CURRICULUM VITAENama : dr. Syafruddin Gaus, Ph.D, Sp.An-KMNTTL : Makassar /19 Oktober 1963Alamat rumah : Perumahan Dosen UNHAS Tamalanrea

Jl. Thomas Alfa Edison Blok AC Baru No. 14 Makassar-90245

Telp/HP/Fax/Email : 0411-4773189 /HP: Flexi: 0411-5764244 GSM: 081543058610

Email : udhingaus@hotmail.com

Alamat kantor : Bagian Ilmu Anestesi, Perawatan Intensif & Manajemen Nyeri

Fakultas Kedokteran UNHAS / RS. Dr. Wahidin Sudirohusodo

Jl. Perintis Kemerdekaan Km.11 Tamalanrea Makassar-90245

Telp/HP/Fax/Email : 0411-582583 / Fax.0411-590290 / HP:081543058610

anestesiologi_unhas@yahoo.co.id / udhingaus@hotmail.com

Riwayat Pendidikan : Lulus dokter umum FK Universitas Hasanuddin tahun 1991 Lulus dokter spesialis anestesi FK Universitas Hasanuddin tahun

2005 Lulus S3 Hiroshima University School of Medicine tahun 2003 Konsultan Manajemen Nyeri (KMN) tahun 2009

CURRICULUM VITAERiwayat Pekerjaan: Jabatan: - Staf Pengajar Bagian Anestesiologi: 1996-sekarang

- Sekeretaris Program Studi Bagian Anestesiologi: 2006-sekarang

- Institusi Kesehatan :1. Bagian Anestesiologi & ICU FK Universitas Hasanuddin – RS Dr. Wahidin Sudirohusodo Makassar2. Bagian Anestesi & ICU di RS. Polisi Bhayangkara mappa Oddang Makassar mulai tahun 2006 sampai sekarang3. Bagian Anestesi & ICU di RS. Ibnu Sina Makassar mulai tahun 2006 sampai sekarang 4. Bagian Anestesi di RSB. Siti Miriam Makassar mulai tahun 2006 sampai sekarang 5. Bagian Anestesi di RSIB Siti Khadijah I mulai tahun 2006 sampai sekarang

COMPLEX REGIONAL PAIN

SYNDROMESyafruddin Gaus

Dibawakan pada Simposium ISAPM 16-17 September 2011, Hotel Clarion - Makassar

Synonyms

Causalgia

Algodystrohy Algoneurodystrohy Shoulder-hand

syndrome Hyperpathic pain Traumatic

vasospasm Traumatic

angiospasm Peripheral acute

toponeurosis Postinfarctional

sclerodactyly

Also known as: Reflex Sympathetic

Dystrophy (RSD)

Sympathalgia Sympathetic

Maintained Pain Sudek’s

osteodystrophy Reflex Neurovascular

Dystrophy Reflex dystrophy Acute atrophy of

bone Post-traumatic

osteoporosis

History (1) Galen (1528):

Described nerve trunk along rib heads connecting to the spinal cord

Initiated concept of sympathy between different body parts

Potts (1700):“Atrophy and burning pain in an injured extremity”

Bernard (1853):“Role of sympathetic system in temperature control”

Colonel Weir Mitchell, MD (1864):“Severely painful dystrophic syndrome following

ballistic injuries” in US Civil War soldiersCausalgia

History (2) Leriche (1926):

“Sympathetic nerve root dysfunction as a cause of pain” First to use surgical sympathectomy to relieve pain of

causalgia Bonica (1953):

Popularized the term RSDStages I, II, and III of RSD: - Stage I (acute): immediately or within weeks, pain,

edema, allodynia, and hyperesthesia - Stage II (dystrophic): in 3-6 months, pain, cooling,

brawny discoloration, bone demineralization - Stage III (atrophic): thin skin, atrophy of muscles,

joints, and bones, some attenuation of pain, psychological issues

History (3) International Association for the Study

of Pain (1994):CRPS type I = RSDCRPS type II = Causalgia

Introduction (1) Complex Regional Pain Syndrome

(CRPS) is a disorder of the extremities.

A diagnosis of CRPS requires the presence of regional pain and sensory changes following a noxious event.

The pain is more severe than expected from the injury which caused it.

Unclear pathophysiology.

Introduction (2)CRPS is characterized

by: - Pain - Swelling/edema - Limited range of motion (ROM)

- Vasomotor instability - Skin changes/abnormal skin

color - Patchy bone demineralization - Temperature changes - Atrophy

Fig. 1. Clinical features of Complex Regional Pain Syndrome type I (Reflex Sympathetic Dystrophy)

A consensus development conference in 1994 grouped these disorders under the single heading CRPS.

Two types of CRPS have been recognized:CRPS Type I:

○ No definable nerve lesion is present.○ Represents about 90% of clinical cases.○ Formerly termed Reflex Sympathetic Dystrophy

(RSD).CRPS Type II:

○ A definable nerve lesion is present.○ Formerly termed Causalgia.

Introduction (3)

Merskey H, Bogduk N. Classification of Chronic Pain: Descriptions of Chronic Pain Syndromes and Definitions of Pain Terms, 2nd ed. Seattle: IASP Press; 1994.

Harden R.N, Bruehl SP. Diagnosis Criteria: The Statistical Derivation of the Four Criterion Factors. Progress in Pain Research and Management, Vol. 32. Seattle: IASP Press; 2005:45-58

(1) (2) (3) (4)Positive sensory

abnormalities

Vascular abnormalitie

s

Edema, sweating

abnormalities

Motor, trophic changes

Spontaneous pain

Mechanical hyperalgesia

Thermal hyperalgesia

Deep somatic hyperalgesia

Vasodilatation Vasoconstricti

on Skin

temperature asymemetries

Skin color changes

Swelling Hyperhidrosis hypohidrosis

Motor weakness Tremor Dystonia Coordination

deficits Nail, hair

changes Skin atrophy Joint stiffness Soft tissue

changesInterpretation for Clinical Use:> 1 symptom of > 3 categories each AND > 1 sign of > 2

categories eachSenstivity 0.85; Specifity 0.60Interpretation for Research Use::> 1 symptom of > 4 categories each AND > 1 sign of > 2 categories eachSenstivity 0.70; Specifity 0.96

Revised Diagnostic Criteria for CRPSCategories of Clinical Signs/Symptoms

Baron R et al. CRPS: a neuropathic disorder?. Pain 2010, An Updated Review.

Epidemiology Age - common in younger adults:

• Mean: 41.8 years• Mean age at time of injury: 37.7 years

Mean duration of symptoms before pain center evaluation: 30 months

2.3 to 3 times more frequent in females than males.1

Usually involves a single limb in the early stage.2

1. Raja SN et al. Anesthesiology. 2002;96:1254-1260. 2. Galer BS et al. In: Loeser, ed. Bonica’s Management of Pain. 2001, 388-411.

Epidemiology USA: Incidence: 5.5 per 100,000

person-years Prevalence: 2.1 per 100,000

Europe: Incidence: 26.2 per 100,000

person-years1. Raja SN et al. Anesthesiology. 2002;96:1254-1260.

2. Galer BS et al. In: Loeser, ed. Bonica’s Management of Pain. 2001, 388-411.

Natural History of CRPS Triggered by a variety of events:

An injury or trauma (often minor) ranks as the leading provocative event

Ischemic heart disease and myocardial infarction Cervical spine or spinal cord disorders Cerebral lesions (stroke)Infections Surgery Repetitive motion disorder or cumulative trauma,

causing conditions such as carpal tunnel In approximately 10% of patients, no

precipitant can be identified

Etiology (1) The pathogenesis of CRPS is

unclear. It is thought to involve the

formation of a reflex arc after an inciting event.

The reflex arc follows the routes of the sympathetic nervous system.

It is modulated by cortical centers which produce peripheral vascular changes.

Etiology (2) Autonomic features are thought

to be due to catecholamine hypersensitivity and include:Cyanosis MottlingIncreased sweatingAbnormal growth of hair Diffuse swellingColdness

Etiology (3) A proposed mechanism for the

persistent pain & allodynia is the release of inflammatory mediators & pain producing peptides by peripheral nerves, including:Substance PNeuropeptide YCalcitonin gene related peptide

(CGRP)IL-6, IL-8, IL-1βTNF-α

Normal terminations of primary afferents in the dorsal horn

After Nerve Injury

Allodynia: Nerve injury leads to central reorganization in the spinal dorsal horn

Clinical Manifestations CRPS may occur in either the

upper or lower extremities. Involvement of both upper and

lower extremities in the same patient is unusual.

It may be recurrent. Three clinical stages can occur

during the course of illness.

Stage I (Acute Stage) The patient develops pain in a limb

following an event or without apparent cause.

Symptoms: burning or throbbing pain, diffuse aching, sensitivity to touch or cold, and localized edema.

Vasomotor disturbances occur with variable intensity, producing altered color and temperature.

Radiographs are usually normal but may show patchy demineralization of the involved bones.

Stage I (Acute Stage)

Stage II (Dystropic Stage) Is characterized by:

Progression of soft tissue edema Thickening of the skin and articular soft

tissues Muscle wasting Development of brawny skin

Symptoms typically last for three to 6 months.

Stage II (Dystropic Stage)

Stage III (Atrophic Stage) The most severe stage. It is characterized by:

Limitation of movement Shoulder-hand syndrome Contractures of digitsWaxy trophic skin changesBrittle ridged nails

Radiographs reveal severe bone demineralization.

Stage III (Atrophic Stage)

Diagnostic Test (1)

The diagnosis of CRPS is a clinical diagnosis, predominantly based on signs and symptoms

Majority of tests, sensitivity and specificity have not been determined

The diagnostic value of laboratory test can only be established in patients who have received a reliable clinical diagnosis

No gold-standard laboratory test Useful in early stages of the disease may

fail later onRommel O, Habler H-J, Schurmann M. Laboratory Test for Complex Regional Pain Syndrome. Progress in Pain Research and Management, Vol. 32. Seattle: IASP Press; 2005:139-159.

Diagnostic Test (2) Test to verify clinical findings: - Edema, impaired joint movement and

pain - Bilateral differences in skin

temperature - Evaluation of sensory dysfunction:

quantitative sensory testing

Sympathetic function tests: - Peripheral vasoconstrictor reflex - Sudomotor function test - Sympathetic skin response

Bilateral differences in skin temperature

Thermography: warmer early, cooler late

Temperature measurement: 2°C difference is significant

Diagnostic Test (3) Neurophysiological procedures: - Nerve conduction velocity - Somatosensory evoked potentials - Electromyography Psychological assessment Imaging method: - Radiograpy - Three-phase of bone scan - MRI

Radiography:

Patchy osteoporosis (late in the course)

Sudek’s atrophy- periarticular osteoporosis

Cortical thinning and cortical bone loss secondary to an increase in osteoclastic activity (2-3weeks.)

Abnormal third phase that is characterized by a diffusely increased uptake (very low sensitivity & specificity)

Three-phase bone scintigraphy:

Management of CRPS (1) Multidisciplinary Early intervention: delay in

diagnosis and treatment leads to poor outcomes (Stanton-Hicks, 2001)

Primary aim: return to normal function via gradual progression from gentle movements to load-bearing activities (Harden, 2001)

Desensitization (Stanton-Hicks et al, 2001)

Management of CRPS (2) Physical and occupational

therapies Pharmacologic management Psychological interventions Traditional interventional

therapies Implanted therapies Miscellaneous and experimental

therapies

Pharmacologic Management Must be secondary & supportive of

effort to mobilize the affected limb & to restore its function.

Major treatment for the patients whose symptoms do not improve substantially despite aggressive rehabilitation efforts within the first year after onset.

Most drugs used for neuropathic pain are used to treat CRPS

Evidence-Based Pharmacotherapy for

CRPS

Pharmacotherapy for early CRPSPharmacotherapy for chronic

CRPS

Pharmacotherapy for Early CRPS

Modes of action: Decreasing inflammation & minimizing ectopic electrical activity after nerve injury through neuronal membrane stabilization (Devor et al. 1985)

Oral prednisone 30 mg/day, methylprednisolone 32 mg/day (Christensen et al. 1982, Braus et al. 1994)

Corticosteroid:

Level 3

Pharmacotherapy for Early CRPS

Modes of action: Inhibit bone resorption by osteoclast

and direct antihyperalgesic effects independent of its effect on bone (Braga 1994)

Calcitonin 100-400 IU intranasally (Bickerstaff & Kanis 1991; Gobelet et al. 1992; Hamamci et al. 1996; Zyluk 1998)

Calcitonin:

Level 1

Pharmacotherapy for Early CRPS

Modes of action: Inhibitors of osteoclast-mediated bone

resorption, prostaglandin E2, proteolytic enzyme, lactid acid, and proinflammatory cytokines (Ohya et al.1985; Van Offel et al. 2001)

Pamidronate 30 mg/day for 3 days (acute and chronic CRPS) (Maillefert et al. 1999)

Bisphosphonate:

Level 2

Pharmacotherapy for Early CRPS

Modes of action: Hypothesis that CRPS is caused by

oxygen-derived free radical damage that initiates or potentiates inflammation and microangiopathy.

Benefit for topical dimethylsulfoxide (DMSO) in fatty cream (Zuurmond et al.1996)

500 mg of vitamin C in reducing prevalence of CRPS (Zollinger et al..1999)

Antioxidants & Free-radical Scavengers:

Pharmacotherapy for Early CRPS

Phenoxybenzamine in early CRPS type I (Muizelaar et al.1997) & chronic CRPS type II (Ghostine et al..1984) were helpful

Ca channel blocker: nifedifine (Prough et al..1985; Muizelaar et al. 1997)

Alpha-adrenergic antagonist & vasodilators:

Level 4

Pharmacotherapy for Chronic CRPS

Available in several forms: viscous lidocaine, gel, creams, sprays, and patch.

5% lidocaine patch is currently the most popular route of administration because protect allodynic skin from contact.

Meier et al. 2003; found efficacy of lidocaine for patients with focal neuropathic pain including CRPS.

Topical local anesthetics:

Level 2

Pharmacotherapy for Chronic CRPS Modes of action: Potentiation of serotonergic and especially

noradrenergic descending inhibitory pathway to decrease dorsal horn hyperactivity, μ-opioid activity, and cation channel blockade (Jensen 2002)

Nortriptyline or desipramine 50-75 mg once/day are the best choise for most patient with CRPS (Max et al. 1992)

May be the single medication for CRPS available today (Oaklander 2005)

Tricyclic antidepressants (TCAs):

Level 2

Pharmacotherapy for Chronic CRPS

Mode of action: Decreasing central neuronal

hyperexcitability and decreasing calcium-mediated synthesis and release of excitatory neurotransmitter (Gee et al. 1996)

Gabapentin 600 mg/day is efficacious and safe in CRPS patient (Mellick and Mellick 1997)

Pregabalin, an analoque of gabapentin is useful for CRPS (Dworkin et al. 2003)

Antiepileptic drugs:

Level 1 & 2

Pharmacotherapy for Chronic CRPS

Controlled-release oxycodone 60 mg/day reported about 30% reduction in pain (Gimbel et al. 2003; Watson et al. 2003)

Tramadol was effective at doses up to 400 mg/day (Harati et al. 1998)

Well-designed study found 27% pain relief attributed to use of controlled-release morphine 30 mg/day or methadone 15 mg/day (Raja et al. 2002)

Opioids:

Level 2

Challenges of CRPS Natural course and pathophysiology

remain elusive1

Therapies remain controversial2

Underdiagnosed and undertreated3

Significant morbidity and loss of quality of life

1. Jänig W. In: Harden , Baron Janig, eds. Complex regional Pain Syndrome, Progress in Pain Research and Management. 2001: 3-15.2. Bogduk N. Current Opinions in Anesthesiology. 2000;14:541-546.3. Raja SN et al. Anesthesiology. 2002;96:1254-1260.

Prognosis Difficult to predict Earlier intervention may be more

likely to be successful Some patients experience reduced

symptoms or apparently full recovery

Some patients continue to experience significant disability

Raja SN et al. Anesthesiology. 2002;96:1254-1260.

Summary: Early diagnosis, appropriate

treatment, and intervention is essential

Ideal treatment should be multidisciplinary

THANKS FOR YOUR ATTENTION!