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European Interactive Pain Course31.8-05.09.08
Friday Pain therapy of osteoarthritis
European Interactive Pain Course03.-07.09.07
Frioday Chronic non-cancer pain syndromes
Workshop Part I Opioids in non-cancer pain Pain therapy of osteoarthritis
Workshop Part II Pain in the elderly Treatment of osteoporosis Opioids in the elderly (new studies)
Workshop Part III Treatment of low back pain (Case report)
Summary
End of Workshop
European Interactive Pain Course03.-07.09.07
Arthritis (arthritis deformans, osteoarthritis) is a disease of the joint cartilage, which in some cases is intermittent, in some cases pro-gresses continuously, and is accompanied by degenerative changes in the bones (subchondral sclerosis, osteophytes, subchondral cysts) and reactive changes in the joint capsule.
Arthritis – Definition
Prof. Swoboda Erlangen University Orthopaedic Clinic 2004
European Interactive Pain Course03.-07.09.07
Arthritis – Classification
Primary (idiopathic): cause unknown
Secondary: posttraumatic, postinfectious
Other possible causes: articular malpositioning
axial deviation
crystallopathy (gout)
endocrine, haematological and metabolic primary diseases
European Interactive Pain Course03.-07.09.07
Arthritis – Risk Factors
Old age
Obesity (osteoarthritis of the knee)
Genetic factors
Congenital/acquired joint deformities
Joint trauma
Previous joint surgery (e.g. meniscectomy)
Individual joint strain (occupation, hobbies, sport)
European Interactive Pain Course03.-07.09.07
Arthritis – Classification
Life-long disease Episodic course
ClassificationLatent: asymptomatic radiological signs
Manifest: radiological signs with clinical symptoms of arthritis
Active: radiological signs, synovitis, very severe pain
European Interactive Pain Course03.-07.09.07
Arthritis - Classical Radiological Criteria
Narrowing of joint cavity
Osteophytes
Subchondral sclerosis
Subchondral cysts
Epiphyseal deformity
European Interactive Pain Course03.-07.09.07
Arthritis – Clinical Picture
Pain (on strain, movement, rest, nocturnal pain)Morning stiffness (usually < 30 min.) pain on getting goingSwellingMuscular atrophy as a result of avoiding exerciseRestricted movement (contractures)CrepitationEradication of joint contoursSynovial irritationJoint effusionAxial deviationPalpable osteophytes
European Interactive Pain Course03.-07.09.07
Differentiating between osteoarthritis and rheumatoid arthritis
Arthritis in at least 3 joint regions
Fluctuating capsule swelling > 6 weeks
Symmetrical arthritis > 6 weeks
Morning stiffness of the joints (at least 1 h)
Rheumatic nodules
Rheumatoid factor detected
Radiological lesions
4 of the 7 criteria must be met to warrant a diagnosis of RA.
Classification criteria according to the College of Rheumatology (ACR)
European Interactive Pain Course03.-07.09.07
Case Report: Mr Bode
65 years, pronounced osteoarthritis of the left hip
Concomitant diseases Coronary heart disease Diabetes mellitus type II
Medication Diclofenac 3 x 50 mg OmeprazoleOral antidiabetic, ASA, beta-blockers, ACE inhibitors and a diuretic
Aortocoronary bypass (ACB) scheduledCreatinine value: 0.98 mg/dl
European Interactive Pain Course03.-07.09.07
Recommended Medicinal Arthritis Therapy with Non-opioids
Case history, clinical examination, radiological diagnosisCase history, clinical examination, radiological diagnosis
Drug Commission of the German Medical Council, December 2001
Indication for NSAIDIndication for NSAID
ParacetamolParacetamol
Adequate effectAdequate effect Inadequate effectInadequate effect
High gastrointestinal riskHigh gastrointestinal risk
PresentPresent AbsentAbsent
Selective COX-2 inhibitors?Combination: conventional NSAID
and omeprazole/misoprostol
Selective COX-2 inhibitors?Combination: conventional NSAID
and omeprazole/misoprostol
Conventional NSAIDConventional NSAID
Painful arthrosisPainful arthrosis Activated arthritisActivated arthritis
European Interactive Pain Course03.-07.09.07
Recommendation for pharmacological osteoarthritis therapy with non-opioids
Koelz, HR, Michel, B. Deutsches Ärzteblatt 45: 2004
Therapeutic indication for antiinflammatory drug
Elevated gastrointestinalrisk
no yes
Low-dose-Aspirin
no
NSAID(2nd line: coxib)
yes
NSAID*(2nd line: coxib)
H. Pylori?**
Low-dose-Aspirin
no
NSAID + PPIor coxib
yes
NSAID*+PPI
* Not ibuprofen** Test and eradication
if history of ulcer or if unknown
European Interactive Pain Course03.-07.09.07
Recommended Arthritis Therapy with NSAIDs
No long-term treatment, but long enough to treat signs of inflammation
No combination with other NSAIDs
Adjustment of the dose to circadian rhythm of the pain
Single dose as low as possible, but as high as necessary
In elderly patients (> 65/70 years)preferably NSAID with short half-life
if necessary same procedure as with patients with high GI risk
close monitoring of GI tract, renal function and cardiovascular system
Modified according to the Drug Commission of the German Medical Council, December 2001
European Interactive Pain Course03.-07.09.07
Topical Application of NSAIDs
Comparison Diclofenac emulgel (4 x daily. 10 cm strip), topicallyIbuprofen (3 x daily 400 mg), orally
Patient groupActive Heberden’s and/or Bouchard’s arthritisAt least 3 jointsVAS >40/100
Study duration 21 days
Conclusions... The efficacy of treatment with topical diclofenac emulgel is at least comparable to that of systemic ibuprofenPercutaneous diclofenac emulgel treatment has advantages as regards tolerability
Zacher et al., Akt Rheumatol. 26 (2001) 7-14
European Interactive Pain Course03.-07.09.07
Osteoarthritic Pain on Strain: Treatment with Strong Immediate-release Opioids
Morphine (approx. 1/10 - 1/6 of the total daily dose)
Oral – immediate-release tablets and drops
Rectal – suppositories
Buprenorphine (0.2 –
0.4 mg)
Sublingual
Hydromorphone (1.3 – 2.6 mg)
Oral - immediate-release capsules
European Interactive Pain Course03.-07.09.07
Intra-articular Morphine in Pain Patients with Chronic Arthritis
0
20
40
60
100
80
120
1 2 3 4 6 2 3 40
Hours Days
VAS [% BL]
4 mg dexamethasone 3 mg morphine NaCl
N=44; P < 0.05 ANOVA
Stein A. Yassouridis, C. Szoko, K. Helmke, Stein C.:Intra-articular Morphine versus Dexamethasone in Chronic Arthritis Pain 1999 83:525-32
European Interactive Pain Course03.-07.09.07
Summary – Peripheral Opioid Effects
The local administration of opioids produces clinically relevant
analgesia in patients with acute and chronic inflammatory pain.
The analgesic effect is dose-dependent and can be antagonised
by naloxone.
The advantage of local opioids versus systemic opioids is the
absence of central nervous side-effects.
European Interactive Pain Course03.-07.09.07
Arthritic Treatment
3 pillarsNon-medicinal treatmentMedicinal treatmentSurgery
Therapeutic conceptsMultimodalLong-term Individual Adapted to the current clinical picture
European Interactive Pain Course03.-07.09.07
Geriatric Muscle Training
… indicate that high-intensity strength training results in substantial, continuous increases in strength in postmenopausal women for at least 12 months, with the greatest gains seen in the first 3 months
M. Morganti et al., 1995
For overview see:M.A. Fiatarone, W.J. Evans: The etiology and reversibility of muscle dysfunction in the aged. J. Gerontol., 48 (1993) 77-83
European Interactive Pain Course03.-07.09.07
Intra-articular Glucocorticoids
Comments of the Drug Commission of the German Medical Council, 2001:
“The data base on the efficacy of intra-articular injections of glucocorticoids is sparse. Nevertheless, the results of several studies seem to show that they reduce pain at least short-term.”
EULAR recommendations for management of OA of the knee, Ann. Rheumat. Dis., 2003
Expert opinion: Intra-articular injection of long acting corticosteroids is indicated for flares of knee pain, especially if accompanied by effusion
European Interactive Pain Course03.-07.09.07
I.a. Hyaluronic Acid Preparations
Open questionsMechanism of action – e.g.
• Hyaluronic acid synthesis ↑• Regeneration after cartilage damage in an animal model
(interleukin-1) ↑Structure-modifying effect?Differences between various preparations?Cost analysis?
In meta-analyses there is some controversy over the efficacy of hyaluronic acid preparations.
Meta-analyses:• Lo GH et al., JAMA (2003) 290: 3115-21• Aggarwal A et al., Can Fam Physician (2004) 50:249-56• Wang CT et al., J Bone Joint Surg (Am) (2004) 86:538-45
European Interactive Pain Course03.-07.09.07
Weight reduction in osteoarthritis
109 patients BMI > 28 with osteoarthritis intervention: 8 weeks special diet – 800 kcal.
Control group: conventional dietOutcome criteria: WOMAC pain index and WOMAC total index
ResultsReduction in WOMAC pain index: 22%Reduction in WOMAC total index: 30.9%The results are better than three years’ intervention with glucosamine sulphate
Bliddal: Proceedings of the World Congress of Pain(2006); (851-858)
European Interactive Pain Course03.-07.09.07
SYSADOA „SYmptomatic Slow Acting Drugs in OsteoArthritis“
Ademetionine (Gumbaral®)
D-glucosamine sulphate (Dona 200®)
Oxaceprol (AHP 200®)
Hyaluronic acid preparations (Hyalart®, Synvisc®, Hyalubrix®, ..)
European Interactive Pain Course03.-07.09.07
Case Report: Mr Bode
Findings: X-ray Pronounced osteoarthritis of the knee, hip surgery recommended
Within 8 weeks dose increased to 2 x 80 mg immediate-release morphine
Pain values: 2/4SE:
• severe sedation
• severe constipation despite laxative
Patient very discontented with the current situation. He would like to switch therapy as hip surgery is only scheduled in three months’ time.
European Interactive Pain Course03.-07.09.07
Opioid Conversion for Oral and Transdermal Applications
Morphine
Buprenorphine
100:1
Hydromorphone
7,5:1
Oxycodone 1:2 Fentanyl100:1
Tramadol
1:5
Sittl R, Likar R, Nautrup PB: Equipotent doses of transdermal fentanyl and transdermal buprenorphine in patients with cancer and noncancer pain: results of a retrospective cohort study. Clin Ther. 2005 Feb;27(2):225-37.
CharacteristicsHigh initial dosage requires individual titrationReduce dose (30-50%) with conversion because of side-effectsUsable for dosages between 60 and 250 mg morphine equivalen
Morphine i.v3:1
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Reasons for Opioid Rotation
Inadequate pain relief
Tolerance development
Side-effects
Patient peculiarities
European Interactive Pain Course03.-07.09.07
Procedure on Opioid Rotation
Determination of the baseline opioid dose
Calculation of the morphine equivalent
Calculation of the daily dose of the new opioid
Possible dose reduction by 30%
Administration of the prolonged-release single dose or attachment of the patch
Provision of rescue medication
Close monitoring of the patient in the transition phase
European Interactive Pain Course03.-07.09.07
Opioid Rotation
No randomised studies in which opioid was to be used as first
or second line
No standardised conversion rates on the basis of good studies
Recommendations based on uncontrolled studies and personal
observations
Opioid switching to improve pain relief and drug tolerability, Quigley C.Cochrane Database Syst Rev. 2004;(3):CD004847.
European Interactive Pain Course03.-07.09.07
Geriatric Pain
Patient doesn’t complain!
Doctor doesn’t ask!
European Interactive Pain Course03.-07.09.07
Characteristics of a Geriatric Patient
Biological age is advanced, not the calendar age
Multimorbidity
Multiple medication
Rehabilitation necessary
Imminent intellectual degeneration
Social restrictions
Basler et al. 2004
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Age and Pain Threshold
The results of studies on the pain threshold in
geriatric patients varied.
Old age is not necessarily associated with an
increase in the pain threshold!
European Interactive Pain Course03.-07.09.07
“Age is not an analgesic!”
Harkins/Price 1992
European Interactive Pain Course03.-07.09.07
Geriatric Pain Syndromes
Osteoarthritis of the knee/hip
Degenerative spinal diseases
Rheumatoid arthritis
Osteoporosis
PAD
Angina pectoris
Temporal arteritis
Postherpetic neuralgia
Polyneuropathy
Trigeminal neuralgia
Cancer pain
etc.
European Interactive Pain Course03.-07.09.07
Case Report
Mrs Tucher, 70 years
Primary diseases
Hypertension, osteoporosis (old vertebral fractures)
Other special features
Sulphonamide allergy
Medication
ACE inhibitors, ASA (100 mg/day)
Calcium, vitamin D
Paracetamol when required
• (maximum 3 g/day, tablets and suppositories) for two years
European Interactive Pain Course03.-07.09.07
Case Report
Findings
Bone densimetry (DXA, LS): T score – 3.0
No neurological deficits
X-ray
• old lumbar vertebral fracture
• degenerative changes normal for age
• no signs of cancer
BSR, CRP normal
European Interactive Pain Course03.-07.09.07
Proposed Non-opioid Dosage Geriatric Analgesia
NSAIDs (e.g. ibuprofen)2 - 3 x 400-600 mg
Coxibs (e.g. celecoxib) 2 x 100 mg
Dipyrone 4 - 5 x 500-1000 mg
Paracetamol 4 x 500-1000 mg
Flupirtine 3 x 100 mg
European Interactive Pain Course03.-07.09.07
Non-medicinal Therapeutic Options
PhysiotherapyTENS, acupuncture Medical training therapyRelaxation training, hypnosisPain coping trainingPatient education
European Interactive Pain Course03.-07.09.07
Medical Training – Motorial Level
Stamina deficitsStrength deficitsMobility deficitsStrain/strain avoidanceNeuromuscular coordination disorder
European Interactive Pain Course03.-07.09.07
Psychological Pain Therapy
Relaxation therapyBiofeedbackHypnosisCognitive behaviour therapy
Individual or group therapye.g.
Pain coping trainingStress coping training
European Interactive Pain Course03.-07.09.07
The success of interdisciplinary pain therapy does not
depend on age, provided treatment is adapted to the target
group.
Kerns (1985); Middaugh (1988); Sorkin (1990); Cutler (1994); Kee (1996)
Geriatric PainInterdisciplinary Pain Therapy
European Interactive Pain Course03.-07.09.07
Pain and Dementia
Incidence of dementia
> 80 years ~ 10 %
> 85 years ~ 20 %
Incidence of pain
> 75 years ~ 90 %
Demented elderly people are
prescribed fewer analgesics than
non-demented people, both
when “required” and regularly.
Kassalainen et al.; Gerontol. Nursing, 1998
Demented elderly people are
prescribed fewer analgesics than
non-demented people, both
when “required” and regularly.
Kassalainen et al.; Gerontol. Nursing, 1998
After hip fracture non-
demented elderly people
receive three times as much
morphine equivalent than
demented elderly people.
Morrison et al, J Pain and Symptom Management,
2000; 19:240-48
After hip fracture non-
demented elderly people
receive three times as much
morphine equivalent than
demented elderly people.
Morrison et al, J Pain and Symptom Management,
2000; 19:240-48
European Interactive Pain Course03.-07.09.07
Pain in Demented Patients
Behavioural changes
Autonomic nervous signs
Tachycardia
Hypertension
Shallow breathing, panting
Pale, sweating face
European Interactive Pain Course03.-07.09.07
Pain in Demented Patients
Satisfactory verbal communication is usually impossible
Expressions of pain:
Crying (tending more to whimpering)
Quiet and withdrawn
Foetal position
Holds hand on painful site
Facial expression (frowning, but also rigid expression)
European Interactive Pain Course03.-07.09.07
Geriatric Pain Pharmacokinetics/Pharmacodynamics
Reduced absorption of oral medicines
Reduced plasma protein
Reduced distribution volume of hydrophilic medicines (reduced body fluid)
Elevated distribution volume of lipophilic medicines (elevated body fat)
Reduced hepatic metabolism
Reduced creatinine clearance
Increased CNS sensitivity (opioids)
European Interactive Pain Course03.-07.09.07
Geriatric Pain Opioids
Monotherapy preferable
Treatment according to the WHO ladder
Reduce the initial dose by 30-50%
Caution on concomitant administration of sedatives, antidepressants and neuroleptics
Check renal function
Constipation prophylaxis
European Interactive Pain Course03.-07.09.07
Opioids in Renal Insufficiency
Accumulation of active metabolites of morphine
(morphine-6-glucuronide) and tramadol(1)
Prolonged half-life of oxycodone, tramadol(1)
Fentanyl accumulation on continuous administration(2)
Buprenorphine pharmacokinetics are unchanged in renal failure,
therefore buprenorphine can be used in renal insufficiency(3)
(1) Tegeder, I. et al: Der Schmerz, 1999.13:183-195;(2) Höhne et al: Der Anaesthesist, 2004.3:291-303(3) Fielitz et al: EAPC Abstractbook 2005
European Interactive Pain Course03.-07.09.07
Concomitant Medication
Antiemetics
Metoclopramide
Haloperidol
Ondansetron
Dimenhydrinate
Corticosteroids
Benzodiazepines
Cannabinoids
NK1-receptor antagonists
European Interactive Pain Course03.-07.09.07
Treatment of Opioid-related Side-effects - Constipation -
Basic treatment
Roughage
Sufficient fluids
Sufficient exercise
Medication
Sodium picosulphate 10-20 drops
Macrogol 1-3 x one sachet
Lactulose 3 x 1 (15-30 ml)
Enema (e.g. sorbitol)
European Interactive Pain Course03.-07.09.07
Case Report
Gradual reduction of the buprenorphine dose and switch from
buprenorphine to tramadol: weekly dose reduction:
52.5 µg/h => 35 µg/h => 17.5 µg/h
Switch to PR tramadol 2 x 100 mg
Participation in a special programme with exercises to strengthen
muscles and coordination training
European Interactive Pain Course03.-07.09.07
Multimodal Programmes for Optimal Geriatric Pain Therapy
1) Training therapy2) Physiotherapy3) Pain coping programmes
RelaxationStress copingChanges in behaviour
4) Medicinal pain therapy
Activation and reinforcement of the patient’s own initiative
European Interactive Pain Course03.-07.09.07
Efficacy and safety of transdermal buprenorphine in patients over and under
65 years of age
Rudolf Likar, MDPain Clinic, General Hospital Klagenfurt
Klagenfurt, Austria
European Interactive Pain Course03.-07.09.07
The elderly patient
Multimorbid and multimedicated patients
Pharmakokinetics and pharmacodynamics altered
Adverse drug reactions are common
„Elderly patient“ here defined as ≥
65 years of age
European Interactive Pain Course03.-07.09.07
Why buprenorphine in elderly patients?
Buprenorphine – current status:
excellent safety profile
respiratory, immunological, renal
efficacious in cancer, nociceptive and neuropathic pain
advantageous interaction profile
Remaining questions:
metabolism of buprenorphine in the elderly
safety and efficacy profile in the elderly
European Interactive Pain Course03.-07.09.07
Study - objectives
a) Investigate the efficacy and safety of transdermal buprenorphine in the elderly patient (>65 years of age) and compare to younger ones (<65 years of age)
b) Establish its position in the treatment of elderly patients with chronic pain conditions
European Interactive Pain Course03.-07.09.07
Patient Demographics / Diagnoses
Number of Patients: 82Mean age: 59.5 years (range 32 - 83)Gender: male 36 (44 %)
female 46 (56 %)
Diagnosis: 65,2 % musculoskeletal pain 13,0 % neuropathic pain 21,5 % other non-malignant pain indications
5,2 % cancer related pain
European Interactive Pain Course03.-07.09.07
Age Groups
Age Group A 30 patients (≥65 years of age)
Mean age: 74.3 years (range 67 - 83)Gender: male 12 (40 %)
female 18 (60 %)
Age Group B 52 patients (<65 years of age)
Mean age: 51 years (range 32 - 63)Gender: male 24 (46 %)
female 28 (54 %)
European Interactive Pain Course03.-07.09.07
Pain intensity –
changes until treatment day 28
20
46,733,3 30
45
25
17,3
42,3
38,5 48,634,3
14,3
1,9 2,9
0
20
40
60
80
100
No Mild Moderate Severe No Mild Moderate Severe
% p
atie
nts
(VA
S)
Group A (≥65 years) Group B (<65 years)
Baseline (n=82) Day 28 (n=56)
European Interactive Pain Course03.-07.09.07
Pain Relief – Changes until Treatment Day 28
all patients <65 years>65 years
Vis
ual
An
alog
ue
Scal
e
(%)
0
20
40
60
80
p < 0.001
Mean ± SEM
pre post pre post pre post
p = 0.006 p = 0.001
age group A age group B
European Interactive Pain Course03.-07.09.07
Analgesic Concomitant Medication%
pat
ien
tsw
ith
con
com
itan
tan
alge
sic
med
icat
ion
0
20
40
60
80
100
n = 30
n = 52
n = 82
AllPatients
≥65 years
<65 years
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Tolerability (1)
allpatients
>65 years
adve
rse
even
tspe
r pa
tient
00,5
0,6
0,7
0,8
0,9
1
<64 years
>65 years51 - 64 years<50 years
n = 30
n = 30
n = 52
n = 27
n = 25
n = 82
European Interactive Pain Course03.-07.09.07
Tolerability (2)
Age-Group B1Patients 51 - 64 years(27)
>
Age-Group B2Patients <50 years (25)
adve
rse
even
tspe
r pa
tien
t
0
0,2
0,4
0,6
0,8
1
Dizziness
Age-Group APatients 65 years (30)
Nausea Malaise & Fatigue VomitingPruritus
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Daily Dose (at Day 28)
AllPatients
≥65 years
bupr
enor
phin
e(µ
g/h
)
0
15
30
45
60
75
n.s.p = 0.062
<65 years
n = 20
n = 36
Mean ± SEM
n = 56
European Interactive Pain Course03.-07.09.07
Plasma Levels of Buprenorphine and Norbuprenorphine at Day 28
AllPatients
≥65 years
[pla
sma
bupr
enor
phin
e] (
ng/
ml)
0,0
0,2
0,4
0, 6
0,8
n.s.p = 0.954
<65 years
n = 18
n = 27
Mean ± SEM
n = 45
AllPatients
≥65 years
[pla
sma
nor
bupr
enor
phin
e] (
ng/
ml)
0,00
0,05
0,10
0,15
0,20
0,25
0,30
n.s.p = 0.494
<65 years
n = 18
n = 27
Mean ± SEM
n = 45
European Interactive Pain Course03.-07.09.07
Conclusions
Clinically, no age-related differences regarding safety and efficacy could be observed in patients treated with transdermal buprenorphine for chronic pain conditions of moderate to severe intensity.
Plasma levels of buprenorphine as well as norbuprenorphine are in a comparable range in the investigated age groups, showing no evidence for any accumulation of either the mother compound or its major metabolite.
⇒
These results show that transdermal buprenorphine is suitable for treatment of chronic pain also in elderly patients, not only due to easy handling and long duration (up to 96 hours) of patch application, but especially because of its unaltered profile in the elderly.
European Interactive Pain Course03.-07.09.07
EFFICACY & SAFETY OF TRAMADOL AND TRAMADOL SR
IN ELDERLY PATIENTS
European Interactive Pain Course03.-07.09.07
INTRODUCTION
Tramadol is a centrally acting analgesic, synergistically combining weak opioid and monoaminergic modes of action.
Tramadol undergoes hepatic metabolism and the active metabolite M1 is mainly eliminated via the kidneys.
Due to worsening of liver and renal function with age, pharmacological changes in the elderly population may be expected.
European Interactive Pain Course03.-07.09.07
AIM OF THE STUDY
Although tramadol is widely prescribed even to very elderly patients, its pharmacokinetics and pharmacodynamics have never been directly compared to younger age-groups.
therefore
The analgesic efficacy and pharmacokinetics of two Galenic formulations of tramadol were examined in (and compared between) three age-related populations in daily clinical routine.
European Interactive Pain Course03.-07.09.07
PATIENTS (1)
Age < 65 years
Age > 74 years
Age 65 - 74 years
Mean ± SEM = 49.9 ± 1.8 yearsRange = 19 - 64 years
Body Mass =75.3 ± 3.4 kg
n = 3917 females / 22 males
Mean ± SEM = 80.6 ± 0.9 yearsRange = 75 - 91 years
23
Body Mass =75.4 ± 2.9 kg
n = 30 females / 7 males
Body Mass =70.8 ± 2.8 kg
n = 3118 females / 13 males
Mean ± SEM = 69.7 ± 0.5 yearsRange = 65 - 74 years
The enrolled The enrolled patients were patients were stratified into stratified into three equally three equally
sized age sized age groups.groups.
European Interactive Pain Course03.-07.09.07
PATIENTS (2)
Serumlevels
ofCreatinine
andASAT
(Mean ± SEM)
Age < 65 years
Age > 74 years
Age 65 - 74 yearsSerum ASAT (GOT) =0,79 ± 0,04mg/dL
17,2 ± 2,1 U/L
Serum Creatinine =
Serum Creatinine =
Serum ASAT (GOT) =0,93 ± 0,06 mg/dL
12,0 ± 1,0 U/L
Serum Creatinine =
Serum ASAT (GOT) =
0,90 ± 0,05 mg/dL
19,6 ± 5,0 U/L
No major worsening in renal function and no difference in hepatic function with increasing age was detected in these age-groups.
European Interactive Pain Course03.-07.09.07
STUDY DESIGN
Tramadol
ImmediateReleaseGalenic
Tramadol SR
SustainedReleaseGalenic
EldestPatients> 74 years
ElderlyPatients65-74 years
YoungerPatients< 65 years
Stea
dy S
tate
Vis
it 2
Phar
mac
okin
etic
s &
Phar
mac
odyn
amic
s
Stea
dy S
tate
Vis
it 1
Phar
mac
okin
etic
s &
Phar
mac
odyn
amic
s
Enro
lmen
t Vis
itBa
selin
e Ph
arm
acod
ynam
ics
Chronic intake of tramadol until steady state was achieved, followed by tramadol SR.
European Interactive Pain Course03.-07.09.07
DiagnosisDiagnosis
DIAGNOSES / CAUSES OF PAIN
Neoplasms and injuries were the leading causes of pain in younger, while musculoskeletal disorders were predominant in elderly patients.
ICD-10 CodeICD-10 Code <65<65 65 - 7465 - 74 >74>74
NeoplasmsNeoplasms C 00 – D 48C 00 – D 48 28 (34%)28 (34%) 14 (24%)14 (24%) 12 (21%)12 (21%)
MusculoskeletalMusculoskeletal M 00 – M 99M 00 – M 99 9 (11%)9 (11%) 12 (20%)12 (20%) 18 (32%)18 (32%)
Injuries & External CausesInjuries & External Causes S 00 – T 98S 00 – T 98 23 (28%)23 (28%) 8 (14%)8 (14%) 10 (18%)10 (18%)
Nervous SystemNervous System G 00 – G 99G 00 – G 99 5 (6%)5 (6%) 7 (12%)7 (12%) 5 (9%)5 (9%)
Unspecific SymptomsUnspecific Symptoms R 00 – R 99R 00 – R 99 13 (16%)13 (16%) 12 (20%)12 (20%) 6 (11%)6 (11%)
Other CausesOther Causes C 00 – D 48C 00 – D 48 4 (5%)4 (5%) 6 (10%)6 (10%) 5 (9%)5 (9%)
Group of Patients Age (years)/Frequency (%)
Group of Patients Age (years)/Frequency (%)
European Interactive Pain Course03.-07.09.07
DAILY TREATMENT DOSES
At steady state conditions, elderly patients required slightly (however non-significantly) lower doses of both, tramadol and tramadol SR.
Mean ± SEM
ANOVAp=0.184n.s.
ANOVAp=0.445n.s.
ANOVA =
Comparison of respective treatment
doses between three age-
groups
TramadolD
ose
(mg/day)
0
100
200
300
400
500
n.s.
< 65 years(n = 20)
> 74 years(n = 18)
65-74 years(n = 17)
n.s.n.s.
Tramal SR Tramal
European Interactive Pain Course03.-07.09.07
CONCOMITANT ANALGESICS
Elderly patients required less often concomitant analgesic medication as compared to patients being younger than 65 years.
Concomitant Analgesic MedicationNumber of Patients (& Incidences)Concomitant Analgesic MedicationNumber of Patients (& Incidences)
<65<65 65 - 7465 - 74 >74>74
Concomitant Analgesic Medication (overall)
Concomitant Analgesic Medication (overall) 33 (85%)33 (85%) 20 (65%)20 (65%) 20 (67%)20 (67%)
Non – Steroidal Anti-Inflammatory Drugs NSAID‘s
Non – Steroidal Anti-Inflammatory Drugs NSAID‘s 24 (62%)24 (62%) 15 (48%)15 (48%) 15 (50%)15 (50%)
OpioidsOpioids 1 (3%)1 (3%) 0 (0%)0 (0%) 2 (7%)2 (7%)
Non Antiphlogistic Analgesic Drugs (Metamizol / Paracetamol)
Non Antiphlogistic Analgesic Drugs (Metamizol / Paracetamol) 19 (49%)19 (49%) 10 (32%)10 (32%) 11 (37%)11 (37%)
OthersOthers 1 (3%)1 (3%) 0 (0%)0 (0%) 1 (3%)1 (3%)
Group of Patients Age (years)/Frequency (%)
Group of Patients Age (years)/Frequency (%)
European Interactive Pain Course03.-07.09.07
PAIN INTENSITY (1)
******
****
**
Num
eric
al P
ain
Scal
e(a
U)
0
1
2
3
4
5
6
7
8
< 65 years(n = 20)
> 74 years(n = 18)
65-74 years(n = 17)
Tramal
Tramal SR
Baseline
Pain intensity before treatment was comparably high among all groups. Treatment-induced pain-reductions were similar for all age-groups.
Mean ± SEMMaximum Pain = 10 aU
** p<0.001
European Interactive Pain Course03.-07.09.07
PAIN INTENSITY (2)
Visu
al A
nalo
gue
Scal
e(%
)
0
10
20
30
40
50
60
70
80
****** ****
**
< 65 years(n = 20)
> 74 years(n = 18)
65-74 years(n = 17)
Mean ± SEMMaximum Pain = 100 %
Tramal
Tramal SR
Baseline** p<0.001
Independent of the method applied to quantify pain, similarly considerable pain relief was observed in all age-groups.
European Interactive Pain Course03.-07.09.07
PHARMACOKINETICS (1)[S
erum
Tra
mad
ol]
(+) T
ram
adol
(ng/
mL)
0
100
200
300
400Patients < 65 years Patients 65 - 74 years Patients > 74 years
2,5 hours 5,0 hoursfollowing
Immediate Release Tramadol
5,0 hours 10,0 hoursfollowing
Sustained Release Tramadol
No accumulations of (+) or (-)tramadol were observed with increasing age, suggesting that their hepatic metabolism is not reduced in elderly.
ANOVAp=0.278n.s. ANOVA
p=0.363n.s.
ANOVAp=0.398n.s.
ANOVAp=0.694n.s.
Mean ± SEM
European Interactive Pain Course03.-07.09.07
PHARMACOKINETICS (2)
[Ser
um M
1](+
) Tra
mad
ol-M
etab
olite
(ng/
mL)
0
20
40
60
80
100
120Patients < 65 years Patients 65 - 74 years Patients > 74 years
2,5 hours 5,0 hoursfollowing
Immediate Release Tramadol
5,0 hours 10,0 hoursfollowing
Sustained Release TramadolNo accumulations of (+) or (-)M1 were observed with increasing age, suggesting that their renal elimination is not deteriorated in the elderly.
Mean ± SEM
ANOVAp=0.244n.s.
ANOVAp=0.100n.s.
ANOVAp=0.329n.s.
ANOVAp=0.164n.s.
No accumulation of (+) or (-)M1 was observed with increasing age, suggesting that renal elimination is not deteriorated in the elderly.
[Ser
um M
1](+
) Tra
mad
ol-M
etab
olite
(ng/
mL)
0
20
40
60
80
100
120Patients < 65 years Patients 65 - 74 years Patients > 74 years
2,5 hours 5,0 hoursfollowing
Immediate Release Tramadol
5,0 hours 10,0 hoursfollowing
Sustained Release Tramadol
ANOVAp=0.244n.s.
ANOVAp=0.100n.s.
ANOVAp=0.329n.s.
ANOVAp=0.164n.s.
European Interactive Pain Course03.-07.09.07
ADVERSE EVENTS
Total AE-incidences were similar for all age-groups. No increase in favour of any type of AE, nor any unknown AE were found with increasing age.
Nausea Dizziness Malaise & Fatigue Vomiting Constipation
Predom
inan
tA
dverseEven
ts
Inciden
ces(%
)
0
20
40
60
80
100Patients < 65 years Patients 65 - 74 years Patients > 74 years
European Interactive Pain Course03.-07.09.07
SUMMARY
Considerable improvements in pain intensity were detected during both treatment phases, being identical for patients of all three age-groups.
Serum concentrations of both stereoisomeric forms of tramadol and of its metabolite M1 were comparable for all three age-groups. No age-related accumulation of tramadol and M1 was found.
The adverse event profile was similar for all three age-groups, in line with from known tramadol profiles.
European Interactive Pain Course03.-07.09.07
CONCLUSION
Tramal and Tramal SR are both safe and effective analgesics for the treatment of moderate to severe pain.
Pharmacokinetics and pharmaco-dynamics are not changed when given to elderly patients.
European Interactive Pain Course03.-07.09.07
Multimodal therapy of chronic pain
R. Sittl
European Interactive Pain Course03.-07.09.07
Interdisciplinary Pain Center University Hospital Erlangen - Germany
European Interactive Pain Course03.-07.09.07
Patient - characteristics
Low back pain - neuropathic pain - headache
Multi-localisation
A long history of pain
Psycho-social problems
A large number of ineffective
treatment trials
Pain syndromes
Characteristics
European Interactive Pain Course03.-07.09.07
Pretreatment strategies
Non-opioids
Non-opioids andweak opioids
Non-opioids andstrong opioids
Co- analgesics
Physical , physio-
therapeutic , psycho-
therapeutic treatments
TENSacupuncture
European Interactive Pain Course03.-07.09.07
Deficit in endurance, strenghts, coordination etc
Fear movement could cause pain,
Patients see themselves in a passive role
Feeling angry (why me), helpless, sometimes depressed,
Frustration (I cannot do things I used to do)
Fear to talk to others about their pain
Social isolation – resulting in more pain............
Chronic pain patients‘ problems
The challenge for us and the patient is to ‘unlock the patients potential’ in helping them to help themselves.
European Interactive Pain Course03.-07.09.07
Movement therapy, medical training
Psychological pain treament- active coping strategies
Education Relaxation
Faithful relationto the patient
optimal pharmacological
treatment
Multimodal therapeutic group - programms for chronic pain patients
Treatment strategies
European Interactive Pain Course03.-07.09.07
Orthopedic specialist
Orthopedic specialist
Precondition of multimodal therapy is an interdisciplinary team
Psychsomatic specialist
Psychsomatic specialist PsychiatristPsychiatrist
Sport therapy specialist
Sport therapy specialist PsychologistsPsychologists Physio-
therapist Physio-
therapist
Nursing stuff – co-therapistsNursing stuff – co-therapists
Staff for organisation and documentationStaff for organisation and documentation
Pain specialist Neurologist
Pain specialist Neurologist
Pain specialist Anesthesist
Pain specialist Anesthesist
Team structure in the Erlangen pain clinic
European Interactive Pain Course03.-07.09.07
Interdisciplinary pain day clinic
Implementational principles
Checking the quest.and patients history
Patient, doctor or psychologist enquirees
AlternativePain ambulanceappointment Day clinical
appointment (4-6 hrs)
The questionnaire from the german
pain society is sent
European Interactive Pain Course03.-07.09.07
Interdisciplinary pain day clinic
Day clinic – patient screening
Group therapy for patient with somatic pain
disorders (1- 2 times a week for 6
months
Headache group therapy, twice a week
for 8 weeks
Day clinical treatment, multimodal treatment
Pain group therapy
(4 weeks,7 hours/d)
Outpatient therapy concepts
Recommend a stationary therapy
Screening meeting
Psychological examination 90 min
Medical examination 90 – 120 min.
„MediTrain“ diagnostics 120 min
European Interactive Pain Course03.-07.09.07
Discuss realistic therapeutic aims with the patient
Pain reduction not freedom
Change how pain is perceived
Learn active ways of coping with pain
Functional improvements
Reduce doctor - shopping
Return to work
The patient must take an active role
Multidisciplinary bio-psycho-social rehabilitation for chronic low back painGuzman J. et al: Cochrane Database Syst Rev 2002
European Interactive Pain Course03.-07.09.07
Pharmaco-therapy
Non-pharmacological-therapy
Physiotherapy
Movement therapy(sport)Relaxation education, hypnosis„Coping with pain“ education
Psychotherapeutical groupPatient educationMedicinal consultingPsychotherapeutical consulting„Experiencing nature“, acupressure, Qi Gong
Usually no invasive and passive therapeutic approachesduring group therapy!
We want to re-activate patients and generate self-responsibility for their pain disease.
Usually no invasive and passive therapeutic approachesduring group therapy!
We want to re-activate patients and generate self-responsibility for their pain disease.
Multimodal pain therapy
Treatment elements
European Interactive Pain Course03.-07.09.07
Monday Tuesday Wednesday Thursday Friday
8.00 Meditrain(Movement
therapy Physiotherap y
10.30: Hypnosis
Relaxation
Meditrain8.30:
„Coping with pain“ group
Meditrain
10.3 0 Psycho-
therapeutic group
Break Break Break
11.0 0
Water-gymnastics
RelaxationWater
gymnastics
12.0 0
Break for lunch
11.30-12.30: Lunch
13.0 0
Medical consulting or
TENS „Coping with pain“ group
Back pain
13.00: Meditrain- education
Training
Relaxation
14.0 0 Break Break Break
14.1 5 Analgesics Psychotherap
eutic group
EducationNeuropathik
painMedical
consulting orTENS15.1
5 Relaxation
Weekly plan of the 4-week pain group
European Interactive Pain Course03.-07.09.07
Improvement is possible by movement therapy (individual physical exercise)
Lack of enduranceLack of strengthMovement deficitsLack of flexibilityNeuro muscular coordination faults
Patient characeristics: deficits in physical capacity
European Interactive Pain Course03.-07.09.07
Exercises to improve endurance, strength, flexibility and coordination......... Training duration: 2 h/d, individual training plans, cont. adaption
European Interactive Pain Course03.-07.09.07
Increase in strengthIncrease in enduranceIncrease in self confidenceFeeling successSocial contactsPositive social experiences
Active improvement of physical capacity- acceptance of active coping stregies
What a focussed movement training can achieve
European Interactive Pain Course03.-07.09.07
Schmerz
Education
Bio-psycho social-pain modelBasic pharmacologyBasic anatomyAcupressure, tensWeight management...Information on special pain syndromes
Sofia 2005/ Sittl
Socialenvironmente.g. inter-relationshipproblems, mobbing at
work, …
Psychee.g. anxiety, depression,
overdemands, ...
Social conditionse.g. health system, economic situation, …
Successful treatment of chronic pain is based on the ….Bio - psycho - social pain model
Pain
European Interactive Pain Course03.-07.09.07
Psychological pain therapy methods
Relaxation therapyBiofeedbackIn depth relaxation (hypnosis)
Cognitive behavior therapy as singularor group therapy
„Coping with pain“„Coping with stress“
European Interactive Pain Course03.-07.09.07
„Coping with pain“ education
InformationPerceptive controllingEnjoyment trainingChanging negative thoughts and emotions
n. Basler 2001
European Interactive Pain Course03.-07.09.07
What is the function of chronic pain for patients?
What „painful“ experiences (i.e. loss of a loved one etc.) or psychosocial stress are connected to the pain experience?
Psychosomatic groupsession
Thematics:
European Interactive Pain Course03.-07.09.07
Chronic pain must be treated interdisciplinary
Group programms are suitable for chronic pain patients
movement, education, learning of coping strategies and relaxation-methods are the basic elements of multimodal programmes
The exchange of experience with other patients is one of the most important factors to improve pain perception
Conclusion
Activationis the key!!!
European Interactive Pain Course03.-07.09.07
Thank you for attention!
European Interactive Pain Course03.-07.09.07
Treatment of low back pain
European Interactive Pain Course03.-07.09.07
Classification according to duration
Acute painIs caused by external or internal injury or damageIts intensity correlates with the triggering stimulusIt can be easily locatedHas a distinct warning and protective function
Chronic painLasts longer than expectedIs uncoupled from the causative eventBecomes a disease in its own rightIts intensity no longer correlates with a causal stimulusHas lost its warning and protective functionIs a special therapeutic challengeRequires interdisciplinary procedures
European Interactive Pain Course03.-07.09.07
Case report 1: Mrs B.
Case history 72-year-old, obese pensioner
Three years of increasing back pain radiating to both gluteal regions
Walking distance reduced to 300 m Pain relief after correction of lordosis
Findings Slight deficit on raising right hallux
Bilateral Achilles’ tendon reflex absent
Bilateral anterior femoral paraesthesia
Suspected spinal canal stenosis
128
European Interactive Pain Course03.-07.09.07
Spinal canal width: normal
129
European Interactive Pain Course03.-07.09.07
Case report 2: Mrs B.
DiagnosisPost-myelo-CT revealed spinal canal stenosis
130
European Interactive Pain Course03.-07.09.07
Case report 3: Mrs B.
Spinal canal stenosis confirmed on functional myelography.
131
European Interactive Pain Course03.-07.09.07
Spinal canal stenosis on MRT
132
European Interactive Pain Course03.-07.09.07
Spinal canal stenosis – typical clinical symptoms
GaitLegs wide apart, leaning forward slightly, flat lumbar lordosisPain after walking a certain distance (spinal claudication)
Posture Forward inclination after walking a certain distance with hands on thighs for support or sitting down (stopping not sufficient)
Pain radiating to Thighs
Discrete neurological deficits
Multisegmental, reduced proprioception
UnproblematicCycling, climbing, sitting
133
European Interactive Pain Course03.-07.09.07
Spinal canal stenosis
Symptoms with narrowspinal canal %
Walking distance limited 90
Low-back pain 87
Leg pain 84
Numbness/paraesthesia 51
Weak legs 44
Clinical symptoms with narrowspinal canal %
ATR absent 58
Sensory disturbances 52
Myasthenia 51
Positive Lasègue’s sign 49
Patellar reflex absent 24
134Modified after: Dt. Ges. f. Orthopädie und orthopäd. Chirurgie + BV d. Ärzte f. Orthopädie (Hrsg.) Leitlinien der Orthopädie, Dt. Ärzte-Verlag, 2. Auflage, Cologne 2002
European Interactive Pain Course03.-07.09.07
Spinal canal stenosis
135
Therapeutic LadderOrientation criteria Pain, extent of stenosis, walking distance, refractory, suffering, concomitant diseaseStep 1: outpatient treatment Counselling, physiotherapy, analgesic and/or anti-inflammatoryagents, corset to correct lordosis (new: TENS belt)Step 2: outpatient/inpatient treatment Step 1, with additional epidural injectionsStep 3: inpatient treatment Surgery(partial removal of vertebral arches and joints,in rare cases spondylodesis)
Mod. after: Dt. Ges. f. Orthopädie und orthopäd. Chirurgie + BV d. Ärzte f. Orthopädie (Hrsg.) Leitlinien der Orthopädie, Dt. Ärzte-Verlag, 2. Auflage, Cologne 2002
European Interactive Pain Course03.-07.09.07
Mrs G.39 years old, profession: shop assistant, unemployed for 2 yearsNo relevant previous diseases
Case historySevere acute back pain since the morningRadiating along the rear of the right thigh to the foot
FindingsRight Lasègue’s sign positiveReduced sensation in segment right S1Right ATR absentUnable to stand on toes of right foot
Case report 1: Mrs G.
European Interactive Pain Course03.-07.09.07
Case report 5: Ms. G. – back at the doctor‘s
Invasive therapeutic measures (epidural catheter, root blockades, facet blockades) were effective for a brief period only
The patient has worse back pain with pseudoradicular radiation; pain scores (VAS): at rest 4, during exertion 8
Occasional diffuse tingling / paraesthesia L5/S1 vertebrae
Pain management to date: Diclofenac 75 mg TID and tramadol SR 200 mg BID
European Interactive Pain Course31.08-05.09.08
Put on morphine 60 mg BID
Participated in a multimodal treatment program
after approval of a temporary disability pension
Case report 6: Mrs G. Procedure
Video statement: “G in der Sonne.mpg”
European Interactive Pain Course31.08-05.09.08
Back pain – summary of treatment principles
Acute back pain (without red flags)
PhysicalBed rest for a short period onlyApplication of heat / cold treatmentPhysiotherapyShort AU
Drug treatmentAnalgesicsCoanalgesics
StimulationTENS, acupuncture
InterventionsLocal/regional infiltration or nerve blockades
If there is no improvement within 2 – 4 weeks, order further tests.
European Interactive Pain Course31.08-05.09.08
Back pain – summary of treatment principles
Chronic back painPhysiotherapy and sportstherapy
Activating physiotherapyMedical training therapy
PharmacologicalAnalgesicsCoanalgesics
StimulatoryTENS, acupunctureSpinal cord stimulationAlternative methods
PsychologicalRelaxation techniques, pain coping strategies
Multimodal painmanagement –“Group programs”
Duration 4-5 weeks, ~ 160 h
Back pain and social insurance: Author Dr. Leifeld, RendsburgDownload: www.schmerzzentrum.klinikum.uni-erlangen.de
European Interactive Pain Course31.08-05.09.08
Multimodal pain mangement group: goals of treatment
Reduction of pain, not freedom from pain
Changed perception of pain
Learning active coping strategies
Improvement of performance
Improved quality of life
Reduced uptake of healthcare services
Return to work