Pain therapy of osteoarthritis

Page 1

European Interactive Pain Course 31.8-05.09.08

Friday Pain therapy of osteoarthritis

European Interactive Pain Course 03.-07.09.07

Frioday Chronic non-cancer pain syndromes Workshop Part I Workshop Part II

Workshop Part III

Opioids in non-cancer pain Pain therapy of osteoarthritis Pain in the elderly Treatment of osteoporosis Opioids in the elderly (new studies)

Treatment of low back pain (Case report)

Summary End of Workshop

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Arthritis – Definition 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.

Prof. Swoboda Erlangen University Orthopaedic Clinic 2004

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Arthritis – Classification Primary (idiopathic): cause unknown Secondary:

posttraumatic, postinfectious Other possible causes: articular malpositioning axial deviation crystallopathy (gout) endocrine, haematological and metabolic primary diseases

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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)

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Arthritis – Classification Life-long disease Episodic course Classification Latent:

asymptomatic radiological signs

Manifest:

radiological signs with clinical symptoms of arthritis

Active:

radiological signs, synovitis, very severe pain

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Arthritis - Classical Radiological Criteria

Narrowing of joint cavity Osteophytes Subchondral sclerosis Subchondral cysts Epiphyseal deformity

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Arthritis – Clinical Picture Pain (on strain, movement, rest, nocturnal pain) Morning stiffness (usually < 30 min.) pain on getting going Swelling Muscular atrophy as a result of avoiding exercise Restricted movement (contractures) Crepitation Eradication of joint contours Synovial irritation Joint effusion Axial deviation Palpable osteophytes

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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)

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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 Omeprazole Oral antidiabetic, ASA, beta-blockers, ACE inhibitors and a diuretic Aortocoronary bypass (ACB) scheduled Creatinine value: 0.98 mg/dl

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Recommended Medicinal Arthritis Therapy with Non-opioids Case Case history, history, clinical clinical examination, examination, radiological radiological diagnosis diagnosis Painful Painful arthrosis arthrosis

Activated Activated arthritis arthritis

Paracetamol Paracetamol Inadequate Inadequate effect effect

Adequate Adequate effect effect

Indication Indication for for NSAID NSAID High High gastrointestinal gastrointestinal risk risk Present Present

Absent Absent

Selective Selective COX-2 COX-2 inhibitors? inhibitors? Combination: Combination: conventional conventional NSAID NSAID and and omeprazole/misoprostol omeprazole/misoprostol

Conventional Conventional NSAID NSAID

Drug Commission of the German Medical Council, December 2001

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Recommendation for pharmacological osteoarthritis therapy with non-opioids Therapeutic indication for antiinflammatory drug

Elevated gastrointestinal risk

no

yes H. Pylori?**

Low-doseAspirin no NSAID (2nd line: coxib)

yes

* Not ibuprofen ** Test and eradication if history of ulcer or if unknown

NSAID* (2nd line: coxib)

Koelz, HR, Michel, B. Deutsches Ă„rzteblatt 45: 2004

Low-doseAspirin no NSAID + PPI or coxib

yes NSAID* +PPI

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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

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Topical Application of NSAIDs Comparison Diclofenac emulgel (4 x daily. 10 cm strip), topically Ibuprofen (3 x daily 400 mg), orally Patient group Active Heberden’s and/or Bouchard’s arthritis At least 3 joints VAS >40/100 Study duration 21 days Conclusions ... The efficacy of treatment with topical diclofenac emulgel is at least comparable to that of systemic ibuprofen Percutaneous diclofenac emulgel treatment has advantages as regards tolerability Zacher et al., Akt Rheumatol. 26 (2001) 7-14

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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

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Intra-articular Morphine in Pain Patients with Chronic Arthritis VAS 120 [% BL] 100 80 60 40 20

N=44; P < 0.05 ANOVA

0 0 1 2 3 4

6

2

4

Days

Hours 4 mg dexamethasone

3

3 mg morphine

Stein A. Yassouridis, C. Szoko, K. Helmke, Stein C.: Intra-articular Morphine versus Dexamethasone in Chronic Arthritis Pain 1999 83:525-32

NaCl

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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.

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Arthritic Treatment 3 pillars Non-medicinal treatment Medicinal treatment Surgery Therapeutic concepts Multimodal Long-term Individual Adapted to the current clinical picture

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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

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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

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I.a. Hyaluronic Acid Preparations Open questions Mechanism 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

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Weight reduction in osteoarthritis 109 patients BMI > 28 with osteoarthritis intervention: 8 weeks special diet – 800 kcal. Control group: conventional diet Outcome criteria: WOMAC pain index and WOMAC total index Results Reduction 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)

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SYSADOA „SYmptomatic Slow Acting Drugs in OsteoArthritis“ Ademetionine (Gumbaral®) D-glucosamine sulphate (Dona 200®) Oxaceprol (AHP 200®) Hyaluronic acid preparations (Hyalart®, Synvisc®, Hyalubrix®, ..)

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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: 2/4 SE: • 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.

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Opioid Conversion for Oral and Transdermal Applications Buprenorphine 1:5

100:1 Oxycodone

1:2

Morphine

Tramadol

100:1

7,5:1 Hydromorphone

Fentanyl

3:1 Morphine i.v

Characteristics

High initial dosage requires individual titration Reduce dose (30-50%) with conversion because of side-effects Usable for dosages between 60 and 250 mg morphine equivalen

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.

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Reasons for Opioid Rotation

Inadequate pain relief Tolerance development Side-effects Patient peculiarities

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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

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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.

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Geriatric Pain Patient doesn’t complain!

Doctor doesn’t ask!

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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!

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“Age is not an analgesic!�

Harkins/Price 1992

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Geriatric Pain Syndromes Osteoarthritis of the knee/hip

Postherpetic neuralgia

Degenerative spinal diseases

Polyneuropathy

Rheumatoid arthritis

Trigeminal neuralgia

Osteoporosis

Cancer pain

PAD

etc.

Angina pectoris Temporal arteritis

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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

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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)

2x

100 mg

Dipyrone

4-5 x

500-1000 mg

Paracetamol

4x

500-1000 mg

Flupirtine

3x

100 mg

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Non-medicinal Therapeutic Options Physiotherapy TENS, acupuncture Medical training therapy Relaxation training, hypnosis Pain coping training Patient education

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Medical Training – Motorial Level Stamina deficits Strength deficits Mobility deficits Strain/strain avoidance Neuromuscular coordination disorder

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Psychological Pain Therapy Relaxation therapy Biofeedback Hypnosis Cognitive behaviour therapy Individual or group therapy e.g. Pain coping training Stress coping training

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Geriatric Pain Interdisciplinary Pain Therapy

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)

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Pain and Dementia Incidence of dementia > 80 years ~ 10 %

Incidence of pain > 75 years ~ 90 %

> 85 years ~ 20 % Demented elderly people are

After hip fracture non-

prescribed fewer analgesics than

demented elderly people

non-demented people, both

receive three times as much

when “required� and regularly.

morphine equivalent than demented elderly people. Morrison Morrison et et al, al, JJ Pain Pain and and Symptom Symptom Management, Management,

Kassalainen Kassalainen et et al.; al.; Gerontol. Gerontol. Nursing, Nursing, 1998 1998

2000; 2000; 19:240-48 19:240-48

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Pain in Demented Patients Behavioural changes Autonomic nervous signs Tachycardia Hypertension Shallow breathing, panting Pale, sweating face

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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)

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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)

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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

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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) Hรถhne et al: Der Anaesthesist, 2004.3:291-303 (3) Fielitz et al: EAPC Abstractbook 2005

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Concomitant Medication Antiemetics Metoclopramide

Corticosteroids

Haloperidol

Benzodiazepines

Ondansetron

Cannabinoids

Dimenhydrinate

NK1-receptor antagonists

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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)

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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

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Multimodal Programmes for Optimal Geriatric Pain Therapy 1) Training therapy 2) Physiotherapy 3) Pain coping programmes Relaxation Stress coping Changes in behaviour 4) Medicinal pain therapy Activation and reinforcement of the patient’s own initiative

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Efficacy and safety of transdermal buprenorphine in patients over and under 65 years of age

Rudolf Likar, MD Pain Clinic, General Hospital Klagenfurt Klagenfurt, Austria

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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

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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

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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

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Patient Demographics / Diagnoses Number of Patients: Mean age: Gender:

82 59.5 years (range 32 - 83) male 36 (44 %) female 46 (56 %)

Diagnosis:

65,2 % 13,0 % 21,5 % 5,2 %

musculoskeletal pain neuropathic pain other non-malignant pain indications cancer related pain

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Age Groups Age Group A (≼65 years of age) Mean age: Gender:

Age Group B (<65 years of age) Mean age: Gender:

30 patients 74.3 years (range 67 - 83) male 12 (40 %) female 18 (60 %)

52 patients 51 years (range 32 - 63) male 24 (46 %) female 28 (54 %)

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Pain intensity – changes until treatment day 28 Baseline (n=82)

Day 28 (n=56)

% patients (VAS)

100 80 42,3

60

34,3 48,6

38,5

40 17,3

20 0

14,3 46,7

45

33,3 1,9

20

No

Mild

2,9 Moderate

Severe

Group A (≼65 years)

No

30

Mild

25

Moderate

Group B (<65 years)

Severe

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Pain Relief – Changes until Treatment Day 28

Visual Analogue Scale

(%)

80

60

Mean Âą SEM

p < 0.001

p = 0.006

p = 0.001

40

20

0

pre

post

all patients

pre

post

pre

post

>65 years

<65 years

age group A

age group B

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Analgesic Concomitant Medication

80

60

40

20 n = 52 < 65

5 ≼6

s ar ye

s ar ye

All Patients

n = 30

0

n = 82

% patients with concomitant analgesic medication

100

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1 0,9 0,8 0,7 n = 25

50 < ar s

s

ar ye

ar

ye

ye

s

s

ar

ar

ye

ye

4 -6

51

65 >

n = 27

n = 30

64 <

65 >

all patients

n = 52

0,5 0

n = 30

0,6

n = 82

adverse events per patient

Tolerability (1)

s

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Tolerability (2)

Age-Group A

adverse events per patient

1

Patients >65 years (30)

Age-Group B1 Patients 51 - 64 years(27)

0,8

Age-Group B2 Patients <50 years (25) 0,6

0,4

0,2

0

Dizziness

Nausea

Malaise & Fatigue

Pruritus

Vomiting

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Daily Dose (at Day 28)

buprenorphine (µg/h)

75

Mean ± SEM

60

n.s. p = 0.062

45

30

15 n = 36

n = 20

n = 56

0 < 65

5 ≥6

s ar ye

s ar ye

All Patients

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Mean ± SEM

n.s. p = 0.954

0, 6 0,4

0,2

0,30

Mean ± SEM

0,25

n.s. p = 0.494

0,20 0,15 0,10

s ar ye 65 < s ar ye

5 ≥6

All Patients

n = 27

0,00

n = 18

0,05

n = 45

n = 27

s ar ye 65 < s ar ye

5 ≥6

All Patients

n = 18

0,0

[plasma norbuprenorphine] (ng/ml)

0,8

n = 45

[plasma buprenorphine] (ng/ml)

Plasma Levels of Buprenorphine and Norbuprenorphine at Day 28

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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.

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EFFICACY & SAFETY OF TRAMADOL AND TRAMADOL SR IN ELDERLY PATIENTS

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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.

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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.

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PATIENTS (1) Age > 74 years Mean ± SEM = 80.6 ± 0.9 years Range = 75 - 91 years

Age < 65 years Mean ± SEM = 49.9 ± 1.8 years Range = 19 - 64 years n = 39 17 females / 22 males Body Mass = 75.3 ± 3.4 kg

n = 30 23 females / 7 males Body Mass = 75.4 ± 2.9 kg

Age 65 - 74 years Mean ± SEM = 69.7 ± 0.5 years Range = 65 - 74 years n = 31 18 females / 13 males Body Mass = 70.8 ± 2.8 kg

The enrolled patients were stratified into three equally sized age groups.

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PATIENTS (2) Age > 74 years Serum Creatinine = Age < 65 years

Serum Creatinine = 0,79 ± 0,04mg/dL Serum ASAT (GOT) = 17,2 ± 2,1 U/L

0,93 ± 0,06 mg/dL Serum ASAT (GOT) = 12,0 ± 1,0 U/L Age 65 - 74 years Serum Creatinine =

Serum levels of Creatinine and ASAT (Mean ± SEM)

0,90 ± 0,05 mg/dL Serum ASAT (GOT) =

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.

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Younger Patients Elderly Patients 65-74 years

Eldest Patients

Pharmacokinetics & Pharmacodynamics

Pharmacokinetics & Pharmacodynamics

< 65 years

Steady State Visit 2

Steady State Visit 1

Enrolment Visit

Baseline Pharmacodynamics

STUDY DESIGN

> 74 years

Tramadol

Tramadol SR

Immediate Release Galenic

Sustained Release Galenic

Chronic intake of tramadol until steady state was achieved, followed by tramadol SR.

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DIAGNOSES / CAUSES OF PAIN Group Group of of Patients Patients Age Age (years)/Frequency (years)/Frequency (%) (%)

Diagnosis Diagnosis ICD-10 ICD-10 Code Code

<65 <65

65 65 -- 74 74

>74 >74

Neoplasms Neoplasms

CC 00 00 –– D D 48 48

28 28 (34%) (34%)

14 14 (24%) (24%)

12 12 (21%) (21%)

Musculoskeletal Musculoskeletal

M M 00 00 –– M M 99 99

99 (11%) (11%)

12 12 (20%) (20%)

18 18 (32%) (32%)

Injuries Injuries & & External External Causes Causes

SS 00 00 –– TT 98 98

23 23 (28%) (28%)

88 (14%) (14%)

10 10 (18%) (18%)

Nervous Nervous System System

G G 00 00 –– G G 99 99

55 (6%) (6%)

77 (12%) (12%)

55 (9%) (9%)

Unspecific Unspecific Symptoms Symptoms

R R 00 00 –– R R 99 99

13 13 (16%) (16%)

12 12 (20%) (20%)

66 (11%) (11%)

Other CC 00 44 (5%) 66 (10%) 55 (9%) 00 –– D D 48 48 (5%) (10%) (9%) Other Causes Causes Neoplasms and injuries were the leading causes of pain in younger, while musculoskeletal disorders were predominant in elderly patients.

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DAILY TREATMENT DOSES 500

(mg/day)

Tramadol Dose

400

Tramal

n.s.

ANOVA p=0.184

n.s.

n.s.

Tramal SR ANOVA p=0.445

n.s.

n.s.

ANOVA = Comparison of respective treatment doses between three agegroups

300 200 100 0

< 65 years

65-74 years

> 74 years

(n = 20)

(n = 17)

(n = 18)

Mean Âą SEM

At steady state conditions, elderly patients required slightly (however non-significantly) lower doses of both, tramadol and tramadol SR.

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CONCOMITANT ANALGESICS Concomitant Concomitant Analgesic Analgesic Medication Medication Number Number of of Patients Patients (& (& Incidences) Incidences)

Group Group of of Patients Patients Age Age (years)/Frequency (years)/Frequency (%) (%) <65 <65

65 65 -- 74 74

>74 >74

33 33 (85%) (85%)

20 20 (65%) (65%)

20 20 (67%) (67%)

24 24 (62%) (62%)

15 15 (48%) (48%)

15 15 (50%) (50%)

Opioids Opioids

11 (3%) (3%)

00 (0%) (0%)

22 (7%) (7%)

Non Non Antiphlogistic Antiphlogistic Analgesic Analgesic Drugs Drugs (Metamizol (Metamizol // Paracetamol) Paracetamol)

19 19 (49%) (49%)

10 10 (32%) (32%)

11 11 (37%) (37%)

Others Others

11 (3%) (3%)

00 (0%) (0%)

11 (3%) (3%)

Concomitant Concomitant Analgesic Analgesic Medication Medication (overall) (overall) Non Non –– Steroidal Steroidal Anti-Inflammatory Anti-Inflammatory Drugs Drugs NSAID‘s NSAID‘s

Elderly patients required less often concomitant analgesic medication as compared to patients being younger than 65 years.

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(aU)

Numerical Pain Scale

PAIN INTENSITY (1) 8

**

7

p<0.001

6 Baseline

5 4 3

**

** **

Tramal

** **

**

Tramal SR

2 1 0

Mean Âą SEM Maximum Pain = 10 aU

< 65 years

65-74 years

> 74 years

(n = 20)

(n = 17)

(n = 18)

Pain intensity before treatment was comparably high among all groups. Treatment-induced pain-reductions were similar for all age-groups.

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(%)

Visual Analogue Scale

PAIN INTENSITY (2) 80

**

70

p<0.001 Baseline

60

Tramal

50

Tramal SR

40 30 20

**

** **

** **

**

10 0

Mean Âą SEM Maximum Pain = 100 %

< 65 years

65-74 years

> 74 years

(n = 20)

(n = 17)

(n = 18)

Independent of the method applied to quantify pain, similarly considerable pain relief was observed in all age-groups.

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PHARMACOKINETICS (1) Patients < 65 years

Patients 65 - 74 years

(+) Tramadol (ng/mL)

[Serum Tramadol]

400 ANOVA p=0.278

300

n.s.

Patients > 74 years ANOVA p=0.398

ANOVA p=0.363

n.s.

ANOVA p=0.694

n.s.

n.s.

200

100 Mean Âą SEM

0 2,5 hours 5,0 hours following Immediate Release Tramadol

5,0 hours 10,0 hours following Sustained Release Tramadol

No accumulations of (+) or (-)tramadol were observed with increasing age, suggesting that their hepatic metabolism is not reduced in elderly.

European Interactive Pain Course 03.-07.09.07

PHARMACOKINETICS (2) Patients 65 - 74 years

Patients > 74 years

120 100 80 60 40 20 0

(+) Tramadol-Metabolite (ng/mL)

Patients < 65 years

[Serum M1]

(+) Tramadol-Metabolite (ng/mL)

[Serum M1]

Patients < 65 years

Patients 65 - 74 years

120 100

ANOVA p=0.329

n.s.80

ANOVA p=0.244

n.s.

ANOVA ANOVA p=0.164 p=0.329

n.s. n.s.

ANOVA ANOVA p=0.100 p=0.244

n.s. n.s.

Patients > 74 years

ANOVA p=0.100

n.s.

ANOVA p=0.164

n.s.

60 40 20

Mean Âą SEM

2,5 hours 5,0 hours 5,0 hours 10,0 hours following following 0 Immediate Release Tramadol Sustained Release Tramadol 2,5 hours 5,0 hours 5,0 hours 10,0 hours following following Immediate Release Tramadol Sustained Release Tramadol

No accumulation of (+) or (-)M1 was observed with increasing No accumulations of (+) or (-)M1 were observed with increasing age, age, suggesting that renal elimination is not deteriorated in the suggesting that their renal elimination is not deteriorated in the elderly. elderly.

European Interactive Pain Course 03.-07.09.07

ADVERSE EVENTS 100 Patients 65 - 74 years

Patients > 74 years

80

Incidences (%)

Predominant Adverse Events

Patients < 65 years

60 40 20 0

Nausea

Dizziness Malaise & Fatigue Vomiting

Constipation

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.

European Interactive Pain Course 03.-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 Course 03.-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 Course 03.-07.09.07

Multimodal therapy of chronic pain R. Sittl

European Interactive Pain Course 03.-07.09.07

Interdisciplinary Pain Center University Hospital Erlangen - Germany

European Interactive Pain Course 03.-07.09.07

Patient - characteristics Pain syndromes Low back pain - neuropathic pain - headache Characteristics Multi-localisation A long history of pain Psycho-social problems A large number of ineffective treatment trials

European Interactive Pain Course 03.-07.09.07

Pretreatment strategies

Physical , physiotherapeutic , psychotherapeutic treatments TENS acupuncture

Non-opioids and strong opioids Coanalgesics

Non-opioids and weak opioids Non-opioids

European Interactive Pain Course 03.-07.09.07

Chronic pain patients‘ problems 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............ The challenge for us and the patient is to ‘unlock the patients potential’ in helping them to help themselves.

European Interactive Pain Course 03.-07.09.07

Multimodal therapeutic group - programms for chronic pain patients Treatment strategies Movement therapy, medical training

Psychological pain treament- active coping strategies

Faithful relation to the patient optimal pharmacological treatment

Education

Relaxation

European Interactive Pain Course 03.-07.09.07

Precondition of multimodal therapy is an interdisciplinary team

Team structure in the Erlangen pain clinic Pain Pain specialist specialist Neurologist Neurologist

Pain Pain specialist specialist Anesthesist Anesthesist

Orthopedic Orthopedic specialist specialist

Psychsomatic Psychsomatic specialist specialist

Psychiatrist Psychiatrist

Sport Sport therapy therapy specialist specialist

Psychologists Psychologists

PhysioPhysiotherapist therapist

Nursing Nursing stuff stuff –– co-therapists co-therapists Staff Staff for for organisation organisation and and documentation documentation

European Interactive Pain Course 03.-07.09.07

Interdisciplinary pain day clinic Implementational principles

Patient, doctor or psychologist enquirees Checking the quest. and patients history Pain ambulance appointment

Day clinical appointment (4-6 hrs)

The questionnaire from the german pain society is sent

Alternative

European Interactive Pain Course 03.-07.09.07

Interdisciplinary pain day clinic Day clinic – patient screening Medical examination 90 – 120 min.

Psychological examination 90 min

„MediTrain“ diagnostics 120 min Outpatient therapy concepts

Screening meeting

Recommend a stationary therapy

Day clinical treatment, multimodal treatment

Headache group therapy, twice a week for 8 weeks

Pain group therapy (4 weeks,7 hours/d)

Group therapy for patient with somatic pain disorders (1- 2 times a week for 6 months

European Interactive Pain Course 03.-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 pain

Guzman J. et al: Cochrane Database Syst Rev 2002

European Interactive Pain Course 03.-07.09.07

Multimodal pain therapy Treatment elements Pharmaco-therapy Non-pharmacological-therapy Physiotherapy Movement therapy(sport) Relaxation education, hypnosis „Coping with pain“ education

Psychotherapeutical group Patient education Medicinal consulting Psychotherapeutical consulting „Experiencing nature“, acupressure, Qi Gong

Usually Usually no no invasive invasive and and passive passive therapeutic therapeutic approaches approaches during during group group therapy! therapy!

We want to re-activate patients and generate self-responsibility for their pain disease.

European Interactive Pain Course 03.-07.09.07

Weekly plan of the 4-week pain group Monday 8.00

Meditrain (Movement therapy

10.3 0 11.0 0

Tuesday

Psychotherapeutic group

Physiotherap y 10.30: Hypnosis Relaxation

12.0 0 13.0 0 14.0 0 14.1 5 15.1 5

Medical consulting or TENS Break Analgesics

Relaxation

Wednesday

Thursday

Friday

Meditrain

8.30: „Coping with pain“ group

Meditrain

Break

Break

Break

Watergymnastics

Relaxation

Water gymnastics

Break for lunch

11.30-12.30: Lunch

Back pain „Coping with pain“ group

Medical consulting or TENS

Break

Psychotherap eutic group

Relaxation 13.00: Meditraineducation

Training

Break Education Neuropathik pain

European Interactive Pain Course 03.-07.09.07

Patient characeristics: deficits in physical capacity Lack of endurance Lack of strength Movement deficits Lack of flexibility Neuro muscular coordination faults

Improvement is possible by movement therapy (individual physical exercise)

European Interactive Pain Course 03.-07.09.07

Exercises to improve endurance, strength, flexibility and coordination.........

Training duration: 2 h/d, individual training plans, cont. adaption

European Interactive Pain Course 03.-07.09.07 What a focussed movement training can achieve

Increase in strength Increase in endurance Increase in self confidence Feeling success Social contacts Positive social experiences

Active improvement of physical capacity - acceptance of active coping stregies

European Interactive Pain Course 03.-07.09.07

Education Bio-psycho social-pain model Basic pharmacology Basic anatomy Acupressure, tens Weight management... Information on special pain syndromes

Sch mer z

Sofia 2005/ Sittl

Successful treatment of chronic pain is based on the …. Bio - psycho - social pain model

Psyche

e.g. anxiety, depression, overdemands, ...

Pain

Social conditions e.g. health system, economic situation, …

Social environment e.g. inter-relationship problems, mobbing at work, …

European Interactive Pain Course 03.-07.09.07

Psychological pain therapy methods Relaxation therapy Biofeedback In depth relaxation (hypnosis)

Cognitive behavior therapy as singular or group therapy

„Coping with pain“ „Coping with stress“

European Interactive Pain Course 03.-07.09.07

„Coping with pain“ education Information Perceptive controlling Enjoyment training Changing negative thoughts and emotions

n. Basler 2001

European Interactive Pain Course 03.-07.09.07

Psychosomatic groupsession Thematics:

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?

European Interactive Pain Course 03.-07.09.07

Conclusion 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

Activation is the key!!!

European Interactive Pain Course 03.-07.09.07

Thank you for attention!

European Interactive Pain Course 03.-07.09.07

Treatment of low back pain

European Interactive Pain Course 03.-07.09.07

Classification according to duration Acute pain Chronic pain Lasts longer than expected Is caused by external or Is uncoupled from the internal injury or damage causative event Its intensity correlates Becomes a disease in with the triggering its own right stimulus Its intensity no longer correlates It can be easily located Has a distinct warning with a causal stimulus and protective function Has lost its warning and protective function Is a special therapeutic challenge Requires interdisciplinary procedures

European Interactive Pain Course 03.-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 Course 03.-07.09.07

Spinal canal width: normal

129

European Interactive Pain Course 03.-07.09.07

Case report 2: Mrs B.

Diagnosis Post-myelo-CT revealed spinal canal stenosis

130

European Interactive Pain Course 03.-07.09.07

Case report 3: Mrs B.

Spinal canal stenosis confirmed on functional myelography.

131

European Interactive Pain Course 03.-07.09.07

Spinal canal stenosis on MRT

132

European Interactive Pain Course 03.-07.09.07

Spinal canal stenosis – typical clinical symptoms Gait Legs wide apart, leaning forward slightly, flat lumbar lordosis Pain 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

Unproblematic Cycling, climbing, sitting 133

European Interactive Pain Course 03.-07.09.07

Spinal canal stenosis Symptoms with narrow spinal canal

%

Clinical symptoms with narrow spinal canal %

Walking distance limited

90

ATR absent

58

Low-back pain

87

Sensory disturbances

52

Leg pain

84

Myasthenia

51

Numbness/paraesthesia

51

Positive Lasègue’s sign

49

Weak legs

44

Patellar reflex absent

24

Modified after: Dt. Ges. f. Orthopädie und orthopäd. Chirurgie + BV d. Ärzte f. Orthopädie (Hrsg.) Leitlinien der Orthopädie, Dt. Ärzte-Verlag, 2. Auflage, Cologne 2002

134

European Interactive Pain Course 03.-07.09.07

Spinal canal stenosis Therapeutic Ladder

Orientation criteria Pain, extent of stenosis, walking distance, refractory, suffering, concomitant disease Step 1: outpatient treatment Counselling, physiotherapy, analgesic and/or anti-inflammatory agents, corset to correct lordosis (new: TENS belt) Step 2: outpatient/inpatient treatment Step 1, with additional epidural injections Step 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

135

European Interactive Pain Course 03.-07.09.07

Case report 1: Mrs G. Mrs G. 39 years old, profession: shop assistant, unemployed for 2 years No relevant previous diseases Case history Severe acute back pain since the morning Radiating along the rear of the right thigh to the foot Findings Right Lasègue’s sign positive Reduced sensation in segment right S1 Right ATR absent Unable to stand on toes of right foot

European Interactive Pain Course 03.-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 Course 31.08-05.09.08

Case report 6: Mrs G. Procedure

Video statement: “G in der Sonne.mpg�

Put on morphine 60 mg BID Participated in a multimodal treatment program after approval of a temporary disability pension

European Interactive Pain Course 31.08-05.09.08

Back pain – summary of treatment principles Acute back pain (without red flags) Physical Bed rest for a short period only Application of heat / cold treatment Physiotherapy Short AU

Drug treatment Analgesics Coanalgesics

Stimulation

TENS, acupuncture Interventions

Local/regional infiltration or nerve blockades If there is no improvement within 2 – 4 weeks, order further tests.

European Interactive Pain Course 31.08-05.09.08

Back pain – summary of treatment principles Chronic back pain Physiotherapy and sports therapy

Activating physiotherapy Medical training therapy

Pharmacological

Analgesics Coanalgesics

Stimulatory

TENS, acupuncture Spinal cord stimulation Alternative methods

Back pain and social insurance: Author Dr. Leifeld, Rendsburg Download: www.schmerzzentrum.klinikum.uni-erlangen.de

Psychological

Relaxation techniques, pain coping strategies Multimodal pain management – “Group programs”

Duration 4-5 weeks, ~ 160 h

European Interactive Pain Course 31.08-05.09.08

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

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