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Invasive Analgesia Techniques for Advanced Cancer Pain
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THE SURGEON AND PALLIATIVE CARE
INVASIVE ANALGESIA TECHNIQUES FOR ADVANCED CANCER PAIN Mark J. Lema, MD, PhD
SCOPE OF THE PROBLEM
Although approximately 85%of all cancer pain can be managed satisfactorilyby pharmacologic therapy,2OCleeland et a15queried Eastern Cooperative Oncology Group (ECOG)physicians and revealed that cancer pain is under-diagnosed and under-treated. Physicians unfamiliar with current pain treatment modalities also are more likely to support assisted suicide for their patients. Nerve blocks and implantable devices are often used in the remaining 15%of patients who fail conventional oral therapy. In those with advanced disease, virtually 100%of all cancer pain can be alleviated, but sometimes at the expense of limiting bodily function. Because most cancer pain involves multiple anatomic sites, invasive techniques are intended to be analgesic adjuvants and not serve as the definitive treatment. These procedures often allow patients to reduce their dosages in their current drug regimens or to derive greater pain relief from their present doses in order to improve their quality of life. The referring physician or the pain physician should not promise complete relief, even in the case of celiac plexus blocks, because the patient's disease progression reported that 80% eventually results in the recurrence of pain. Twycro~s'~ of cancer patients at the time of referral for pain have at least two anatomically distinct pain sites and over 40% have four or more sites. It is unrealistic to expect that one regional block or analgesicinfusion eliminates all sources of pain. On the contrary,medical care of the suffering pain patient requires a multimodality, multispecialty approach combining psychotherapy, social support, and pain management to provide the best possible quality of life or quality of dying. -
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From the Department of Anesthesiology, State University of New York at Buffalo, Roswell Park Cancer Institute, Buffalo, New York
SURGICAL ONCOLOGY CLINICS OF NORTH AMERICA VOLUME 1 NUMBER 1 JANUARY 2001
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APPROPRIATE SELECTION OF THE INVASIVE TECHNIQUE
Invasive techniques for managing cancer pain often involve the use of neurolytic substances such as ethanol or phenol and are employed in intractable pain states. A thorough knowledge of the block and the mechanism of action by which the agent destroys neural tissue is essential to alleviate irreversible complications. Only physicians with extensive experience and skill should consider performing neurolytic blocks. Patients should be thoroughly informed about the possible sensory neural deficits that are likely to occur when peripheralnerve blocks are performed. Inmost cases, local anesthetic diagnostic blocks should be performed to allow the patient to sense the changes that may occur. The results of the block need to be followed over a few days. The physician should evaluate the patient's predominant pain to determine if a block or infusion is likely to alleviate 50% of its current intensity. Next, it should be determined if a neurolytic procedure is likely to reduce the pain. If not, an implantable intraspinal device should be considered. In cancer patients, spinal cord stimulators have been shown to be unpredictable in reducing pain. Finally opioid reduction after a successful neurolytic block or implanted device should proceed in step-reduction of a quarter to a third of the dose to prevent somnolence and respiratory depression. NEUROLYTIC AGENTS Ethanol (Alcohol)
Ethanol has been used most extensively for neurolytic procedures in concentrations from 3% to 100%.It acts by destroying nerves and producing Wallerian degeneration without disruption of the Schwann cell tube. Axonal regeneration can and will occur over a few months. Neuroma formation is less likely to develop because of this phenomenon. If cell body destruction occurs, however, regeneration of any type is not possible. Recent studies have shown that ethanol destroys nervous tissue by extraction of cholesterol and other lipids from the cell membrane and by protein precipitation. Topical application of alcohol to exposed nerves has resulted in axon and Schwann cell destruction.16 Early studies demonstrated that about a 50% to 70% alcohol solution was required for analgesia when performing major nerve blocks. Labat showed that 33% alcohol could successfully produce analgesia without motor paralysis when applied to peripheral nerves. When alcohol is applied to autonomic nerves and ganglia all efferent organ input is blocked. Permanent blocks occur when postsynaptic nerves in the ganglia are affected. If blockage only occurs in the rami or preganglionic fibers, it produces temporary analgesia. Following blockage of the rami alone, sensation returns in about 3 to 6 months. Subarachnoidinjection of 100%alcohol produces limited spinal cord damage to the dorsal roots, Lissauer's tract,
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and posterior columns. Wallerian degeneration follows nerve destruction. Almost 90% of injected alcohol is removed by the cerebrospinal fluid (CSF) within 10 minutes after subarachnoid injection. Clinically, alcohol is used in concentrations of 33% to 100%.It is hypobaric (specific gravity [sg] = 0.8) compared with CSF (sg = 1.2) so affected areas in the svinal cord should be above the site of intrathecal iniection to allow the a1;ohol to diffuse upward. Injection of alcohol into pkripheral nerves or ganglia not surrounded by fluid requires no special positioning. Effective duration of intrathecal alcohol is about 6 months. Complete analgesia of indeterminate duration can be accomvlished if cell bodies are " destroyed along with axons in peripheral and autonomic nervous tissue. High concentrations of alcohol (90°/~-1000/~) have reportedly produced a chemical neuritis under clinical conditions probably caused by residual partial neural destruction of surrounding tissues.
Phenol Studies have revealed that 6% phenol application to animal cervical ganglia produced necrosis in 24 hours, complete degeneration by 45 days, and regeneration in 75 days.1° Neural recovery from phenol appears to be faster than alcohol. Phenol has been used also for subarachnoid space, peripheral nerve, and ganglion neurolysis. In the subarachnoid space, phenol is hyperbaric with respect to CSF. The affected site should be below the site of intrathecal injection to allow the phenol to migrate downward. Concentrations of 5% to 10% produce nonspecific neural destruction similar to alcohol. Some studies suggest that larger diameter fibers are damaged to a greater extent than smaller diameter fibers. Extensive fibrosis and thickening of the arachnoid can also occur. Phenol destroys axons along the dorsal roots and posterior columns without disrupting cell bodies. Peripheral nerves are destroyed when 3% to 6% phenol is used. Acute and chronic damage to axons and myelin occur.In addition, protein coagulation and necrosis ultimately result in axonal and Wallerian degeneration. The range in concentration for phenol injection is between 3% and 15%. The suggestion that phenol maybe more destructive to vascular tissue than neural tissue has not been shown to be a problem clinically. Lema et a18 reported that autopsy samples, after using a total of 3.4 grams of phenol interpleurally, failed to substantiate these concerns of vascular, organ, and neural histologic destruction.
INVASIVE TECHNIQUES Patient-controlled analgesia using intravenous, subcutaneous, or epidural sites is an invasive technique that is frequently employed when oral or transdermal therapies fail. Other invasive procedures using needles, catheters, or scalpels can be separated into three general areas: autonomic
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nervous system, peripheral nerve, and central axis procedures. A brief description of each technique is described.
Patient-Controlled Analgesia Patient-controlled analgesia (PCA) allows patients to treat their own pain by self-administeringprescribed doses of opioids parenterally using a small, programmable computerized pump. This technique has been used widely in the management of postoperative pain and was developed in response to the under-treatment of pain in hospitalized patients. Intravenous, subcutaneous, or epidural routes are used in the hospital or the home setting. The pump can be programmed to deliver a continuous infusion, in addition to which the patient can administer bolus injections at a preset dose and time interval. There appears to be no difference in the effects on respiratory function compared with other therapies because similar daily opioids usage was detected when PCA was compared with IV opioid injections at regular intervak4 This mode of delivery is useful when the oral route is unavailable or when the total oral dose required is excessive. Psychologic benefit may be derived from providing increased patient control, and immediate relief for breakthrough pain is essential to suffering individuals. This method has an important application in the rapid relief and titration of dosage in patients with severe exacerbations of cancer pain. It can be used in the home setting but requires regular nursing visits. With the increasing use of transdermal fentanyl patches, however, many patients are now able to achieve good pain control without PCA devices, which is a more expensive technique in the home setting. Epidural PCA can combine opioids, local anesthetics, and clonidine to control somatic, visceral, and neuropathic pain limited to a body region. Continuous low dose infusions along with the ability to administer bolus breakthrough doses makes the epidural site an effective alternative to parenteral PCA.
Autonomic Nervous System Blocks The autonomic nervous system is largely responsible for visceral nociception. A diagnostic local anesthetic block of a sympathetic nerve or plexus establishes the relative contribution of autonomic and visceral pain. It may also determine whether repeated blocks with a local anesthetic or a neurolytic agent will be beneficial (Table 1). Stellate Ganglion Block The stellate (cervicothoracic)ganglion lies anterior to the lateral process of the C7 vertebra. Autonomic nerve conduction to the ipsilateralhead and upper extremity is interrupted by blocking this ganglion. Because of the proximity of other vital structures like the carotid artery, many clinicians are reluctant to perform neurolytic blocks in this area. Serial blocks
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Table 1. AUTONOMIC NERVE BLOCKS Neurolytic Block
Condition Treated
stellate (cervicothoracic) ganglion gasserian ganglion interpleural (thoracic sympathetic chain)
head, neck, arms trigeminal neuralgia and facial pain upper-head, neck, arms middle-thorax, heart, lung lower-bladder, abdominal organs, uterus pancreatitis, abdominal visceral cancer pain lower limb pain perineal, pelvic, lower limb pain rectal, perianal pain
celiac plexus (splanchnic nerves) lumbar sympathetic superior hypogastric plexus sacrococcygeal ganglion (Impar, Walther's)
with neurolytic agents in dilute concentrations (3%-6% phenol) after a diagnostic local anesthetic block have been recommended and may be of benefit to head and neck cancer pain patients with progressive disease. Potential complications include intravascular injection of the carotid or vertebral artery, phrenic and superior laryngeal nerve block, and rarely, intrathecal injection. Celiac Plexus Block The celiac plexus is on the anterolateralsurface of the aorta at the T12 to L2 vertebral level in proximity to the anterior spinal artery of Adamkowitz. A block of this plexus affects visceral pain in many abdominal organs and has gained widespread acceptance for the treatment of pancreatic cancer pain. The incidence of pain relief has been reported to be more than 84%, although occasionally repeat blocks are r e q ~ i r e d Documented .~ complications include hypotension; intrathecal, epidural or interpsoas muscle injection; intravascular injection of the aorta or vena cava; puncture of the kidney, intestine, or lung; paraplegia; anterior spinal artery syndrome; and death. Despite this ominous list of adverse effects, this block is the mainstay of analgesia for abdominal cancer. Lillimoe et a19showed that a subset of patients receiving adequate analgesia from parenteral opioids and alcohol splanchnicectomy for pancreatic cancer pain live 3.5 times longer if the block was performed (22 months vs. 6 months). They speculated that improved function because of better pain control resulted in longer survivability. Hypogastric Plexus Block The superior hypogastric plexus lies anterior to the bodies of the L5 and S1 vertebrae. It controls autonomic activity to the pelvis and lower limbs. Because this plexus is devoid of voluntary and autonomic sphincter control neurons, block of these nerves has been described for the treatment of pain associated with pelvic malignancy.13Injury to sacral nerves, bladder, or bowel perforation, intravascular injection, and urinary or fecal incontinence caused by uncontrolled neurolytic solution spread are
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potential complications but have not been extensively described in the literature.
Ganglion lmpar Intractableperineal pain is clinically problematic because somatic, visceral, and autonomic nerves controlling excretory and sexual functions converge in the pelvis region. Blockade of the ganglion impar (ganglionof Walther, sacrococcygeal ganglion)provides pain relief in the absence of significant somatovisceral dysfunction for many patients with advanced cancer. The ganglion impar is the only unpaired autonomic ganglion, sits anterior to the sacrococcygeal junction, and can be blocked with 5 to 10 mL of solution administered through a needle penetrating the anococcygeal ligament or directly passing through the sacrococcygeal (calcified) ligament.6 Patients experiencingsignificant rectal discomfort or pain after abdominalperineal resections often benefit from this technique.
Interpleural Analgesia Interpleural analgesia has been successfully used for minor surgical anesthesia and in the management of some chronic states, such as pancreatic pain and post-thoracotomy pain syndrome. It has also been used to alleviate acute exacerbations in various advanced cancer conditions.12The mechanism of action of interpleural analgesia appears to be by somatic neural block, but an autonomic block has also been inferred.15Diffusion of local anesthetic into the brachial plexus has resulted in the relief of upper extremity pain syndromes with the production of Horner's syndrome. The success of this block depends on the correct positioning of the patient such that the solution gravitates to the appropriate paravertebral area. Interpleural administration of phenol has also been used successfully in the long-term control of cancer pain.8 Possible complications associated with this technique include tension pneumothorax, pleural infection, bronchopleural fistula (if a catheter is implanted), and local anesthetic systemic toxicity from extensive tissue absorption. PERIPHERAL NERVE BLOCKS Neurolytic blockade of peripheral nerves can be effective as an analgesic adjuvant to oral therapy but also controversialin that some clinicians believe they are of little benefit. One concern regarding neurolytic blocks is directed toward the impermanence of the neurolysis and its resultant neuritis or deafferentation pain experienced after the block wears off.l18 This problem often is eliminated by selecting patients likely to expire in 4 to 6 months before development of the neuropathic pain. Injection doses can vary from 0.5 to 10 mL depending on the location of the nerve, its surrounding structures, the relative size of the compartment where it resides,
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Table 2. PERIPHERAL NERVE BLOCKS Neurolytic Block
Condition Treated
ophthalmic maxillary, mandibular glossopharyngeal phrenic nerve vagus, tracheobronchial intercostal ilioinguinal/ilohypogastric sacral nerves
eye pain (glaucoma,uveitis) tic doloureux or cancer pain tic-like jaw hiccoughs, diaphragmatic pain cancer of trachea thoracotomy scar pain, rib metastases groin pain pelvic, rectal pain (alternative to spinal or caudal epidural blocks)
and the degree of solution diffusion desired. Some common peripheral blocks performed are listed in Table 2 with the conditions treated by their neurolysis. CENTRAL AXIS PROCEDURES lntraspinal Therapies Intraspinal administration of opioids is used frequently in the treatment of pain, especially when not controlled with oral medications. Opioids can be delivered by the spinal or epidural routes providing profound analgesia, often at a much lower opioid dose without the motor, sensory, or sympathetic block associated with intraspinal local anesthetic administration.14 Combinations of low-dose opioids given epidurally and a local anesthetic act synergistically to produce effective analgesia while decreasing the side effects.ll Opioids can be delivered by intermittent bolus injection or by continuous infusion. Morphine is the most commonly used opioid, although hydromorphone, fentanyl, sufentanil,and oxymorphone have also been used successfully. Opioids in combination with clonidine have an additive effect and are effective in patients with advanced cancer pain amenable to epidural the rap^.^ Sedation and hypotension, however, can limit titration up to 30 ~ g / h when r delivered epidurally. Three systems used for chronic intraspinal opioid administration include percutaneous tunneled epidural catheters, tunneled epidural or intrathecal catheters connected to subcutaneouslyimplanted injection ports, and implanted intrathecal infusion pump systems. Implantable pumps, although more convenient and less likely to cause infection, appear to be more costly if life expectancy is less than 6 month^.^ Tolerance to chronic intraspinal administration of opioids can occur and is managed by increasing infusion doses, changing to another opioid, or substitutinglocal anesthetic agents for a short period. Other side effects include pruritus, urinary retention, somnolence, myoclonus, catheter infection, and rarely, respiratory depression (Table 3).
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Table 3. CENTRAL AXIS BLOCKS Neurolytic Block
Condition Treated
subarachnoid epidural neurolytic continuous infusion
unilateral segmental terminal cancer pain same except used in nonterminal patient and can be used for bilateral segmental pain
Neurosurgical Procedures
With the development of the multidisciplinary approach to pain management and an increasing range of available pharmacologic agents, few patients require neuroablative surgical intervention.The aim is to interrupt the nociceptive pathways in the peripheral nerves or at certain sites along the nociceptive neuraxis. The most commonly performed surgical procedure for cancer pain relief is anterolateral cordotomy, which targets the spinothalamic tract. This procedure can be done by open technique but has a significant morbidity; the complications include hemiparesis, urinary retention, and sexual impotence. Percutaneous cordotomy has replaced the open method and usually is performed using local anesthesia with fluoroscopic guidance. It is probably ineffective in neuropathic pain because of a central mechanism component and has only limited use in visceral pain. Immediate complete
Rhizotomy
/
Comrnissurotomy
Entry Zone
Figure 1. Dorsal root ganglionectomy. (FromSaberski L, Ligham D: Neuroablative techniques for cancer pain management.Techniques in Regional Anesthesia and Pain Management 154, 1997; with permission.)
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pain relief is achieved in 60% to 80% of patients, but this decreases about 50% at 6 to 12 months.17 Many patients in whom pain recurs also have paresthesias or dysesthesias develop. Other less often used procedures include rhizotomy, dorsal root entry zone (DREZ) lesioning, commissurotomy, and dorsal root ganglionectomy (Fig. 1). SUMMARY
Approximately 15% of all cancer pain patients require an invasive technique as an analgesic supplement to their current regimen. Neurolytic blocks should be considered first if they can reduce the present pain intensity by at least 50%. If a one-shot technique is not feasible intraspinal infusions may be beneficial. In general, intrathecal pumps should be used in cases where survival of greater than 6 months is anticipated. Otherwise, implanted epidural infusions seem to be more cost-effective.Finally, for intractable pain in terminally ill patients where loss of bodily function is an acceptable side effect, neuro-ablative surgical procedures should be considered. References 1. Abram SE: Neurolytic blocks of peripheral nerves. In Racz GB (ed): Techniques of Neurolysis. Boston, Kluwer Academic, 1989,pp 185-192 2. Bedder MD, Burchiel K, Larson A: Cost analysis of two implantable narcotic delivery systems. J Pain Symptom Manage 6:368-373,1991 3. Brown DL, Bulley CK, Quiel EL: Neurolytic celiac plexus block for pancreatic cancer pain. Anesth Analg 66:869-873,1987 4. Callam CM: An analysis of complaints and complications with patient-controlled analgesia. In Ferrante FM, Ostheimer GW, Covino BG (eds): Patient-Controlled Analgesia. Boston, Blackwell, 1990, p 144 5. Cleeland CR, Gonin R, Hatfield AK, et al: Pain and its treatment in outpatients with metastatic cancer. N Engl J Med 330:552-596,1994 6. DeLeon-Casasola OA: Superior hypogastric plexus block and ganglion impar neurolysis for pain associated with cancer. Tech Reg Anesth Pain Mgmt 1:27-31,1997 7. Eisenach JC, DuPen S, DuBois M, et al: The Epidural Clonidine Study Group. Epidural clonidine analgesia for intractable cancer pain. Pain 61:391-399,1995 8. Lema MJ,Myers DP, deleon-Casasola OA: Neurolytic interpleural block in the treatment of advanced cancer pain from metastatic esophageal carcinoma. Reg Anesth 17166-170, 1992 9. Lillimoe KD, Cameron JL,Kaufman HS, et al: Chemical splanchnicectomyinpatients with unresectable pancreatic cancer: A prospective randomized trial. Ann Surg 217447455, 1993 10. Mandl F: Aqueous solution of phenol as a substitute for alcohol in sympathetic block. J Int Coll Surg 13:566-572,1950 11. Maves TJ, Gebhart GF: Antinociceptive synergy between intrathecal morphine and lidocaine during visceral and somatic nociception in the rat. Anesthesiology 76:91-99,1992 12. Myers DP, Lema MJ, deleon-Casasola OA, et al: Interpleural analgesia for the treatment of severe cancer pain in terminally ill patients. J Pain Symptom Manage 8:505-509,1993 13. Plancarte R, deleon-Casasola OA, El-Healy M, et al: Neurolytic superior hypogastric plexus block for chronic pelvic pain associated with cancer. Reg Anesth 22:562-568,1997
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14. Plummer JL, Cherry DA, Cousins MJ, et al: Long-term spinal administration of morphine in cancer and non-cancer pain: A retrospective study. Pain 144:215-220,1991 15. Riegler FX, Vade Boncouer TR, Pelligrino DA. Interpleural anesthetics in the dog: Differential somatic neural blockade. Anesthesiology 171:744-750,1989 16. Rumbsy MG, Finean JB: The action of organic solvents on the myelin sheath of peripheral nerve tissue-I1 (short-chain aliphatic alcohols).J Neurochem 13:1509-1513,1966 17. Saberski L, Ligham D. Neuroablative techniques for cancer pain management. Tech Reg Anesth and Pain Manage 1:53-58,1997 18. Seltzer Z, Devor M: Ephoptic transmission in chronically damaged peripheral nerves. Neurology 29:1061-1064,1979 19. Twycross RG, Fairfield S: Pain in far-advanced cancer. Pain 14303-310,1982 20. Zech DFJ, Grond S, Lynch J, et al: Validation of World Health Organization guidelines for cancer pain relief: A 10-year prospective study. Pain 63:65-76,1995
Address reprint requests to Mark J. Lema, MD, PhD Department of Anesthesiology Roswell Park Cancer Institute Buffalo, N Y 14263
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THE SURGEON AND PALLIATIVE CARE
INVASIVE ANALGESIA TECHNIQUES FOR ADVANCED CANCER PAIN Mark J. Lema, MD, PhD
SCOPE OF THE PROBLEM
Although approximately 85%of all cancer pain can be managed satisfactorilyby pharmacologic therapy,2OCleeland et a15queried Eastern Cooperative Oncology Group (ECOG)physicians and revealed that cancer pain is under-diagnosed and under-treated. Physicians unfamiliar with current pain treatment modalities also are more likely to support assisted suicide for their patients. Nerve blocks and implantable devices are often used in the remaining 15%of patients who fail conventional oral therapy. In those with advanced disease, virtually 100%of all cancer pain can be alleviated, but sometimes at the expense of limiting bodily function. Because most cancer pain involves multiple anatomic sites, invasive techniques are intended to be analgesic adjuvants and not serve as the definitive treatment. These procedures often allow patients to reduce their dosages in their current drug regimens or to derive greater pain relief from their present doses in order to improve their quality of life. The referring physician or the pain physician should not promise complete relief, even in the case of celiac plexus blocks, because the patient's disease progression reported that 80% eventually results in the recurrence of pain. Twycro~s'~ of cancer patients at the time of referral for pain have at least two anatomically distinct pain sites and over 40% have four or more sites. It is unrealistic to expect that one regional block or analgesicinfusion eliminates all sources of pain. On the contrary,medical care of the suffering pain patient requires a multimodality, multispecialty approach combining psychotherapy, social support, and pain management to provide the best possible quality of life or quality of dying. -
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From the Department of Anesthesiology, State University of New York at Buffalo, Roswell Park Cancer Institute, Buffalo, New York
SURGICAL ONCOLOGY CLINICS OF NORTH AMERICA VOLUME 1 NUMBER 1 JANUARY 2001
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APPROPRIATE SELECTION OF THE INVASIVE TECHNIQUE
Invasive techniques for managing cancer pain often involve the use of neurolytic substances such as ethanol or phenol and are employed in intractable pain states. A thorough knowledge of the block and the mechanism of action by which the agent destroys neural tissue is essential to alleviate irreversible complications. Only physicians with extensive experience and skill should consider performing neurolytic blocks. Patients should be thoroughly informed about the possible sensory neural deficits that are likely to occur when peripheralnerve blocks are performed. Inmost cases, local anesthetic diagnostic blocks should be performed to allow the patient to sense the changes that may occur. The results of the block need to be followed over a few days. The physician should evaluate the patient's predominant pain to determine if a block or infusion is likely to alleviate 50% of its current intensity. Next, it should be determined if a neurolytic procedure is likely to reduce the pain. If not, an implantable intraspinal device should be considered. In cancer patients, spinal cord stimulators have been shown to be unpredictable in reducing pain. Finally opioid reduction after a successful neurolytic block or implanted device should proceed in step-reduction of a quarter to a third of the dose to prevent somnolence and respiratory depression. NEUROLYTIC AGENTS Ethanol (Alcohol)
Ethanol has been used most extensively for neurolytic procedures in concentrations from 3% to 100%.It acts by destroying nerves and producing Wallerian degeneration without disruption of the Schwann cell tube. Axonal regeneration can and will occur over a few months. Neuroma formation is less likely to develop because of this phenomenon. If cell body destruction occurs, however, regeneration of any type is not possible. Recent studies have shown that ethanol destroys nervous tissue by extraction of cholesterol and other lipids from the cell membrane and by protein precipitation. Topical application of alcohol to exposed nerves has resulted in axon and Schwann cell destruction.16 Early studies demonstrated that about a 50% to 70% alcohol solution was required for analgesia when performing major nerve blocks. Labat showed that 33% alcohol could successfully produce analgesia without motor paralysis when applied to peripheral nerves. When alcohol is applied to autonomic nerves and ganglia all efferent organ input is blocked. Permanent blocks occur when postsynaptic nerves in the ganglia are affected. If blockage only occurs in the rami or preganglionic fibers, it produces temporary analgesia. Following blockage of the rami alone, sensation returns in about 3 to 6 months. Subarachnoidinjection of 100%alcohol produces limited spinal cord damage to the dorsal roots, Lissauer's tract,
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and posterior columns. Wallerian degeneration follows nerve destruction. Almost 90% of injected alcohol is removed by the cerebrospinal fluid (CSF) within 10 minutes after subarachnoid injection. Clinically, alcohol is used in concentrations of 33% to 100%.It is hypobaric (specific gravity [sg] = 0.8) compared with CSF (sg = 1.2) so affected areas in the svinal cord should be above the site of intrathecal iniection to allow the a1;ohol to diffuse upward. Injection of alcohol into pkripheral nerves or ganglia not surrounded by fluid requires no special positioning. Effective duration of intrathecal alcohol is about 6 months. Complete analgesia of indeterminate duration can be accomvlished if cell bodies are " destroyed along with axons in peripheral and autonomic nervous tissue. High concentrations of alcohol (90°/~-1000/~) have reportedly produced a chemical neuritis under clinical conditions probably caused by residual partial neural destruction of surrounding tissues.
Phenol Studies have revealed that 6% phenol application to animal cervical ganglia produced necrosis in 24 hours, complete degeneration by 45 days, and regeneration in 75 days.1° Neural recovery from phenol appears to be faster than alcohol. Phenol has been used also for subarachnoid space, peripheral nerve, and ganglion neurolysis. In the subarachnoid space, phenol is hyperbaric with respect to CSF. The affected site should be below the site of intrathecal injection to allow the phenol to migrate downward. Concentrations of 5% to 10% produce nonspecific neural destruction similar to alcohol. Some studies suggest that larger diameter fibers are damaged to a greater extent than smaller diameter fibers. Extensive fibrosis and thickening of the arachnoid can also occur. Phenol destroys axons along the dorsal roots and posterior columns without disrupting cell bodies. Peripheral nerves are destroyed when 3% to 6% phenol is used. Acute and chronic damage to axons and myelin occur.In addition, protein coagulation and necrosis ultimately result in axonal and Wallerian degeneration. The range in concentration for phenol injection is between 3% and 15%. The suggestion that phenol maybe more destructive to vascular tissue than neural tissue has not been shown to be a problem clinically. Lema et a18 reported that autopsy samples, after using a total of 3.4 grams of phenol interpleurally, failed to substantiate these concerns of vascular, organ, and neural histologic destruction.
INVASIVE TECHNIQUES Patient-controlled analgesia using intravenous, subcutaneous, or epidural sites is an invasive technique that is frequently employed when oral or transdermal therapies fail. Other invasive procedures using needles, catheters, or scalpels can be separated into three general areas: autonomic
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nervous system, peripheral nerve, and central axis procedures. A brief description of each technique is described.
Patient-Controlled Analgesia Patient-controlled analgesia (PCA) allows patients to treat their own pain by self-administeringprescribed doses of opioids parenterally using a small, programmable computerized pump. This technique has been used widely in the management of postoperative pain and was developed in response to the under-treatment of pain in hospitalized patients. Intravenous, subcutaneous, or epidural routes are used in the hospital or the home setting. The pump can be programmed to deliver a continuous infusion, in addition to which the patient can administer bolus injections at a preset dose and time interval. There appears to be no difference in the effects on respiratory function compared with other therapies because similar daily opioids usage was detected when PCA was compared with IV opioid injections at regular intervak4 This mode of delivery is useful when the oral route is unavailable or when the total oral dose required is excessive. Psychologic benefit may be derived from providing increased patient control, and immediate relief for breakthrough pain is essential to suffering individuals. This method has an important application in the rapid relief and titration of dosage in patients with severe exacerbations of cancer pain. It can be used in the home setting but requires regular nursing visits. With the increasing use of transdermal fentanyl patches, however, many patients are now able to achieve good pain control without PCA devices, which is a more expensive technique in the home setting. Epidural PCA can combine opioids, local anesthetics, and clonidine to control somatic, visceral, and neuropathic pain limited to a body region. Continuous low dose infusions along with the ability to administer bolus breakthrough doses makes the epidural site an effective alternative to parenteral PCA.
Autonomic Nervous System Blocks The autonomic nervous system is largely responsible for visceral nociception. A diagnostic local anesthetic block of a sympathetic nerve or plexus establishes the relative contribution of autonomic and visceral pain. It may also determine whether repeated blocks with a local anesthetic or a neurolytic agent will be beneficial (Table 1). Stellate Ganglion Block The stellate (cervicothoracic)ganglion lies anterior to the lateral process of the C7 vertebra. Autonomic nerve conduction to the ipsilateralhead and upper extremity is interrupted by blocking this ganglion. Because of the proximity of other vital structures like the carotid artery, many clinicians are reluctant to perform neurolytic blocks in this area. Serial blocks
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Table 1. AUTONOMIC NERVE BLOCKS Neurolytic Block
Condition Treated
stellate (cervicothoracic) ganglion gasserian ganglion interpleural (thoracic sympathetic chain)
head, neck, arms trigeminal neuralgia and facial pain upper-head, neck, arms middle-thorax, heart, lung lower-bladder, abdominal organs, uterus pancreatitis, abdominal visceral cancer pain lower limb pain perineal, pelvic, lower limb pain rectal, perianal pain
celiac plexus (splanchnic nerves) lumbar sympathetic superior hypogastric plexus sacrococcygeal ganglion (Impar, Walther's)
with neurolytic agents in dilute concentrations (3%-6% phenol) after a diagnostic local anesthetic block have been recommended and may be of benefit to head and neck cancer pain patients with progressive disease. Potential complications include intravascular injection of the carotid or vertebral artery, phrenic and superior laryngeal nerve block, and rarely, intrathecal injection. Celiac Plexus Block The celiac plexus is on the anterolateralsurface of the aorta at the T12 to L2 vertebral level in proximity to the anterior spinal artery of Adamkowitz. A block of this plexus affects visceral pain in many abdominal organs and has gained widespread acceptance for the treatment of pancreatic cancer pain. The incidence of pain relief has been reported to be more than 84%, although occasionally repeat blocks are r e q ~ i r e d Documented .~ complications include hypotension; intrathecal, epidural or interpsoas muscle injection; intravascular injection of the aorta or vena cava; puncture of the kidney, intestine, or lung; paraplegia; anterior spinal artery syndrome; and death. Despite this ominous list of adverse effects, this block is the mainstay of analgesia for abdominal cancer. Lillimoe et a19showed that a subset of patients receiving adequate analgesia from parenteral opioids and alcohol splanchnicectomy for pancreatic cancer pain live 3.5 times longer if the block was performed (22 months vs. 6 months). They speculated that improved function because of better pain control resulted in longer survivability. Hypogastric Plexus Block The superior hypogastric plexus lies anterior to the bodies of the L5 and S1 vertebrae. It controls autonomic activity to the pelvis and lower limbs. Because this plexus is devoid of voluntary and autonomic sphincter control neurons, block of these nerves has been described for the treatment of pain associated with pelvic malignancy.13Injury to sacral nerves, bladder, or bowel perforation, intravascular injection, and urinary or fecal incontinence caused by uncontrolled neurolytic solution spread are
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potential complications but have not been extensively described in the literature.
Ganglion lmpar Intractableperineal pain is clinically problematic because somatic, visceral, and autonomic nerves controlling excretory and sexual functions converge in the pelvis region. Blockade of the ganglion impar (ganglionof Walther, sacrococcygeal ganglion)provides pain relief in the absence of significant somatovisceral dysfunction for many patients with advanced cancer. The ganglion impar is the only unpaired autonomic ganglion, sits anterior to the sacrococcygeal junction, and can be blocked with 5 to 10 mL of solution administered through a needle penetrating the anococcygeal ligament or directly passing through the sacrococcygeal (calcified) ligament.6 Patients experiencingsignificant rectal discomfort or pain after abdominalperineal resections often benefit from this technique.
Interpleural Analgesia Interpleural analgesia has been successfully used for minor surgical anesthesia and in the management of some chronic states, such as pancreatic pain and post-thoracotomy pain syndrome. It has also been used to alleviate acute exacerbations in various advanced cancer conditions.12The mechanism of action of interpleural analgesia appears to be by somatic neural block, but an autonomic block has also been inferred.15Diffusion of local anesthetic into the brachial plexus has resulted in the relief of upper extremity pain syndromes with the production of Horner's syndrome. The success of this block depends on the correct positioning of the patient such that the solution gravitates to the appropriate paravertebral area. Interpleural administration of phenol has also been used successfully in the long-term control of cancer pain.8 Possible complications associated with this technique include tension pneumothorax, pleural infection, bronchopleural fistula (if a catheter is implanted), and local anesthetic systemic toxicity from extensive tissue absorption. PERIPHERAL NERVE BLOCKS Neurolytic blockade of peripheral nerves can be effective as an analgesic adjuvant to oral therapy but also controversialin that some clinicians believe they are of little benefit. One concern regarding neurolytic blocks is directed toward the impermanence of the neurolysis and its resultant neuritis or deafferentation pain experienced after the block wears off.l18 This problem often is eliminated by selecting patients likely to expire in 4 to 6 months before development of the neuropathic pain. Injection doses can vary from 0.5 to 10 mL depending on the location of the nerve, its surrounding structures, the relative size of the compartment where it resides,
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Table 2. PERIPHERAL NERVE BLOCKS Neurolytic Block
Condition Treated
ophthalmic maxillary, mandibular glossopharyngeal phrenic nerve vagus, tracheobronchial intercostal ilioinguinal/ilohypogastric sacral nerves
eye pain (glaucoma,uveitis) tic doloureux or cancer pain tic-like jaw hiccoughs, diaphragmatic pain cancer of trachea thoracotomy scar pain, rib metastases groin pain pelvic, rectal pain (alternative to spinal or caudal epidural blocks)
and the degree of solution diffusion desired. Some common peripheral blocks performed are listed in Table 2 with the conditions treated by their neurolysis. CENTRAL AXIS PROCEDURES lntraspinal Therapies Intraspinal administration of opioids is used frequently in the treatment of pain, especially when not controlled with oral medications. Opioids can be delivered by the spinal or epidural routes providing profound analgesia, often at a much lower opioid dose without the motor, sensory, or sympathetic block associated with intraspinal local anesthetic administration.14 Combinations of low-dose opioids given epidurally and a local anesthetic act synergistically to produce effective analgesia while decreasing the side effects.ll Opioids can be delivered by intermittent bolus injection or by continuous infusion. Morphine is the most commonly used opioid, although hydromorphone, fentanyl, sufentanil,and oxymorphone have also been used successfully. Opioids in combination with clonidine have an additive effect and are effective in patients with advanced cancer pain amenable to epidural the rap^.^ Sedation and hypotension, however, can limit titration up to 30 ~ g / h when r delivered epidurally. Three systems used for chronic intraspinal opioid administration include percutaneous tunneled epidural catheters, tunneled epidural or intrathecal catheters connected to subcutaneouslyimplanted injection ports, and implanted intrathecal infusion pump systems. Implantable pumps, although more convenient and less likely to cause infection, appear to be more costly if life expectancy is less than 6 month^.^ Tolerance to chronic intraspinal administration of opioids can occur and is managed by increasing infusion doses, changing to another opioid, or substitutinglocal anesthetic agents for a short period. Other side effects include pruritus, urinary retention, somnolence, myoclonus, catheter infection, and rarely, respiratory depression (Table 3).
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Table 3. CENTRAL AXIS BLOCKS Neurolytic Block
Condition Treated
subarachnoid epidural neurolytic continuous infusion
unilateral segmental terminal cancer pain same except used in nonterminal patient and can be used for bilateral segmental pain
Neurosurgical Procedures
With the development of the multidisciplinary approach to pain management and an increasing range of available pharmacologic agents, few patients require neuroablative surgical intervention.The aim is to interrupt the nociceptive pathways in the peripheral nerves or at certain sites along the nociceptive neuraxis. The most commonly performed surgical procedure for cancer pain relief is anterolateral cordotomy, which targets the spinothalamic tract. This procedure can be done by open technique but has a significant morbidity; the complications include hemiparesis, urinary retention, and sexual impotence. Percutaneous cordotomy has replaced the open method and usually is performed using local anesthesia with fluoroscopic guidance. It is probably ineffective in neuropathic pain because of a central mechanism component and has only limited use in visceral pain. Immediate complete
Rhizotomy
/
Comrnissurotomy
Entry Zone
Figure 1. Dorsal root ganglionectomy. (FromSaberski L, Ligham D: Neuroablative techniques for cancer pain management.Techniques in Regional Anesthesia and Pain Management 154, 1997; with permission.)
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pain relief is achieved in 60% to 80% of patients, but this decreases about 50% at 6 to 12 months.17 Many patients in whom pain recurs also have paresthesias or dysesthesias develop. Other less often used procedures include rhizotomy, dorsal root entry zone (DREZ) lesioning, commissurotomy, and dorsal root ganglionectomy (Fig. 1). SUMMARY
Approximately 15% of all cancer pain patients require an invasive technique as an analgesic supplement to their current regimen. Neurolytic blocks should be considered first if they can reduce the present pain intensity by at least 50%. If a one-shot technique is not feasible intraspinal infusions may be beneficial. In general, intrathecal pumps should be used in cases where survival of greater than 6 months is anticipated. Otherwise, implanted epidural infusions seem to be more cost-effective.Finally, for intractable pain in terminally ill patients where loss of bodily function is an acceptable side effect, neuro-ablative surgical procedures should be considered. References 1. Abram SE: Neurolytic blocks of peripheral nerves. In Racz GB (ed): Techniques of Neurolysis. Boston, Kluwer Academic, 1989,pp 185-192 2. Bedder MD, Burchiel K, Larson A: Cost analysis of two implantable narcotic delivery systems. J Pain Symptom Manage 6:368-373,1991 3. Brown DL, Bulley CK, Quiel EL: Neurolytic celiac plexus block for pancreatic cancer pain. Anesth Analg 66:869-873,1987 4. Callam CM: An analysis of complaints and complications with patient-controlled analgesia. In Ferrante FM, Ostheimer GW, Covino BG (eds): Patient-Controlled Analgesia. Boston, Blackwell, 1990, p 144 5. Cleeland CR, Gonin R, Hatfield AK, et al: Pain and its treatment in outpatients with metastatic cancer. N Engl J Med 330:552-596,1994 6. DeLeon-Casasola OA: Superior hypogastric plexus block and ganglion impar neurolysis for pain associated with cancer. Tech Reg Anesth Pain Mgmt 1:27-31,1997 7. Eisenach JC, DuPen S, DuBois M, et al: The Epidural Clonidine Study Group. Epidural clonidine analgesia for intractable cancer pain. Pain 61:391-399,1995 8. Lema MJ,Myers DP, deleon-Casasola OA: Neurolytic interpleural block in the treatment of advanced cancer pain from metastatic esophageal carcinoma. Reg Anesth 17166-170, 1992 9. Lillimoe KD, Cameron JL,Kaufman HS, et al: Chemical splanchnicectomyinpatients with unresectable pancreatic cancer: A prospective randomized trial. Ann Surg 217447455, 1993 10. Mandl F: Aqueous solution of phenol as a substitute for alcohol in sympathetic block. J Int Coll Surg 13:566-572,1950 11. Maves TJ, Gebhart GF: Antinociceptive synergy between intrathecal morphine and lidocaine during visceral and somatic nociception in the rat. Anesthesiology 76:91-99,1992 12. Myers DP, Lema MJ, deleon-Casasola OA, et al: Interpleural analgesia for the treatment of severe cancer pain in terminally ill patients. J Pain Symptom Manage 8:505-509,1993 13. Plancarte R, deleon-Casasola OA, El-Healy M, et al: Neurolytic superior hypogastric plexus block for chronic pelvic pain associated with cancer. Reg Anesth 22:562-568,1997
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14. Plummer JL, Cherry DA, Cousins MJ, et al: Long-term spinal administration of morphine in cancer and non-cancer pain: A retrospective study. Pain 144:215-220,1991 15. Riegler FX, Vade Boncouer TR, Pelligrino DA. Interpleural anesthetics in the dog: Differential somatic neural blockade. Anesthesiology 171:744-750,1989 16. Rumbsy MG, Finean JB: The action of organic solvents on the myelin sheath of peripheral nerve tissue-I1 (short-chain aliphatic alcohols).J Neurochem 13:1509-1513,1966 17. Saberski L, Ligham D. Neuroablative techniques for cancer pain management. Tech Reg Anesth and Pain Manage 1:53-58,1997 18. Seltzer Z, Devor M: Ephoptic transmission in chronically damaged peripheral nerves. Neurology 29:1061-1064,1979 19. Twycross RG, Fairfield S: Pain in far-advanced cancer. Pain 14303-310,1982 20. Zech DFJ, Grond S, Lynch J, et al: Validation of World Health Organization guidelines for cancer pain relief: A 10-year prospective study. Pain 63:65-76,1995
Address reprint requests to Mark J. Lema, MD, PhD Department of Anesthesiology Roswell Park Cancer Institute Buffalo, N Y 14263