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Implantable technologies for pain management
PAIN
Implantable technologies for pain management
Learning objectives After reading this article you should be able to: C explain the mechanism of action of modulatory techniques in pain management C list the indications and contraindications for neuromodulatory techniques C outline the evidence base for neuromodulatory techniques in failed back surgery syndrome (FBSS).
Mahesh Chaudhari Alistair McKeown
Abstract Chronic pain occurs in up to half the adult population at some point in their lives, with 10% of this group disabled by pain. Unrelieved chronic pain is a major socioeconomic and healthcare problem and successful management of affected individuals requires a full range of treatment options. Since Melzack and Wall’s Gate Theory of Pain was first proposed, an improved understanding of neuroscience has lead to development of implantable ‘neuromodulatory’ technologies for refractory pain. Simply put, such technologies involve drug delivery to, or electrical stimulation of neural pathways. In the context of pain management, neuromodulation aims to reduce afferent activity within pain pathways by targeted electrical neurostimulation or drug delivery into cerebrospinal fluid. Targets for implanted neurostimulators include the spinal cord, peripheral nerves or brain, while implantable pumps deliver analgesic drugs to intrathecal or intracerebroventricular sites. Implantable neuromodulation therapies are expensive, invasive and prone to side effects and complications. Clinicians and health professionals involved with implantation and aftercare of such devices require a high level of expertise. In spite of these challenges the uptake of these therapies continues to rise worldwide as does the evidence for cost-effectiveness. To optimize outcomes, patients being considered for neuromodulatory therapies must undergo comprehensive biopsychosocial assessment, be fully informed regarding risks and have realistic expectations. This article will focus on spinal cord stimulation and intrathecal drug delivery (ITDD) for the non-expert.
Clinical indications for spinal cord stimulation (SCS) SCS is mainly indicated for conditions associated with ‘neuropathic’ pain. SCS does not inhibit and is ineffective for ‘nociceptive’ pain, e.g. the pain of myocardial infarction is not inhibited by SCS Good indications for SCS (likely to respond) C Neuropathic pain in leg or arm following lumbar or cervical spine surgery (FBSS/FNSS) C Complex regional pain syndrome (CRPS) C Neuropathic pain secondary to peripheral nerve damage C Pain associated with peripheral vascular disease C Refractory angina pectoris (RAP) C Brachial plexopathy: traumatic (partial, not avulsion), post-irradiation
Intermediate indications for SCS (may respond) C
C C
C
Keywords Intrathecal drug delivery; neuromodulation; neurostimulation therapies; peripheral nerve stimulation; spinal cord stimulation
Amputation pain (stump pain responds better than phantom pain) Axial pain following spinal surgery Intercostal neuralgia, such as post-thoracotomy or post-herpetic neuralgia Pain associated with spinal cord damage (other peripheral neuropathic pain syndromes, such as those following trauma may respond)
Poor indications for SCS (rarely respond) C C
Spinal cord stimulation (SCS) C
Pain modulation by SCS involves supraspinal activation via the posterior columns of the spinal cord and the recruitment of endogenous inhibitory pathways. Evidence from animal studies indicates that sympathetic and GABAnergic interneurons play a role in stimulation-induced pain relief and that SCS alters neurotransmitter concentrations in cerebrospinal fluid. There is also a pronounced autonomic effect; the mechanisms of this are
Unresponsive to SCS C C C
Complete spinal cord transection Non-ischaemic nociceptive pain Nerve root avulsion
Contraindications to SCS Coagulopathy C Sepsis C Immunosuppression C Poor general health C Active psychiatric illness C Problem drug use C Inability to cooperate or control the device C Certain pacemakers C
Mahesh Chaudhari FRCA is a Consultant in Anaesthesia and Pain Medicine at Worcestershire Royal Hospital, Worcester, UK. Conflicts of interest: none declared. Alistair McKeown MBChB BSc Med Sci (Hons) MRCP is an ST6 in Palliative Medicine at the Beatson West of Scotland Cancer Centre, Glasgow, UK. Conflicts of interest: none declared.
ANAESTHESIA AND INTENSIVE CARE MEDICINE 12:2
Central pain of non-spinal cord origin Spinal cord injury with clinically complete loss of posterior column function Perineal or anorectal pain
Table 1
58
Ó 2010 Elsevier Ltd. All rights reserved.
PAIN
Set amplitude (in volts) to ascertain perception and discomfort thresholds. The aim of trial screening is to position the SCS electrode so that the area of usual pain is ‘covered’. A percutaneous trial of SCS can last for up to 4 weeks; however, some practitioners proceed directly to implantable pulse generator (IPG) implantation if the patient reports pain relief from initial on-table trial screening. Criteria for a successful trial of SCS vary and may include at least 50% pain relief, at least 80% paraesthesia coverage, functional gains and a reduced need for analgesic medication.
not fully understood. The preservation of topographically appropriate posterior column function seems to be necessary for SCS to be effective, but there is debate regarding which elements are necessary. Table 1 lists the clinical indications for SCS. An SCS system comprises: An epidurally sited electrode e SCS electrodes are available as arrays of multi-contact electrodes on a slim catheter ‘lead’, a larger insulated ‘plate’ or ‘paddle’ electrode. Lead electrodes are inserted percutaneously through a Tuohy needle under fluoroscopic guidance while ‘plate’ electrodes are surgically implanted via a small laminotomy (Figure 1). Electrodes are available with a varying number of contact points (usually four or eight). For bilateral pain, a single electrode in the midline may suffice; however, improved paraesthesia ‘coverage’ may result if two octopolar electrodes are inserted either side of the midline. A pulse-generator supplies electrical input to SCS electrodes, and can be a fully implanted device similar in size to a cardiac pacemaker or an external device that transmits to a small implanted radiofrequency receiver.
Stage 2: implantation e IPGs are powered by lithium-ion batteries and therefore need to be replaced when the battery is exhausted. The average replacement interval for non-rechargeable IPGs is approximately 5 years. However, battery life varies depending on the patient’s daily pattern of SCS use and system current requirements. New rechargeable batteries have been developed that can last up to 9 years. Insertion of the IPG can be performed using local anaesthetic and sedation or general anaesthetic. Neurosurgical plate electrode and IPG implantations are done as a one-stage procedure under general anaesthetic. The position of SCS leads should always be checked prior to second-stage IPG implantation to check for lead migration during the trial period. The most common placement sites for IPG include: the anterior abdominal wall, the fat pad in the posterior iliac area and the infraclavicular area. Radiofrequency (RF) systems consist of a passive receiver implanted under the skin and a battery-powered transmitter worn outside the body. An antenna applied to the skin over the receiver and connected to the transmitter, delivers stimulation energy transcutaneously. Although RF systems can reduce the number of replacement procedures needed, most patients prefer IPGs to RF
Implantation Stage 1: trial of SCS e prophylactic antibiotics and a sterile operating theatre are considered mandatory. In-theatre epidural electrode positioning, trial stimulation or ‘screening’ is performed under local anaesthesia. Initial stimulation parameters that are programmed into the trial stimulator are: Assign positive and negative contact points to create an electrical circuit (e.g. a ‘guarded cathode’) with anodes on either side in the midpoint of the lead. Set pulse width (e.g. 200 ms). Set frequency (e.g. 80 Hz).
Spinal cord stimulation
Electrode lead Lead electrode
Implantable pulse generator
Tuohy needle
Figure 1
ANAESTHESIA AND INTENSIVE CARE MEDICINE 12:2
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Ó 2010 Elsevier Ltd. All rights reserved.
PAIN
systems because the need for an external transmitter and antenna may be cosmetically undesirable, inconvenient and associated with adverse skin reactions.
neuropathic or ischaemic origin in 2008. SCS is recommended as a treatment option for adults with chronic pain of neuropathic origin. This recommendation was based on RCT data and robust cost-effectiveness analyses for trials in FBSS and CRPS. SCS is not, however, recommended for chronic pain of ischaemic origin except in the context of research as part of a clinical trial; this is due to lack of high-quality RCT data and insufficient economic modelling. The cost of SCS is recouped within a few years of implantation in patients with heterogeneous pain diagnoses because of reduced conventional medical management and hospitalizations.
IPG programming e clinician programming of IPGs is done postoperatively when the patient is awake and cooperative, using a hand-held, computerized telemetric device. The overall complication rate reported in the first 12 months following SCS system implantation is 43%, reducing to about 4% thereafter. Most patients who benefit from SCS are able to continue using this therapy in the long term. Table 2 lists the complications and precautions for implantable SCS devices. The complication rate is likely to be lower in a service with experienced implanting clinicians and a multidisciplinary team adhering to principles of best practice.
Intrathecal Intrathecal drug delivery (ITDD) is indicated for the treatment of severe refractory neuropathic pain, nociceptive pain and spasticity in patients who suffer from treatment-limiting side effects on oral medication. Since the oraleintrathecal ratio for morphine is of the order of 300:1, selective spinal opioid analgesia offers the potential for reduced systemic side effects and improved analgesia. Commonly, intrathecal opioids (for nociceptive pain), baclofen (for spasticity) and local anaesthetics are used but guidelines also recommend newer drugs, such as ziconotide. There are practical difficulties, specific side effects and costs associated with ITDD. A good circulation of cerebrospinal fluid (CSF) is essential, and as for SCS, comprehensive biopsychosocial assessment of the patient and full consideration of less invasive treatment options is required before implantation of an ITDD system.
Outcome studies The success rate quoted for SCS therapy varies from 12% to 88% according to published studies, with approximately 60% of implanted patients benefiting from this therapy in the long term. There is clinical evidence from randomized controlled trials (RCTs) to support use of SCS in pain from failed back surgical syndrome (FBSS), complex regional pain syndrome (CRPS), neuropathic pain, and ischaemic pain. The National Institute for Health and Clinical Excellence published guidance on SCS for chronic pain of
Complications and precautions for implantable spinal cord stimulation (SCS) devices
Contraindications Absolute contraindications include, patient refusal, coagulopathies, local infection and septicaemia (with risk of infection of the system leading to abscess, meningitis). Relative contraindications include, inadequate social support, immunosuppression and raised intracranial pressure. Active neurological disease, spinal cord compression and spinal deformity may also be contraindications. ITDD systems comprise two system components: an intrathecal catheter and a drug delivery device or pump. Examples of systems include:
Common and less serious complications include: C Electrode migration C Electrode breakage C System infection C System damage due to ingress of body fluids C System disconnection C Post-dural puncture headache
Low expense
Rare but serious complications include: C Nerve root damage related to electrode placement C Paraplegia from spinal haematoma or abscess Precautions in patients with SCS C Diathermy – unipolar diathermy is contraindicated; however, bipolar diathermy can be used safely, according to manufacturers. Devices emitting short-wave, microwave and ultrasonic diathermy are contraindicated because of the risk of heatinduced neural damage at electrode contact points. C Magnetic resonance imaging (MRI) is potentially hazardous in patients with SCS systems. However, if MRI is essential, then the MRI compatibility of the patient’s specific system should be confirmed by an experienced neuroradiologist. If the SCS system is MRI incompatible or if the clinician is in doubt, an alternative mode of scanning should be performed. C Security devices e SCS devices can activate and be affected by security devices in airports and shops. Consequently, patients are counselled appropriately and given a manufacturer’s identity card to produce at relevant places.
A percutaneous intrathecal catheter with or without subcutaneous tunnelling (e.g. using Portex epidural or Codman Flextip Plus catheters). An implanted intrathecal catheter as above, connected to a subcutaneous injection port (e.g. Port-a-cath). Moderate expense
An implanted intrathecal catheter connected to an implanted, patient-activated pump (e.g. AlgoMed). An implanted totally implanted intrathecal catheter with implanted constant rate infusion pump (e.g. Codman Archimedes or 3000 pumps). High expense
A totally implanted intrathecal catheter with implanted programmable infusion pump (e.g. SynchroMed). A percutaneous system is suitable for a trial of ITDD or in patients with limited life expectancy (e.g. less than 3 months). Such systems require vigilance in order to identify infection as well as displacement or disconnection of the catheter. Fully implanted ITDD systems are suitable for long-term use and allow virtually unrestricted mobility and functional ability of the patient.
Table 2
ANAESTHESIA AND INTENSIVE CARE MEDICINE 12:2
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Ó 2010 Elsevier Ltd. All rights reserved.
PAIN
There are two types of automatic implanted ITDD devices.
devices is performed with radiographic screening to verify the correct positioning of the intrathecal catheter (Figure 2). Complications of ITDD include pharmacological side effects attributable to the drugs used and mechanical complications associated with the pump delivery systems (incidence up to 20%). Common pharmacological side effects comprise nausea and vomiting (25%), urinary retention (19%), pruritus (17%), sedation (17%), myoclonic activity (18%) and respiratory depression (3%). Mechanical complications include catheter dislodgement, kinking, obstruction and migration, CSF leakage, seroma or haematoma formation and pump mechanical failure. A rare but potentially dangerous late complication is catheter tip granuloma formation related to high morphine concentrations.
A fixed rate pump has two hollow chambers divided by a bellows, one chamber is filled with active drug and the other with liquid gas. The liquid gas vaporizes at body temperature, expanding and exerting pressure on the drug reservoir, forcing the drug through an outlet filter into the flow-restricting capillary tube to the silicon rubber delivery tube that is connected to the intrathecal catheter. To accommodate the daily drug dose changes, the concentration of the drug in the reservoir has to be altered by draining and replacing the infusate. This type of system is not power-source dependent and should last for the lifetime of the patient.
Outcomes Malignant pain: a systemic review published in the Cochrane Database in 2005 concluded that intrathecal opioid therapy is effective for pain that is not controlled by conventional modes of analgesia. Smith and colleagues in their randomized controlled trial in 2002 showed improved pain control, significantly less drug toxicity and improved quality of life with ITDD compared to comprehensive medical management.
A programmable pump uses an internal battery and electronic circuitry to vary the flow-rate of the pump over a defined range. It can deliver a fixed or variable rate plus automatic or patientactivated boluses and can be reprogrammed using a telemetric device. Insertion of ITDD The patient’s life expectancy, underlying diagnosis and cost of pump influence the choice of system. As for SCS, a biopsychosocial assessment of the patient and full consideration of less invasive treatment options are required before implantation of an ITDD system. In addition, a trial of ITDD is considered best practice before implantation. Protocols to prevent ITDD system infection are of the utmost importance given the potentially catastrophic risks of central nervous system infection, as well as therapy withdrawal in cancer patients. Implantation of ITDD
Spasticity: the treatment of spasticity using intrathecal baclofen in multiple sclerosis, cerebral palsy and spinal cord injury is well supported by published evidence. Chronic non-malignant pain: although evidence for the effectiveness of ITDD in non-malignant pain is not as strong as for cancer pain or spasticity there are number of studies supporting
Implantable drug delivery systems
Fully implanted – fixed rate
Percutaneous
a b
c
d
Spinal catheter
Codman Archimedes pump (a) Central filling port; (b) side sampling/bolus port; (c) flextip plus catheter; (d) paraumbilical pump pocket
Port-a-cath percutaneous portal Figure 2
ANAESTHESIA AND INTENSIVE CARE MEDICINE 12:2
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Ó 2010 Elsevier Ltd. All rights reserved.
PAIN
NICE technology appraisal guidance 159. Spinal cord stimulation for chronic pain of neuropathic or ischaemic origin. October 2008. Raphael JH, Gnanadurai TV, Southall JL, Mutagi H, Kapur S. Placebocontrolled single blind study of short-term efficacy of spinal morphine in chronic non-malignant pain. Reg Anesth Pain Med 2006; 31: 47. Smith TJ, Coyne PJ, Staats PS, et al. An implantable drug delivery system (IDDS) for refractory cancer pain provides sustained pain control, less drug related toxicity and possibly better survival compared with comprehensive medical management (CMM). Ann Oncol 2005; 16: 825e33. Spinal cord stimulation for the management of pain: recommendations for best clinical practice. The British Pain Society’s consensus document, April 2009.
the effectiveness of ITDD in patients who have severe chronic pain that is refractory to all other appropriate interventions. A
FURTHER READING Ballantyne JC, Carwood C. Comparative efficacy of epidural, subarachnoid, and intracerebroventricular opioids in patients with pain due to cancer. Cochrane Database Syst Rev; 2006. Art no. CD 005178. Deer T, et al. Polyanalgesic Consensus Conference 2007: recommendations for the management of pain by intrathecal (intraspinal) drug delivery: report of an interdisciplinary expert panel. Neuromodulation 2007; 10: 300e28.
ANAESTHESIA AND INTENSIVE CARE MEDICINE 12:2
62
Ó 2010 Elsevier Ltd. All rights reserved.
Implantable technologies for pain management
Learning objectives After reading this article you should be able to: C explain the mechanism of action of modulatory techniques in pain management C list the indications and contraindications for neuromodulatory techniques C outline the evidence base for neuromodulatory techniques in failed back surgery syndrome (FBSS).
Mahesh Chaudhari Alistair McKeown
Abstract Chronic pain occurs in up to half the adult population at some point in their lives, with 10% of this group disabled by pain. Unrelieved chronic pain is a major socioeconomic and healthcare problem and successful management of affected individuals requires a full range of treatment options. Since Melzack and Wall’s Gate Theory of Pain was first proposed, an improved understanding of neuroscience has lead to development of implantable ‘neuromodulatory’ technologies for refractory pain. Simply put, such technologies involve drug delivery to, or electrical stimulation of neural pathways. In the context of pain management, neuromodulation aims to reduce afferent activity within pain pathways by targeted electrical neurostimulation or drug delivery into cerebrospinal fluid. Targets for implanted neurostimulators include the spinal cord, peripheral nerves or brain, while implantable pumps deliver analgesic drugs to intrathecal or intracerebroventricular sites. Implantable neuromodulation therapies are expensive, invasive and prone to side effects and complications. Clinicians and health professionals involved with implantation and aftercare of such devices require a high level of expertise. In spite of these challenges the uptake of these therapies continues to rise worldwide as does the evidence for cost-effectiveness. To optimize outcomes, patients being considered for neuromodulatory therapies must undergo comprehensive biopsychosocial assessment, be fully informed regarding risks and have realistic expectations. This article will focus on spinal cord stimulation and intrathecal drug delivery (ITDD) for the non-expert.
Clinical indications for spinal cord stimulation (SCS) SCS is mainly indicated for conditions associated with ‘neuropathic’ pain. SCS does not inhibit and is ineffective for ‘nociceptive’ pain, e.g. the pain of myocardial infarction is not inhibited by SCS Good indications for SCS (likely to respond) C Neuropathic pain in leg or arm following lumbar or cervical spine surgery (FBSS/FNSS) C Complex regional pain syndrome (CRPS) C Neuropathic pain secondary to peripheral nerve damage C Pain associated with peripheral vascular disease C Refractory angina pectoris (RAP) C Brachial plexopathy: traumatic (partial, not avulsion), post-irradiation
Intermediate indications for SCS (may respond) C
C C
C
Keywords Intrathecal drug delivery; neuromodulation; neurostimulation therapies; peripheral nerve stimulation; spinal cord stimulation
Amputation pain (stump pain responds better than phantom pain) Axial pain following spinal surgery Intercostal neuralgia, such as post-thoracotomy or post-herpetic neuralgia Pain associated with spinal cord damage (other peripheral neuropathic pain syndromes, such as those following trauma may respond)
Poor indications for SCS (rarely respond) C C
Spinal cord stimulation (SCS) C
Pain modulation by SCS involves supraspinal activation via the posterior columns of the spinal cord and the recruitment of endogenous inhibitory pathways. Evidence from animal studies indicates that sympathetic and GABAnergic interneurons play a role in stimulation-induced pain relief and that SCS alters neurotransmitter concentrations in cerebrospinal fluid. There is also a pronounced autonomic effect; the mechanisms of this are
Unresponsive to SCS C C C
Complete spinal cord transection Non-ischaemic nociceptive pain Nerve root avulsion
Contraindications to SCS Coagulopathy C Sepsis C Immunosuppression C Poor general health C Active psychiatric illness C Problem drug use C Inability to cooperate or control the device C Certain pacemakers C
Mahesh Chaudhari FRCA is a Consultant in Anaesthesia and Pain Medicine at Worcestershire Royal Hospital, Worcester, UK. Conflicts of interest: none declared. Alistair McKeown MBChB BSc Med Sci (Hons) MRCP is an ST6 in Palliative Medicine at the Beatson West of Scotland Cancer Centre, Glasgow, UK. Conflicts of interest: none declared.
ANAESTHESIA AND INTENSIVE CARE MEDICINE 12:2
Central pain of non-spinal cord origin Spinal cord injury with clinically complete loss of posterior column function Perineal or anorectal pain
Table 1
58
Ó 2010 Elsevier Ltd. All rights reserved.
PAIN
Set amplitude (in volts) to ascertain perception and discomfort thresholds. The aim of trial screening is to position the SCS electrode so that the area of usual pain is ‘covered’. A percutaneous trial of SCS can last for up to 4 weeks; however, some practitioners proceed directly to implantable pulse generator (IPG) implantation if the patient reports pain relief from initial on-table trial screening. Criteria for a successful trial of SCS vary and may include at least 50% pain relief, at least 80% paraesthesia coverage, functional gains and a reduced need for analgesic medication.
not fully understood. The preservation of topographically appropriate posterior column function seems to be necessary for SCS to be effective, but there is debate regarding which elements are necessary. Table 1 lists the clinical indications for SCS. An SCS system comprises: An epidurally sited electrode e SCS electrodes are available as arrays of multi-contact electrodes on a slim catheter ‘lead’, a larger insulated ‘plate’ or ‘paddle’ electrode. Lead electrodes are inserted percutaneously through a Tuohy needle under fluoroscopic guidance while ‘plate’ electrodes are surgically implanted via a small laminotomy (Figure 1). Electrodes are available with a varying number of contact points (usually four or eight). For bilateral pain, a single electrode in the midline may suffice; however, improved paraesthesia ‘coverage’ may result if two octopolar electrodes are inserted either side of the midline. A pulse-generator supplies electrical input to SCS electrodes, and can be a fully implanted device similar in size to a cardiac pacemaker or an external device that transmits to a small implanted radiofrequency receiver.
Stage 2: implantation e IPGs are powered by lithium-ion batteries and therefore need to be replaced when the battery is exhausted. The average replacement interval for non-rechargeable IPGs is approximately 5 years. However, battery life varies depending on the patient’s daily pattern of SCS use and system current requirements. New rechargeable batteries have been developed that can last up to 9 years. Insertion of the IPG can be performed using local anaesthetic and sedation or general anaesthetic. Neurosurgical plate electrode and IPG implantations are done as a one-stage procedure under general anaesthetic. The position of SCS leads should always be checked prior to second-stage IPG implantation to check for lead migration during the trial period. The most common placement sites for IPG include: the anterior abdominal wall, the fat pad in the posterior iliac area and the infraclavicular area. Radiofrequency (RF) systems consist of a passive receiver implanted under the skin and a battery-powered transmitter worn outside the body. An antenna applied to the skin over the receiver and connected to the transmitter, delivers stimulation energy transcutaneously. Although RF systems can reduce the number of replacement procedures needed, most patients prefer IPGs to RF
Implantation Stage 1: trial of SCS e prophylactic antibiotics and a sterile operating theatre are considered mandatory. In-theatre epidural electrode positioning, trial stimulation or ‘screening’ is performed under local anaesthesia. Initial stimulation parameters that are programmed into the trial stimulator are: Assign positive and negative contact points to create an electrical circuit (e.g. a ‘guarded cathode’) with anodes on either side in the midpoint of the lead. Set pulse width (e.g. 200 ms). Set frequency (e.g. 80 Hz).
Spinal cord stimulation
Electrode lead Lead electrode
Implantable pulse generator
Tuohy needle
Figure 1
ANAESTHESIA AND INTENSIVE CARE MEDICINE 12:2
59
Ó 2010 Elsevier Ltd. All rights reserved.
PAIN
systems because the need for an external transmitter and antenna may be cosmetically undesirable, inconvenient and associated with adverse skin reactions.
neuropathic or ischaemic origin in 2008. SCS is recommended as a treatment option for adults with chronic pain of neuropathic origin. This recommendation was based on RCT data and robust cost-effectiveness analyses for trials in FBSS and CRPS. SCS is not, however, recommended for chronic pain of ischaemic origin except in the context of research as part of a clinical trial; this is due to lack of high-quality RCT data and insufficient economic modelling. The cost of SCS is recouped within a few years of implantation in patients with heterogeneous pain diagnoses because of reduced conventional medical management and hospitalizations.
IPG programming e clinician programming of IPGs is done postoperatively when the patient is awake and cooperative, using a hand-held, computerized telemetric device. The overall complication rate reported in the first 12 months following SCS system implantation is 43%, reducing to about 4% thereafter. Most patients who benefit from SCS are able to continue using this therapy in the long term. Table 2 lists the complications and precautions for implantable SCS devices. The complication rate is likely to be lower in a service with experienced implanting clinicians and a multidisciplinary team adhering to principles of best practice.
Intrathecal Intrathecal drug delivery (ITDD) is indicated for the treatment of severe refractory neuropathic pain, nociceptive pain and spasticity in patients who suffer from treatment-limiting side effects on oral medication. Since the oraleintrathecal ratio for morphine is of the order of 300:1, selective spinal opioid analgesia offers the potential for reduced systemic side effects and improved analgesia. Commonly, intrathecal opioids (for nociceptive pain), baclofen (for spasticity) and local anaesthetics are used but guidelines also recommend newer drugs, such as ziconotide. There are practical difficulties, specific side effects and costs associated with ITDD. A good circulation of cerebrospinal fluid (CSF) is essential, and as for SCS, comprehensive biopsychosocial assessment of the patient and full consideration of less invasive treatment options is required before implantation of an ITDD system.
Outcome studies The success rate quoted for SCS therapy varies from 12% to 88% according to published studies, with approximately 60% of implanted patients benefiting from this therapy in the long term. There is clinical evidence from randomized controlled trials (RCTs) to support use of SCS in pain from failed back surgical syndrome (FBSS), complex regional pain syndrome (CRPS), neuropathic pain, and ischaemic pain. The National Institute for Health and Clinical Excellence published guidance on SCS for chronic pain of
Complications and precautions for implantable spinal cord stimulation (SCS) devices
Contraindications Absolute contraindications include, patient refusal, coagulopathies, local infection and septicaemia (with risk of infection of the system leading to abscess, meningitis). Relative contraindications include, inadequate social support, immunosuppression and raised intracranial pressure. Active neurological disease, spinal cord compression and spinal deformity may also be contraindications. ITDD systems comprise two system components: an intrathecal catheter and a drug delivery device or pump. Examples of systems include:
Common and less serious complications include: C Electrode migration C Electrode breakage C System infection C System damage due to ingress of body fluids C System disconnection C Post-dural puncture headache
Low expense
Rare but serious complications include: C Nerve root damage related to electrode placement C Paraplegia from spinal haematoma or abscess Precautions in patients with SCS C Diathermy – unipolar diathermy is contraindicated; however, bipolar diathermy can be used safely, according to manufacturers. Devices emitting short-wave, microwave and ultrasonic diathermy are contraindicated because of the risk of heatinduced neural damage at electrode contact points. C Magnetic resonance imaging (MRI) is potentially hazardous in patients with SCS systems. However, if MRI is essential, then the MRI compatibility of the patient’s specific system should be confirmed by an experienced neuroradiologist. If the SCS system is MRI incompatible or if the clinician is in doubt, an alternative mode of scanning should be performed. C Security devices e SCS devices can activate and be affected by security devices in airports and shops. Consequently, patients are counselled appropriately and given a manufacturer’s identity card to produce at relevant places.
A percutaneous intrathecal catheter with or without subcutaneous tunnelling (e.g. using Portex epidural or Codman Flextip Plus catheters). An implanted intrathecal catheter as above, connected to a subcutaneous injection port (e.g. Port-a-cath). Moderate expense
An implanted intrathecal catheter connected to an implanted, patient-activated pump (e.g. AlgoMed). An implanted totally implanted intrathecal catheter with implanted constant rate infusion pump (e.g. Codman Archimedes or 3000 pumps). High expense
A totally implanted intrathecal catheter with implanted programmable infusion pump (e.g. SynchroMed). A percutaneous system is suitable for a trial of ITDD or in patients with limited life expectancy (e.g. less than 3 months). Such systems require vigilance in order to identify infection as well as displacement or disconnection of the catheter. Fully implanted ITDD systems are suitable for long-term use and allow virtually unrestricted mobility and functional ability of the patient.
Table 2
ANAESTHESIA AND INTENSIVE CARE MEDICINE 12:2
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Ó 2010 Elsevier Ltd. All rights reserved.
PAIN
There are two types of automatic implanted ITDD devices.
devices is performed with radiographic screening to verify the correct positioning of the intrathecal catheter (Figure 2). Complications of ITDD include pharmacological side effects attributable to the drugs used and mechanical complications associated with the pump delivery systems (incidence up to 20%). Common pharmacological side effects comprise nausea and vomiting (25%), urinary retention (19%), pruritus (17%), sedation (17%), myoclonic activity (18%) and respiratory depression (3%). Mechanical complications include catheter dislodgement, kinking, obstruction and migration, CSF leakage, seroma or haematoma formation and pump mechanical failure. A rare but potentially dangerous late complication is catheter tip granuloma formation related to high morphine concentrations.
A fixed rate pump has two hollow chambers divided by a bellows, one chamber is filled with active drug and the other with liquid gas. The liquid gas vaporizes at body temperature, expanding and exerting pressure on the drug reservoir, forcing the drug through an outlet filter into the flow-restricting capillary tube to the silicon rubber delivery tube that is connected to the intrathecal catheter. To accommodate the daily drug dose changes, the concentration of the drug in the reservoir has to be altered by draining and replacing the infusate. This type of system is not power-source dependent and should last for the lifetime of the patient.
Outcomes Malignant pain: a systemic review published in the Cochrane Database in 2005 concluded that intrathecal opioid therapy is effective for pain that is not controlled by conventional modes of analgesia. Smith and colleagues in their randomized controlled trial in 2002 showed improved pain control, significantly less drug toxicity and improved quality of life with ITDD compared to comprehensive medical management.
A programmable pump uses an internal battery and electronic circuitry to vary the flow-rate of the pump over a defined range. It can deliver a fixed or variable rate plus automatic or patientactivated boluses and can be reprogrammed using a telemetric device. Insertion of ITDD The patient’s life expectancy, underlying diagnosis and cost of pump influence the choice of system. As for SCS, a biopsychosocial assessment of the patient and full consideration of less invasive treatment options are required before implantation of an ITDD system. In addition, a trial of ITDD is considered best practice before implantation. Protocols to prevent ITDD system infection are of the utmost importance given the potentially catastrophic risks of central nervous system infection, as well as therapy withdrawal in cancer patients. Implantation of ITDD
Spasticity: the treatment of spasticity using intrathecal baclofen in multiple sclerosis, cerebral palsy and spinal cord injury is well supported by published evidence. Chronic non-malignant pain: although evidence for the effectiveness of ITDD in non-malignant pain is not as strong as for cancer pain or spasticity there are number of studies supporting
Implantable drug delivery systems
Fully implanted – fixed rate
Percutaneous
a b
c
d
Spinal catheter
Codman Archimedes pump (a) Central filling port; (b) side sampling/bolus port; (c) flextip plus catheter; (d) paraumbilical pump pocket
Port-a-cath percutaneous portal Figure 2
ANAESTHESIA AND INTENSIVE CARE MEDICINE 12:2
61
Ó 2010 Elsevier Ltd. All rights reserved.
PAIN
NICE technology appraisal guidance 159. Spinal cord stimulation for chronic pain of neuropathic or ischaemic origin. October 2008. Raphael JH, Gnanadurai TV, Southall JL, Mutagi H, Kapur S. Placebocontrolled single blind study of short-term efficacy of spinal morphine in chronic non-malignant pain. Reg Anesth Pain Med 2006; 31: 47. Smith TJ, Coyne PJ, Staats PS, et al. An implantable drug delivery system (IDDS) for refractory cancer pain provides sustained pain control, less drug related toxicity and possibly better survival compared with comprehensive medical management (CMM). Ann Oncol 2005; 16: 825e33. Spinal cord stimulation for the management of pain: recommendations for best clinical practice. The British Pain Society’s consensus document, April 2009.
the effectiveness of ITDD in patients who have severe chronic pain that is refractory to all other appropriate interventions. A
FURTHER READING Ballantyne JC, Carwood C. Comparative efficacy of epidural, subarachnoid, and intracerebroventricular opioids in patients with pain due to cancer. Cochrane Database Syst Rev; 2006. Art no. CD 005178. Deer T, et al. Polyanalgesic Consensus Conference 2007: recommendations for the management of pain by intrathecal (intraspinal) drug delivery: report of an interdisciplinary expert panel. Neuromodulation 2007; 10: 300e28.
ANAESTHESIA AND INTENSIVE CARE MEDICINE 12:2
62
Ó 2010 Elsevier Ltd. All rights reserved.