allow the patient and physician to test the therapy before an irreversible result has occurred. Local anesthetic blocks are useful in educating the patient prior to neurodestructive procedures, but cannot always predict the adequacy, extent, or complications of an irreversible destructive procedure. Ir#ection and Local Conditions.

Infection, inflammation, or dermatitis at the proposed cutaneous site of implantation, and the presence of generalized sepsis, represent absolute contraindications to device implantation. More difficult is the management of patients with lesions near the proposed implantation site. For example, many cancer patients have infected pressure sores, colosmmies or iliostomies, or chronic infections in areas of tumor necrosis. Our experience is that an IDDS may be placed if attention is given to sterile technique during implantation, injection, and refiil of the IDDS. Prophylactic antibiotic use should also be considered during placement of implantable ports and pumps. Antiwz@atkm

and Hemat~logic Abnovm&k

The fully anticoagulated patient represents a special problem when considering placement of

Systems

171

an IDDS. Preimplantation trials of spinal drugs for relief of pelvic and lower body pain has been performed safely in the presence of xnticoaglllation by administering the opioid caudally with a 25gauge X l&-cm needle.14 Unfortunately, spinal opioids administered in the lumbar or caudal region may not relieve upper-body pain without a substantial increase in the dose. One must carefully weigh the risk-benefit ratio of stopping anticoagulants in order to proceed with preimplantation trials of cervical or thoracic spinal drugs. Coagulopnhy caused by disease is also common, particularly in cancer patients. Platelet count and function, and tests for procoagulant factor activity should be assessed in all cancer patients, and others whose history or physical examination suggests the possibiiity of roagulopathy. Efforts should be made to reverse the coagulopathy if possible. If this is not possible, the risk-benefit ratio of proceeding with preimplantation trials should be assessed. Physiotogic Abnorr~lihs.

Physiologic abnormalities, such as electrolyte imbalance and drug-induced organic brain syndrome, may impair the patient’s ability to assess the adequacy of symptom relief. lo Many abnormalities are reversible and an effort should be made eo correct them before a trial of spinal drugs is undertaken. It should be remembered that the confusion secondary to these physiologic abnormalities may be incorrectly interpreted as uncontrolled pain by the patient and pain management specialist alike.15 BebirzvirJrd!m~nnul~t&s. Behavioral abnormalities that are often diflicult to identify may affect the patient’s abiiity to assess the adequacy of symptom relief. ‘6~’ These abnormalities may coexist with physiologic factors, but care must be taken not to athribute inadequate symptom relief solely to behavioral factors until all potential causes have been explored.18 S@@rt System. An IDDS requires a level of commitment not only from the patient, but from his or her support system as well. Someone must be available day and night to care for and inject; the IDDS should the patient be unable to do so. Thus, one or more persons must be designated as the patient’s support System for IDDS, and this must be acceptable to the pa-

172

dent. It should be remembered that the cancer patient who injects his own IDDS initially, may be unable to do so later in the course of disease. Inability or unwillingness of the designated support system to care for the IDDS has significant implications when selecting the appropriate system. L@ Ergccacn~y. Although prediction of a cancer patient’s life expectancy can be difficult, an estimate in terms of days, weeks, or months is essential to aid in the selection of an appropriate IDDS. 1s Often, the patient’s general condition will improve when adequate symptom control is provided, and this must be taken into account when estimating lik expectancy.

Tk Choiceof IDDS Catheter. The t,ype I percuppe I Pertaneous catheter has gained wide acceptance for the short term administration of spinal opioids and/or local anesthetics for the palliation of acute pain, including obstetric and postoperative pain. The type I system akso has three applications in cancer pain management. The first is in the acute setting, in which the delivery of opioids into the epidural or subarachnoid space can provide temporary palliation of pain postoperatively or until other concurrent treatments, such as radiotherapy, become effective. The second is in imminently dying patients too ill for more invasive procedures.lOJg*so The third is the use of a percutaneous catheter to administer test doses of spinal opioids prior to placement of a more permanent IDDS. In many centers, the use of a percutaneous catheter for the delivery of epidural and especially subarachnoid opioids Is limited. The improved catheter fixation and reduced risk of infection associated with subcutaneous tunneling, combined with the relative ease of tunneling,“JJs*sr have led many pain specialists to tunnel the spinal catheter to the flank, abdomen, or chest wall. Despite several reports that the type I system can be used for prolonged periods in immunocompromised patients without an increased risk of infection,sP the validity of this observation has not been established. In view of the potentially devastating and life-threatening consequences of catheter-induced spinal infection, as well as the highly favorable risk-tobenefit ratio of the type II tunneled catheter,

WaMmun

Journal of Fain and ~p@tn Management

the use of the type I system should be limited solely to the acute setting.loJg Tvpe ZZ Subcutaneous Tunneled Catheters. Subcutaneously tunneled catheters are usually selected for cancer patients with life expectancies of weeks to months who have experienced excellent palliation of symptoms with trial doses of spinal drugs. The type II system carries significantly less risk of infection than percutaneous catheters.” The simplified catheter care and the ease of injection by both medical and nonmedical personnel are also significant advantages of the type II system. The type II system can also be attached to an external continuous infusion pump. T>$e ZZZTota& Zm@ntubk ReservdrlPort. The totally implantable reservoir is often chosen for patients with life expectanlcies of months to pars who have had excellent relief of symptoms with trial doses of spinal drugs.1”22 The type III system has potentially less risk of infection than with type I and II systems, as well as a decreased risk of catheter failure. Injection of the type III system is more difficult than with type I and II systems, and this can have significant import when training lay people to inject and care for this system. Furthermore. removal or replacement requires a surgical incision. TVpe IV Totally Zmphtable Mechanically Activated Pump. Poletti and collea.guesrs created one of the earliest totally implantable systems for patient activated drug delivery. This system consisted of an implantable sterile blood bag with a hydrocephalus shunt valve in series with the bag and spinal catheter. The valve could be activated by the patient to allow self-administration of an opioid from the implanted bag. This concept has now been extended by Cordis, through introduction of a totally implantable reservoir that is accessed percutaneously through a septum on the surface of the device. The device also has a mechanical valve system activated by a set of buttons on the pump surface. The patient delivers spinal drugs by depressing the buttons in the proper sequence.lg*r4 The type IV system has potentially less risk of infection than the type I-III systems. Subarachnoid delivery is more feasible

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imglantable Drug Delivery Systems

with the type IV system than with type I and II systems. The greatest advantage of the system is that the patient can titrate the dose of the drug based on symptoms and can pretreat symptoms prior to periods of increased activity.

173

However, there are several theoretic advantages for cancer pain patients including the reduction of side effects that may occur with the bolus injections provided by type I-IV IDDS coupled with the added ability to pretreat symptoms associated with periods of increased activity.

Trpe V Totally Imjduntable Znfukon Pump.

The totally implantable infusion pump is also used in patients with life expectancies of months to years who obtained relief of symptoms after trial doses of spinal drugs.1g.25 Type V delivery systems may also be indicated in a cancer patient with a shorter life expectancy, who experiences intermittent confusion secondary to metabolic abnormalities or systemically administered drugs. Clinical experience suggests that such patients may obtain analgesia with fewer side effects with low-dose continuous spinal opioid infusion than repeated bolus injections irrlto a spinal catheter. Alternatively, an implanted port with an external infusion pump may suffice in this situation, although this may be more inconvenient and require more support. Since type V systems require infrequent refills and run continuously, they are ideal for patients with limited medical or nonmedical family support services. The type V system is usually selected with an auxiliary bolus injection port to take advantage of potential drug options, such as local anesthetic injections. Advantages of the type V system include the minimal risk of infection after the perioperative period and the need to inject the pump very infrequently, relative to other IDDS (pump reservoir needs to be refilled approximately every 7-20 days). The overall high cost of the type V system is a disadvantage and may occasionally result in the selection of a less effective or more inconvenient analgesic technique. Trpe VI Totally Implantable Programmable Infusion Pump. The type VI totally implantable

programmable infusion pump is implanted with the same ease as the type V system.*” These systems allow a broad spectrum of delivery rates and modes, including occasional bolus injections. Their principal application to date has been intrathecal infusion, especially in the therapy of spasticity in multiple sclerosis and spinal cord injured patients.g*“@ There is yet no proven advantage of programmable systems over the simpler continuous infusion systems.

Summay The administration of spinal drugs via implantable drug delivery systems is a useful addition to the armamentarium of the pain management specialist. Proper selection of the patient and an appropriate delivery system is crucial if optimal results are to be achieved. It should be recognized that the chronic administration of opioids and other drugs into the epidural or subarachnoid space is in its infancy. Advances in the pharmacology of spinal drugs and the development of new delivery system technology will in time no doubt expand the options available for the relief of cancer pain.6

e~iences 1. Wang JK. Nauss LE, Thomas JE. Pain relief by intrathecally applied morphine in man. Anesthesiology 1979;50:149-151. 2. Yaksh TL. Opiate receptors for behavioral analgesia resemble to the depression of spinal nociceptive neurons. Science 1978;199: 1231. 3. Coombs DW. Newer approaches to chronic pain therapy. Semin Anesth 1985;4:287-299. 4. Coombs DW, F&kin J. Neurotoxicology of spinal analgesics. Anesthesiology 1987;66:724-725. 5. Coombs DW. Newer drugs and delivery systems. Anesthesiol Clin 1986;24:59-74. 6. Onofrio BM, Yaksh TL, Arnold PG. Continuous low-dose intrathecal morphine administration in the treatment of chronic pain of malignant origin. Mayo Clin Proc 1981;56:516-520. 7. Coombs DW, Saunders RL. Gayior LM. Epidural narcotic infusion reservoir: implantation techniques and efficacy. Anesthesiology 1982;56:469-473. 8. Waldman SD, Cronen MC. Thoracic epidural morphine in the palliation of chest wall pain secondary to relapsing polychondritis. J Pain Symptom

Manage 1989;4:60-63. 9. Penn RD, Kroin JS. Long-term intrathecal baclofen infusion for the treatment of spasticity. J Neurosurg 1987;66:181-185. 10. Waldman SD. A simplified approach to the subcutaneous placement of epidural catheters for long-

term administration of morphine sulfate. J Pain Symptom Manage 1987;s: 16% 166. 11. Parke B, Penn RD. Savoy SM. Corocs D. Functional outcome after delivery of intrathecal baclofen. Arch Phys Med Rehab 1989;70:30-33. 12. Wakhnan SD, Feldstein GS, Allen ML. Selection of patients for implantable spinal narcotic delivery systems, Anesth Analg 1986;65:883-885. 13. Arner S, Amer B. Differential effects of epidural morphine in the treatment of cancer related pain. Acta Anaesthesiol Stand 1985;29:32-36. 14, Waldman SD, Feldstein OS, Waldman HJ, et al. Caudal administration of morphine sulfate in anticoagulated and thrombocytopenic patients. Anesth Analg 1987;66:267-268, lb. Washburn KB. Phytical medicine and rehabilitation. New York: Medical Examination Publishing 1981:151-159. 16. Bond MR. Psychological and emotional aspects of cancer pain. In: Bonica JJ, Ventafridda V, cds. Pmceedings of international symposium on pain of advanced cancer: advanced in pain research and therapy, vol2. New York: Raven, 1979:81-88. 17. Stembach RA. Pain patients: traits and treatment. New York: Academic Press, 1974.

20. Crawford ME, Anderson HB, Augustenborg G, et al. Pain treatment on outpatient basis utilizing extradural opiates: a Danish multicenter study comprising 105 patients. Pain 1983;16:41-46. 21. Peder C. Crawford M. Fixation of epidural catheters by means of subcutaneous tissue tunneling. Ugeskr Laeger 1982;144:2631-2633. 22. Downing JE, Busch EH, Stedman PM. Epidural morphine delivered by a percutaneous epidural catheter for outpatient treatment of cancer pain. Anesth Analg 1988;67:1159-1161. 23. Cousin M, Gourley G, Cherry D. A technique for the insertion of an implantable portal system for the long-term epidural administration of opioids in the treatment of cancer pain. Anesth intensive Care 1985;13:145-152, 24. Poletti CB, Cohen AL, Todd DP, et al. Cancer pain relieved by long-term epidural morphine with a permanent indwelling system for self-administration, J Neurosurg 1981;56:581-584. 25. Gestin Y. A totally implantable multidose pump allowing cancer patients intrathecal access for the self-administration of morphine at home: a follow-up of SO cases. Anaesthetist 1987;86:391.

18. Zenz M. Epidural opiates for the treatment of cancer pain. In: Zimmerman M. Drugs P, Wagner G, eds. Recent results in cancer research. Heidelberg: Springer-Verlag, 1989: 107- 1IS.

26. Coombs DW. Continuous spinal morphine analgesia for relief of cancer pain, 1st ed (Monograph, Shiley Infusaid, lnc). Cambridge, MA: Shea Bros, 1985: l-29.

19. Waldtnan SD, Coombs DW. Selection of implantable narcotic delivery systems. Anesth Analg 1989; 68:977-384.

27. Penn RD, Paice JA, Gottshalk W, Ivankovich AD. Cancer pain relief using chronic morphine infusion. J Neurosurg 1984;61:302.