A 15-Year-Old Boy With Primitive Neurectodermal Tumor

Discussion

Peter S. Staats, MD: This was a case where we had poor control to begin with and many options. The pain management team elected to implant an intrathecal pump in this child for several reasons, including the patient’s lumbar plexus problem. We believed he would develop significant problems and that we ought to implant the pump early. I felt that we could better manage this patient long term with bupivacaine(Drug information on bupivacaine) and morphine(Drug information on morphine) delivered by this neuraxial route.

Russell K. Portenoy, MD: How was the boy doing psychologically, and what were some of the issues concerning his parents?

Dr. Staats: The boy’s parents were very supportive of him. The child wanted nothing more than to go back to school. He did have a lot pain, and he was anxious about procedures and needles. I had seen the boy previously because his pain was out of control, and when I explained his options, he said he really didn’t hurt that bad. The patient waited 1 to 2 months before returning to see us, at which time we discussed his concerns about the implanted devices.

Dr. Portenoy: What was the patient’s level of function when systemic opioid therapy with oxycodone(Drug information on oxycodone) was failing because of somnolence?

Dr. Staats: His function was very poor at the time because of sedation, which was really his problem. Once we placed an externalized intrathecal catheter, the sedation improved rapidly and he returned to school. One might question why we chose not to switch opioids since the boy was on a relatively low dose of opioids. Although we thought about this option, we wanted an alternative route of therapy for the local anesthetics that we knew would eventually be needed because the tumor was invading the lumbar plexus.

Decision-Making

Dr. Portenoy: The major decision point in managing this patient appears to be between providing more aggressive pharmacotherapy and undergoing a trial of intraspinal therapy. From the point of view of more aggressive pharmacotherapy, I probably would have tried an opioid switch to methadone(Drug information on methadone) first, and then certainly would have added a psychostimulant before opting for intraspinal therapy. This difference in selection of therapy raises important issues about how much that decision-making in pain management is based on who is available to manage a patient’s therapy.

Dr. Staats: That is a very good point, and something that I’ve struggled with over time. How aggressively does one work to manage a patient medically to get the same level of function? I am not convinced that this was the absolute way to go. There are two viable approaches in this case: 1) opioid switch and 2) intraspinal therapy. I believe that you would have worked a lot harder and that the patient would have been taking a lot more pills by opting for the opioid switch than by intervening very early with intraspinal therapy as we did. But, there are no randomized trials to confirm this, which is one of the reasons we’re having this discussion.

Michael H. Levy, MD, PhD: At Fox Chase Cancer Center we don’t see patients younger than 18 years, so for the sake of discussion, I would like to assume that the patient was 20 years old. We probably would have opted to try different opioids, as Dr. Portenoy discussed. Other than first trying different opioids, our management would not have differed much from that of Dr. Staats in this patient. Even in our hypothetical 20-year-old patient, implanting a pump and administering medications intrathecally to manage most of the pain so that he was not taking multiple drugs (eg, laxatives, coanalgesics, stimulants, opioids) could be in the patient’s best interest and could improve his quality of life.

Anticipating the Course Of Pain

Stuart Du Pen, MD: With severe neuropathic pain in a young patient, I support neuraxial analgesia through a temporary device. Once pain is under control, then other options may be evaluated.

Dr. Staats: This case is very unusual, which is one reason I chose to present it for discussion. My belief was that some of you might disagree with implanting a device in a patient who was receiving only 5 mg of oxycodone q4h. However, my thought process in selecting intraspinal therapy included anticipation of what was foreseeable over the life of this patient.

In a much more typical case at Johns Hopkins, we would have tried two or three opioid rotations. This case, however, demonstrated some principles worth discussing. One principle is to think through what you anticipate the problem is going to be, for example, the issue of neuropathic pain vs nociceptive pain, and the addition of local anesthetics. This is not a static disease, and the oncologist or pain specialist needs to work with the patient and the course of his or her pain. You cannot just implant a device and hope that 1 mg/d of intrathecal morphine will effectively relieve the patient’s pain until he or she dies.

Dr. Portenoy: After the pump was implanted, why did you add bupivacaine when the patient was actually still taking very low doses of intrathecal morphine?

Dr. Staats: The quality of the pain was changing to more of a burning pain that was neuropathic. The additional local anesthetic was what I believed to be in the child’s best interest. Clearly, another option could have been to increase the intrathecal morphine.

Dr. Portenoy: It seems like that decision was similar to what we noninterventionists do when we’re choosing adjuvant analgesics. The decision is completely idiosyncratic. Some clinicians will choose to increase the morphine to some arbitrary ceiling based on the fear of hyperalgesia syndrome, whereas others will increase the morphine until patients get side effects; still others will add bupivacaine early. Do you feel the decision is basically clinician-specific without any justification?

Elliot S. Krames, MD: This is the art of medicine. We do not have randomized controlled studies to guide us to the appropriate time to add bupivacaine. My art of medicine would be to increase the dose of morphine. I basically give the opioid the benefit of the doubt. When I approach, in my art, 20 mg/day, then I add bupivacaine and/or clonidine(Drug information on clonidine).

Dr. Portenoy: There seems to be a general feeling among you that a painful lumbosacral plexopathy would not be as responsive to opioids as would, for example, a somatic pain. I only bring up this point for the oncologists who may be reading this because it does vary with the guideline for systemic opioid therapy discussed in my article on page 25. If you accept the concept that you select an opioid drug, and then you individualize the dose by escalating until you get to treatment-limiting toxicity, which defines the responsiveness to that drug by that route, then the appropriate intervention would always be opioid dose titration first, before addition of another drug.

Dr. Staats: If a patient presented with a lumbar plexopathy with tumor invading the right hip and you believed that this lumbar plexopathy neuropathic component might respond well to Neurontin or to carbamazepine(Drug information on carbamazepine) (Tegretol), or to something else if there was a shooting or lancinating component, you might start that agent. And if the tumor was invading the spine, I might use opioids or steroids or something else to manage this nociceptive component. Conceptually, that’s what I believed I was doing in this case.

Systemic Pharmacologic Approach

Dr. Portenoy: A problem with very early use of combination therapy is the possibility of additive side effects. If a person has a painful lumbosacral plexopathy, our teaching about systemic therapy would be to increase the systemic opioid first, and to do so very quickly. Once the patient starts to become somnolent without adequate pain relief, you could reduce the opioid dose and quickly administer adjuvant analgesics. There is just no evidence behind the rationale for adding adjuvant analgesics when the opioid dose is very low and is not associated with any toxicity because you assume that the efficacy of the opioid won’t be adequate to treat that pain.

Dr. Levy: In a systemic pharmacologic approach, it is much like what Dr. Staats did in this case. Our experience indicates that it is uncommon for a patient’s burning pain to go away; the typical response to opioids is that the pain is reduced in intensity, but the burning sensation is not gone. And if you choose to use a tricyclic antidepressant, it will take weeks to reach a therapeutic dose with minimal side effects. We do a lot of anticipatory use of coanalgesics, particularly of the neuropathic drugs, to perhaps prevent or minimize the side effects of increasing doses of opioids. We use combination chemotherapy in oncology in the same way. Moderate doses of several agents with different mechanisms of action work better and with less toxicity than high doses of just one agent. We don’t have the data, but I believe our experience, particularly with neuropathic pain, is that it’s the rare patient in whom most symptoms can be controlled with just opioids. And because it takes some titration to reach the full effect (even Neurontin can take days, or weeks), we do that same kind of anticipatory approach that Dr. Staats used in this case.

Dr. Krames: Many patients with neuropathic pain do not respond to intrathecal morphine at 1 mg/d but may respond to 2.5 mg/d or even higher. Once you’ve started therapy, unless you’ve titrated to either efficacy or side effects, you’re not really giving that therapy an adequate trial. In some patients we’ll add Neurontin or desipramine. With intrathecal therapy, however, there is evidence that higher doses of opioids are better in neuropathic pain states, and I believe you should titrate until efficacy is achieved or side effects occur. In a patient with severe neuropathic pain, I’ll increase the dosage by 50%, and if the patient is still in pain, will increase another 50% a day or two later, and still again until toxicity occurs or efficacy is achieved. I’ll stop once dosage has reached 20 mg/d and then consider the addition of a nonopioid such as clonidine or bupivacaine.

Dr. DuPen: In my practice, we strongly support the use of opioids and adjuvant drugs through an algorithm. However, this is a 15-year-old child with out-of-control pain who is not responding to opioids. My therapeutic choice is intravenous sedation, with a temporary epidural catheter with bupivacaine to get pain control, then a progressive effort to use drug trials and adjuvant therapy to determine the role for long-term intrathecal therapy.