CASE

• 68 yr old male patient diagnosed with Ca colon came to your office with severe lower back pain radiate to L lower limb. What is your plan for his management?

INTERVENTIONAL PAIN THERAPY FOR CANCER PATIENT WHEN TO

START & WHAT TO DO? ABDULLAH M KAKI, MD, FRCPC

PROFESSOR & CONSULTANT OF ANESTHESIOLOGY & PAIN MEDICINE

FACULTY OF MEDICINE, KING ABDULAZIZ UNIVERSITY, JEDDAH, SAUDI ARABIA

DUBAI PAIN DIPLOMA, MAY 14, 2017

DISCLOSURE

I have nothing to disclose

�  Prevalence of Chr pain in solid tumors 15 -75%,

(extent of cancer, type of cancer, treatment setting, and other factors).

�  When etiology of pain is related to active cancer, there is consensus that opioid is 1ST line therapy.

�  WHO recommendation.

�  Unfortunately, neither consensus nor EB publications has corrected problem of undertreatment, as a result of limited professional education and limited access to opioid drugs.

•  Goudas LC, et al. The epidemiology of cancer pain Cancer Invest 23:182– 190,2005.•  Caraceni A, et al. Use of opioid analgesics in the treatment of cancer pain: Evidence-based recommendations from the EAPC Lancet Oncol 13: e58– 

e68,2012 . •  Cancer Pain Relief 1986 World Health Organization Geneva, Switzerland World Health Organization, Office of Publications•  Deandrea S, et al.  Prevalence of undertreatment in cancer pain: A review of published literature Ann Oncol19: 1985– 1991,2008  •  Breuer B, et al. Medical oncologists' attitudes and practice in cancer pain management: A national survey J Clin Oncol 29: 4769– 4775,2011

• 30 -50 %: severe chr cancer pain, not controlled with opioids among pts undergoing active antineoplastic therapy

• 75 - 90 % of those with advanced disease.

• Treatment guidelines for cancer pain: primary role of systemic opioid (70-90%).

• Limited access to opioid-based systemic pharmacotherapy for moderate to severe cancer pain.

• However, despite optimization of opioid and use of analgesic adjuvants, a substantial number of pts with cancer pain do not obtain satisfactory relief with first-line analgesic therapy

•  VAN DEN BEUKEN-VAN EVERDINGEN MH, DE RIJKE JM, KESSELS AG, ET AL. HIGH PREVALENCE OF PAIN IN PATIENTS WITH CANCER IN A LARGE POPULATION-BASED STUDY IN THE NETHERLANDS. PAIN 2007; 132:312.

•  TEUNISSEN SC, ET AL. SYMPTOM PREVALENCE IN PATIENTS WITH INCURABLE CANCER: A SYSTEMATIC REVIEW. J PAIN SYMPTOM MANAGE 2007; 34:94. •  WHO. CANCER PAIN RELIEF, 2ND, WORLD HEALTH ORGANIZATION, GENEVA 1996. •  AMERICAN PAIN SOCIETY. PRINCIPLES OF ANALGESIC USE IN THE TREATMENT OF ACUTE PAIN AND CANCER PAIN, 6TH, AMERICAN PAIN SOCIETY, GLENVIEW, IL, 2008. •  FINE, P, PORTENOY, RK. OPIOD ANALGESIA, MCGRAW HILL, NEW YORK 2004. •  QUIGLEY C. OPIOIDS IN PEOPLE WITH CANCER-RELATED PAIN. BMJ CLIN EVID 2008; 2008.

•  Interventional strategies comprise a very diverse group of invasive therapies.

•  Include: injections, non-neurolytic and neurolytic nerve blocks, and implanted neurostimulation and neuraxial drug infusion techniques.

•  Evidence base for all of these approaches is limited and includes very few controlled trials.

•  Interventional therapies for pain management are implemented by professionals who have received specialized training.

INJECTION THERAPIES

• Soft tissue and joint injections :

•  TP injection

•  Intra-articular injection

•  Injections for LBP (epidural, facets & SIJ inj)

• Although the evidence to support benefit of trigger point injections in cancer patients is limited to anecdotal experience

• Patients with myofascial pain and no contraindication to injection, such as a coagulopathy or severe leukopenia

•  SIST T, MINER M, LEMA M. CHARACTERISTICS OF POSTRADICAL NECK PAIN SYNDROME: A REPORT OF 25 CASES. J PAIN SYMPTOM MANAGE 1999; 18:95 •  SIST T, WONG C. DIFFICULT PROBLEMS AND THEIR SOLUTIONS IN PATIENTS WITH CANCER PAIN OF THE HEAD AND NECK AREAS. CURR REV PAIN 2000; 4:206.

PATHOLOGIC VERTEBRAL COMPRESSION FRACTURES 

•  Initial trial of IV pamidronate or nasal calcitonin => if pain persist or not controlled => Vertebroplasty and kyphoplasty 

•  Contraindications:

•  Patients with epidural disease.

•  Presence of neurologic damage related to fracture

•  Fractures with a burst component (where bone fragments extend into the spinal canal),

•  Systemic or local infection, uncorrected hypercoagulable state, and severe cardiopulmonary disease.

•  CHWISTEK M, MEHTA RS. VERTEBROPLASTY AND KYPHOPLASTY FOR VERTEBRAL COMPRESSION FRACTURES #202. J PALLIAT MED 2012; 15:1151. •  HULME PA, KREBS J, FERGUSON SJ, BERLEMANN U. VERTEBROPLASTY AND KYPHOPLASTY: A SYSTEMATIC REVIEW OF 69 CLINICAL STUDIES. SPINE (PHILA PA 1976) 2006;

31:1983. •  TAYLOR RS, TAYLOR RJ, FRITZELL P. BALLOON KYPHOPLASTY AND VERTEBROPLASTY FOR VERTEBRAL COMPRESSION FRACTURES: A COMPARATIVE SYSTEMATIC REVIEW OF

EFFICACY AND SAFETY. SPINE (PHILA PA 1976) 2006; 31:2747.

• Vertebroplasty: percutaneous injection of bone cement (methylmethacrylate) under fluoroscopic guidance into a collapsed vertebral body.

• Kyphoplasty: involves introduction of inflatable bone tamps into vertebral body; once inflated, the bone tamps variably restore the height of the vertebral body, while creating a cavity that can then be filled with viscous bone cement

EVIDENCE SUPPORTS THE SAFETY & EFFICACY OF V & K IN PATIENTS WITH MALIGNANT VERTEBRAL COMPRESSION FRACTURES IS:

•  A 2011 systematic review of vertebroplasty in pts with multiple myeloma or metastatic bone disease included 1 randomized trial of vertebroplasty with or without brachytherapy, 6 prospective but uncontrolled studies, 21 retrospective case series, and 2 additional uncharacterized reports;

•  987 pts were included. Pain reduction 87 to 47%, and there was no correlation between pain reduction and cement volume. The duration of benefit was not addressed. 5 deaths were attributed to the procedure, and 19 others suffered a serious complication (12 neuropathies and 1 hematoma requiring emergency surgery, 1 hemothorax, 1 DVT, and 4 symptomatic cement PE).

CHEW C, CRAIG L, EDWARDS R, ET AL. SAFETY AND EFFICACY OF PERCUTANEOUS VERTEBROPLASTY IN MALIGNANCY: A SYSTEMATIC REVIEW. CLIN RADIOL 2011; 66:63

• Benefit of kyphoplasty: 2009-meta-analysis of 7 uncontrolled studies involving 306 pts with multiple myeloma or osteolytic bone metastases: reduced pain and improved functional outcome, up to 2 yrs postprocedure.

• Balloon kyphoplasty also improved early vertebral height loss and spinal deformity but were not sustained. No serious procedure-related complications were described, and asymptomatic cement leakage occurred in 6 %.

BOUZA C, ET AL. BALLOON KYPHOPLASTY IN MALIGNANT SPINAL FRACTURES: A SYSTEMATIC REVIEW AND META-ANALYSIS. BMC PALLIAT CARE 2009; 8:12.

NEURAL BLOCKADE  •  Diagnostic, prognostic, therapeutic, or anesthetic/analgesic

•  Diagnostic n block: localizes afferent pathway involved in sustaining the pain.

•  Non-neurolytic (analgesic) nerve blocks using bolus or infusion. Visceral cancer pain, which can be difficult to control with opioids and other analgesics, is especially suited to sympathetic blockade.

•  Neurolytic (anesthetic) techniques produce analgesia by destroying afferent neural pathways or sympathetic structures. With exceptions of coeliac plexus and superior hypogastric plexus neurolysis, these techniques are considered “last resort” options.

•  Prior to a planned neurolytic block, prognostic nerve block using LA should be performed.

SOMATIC NERVE BLOCKS

• Paravertebral or intercostal blocks to denervate a region of chest or abdominal wall.

• Brachial plexus block to denervate the shoulder or arm.

• Gasserian ganglion block to denervate a part of the face.

•  Epidural or intrathecal blocks to denervate various areas of the body.

• Anesthetic infusions to denervate peripheral nerves may also be used when the spinal approach is not possible.

LEMA, MJ. INVASIVE PROCEDURES FOR CANCER PAIN. PAIN: CLINICAL UPDATES; 6:1. INTERNATIONAL ASSOCIATION FOR THE STUDY OF PAIN ( IASP) AVAILABLE ONLINE AT HTTP://WWW.IASP-PAIN.ORG/AM/AMTEMPLATE.CFM?SECTION=HOME&TEMPLATE=/CM/CONTENTDISPLAY.CFM&CONTENTID=7603.

SYMPATHETIC BLOCKS

• Visceral pain, difficult to control, interrupts both afferent, efferent, & sympathetic fibers.

• Pain in somatic structures, CRPS.

BURTON, AW, PHAN, PC, COUSINS, MJ. TREATMENT OF CANCER PAIN: ROLE OF NEURAL BLOCKADE AND NEUROMODULATION. IN: COUSINS AND BRIDENBAUGH'S NEURAL BLOCKADE IN CLINICAL ANESTHESIA AND PAIN MEDICINE, 4TH, LIPPINCOTT, WILLIAMS & WILKINS, 2009. P.1122.

STELLATE GANGLION BLOCK

•  Fusion of 1st thoracic and infer cervical sympathetic ganglion (T1-T4).

• Cover head, neck, upper extremities, and intrathoracic structures

LUMBAR SYMPATHETIC BLOCK

• A sympathetic block of lower extremities

• Paraspinal lumbar sympathetic block

BLOCK OF SYMPATHETIC NERVES INNERVATING ABDOMINAL AND PELVIC VISCERA

• originate from T5-L2 and distribute: greater (T5-T10), lesser (T10-T12) and least (T12-L2) splanchnic nerves, which coalesce in celiac plexus, superior hypogastric plexus, and ganglion impar

NEUROLYTIC BLOCKS WHEN AND HOW TO DO IN 2017 WITH ALL THE

TREATMENTS AVAILABLE? ABDULLAH M KAKI, MD, FRCPC

PROFESSOR & CONSULTANT OF ANESTHESIOLOGY & PAIN MEDICINE

FACULTY OF MEDICINE, KING ABDULAZIZ UNIVERSITY, JEDDAH, SAUDI ARABIA

DUBAI PAIN DIPLOMA, MAY 14, 2017

NEUROLYTIC BLOCKS 

• Produce analgesia by destroying afferent neural pathways or sympathetic structures (efferents or afferent).

• Chemical neurolysis using alcohol or phenol is usually applied for refractory pain associated with advanced cancer.

• Result in Wallerian degeneration.

• Carry the risk of producing a new “deafferentation pain.” •  ROWE DS. NEUROLYTIC TECHNIQUES FOR PAIN MANAGEMENT. JACKSONVILLE MEDICINE; OCTOBER 1998. HTTP://WWW.DCMSONLINE.ORG/JAX-MEDICINE/

1998JOURNALS/OCTOBER98/NEUROLYTIC.HTM (ACCESSED ON MARCH 28, 2011). •  GANJI, A. CANCER PAIN MANAGEMENT. BIOMEDICAL IMAGING AND INTERVENTION JOURNAL 2007; 3(1):E12, ACCESSED ONLINE AT HTTP://WWW.BIIJ.ORG/2007/1/E12/

ABSTRACT.ASP?ID=230 (ACCESSED ON AUGUST 30, 2010).

INDICATIONS

•  To control resistant pain syndromes (malignant or benign etiology).    

• Pain from the cranial nerves (particularly trigeminal nerve)

• Pain originating in major plexuses (brachial and lumbar)

• Pain associated with sympathetic-medially pain (celiac plexus, lumbar sympathetic ganglia, ganglion impar, and superior hypogastric plexus)

• Pain originating in the periphery (sacroiliac joints)

• Before considering the use of chemical or thermal neurolysis, clinician should try all alternative means of providing analgesia.

SELECTION CRITERIA

• Duration of action of neurolytic agents is unpredictable

• Patients must be completely apprised of the possibility of debilitating S/E and other serious complications (motor weakness and incontinence).

• Diagnosis is well established.

• Patient’s life expectancy is short, (6 -12 months).

• Patient’s pain is unresponsive to antineoplastic therapy (chemotherapy, radiation) and failed to respond to adequate trials of analgesic agents and adjunctive drugs.

•  The pain is localized to 2 or 3 dermatomes.

INFORMED CONSENT

•  Not only patient, but also family fully understand the anticipated procedure, its potential risks, the alternative forms of therapy available, and, most importantly, the possibility of serious complications.

•  The procedure does not simply “take away pain,” but rather substitutes numbness (loss of sensation) for the pain.

•  Prognostic block using LA so that patient can experience the pain relief that may be anticipated after a neurolytic block and the accompanying sensory block.

PREOPERATIVE CONSIDERATIONS

• Obtaining an informed, written consent.

•  NPO

•  Ascertaining the absence of contrast allergies and no use of anticoagulant medications.

•  Standard American Society of Anesthesiologists (ASA) monitors are applied and baseline vital signs are assessed and documented.

•  An intravenous cannula should be placed to give IV fluids and supportive drugs.

Agents and procedures that can be utilized for neurolytic blocks

I. Typically reversible procedures - Cryoneurolysis

II. Typically reversible agents

A. 5% lidocaine

B. Botulinum toxin

C. Hypertonic saline

D. Water

E. Low concentration phenol

III. Destructive procedures

A. Radiofrequency lesioning

B. Surgical lesioning

IV. Destructive agents

A. High concentration phenol

B. Alcohol

C. Glycerol

CONTRAINDICATIONS

• Patient refusal

• Patient who has bleeding problems, or irreversible inhibitors of platelet aggregation

• Has history of allergy to iodine-based contrast agents

• Has an infection at the injection site

• Patient who is unable to remain motionless during the procedure, which may cause unexpected injury during the intervention

LUMBAR SYMPATHETIC NEUROLYSIS

CELIAC PLEXUS NEUROLYSIS

• Upper abdominal malignancy, particularly pancreatic cancer.

• Sufficiently safe and effective, recommended as the next step if 1-2 trials of systemic opioid therapy are ineffective.

•  The celiac plexus can be accessed intraoperatively, percutaneously, or endoscopically, using ultrasound guidance.

• A meta-analysis:1145 pts from 24 studies => coeliac block provided long-lasting benefit for 70-90% of pts with pancreatic (63%) and other upper abdominal cancers.

• Good to excellent pain relief in 89% of pts during first 2 wks after block. Pain relief persisted in 90% of alive pts 3 months later.

• RCT double-blind prospective study of 100 pts showed significant sustained improvement in pain relief until death.

•  EISENBERG E, CARR DB, CHALMERS TC. NEUROLYTIC COELIAC PLEXUS BLOCK FOR TREATMENT OF CANCER PAIN: A META-ANALYSIS. ANESTH ANALG 1995;80:290E295. •  WONG GY, ET AL. EFFECT OF NEUROLYTIC CELIAC PLEXUS BLOCK ON PAIN RELIEF, QUALITY OF LIFE, AND SURVIVAL IN PATIENTS WITH UNRESECTABLE PANCREATIC

CANCER: A RANDOMIZED CONTROLLED TRIAL. JAMA 2004;291:1092E1099.

SUPERIOR HYPOGASTRIC PLEXUS NEUROLYSIS

• Visceral pelvic pain that is refractory to medical management.

•  Lies retroperitoneal and extends from ant. aspect of L5 to superior sacrum. Afferent fibers from the pelvic viscera pass through the plexus, which also contains sympathetic postganglionic fibers.

•  Initial LA block is used to predict response to neurolytic block.

•  Lumbar plexus injury, bladder puncture, and iliac artery puncture with retroperitoneal bleeding or cholesterol plaque embolization can occur.

PLANCARTE R, ET AL. NEUROLYTIC SUPERIOR HYPOGASTRIC PLEXUS BLOCK FOR CHRONIC PELVIC PAIN ASSOCIATED WITH CANCER. REG ANESTH 1997; 22:562

GANGLION IMPAR NEUROLYSIS

NEURAXIAL NEUROLYTIC BLOCKADE •  Less common in recent years, increasing use of neuraxial analgesic infusion, to

avoid inadvertent motor blockade and interference with bladder or bowel function.

• Hyperbaricity of phenol in glycerin in semisupine pt => selective unilateral sensory root block or to give saddle block (advanced perineal malignancy)

•  Epidural neurolytic agents to target spinal nerve roots, either by bolus or by catheters, or transforaminal injection.

•  FINNEGAN C, ET AL. THE ROLE OF EPIDURAL PHENOL IN CANCER PATIENTS AT THE END OF LIFE. PALLIAT MED 2008;22:777E778. •  SLATKIN NE, RHINER M. PHENOL SADDLE BLOCKS FOR INTRACTABLE PAIN AT THE END OF LIFE: REPORT OF FOUR CASES AND LITERATURE REVIEW. AM J HOSP PALLIAT CARE

2003;20:62E66. •  ISCHIA S, ET AL. SUBARACHNOID NEUROLYTIC BLOCK (L5-S1) AND UNILATERAL PERCUTANEOUS CERVICAL CORDOTOMY IN THE TREATMENT OF PAIN SECONDARY TO PELVIC

MALIGNANT DISEASE. PAIN 1984;20:139.

RISKS ASSOCIATED WITH NEUROLYTIC BLOCKADE FOR PAIN RELIEF

• Anesthesia of the area innervated by the destroyed nerve

• Anesthesia dolorosa (pain superimposed in an area that lacks or has impaired sensation

• Autonomic dysfunction

• Motor paresis

• Bladder/bowel dysfunction

• Dysesthesias

• Orthostatic hypotension

• Neuritis

PERCUTANEOUS CORDOTOMY •  Percutaneous cervical cordotomy for unilateral pain below C5 (mesothelioma).

•  Inserting a needle into the anterolateral aspect of the cord on side opposite to pain (spinothalamic tract), under I.I. RF lesioning is carried out after ensuring correct positioning by electrical stimulation.

•  Bilateral procedures interfere with respiratory control => sleep apnoea.

•  Cordotomy at lower spinal levels is more invasive procedure and is rarely done. In a series of 43 pts with severe unilateral pain due to cancer, resistant to systemic therapy, a good result was obtained in 95%, sustained in 69% at end of life.

•  SANDERS M, ZUURMOND W. SAFETY OF UNILATERAL AND BILATERAL PERCUTANEOUS CERVICAL CORDOTOMY IN 80 TERMINALLY ILL CANCER PATIENTS. J CLIN ONCOL 1995;13:1509E1512.

•  JACKSON MB, ET AL. PERCUTANEOUS CERVICAL CORDOTOMY FOR THE CONTROL OF PAIN IN PATIENTS WITH PLEURAL MESOTHELIOMA. THORAX 1999;54:238E241. •  CRUL BJ, ET AL. THE PRESENT ROLE OF PERCUTANEOUS CERVICAL CORDOTOMY FOR THE TREATMENT OF CANCER PAIN. J HEADACHES PAIN 2005;6(1):24E29.

BONY METASTASES

• Bony metastases are a common source of pain.

• Case series of intra-lesional injection of steroids => 70% prolonged relief.

•  Intralesional injection of ethanol under CT scan reduces analgesia in 74% of pts.

• Radiofrequency with or without cementoplasty

•  ROWELL NP. INTRALESIONAL METHYLPREDNISOLONE FOR RIB METASTASES: AN ALTERNATIVE TO RADIOTHERAPY? PALLIAT MED 1988;2: 153E155. •  ROUSSEFF RT, SIMEONOV S. INTRALESIONAL TREATMENT IN PAINFUL RIB METASTASES. PALLIAT MED 2004;18:259. •  GANGI A, ET AL. INJECTION OF ALCOHOL INTO BONE METASTASES UNDER CT GUIDANCE. J COMPUT ASSIST TOMOGRAPHY 1994;18:932E935. •  MUNK PL, ET AL. COMBINED CEMENTOPLASTY AND RADIOFREQUENCY ABLATION IN THE TREATMENT OF PAINFUL NEOPLASTIC LESIONS OF BONE. J VASC INTERVEN

RADIOL 2009;20:903E911. •  THANOS L, ET AL. RADIOFREQUENCY ABLATION OF OSSEOUS METASTASES FOR THE PALLIATION OF PAIN. SKELETAL RADIOL 2008;37(3):189E194.

• According to the Evidence-Based Medicine (EBM) guidelines, randomized controlled trials (RCTs) have the highest scientific value. However, RCTs on interventional pain management techniques face methodological problems often leading to power problems because inadequate number of subjects can be recruited

• Unfortunately the results of those underpowered studies are included in systematic reviews and meta analyses and they may negatively influence the general recommendations.

IMPLANTED NEUROSTIMULATION AND NEURAXIAL INFUSION TECHNIQUES

•  limiting S/E associated with systemic pharmacotherapy.

• Main disadvantages: cost, risk of infection, and mechanical failure.

• Proper patient selection: best candidate for SCS or peripheral nerve stimulation is focal, isolated pain of neuropathic origin (eg, a painful lumbosacral plexopathy).

• Preliminary percutaneous trial with a temporary electrode or catheter.

•  LANDAU B, LEVY RM. NEUROMODULATION TECHNIQUES FOR MEDICALLY REFRACTORY CHRONIC PAIN. ANNU REV MED 1993; 44:279. •  FERRANTE FM. NEURAXIAL INFUSION IN THE MANAGEMENT OF CANCER PAIN. ONCOLOGY (WILLISTON PARK) 1999; 13:30. •  SMITH TJ, STAATS PS, DEER T, ET AL. RANDOMIZED CLINICAL TRIAL OF AN IMPLANTABLE DRUG DELIVERY SYSTEM COMPARED WITH COMPREHENSIVE MEDICAL MANAGEMENT

FOR REFRACTORY CANCER PAIN: IMPACT ON PAIN, DRUG-RELATED TOXICITY, AND SURVIVAL. J CLIN ONCOL 2002; 20:4040. •  GILDENBERG, PL. HISTORY OF ELECTRICAL NEUROMODULATION FOR CHRONIC PAIN. PAIN MEDICINE 2006; 7:S7. AVAILABLE ONLINE AT HTTP://WWW.SLD.CU/GALERIAS/PDF/

SITIOS/REHABILITACION-FIS/HISTORY_OF_ELECTRICAL_NEUROMODULATION_FOR_CHRONIC_PAIN.PDF (ACCESSED ON AUGUST 30, 2010).

• Neuraxial infusion: one or more drugs are infused into the epidural or intrathecal (subarachnoid) space.

• Patients who are refractory or intolerant of systemic pharmacotherapy.

• Decision depends on medical status of pt, goals of care, availability of professional and family support, and cost.

•  The development of other nondestructive analgesic approaches to blocking somatic and sympathetic nerves, limited to population of cancer pts with advanced disease whose pain is not amenable to more conservative therapies.

• Given the risks of late deafferentation pain, possibility of unwanted tissue damage induced by the neurolytic process at the time of administration, and the likelihood that even successful neurolysis may not provide more than a few months of relief => “last resort”, with two major exceptions:

CHAMBERS WA. NERVE BLOCKS IN PALLIATIVE CARE. BR J ANAESTH 2008; 101:95. SLATKIN NE, RHINER M. PHENOL SADDLE BLOCKS FOR INTRACTABLE PAIN AT END OF LIFE: REPORT OF FOUR CASES AND LITERATURE REVIEW. AM J HOSP PALLIAT CARE 2003; 20:62.

Celiac plexus/splanchnic nerve blocks for abdominal pain

Hypogastric plexus/ganglion impar block for pelvic pain

Intercostal blocks for rib fractures

Kyphoplasty and vertebroplasty for vertebral compression fractures

Lumbar sympathetic block for rectal tenesmus

Myofascial injections for muscle spasm

Neuraxial infusions

Suprascapular block for shoulder pain

Common interventional therapies for cancer pain management

THANK YOU