Pain therapy of osteoarthritis

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


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


Arthritis – Classification

Primary (idiopathic): cause unknown

Secondary: posttraumatic, postinfectious

Other possible causes: articular malpositioning

axial deviation

crystallopathy (gout)

endocrine, haematological and metabolic primary diseases


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)


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


Arthritis - Classical Radiological Criteria

Narrowing of joint cavity

Osteophytes

Subchondral sclerosis

Subchondral cysts

Epiphyseal deformity


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


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)

Vorführender

Präsentationsnotizen

Team 2 (o) Morning stiffness > 1h? Team 3 (o) Please consider a chart on new aspects of rheumatoid factor lab tests because things have changed here considerably. Of interest to basisversorger Example CCP etc. Chart on : Heberden osteoarthritis and Bouchard osteoarthritis Team 7 (o) DD: Gout arthritis, psoriatic arthritis Team 8 (-) The difference vs. inflammatory rheumatic disease is important but cannot be represented thus.


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


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


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

Vorführender


Team 2 (o) ASS + NSAR immer PPI, linke Spalte auch NSAR o. Coxib Team 5 (o) Erklärungsbedarf Team 6 (o) Erklärung des Schemas notwendig! Team 7 (o) Sinnhaftigkeit nicht erkennbar Team 8 (o) Das war einmal! Diverse Studien und Empfehlungen (z.B. FDA) aus März und Juni 2005 legen ein anderes Vorgehen nahe! Abgewandeltes Brune- oder Bolten-Schema besser!!! <br>Überschrift missverständlich Folie 2 oder Indikation NSAR Team 9 (o) dringend kritische Bewertung (Coxibe/NSAR) erforderlich!!! Team 10 (o) Warum bei NSAR-Dauertherapie nicht PPI? Team 11 (o) als Hand-Out oder Internet--Hinweis Algorithmus schlecht


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


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

Vorführender


Eva: BMJ, Metaanalyse


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


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


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.


Arthritic Treatment

3 pillarsNon-medicinal treatmentMedicinal treatmentSurgery

Therapeutic conceptsMultimodalLong-term Individual Adapted to the current clinical picture


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

Vorführender


Hr. Hann übersezt auf Deutsch


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


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


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)


SYSADOA „SYmptomatic Slow Acting Drugs in OsteoArthritis“

Ademetionine (Gumbaral®)

D-glucosamine sulphate (Dona 200®)

Oxaceprol (AHP 200®)

Hyaluronic acid preparations (Hyalart®, Synvisc®, Hyalubrix®, ..)


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.


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


Reasons for Opioid Rotation

Inadequate pain relief

Tolerance development

Side-effects

Patient peculiarities


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


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.


Geriatric Pain

Patient doesn’t complain!

Doctor doesn’t ask!

Vorführender



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!

Vorführender



“Age is not an analgesic!”

Harkins/Price 1992

Vorführender



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.

Vorführender



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

Vorführender



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

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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

Vorführender



Non-medicinal Therapeutic Options

PhysiotherapyTENS, acupuncture Medical training therapyRelaxation training, hypnosisPain coping trainingPatient education

Vorführender



Medical Training – Motorial Level

Stamina deficitsStrength deficitsMobility deficitsStrain/strain avoidanceNeuromuscular coordination disorder

Vorführender



Psychological Pain Therapy

Relaxation therapyBiofeedbackHypnosisCognitive behaviour therapy

Individual or group therapye.g.

Pain coping trainingStress coping training

Vorführender



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

Vorführender



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

Vorführender



Pain in Demented Patients

Behavioural changes

Autonomic nervous signs

Tachycardia

Hypertension

Shallow breathing, panting

Pale, sweating face


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)

Vorführender



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)

Vorführender



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

Vorführender



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

Vorführender



Concomitant Medication

Antiemetics

Metoclopramide

Haloperidol

Ondansetron

Dimenhydrinate

Corticosteroids

Benzodiazepines

Cannabinoids

NK1-receptor antagonists

Vorführender



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)


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


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


Efficacy and safety of transdermal buprenorphine in patients over and under

65 years of age

Rudolf Likar, MDPain Clinic, General Hospital Klagenfurt

Klagenfurt, Austria


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


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


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


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


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 %)


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)

Vorführender


At baseline, most patients (80, 5%) suffered from moderate to severe pain: 80% in age group A and 80,8% in age group B. At day 28, the percentage of patients with none and mild pain had increased, while moderate to severe had decreased. There was no statistically significant difference between the two age groups, although at day 28 a slightly better pain intensity was seen in the elderly patients (no or only mild pain in 50% group A patients vs. 58.8% of group B patients).


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

Vorführender


Hier evtl. noch erwähnen, daß die numerische Skala dieselben Resultate liefert.


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


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


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


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


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


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.


EFFICACY & SAFETY OF TRAMADOL AND TRAMADOL SR

IN ELDERLY PATIENTS

Vorführender


Tramadol presentations (I) Tramadol is available in many countries in a wide range of presentations allowing individual treatment of patients.


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.

Vorführender




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.

Vorführender




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


23






The enrolled The enrolled patients were patients were stratified into stratified into three equally three equally

sized age sized age groups.groups.


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.


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.


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 (%)


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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

Vorführender




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%)



Vorführender




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

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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.

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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


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

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PHARMACOKINETICS (2)

[Ser

um M

1](+

) Tra

mad

ol-M

etab

olite

(ng/

mL)

0

20

40

60

80

100





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





Sustained Release Tramadol

ANOVAp=0.244n.s.

ANOVAp=0.100n.s.

ANOVAp=0.329n.s.

ANOVAp=0.164n.s.

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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


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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.

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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.

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Multimodal therapy of chronic pain

R. Sittl


Interdisciplinary Pain Center University Hospital Erlangen - Germany

Vorführender


Dear Colleagues, In the next 20 minutes I would like to present our multimodal group programm for chronic pain patients At the beginning focu After that talk about… At the end I will show you how we are working very closely with the patient


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

Vorführender


In our day-care pain clinic we treat patients with chronic back pain, neuropathic pain and chronic headache. In many cases the pain is multiloculated, patients have a long history of pain and on top of this psychosocial problems. Many of them have tried other forms of treatment, but without success


Pretreatment strategies

Non-opioids

Non-opioids andweak opioids

Non-opioids andstrong opioids

Co- analgesics

Physical , physio-

therapeutic , psycho-

therapeutic treatments

TENSacupuncture

Vorführender


The patients in our pain clinic weree normally pretreated for example with non-opioids, but also weak and strong opioids were given. In neuropathic pain co-analgesics were usually administered. Many patients in Germany have also had experience with acupuncture or TENS, and a minority had already received pain pumps or SCS without adequate pain relief


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.

Vorführender


Pain patients have many other problems besides their pain, for example deficits in endurance , they are in fear movement could cause pain, they see themselves in a passive patient role, they feel themselves helpless. They feel angry frustrated and sometimes depressed. As a result of chronic pain many patients become socially isolated. The challenge for you and the patient is to be able to ‘unlock the patients potential’ in helping them to help themselves. For people to self-manage, take more control – they need to learn how they can break this cycle.


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

Vorführender


With multimodal therapeutic group programmes we have a chance to help patients how to break this circle. A precondition - a door opener is on one side a optimised pharmacological treatment and on the other hand a faithfull relation to the patient, we must spend time to the patient and believe patients when they say they are in pain Important elements in this group programme are movement therapy (medical training therapy), psychological pain treatment, teaching relaxation techniques, and educating patients in a fashion they can comprehend.


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

Vorführender


A prerequisite for multimodal pain treatment is an interdisciplinary team. These are the professional groups working together at our pain clinic. One essential point as regards a team is that they really do work as a team in an own department. Communication between the team members is important that they all represent the same pain model.


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

Vorführender


How do we in Erlangen work? We receive enquiries from patients, physicians and psychologists. We then send them the detailed "German Pain Questionnaire", (containing also validated psychometric tests.) which patients then return together with medical reports or information of their pain history. After evaluation of the documents (records) we decide whether the patient is given an appointment (in our pain clinicic) made with our pain clinic. a brief outpatient appointment, whether we propose an alternative solution, or whether an appointment is made with our pain clinic.


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

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If the patient has an appointment at our pain department (in the day clinic), the case history is taken and the patient given an examination lasting 90-120 minutes. (Order further tests or further examination with our neurolgist or orthopaedic specialist A psychologist then takes the case history. It is important that patients see from the very beginning that physicians and psychologists in our department work closely hand in hand. Our sport therapists then examine the patient by testing endurance, coordination, flexibility and strength making a ind.physical capacity evaluation (establishing the initial status.) A screening conference then decides on what happens next. (Either we propose an appointment in our pain ambulance or recommend admission to a pain hospital, or the patients join our day group programme.) We offer three different programmes: one with a group over a period of four weeks. The group consists mainly of patients with back pain and neuropathic pain. In the headache group, patients with chronic headache are treated twice a week for eight weeks. A daily session lasts about five hours. We also have a group for somatoform pain, e.g. generalised pain resulting from emotional trauma.


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

Vorführender


Before starting the patients in our group programme, we discuss the therapeutic objectives with them. We point out that it is extremely difficult to achieve complete pain relief, and our aim is to reduce pain and change pain experience. Our objective is to enable patients to cope better with their pain. We explain to them that active coping strategies are important for chronic pain patients. We also point out that the aim of treatment is to improve function and reduce the burden on the health system. At best the patient should be able to return to work. To reach that the patient must take an active role


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

Vorführender


Multimodal pain therapy is made up of a wide variety of therapeutic procedures. In our opinion as I mentioned before the main components should be Movement therapy, relaxation training, pain-coping training, and education. The programme does not involve any invasive or passive therapeutic procedures. We want to re-activate patients and generate self-responsibility for their pain disease.


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

Vorführender


I would now like to give an example of a schedule for our normal pain group. ended!! Main focus


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

Vorführender


As you saw from the schedule we focus in our programm to the deficits of the patients in…., endurance, strength, flexibility etc We know from our experience that movement….. Can improve ….. If patient improve actively their physical capacity that is more likely that they accept active coping strategies


Exercises to improve endurance, strength, flexibility and coordination......... Training duration: 2 h/d, individual training plans, cont. adaption

Vorführender


Our patients train in our center every day in minimum of 2 hours. Our patients carry out exercises to improve endurance, strength, coordination and flexibility. The group training programmes here shown with the pezzi ball , in particular, are very popular.


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

Vorführender


Medical training increases strength, improves endurance, raises self-confidence, And patients have a feeling of success, the group provides social contacts and they experience positive social experiences. If patient improve actively their physical capacity that is more likely that they accept active coping strategies


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

Vorführender


Another important factor in the group programme is education. We explain the biopsychosocial pain model once more, provide basic information on physiology and drugs, and orthopaedic surgeons and the member of the training center show(s) the basics of anatomy. They explain to the patient that inactivity leads to more pain, activity to a reduction of the pain Patients are familiarised with non invasive procedures f.e acupressure and transcutaneous electrical nerve stimulation, all procedures that they can apply themselves. They are also given information on the pain syndromes actually experienced in the group.


Psychological pain therapy methods

Relaxation therapyBiofeedbackIn depth relaxation (hypnosis)

Cognitive behavior therapy as singularor group therapy

„Coping with pain“„Coping with stress“

Vorführender


A third point I would like to mention is psychological pain therapy, consisting of relaxation procedures, such as progressive muscle relaxation, and biofeedback training for our headache patients. In this programme patients learn how to the influence the dilatation of their cerebral vessels. Some patients are given in-depth relaxation or hypnosis. The group is then taught in pain-coping procedures and the headache group stress-coping procedures.


„Coping with pain“ education

InformationPerceptive controllingEnjoyment trainingChanging negative thoughts and emotions

n. Basler 2001

Vorführender


Pain-coping training comprises providing information and distracting attention from the pain. Another part of the programme is that they also learn how to give themselves a treat again. We call it "enjoyment training". We also teach them that a change from negative thoughts and feelings to positive thoughts may also provide relief. Patients also make very positive comments on the exchange of experience within the group.


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:

Vorführender


The psychotherapeutic group discusses the question of the function of chronic pain for them by trying to find out whether painful experiences or psychosocial stress factors are essentially involved in pain experience. This is often the case, and here long-term therapeutic strategies must be initiated.


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!!!

Vorführender


Summing up, difficult chronic pain is an issue requiring interdisciplinary treatment. Group programmes are suitable for chronic pain patients, physical exercise, education, learning coping strategies and relaxation methods being the basic elements of multimodal treatment. Inter-patient exchange may contribute considerably to changing pain parception. According to the literature, multimodal pain therapy achieves better results than monodisciplinary procedures. However, they involve a lot of work and are expensive, but currently there is no alternative.


Thank you for attention!


Treatment of low back pain


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


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


Spinal canal width: normal

129

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DiagnosisPost-myelo-CT revealed spinal canal stenosis

130



Spinal canal stenosis confirmed on functional myelography.

131


Spinal canal stenosis on MRT

132


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


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


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

Vorführender



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.


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


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”

Vorführender



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.

Vorführender



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


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

Vorführender


Pain therapy of osteoarthritis

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