A 15-Year-Old Boy With Primitive Neurectodermal Tumor
A 15-Year-Old Boy With Primitive Neurectodermal Tumor
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 patients 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 and 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 boys 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 didnt 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 patients level of function
when systemic opioid therapy with 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.
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 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 patients therapy.
Dr. Staats: That is a very good point, and something that
Ive 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 were having this discussion.
Michael H. Levy, MD, PhD: At Fox Chase Cancer Center we
dont 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
patients 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 patients 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 childs 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 were 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
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 (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,
thats 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 wont 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 patients 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
dont have the data, but I believe our experience, particularly
with neuropathic pain, is that its 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 youve started therapy, unless youve titrated
to either efficacy or side effects, youre not really giving
that therapy an adequate trial. In some patients well 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,
Ill 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. Ill 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.