Controlling the pain of cancer is multifaceted. Some patients will
experience very little pain requiring only mild non-narcotic analgesics. Other
patients will suffer through horrendous pain experiences defying even the most
exotic pain management techniques. Recognizing how much pain an
individual patient has and how well the patient is managing the pain is not
always an easy task. Patients will not always openly articulate their
pain-related problems. As a dynamic disease, the pain from cancer can
change daily necessitating frequent questioning. Most clinical
interactions with the cancer patient should include questions concerning their
pain. Successful management depends upon awareness by the clinician of
the importance concerning pain management, constant vigilance, and utilization
of resources available for difficult patients.
Successful medical management of cancer pain requires knowledge of more
than one or two narcotic medications. Non-narcotic medications in
combination with an increasing number of narcotic preparations demand
individual titration. Changing drug, when appropriate, to match the
changing clinical condition yields the best results. Nonsteroidal
anti-inflammatory drugs (NSAIDs) are frequently utilized. Bony metastases
are common, periosteal swelling produces intense pain, and NSAIDs are
particularly effective in controlling this pain. Other malignancies where
inflammatory pain is likely will benefit from a trial of NSAIDs. Like
other non-narcotic medications, a ceiling effect for NSAIDs exists beyond which
increased side effects will predominate. GI and renal intolerance
represent the most common reasons for discontinuation.
Tricyclic antidepressants and their analogues have been useful in many
clinical situations. They elevate the pain threshold by their effects on
serotonin reuptake blockade. They can be particularly useful as an
adjunct medication in patients who are clinically depressed. Single
dosing at bedtime is often effective for both pain management and sedative
properties. Rarely are anti-depressant doses needed in this
population. Small doses should be used whenever possible to avoid the
sedative qualities which can persist into the following day.
Neuronal membrane stabilizers such as phenytoin and carbamazepine have
been helpful in patients with neuralgic pain. This can occur secondary to
tumors invading neural structures or neuropathic pains resulting from surgery,
radiation, or chemotherapy. In patients with leukemia or other blood
dyscrasias should use carbamazepine with caution and all members of the
treating team should be aware of its intended use.
Except in select cases where GABA-nergic nociceptive processes are
active, benzodiazepines have very limited role in cancer pain management.
Their sedative qualities are unattractive when no analgesia can be
garnered. They do have limited use when anxiolysis is felt to be a major
need in managing a particular pain problem.
Prescribing a particular narcotic depends on many factors.
Propoxyphene can be very effective in some patients while morphine sulfate (MSO4)
can yield discouraging results in other patients.
The use of schedule-III narcotics such as codeine or hydrocodone is
applicable in patients with mild to moderate pain. The short half-life can
necessitate frequent dosing in patients with continuous pain. The amounts
of acetaminophen ingested must by monitored when higher doses are used.
The present development of codeine contin will allow for less frequent dosing
and avoidance of acetaminophen.
Schedule-II narcotics represent a natural progression for many patients
with cancer pain. The use of oxycodone preparations can be very effective
although the short half-life can require frequent dosing intervals.
Hydromorphone and MSO4 are both potent analgesics. MSO4
in oral form is poorly absorbed from the gastrointestinal tract and suffers
from a first pass effect in the liver. Oral potency ranges from 1/3 to
1/6 the IV dose. Hydromorphone has better bioavailability, approximating
50% of the oral dose, which gives it an effective potency of nearly 10 times
that of oral MSO4.
To achieve long dosing intervals from oral narcotic medications, one
must consider either methadone or a sustained release preparation of MSO4.
Methadone's duration of action results from its long elimination
half-life. This can vary from 15-60 hours in individual patients.
Accumulation can occur and may be delayed to the fourth or fifth day.
Ineffective analgesia can result early secondary to the necessity of achieving
steady state prior to intervals the dosing interval. With sustained release
MSO4 or methadone dosing intervals of every 8-12 hours can be
achieved.
Often adequate control of pain requires the use of two separate narcotic
medications. This should be achieved using one long acting medication
such as methadone or sustained release MSO4 plus a potent
schedule-II, short half-life analgesic such as hydromorphone or
oxycodone. The patient should take the long-acting narcotic on a
prescribed around-the-clock basis and the short acting medication on a prn
basis.
IV opiates are reserved for patients in pain crisis or with continuous
unremitting pain. While continuous IV infusions remain useful, it can be
difficult to estimate the necessary dose for any given patient. A
successful alternative to continuous infusions has evolved with the use of
patient controlled analgesia (PCA)1-2. This technique allows
the patient to titrate the amount of narcotic needed to his/her individual
needs. A background infusion rate can be set with incremental boluses
administered on demand. Lockout intervals can be programmed to prevent
the patient from receiving too much medication. Once pain relief has been
achieved, a 24-hour total can be recorded and the dose equivalency calculated
for conversion to oral preparations.
Recently the development of transdermal fentanyl has greatly aided the
management of cancer related pain problems3-4. These patches
last an average of 72 hours and can deliver 25, 50, 75, or 100 ug/hr. The
advantages include delivery of a constant infusion of narcotic medication,
avoidance of peaks and troughs often associated with oral dosing regimens, and
allowing patients to forego taking oral medications. It should be
remembered that 12-16 hours will be required before peak blood levels are achieved
after initiation or changing of concentration. The use of IV PCA fentanyl
with subsequent transdermal fentanyl has been reported with a high degree of
success5.
Subcutaneous administration can also produce steady state plasma
narcotic levels. This can be achieved with small 25-G butterfly needles
into any appropriate subcutaneous tissue space. Small volumes should be
infused; optimally @ 0.1 ml/hr, and additional incremental boluses of 0.1-0.3
ml can be administered through portable PCA devices. These infusions can
control both continuous pain and allow for control of incremental pains.
For some patients, neural blockade represents a distinct advantage over
systemic medications. In some situations, this occurs because of the relative
ineffectiveness of systemic narcotics for specific pain conditions.
Alternatively, the ease and successfulness of some neural blockade procedures
renders it a better alternative to prolong systemic administration of
narcotics.
Individual somatic nerves can be blocked when pain is limited to a
specific dermatome6. Local anesthetic solutions are commonly
utilized initially and occasionally provide long-lasting relief. If the relief
achieved is temporary but effective, then neurolytic solutions may be
injected. To achieve maximum benefit, neurolytic solutions often need to
be repeated for peripheral nerves. Their effectiveness can be impressive
where large amounts of narcotics have failed. Normal physiologic function
of the nerve will be sacrificed and must be explained to the patient prior to
proceeding. Virtually all nerves are accessible to percutaneous
techniques at some point along their pathway. Unfortunately many cancer
related pains are either not relegated to a single somatic nerve or the
consequences of neurolytic blockade outweigh the advantages of pain relief
(e.g., brachial plexus blockade and loss of function in the upper extremity).
No nerve block is simpler to perform nor more effective for cancer pain
of the pancreas and upper abdominal malignancies than celiac plexus block7-8.
Long-lasting relief most commonly occurs following the block and should the
patient outlive the length of pain relief from the procedure, repeating the
block will often reestablish pain control. Considering the poor survival
rate of pancreatic cancer (.2% five year survival) pain management assumes a
major component of treatment. Celiac plexus block remains the most
effective method of achieving pain control. Risks are minimal and most
can be avoided with the use of imaging techniques. Orthostatic
hypotension will occasionally occur but usually resolves over a short period of
time.
Neurosurgical techniques such as percutaneous cordotomy, dorsal root
entry zone (DREZ) lesions, or hypophysectomies have been employed9.
Of these, the most useful clinically has been percutaneous cordotomy.
Performed at C1, it can be achieved percutaneously and is most successful for
unilateral pain at the level caudal to the umbilicus. Risks include loss
of bowel or bladder control or paresis of the involved extremity.
Intraspinal analgesia for cancer pain management represents a
significant advance to patients with refractory advanced pain. A variety
of narcotic and nonnarcotic agents can be instilled through any of several
catheter and/or pump designs. This allows the physician to tailor the
analgesic requirements to meet individual needs. When this technique is
reserved for patients whose terminal pain is unrelieved by alternative
measures, the benefits and quality of life obtained can be readily appreciated.
Any intraspinal catheter that exits through the skin can be considered
an externalized catheter. Nylon catheters can be utilized for long-term
pain management, however, their incidence of dislodgement, kinking, occlusion,
and breakage appears higher than other systems. Infectious risks may also
be greater in these catheters. To lessen this risk, catheters can be
tunneled subcutaneously using a simple 5-1/4" 14- or 16-gauge
angiocath. A small subset of patients with cancer pain will benefit from
intraspinal analgesia, but have a life expectancy of days to three weeks. The
rigors of placing a more permanent system may not be indicated; rather, a
subcutaneously tunneled nylon catheter might be quite adequate.
A more permanent externalized system has been developed by Dupen10.
This packaged system includes a 17-gauge silicone catheter, which is passed
through a Hulstead needle. The catheter system incorporates an
antimicrobial and Dacron? cuff to prevent infection and help prevent
dislodgement should the catheter be caught inadvertently or pulled by external
forces. The benefit of this system involves the ease of placement and the
ability to reinject without having to pierce the skin. The major drawback
is the external catheter, which some patients find unacceptable, and a risk of
tract infections exists by virtue of the continuum of external catheter and
internal tract.
To avoid external catheters, some clinicians prefer to place a
subcutaneous port, which can be connected to the intraspinal catheter.
Silicone or polyurethane catheters have been most commonly used. The
characteristics of a good port include: large dome for easy access, large
base for stability, and a non-penetrable base to avoid misguided needle
injections. Most of these systems require connection in the lateral
abdominal wall, which can be sometimes tedious. Newer systems rely on a
connection only at the portal.
Portal systems can be accessed in two ways: 1) by intermittent
bolus injection when needed for pain, or 2) by continuous infusion with or
without PCA using a Huber needle maintained in the port. Intermittent
injections can be performed with either a 22-gauge Huber needle or a 25-gauge
disposable needle11. Continuous infusions are maintained
using an external portable pump with the solution concentrated such that only
weekly refilling is required. Coincident with the solution change, the
tubing and needle are changed. Strict sterile technique must be followed
when changing the needle site12. The advantages of ports
include excellent patient satisfaction and possibly fewer infections.
Ports, do however, require a small surgical incision and increased cost.
Intraspinal catheter can be connected to an internal pump for
continuous infusion of analgesic agents. Newer pumps allow changes in the
infusion rate and bolus capabilities to be programmed into the pump.
These pumps offer the most patient flexibility by being completely
self-contained, allowing total freedom from any external devices (catheters, Huber
needles, or intermittent needle injections). Significant drawbacks remain
for many patients, however, these include a large, bulky pump, no true PCA
component since changes must include a computer-generated programming change,
and high cost.
Once a system has been chosen and placed, the more difficult issues of
long-term management remain.
Drugs
Selection of drug is based on several factors. Morphine
remains the most popular agent for several reasons:
familiarity
ability to be concentrated in preservative-free form at
50-60 mg/mL
extreme hydrophilicity
low cost.
The most important reason not to use morphine sulfate (MSO4)
is patient intolerance (allergy) or, in a few cases of high-dose intrathecal
use, myoclonic activity.
Hydromorphone maintains many of the qualities
already listed for MSO4 and can be considered a good alternative
drug. It is commercially available in concentrated solutions of 10 mg/mL,
is hydrophilic, and available at reasonable cost.
Meperidine is not appropriate for long-term use
because of potential normeperidine accumulation.
Sufentanil appears more desirable than fentanyl
because of its concentrated preparation. The advantage of sufentanil is
theoretical, but may be related to receptor selectivity. Sufentanil analgesia
has been shown to require only 35-40% receptor occupancy. Tolerance to
spinal opiates may be overcome more easily by an agent like sufentanil, by
merely increasing the dose. The major drawback to sufentanil is its cost,
which can become prohibitive in tolerant patients.
Intraspinal catheters have been placed both intrathecally and
epidurally. The advantages of intrathecal placement include lower drug
requirements and a lower incidence of fibrosis. The biggest risk is
serious infection. The subarachnoid space has very little ability to ward
off infections, and the long-term risk of meningitis may not be insignificant.
Epidural catheters reduce, but do not eliminate, the risk of meningitis.
The dura is an effective barrier and the epidural space contains a high
concentration of macrophages to help ward off infection. However,
epidural placement necessitates more drug, which can produce side effects,
especially in tolerant patients. The risk of fibrosis remains a problem and
can preclude effective analgesia in extreme cases13. This
complication must always be considered whenever deterioration in analgesia has
occurred that cannot be explained by tumor progression.
Infection
The single most frequent reason for removal of catheter systems remains
infection, which can be classified as localized, systemic or life
threatening. No infection can be considered insignificant when a foreign
body is present. The incidence of infection in long-term intraspinal
catheters remains unclear. Intrathecal catheters have been reported to
result in meningitis in as many as 17% of cases (6 of 36)14.
With epidural catheters the incidence has been considerably less.
Tract infections represent the most common type of infection and can
occur either shortly after insertion, or more commonly, secondary to
hematogenous spread from a distant source. Classical teaching states that
it is impossible to treat any foreign- body infection without removal of the
foreign body. With the potent antibiotics we presently have, this may not
be true in all cases. We have successfully treated patients with tract
infections without removal of their catheters.
Systemic infections can also be managed without removal of the
intraspinal catheter. One must watch closely for signs and symptoms of
catheter seeding particularly in the spinal canal. Life-threatening
infections can develop rapidly, but will be easily diagnosed based on patient
symptoms and clinical examination. When in doubt, a lumbar puncture or
aspirate from an intrathecal catheter should be performed.
We have managed one such life-threatening case of meningitis without removal of the catheter. The patient wanted to retain the catheter and was treated with intrathecal antibiotics. We managed this treatment close cooperation of the infectious disease service. Such therapy cannot be recommended for all patients.
Tolerance
Long-term use of epidural narcotics was initially reported not to cause
the tolerance that occurs with systemic and oral routes. Unfortunately,
time has demonstrated that tolerance remains a major problem with narcotics,
irrespective of the route of delivery. Tolerance does not occur in all
patients, nor can one predict which patients are susceptible. Much of the
dose escalation that is attributed to the phenomenon of tolerance actually
occurs because of disease progression. In these patients, if the dose is
increased, the desired effect will often return.
In unusual cases, tolerance can become complete, whereby increasing the
dose produces no further effect and side effects become manifest. This is
rare, more commonly, analgesia will improve, but at the cost of unacceptable
side effects. At this point, options include:
changing the narcotic (cross-tolerance may not be
complete)
use or add local anesthetic to rest the opiate receptor,15
use a non-narcotic agonist, such as an α2-agonist.
It is unclear if tolerance develops more or less quickly when the
narcotic is administered by continuous infusion versus intermittent
injection. The literature has been conflicting to date and more work
needs to be done in this area.
The management of cancer pain has become quite specialized yet many
complex problems can be effectively managed without sophisticated techniques.
Combined with a sensible narcotic regimen, adjuvant oral medications can help
to manage most pain related problems. Attention to detail is critical as
patients often view pain management with extreme importance particularly as
their disease progresses. Intraspinal management of difficult, refractory
pain has been quite gratifying both for clinicians and patients. Patient
selection remains crucial, and the decision to use intraspinal catheters for
protracted periods always involves extra care and commitment when compared to
oral regimens. For those patients whose malignant pain becomes
uncontrollable with oral medications, due to unacceptable side effects,
intraspinal narcotic therapy can return a good quality of life to patients
during their terminal days. Other anesthetic and neurosurgical techniques
are also available and can be individualized to treat refractory cancer
pain. Using this diverse armamentarium few patients should have to suffer
with protracted pain during their disease course.
1. Kerr IG, Sone M,
DeAngelis C, Iscoe N, MacKenzie R, Schueller T: Continuous narcotic
infusion with patient-controlled analgesia for chronic cancer pain in
outpatients. Annals of Internal Medicine 108:554-557, April 1988.
2. Barkas G, Duafala
M: Advances in cancer pain management: a review of patient-controlled
analgesia. Journal of Pain and Symptom Management 3:150-160, Summer 1988.
3. Miser AW, Narang
PK, Dothage JA, Young RC, Sindelar W, Miser JS: Transdermal fentanyl for pain
control in patient with cancer. Pain 37:15-21, 1989.
4. Payne R:
Experience with transdermal fentanyl in advanced cancer. Eur J Pain 11:98-101, 1990b.
5. Zech DFJ, Grond
SUA, Lynch J, Dauer HG, Stollenwerk B, Lehmann KA: Transdermal fentanyl and
initial dose-finding with patient-controlled analgesia in cancer pain. A
pilot study with 20 terminally ill patients. Pain 50:293-301; 1992.
6. Gerbershagen
HU: Blocks with local anesthetics in the treatment of cancer pain.
Advances in Pain Research and Therapy 2:311-323, 1979.
7. Moore DC, Bush
WH, Burnett LL: Celiac plexus block: a roentgenographic, anatomic
study of technique and spread of solution in patients and corpses. Anesth
Analg 60:369-379, 1981.
8. Brown DL:
A retrospective analysis of neurolytic celiac plexus block for nonpancreatic
intra-abdominal cancer pain. Regional Anesth 14:63-65, 1989.
9. Meyerson BA:
The role of neurosurgery in the treatment of cancer pain. Acta
Anaesth Scand Suppl.74:109-113, 1982.
10. DuPen SL,
Peterson DG, Bogosian AC, Ramsey DH, Larson C, Omoto M: A new permanent
exteriorized epidural catheter for narcotic self-administration to control
cancer pain. Cancer 59:986-993, 1987.
11. Long-term
intrathecal versus epidural systems. In: Neural Blockade in
Clinical Anesthesia and Management of Pain, Second Edition. Eds: Michael
J. Cousins and Phillip O. Bridenbaugh. J.B. Lippincott Company,
Philadelphia, 1988. pg. 1008.
12. Priddy-Southern,
J: How to access and epidural implanted port. Nursing90 20:48-51, 1990.
13. Rodan, BA, Cohen
FL, Bean WJ, Martyak SN: Fibrous mass complicating epidural morphine
infusion. Neurosurgery 16:68-70, 1985.
14. Schoeffler P,
Pichard E, Ramboatiana R, Joyon D, Haberer JP: Bacterial meningitis due to
infection of a lumbar drug release system in patients with cancer pain.
Pain 25:75-77, 1986.
15. Sjberg M,
Appelgren L, Einarsson S, Hultman L, Linder E, Nitescu P, Curelaru I:
Long-term intrathecal morphine and bupivacaine in "refractory" cancer
pain. I. Results from the first series of 52 patients. Acta
Anaesthesiol Scand 35:30-43, 1991.
I.
INTRASPINAL PLACEMENT TECHNIQUE
A.
External Catheter
1.
Advantages
2.
Disadvantages
3.
Complications
a.
Obstruction/occlusion
b.
Kinking
c.
Shearing
d.
Dislodgement
B.
Catheter/Port System
1.
Advantages
2.
Disadvantages
3. Complications
a.
Occlusion
b.
Shearing
c. Port
related
C. Internal
Pump
1.
Advantages
2.
Disadvantages
3.
Complications
a.
Pocket-related
b.
Catheter-related
II. LONG-TERM CATHETER MANAGEMENT
A.
Catheter
1.
Fibrosis
2.
Infection
a.
Subarachnoid catheter
b.
Epidural catheter
3.
Catheter material
a.
Nylon
b.
Silicone
c.
Polyurethane
4.
Dislodgement
5.
Occlusion
B. Port
1.
Occlusion
2.
Infection
3.
Erosion
C. Internal
Pump
1.
Mechanical
2.
Intrinsic pump limitations
3.
Refilling