Pain is the most common symptom of patients
with advanced cancer.[1-4] The importance of pain is magnified by the
interaction of pain and its therapies with other common cancer
symptoms such as fatigue, weakness, dyspnea, nausea, constipation,
and delirium.[2,5] A patient with unrelieved pain cannot sleep well
and may become fatigued. If more pain medication is taken than is
needed, sedation occurs. If nausea occurs, then oral therapy is
difficult. Pain medicines can add to confusion or cause constipation
and nausea. Alternatively, opioids for pain can help relieve dyspnea
The fear of pain continues to be one of the greatest concerns of
patients with advanced cancer and has led to such desperate acts as
physician-assisted suicide. This desperation is a real tragedy
because we have the tools and techniques to effectively relieve
cancer pain.[7-11] Cancer pain can be controlled with good comfort
and function in 85% to 95% of patients with an integrated program of
palliative anticancer therapies combined with an individualized
regimen of systemic analgesics and coanalgesics. The appropriate use
of invasive procedures can help most of the remaining
patients.[12-14] In the final days of life, pain not controlled by
therapies aimed at both comfort and function can be relieved by
intentional sedation.[15,16] Based on current knowledge, no cancer
patient needs to live or die with unrelieved pain.
There are three basic approaches to the control of any pain: 1)
modify the source of the pain; 2) alter the central perception of
pain; and 3) block the transmission of the pain to the central
nervous system. For example, dental pain from a severely decayed
tooth may warrant an extraction or a root canal, and treatment with a
regional nerve block using a local anesthetic, a fixed-combination
preparation of an opioid and a nonopioid analgesic. Coanalgesic
therapy for these pains consists of antibiotics and nonsteroidal
anti-inflammatory drugs. Therefore, the basic approach for dental
pain might be a dental procedure, a regional anesthetic block, and
penicillin, ibuprofen, and hydrocodone plus acetaminophen.
The vast majority of cancer patients can have their pain relieved
through direct and indirect modification of the source of their pain
combined with pharmacologic and nonpharmacologic alteration of their
perception of pain.[7-9,18,19] The most common source of cancer pain
is the cancer itself. Alternatively, cancer treatment can produce
both acute pain and chronic pain,
such as mucositis and postsurgical neuropathy, that require their own
specific coanalgesic therapy. Cancer patients can also experience
pain from coincidental sources such as infection or degenerative
arthritis. Clinicians most commonly alter central perception of pain
with opioid analgesics. Perception can also be altered with
psychological and behavioral interventions. Blocking pain
transmission is most suited for patients who have regional pains or
who have pain that is not being controlled with acceptable side
effects despite aggressive pharmacologic tailoring. The most commonly
used procedural interventions include regional neurolysis and spinal
administration of opioids and coanalgesics.[12-14]
A clinical strategy for cancer pain relief consists of five
sequential components: patient assessment, care plan development,
care plan implementation, reassessment, and treatment modification.
Patient assessment begins with determining the intensity, quality,
location, and temporal pattern of each pain. Next, the patients
cancer status, concurrent medical problems, and psychosocial status
must be reviewed. It is critical to determine whether the source of
the pain is progression of the cancer, residual tissue damage from
the cancer and its therapy, or a coincidental problem. If the cancer
is progressive, what is the likelihood that further anticancer
treatment will help? What is the patients prognosis? Concurrent
medical problems can cause pain and can interfere with analgesic
therapy. For example, severe gastric ulcer disease, hypertension, or
coronary artery disease can limit the utility of some of the
coanalgesics. If the patient is infected or has a low platelet count,
invasive procedures will have to be delayed. Assessment of
psychosocial status must include the patients precancer
psychological history as well as any current problems he or she has
coping with pain or cancer.
It is the interface of these four spherespain, cancer, other
medical problems, and psychosocial statusthat guides therapy.
It is critical to use this comprehensive assessment to formulate an
individualized care plan for each patient. What is thought to be
causing this pain? What kind of initial pharmacological therapy is
preferred? What are our second- and third-line therapeutic
considerations? What kind of psychosocial support does the patient
need? What studies are needed to make or confirm a diagnosis of the
source of the pain or the status of concurrent medical conditions?
What kind of procedural interventions could help this patient and
when should the anesthesiologist be consulted? A patient with deep
boring abdominal pain from pancreatic cancer will often benefit from
a celiac plexus block. We try to offer this block to patients before
it becomes infeasible due to depression of the patients
platelet or white blood counts from their anticancer therapy.
Comprehensive assessment facilitates the differential diagnosis of
the source of the pain. To illustrate, a woman was recently referred
for treatment of peripheral neuropathy from her paclitaxel (Taxol)
and platinum chemotherapy for ovarian cancer. She was in such severe
pain that she could not get out of bed for her next appointment. When
assessed, she was found to have both peripheral neuropathy and severe
sciatica. Specifically, she had pain that radiated down into her
buttocks, and the back of her right thigh, which is not consistent
with the usual stocking-glove distribution of peripheral neuropathy.
Her peripheral neuropathy was treated with a tricyclic antidepressant
and low-dose opioids, and initiated a trial of dexamethasone for her
acute sciatic radiculopathy. Her pain and mobility improved
dramatically and her lumbosacral MRI showed lateral spinal stenosis
from degenerative disk disease. Her pain from peripheral neuropathy
improved on nortriptyline, but her sciatic pain returned when the
dexamethasone was lowered. She received an epidural steroid
injection, which reestablished her comfort and function without the
risk of systemic steroid toxicity. The net result of this interactive
process of reassessment and care plan modification was a marked
improvement in the womans quality of life.
Systemic pharmacologic therapy is the mainstay of cancer pain
managment, but oncologists must undertand the potential of neuraxial
application of pharmacologic agents or neurolytic nerve blocks.
Systemic therapy must be optimized by selecting the right analgesic
right dose, right route, and right interval (Table
1). This analgesic is given around-the-clock to prevent
chronic pain and offered as-needed to relieve breakthrough pain.
Analgesic doses must be aggressively titrated and common side effects
must be anticipated, prevented, and treated. Comfort and function can
be further optimized through sequential opioid rotation and
appropriate use of pain-specific coanalgesics.
Pharmacologic management must be individualized for each patient with
the initial aim of keeping things as simple and noninvasive as
possible. Patients with advanced cancer are often overwhelmed by the
progression of their disease and the toxicity of their anticancer
therapy. The easier they find it to gain control of their pain, the
better. Since patients vary in their response to different opioid
analgesics, it is important to have a working knowledge of
equianalgesic tables to be able to switch from one opioid to
another.[7,10,11] It is even more critical to have the time and skill
to talk with patients and their families to assure them that
addiction and tolerance are not real issues in the management of
advanced cancer pain.[7,11]
Selection of the appropriate analgesic depends upon the patients
pain intensity and their current analgesic therapy.[7,10,11] Pain
can be measured with simple unidimensional instruments, like a
numeric scale or visual analogue scale, or more comprehensive scales,
like the Brief Pain Inventory. By correlating pain intensity
scores from the latter instrument with the impact of the pain on
aspects of their quality of life, it has been shown that patients
with a score of 1 to 3 can be considered to have mild pain, 4 to 6,
moderate pain, and 7 to 10, severe pain.
Before selecting an analgesic to treat a patients severe pain,
one has to know what pain medications he or she is already taking. A
pain rated 6 by someone whos not taking any analgesic might go
away with a simple nonsteroidal anti-inflammatory agent. Patients
with a pain of 6 out of 10 who are already taking 300 mg of
controlled-release morphine will most likely need 450 or 600 mg of
controlled-release morphine for relief.
Most patients with advanced cancer will need World Health
Organization (WHO) step three opioids: morphine, oxycodone,
hydromorphone, or fentanyl.[7,11] These single-entity opioid
analgesics are free of the dose-limiting aspects (i.e., the maximal
safe dose of the nonopioid component) of WHO step two
fixed-combinations of opioids plus nonopioids, such as codeine plus
acetaminophen or hydrocodone plus ibuprofen. It is important to use
step three opioids one at a time to allow for sequential trials of
alternative opioids should the patient experience unacceptable side
effects from the first drug.[21-24] Patients receiving
controlled-release morphine should be on immediate-release morphine
for breakthrough pain. Those receiving controlled-release oxycodone
should have immediate-release oxycodone available for rescue doses.
Meperidine (Demerol) should be avoided because of its toxic
metabolite, normeperidine.[7,10] There are new reasons to learn how
to use methadone in sequential opioid trials,[22,24] it is usually
not a first drug due to its prolonged metabolism and risk of delayed accumulation.[7,10,11]
When switching from one opioid to another, and from one route of
opioid administration to another, the clinician must know how to
utilize an opioid equianalgesic table (Table
2).[7,10,11] These tables offer relative analgesic equivalencies
to guide dose conversions. Most cancer patients will need more than
one opioid and more than one route of opioid administration over the
course of their disease.[7,19] The parenteral route is more potent,
but not more effective, than the oral route.[7,11] When switching
from the oral route to the parenteral route or vice versa, dose
adjustments must be made for optimal safety and efficacy.
For most cancer pain patients, most clinicians use controlled-release
morphine and immediate-release morphine,[25,26] controlled-release
oxycodone and immediate-release oxycodone.[27,28] For patients who
cannot swallow or be relied on to take oral medications twice a day,
transdermal fentanyl (Duragesic) is an excellent alternative for
control of their persistent pain.[29,30] A long-acting form of
hydromorphone should be on the market sometime in the next year.
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