14RC1-PERRUCHOUD Interventional management of cancer pain

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1 14RC1-PERRUCHOUD Interventional management of cancer pain Christophe Perruchoud Department of Anaesthesiology and Pain Management, University Hospital Centre and University of Lausanne, Lausanne Background The prevalence of pain amongst cancer patients varies between 30 and 50% and rises to more than 80% of patients with end stage disease. 1 The pain is usually a mixture of nociceptive and neuropathic pain. Metastatic spread of cancer to bone is probably one of the most common causes of cancer pain. 2 Pressure on surrounding organs, stretching hollow viscera and distortion of the capsule of solid organs results in visceral pain, and infiltration of sensory nerves and plexuses causes neuropathic pain, representing important origins of pain. Cancer pain may also be related to adverse effects of anticancer treatment, including chemotherapy, radiotherapy, hormonal therapy or surgery. Opioid therapy remains the mainstay of cancer pain control and adherence to the WHO analgesic threestep ladder achieves pain relief in most patients. 3 However, about one third of cancer patients have inadequate pain relief, often due to unacceptable side-effects of opioids that limit dosage, especially in late stages of disease. 4 For this reason, the inclusion of a fourth step to the WHO analgesic ladder to include advanced interventional approaches has been proposed. However, earlier application of interventional pain management techniques can be recommended before even considering the use of strong opioids. About 20% of oncology patients may benefit from interventional procedures. 5 Interventional therapy ranges from less invasive techniques, such as reversible nerve blocks, to more invasive techniques such as implantable devices or irreversible nerve destruction. Interventional procedures can be divided into procedures affecting the spinal canal, intrathecal or epidural space or neuraxial techniques, and those targeting individual nerves or plexuses, called neurolytic techniques. Neuraxial techniques The main indication for intrathecal and epidural analgesics is failure of oral or transdermal analgesics despite suitable doses. Compared to the systemic administration of opioids, the central route, epidural or intrathecal, provides equal or better pain relief with lower doses and fewer adverse effects. Moreover it allows simultaneous administration of other analgesics, such as bupivacaine or clonidine. Epidural infusion Epidural infusion is a simple method for short-term, i.e. less than three months, use in patients with advanced cancer and difficult-to-control pain. A percutaneous or subcutaneous implantable port can be connected to the catheter. Patients are then discharged with portable infusion pumps. Percutaneous catheters may exit directly at the dorsal site or be tunnelled to the flank areas. The main indication for subcutaneous port implantation is a life expectancy greater than six weeks. The most frequently infused drugs are local anaesthetics, opioids and clonidine. Complications include urinary retention, superficial infections (4-40%), epidural abscess (1-15%) and catheter-related complications such as leakage, obstruction or dislodgment, requiring exchange or removal of the catheter in 15 % of patients. 6 A meta-analysis calculated an incidence of catheter-related infections of 0.4/1000 catheter days. 7 1/7

2 Intrathecal drug delivery Intrathecal (IT) drug administration can be achieved by using an external catheter, a subcutaneous access port or an implantable pump. External catheters and subcutaneous access ports are reserved for patients with short life expectancies. For long-term administration, a pump is implanted surgically in the subcutaneous abdominal tissue and acts as a drug reservoir and delivery mechanism. Although IT drug delivery systems may represent an effective option for pain management, not all patients are appropriate candidates for implants. Selection requires evaluation of comorbidities, psychosocial factors and life expectancy. A cost-effectiveness analysis has shown that implantable systems are better than external pumps if the patient has a life expectancy of at least three months. 8 An IT trial should be performed before surgical implantation to assess the efficacy and side-effects of the intended drug. The trial may be performed with a single injection, multiple injections or a continuous infusion. Prospective studies have shown that patients randomized to receive an intrathecal drug delivery system (IDDS) or who received it after failure of comprehensive medical management had reduced pain scores, significant relief of most pain, control of drug toxicities, and possibly improved survival, at least for the duration of the trial. 9,10 If monotherapy becomes insufficient and dose escalation is no longer safe, combinations of drugs may maintain effective pain relief. Many drugs, bupivacaine, ropivacaine, hydromorphone, fentanyl, sufentanil, buprenorphine, clonidine, and midazolam, are not licensed for IT use in the USA but are licensed in other countries. Consensus statements suggesting different algorithms for nociceptive or neuropathic pain have been developed to guide physicians. 11 Complications resulting from IT therapy are common and include hypotension, sedation, respiratory depression, inflammatory masses, infection and catheter-related complications, such as migration or leakage, and withdrawal syndrome. Excess mortality, especially in the first days after implantation, has been reported in non-cancer patients due to rapid opioid dose escalation in the absence of proper monitoring. Those observations could be translated to the cancer population. 12 Neurolytic techniques Neurolysis describes intentional injury to a nerve or group of nerves by chemical (absolute alcohol, glycerin or phenol), thermal (heat), surgical or cryogenic (freezing) methods to produce pain relief. Neurolytic agents predominantly affect neuronal axons, not cell bodies. Pain relief, therefore, is temporary secondary to axonal regeneration and neural plasticity. The effects of neurolytic therapy typically persist between 3 6 months, although the response may vary widely. Alcohol was the first agent used in 1902 to treat trigeminal neuralgia. 13 Alcohol usually induces a burning sensation in the region where it is injected. Pre-treatment with a local anaesthetic is recommended strongly. Phenol was then introduced in the 1950s and gained widespread popularity, in part because of its analgesic as well as neurolytic properties. Several sites are described for neurolytic block of sympathetically mediated pain associated with gastrointestinal and genitourinary cancers (Figure 1). Since the recent development of neurodestructive techniques such as cryoablation or radiofrequency, and advances in spinal analgesia with continuous infusion, indications for neurolytic blocks have significantly decreased. 2/7

3 Figure 1 : Possible sites for neurolytic block of sympathetically mediated pain according to tumour location. Coeliac plexus The coeliac plexus is a network of neuronal ganglia located underneath the diaphragmatic crus in the retroperitoneal space, at the level of the first lumbar vertebra. Structures immediately adjacent to the coeliac plexus include the coeliac artery and aorta. The coeliac ganglia contain pre- and post-ganglionic sympathetic efferent fibres, preganglionic parasympathetic fibres and visceral sensory afferent fibres. The role of coeliac plexus block to relieve intractable pain caused by upper abdominal malignancies, such as pancreas, liver and stomach, is well established. Several percutaneous techniques are described to access the coeliac plexus, including three posterior approaches, paravertebral, transdiscal and transaortic, and one anterior approach (Figure 2). Fluoroscopy or CT-scan may be used for all except the anterior approach, which requires CT scan or ultrasound guidance. Neurolytic block of the coeliac plexus can be associated with transient hypotension and diarrhoea from sympathetic block. The most serious complication is paraplegia, occurring in approximately 1% of cases, secondary to alcoholinduced vasospasm or mechanical injury to the artery of Adamkiewicz. A meta-analysis of the efficacy and safety of neurolytic coeliac plexus block showed long-lasting (i.e. greater than three months) benefit for 70%-90% of patients with pancreatic and other intra-abdominal cancers, regardless of the approach used. 14 3/7

4 Figure 2 : Percutaneous approaches for coeliac plexus block at L1 level. Splanchnic plexus The splanchnic nerve block is a useful alternative to paravertebral coeliac plexus block, especially in cases of pancreatic tumours. It targets the splanchnic nerves, branches of the thoracic truncus sympathicus and the nerve supply to the coeliac plexus. The needles are inserted paravertebrally, using a tunnel view, in the direction of the concave mid-portion of the D11 body until bony contact is made. Under lateral view, the needle is advanced to the anterolateral aspect of D11. The tip of the needle should be placed just within the contour of the D11 body in an anteroposterior view, just at the anterior border of the D11 vertebra in a lateral view. Before the neurolytic agent is injected, a small amount of contrast is injected to check dispersion along the anterolateral aspect of the vertebral body. Ganglion Impar (GI) The GI is a retroperitoneal structure usually positioned in the midline at the level of the sacrococcygeal junction. It represents the termination of the paravertebral sympathetic chains. It contains visceral afferent fibres that innervate the perineum, distal part of the rectum, anus, distal urethra, distal third of the vagina and vulva. Several approaches have been described to target the GI. All are performed under fluoroscopy. In the trans-sacrococcygeal approach, the needle is placed midline through the sacrococcygeal ligament into the retroperitoneal space. After proper spread of contrast medium, local anaesthetic or neurolytic agent is injected to ensure block of the GI. 4/7

5 Intrathecal neurolysis Intrathecal neurolysis involves the injection of very small amounts of neurolytic agents, 0.1 ml increments to a total of ml for treatment of one to two dermatomal levels, usually hyperbaric phenol (7-12%) or hypobaric alcohol (50-100%). The aim is to produce segmental sensory block, lasting from weeks to months, without affecting motor function. 15 This is possible because of the separation between sensory and motor fibres in the spinal cord. The dorsal roots carry sensory fibres and the ventral root carries motor and sympathetic fibres. Epidural neurolytic blocks can be used as an alternative approach to intrathecal block, but the degree of analgesia produced is usually less profound. Moreover, intrathecal injections offer greater control over drug spread due to their hypobaricity or hyperbaricity in the cerebrospinal fluid. Potential complications vary from weakness to complete paralysis of the lower limb muscles as well as rectal and bladder sphincter dysfunction. Usually performed at the lumbar level, called a saddle block, some case series describe thoracic and cervical intrathecal neurolysis. Vertebroplasty and Kyphoplasty Percutaneous vertebroplasty (PV) is a radiologically guided procedure in which surgical bone cement is injected into a vertebra under imaging guidance. The aim of PV is to provide pain relief and bone strengthening in painful compression fractures involving the vertebral body. This technique is widely used to treat osteoporotic vertebral fractures and can also be applied to treat fractures caused by metastatic disease. Selected patients should have focal, intense and intractable midline spinal pain at the level of, or within two vertebral levels below the fracture, without evidence of definite radicular signs and symptoms, in which conservative management has failed. 16 Complications are rare, but the main one is caused by cement leaking through cortical defects and causing epidural compression of the spinal cord or neural elements. Kyphoplasty is a modification of PV and involves a balloon being placed percutaneously into the vertebral body. Inflation and deflation of the balloon creates a cavity before the injection of cement. Conclusion Until recently, interventional procedures have been used mostly as a last resort in patients with cancer pain. Several recent publications and guidelines on the management of cancer pain have recommended the use of certain interventional techniques at an earlier stage, possibly even at the stage, where opioid treatment is first being considered. Reserving the use of these techniques until the last few days of life is certainly not a good idea. However, every procedure has its complications. Notwithstanding your best intention, always remember there is no situation, so bad, that you cannot make it worse. 5/7

6 Key Learning Points The prevalence of pain among cancer pain is high. About one third of patients suffer from insufficient pain relief. Early adoption of interventional pain procedures can be recommended before even considering the use of strong opioids. Commonly used interventional therapies for cancer pain include spinal administration of analgesics, neurolytic block and vertebroplasty. Proper patient selection and meticulous technique are required to achieve best results and avoid complications 6/7

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