Transcript Intraspinal Drug Infusion for Chronic Pain

Principles and Practice of
Intraspinal Drug Infusion for
Chronic Pain
Richard K. Osenbach, M.D.
Director of Neurosciences and Neurosurgery
Cape Fear Valley Health System
Fayetteville, NC
History of Opiate Analgesia
1901 - intrathecal injection of morphine
1915 - antagonist of morphine discovered
1951 - 1st human use of morphine antagonists
1976 - 1st use of IT morphine in animals
1980 - spinal morphine used for cancer pain
Spinal Opiate Analgesia
Discovery of CNS opiate receptors
Identification of endogenous opiate peptides
Isolation of receptors
Endogenous Opioid Peptides
Proopiomelanocortin (POMC)


Endorphins
Beta-lipotropin
Proenkephalin A


Met-enkephalin, leu-enkephalin
Other enkephalins, peptide E
Prodynorphin


dynorphin A & B
neoendorphins ( and )
Opioid Receptors and Ligands
Opioid
Receptor
Endogenous
Agonist
Synthetic
Agonists
Antagonists
ß-Endorphin
Endomorphins
Morphine
DAMGO
Naloxone
ß-FNA
Delta (20-30%)
Met-Enkephalin
Leu-Enkephalin
DPDPE
SNC-80
DSTBULET
Naltrindole
Naloxone
Kappa (5-10%)
Dynorphine A
Dynorphine B
Mu (70%)
hORL1
Nociceptin/OFQ
None
Mu Receptor
Defined by affinity for morphine

Less affinity for other receptor subtypes
Most clinically important opioids selective for
Mu receptor
 Cross react at higher doses

1 - supraspinal
2 – spinal
Most analgesic effects of systemic morphine
mediated through 1 effects
70% located pre-synaptically
Morphine
High affinity for the Mu receptor
50x less affinity for delta receptor
 Minimal affinity for kappa, hORL1 receptor

Most physiological effects through action at
Mu receptor
Non-Mu effects with very high doses
No evidence fo Mu-Delta cross tolerance
Opioid Recptor Physiology
G-protein-coupled
receptor family
Synthesized in DRG
Second messenger using
camp
Negative coupling
 Inhibit camp via Giprotein
 And  - opening of K+
channels
 - Closing of ca2+
Opioid Receptor Physiology
 And  - opening of
K+ channels
 - Closing of ca2+
Opiate Receptors
Distributed pre- and post-synaptically
High affinity binding
Binding stereospecific
Optimal binding in ph range 7-8
Opioid Recetors
Analgesia
Dorsal horn


Lamina I
Substantia gelatinosa
Brainstem

Nucleus caudalis
Supraspinal



PAG
Medial and intralaminar thalamic nuclei
Striatum
Opioid Recptors
Autonomic Effects
Cough suppression, orthostatic hypotension

Nucleus tractus solitarius and ambiguous, locus ceruleus
Respiratory depression

Nucleus tractus solitarius, parabrachial nucleus
Nausea/vomiting

Area postrema
Meiosis

Superior colliculus, pretectal nuclei
Opioid Receptors
Miscellaneous Effects
Endocrine effects
Posterior pituitary – inhibition of vasopressin
 Hormonal effects – hypothalamic infundibulum

Behavioral effects

Amygdala, hippocampus, nucleus accumbuns,
basal ganglia
Motor rigidity

Striatum
Actions of Spinal Opiates
Application to spinal cord produces rapid and
potent analgesia
Reduction in activity in spinal projection neurons
in lamina V
Increases latency of pain behavior responses in
animals
Effects reversed with naloxone
Spinal Opiate Analgesia
Pre-synaptic Actions
Presynaptic action at neuron terminals
 C-fiber terminal zones in lamina I & II
Receptors synthesized in DRG
 rhizotomy - 70% reduction
Activation - inhibition of nerve terminal
 Reduction in transmitter release



tachykinins, excitatory AA, SP
Opening of K+ channels
Closing of ca+2 channels
Spinal Opiate Analgesia
Post-synaptic Actions
Receptors on neuronal cell body or dendritic
projections
Post-synaptic hyperpolarization
 identical ionic mechanisms
Reduction in evoked electrical activity
25% Mu and Delta receptors located on
neurons
Requires higher doses of systemic morphine

eg. A-fiber mediated allodynia
Spinal Opiate Analgesia
Disinhibitory Effect
Indirect post-synaptic action involving 3
neuron circuit


Enkephalin neurons in SG
GABA effect
Inhibition of inhibitory interneuron
Increased activity of second inhibitory
interneuron (release from inhibition)
Depression of activity in output neurons
Supraspinal Descending Modulation
1)
wall: transection of spinal cord results in increased activity of
lamina V neurons to noxious input  Bulbospinal pathway exerts
tonic inhibitory control on nociceptive neurons
2)
stimulation of specific brainstem sites produces a highly specific
suppression of the responses to noxious stimuli that is reversed by
monoamine receptor antagonists
3)
discreet lesions of the DLF block the inhibitory effects of
stimulation-produced analgesia
4)
microinjection of local anesthetics into the NRM blocks
stimulation-produced analgesia from PAG stimulation
Descending Modulation
Rationale for IT Drug Delivery
Provide high concentration of drug
at the site of interaction with
spinal receptors and minimize
spread to other regions in the
brain
Factors Affecting Drug Distribution
Patient characteristics
CSF properties
Drug properties
Injection technique
Injection Factors
Site of injection

Subarachnoid vs. Epidural
Velocity of injection
Turbulence (barbotage)
Bolus vs. continuous infusion
Drug Properties
Lipid solubility
Dose and volume
Baricity
Vasoconstrictors
Pharmacokinetics of IT Opioids
Uptake by spinal cord

Depends lipid solubility of
drug
Rostral - caudal
distribution by bulk flow
Transdural absorption systemic uptake
Continuous IT Drug Infusion
Hydrophilic Drugs
Concentration gradually increases and concentration
gradient develops
5 -7 half-lives to reach steady state
Distribution ratio constant regardless of drug
concentration
Final steady state concentration proportional to dose
infused
Continuous IT Drug Infusion
Lipophilic Drugs
Rapidly absorbed after contacting cell membranes,
blood vessels, BBB
Rapidly lost from CSF and systemically redestributed
Localized distribution
 catheter tip must be close to intended site of action
or high infusion dates must be used
Epidural Infusion
Epidural space acts as a reservoir for slow release of drug
 Release variable
 Timing of drug effects more unpredictable
2 - 3% epidural morphine crosses dura into CSF
Equi-analgesic effect requires 10x the amount of drug
given epidurally
Intraspinal Morphine
Conversion Ratios
300 mg oral morphine =
100 mg parenteral morphine =
10 mg epidural morphine =
1 mg intrathecal morphine
* May not be accurate at high doses
Alternative Agents
Alpha-2 agonists
 clonidine, tizanidine, dexmedotomidine
Local anesthetics

Bupivicaine, ropivicaine
Somatostatin analogs
 octreotide
Calcium channel blockers
 SNX-111 (zicontide)
NMDA Antagonists
 ketamine, dextrmethorphan, methadone
Miscellaneous agents

Adenosine, midazolam, gabapentin, aspirin
 - 2 Adrenergic Agonists
Inhibition of SP release
Inhibition of nociceptive neurons
Site of action separate from opiates and local
anesthetics
Synergistic with opiates
Approved for medium-term epidural
infusion for cancer pain
Daily dose 50 - 900 g
Side effects: hypotension
Calcium Channel Blockers
SNX-111
Antagonists of N-type Ca+2 channels antinociceptive in animals models of acute,
chronic, & neuropathic pain
synthetic form of -conopeptide MVIIA
Inhibits evoked nociceptive behavior in rats
when given IT
Staats Et Al, 1998
Chronic,intractable neuropathic Pain:
Marked Analgesic Efficacy of ziconotide
Randomized, prospective,
double-blind, placebocontrolled trial
N=102, VASPI score  50
Response =  30%
reduction in VASPI from
baseline without an inc. in
opiate requirements
Percent reduction
from baseline in
VASPI
40
30
20
10
0
SNX-111
Placebo
Penn et al, 1992
Octreotide for Cancer Pain
25
20
15
Octreotide
Pain level
10
5
0
0
10
20
30
40
50
60
Drug Selection
Patient Selection
Observable concordant pathology
Opioid-responsive pain
Failure of less invasive, complex therapy
Failure of long-acting oral opioids
Surgically-correctable pathology excluded
Psychological clearance
Successful screening trial
Life expectancy > 3 months (cancer pain)
Exclusion Criteria
Major psychological issues
Substance abuse history
Unresolved secondary gain issues
Medical contraindication for surgery
Spinal pathology precluding catheter placement
Allergy to opiates
Principles of Screening
Accurately select candidates for long-term IT drug
delivery
Physician and patient should define goals for IT drug
delivery BEFORE proceeding with a trial
Goals defined on a case-by-case basis
Theoretically, the trial should approximate as closely as
possible the conditions of long-term therapy
IT drug delivery is represents only a SINGLE element in
overall long-term pain management for a given patient
• A SUCCESSFUL TRIAL
DOES NOT GUARANTEE
LONG-TERM SUCCESS
OF IT INFUSION
Trial Assessment
Goals of Screening
Success of an IT drug trial must be defined in the context
of the goals that are set
Analgesic response
 What is significant?
 “One man’s junk is
another man’s treasure”
Drug-related side effects
Mood
Functional improvement
Trialing for IT Therapy
What do we know about screening?
Multiple accepted methods
No consensus as to the single best method
Screening Methods*
Single bolus
Multiple boluses
Continuous infusion, “functional trial”
*Intrathecal or epidural
Survey of Trialing Methods
epidural
infusion
35.3%
1999Continous
Survey of
Academic
Teaching Programs
52%Bolus
usingITcontinuous
injection infusion
33.7%
59% using IT route
Bolus epidural injection
17% using epidural route only
22%Continuous
using bothITroutes
infusion
24.5%
6.4%
Single IT Bolus Trial
ADVANTAGES



Procedurally simple
Low cost
Low risk and morbidity
DISADVANTAGES





Sub-analgesic drug levels; “false negative trial”
Side effects may obscure analgesic response
Higher likelihood of placebo response
Inability to determine accurate starting dose
Inability to evaluate ADL
Multiple Bolus Injections
ADVANTAGES



Ability to titrate dose
Establish dose-response curve
Placebo injections for comparison with active drug administration
DISADVANTGES

Increased incidence of side effects




Transient vs. sustained
Lack of correlation with continuous infusion
Multiple dural punctures required for IT delivery unless
temporary catheter used
More costly and time-consuming
Functional (Continuous) Trial
ADVANTAGES





Controlled dose titration
Assess starting dose for IT therapy
Reduce risk of drug-related side effects
Dissipates placebo effect over time
Assessment of functional outcome
DISADVANTGES




Procedurally more complicated
Requires greater expertise
Higher morbidity
More costly
Epidural vs. Intrathecal
CRITERIA
EPIDURAL
INTRATHECAL
Onset of Action
Slower onset of
analgesia
Faster onset of analgesia
Systemic Effects
Greater systemic
effects
Minimal systemic effects
Shorter-lasting
Longer-lasting
Higher dose to achieve
effect
Lower dose required (1/10
epidural dose)
 Higher incidence of
 Post-LP headache
systemic side effects
 Risk of epidural
abscess
 Respiratory depression
Duration of Effect
Dose
Adverse Effects/Risks
 Meningitis
Placebo Administration
Rationale: reduce the likelihood of a false positive trial
Normal individuals may exhibit a placebo response
Difficulty interpreting placebo response
A positive placebo response should not necessarily mean
“no pump”
Functional trialing with dose titration dissipates the
placebo response over time
Dosing
Primary determinants:


Route of administration
Current dose of systemic opioids
Large doses of systemic opioids will confer some
degree of tolerance

Higher IT dose tolerated (required)
Convert total daily dose of opioid to intraspinal
morphine equivalent


Epidural: 10% systemic dose
Intrathecal: 0.5-1% systemic dose
Oral Opioids During Trial
No consensus on alteration of systemic opioids
during the trial
Maintaining the patient on a portion of their daily
dose will lessen the likelihood of withdrawal
Withdrawal from systemic opioids may result in
reduction in opioid-induced hyperalgesia

May produce a “false positive” result
50-75% reduction in systemic dose
Liberal use of “breakthrough” medication

Minimal use of “breakthough” medication can be taken
as one objective measure of pain relief
Monitoring During Trial
Vital signs, pulse oximetry, apnea monitor
Pain reduction


VAS
Percent pain relief
Assessment of mood
Functional assessments



SF-36
MPQ
Oswestry disability index
Drug-related side effects
Supplemental opioid use
Side Effects of Spinal Opioids
Pruritis
Urinary retention
Nause/vomiting
Sedation
Respiratory depression
Continuous Epidural Infusion
Trial
Tunneled epidural catheter
Morphine infusion, 0.2mg/cc
Starting dose, 0.2mg/hr (1cc/hr)
Dose titration for 36-48 hours
Final dose: 4.8-48mg/day

IT dose: 0.48 – 4.8mg MS/day
Continuous IT Trial
Tunneled IT catheter


Algoline catheter, 33.5 inches
.0156 m./in = 0.5226 ml catheter volume
Calculate IT equi-analgesic dose
Morphine used as 1st line agent
Reduce systemic opioids by 50%
Assess VAS scores every 2 hours
Monitor development of side effects
Titrate infusion to analgesic effect
Quantitative Crossover Doubleblind IT Trial
Phase I – Dose Escalation Trial
Baseline VAS score
Bolus injections of IT morphine separated by 30 minute
Drop in VAS < 3, repeat IT morphine
Drop in VAS > 3, proceed to Phase II
Levy R, M.D, Ph.D.
Quantitative Crossover Doubleblind IT Trial
Phase II – Double-Blind Crossover Trial
IT Morphine vs. Saline
Day 1



Drug A – VAS scores for 6 hours
VAS scores within 1 point of baseline
Drug B
Day 2



Drug A – VAS scores for 6 hours
VAS scores within 1 point of baseline
Drug B
Levy R, M.D, Ph.D.
IT Bolus (ITB) vs. Continuous Epidural
Infusion (CEI)
86 patient screened for inclusion

28 excluded from inclusion
58 patients approached

18 declined inclusion
40 patients randomized

ITB (n=18) or CEI (n=19)
27 successful trial - pump implantation



ITB, 67% (12/18)
CEI, 79% (15/19)
3 patients lost to follow-up
ITB (n=10), CEI (n=14
Anderson V, Burchiel K, Cooke B: A Prospective Randomized Trial of Intrathecal Injection vs.
Epidural Infusion in the Selection of Patients for Continuous Intrathecal Opioid Therapy.
Neuromodulation, 2003
IT Bolus vs. CEI
No significant difference in 6 month
outcomes between ITB and CEI
ITB – 60% “successful” response
 CEI – 64% “successful” response

Drug-related complications more common
in ITB group (88%) vs. CEI group (70%)
CEI 2.5 times more costly ($4,762 vs. 1,862)
CONCLUSION: Differences in pain and functional
response to long-term IT opioids among patients
selected by either trial method are not large
IT Bolus vs. CEI
VAS Pain Scores
100
80
60
IT
CEI
40
20
0
Baseline
6 Months
% Change
Anderson V, Burchiel K, Cooke B: A Prospective Randomized Trial of Intrathecal Injection vs.
Epidural Infusion in the Selection of Patients for Continuous Intrathecal Opioid Therapy.
Neuromodulation, 2003
Questions Regarding Trialing
Screening method
Duration of trial
Drug and dose
Use of placebo
Systemic opioids
Criteria for success
Pump Implantation
Catheter insertion
Tunneling and anchoring of catheter
Pump pocket preparation
Preparation and filling of pump
Connection of catheter to pump
Anchoring of pump
Catheter Complications
 Fractures
 Occur around spinous processes with midline catheter placement
 Withdrawal of catheter through needle
 Kinks
 Occur at connections and anchors from lack of slack and/or not using a
strain relief sleeve
 Holes
 Missing or failed strain relief sleeve at pump connector on
one-piece catheter
 Several reports of small holes in one-piece catheter under pump. No
reports of holes under the pump with the two-piece catheter
 Dislodgements
 Occur from pump movement and lack of slack at pump and catheter
causing the catheter to slip through anchor
 Occur from ligament motion or CSF pressure and no anchor or purse
string suture at fascial entry point
7/7/2015
Confidential
62
Catheter Complications
Medtronic Clinical Study
7.0%
0.061
6.0%
0.051
5.0%
0.04
4.0%
0.03
3.0%
2.0%
1.0%
0.0%
0.007
0.004
0.003
0.003
0.001
0.001
0.001
Catheter Complications
20-25% incidence
20,000 implants annually
5,000 catheter revisions annually
Estimated revision cost $10,000
$50,000,000 yearly revision cost
Proper catheter placement is
probably the single most
important aspect of pump
implantation for avoiding
device-related complications
Catheter Fracture - Midline Insertion
Midline
Two Piece Catheter (8731)
Pre-attached catheter
anchor/connecting pin
Sutureless strain relief
sleeve (distal)
Pre-attached
pump connector
8711 catheter
8731 Catheter
Pre-attached proximal
strain relief sleeve
Catheter Insertion Technique
Paramedian entry



1.5-2 cm off midline toward side of pump pocket
1 to 1 ½ vertebral levels caudal to dural entry
Avoid midline insertion
Shallow angle of insertion, 30 degrees

Facilitates catheter insertion
Position catheter just below conus
Catheter Insertion
~ 30°
Catheter Insertion
Catheter Fracture/Tears
Pulling the catheter back
through the introducer
needle may shear or
create holes in the
catheter
Gently remove stylet with
catheter fully stretched;
Using excessive force can
produce tears in the
catheter
Expose Lumbodorsal Fascia
5-6 cm incision down to
fasica
Leave needle in place to
avoid cutting catheter
Undermine each side to
facilitate anchoring
Pump Pocket
Upper quadrant of abdomen; 2
inches below/parallel to costal
margin
Big enough, but not too big
AVOID





incision directly over refill port
site of current/future surgery
site of previous radiation
iliac crest, rib cage
placing directly beneath beltline
Tunneling and Anchoring
Back-to-Front
Strain relief loop
of catheter
Anchor at fascial
insertion site
Anchoring Pump
Connect catheter to pump and secure
Coil excess tubing behind pump
Place pump in pocket and secure with nonabsorbable sutures
Suture loop
 Dacron pouch

Aspirate/inject through CAP to confirm
patency
Catheter tip
Dural
puncture
Pump anchored
with sutures or
pouch
Paramedian
Oblique Entry
V-wing anchor
5 cm of slack in
catheter
Loop of excess
catheter under
pump
Catheter connector which
also functions as the
primary anchor
Complications
Infection
 most often occurs at pump pocket
 REMOVE the system
Post-dural puncture headache
CSF leak
Mechanical problems



Misplaced catheter
Catheter disconnection
Catheter migration
Pump pocket seroma
Spinal Opiates for Benign Pain
Accepted yet controversial
Mixed reviews and results
Long-term effectiveness is unclear given the
non-uniformity of reporting outcomes
No definitive end-point for therapy
Spinal Opiates For Non-Cancer Pain
PAIN DISTRIBUTION
Axial lower back pain
Diffuse bilateral leg pain
Unilateral leg pain

failed trial of spinal cord stimulation
Spinal Opiates
Non-Malignant Pain
U.S. experience, 1981-1992
14 authors, 156 patients
69% (107) good-excellent pain relief
75% (126 of 169) with cancer pain had
good-excellent pain relief
Krames E: Spinal Administration of Opioids for Nonmalignant
Pain Syndromes: A U.S. Experience
Spinal Opiates
Non-Malignant Pain
120 patients

63% (n=76) with FBSS or LBP
Mean age: 54.0 + 11.2 years (28-79)
Follow-up period

mean: 3.4 + 1.3 years (0.5 - 5.7 years)
Winkellmuller et al.: J Neurosurgery 85:458-467, 1996
Spinal Opiates
Non-malignant Pain
Mean morphine dose
initial: 2.7 mg/day (0.3-12 mg/day)
 after 3.4 years: 4.7 mg/day (0.3-12 mg/day)

28 patients followed more than 4 years
64% (n=18) constant dosage history
 36% (n=10) increase in morphine dose >
6mg/day after 1 year

Winkellmuller et al.: J Neurosurgery 85:458-467, 1996
Mean Pain Scores
100
Mean VAS
80
• 74% benefit from therapy
•Avg. pain reduction
• 67% at 6 months
•58% last follow-up
60
40
• 81% improve quality of life
20
•92% “satisfied”
0
Before
1st FU
Last FU
Winkellmuller et al.: J Neurosurgery 85:458-467, 1996
Mean IT Morphine Dose (mg/day)
Mean Daily Morphine Dose
5
LBP
4.5
4
3.5
3
2.5
2
Initial exam
First FU
Last FU
Winkellmuller et al.: J Neurosurgery 85:458-467, 1996
Totals
Multicenter Review of Spinal Opiates
Retrospective review of 429 patients
66% non-malignant pain
Physician assessment
 global pain relief scores
 percent pain relief
 VAS scores for pain intensity
 ADL, overall activity level
 Employment
Paice: J Pain Symptom Management, 1996
Global Pain Relief
43%
Excellent 52.4%
5%
Good
42.9%
Poor
4.8%
52%
Paice: J Pain Symptom Management, 1996
Changes in ADL
14%
4%
82%
Increased
82%
No Change
14%
Decreased
4%
Paice: J Pain Symptom Management, 1996
Daily Opiate Dosage
Mean daily dose, 9.2 mg/day
Initial dose higher for non-malignant
pain
Gradual linear dose escalation in nonmalignant pain
At 24 months, dosages similar in
patients with non-malignant and cancer
pain
Paice: J Pain Symptom Management, 1996
Conclusions of Multicenter Review
Nociceptive pain responds best to spinal
opiates
Neuropathic pain responds to spinal opiates but
may require higher dosages
Addition of local anesthetics may by
synergistic in neuropathic pain
Prospective Study - Spinal Opiates
40 patients with non-malignant pain
 mostly FBSS with > 3 operations
Mean duration of pain, 8 + 9 years (6mos-40yrs)
30 (75%) had successful screening trial
 minimum of 50% pain reduction by VAS
Follow-up 6, 12, 18, 24 months
 complete data for 20 patients followed for 2
years
Outcome by VAS, CIPI, BDI, MPQ
Anderson V,Burchiel K: Neurosurgery, Feb. 1999
Results
VAS for pain and pain coping scores
remained improved
CIPI and MPQ scores improved and
persisted
Initial morphine dose 1.96 + 1.8 mg/day,
inc. to 6.0 + 7.0 at 3 months, 9.43 + 8.8 at
15 months
Device complications, 20%
Anderson V,Burchiel K: Neurosurgery, Feb. 1999
Visual Analog Scores
Mean initial VAS
78.5 ± 15.9 (39-100)
Percent change in VAS
significantly decreased
at each interval
Decrease in VAS
greatest during the
initial 3 months
Reduction in VAS
remained relatively
constant
80
70
60
50
40
30
20
10
0
Initial
Anderson V,Burchiel K: Neurosurgery, Feb. 1999
6-mo
18-mo
McGill Pain Scores
40
35
30
25
PRI
20
MP
Q-s
15
10
5
0
Baseline
3
6
12
18
24
Anderson V,Burchiel K: Neurosurgery, Feb. 1999
CIPI Scores
30
CIPI improved for 1218 months
25
Several CIPI subscales
showed trends toward
sustained improvement
15
20
10
5
0
Initial
Anderson V,Burchiel K: Neurosurgery, Feb. 1999
6
18
Medication Intake
Daily IT morphine dose  25mg
Mean equianalgesic opioid dose increased
significantly over time
 initial: 1.96 ± 1.75 mg/day
 24 months: 14.59 ± 20.52 mg/day
Dose escalation most rapid during initial 3
months
Oral narcotic intake


initial: 90% (28/30)
24 months: 30% (6/30)
Spinal Opiates for Benign Pain
Maron J, Loeser J: The Clinical Journal Pain, 1996
Data insufficient to permit formal analysis
The proper role of intraspinal opioids in the
treatment of non-malignant pain cannot be
determined from the existing literature
Spinal opiates for benign pain should be
considered experimental
All patients who receive such therapy
should be part of a clinical protocol
Unresolved Issues
How should outcome be measured?
Management of tolerance
Question of neurotoxicity
Development of hyperalgesia
Indefinite requirement for medical care
The Dilemma of Outcomes
A lack of consensus complicates
the interpretation of many if not
the majority of efficacy studies
The Bottom Line
There can be no substitute for sound
clinical judgement based on a detailed
assessment of each patient !
Conclusions
Intraspinal opiates can be safely used in patients
with non-malignant pain syndromes without fear of
drug abuse
Intraspinal opiates are effective in reducing pain in
carefully selected patients with non-malignant pain
syndromes including FBSS
Most patient with non-malignant pain express
satisfaction with the therapy
Patients experience improvements in ADL
Whether intraspinal opiates improve return to work
rates in patients with FBSS remain unresolved
Conclusions
Spinal opiates are effective in patients with
pain due to cancer
Long term issues regarding tolerance,
neurotoxicity, etc. are generally irrelevant
Choice of device depends on anticipated life
expectancy