Developments in the Treatment of Chronic Pain

1
Developments in the Treatment of Chronic Pain
2
Agenda

• Welcome
• Types of pain
• Common chronic pain conditions
• Introduction to Medtronic neurostimulation
• Introduction to Medtronic intrathecal drug
  delivery
• Patient selection
• Neurostimulation clinical evidence
• Intrathecal drug delivery clinical evidence
• Role of interventional pain specialist
• Case study

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Welcome

• ltInsert name(s) of physician presenter(s),
  practice name/logo, physician photo(s)gt
• ltInsert patient speaker(s) name(s), type of
  therapygt

4
Types of Pain
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Types of Neuropathic Pain

• Results from damage to nerves
• Direct nerve root injury Radiculopathy
• Battered root syndrome
• Perineural fibrosis
• Intrafascicular fibrosis
• Adhesive arachnoiditis
• Peripheral deafferentation
• Phantom limb pain
• Sympathetic-mediated pain syndrome
• Herpetic neuralgia
• Diabetic polyneuropathy
• Central deafferentation-thalamic stroke

Cole AJ. In Low Back Pain Handbook, 2nd ed. 2003
pg 361-374
6
Types of Nociceptive Pain

• Results from damage to muscle, tissue, and organs
• Cuts and bruises
• Bone fractures
• Burns
• Mechanical low back pain
• Most postsurgical pain

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Combined Nociceptive and Neuropathic Pain

• Failed back surgery syndrome (FBSS)
• Idiopathic chronic pain syndrome
• Cancer pain
  
• Also referred to as postsurgical chronic
  back pain

Cole AJ. In Low Back Pain Handbook, 2nd ed. 2003
pg 361-374.
8
Some Chronic Pain Conditions

• Postsurgical chronic back pain or failed back
• Radicular pain syndrome or radiculopathies
• Fibromyalgia
• Peripheral causalgia
• Arachnoiditis
• Complex regional pain syndrome

9
Rethinking the Pain Treatment Ladder
In contrast to earlier thinking on the order of
treatments in the pain treatment continuum,1 it
has been proposed that device therapies be
considered at an earlier stage.2
1Krames ES. Intraspinal Opioid Therapy for
Nonmalignant Pain Current Practices and Clinical
Guidelines. J Pain Symptom Manage
199611333-352. 2Stamatos JM, et al. Live Your
Life Pain Free, October 2005. Based on the
interventional pain management experience of Dr.
John Stamatos.
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Introduction to Medtronic Neurostimulation
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Neurostimulation Therapy

• Delivers electrical signals to the epidural space
• Inhibits pain signals before they reach the brain
  and replaces them with a tingling sensation that
  covers the specific areas where pain is felt
• Indicated for management of chronic, intractable
  pain of the trunk and/or limbs, including
  unilateral or bilateral pain

12
Benefits of Neurostimulation

• An effective method of pain control for many
  patients when used as directed
• May reduce the need for pain medications
• Less invasive than surgical alternatives
• Reversiblecan be discontinued or, if desired by
  the patient, surgically removed
• Systems reprogrammable without surgery
• Trial helps assess patient response
• Patient control within preprogrammed limits

Kumar K, Taylor R, Jacques L, et al.
Neurosurgery. 200863762-770. Burchiel KJ,
Anderson VC, Brown FD, et al. Prospective,
multicenter study of spinal cord stimulation for
relief of chronic back and extremity pain. Spine.
1996212786-2794.
13
Neurostimulation Trial

• Neurostimulation therapy trial provides an
  opportunity to assess the effectiveness of
  neurostimulation without making a long-term
  commitment
• Gauge patient response
• Provide an adjustment period
• Explore therapy parameters
• Improve therapy cost-effectiveness
• The goal is at least a 50 reduction in pain
• Patient-specific goals may include less pain
  reduction but improved quality of life

Kumar K, Hunter G, Demeria D. Spinal cord
stimulation in treatment of chronic benign pain.
Challenges in treatment planning and present
status, a 22-year experience. Neurosurgery.
200658(3)481-496.
14
Neurostimulation Risks

• The most frequently reported problems following
  the spinal cord stimulator implant surgery
  include
• infection,
• lead movement,
• pain at the implant site,
• loss of therapy effect, and
• therapy which did not meet the patient's
  expectations.
• Some of the most severe reported problems
  following spinal cord simulator implant surgery
  include epidural hemorrhage, spinal fluid
  leakage, and paralysis.

For more details on risks/complications, refer to
product package insert or visit www.medtronic.com.
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Neurostimulation Risks (cont.)
Information sources Medtronic Neurostimulation
Therapy for Chronic Pain Percutaneous Lead
Implantation Guide. Minneapolis, MN Medtronic,
Inc. 2008. Medtronic Implantable Systems
Performance Registry (ISPR) 2007 Annual Report
Protocol NSP0010-10000. Minneapolis, MN
Medtronic, Inc. October 2, 2008. Medtronic
Neurostimulation Systems for Pain Therapy Brief
Summary Minneapolis, MN Medtronic, Inc.
December 2004.
16
Introduction to Medtronic IntrathecalDrug
Delivery (IDD)
17
Intrathecal Drug Delivery (IDD) Therapy

• IDD therapy involves the delivery of pain
  medicine into the intrathecal space
• The pump is connected to a thin, flexible
  catheter both are implanted under the skin
• Smaller doses of medication are needed for
  effective pain relief because drug is delivered
  directly to the pain receptors

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Synchromed II Drug Infusion System Indications

• Chronic intrathecal infusion of preservative-free
  morphine sulfate sterile solution in the
  treatment of chronic intractable pain
• Also indicated for chronic intrathecal infusion
  of preservative-free ziconotide sterile solution
  for the management of severe chronic pain

19
Approximate Equivalent Daily Doses of Morphine
Route of Administration Relative Potency (mg)
Oral Intravenous Epidural Intrathecal 300 100 20 1
Relative approximations based on clinical
observations.
Lamer TJ. Treatment of cancer-related pain when
orally administered medications fail. Mayo Clin
Proc. 199469473-480.
20
Benefits of IDD Therapy

• Pain relief for patients who have not received
  adequate relief with conventional therapies
• May reduce adverse effects from oral opioids such
  as nausea, vomiting, sedation, and constipation
• May decrease or eliminate use of oral analgesics
• Increased ability to perform activities of daily
  living
• Patient control of medication within
  physician-set limits
• May be effective for patients who do not
  experience relief from neurostimulation therapy

Lamer TJ Mayo Clin Proc. May 199469(5)473-80.
Paice JA. Intraspinal morphine for chronic pain
a retrospective, multicenter study. J Pain
Symptom Manage. 19961171-80.
21
IDD Trial

• The purpose of the trial is to assess the
  efficacy and side effects of intrathecal morphine
• Trialing methods include
• Continuous epidural
• Continuous intrathecal
• Bolus epidural
• Bolus intrathecal
• Patients who report at least 50 reduction in
  pain may be candidates for long-term therapy

22
IDD Therapy Risks
The most frequently reported problems following
drug infusion system implant surgery include

• infection
• spinal fluid leak
• pump inversion
• dislodged or blocked catheter
• skin erosion

• drug side effects
• loss of therapy effect
• therapy which did not meet the patients
  expectations

Other complications may occur, and may require
surgery to correct. Some of the most severe
reported problems associated with intrathecal
drug delivery therapy for chronic pain include
inflammatory mass, spinal cord damage,
meningitis, life threatening drug adverse effects
due to over infusion as a result of programming
or patient monitoring errors or device
malfunction, and complications due to use of
unapproved drugs and/or not using drugs in
accordance with drug labeling.
For more details on risks/complications, refer to
product package insert or visit www.medtronic.com.
23
IDD Therapy Risks (cont.)
Information sources Medtronic Synchromed II
Programmable Infusion System Clinical Reference
Guide Intrathecal Morphine for Pain Management.
Minneapolis, MN Medtronic, Inc. May
2007. Medtronic Implantable Systems Performance
Registry (ISPR) 2007 Annual Report Protocol
NSP0010-10000. Minneapolis, MN Medtronic, Inc.
October 2, 2008. Synchromed II Drug Infusion
System Brief Summary Minneapolis, MN Medtronic,
Inc. January 2008. Coffey R. Mortality
Associated with Intrathecal Opioid Drug Infusion
to Treat Non-Cancer Pain Risk Factors and
Mitigation. Paper presented at the North American
Neuromodulation Society 12th Annual Meeting
December 4-7, 2008 Las Vegas, NV.
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Patient Selection
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Indications for Neurostimulation and Intrathecal
Drug Delivery Therapy
Cole AJ. In Low Back Pain Handbook, 2nd ed. 2003
pg 362. Refer to full prescribing information
for Medtronic Neurostimulation Systems and
Synchromed II Drug Infusion Systems.
26
Patient Selection Considerations

• Patients who have neuropathic pain in a
  concordant anatomic distribution usually respond
  best to neurostimulation (NS) therapy.
• Patients who have nociceptive pain in a
  concordant distribution usually respond best to
  intrathecal drug delivery (IDD).
• Patients who do not respond well to NS may be
  candidates for IDD therapy.

Cole AJ. In Low Back Pain Handbook, 2nd ed. 2003
pg 362.
27
Patient Selection Checklist

• Failure of oral/transdermal opiate use or
  intolerable side effects
• More conservative therapies have failed
• An observable pathology exists that is concordant
  with the pain complaint
• Further surgical intervention is not indicated
• No serious untreated drug habituation exists
• Psychological evaluation and clearance for
  implantation has been obtained
• No contraindications to implantation exist

• Refer Patient for a Pain Therapy Trial

Cole AJ. In Low Back Pain Handbook, 2nd ed. 2003
pg 362.
28
Neurostimulation Clinical Evidence
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Medtronic PROCESS Study Results

• Primary outcome
• Number of SCS CMM patients with 50 leg pain
  relief ( 50 reduction in leg VAS) is
• at 6 months, 23 of 42 or 55
• at 12 months, 16 of 42 or 38
• at 24 months, 17 of 42 or 40

Kumar K, Taylor R, Jacques L, et al.
Neurosurgery. 200863762-770.
30
Medtronic PROCESS Study Results

• Secondary outcomes evaluated at 1, 3, 6, 9, 12,
  18 and 24 months (24 month data presented)

Leg pain relief (leg VAS) Leg Significant improvement (plt0.0001)
Back pain relief (axial back VAS) No significant difference
Quality of life (SF-36 and EQ-5D) SF-36 significant improvement for 7 of 8 dimensionsEQ-5D significant improvement
Function (Oswestry Disability Index) Significant improvement (p0.0002)
Patient satisfaction 93 satisfied with treatment
Need for drug or nondrug therapy for pain No clear pattern of change
Work status Increased from 21 to 27
Adverse events See Adverse Events slide
Kumar K, Taylor R, Jacques L, et al.
Neurosurgery. 200863762-770.
31
Significant Improvement in Function
Key Findings Significant improvement in
function (Oswestry Disability Index) in SCSCMM
group over 24 months.
Kumar K, Taylor R, Jacques L, et al.
Neurosurgery. 200863762-770.
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More Effective than Repeat Surgery
Key Findings Among patients available for
long-term follow up, SCS was significantly more
successful than reoperation 9 (47) of 19
patients randomized to SCS and 3 (12) of 26
patients randomized to reoperation achieved at
least 50 pain relief and were satisfied with
treatment.
North RB, Kidd D, Shipley J, et al. Spinal cord
stimulation versus reoperation for failed back
surgery syndrome a cost effectiveness and cost
utility analysis based on a randomized,
controlled trial. Neurosurg. 200761361-369.
33
Efficacy of Spinal Cord Stimulation
Neurostimulation Improves Quality of Life

• Subjects were implanted with SCS over a period of
  10 years at one pain center
• Efficacy assessed after an average follow-up of
  almost four years

Van Buyten JP, Van Zundert J, Vueghes P,
Vanduffel L. Efficacy of spinal cord stimulation
10 years of experience in a pain centre in
Belgium. Eur J Pain 20015299-307. n125 pain
cases Plt0.01 for all activities
34
Intrathecal Drug Delivery Clinical Evidence
35
Decreased Use of Pain Medications
88.2 of patients were taking systemic opioids at
baseline.
Key Findings At 6 months, 65 of patients
decreased their use of systemic opioids from
baseline. At 12 months, 42 of patients
decreased their usage compared with the 6-month
follow-up.
Deer T, Chapple I, Classen A, et al. Intrathecal
drug delivery for treatment of chronic low back
pain report from the National Outcomes Registry
for Low Back Pain. Pain Med. 200456-13. n136
36
Overall Global Pain Relief
Key Findings Overall pain relief of 50 was
reported by 82 of patients (40 of 49).
Roberts LJ, Finch PM, Goucke CR, et al. Outcome
of intrathecal opioids in chronic non-cancer
pain. Eur J Pain. 20015353-361. n88
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Role of InterventionalPain Specialist
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Practice Management Collaboration
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Interventional Pain SpecialistPain Management
Approach

• Recognizes unique benefits of technological
  advances and interventions
• Communicates with all concerned parties to ensure
  best treatment possible
• Develops follow-up plan once pain successfully
  treated
• Collaborates with referring physician when
  treatment overlaps with general health care
• Follows up with referring physician when pain is
  under better control

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Interventional Pain Specialist Referral
Considerations

• Intractable pain
• Intolerable side effects from systemic analgesics
• Conservative therapies ineffective
• Patients functional status declines
• Uncomfortable prescribing or monitoring opioids

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Case Study Sample Referral Profile

• Male, 45, office manager, no major psychosocial
  issues
• One spine surgery to treat herniated disc
• Referred from primary care physician to address
  axial back pain and secondary radicular pain that
  persists 6 months following anatomically
  corrective surgery
• Average back pain score (VAS) of 80/100 with
  diminished functional capacity
• Relief from physical rehabilitation therapy was
  not satisfactory
• Unsuccessfully treated with neuropathic pain
  agents and two systemic opioids, patient
  experienced extreme sedation and constipation
• Treated with nerve block series but relief was
  temporary

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Device Therapy Referral Interventional Pain
Specialist Role

• Conduct a thorough patient history and physical
  exam
• Develop an interventional pain treatment plan
• Conduct a Medtronic pain therapy trial
• Perform the Medtronic pain therapy implantation
  or refer after the trial
• Develop a follow-up plan with the patient and
  primary/referring physician

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Summary

• Patients should not have to wait for effective
  pain relief.
• By partnering, we can help patients find the
  right pain treatment.
• Together we can improve the quality of life for
  chronic pain patients.
• Our decisions may change the course of a
  patients life.

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SynchroMed Infusion SystemBrief Summary
Product technical manuals and the appropriate
drug labeling must be reviewed prior to use for
detailed disclosure. Indications US Chronic
intraspinal (epidural and intrathecal) infusion
of preservative-free morphine sulfate sterile
solution in the treatment of chronic intractable
pain, chronic intrathecal infusion of
preservative-free ziconotide sterile solution for
the management of severe chronic pain, and
chronic intrathecal infusion of Lioresal
Intrathecal (baclofen injection) for the
management of severe spasticity chronic
intravascular infusion of floxuridine (FUDR) or
methotrexate for the treatment of primary or
metastatic cancer. Outside of US Chronic
infusion of drugs or fluids tested as compatible
and listed in the product labeling. Contraindicati
ons When infection is present when the pump
cannot be implanted 2.5 cm or less from the
surface of the skin when body size is not
sufficient to accept pump bulk and weight when
contraindications exist relating to the drug
drugs with preservatives. Do not use the
Personal Therapy Manager accessory to administer
opioid to opioid-naïve patients or to administer
ziconotide. Warnings Comply with all product
instructions for initial preparation and filling,
implantation, programming, refilling, and
injecting into the catheter access port (CAP) of
the pump. Failure to comply with all instructions
can lead to technical errors or improper use of
implanted infusion pumps and result in additional
surgical procedures, a return of underlying
symptoms, or a clinically significant or fatal
drug under- or overdose. Refer to the appropriate
drug labeling for specific under- or overdose
symptoms and methods of management. Avoid using
short wave (RF) diathermy within 30 cm of the
pump or catheter. Diathermy may produce
significant temperature rises in the area of the
pump and continue to heat the tissue in a
localized area. If overheated, the pump may over
infuse the drug, potentially causing a drug
overdose. Effects of other types of diathermy
(microwave, ultrasonic, etc.) on the pump are
unknown. An inflammatory mass that can result in
serious neurological impairment, including
paralysis, may occur at the tip of the implanted
catheter. Clinicians should monitor patients on
intraspinal therapy carefully for any new
neurological signs or symptoms. For intraspinal
therapy, use only preservative-free sterile
solution indicated for intraspinal use. Use only
Medtronic components indicated for use with this
system. Failure to firmly secure connections can
allow drug or cerebrospinal fluid (CSF) leakage
into tissue and result in tissue damage or
inadequate therapy. A postoperative priming bolus
should not be programmed if the pump is a
replacement and the catheter has not been
aspirated.
45
SynchroMed Infusion SystemBrief Summary
continued
Refer to appropriate drug labeling for
indications, contraindications, warnings,
precautions, dosage and administration
information, and screening procedures. Physicians
must be familiar with the drug stability
information in the technical manual and must
understand the dose relationship to drug
concentration and pump flow rate before
prescribing pump infusion. Implantation and
ongoing system management must be performed by
individuals trained in the operation and handling
of the infusion system. Inform patients of the
signs and symptoms of drug under- or overdose,
appropriate drug warnings and precautions
regarding drug interactions, potential side
effects, and signs and symptoms that require
medical attention. Instruct patients to notify
their clinician of travel plans, to return for
refills at prescribed times, avoid activities
such as strenuous exercise or contact sports that
jar, impact, twist, or stretch the body, to
always carry their Medtronic device
identification card, to avoid manipulating the
pump through the skin, and to notify healthcare
professionals of the implanted pump before
medical tests/procedures. Patients must consult
their physician before engaging in activities
involving pressure or temperature changes (e.g.,
scuba diving, saunas, hot tubs, hyperbaric
chambers, flights, skydiving, etc.) Inform
patients that pump has an Elective Replacement
Indicator (ERI) that sounds when the pump is
nearing its end of service. When the alarm
sounds, patients must contact their doctor to
schedule pump replacement. Precautions The pump
is ethylene oxide sterilized. Do not use if the
product or package is damaged, the sterile seal
is broken, or the Use By date has expired. Do
not reuse or resterilize the pump it is intended
for single use only. Do not expose the pump to
temperatures above 43C or below 5C. Consider
use of peri- and post-operative antibiotics for
pump implantation, for any subsequent surgical
procedure, or if infection is present. For
patients prone to CSF leaks, clinicians should
consider special procedures, such as a blood
patch. Follow instructions for emptying and
filling the pump during a replacement or
revisions that require removal of the pump from
the pocket. Explant the pump postmortem if
incineration is planned (to avoid explosion), or
if local environmental regulations mandate
removal. Return explanted devices to Medtronic
for analysis and safe disposal. Do not implant a
pump dropped onto a hard surface or showing signs
of damage. Implant the pump less than 2.5 cm from
the surface of the skin. Ensure pump ports will
be easy to access after implant, that the
catheter is not kinked and secured well away from
pump ports before suturing. Keep the implant site
clean, dry, and protected from pressure or
irritation. If therapy is discontinued for an
extended period of time, fill the reservoir with
preservative-free saline in intraspinal
applications or appropriate heparinized solution
(if not contraindicated) in vascular
applications.
46
SynchroMed Infusion SystemBrief Summary
continued
The magnetic field or telemetry signals produced
by the programmer may cause sensing problems and
inappropriate device responses with an
implantable pacemaker and/or defibrillator.
Electromagnetic interference (EMI) is an energy
field generated by equipment found in the home,
work, medical, or public environments. Most EMI
normally encountered will not affect the
operation of the pump. Exceptions include injury
resulting from heating of the pump which can
damage surrounding tissue (diathermy, MRI),
system damage which can require surgical
replacement or result in loss/change in symptom
control (defibrillation, electrocautery,
high-output ultrasonics, radiation therapy), and
operational changes to the pump causing the motor
to stop, loss of therapy, return of underlying
symptoms, and require confirmation of pump
function (diathermy, high magnetic field devices,
hyperbaric/hypobaric conditions, magnetic
resonance imaging (MRI)). MRI will temporarily
stop the pump motors rotor due to the magnetic
field of the MRI scanner and suspend drug
infusion during MRI exposure which will cause the
pump alarm to sound. The pump should resume
normal operation upon termination of MRI
exposure. Prior to MRI, the physician should
determine if the patient can safely be deprived
of drug delivery. If not, alternative delivery
methods for the drug can be utilized during the
MRI scan. Prior to scheduling an MRI scan and
upon its completion, pump status should be
confirmed. Adverse Events Include, but are not
limited to, cessation of therapy due to end of
device service life or component failure, change
in flow performance due to component failure,
inability to program the device due to programmer
failure, CAP component failure inaccessible
refill port due to inverted pump, pocket seroma,
hematoma, erosion, infection, post-lumbar
puncture (spinal headache), CSF leak,
radiculitis, arachnoiditis, bleeding, spinal cord
damage, meningitis (intrathecal applications),
anesthesia complications, damage to the pump,
catheter and catheter access system due to
improper handling and filling before, during, or
after implantation change in catheter
performance due to catheter kinking,
disconnection, leakage, breakage, occlusion,
dislodgement, migration, or catheter fibrosis
body rejection phenomena, surgical replacement of
pump or catheter due to complications local and
systemic drug toxicity and related side effects,
complications due to use of unapproved drugs
and/or not using drugs in accordance with drug
labeling, or inflammatory mass at the tip of the
catheter. USA Rx Only Rev 0209
47
Neurostimulation Systems for Pain Therapy
Disclosure

• Brief Summary Product manuals must be reviewed
  prior to use for detailed disclosure.
• Indications
• Implantable neurostimulation systems - A
  Medtronic implantable neurostimulation system is
  indicated for spinal cord stimulation (SCS)
  system as an aid in the management of chronic,
  intractable pain of the trunk and/or
  limbs-including unilateral or bilateral pain
  associated with the following conditions
• Failed Back Syndrome (FBS) or low back syndrome
  or failed back
• Radicular pain syndrome or radiculopathies
  resulting in pain secondary to FBS or herniated
  disk
• Postlaminectomy pain
• Multiple back operations
• Unsuccessful disk surgery
• Degenerative Disk Disease (DDD)/herniated disk
  pain refractory to conservative and surgical
  interventions
• Peripheral causalgia
• Epidural fibrosis
• Arachnoiditis or lumbar adhesive arachnoiditis
• Complex Regional Pain Syndrome (CRPS), Reflex
  Sympathetic Dystrophy (RSD), or causalgia
• Contraindications
• Diathermy - Do not use shortwave diathermy,
  microwave or therapeutic ultrasound diathermy
  (all now referred to as diathermy) on patients
  implanted with a neurostimulation system. Energy
  from diathermy can be transferred through the
  implanted system and cause tissue damage at the
  locations of the implanted electrodes, resulting
  in severe injury or death.
• Warnings

48
Neurostimulation Systems for Pain Therapy
Disclosure continued

• in stimulation. Rupture or piercing of the
  neurostimulator can result in severe burns. An
  implanted cardiac device (eg, pacemaker,
  defibrillator) may damage a neurostimulator, and
  the electrical pulses from the neurostimulator
  may result in an inappropriate response of the
  cardiac device.
• Precautions
• The safety and effectiveness of this therapy has
  not been established for pediatric use (patients
  under the age of 18), pregnancy, unborn fetus, or
  delivery. Patients should be detoxified from
  narcotics prior to lead placement. Clinicians and
  patients should follow programming guidelines and
  precautions provided in product manuals.
  Patients should avoid activities that may put
  undue stress on the implanted neurostimulation
  system components. Patients should not scuba dive
  below 10 meters of water or enter hyperbaric
  chambers above 2.0 atmosphere absolute (ATA).
  Electromagnetic interference, postural changes,
  and other activities may cause shocking or
  jolting.
• Adverse Events
• Adverse events may include undesirable change in
  stimulation described by some patients as
  uncomfortable, jolting or shocking hematoma,
  epidural hemorrhage, paralysis, seroma, CSF
  leakage, infection, erosion, allergic response,
  hardware malfunction or migration, pain at
  implant site, loss of pain relief, chest wall
  stimulation, and surgical risks.
• For further information, please call Medtronic at
  1-800-328-0810 and/or consult Medtronics website
  at www.medtronic.com.
• USA Rx Only Rev 0209

49
Thank You