Intrathecal Chemical Neurolysis With Phenol

CANCER PAIN

Intrathecal neurolysis with 6% phenol for intractable and opiate resistant perineal pain secondary to terminal bladder cancer .

Name : Dr R Srivastava

Department: Heart of England NHS Trust, Solihull.

E-mail: rajcube@hotmail.com

Abstract

Background:

Intrathecal chemical neurolysis with Phenol is a neurodestructive technique to provide saddle anaesthesia for perineal pain, in patients unresponsive to pharmacological therapy or not ameneable to surgical treatment. Its use has been advocated in patients with terminal illness with a short life expentancy of less than a year. Phenol’s neurodestructive mechanism relies on precipitation of proteins in the nerves with myelin sheath separation and axonal oedema, resulting in fibrosis. Neurolysis can be induced with chemicals like phenol or alcohol or by physical methods of radiofrquency or cryoablation

Neurolytic saddl block is a high risk procedure leading to almost irreversible neuro-destruction with significant risks including failure, paralysis and incontinence.Careful patient selection and psychological evaluation is mandatory and comprehensive risks and benefits assessment should be carried out before embarking on this technique. Communication with patient is vital due to the resultant side effects of the block.

Results:

Patient was extensively evaluated for the procedure with all co-morbidities and life expectancy considered and underwent subarachnoid chemical neurolysis with hyperbaric 5% phenol leading to drastic pain relief and significant reduction in opiate consumption.

Case Report:

Mr JJ ,a 73 year old gentleman was referred form a hospice with complaints of severe abdominal and anal pain due to a surgically inoperable bladder tumor with extensive pelvic involvement and distant metastases . He was referred to our clinic from hospice with severe opiate resistant pain.

Mr JJ was diagnosed with the Transitional Cell Carcinoma: T2a N0 MX(Pulmonary nodules) G3,TCC Bladder, eight months ago when he initially presented with back and pelvic pain. He had pulmonary metastases and bladder biopsy and cystoscopy revealed a large tumor on the back wall of the bladder. Mr JJ underwent a radical course of radiotherapy. Subsequently he was admitted to the hospital with rectal pain . Examination under anaesthetic revealed a large mass extending from the bladder in to the prostrate.

MRI scan confirmed the tumor with invasion of seminal vesicles and of the prostrate.He underwent ureteric stenting for his right hydronephrosis and hydroureter.

His background included history of chronic obstructive airway disease, hypertension, diabetes, Ischaemic heart disease(Coronary stenting 5 years ago) and hypothyroidism.

His pain at the time remained unsettled with associated symptoms of tenesmus, nausea and vomiting and profound weakness. Mr JJ lived alone and was unable to cope on his own and was referred to hospice for further palliative care.

He was initially treated with Zomorph 30mg twice a day and with Oromorph as a PRN dose for breakthrough pain. Pain worsened over a period of six weeks when it was decided to start him on a syringe driver of diamorphine 30 mgs and metoclopramide30 mgs. Inspite of some relief, he remained extremely confused and constipated.

His syringe driver was changed to alfentanil 5mgs and haloperidol 3 mgs to reduce the confusion and drowsiness. Subsequent increment of alfentanil dose via the syringe driver did not resolve his rectal pain.

In view of his worsening symptoms and prognosis ,saddle block with phenol for rectal pain remained the only viable option.

After a careful assessment and explanation of the risks ( double incontinence and possible paralysis) and benefits of the procedure explained, patient was transferred to our centre as a day case and underwent intrathecal neurolysis with phenol.

1 ml of 5% phenol in glycerol was injected intrathecally and flushed with 0.2 mls of 0.5% hyperbaric bupivacaine. Patient was sat up for 30 minutes to achieve a saddle block.

In recovery he seemed to be pain free with no loss of motor power. Mr JJ was transferred back to the hospice the same day.

During follow up it was noted that within a few days Mr JJ’s alfentanil infusion was stopped and he was more awake and was managing on small doses of oral morphine of up to 40 mgs a day. His tenesmus completely disappeared but he still complained of some dull aching and deep visceral pain.

Case discussion:

There are more than 5000 deaths/year related to bladder cancer in the UK and it is the seventh commonest cause of cancer related deaths. Our patient had an extensive spread of his bladder tumor resulting in a combination of background visceral pain involving the rectum causing intractable tenesmus

Prevalence of cancer pain in patients with incurable or advanced disease ranges from 43 -63%. More than one third of the patients complain of significant pain during the terminal stages of the disease.[1]

Pathophysiological Mechanisms:

The mechanisms involving cancer pain are complex and can not be solely attributed to either nociceptive ,musculoskeletal , visceral or neuropathic pain .

Pain presents itself as a combination of various mechanisms, which would be dependent on the characteristics of disease progression.

Visceral pain as was the case with our patient has both spinal and vagal innervation with feature of dull and diffuse pain with poor localization.

Cancer cells in combination with the stromal cells will result in release of inflammatory markers like endothelin, bradykinin , tyrosine kinase and proteases which would lead to sensitization of the nerve fibres.

Tyrosine kinase seems to play an important role in the sensitization of the afferent nociceptors.[2]

Growth of the tumor may cause direct compression of the nerve fibres resulting in ischemia related neuropathic pain.

Cancer induced bone pain is a result of proliferating osteoclasts which lead to bone resorption. This also leads to stimulation of TRPV1 and acid sensing channels expressed on the nerve fibres resulting in cancer associated bone pain.

Periosteal sensitization of afferent fibres in an acidic melieu contributes to the persistence of cancer pain.[3]

Assessment of cancer pain remains complex and is influenced by patient population, variability in assessment tool ,scoring systems and under reporting of severity of pain by patients.[4]

Assessment of patients with cancer requires a multidimensional approach in order to evaluate the physiological, psychological and social impact on life.

A careful assessment of history, symptoms, signs and disease progression is crucial. Patient’s expectations with regards to treatment should be discussed and the impact of pain on patients functional activity should be assessed. Patients with cancer complain of background pain and exacerbation of pain (Breakthrough Pain), which might be related to movement or due to progression of tumor resulting in compression of underling tissues and organs . Metastases to the bone can be the primary cause of pain in up to 75% of the patients.

Assessment of localization, severity, duration, exacerbating and relieving factors is a must.

Cancer pain patients are often on high dose of opiates for their pain control, which may have a detrimental effect on their daily living due to side effects of tolerance to opiates, opioid induced hyperalgesia, leading to inadequate pain control.

Management of cancer pain:

Cancer pain management in a palliative patient is challenging and requires consideration of all aspects of pain in the terminally ill.

Optimum control can only be achieved if pharmacological and bio-psycho-social element of treatment are carefully reviewed.

Most patients understandably are depressed and more than 75% suffer from moderate to severe pain.

Surgical management is rarely appropriate in patients with distant metastases but may be indicated in some circumstances like internal fixation for pathological long bone fracture. Chest drainage may be required for patients with mesothelioma for recurrent pleural effusion.

Radiotherapy which can be localized or wide field and may be useful in patients with metastatic bone disease with proven efficacy of up to 60%. and 25% respectively.

Radioisotopes like strontium are also used to treat metastatic bone disease but may not be cost effective in all healthcare systems.

Chemotherapy may be helpful in some types of cancer,provided that the tumor remains chemo-sensitive. Assessing the benefits of chemotherapy with regards to prognosis and life expectancy is crucial as the side effects of chemotherapy may be more detrimental to the patient than the pain itself.

Hormonal therapy has been useful in prostrate and breast cancer with anti-androgen and anti-oestrogens as both types of cancer are hormone sensitive.

Pelvic pain may result from the tumor invasion to organs and

The World Health Organisation (WHO) 3 step analgesic ladder of 1986 recommends a staged approach from non-opiods like paracetamol and non-steroidal anti-inflammatory drugs to weak opioids and if necessary ,strong opioids for moderate to severe pain. However, the role of adjuvants like tricyclic anti-depressants, selective serotonin reuptake inhibitors and anticonvulsants like gabapentin and pregabalin should be considered and individualized depending on the symptomatology of the patient. NMDA antagonist like ketamine may help reduce central sensitization[6]

Heavy reliance on strong opioids can lead to troublesome side –effects which should be appropriately managed with laxatives and anti-emetics. Opioid rotation should be considered for opioid induced hyperalgesia as in the case of Mr JJ where diamorphine was substituted for alfentanil infusion.

Evaluation of psychological factor of perception of pain and the behavioural responses has a significant impact on patient’s lifestyle. Cognitive behavioral therapy may help elicit these perception and help individuals with chronic pain ,forming coping strategies.

Pain management programme is helpful for the patient in identifying all aspects of pain and are aimed at improving the quality of life.

Physical therapy for pain is aimed at improving functionality and reducing the physiological deconditioning.

Lifestyle adjustment in terms of daily routines ,tasks and adapting to new envoirement should be planned for facilitating any coping strategies.

Intervention techniques are aimed at targeting the source of pain involving destructive and non-destructive techniques which could involve local anesthetics and steroids for nerve blocks .Continuous infusions of local anaesthetics and opioids via a catheter placed intrathecally, can be used for spinal cord modulation and pain control. Catheter is connected to a programmable pump to administer the desired dose.

Nerve destructive techniques should be only considered in a multidisciplinary framework . Patient selection and progonostication of the illness is paramount.

It is important that the patient has a full understanding of the procedure and the benefits at the expense of the undesired consequences of such a block like incontinence or motor paralysis.

Trial of local anaesthetic is desirable in most cases to predict efficacy of further neurolysis.

Neurolytic blocks necessiate the need for close monitoring and evaluation of patient’s pain scores in order to titrate the strong opioids accordingly.

Indications and contraindications to Intrathecal neurolysis:

Although there has been a decreasing trend in the use of intrathecal neurolysis following advancement in the techniques of spinal blocks with infusions of local anaesthetics and opioids; intrathecal neurolysis has its place in a select subset of patients in whom the pain remains refractory inspite of conventional therapies

and treatment with strong opioids .

The distinct advantage with neurolysis is of reduction in the opiate consumption and the associated side effects. Complications of subarachanoid block include bladder and bowel dysfuction along with motor weakness .[5].

Pain relief associated with neurolytic blocks is short lived(less than 6 months), and disease progression may lead to refractory pain .In view of our patient’s limited life expectancy of less than two months with pre- exsisting bowel and bladder dysfunction ,intrathecal neurolysis was the quickest and the most cost effective way to provide pain relief.

Neurodestructive techniques used in clinical practice range from cryoablation, radiofrequency lesioning to chemical neurolysis with Alcohol (50-100%),Phenol (7-12%) , Hypertonic saline and glycerol.

Intrathecal neurolysis:

It involves the destruction of nociceptive afferent fibres ,both myelinated and unmyelinated leading to almost instant pain relief. It is effective in well localized pain. The effect of neurolysis is short lived but it involves a short period of hospitalization in comparision to neurosurgical procedures like cordotomy.

Phenol(7-12%) causes nerve destruction by coagulating protein in both small and large fibres which leads to degeneration of the nerves within the nerve roots involving more of the posterior than anterior columns. Nerves tend to regenerate faster with phenol than alcohol .

Phenol is hyperbaric and when mixed with glycerol, it tends to diffuse more slowly out of the solution causing a more targeted destruction compared to alcohol. It can be mixed with water but the nerve destruction will be more extensive.

Phenol compared to alcohol is not painful on injection and for this reason alcohol injections are administered with a local anaesthetic. In concentrations of lower than 5%, phenol tends to exert local anaesthetic action rather than neurodestructive. Phenol when mixed with glycerol or radiopaque dye can provide a higher concentration of up to 15%.

Neurolysis with phenol in comparision to alcohol is milder and short lived. Due to the hyberbaric nature of phenol in comparision with alcohol, the patient is positioned with the affected side down to target the dorsal roots. Phenol being highly viscous requires a wider bore spinal needle for injection. Phenol can cause skin and tissue necrosis along with neuritis if the nerve destruction is incomplete.

For patients undergoing neurolysis with alcohol the targeted side is positioned up due to the hypobaric nature of the solution. Patients are initially in the lateral position followed by proning to 45 degrees to target the dorsal roots. Alcohol may cause mild burning on injection.

Hypertonic saline(10-15%) for intrathecal neurolysis can provide a significant relief of more than 50% but has significant side effects.

Conclusion:

Management of cancer pain is very complex and challenging and requires considerable expertise in providing appropriate care to terminally ill patients. Significant reliance on strong opioids is not without it’s side effects and a multifaceted approach towards pain control is warranted. Our patient was treated with chemical neurolysis as a last resort since all other measures had failed. Although it helped in reduction of opiate requirement and drowsiness, it still remains difficult to judge the correct dosage and concentration of phenol and balance it against the duration of pain free interval with minimum side effects for the patient before leading to death.

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Intrathecal neurolysis is not a routine procedure and outcomes of this type of intervention are variable. The extreme complications of this procedure and availability of other techniques makes clinicians reluctant to use in their regular clinical practice. However, cancer pain treatment needs to be tailored in accordance with the patients condition and chemical neurolysis may perhaps be the only option to relieve pain in specific patients.

References:

[1]M. H. J. van den Beuken-van Everdingen, J. M. de Rijke, A. G. Kessels, H. C. Schouten, M. van Kleef, and J. Patijn, “Prevalence of pain in patients with cancer: a systematic review of the past 40 years,” Ann. Oncol. Off. J. Eur. Soc. Med. Oncol. ESMO, vol. 18, no. 9, pp. 1437–1449, Sep. 2007.

[2]S. Pezet and S. B. McMahon, “NEUROTROPHINS: Mediators and Modulators of Pain,” Annu. Rev. Neurosci., vol. 29, no. 1, pp. 507–538, 2006.

[3]“Review of Cellular Mechanisms of Tumor Osteolysis. : Clinical Orthopaedics and Related Research,” LWW. [Online]. Available: http://journals.lww.com/corr/Fulltext/2000/04000/Review_of_Cellular_Mechanisms_of_Tumor_Osteolysis_.13.aspx. [Accessed: 23-Nov-2014].

[4]C. Shute, “The Challenges of Cancer Pain Assessment and Management,” Ulster Med. J., vol. 82, no. 1, pp. 40–42, Jan. 2013.

[5]A. Watanabe and M. Yamakage, “Intrathecal neurolytic block in a patient with refractory cancer pain,” J. Anesth., vol. 25, no. 4, pp. 603–605, Aug. 2011.

[6]Cancer Pain Management. The British Pain Society 2010