Review

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Pain relief in palliative care:

a focus on interventional
pain management
Expert Rev. Neurother. 10(5), 747–756 (2010)

Mandar Joshi†1 and
William A Chambers2
1
Western General Hospital,
Edinburgh, UK
2
Aberdeen Royal Infirmary,
Aberdeen, UK
†
Author for correspondence:
mandarjoshi@nhs.net
Pharmacological treatment forms the foundation of the management of pain in patients with
advanced cancer. Although the majority of patients in the realm of palliative care can be provided
with acceptable pain relief using the three-step WHO cancer pain guidelines, a significant
minority still have pain that is not adequately controlled by conventional pharmacological
management. Development of pain management strategies using a multidisciplinary input with
appropriate and timely use of interventional pain management techniques can provide
satisfactory pain relief for these patients, helping to reduce distress in the patient and their
relatives during this difficult period. This clinical review aims to discuss the commonly used
interventional techniques in pain management in palliative care. As patients with advanced
cancer are the major recipients of palliative care services, the main focus of this article remains
on pain management in advanced cancer. The use of central neuraxial blockade, autonomic
blockade and peripheral nerve blocks are summarized.

Keywords : anesthetic technique • pain • palliative care • regional

Pain is the most feared and common symptom
related to an end-of-life event. It is also probably
the most under-treated symptom. A review of
published literature by Deandrea et al. looking
at the prevalence of under-treatment in cancer
pain concluded that pain is under-treated in
nearly 50% of cancer patients  [1] . All chronic
pain was once acute, and the longer the pain is
left untreated the more difficult it becomes to
achieve good pain relief. Acute persistent pain
may promote biochemical, physiological and
pharmacological changes in the PNS and CNS,
which may promote the continuation of pain [2] .
Patients with advanced cancer form a major
subgroup of patients who benefit from appropri-
ate pain relief in a palliative care setting. Non-
malignant diseases that may benefit from pallia-
tive care input include end-stage congestive heart
failure, chronic obstructive pulmonary disease
and progressive neurological diseases, such as
dementia, parkinsonism and multiple sclerosis.
Pain is also a well-recognized, significant prob-
lem in patients with AIDS, who may need pallia-
tive care services for pain management [3] . This
article is a clinical overview of pain management
in palliative care with a particular focus on inter-
ventional techniques. As patients with advanced
cancer form the major proportion of recipients of
palliative care, the emphasis in this article will be
on pain management in patients with advanced
cancer. However, the same principles of pain
management apply to non-malignant diseases.
The National Cancer Institute (MD, USA)
has estimated that approximately 1.5  million
new cancer cases will be diagnosed in 2009
in the USA, with approximately half a million
deaths [4] . There were on average approximately
293,000 newly diagnosed cancer cases and
154,000 deaths from cancer each year in the UK
between 2004 and 2006 [5] . A systematic com-
parison of symptoms in patients with advanced
cancer and end-stage non-malignant diseases
(e.g., AIDS, heart disease, chronic obstructive
pulmonary disease and renal disease), found that
more than 50% of patients had symptoms of
pain, breathlessness and fatigue [6] . These figures
highlight the magnitude and need for attention
to this problem.
Apart from being a global challenge, under-
treatment of cancer pain is a significant problem
in developed countries where palliative care ser-
vices are comparatively well established. In total,
20–50% of cancer patients will present with pain
at diagnosis and approximately 70% of patients

www.expert-reviews.com 10.1586/ERN.10.47 © 2010 Expert Reviews Ltd ISSN 1473-7175 747

 Review Joshi & Chambers
with advanced disease will have significant pain needing opioids
for pain management [7–9] . It has been estimated that between 5
and 10% of patients with advanced cancer have pain that could
not be adequately controlled by conventional pharmacological
management [7,10] .
Pain caused by cancer and other medical illnesses may be caused
by direct effects of the primary pathology (e.g., local tissue inva-
sion by tumor, distant metastasis, nerve compression) or by treat-
ment (e.g., surgery, chemotherapy and radiation therapy). Cancer
pain is quite complex as it can present as a combination of acute
and chronic pain and the treatment strategies need to be planned
according to the physiological nature of the pain. The pain can
be nociceptive or neuropathic, although it very commonly exists
as a combination of various mechanisms, specifically, somatic or
visceral, nociceptive or neuropathic. Cancer patients will often
have more than one pain that may or may not be cancer-related
and frequently need different treatment modalities. Several cancer
pain syndromes have been described in literature.
Opioids form the cornerstone of pain management in the
majority of cancer patients. The three-step WHO pain ladder
for cancer pain recommends the use of opioids for management
of moderate-to-severe cancer pain (Figure 1) [11] . However, the use
of opioids is not without significant problems. These drugs are
still not fully available throughout all parts of the world and their
use may be accompanied by unwanted or even intolerable side
effects. Common side effects associated with opioid use include
nausea, constipation, confusion and sedation/cognitive dysfunc-
tion [12] . Opioid-induced hyperalgesia is a well-recognized clinical
entity associated with use of opioids and can pose a significant
challenge in pain management in these patients [13] . Reduction in
opioid usage, opioid rotation and use of NMDA receptor antago-
nists are some of the recommended prophylactic and therapeutic
options for opioid side effects and opioid-induced hyperalgesia.
Other adjuvant medications used in pharmacological manage-
ment of pain in palliative care include tricyclic antidepressants,
anticonvulsants (gabapentin, pregabalin), NSAIDs, ketamine,
bisphosphonates and steroids.
Freedom from
cancer pain
Opioid for mod
erate-
to-severe pain
± nonopioid ± ad
juvant
Pain persisting or
increasing
Opioid for mild-to-
moderate
pain ± nonopioid
± adjuvant
Pain persisting
or increasing
Nonopioid ± adjuv
ant
PAIN
Figure 1. WHO pain ladder.
Reproduced with permission from [11] .
748
The fact that a considerable proportion of patients will not have
good pain control on the final step of the WHO analgesic algo-
rithm warrants the use of additional strategies for the provision of
pain relief that incorporates interventional pain treatment.
Interventional pain management techniques involve the deliv-
ery of drugs (often local anesthetic agents and/or opioids) to
the spinal cord or major nerve plexuses/trunks, application of
neurolytic agents (alcohol, phenol) to neural structures or other
destructive procedures (neurolytic nerve blocks, cordotomy). In
recent years the equipment available for the convenient continued
infusion of solutions neuraxially has improved to the extent that
providing this form of treatment is much easier than before. For
that reason, destructive procedures, with the possible exception
of celiac plexus block and percutaneous cervical cordotomy, have
been used much less commonly than they were previously.
Neuraxial techniques
Neuraxial administration of morphine for pain control in cancer
patients was first reported in 1979 [14] , and since then several other
opioids and nonopioids have been used by the epidural or intra-
thecal route. Neuraxial (epidural or intrathecal) administration
of opioids can produce good analgesia in cancer and noncancer
patients who have inadequate pain control in spite of conventional
medical therapy or have unacceptable side effects associated with
pharmacological analgesic therapy [15,16] . Smith et al. compared
comprehensive medical management with comprehensive medical
management combined with intrathecal opioid therapy for pain
control in a randomized controlled study in 202 cancer patients.
They suggested that a better pain control and side effect profile
was obtained in patients treated with intrathecal drug delivery
and comprehensive medical management, compared with com-
prehensive medical management alone (84.5 vs 70.8%; p = 0.05).
The study also suggested a possible improved survival in patients
treated by the intrathecal route as a secondary outcome  [17] .
Although central neuraxial opioids are predominantly used for
cancer pain in palliative care, they have also been used for certain
noncancer conditions, including intractable angina [18] and severe
inoperable ischemic pain. Before embarking on such invasive pro-
cedures for chronic benign pain it is important to confirm that
other avenues for pain control have been fully explored, but in
patients with advanced cancer, time may be pressing and a balance
has to be sought between embarking on interventional therapy
before a full trial of other options and leaving things too late.
Opioids administered via the epidural or intrathecal route pro-
duce analgesia by binding to the opioid receptors in the substantia
gelatinosa in the gray matter of the spinal cord. Substantially lower
doses of opioids are required to produce the same analgesic effect
compared with opioids administered by an oral or parenteral route,
which in turn is usually associated with a lower incidence of the side
effects related to opioid usage. However, their use introduces the
potential for other serious side effects, including the introduction
of infection near the spinal cord.
A number of opioids, including morphine, diamorphine, hydro-
morphone, fentanyl, sufentanil and methadone, have been admin-
istered by the neuraxial route for management of cancer pain, but
Expert Rev. Neurother. 10(5), (2010)
 Pain relief in palliative care: a focus on interventional pain management
most clinical experience is available with morphine. The neuraxial
opioid dose used varies considerably according to the individual
patient. The approximate dose is 10% and 1% of the total daily
parenteral opioid equivalent dose for epidural and intrathecal
use, respectively. The onset, duration of analgesia and cephalad
spread of an opioid in the intrathecal and epidural space depend
on its pharmacokinetic properties. As a general principle, higher
lipid solubility of a drug is associated with a shorter duration
of action  [19] . Morphine and hydromorphone, which are more
hydrophilic and have lower lipid solubility than fentanyl, produce
longer lasting analgesia; although there is also a risk of respiratory
depression related to increased cephalad spread of the long-acting
opioid in the cerebrospinal fluid (CSF).
It is common to combine an opioid with another drug or drugs
and those used include local anesthetic agents (most often bupiva-
caine) and clonidine. The combination of opioids and nonopioids
for neuraxial administration improves the quality of analgesia.
Intrathecal bupivacaine combined with morphine is suggested
to have an additive effect in the management of cancer pain,
which can result in reduced opioid requirements [16,20,21] . The use
of a local anesthetic agent (bupivacaine 2–30 mg/day) could be
particularly useful for incident pain. Clonidine (25–800 µg/day),
a centrally acting a-2 adrenergic receptor agonist exerting its
analgesic effects by inhibitory interactions with presynaptic and
postsynaptic afferent fibers in the dorsal horn of the spinal cord,
is used in conjunction with opioids for the treatment of neuro-
pathic pain [22] . Baclofen is a GABA-B receptor agonist primarily
used for treatment of severe spasticity due to upper motor neuron
lesions. It is also used intrathecally, either alone or in combination
with opioids, for treating musculoskeletal pain due to spastic-
ity and chronic neuropathic pain. A trial of a single intrathecal
dose of baclofen is recommended to test the responsiveness to
treatment before initiating a continuous infusion. Common side
effects associated with baclofen use include muscle weakness,
dizziness, sedation and the possibility of a serious withdrawal
after abrupt cessation of therapy [23] . It is important to obtain
expert assessment of the patient’s condition immediately after the
injection of a trial dose to ensure that the reduction in spasticity
is not outweighed by increased muscle weakness. Ziconotide, a
nonopioid analgesic, has recently been added to the armamen-
tarium of drugs for use via the neuraxial route. It is a selective,
reversible blocker of neuronal N-type voltage-sensitive calcium
channels and inhibits neuro­transmission from primary nocicep-
tive afferents in the spinal cord [24] . Although intrathecal adminis-
tration of ziconotide can produce good quality analgesia in cancer
patients, its usefulness has been questioned owing to severe and
frequent side effects. Dizziness, nausea, confusional state, ataxia
and memory impairment are the common side effects observed
with ziconotide therapy [25–27] . Higher doses and faster titration
are associated with an increased incidence of side effects and a
gradual increase in ziconotide dose is recommended, starting at a
low dose and gradually titrating up to a maximum recommended
dose of 19.2 µg/day over a period of 3 weeks. This may not always
be possible owing to the limited time available in patients with
very short life expectancy.
www.expert-reviews.com
Review
Neurolytic agents used by the epidural route have been shown
to produce good pain relief in patients with very limited life expec-
tancy and in whom the pain is not controlled by use of a combi-
nation of epidural opioid, local anesthetics and other adjuvants.
Alhough sparingly used in the palliative care setting by the epidural
route, an injection of 6–10% phenol can be used for intractable
pain that is not responding to conventional drugs administered
by the neuraxial route in patients who have a life expectancy of a
few days [28] . Epidural neurolysis with repeated epidural injections
of alcohol have been documented in Japanese literature for severe
cancer pain and significant reduction of Visual Analogue Scale
(VAS) pain scores were observed – perhaps surprisingly without
any serious side effects or complications [29] .
Contraindications
Contraindications for performing central neuraxial procedures for
control of intractable pain in advanced cancer are similar to contra-
indications for regional anesthesia. A careful consideration of risk
versus benefit is required, frequently with a multidisciplinary input
to formulate a management plan in these patients. Certain clinical
situations that are absolute contraindications to regional anesthesia
in management of acute pain, specifically, coagulopathy or risk of
infection, may not be the same for placement of an epidural or intra-
thecal catheter for control of pain in advanced cancer. Patients with
advanced cancer may be coagulopathic and at a risk of infection due
to an immunocompromised status, but a careful balance must be
struck between the risk related to performance of central neuraxial
procedures and the benefits gained from analgesia. The risk of spinal
cord compression is increased in the presence of spinal metastasis,
either due to injury to the friable metastatic tissue or formation of
spinal hematoma during insertion of a catheter. Furthermore, spinal
metastasis can cause obstruction to the flow of CSF; therefore, it is
recommended that spinal catheters should be placed cephalad to the
known or suspected epidural or spinal metastasis. A recent meta-
ana­lysis and systematic review of serious complications associated
with external intrathecal catheters used in cancer pain patients by
Aprili et al. included ten clinical trials with a total of 821 patients.
The incidence of superficial and deep infections was found to be
2.3% (95% CI: 0.8–6.1) and 1.4% (95% CI: 0.5–3.8), respectively,
and was comparable to other intrathecal catheter techniques. The
risk of bleeding was found to be 0.9% (95% CI: 0–2.0), and for
neurologic injury 0.4% (95% CI: 0–1.0). The review concluded
that the ana­lysis supports the reasoning that the potential benefit of
intrathecal catheters in the treatment of severe cancer pain is likely
to outweigh the potential for serious complications associated with
this technique [30] .
Consent
Obtaining an ‘informed’ consent in patients who are already on
high-dose opioids in these clinical situations is a difficult task.
By the time interventional pain therapy is considered the major-
ity of these patients are on high-dose systemic opioids and their
cognitive abilities are almost certainly impaired. Often multi-
disciplinary input from the pain physician, palliative care physi-
cian, oncologist and the patient is needed to come to a decision
749
 Review Joshi & Chambers
regarding the recommended best course of action [31] . In some
palliative care units, patients who are considered likely to need
interventional pain management are identified early and given
time to consider the possible treatment options if needed in the
future. Appropriate patient selection is the most important factor
to determine the choice and outcome of treatment.
Dosage
The opioid dose for intrathecal or epidural use is estimated accord-
ing to the total daily morphine dose or its equivalent (including
the breakthrough analgesic requirements). The first step is to
calculate the total daily parenteral morphine dose equivalent. For
patients taking opioids by mouth it would be usual to take 30%
of this as the parenteral equivalent. The daily dose by the epidural
route will then be between 5 and 10% of the total daily parenteral
equivalent and total daily intrathecal dose will be between 0.5
and 1% of the total daily parenteral dose [32] . Some clinicians use
higher doses that are similar fractions of total daily oral morphine
dose or its equivalent [33] .
Opioid conversion factors are published but it is important to
recognize that these are not to be regarded as an exact equivalence
in individual patients. The conversion factors used to estimate equi-
analgesic doses of opioids are not an exact science. Furthermore,
conversion factors for systemic analgesia cannot be applied to the
central neuraxial route, owing to the variations in pharmaco­
kinetics of the drug given by the neuraxial route as compared with
the parenteral route. Given the wide variation between individual
patients in terms of opioid requirement and handling, it is safer to
start cautiously with a lower than calculated dose and add further
increments according to effect. In some cases, it may be several days
before dose escalation or inclusion of another drug is needed to
achieve an optimal response [34] . An algorithm developed by Coyne
et al. for initiating and titrating intrathecal analgesic therapy treat-
ment in refractory cancer pain is illustrated in Figure 2 [35,36] and
there are others that have been developed [37,38] . In a randomized
trial of routine oncology care versus algorithms, Du Pen and col-
leagues observed an improvement in pain reduction with the use
of algorithms [39] . A screening trial of intrathecal opioids before
implantation of an intra­thecal drug delivery (ITDD) system is
recommended to assess the efficacy of intrathecal drug delivery [37] .
It gives the physician an opportunity to evaluate patient response
and potential side effects to specific medications, which helps in
selecting appropriate agents and their dosage.
A variety of neuraxial drug delivery systems are available, rang-
ing from percutaneous catheters for short-term use, tunneled cath-
eters with external drug delivery systems and totally implantable
drug delivery systems that can be programmed for changes in
infusion rates or on demand bolus delivery. There is very little
consensus concerning which route to use for neuraxial drug deliv-
ery in a particular patient population. In addition, particularly for
intrathecal administration, a decision needs to be made on whether
to use a percutaneous or an implantable drug delivery system. It is
generally recommended that percutaneously inserted epidural or
intrathecal catheters are confined to short-term use (i.e., less than
a few months) owing to the inherent risk of introducing infection
750
and the increased incidence of catheter-related complications, such
as blockage, displacement or disconnection, as compared with
implantable intrathecal devices (ITDD systems). A study compar-
ing the cost–effectiveness of implantable versus external pumps,
revealed a 3-month life expectancy to be the approximate ‘break-
even’ point for the implanted pump to become more cost-effective
than the external system [40] .
Percutaneous insertion of epidural or intrathecal catheters may
be performed in the patient’s bed if it is very disruptive to move
the patient to an operating theatre environment. Although the
risks of introducing infection may be greater, the ease of carrying
out the procedure in a terminally ill patient may make this the
most appropriate option. If an externally driven pump is used for
medication delivery, patient mobility for performing day-to-day
activities can be restricted, causing inconvenience. Despite these
disadvantages, with appropriately vigilant medical and nursing
support in the community, percutaneous neuraxial drug therapy
can be an effective method of providing pain relief in very ill
patients with very limited life expectancy [15] . ITDDs do require
insertion in a fully aseptic manner, preferably under fluoro­scopic
guidance. Gas-driven ITDDs infuse at a constant rate and there-
fore need a change in concentration of the infusate if a dose altera-
tion is needed. Computer programmed telemetrically controlled,
battery-driven ITDDs can be programmed to deliver medication
at variable rates and also provide an on-demand bolus facility.
For long-term use, ITDDs are safer and more convenient for the
patient owing to the reduced risk of infection and other catheter-
related technical complications [41] . Gestin et al. have shown that
in long-term treatment, intrathecal morphine administration may
give more satisfactory pain relief with lower doses of morphine
and fewer side effects than epidural administration [42] .
Adverse effects & complications
Pharmacological side effects and complications encountered dur-
ing neuraxial pain management are caused either by the opioids
or other adjuvant drugs (local anesthetics, clonidine, ziconotide).
Sedation, nausea, urinary retention and pruritus are the more
frequent complications of neuraxial opioid administration. Other
side effects include constipation, vomiting, fatigue, dry mouth,
sweating, edema, impotence and sleep disturbance [32] . The major-
ity of patients needing neuraxial opioids are already tolerant to
these side effects and their extent is thus lower than with systemic
administration. Respiratory depression, although a theoretical
possibility, is relatively uncommon owing to opioid tolerance.
Administration of intrathecal opioids and adjuvant medications
also allows significant reductions in the amount of administered
oral or parenteral medication [16,43,44] , which consequently leads
to a reduction in side effects.
Nonpharmacological complications during neuraxial drug
delivery are either route-specific, that is, epidural or intrathecal,
or due to technical problems related to the drug delivery system.
Infections associated with neuraxial drug delivery range from
localized skin/wound infections at the catheter or pump implanta-
tion site to epidural abscess, which could lead to permanent neuro­
logical consequences. In a systematic review and meta-ana­lysis,
Expert Rev. Neurother. 10(5), (2010)
 Pain relief in palliative care: a focus on interventional pain management Review

In-patient Monitor level of sedation, Inadequate relief

Morphine or hydromorphone.
May increase by as much as
20% every 12 h as needed.
Out-patient
Morphine or hydromorphone.
May increase by as much as
20% every 24 h as needed.
If the dose of clonidine reaches 850 µg/day,
consider adding to or replacing clonidine with
one of the following medications:
• Droperidal 25–250 µg/day
• Ketamine 25–1000 µg/day
• Baclofen 10–1000 µg/day
• Midazolam 50–2000 µg/day
• Ziconotide
A cancer pain, acute pain service or palliative
care consultant is highly recommended.
pain assessment scores,
function and side effects.
Consider initiating bupivacaine
if morphine dose is greater than
25 mg/day or hydromorphone
dose is >6 mg/day.
Start bupivacaine at 3 mg/day. May increase by
15% every 12 h as needed as in-patient or every
24 h as needed as out-patient.
With local anesthetics, monitor for leg weekness,
dermatome (sensory) level, postural hypotension
and urinary retention.
Inadequate relief
If no relief is achieved with bupivacaine, it should
be stopped. Consider initiating clonidine.

Start clonidine at 50 µg/day. May increase by 15%

Inadequate relief every 12 h as in-patient or every 24 h as out-patient.
Monitor for hypotension.

Figure 2. Intrathecal titration guidelines.

Note that if patients require frequent refills the pharmacy should be consulted to determine whether higher concentrations are available.
Doses are guidelines only; individual patient needs may vary.
From “Effectively starting and titrating intrathecal analgesic therapy in patients with refractory cancer pain” by PJ Coyne, T Smith, J Laird,
LA Hansen and D Drake, 2005, Clinical Journal of Oncology Nursing, 9(5), p. 583. Copyright 2005 by the Oncology Nursing Society.
Reprinted with permission [35] . Based on information from [36] .

Ruppen et al. specifically looked at infection rates associated with
indwelling epidural catheters used for 7 or more days [45] . A total
of 12 studies in cancer and noncancer patients were included, with
a total of 4628 patients. The total incidence of epidural catheter-
related infections was 6.1% (257), with 4.6% (211) superficial
infections and 1.2% (57) deep infections. In nine out of 12 studies,
which predominantly included cancer patients who had indwelling
epidural catheters for a longer duration (average duration 74 days),
the incidence of deep-seated infection was much higher (2.8%).
They estimated that one person in 35 with an epidural catheter
in place for 74 days for relief of cancer pain can be expected to
have a deep epidural infection. Although it might be expected that
meningitis would be more common or almost exclusively associ-
ated with intrathecal delivery, similar infection rates have been
reported with intrathecal and epidural administration. A thorough
neurological evaluation should be performed before carrying out
any interventional procedure and later at regular intervals for early
detection of neurological complications. Adherence to strict aseptic
techniques, bacterial filters and minimal changing of the drug
delivery system/tubing, should be practised to reduce the risk of
infection [46] . The use of adequate barrier precautions including
face masks should be encouraged. As the majority of patients with
advanced cancer are immunocompromised, any infection should
be aggressively treated with antibiotics, aspiration and surgical
drainage to prevent further complications. If infection does not
respond promptly to conventional treatment it may be necessary
to remove the entire implanted system.
Other relatively common complications associated with intra-
thecal drug delivery were found to be post-dural puncture head-
ache, mechanical complications, pain on injection, skin break-
down at the insertion site, external leakage of CSF, catheter tip
dislodgement, accidental catheter withdrawal and catheter (sys-
tem) leakage [47] . The incidence of these complications is quite
variable in the published literature.
Epidural fibrosis is a problem specifically related to drug deliv-
ery by the epidural route. Fibrosis in the epidural space probably
occurs as a foreign body reaction to the presence of the catheter
in the epidural space after long-term administration of opioids or
nonopioids. This manifests as pain on injection, increased resis-
tance to injection, obstruction of the catheter and poor spread
of the injectate leading to reduced efficacy and finally failure
of analgesia. The incidence of these complications, which are
presumably due to epidural fibrosis, is quite variable. In a review
of 140 cases, Crul et al. found the most frequent complication

www.expert-reviews.com 751
 Review Joshi & Chambers
associated with epidural drug delivery was obstruction and dislo-
cation of the catheter, probably due to the development of epidural
fibrosis. The problem became apparent in 50% of patients during
the treatment period from day 20 to 366 [48] . In a retrospective
study by Plummer et al. looking at 284 cases of long-term epidural
administration of morphine for cancer pain, the incidence of pain
on injection and obstruction was 12 and 10.9%, respectively [49] .
Aldrete found eight cases of epidural fibrosis amongst 41 patients
receiving long-term epidural analgesia for non-malignant pain
manifested by pain on injection, increased resistance to injection
and reduced analgesic effect [50] .
A number of strategies have been employed to manage this
situation including administration of epidural steroids, utilizing
a very slow injection technique or repositioning/replacement of
the epidural catheter.
Cerebrospinal fluid leak can occur after insertion of the ITDD
system and persistent leakage around the catheter site can lead to
post-dural puncture headache and CSF hygroma. Rare compli-
cations, such as potine hemorrhage [51] , cranial nerve palsy and
subdural hematoma [52] , have been attributed to the intracranial
hypotension [53] caused by persistent CSF leak.
The formation of an inflammatory mass or granuloma at the
tip of the intrathecal catheter is a potentially serious complication
that could cause spinal cord compression necessitating surgical
decompression [54–56] . The exact cause for the formation of these
granulomas is not known but an association with high-dose opi-
oid therapy (morphine or hydromorphone) has been postulated.
These masses are mainly reported from studies for non-malignant
pain and tend to occur approximately 2 years from the insertion
of the ITDD. Considering the timescale, this is unlikely to cause
a problem in the palliative care setting, although this emphasizes
the importance of regular neurological evaluation of the patient
for early detection of signs of spinal cord compression either by
granuloma or by metastasis. To reduce the risk of catheter tip
granuloma, maximum upper limits on concentration and dosage
of drugs delivered by the intrathecal route have been suggested [43] .
Autonomic nervous system blockade
Neurolytic celiac plexus block
The celiac plexus is the largest of the sympathetic plexuses that
supplies most of the abdominal viscera, including stomach, liver,
pancreas, adrenals, kidneys, large and small intestines and gonads.
It receives preganglionic fibers originating in the splanchnic nerves
(greater, lesser and least) that synapse in the celiac ganglia to give
rise to the postganglionic fibers that innervate the abdominal vis-
cera. The celiac plexus is consistently positioned anterior to the
celiac trunk at the level of the body of the L1 vertebra where it
could be blocked by an anterior or posterior approach. It is closely
related to aorta, inferior vena cava, kidneys and adrenals, which
emphasizes the importance of accurate needle positioning while
performing of injection using neurolytic agents.
Neurolytic celiac plexus block (NCPB) using alcohol or phenol
is performed for management of intractable visceral pain with the
aim of selectively destroying the celiac plexus to block the affer-
ent nociceptors to relieve abdominal pain. NCPB is considered in
752
patients with upper abdominal cancer if pain relief from systemic
analgesia is inadequate or is associated with undesirable side effects.
Although primarily used in pain management for pancreatic can-
cer it has also been used for pain secondary to other upper abdomi-
nal malignancies�������������������������������������������������
. Various
�����������������������������������������������
approaches, techniques and their varia-
tions have been described. Radiological guidance (fluoroscopy,
computerized tomography, MRI, ultrasound guidance) has been
used in an attempt to increase the efficacy and reduce the incidence
of complications associated with NCPB. Endoscopic ultrasound-
guided celiac plexus neurolysis using the anterior approach is also a
reasonable alternative to traditional percutaneous techniques [57,58] .
Neurolytic celiac plexus block can provide effective pain relief
for patients with visceral pain from pancreatic and other upper
abdominal cancers with reduction in opioid analgesic require-
ments [59] . A meta-ana­lysis of efficacy and safety of NCPB per-
formed by Eisenberg et al. found partial to complete pain relief
in 90% of patients with pancreatic and nonpancreatic cancer
in whom blocks were performed with and without radiological
guidance. Good-to-excellent pain relief was reported in 89% of
patients during the first 2 weeks after NCPB and long-term fol-
low-up revealed partial to complete pain relief in 90% of patients
at 3 months post-NCPB and in 70–90% of patients until death.
Patients with pancreatic cancer responded similarly to those with
other intra-abdominal malignancies [60] .
In a systematic review conducted by Yan and Myers assessing the
efficacy and safety of NCPB compared with standard treatment
in five randomized controlled trials involving 302 patients with
unresectable pancreatic cancer, NCPB was associated with lower
VAS scores for pain at 2, 4 and 8 weeks, reduced opioid usage
and reduction in constipation but no other adverse events. No
differences in survival were observed [61] . The effect of NCPB on
survival of patients with upper abdominal malignancies remains
unclear, despite the publication of a number of studies [61–64] .
Common side effects associated with NCPB are postural
hypotension and diarrhea, which are secondary to sympathetic
blockade of the abdominal viscera. These side effects are normally
self-limiting and transient but may rarely need treatment with
vasoconstrictors and opioids, respectively. Major complications
associated with NCPB are caused by injection or spread of the
neurolytic agent in the wrong place (i.e., neuraxial, intravascular)
or due to accidental injury to related structures (i.e., aorta, kid-
ney) during the performance of injection. Permanent paraplegia
is a rare but dreaded complication associated with NCPB with
an incidence quoted to be approximately 0.15%  [65] . The exact
mechanism for this complication is unclear and is postulated to be
due to neuraxial spread of the neurolytic agent or vascular spasm
resulting in ischemic injury to the spinal cord. Other rare com-
plications include aortic dissection [66] and retroperitoneal abscess
formation [67] . A meticulous technique and radiological guidance
should reduce the incidence of these complications.
Other autonomic blocks include superior hypogastric plexus
block for pelvic pain and blockade of ganglion impar for peri-
neal pain. The superior hypogastric plexus is a retroperitoneal
structure extending to both sides of the midline at L5/S1 level
in proximity of the bifurcation of common iliac vessels. It is
Expert Rev. Neurother. 10(5), (2010)
 Pain relief in palliative care: a focus on interventional pain management
traditionally blocked in prone position under fluoroscopic guid-
ance but recently computerized tomography [68] and ultrasound-
guided techniques [69] have been described. Superior hypogastric
plexus neurolysis is performed by using bilateral injections with
10% phenol. It can provide effective pain relief from pelvic pain
secondary to gynecologic, colorectal or genitourinary cancer,
which tends to spread locally by direct invasion or by regional
lymph node metastasis [70,71] . Kitoh et al. have suggested the pos-
sibility of combining NCPB with superior hypogastric plexus
block and inferior mesenteric plexus block for management of
diffuse, extensive, intractable abdominal pain caused by extensive
abdominal and/or pelvic cancer [72] .
Neoplastic perineal pain of sympathetic origin can be treated
by block of ganglion impar (walther). Ganglion impar is a soli-
tary retroperitoneal structure at the termination of paired para­
vertebral sympathetic chains located at the level of the sacrococcy-
gel junction. Neurolytic blockade of ganglion impar can produce
good pain relief in patients with genitourinary, colorectal cancer
with perineal pain without any adverse effects [73–75] .
Neural blockade of the lumbar sympathetic chain has been
used in the palliative care setting for lower extremity pain from
inoperable peripheral vascular disease. Less common indications
are visceral abdominal and pelvic cancer pain [76] and rectal
tenesmus [77] .
Sympathetically mediated pain in the head, neck and upper
extremities can be managed by stellate ganglion block. As the
cervical sympathetic chain is not enclosed in a confined fascial
space, neurolytic agents are avoided in this anatomical loca-
tion to prevent injury to adjacent structures (vertebral artery,
epidural/subarachnoid nerves, brachial plexus).
Peripheral nerve blocks
Cancer pain in the distribution of a peripheral nerve or nerve
plexus can be moderated by performing nerve blocks with local
anesthetics or neurolytic agents. If effective there may be an asso-
ciated reduction in opioid usage leading to a reduction in opioid-
related side effects. Although neurolytic peripheral nerve/plexus
blocks provide good initial pain relief, the development of neuritis
shortly thereafter means that there are relatively few patients in
whom this is the most appropriate therapy. Nerve blockade using
continuous infusion of a local anesthetic with or without an opioid
using a catheter technique can provide good analgesia. Temporary
pain relief provided by local anesthetic blocks can also be use-
ful to facilitate other treatments, such as physiotherapy, fracture
fixation and neurolytic blocks. The approach to perform these
blocks may have to be modified to suit patient comfort and may
be technically difficult owing to distorted anatomy due to sur-
gery or radio­therapy and difficult patient positioning due to pain.
Complications associated with these blocks include infection, local
anesthetic toxicity and catheter displacement.
Brachial plexus block at various anatomical locations (inter-
scalene, axillary) using continuous infusion of local anesthetic
has been used for intractable neuropathic upper extremity pain
associated with breast and lung cancer [78,79] . A typical example
includes insertion of brachial plexus catheter guided by ultrasound
www.expert-reviews.com
Review
or nerve stimulation followed by infusion of local anesthetic
(e.g., bupivacaine 0.125%) at 3–6 ml/h titrated according to the
analgesia and side effects (motor block). Persistent analgesia has
been reported even after cessation of infusion [80] .
Intrapleural analgesia, using infiltration of local anesthetic in
the pleural space using tunneled catheters, can be used for pain
in the chest, arm and neck due to metastatic or primary cancer.
These catheters can be used for weeks to months and provide
effective pain control towards the end of life [81–83] .
Other peripheral nerve blocks described in the literature include
suprascapular block [84,85] , paravertebral block [86] , intercostal
nerve block [87] , lumbar plexus block [88] , psoas compartment
block [89] , obturator nerve block [90] , femoral nerve block [91]
and sciatic nerve block [92] . With the increasing use of neuraxial
analgesia in palliative care the indications for use of neurolytic
peripheral nerve blockade are limited.
Expert commentary
Although the majority of patients with advanced cancer will have
their pain well controlled with the rational use of opioids and
adjuvant drugs, there are a significant proportion who would ben-
efit from the judicious use of a neuraxial technique. There are a
wide variety of techniques available and it calls for considerable
expert judgment to select the best option in an individual patient.
It is most unlikely that a single interventional technique will com-
pletely obviate the need for analgesics administered either orally,
transdermally or systemically. However, the dose requirements
may change dramatically with a major improvement in analgesia
or avoidance of opioid side effects.
Five-year view
Despite the increase in cancer survival rates, the progressive
increase in the number of cases diagnosed with cancer over the
past few years means that the case load on palliative care and allied
services is bound to increase. Even though new analgesic agents
are being developed, their safety and efficacy remains to be ade-
quately assessed, which means that the majority of palliative care
patients will still heavily rely on time-tested treatment strategies
for pain management. The expansion of specialist palliative care
services and the use of integrated care pathways should lead to an
improvement in the management of patients with advanced cancer
and other medical illnesses. Continued improvements in neur-
axial drug delivery systems and equipment design has increased
its safety and efficacy subsequently leading to increased usage.
In spite of all the technological advances and innovation of new
drugs, a better application of basic principles of pain management
and existing knowledge will certainly benefit more patients.
Financial & competing interests disclosure
The authors have no relevant affiliations or financial involvement with any
organization or entity with a financial interest in or financial conflict with
the subject matter or materials discussed in the manuscript. This includes
employment, consultancies, honoraria, stock ownership or options, expert
testimony, grants or patents received or pending, or royalties.
No writing assistance was utilized in the production of this manuscript.
753
 Review Joshi & Chambers

Key issues
• Pain is under-treated in a significant number of cancer patients. Treatment of pain using the WHO cancer pain guidelines can provide
satisfactory pain relief in the majority of patients.
• In total, 5–10% of patients with advanced cancer will not achieve adequate pain relief in spite of optimal conventional pharmacological
management or due to untoward side effects. These patients could benefit from the use of interventional pain
management techniques.
• Interventional pain management can provide better pain relief using reduced doses of opioids and fewer side effects.
• The utilization of these techniques needs multidisciplinary decision making and timely involvement of the concerned medical and
non-medical staff, including the patient and relatives, to simplify consent issues and achieve the best possible results.
• Neuraxial drug delivery using intrathecal or epidural routes, autonomic nervous system blockade and peripheral nerve blocks are some
of the techniques used. A careful consideration of risks and benefits is necessary before embarking on these techniques.
• Even though new analgesic agents and better equipment will be available in future, better application of existing knowledge will
probably be the most important single factor in helping a large number of patients.

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