AĞRI 2009;21(4):133-140 REVIEW - DERLEME

Neurolytic blocks: When, How, Why

Nörolitik bloklar: Ne zaman, Nasıl, Niçin

Serdar ERDİNE1

Summary Interventional techniques are divided into two categories: neuroablative and neuromodulatory procedures. Neuroablation is the physical interruption of pain pathways either surgically, chemically or thermally. Neuromodulation is the dynamic and functional inhibition of pain pathways either by administration of opioids and other drugs intraspinally or intraventricularly or by stimulation. Neuroablative techniques for cancer pain treatment have been used for more than a century. With the de- velopment of imaging facilities such as fl uoroscopy, neuroablative techniques can be performed more precisely and effi ciently. Key words: Neuroablative techniques; neurolytic blocks; radiofrequency thermocoagulation.

Özet Girişimsel teknikler nöroablatif ve nöromodülatör işlemler olarak iki gruba ayrılırlar. Nöroablasyon, cerrahi, kimyasal veya ısı uy- gulamalarıyla ağrı yolaklarında fi ziksel iletinin kesilmesidir. Nöromodülasyon, stimülasyon uygulamasıyla veya intraventriküler ya da intraspinal uygulanan opioidler ve diğer ajanlarla ağrı yolaklarının dinamik ve fonksiyonel inhibisyonudur. Nöroablatif teknik- ler kanser tedavisinde yüzyıldan fazla zamandır kullanılmaktadır. Fluroskopi gibi görüntüleme araçlarındaki gelişmelerle nöroabla- tif uygulamalar daha doğru ve etkili bir şekilde gerçekleştirilmektedir. Anahtar sözcükler: Nöroablatif teknikler; nörolitik bloklar; radyofrekans termokoagulasyon.

1Department of Algology, İstanbul University, İstanbul Faculty of Medicine, İstanbul, Turkey 1İstanbul Üniversitesi, İstanbul Tıp Fakültesi, Anesteziyoloji Anabilim Dalı, Algoloji Bilim Dalı, İstanbul Submitted - August 20, 2009 (Başvuru tarihi - 20 Ağustos 2009) Accepted - September 15, 2009 (Kabul tarihi - 15 Eylül 2009) Correspondence (İletişim): Serdar Erdine, M.D, FIPP. Istanbul University, Istanbul Faculty of Medicine, Depratment of Algology, Monoblok, Çapa 34390 Istanbul, Turkey. Tel: +90 - 212 - 531 31 47 e-mail (e-posta): [email protected]

EKİM - OCTOBER 2009 133 AĞRI

Introduction Th e life expectancy of the patient is another impor- Cancer pain is one of the most witnessed pain syn- tant criterion for selecting the interventional tech- dromes throughout the world.[1] Th e World Health nique. Most of the cancer patients referred for in- Organization (WHO) analgesic ladder has been terventional treatment are in the terminal stage with reported to be effi cacious in controlling pain in short life expectancy. Th e interventional technique approximately 90% of the patients.[2-5] Th ere thus to be applied should sustain a better quality of life remain quite a number of patients who require in- with the least complications or side eff ects. terventional treatment of cancer pain. Interventional techniques should be applied when Interventional techniques are divided into two cat- more conservative pain modalities fail. Generally, egories: neuroablative and neuromodulatory pro- the WHO ladder is applied, and when all drugs in- cedures.[6] Neuroablation is the physical interrup- cluded in the ladder are inadequate, interventional tion of pain pathways either surgically, chemically techniques are considered. However, in some cases, or thermally. Neuromodulation is the dynamic and interventional techniques may be applied earlier, functional inhibition of pain pathways either by and this will be addressed in a later section. administration of opioids and other drugs intraspi- nally or intraventricularly or by stimulation. Th ere should be no general contraindications such as sepsis or coagulopathy while performing the in- terventional techniques. Patient selection for neuroablation Th e use of neuroablative techniques for the control Neuroablative techniques for cancer pain of cancer pain necessitates training of the pain phy- sician, development of facilities for applying these treatment techniques and follow-up of the patients. Patients Neuroablative techniques for cancer pain treatment who are candidates for interventional therapies re- have been used for more than a century. With the quire special care and follow-up. development of imaging facilities such as fl uoros- copy, neuroablative techniques can be performed Patient selection is very important prior to the in- more precisely and effi ciently. terventional pain treatment. A thorough history of the patient related with his disease and pain should Neuroablative techniques are used less frequently be evaluated, including the onset, duration, inten- than before with the improvement in new drugs sity, localization, and course of the pain. In addi- and use of new routes, such as transdermal applica- tion to the knowledge regarding the disease itself, a tion of opioids, and use of long-acting opioids and complete evaluation of the patient related with pain adjuvant drugs. Although more limited than before, should be done, and should include a general medi- neuroablative techniques still have a certain role cal and neurological evaluation, laboratory tests and in the treatment of intractable cancer pain. Th ese radiographic evaluation. Most of the interventional techniques are indicated when administration of techniques target the nervous system; thus, a recent analgesics according to the “ladder” is inadequate. radiological evaluation is a must in order to identify Life expectancy of the patient should be limited and the cause of the pain as well as to prevent complica- the pain should be localized to a part of the body. tions related with the technique. It is also important Neuroablative techniques can be used for somatic or to verify the objective fi ndings of pain, which will visceral pain. Th ey do not have a real place in neu- help to clarify the type of intervention to be used. ropathic pain syndromes, except for sympathetic blocks. Th e emotional and psychological status of the pa- tients should be assessed prior to the intervention. Although neuroablative techniques should be per- Th e psychological assessment of the patient will formed when the “ladder” is inadequate in certain guide the physician in determining if the patient is cancer pain syndromes, they may be performed at suitable for an intervention, and if so, which type. an earlier stage. Localized pain at the innervation of

134 EKİM - OCTOBER 2009 Neurolytic blocks: When, How, Why the trigeminal nerve may be interrupted either by to cancer of the region. It should be performed at an neurolytic block or radiofrequency thermocoagula- earlier stage, before the anatomy of the region is dis- tion of the gasserian ganglion. Celiac and splanch- torted by the growth of the cancer to obtain a better nic blocks may also be performed at an earlier stage result. It eff ect lasts for months to years. before the anatomy of the region is distorted. It should be performed under fl uoroscopy. Th e fora- Th e advantages of neuroablative techniques are: men ovale is easily seen under the fl uoroscope, and they require less follow-up of the patient when the neurolytic solution, either alcohol or phenol, compared with neuromodulatory techniques, they which should not exceed 1 ml, is given in smaller ali- are more cost-eff ective, and they may have a place quots. Otherwise, it may spread to the brainstem and in patients with short life expectancy. Th eir disad- cause severe complications. Currently, the use of ra- vantages include: greater potential risks such as of diofrequency lesioning is preferred to the neurolytic permanent motor loss, paresthesia and dysesthesia, agents. More precise location of the nerve is possible their requirement of very well-trained physicians, with radiofrequency lesioning, and there is no risk of and their limited use only for localized pain. spread of neurolytic solution to the brainstem.

Neurolytic nerve blocks Trigeminal ganglion neurolysis is not free of com- plications.[10] Facial numbness develops as a result Neurolytic agents of the neurolysis in all cases. Th e patients should Neurolytic agents are chemical substances that be informed in advance regarding facial numbness. destruct the nerve, including 50-100% alcohol, In fact, it may be considered a result of neurolysis 5-15% phenol, glycerol, and hypertonic saline. rather than a complication. Loss of corneal refl ex may occur as a result of the destruction of the oph- Alcohol is the oldest agent, generally used for celiac thalmic branch of the trigeminal nerve. Anesthesia plexus, gasserian ganglion, sympathetic chain, or in- dolorosa is the most severe complication. Th e pain trathecally. Several concentrations varying between 50- is relieved but burning pain and dysesthesia develop 100% are used. Damage to the nerve is nonselective. in the region, and this is diffi cult to control.

Phenol is more frequently used in glycerine solu- Intercostal nerve block tions as a hyperbaric solution in concentrations be- By 1922, Labat’s textbook contained an elaborate tween 5-15%. Damage to the nerve is again nonse- description of the intercostal nerve block that is lective, but is more reversible than with alcohol. quite similar to our present-day conceptions.[11] Intercostal nerve block is one of the most eff ective Glycerol is only used for peripheric nerves, but the blocks in the treatment of pain. It may be used in duration of the eff ect is much shorter. the treatment of pain due to fractured ribs and can- cer metastasis. Neurolytic blocks Trigeminal ganglion neurolysis It is much better to perform the block under fl uo- Th e percutaneous trans-foramen ovale approach for roscopy. Th e needle touches the lower edge of the the trigeminal (gasserian) ganglion using absolute rib and slips down the rib while adjacent to it. It alcohol was fi rst described by Hartel in 1912.[7] In is preferable to perform the block fi rst with a lo- the evolution of treatment, radiofrequency lesion- cal anesthetic, 2% lidocaine solution. If it is helpful, ing for this ganglion was described by Sweet and 6-8% phenol (3-5 ml) may be administered. Pneu- Wepsic in 1965[8] and retrogasserian glycerol injec- mothorax and intravascular injection are the main tion by Hakanson in 1981[9]. risks. However, careful performance of the block re- duces the risk of pneumothorax development. Trigeminal ganglion block is generally used for the treatment of idiopathic trigeminal neuralgia, but it Intrathecal and epidural neurolytic blocks has a place in the treatment of secondary pain due Intrathecal neurolysis has been used since 1931,

EKİM - OCTOBER 2009 135 AĞRI and was fi rst performed by Dogliotti.[12] Th e use of celiac, hypogastric and impar ganglion blocks are intrathecal alcohol and phenol has faded in recent used for the treatment of visceral pain arising from years because of the fear of complications such as the upper or lower abdominal organs. motor, autonomic and sensorial loss. Th e concept of the procedure is bathing the posterior, sensory nerve a. Stellate ganglion block root with the neurolytic solution, either alcohol or Selective block of the stellate ganglion was fi rst de- phenol. Very small amounts of the neurolytic solu- scribed by Sellheim and shortly after by Kappis in tion are delivered based on the patient’s position: 1923, and by Brumm and Mandl in 1924.[19,20] if hypobaric alcohol is used, the painful side is up; if phenol is used, the painful side is down.[13,14] It Stellate ganglion block is useful in cancer patients if should be performed by very experienced physicians the patient has a burning pain radiating to the up- in order to prevent dreadful complications. per extremity. It is much better to combine it with the thoracic sympathetic block. It is also eff ective in Phenol may also be delivered epidurally to the af- patients with postherpetic neuralgia. fected route.[15] It should be performed under fl uo- roscopy and the catheter tip should be visible in or- It is contraindicated if the patient had a pneumonec- der to advance to the root; 6% aqueous phenol may tomy on the contralateral side because of the danger then be injected. Th e risk of complications such as of additional pneumothorax on the ipsilateral side. sensorial or motor loss is less than with intrathecal It is also contraindicated if the patient had a recent neurolysis. cardiac infarction. It should fi rst be performed us- ing a local anesthetic solution, and if eff ective, the Neuroadenolysis of the pituitary neurolytic solution should then be given. Currently, In hormone-related cancer such as thyroid or breast the stellate gangliolysis may be performed by radio- cancer with several metastases throughout the body, frequency thermocoagulation. neuroadenolysis of the pituitary may be considered. It was fi rst performed by Moricca in the late 1970’s. Th e two principal complications of stellate ganglion [16] Th e technique is performed under fl uoroscopy. block are pneumothorax and intraspinal injection. With the patient lying in the supine position, the A third risk when neurolysis is performed is the pos- needle is advanced transnasally and transsphenoi- sibility of persistent Horner’s syndrome. If the neu- dally to the pituitary. Following the verifi cation of rolysis is performed under fl uoroscopy, the potential the position, 0.5-3 ml of absolute alcohol is injected risk is minimalized. to destroy the pituitary gland.[17] Cephalalgia, hypo- thyroidea, hypoadrenalism, and diabetes insipidus b. T2-T3 sympathetic neurolysis are the most frequently seen complications. Cur- Previously, T2-T3 sympathetectomy was performed rently the technique has lost its popularity. surgically. With the development of imaging tech- niques, neurolysis is performed more. In 1979, Neurolytic sympathetic blocks Wilkinson devised the technique for radiofrequency Th e relationship of the sympathetic nervous system thermocoagulation with minimal complications. and several chronic pain syndromes including can- cer pain has long been recognized.[18,19] Sympathetic T2 and T3 sympathetic block is considered for pa- blocks may have a place in cancer pain patients if tients who have sympathetically maintained pain. they have neuropathic pain syndromes due to sur- It is contraindicated in respiratory insuffi ciency or gery, chemotherapy or radiotherapy or infi ltration of thoracic aortic aneurysm. the brachial or lumbosacral plexus, or in visceral pain arising from the upper or lower abdominal organs. It is performed in a prone position under fl uoros- copy. 2-3 ml of phenol may be delivered to the sym- Stellate and thoracic and lumbar sympathetic blocks pathetic chain, or radiofrequency thermocoagula- are used in the treatment of neuropathic pain syn- tion is performed. Pneumothorax is the principal dromes related with the cancer, while splanchnic, complication. Another side eff ect of this procedure

136 EKİM - OCTOBER 2009 Neurolytic blocks: When, How, Why is intercostal neuritis. Th is problem can be mini- nique for the celiac plexus block.[22] Th e celiac plex- mized by meticulously performing sensory and mo- us lies anterior to the aorta and epigastrium. It is tor stimulation prior to lesioning.[21] just anterior to the crus of the diaphragma. Post- ganglionic nerves from these ganglia innervate all c. Splanchnic nerve block abdominal viscera, with the exception of part of the Th e fi rst anterior percutaneous approach to transverse colon, the left colon, the rectum and pel- splanchnic nerve block was described by Kappis vic viscera. in 1914.[22] Th e recognition that splanchnic nerve block may provide relief of pain in a subset of pa- Any pain originating from the visceral structures tients who fail to obtain relief from celiac plexus and innervated by the celiac plexus can be eff ectively block has led to a renewed interest in this technique. relieved by the block of the plexus. Th ese structures It was recently revised by Raj for radiofrequency include the pancreas, liver, gallbladder, omentum, thermocoagulation.[21] mesentery, and alimentary tract from the stomach to the transverse portion of the large colon. Splanchnic block is one of the eff ective blocks in relieving cancer pain in the upper abdominal organs Celiac plexus block increases the gastric motility. including the stomach and pancreas. Th is may be benefi cial in patients with chronic constipation due to analgesics. Diarrhea has been Th e technique should be performed under fl uo- reported in a few patients as well as concomitant roscopy with the patient in a prone position. If the decrease in the incidence of nausea and vomiting. pain is unilateral, the splanchnic nerve on the same However, the celiac plexus block should be avoided side is blocked; however, it is generally bilateral and in patients with bowel obstruction.[24] should be performed for both sides. 50-100% alcohol is the agent generally used for the Smaller volumes, 5-8 ml of absolute alcohol, are rec- neurolysis It should be performed under fl uoros- ommended for single needle procedures. Many in- copy guidance to prevent any complication. It may vestigators believe that alcohol as a neurolytic agent either be performed by single needle technique by is superior to phenol in duration of neural blockade. transaortic approach or by double needle technique. 6-10% phenol may also be used.[23] In the hands of an experienced physician, serious complications rarely occur. Because of the proxim- Because splanchnic nerves are contained in a narrow ity of other vital structures, coupled with large vol- compartment, they are accessible for radiofrequen- umes of neurolytic drugs, side eff ects and complica- cy lesioning. To produce a lesion of the splanchnic tions may be seen. nerve, the needle needs to lie on the mid-third por- tion of the lateral side of the T11-T12 vertebral Minor complications include hypotension, diarrhea body. After a sensorial test stimulation in which the and back pain, which fade within days. Moderate patient should report a stimulation in the epigastric complications are mechanical or chemical distur- region, the radiofrequency lesion is created. bance of the organs in the proximity of the ganglion and irritation of the genitofemoral nerve. Major Complications of splanchnic block can be regard- complications include paraplegia due to the incor- ed as minor, moderate or severe. Th ose considered rect placement of the needle near the spinal nerves relatively minor such as hypotension and diarrhea or subarachnoid/vascular injection of the neurolytic are readily reversible. Moderate complications like solution, renal injury, perforation of cysts of tumors, pneumothorax should not occur if performed under and peritonitis. fl uoroscopy, but again are transient. Major compli- cations such as paraplegia are rare. In spite of its risks and complications, celiac plexus block is one of the most eff ective neurolytic blocks d. Celiac plexus block if performed properly. Time to maximal pain relief In 1914, Kappis introduced the percutaneous tech- is variable. In most patients, relief is immediate and

EKİM - OCTOBER 2009 137 AĞRI complete, while in others it will accrue over a few Rectum puncture, neurolytic injection into the days. In addition, pain relief is re-established with nerve roots and rectal cavity and neuritis due to repetition. Its eff ect lasts for months.[25,26] nerve root injection are the potential complications. e. Hypogastric plexus neurolysis Radiofrequency thermocoagulation for Th e fi rst attempts to interrupt the sympathetic path- the treatment of cancer pain ways in the pelvic region date back to the end of the 19th century, with Jaboulay in France and Ruggi in Th e use of current lesions for the treatment of pain Italy in 1899.[27,28] In 1990, Plancarte described the is not new. Kirschner was the fi rst to describe the use technique for hypogastric plexus block.[29] of percutaneous current lesions for the treatment of trigeminal neuralgia using direct current delivered Th e superior hypogastric plexus is the extension of to a needle placed in the gasserian ganglion. Since the aortic plexus in the retroperitoneal space below then, the technique and equipment have been de- the aortic bifurcation. It contains almost exclusively veloping. sympathetic fi bers. Th e anatomic location of the su- perior hypogastric plexus, the sympathetic predomi- In 1965, Mullan and Rosomoff described the percu- nance of the fi bers of the plexus, and its role in the taneous lateral cordotomy for unilateral malignant [31,32] transmission of most of the pain signals from the pain. A few years later (1974), Sweet used ra- pelvic viscera make this structure an ideal target for diofrequency lesions for the treatment of trigeminal [8] neurolysis in the cancer pain arising from the pelvic neuralgia. viscera. In 1975, Shealy used a radiofrequency probe to in- It may be performed by lateral approach using dou- terrupt the posterior primary ramus of segmental ble needle technique trying to reach to the L5-S1 nerves. Uematsu in 1977 described the technique level. It may also be performed with the intra-discal for the radiofrequency of the dorsal root ganglion. [33] approach under fl uoroscopy. Long-lasting pain re- Th e development of a small diameter (22 gauge) lief with this procedure has been achieved in pa- electrode system facilitated the safer use of the ra- tients with pelvic cancer pain. diofrequency procedures. In recent years, Slujter has been the pioneer of developing newer techniques f. Ganglion impar block like pulsed radiofrequency. Th e fi rst report of interruption of the ganglion im- par for the relief of perineal pain came from Plan- What is radiofrequency treatment? carte in 1990.[30] Radiofrequency is an alternating current with an oscillating frequency of 500,000 Hz. Th e heat pro- Th e ganglion impar is also known as the ganglion duced by radiofrequency creates circumscript le- of Walther or the sacrococcygeal ganglion and it is sions by which selective nerve lesioning is possible. the most caudal ganglion of the sympathetic trunk. Th e eff ect of heat on neural tissue becomes destruc- Visceral pain or sympathetically maintained pain in tive after 45° C. Lesions are generally created with the perineal area associated with malignancies of the heat over 60° C. pelvis may be treated with neurolysis of the ganglion impar. Patients with colostomy with tenesmic-like Currently, radiofrequency thermocoagulation is pain and patients with a clinical picture of vague, used for the treatment of various non- malignant burning localized pain may benefi t from this block, and malignant pain syndromes. but the duration is shorter than with other sympa- thetic blocks. Th e main procedures of radiofrequency lesioning used in the treatment of cancer pain are: Th ere are multiple approaches to this block such as a. percutaneous cordotomy lateral approach and trans-discal approach. All ap- b. radiofrequency thermocoagulation of the gasse- proaches should be performed under fl uoroscopy. rian ganglion

138 EKİM - OCTOBER 2009 Neurolytic blocks: When, How, Why c. percutaneous rhizotomy is the most unpleasant complication, in which the d. percutaneous radiofrequency sympathectomy patient defi nes an unpleasant sensation on the origi- nally painful side of the body. Th is usually develops a. Percutaneous cordotomy after several months. At present, percutaneous cervical cordotomy is one of the most important neuroablative techniques in Percutaneous cordotomy is the most dangerous of the treatment of cancer pain. In recent years, use of all percutaneous neuroablative techniques. It should the technique has been declining. Th e number of be performed only by highly experienced experts. patients referred for cordotomy has decreased dra- matically since the introduction of intraspinal tech- b. Percutaneous radiofrequency lesioning of the tri- niques. Th ere are only very few experts in the world geminal ganglion who perform cordotomy. Nevertheless, it still has Generally, neurolysis of the gasserian ganglion is a place in the treatment of severe cancer pain. Th e used for the treatment of cancer pain related with aim of percutaneous cordotomy is to interrupt the the trigeminal nerve. However, radiofrequency le- spinothalamic tract in the anterolateral quadrant, sioning is less risky than neurolysis. If phenol or the most prominent ascending nociceptive pathway glycerol is used, the solution may spread to the in the spinal cord. brainstem, resulting in serious side eff ects like nau- sea and vomiting for several days. Lesioning of the Th e cordotomy is performed at the cervical level nerve is more precise with thermocoagulation. between C1-C2 where the fi bers of the lateral spi- nothalamic tract are closely compact in the antero- In cancer pain, all three branches of the trigemi- lateral quadrant and present a precise somatotropy. nal nerve are generally aff ected. Th us, all branches Th e fi bers coming from the lumbosacral segments should be thermocoagulated. Th e complications are lie in the dorsolateral position, whereas those of the same as with neurolysis. thoracic-cervical origin are more ventral. c. Percutaneous dorsal root ganglion rhizotomy Th e cordotomy is performed with the patient awake A diagnostic block before rhizotomy is a require- and able to collaborate so as to have a continuous ment. One of the biggest concerns is damaging the control of precise positioning of the electrode in the nerve root while positioning the electrode or during spinal cord. radiofrequency lesioning. It is seldom used.

It may be performed under either fl uoroscopy- or d. Lumbar and thoracic sympathetic radiofrequency CT-guided technique. lesioning Lumbar or thoracic sympathetic radiofrequency le- Percutaneous cordotomy is indicated for strictly sioning may be used; however, neurolytic agents are unilateral pain of malignant origin. It is contraindi- generally preferred. cated in bilateral pain, pain extending to levels cra- nial to C5, in patients with a life expectancy of more than one year, in those with poor lung function, and Conclusion in vertebral and epidural metastasis. Neurolytic blocks should only be considered when less invasive methods are inadequate, and the pro- Percutaneous cordotomy carries the risk of very se- cedures should be performed in well-established rious complications. Th ere is risk of motor loss if centers. Pain practitioners should consider the role the lesion has been made too close to the pyramidal of these blocks in adjuvant therapy for the optimal tract. Paraplegia may also develop. Transient urinary treatment of cancer pain. retention may develop for the fi rst 48 hours follow- ing the procedure. Ondine syndrome, in which a Unfortunately, long-term follow-up and results are patient can breathe voluntarily but in whom respi- still lacking for all the methods. However, the clini- ration stops during sleep, may develop. Dysesthesia cal perspective off ered by interventional pain tech-

EKİM - OCTOBER 2009 139 AĞRI niques opens a challenging fi eld for the management Rev 1981; 8: 14-20. of pain in cancer. Finally, this topic represents an 16. Morrica G. Chemical hypophysectomy for cancer pain. In: Bonica JJ, editor. Advances in Neurology. Vol. 4. Pain. New important opportunity for new research, and mul- York: Raven Press; 1974. p. 707-14. ticenter studies can be carried out on this subject. 17. Butler SH, Charlton JE. Neurolytic blockade and hypophysec- tomy. In: Loeser JD, editor. Bonica’s Management of Pain. 3rd References ed. Philadelphia: Lippincott Williams & Wilkins; 2001. p. 1967- 2006. 1. World Health Organization. Cancer as a global problem. 18. Bonica JJ. Sympathetic Nerve Blocks for Pain Diagnosis and Weekly epidemiological record 1984;59:125-6. Therapy: Fundamental considerations and clinical applica- 2. World Health Organization. Cancer Pain Relief. 2nd ed. Ge- tions. Vol. 1, New York: Breon Laboratories; 1984. neva: World Health Organization; 1989. 19. 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