Toronto Physical Medicine & Rehabilitation Conference - …torontopmrconference.com/2019/wp-content/uploads/2019/11/... · 2019-11-03 · • For CRPS, there is moderate evidence

Treatment of Complex Regional Pain SyndromeDr. Paul S. TumberAssistant Professor of AnesthesiologyDirector of Transitional Pain Service at TWH,Pain Management Consultant UHN-SHS, Wasser Pain Clinic, WCH

Disclosure Slide• Nothing to disclose in terms of this

presentation

Objectives

Discuss various options for the treatment of CRPS

List the pharmacologic agents used to treat CRPS

Explain the role of interventional pain medicine for CRPS

Case example to consider:• 40 year old female. Fell

6 weeks ago. • Does not want to use

the arm, drops things easily. Fearful of touch and re-injury.

• Taking Tylenol #3 and Ibuprofen with no benefit

Treatment overview• Individualized, patient-centered • Multi-disciplinary• Pillars of Pain Management

– Physical Therapy – Psychologic– Pharmacologic– Procedural

Treatment overview• Individualized, patient-centered • Multi-disciplinary • Pillars of Pain Management


Individualized Care• Appropriate assessment / diagnosis• Assess the severity of CRPS and risk

– ? Interference with daily activity / work – ? Anxiety/depression, sleep, PTSD, fear-

avoidance, workplace demands, deconditioned, weight gain,

– ? Duration of greater than 2-3 months• Educate the patient

– Explain need for tailored physiotherapy Standards for the diagnosis and management of CRPS:Results of a European Pain Federation task force. Eur J Pain. 2019; 23

www.crpsnetworkuk.org

Treatment overview• Individualized, patient-centered • Multi-disciplinary • Pillars of Pain Management


Multidisciplinary ApproachWhy?- CRPS is complex! - Involves central sensitization (brain)

and peripheral sensitization (limb)- Dysfunction in sympathetic nervous

system, musculoskeletal, immune systems

- Likely genetic, psychological factors

Bruehl, S. BMJ 2015; 350

CRPS and the CNS• Affective-motivational changes (amygdala)• Dysregulation of thalamo-cortical nociceptive

pathways– Distortion of cutaneous sensation– Inability to suppress nociception

• Motor symptoms reflect CNS alterations in processing/representation– Paresis, tremor, dystonia, myoclonus

Goebel A, Barker CH, Turner-Stokes L et al. CRPS in adults: UK guidelines for diagnosis, referral and management in primary and secondary care. London: RCP, 2018.

Goebel A, Barker CH, Turner-Stokes L et al. CRPS in adults: UK guidelines for diagnosis, referral and management in primary and secondary care. London: RCP, 2018.

Treatment overview• Multi-disciplinary • Individualized, patient-centered • Pillars of Pain Management


Physical Therapy• Goal: improve function, range of motion and

ability to manage ADL’s • Gentle, graded (quota based) • Avoid immobility• Occupational Therapy, vocational counsel• Treatments: individualized

– Need for more evidence – Graded Motor Imagery– Mirror Therapy– Biofeedback

Ballantyne, Jane C.,Fishman, Scott M.,Rathmell, James P.. Bonica'sManagement of Pain





the arm, drops things easily. Fearful of touch and re-injury


PsychologyTreatment• Issues:

– fear – avoidance behavior, catastrophizing, emotional stress

• Treatment:– Coping mechanisms, cognitive behavioral

treatment (CBT)– Relaxation / deep breathing– Acceptance and commitment– Self management

Nonspecific Effects of TreatmentSatisfaction with care correlates with doctor-patient relationship:

Trust, mutual respect, communication, enthusiasm

Patients expectations:– feel welcome?– Informed?– believe their perspective is understood?– feel secure that their basic needs have been met?

– attention to details specific to the patient?– adequate time spent with the patient?

Robert N. Jamison, PhD

Optimal Health Care Provider Interaction:

Robert N.Jamison, PhD

• Set realistic expectations• Assess patient knowledgeEducate

• Posture / Eye contact• Understand concernsEngage• Active listening• Reflection• Appropriate humour

Empathize

• Provide options• Seek agreement• Welcome input

Enlist• Summarize• Indicate next steps• Follow up

End





the arm, drops things easily. Fearful of touch and re-injury.


Pharmacotherapy References• Giovanni Iolascon & Antimo Moretti.

Pharmacotherapeutic options for complex regional pain syndrome, Expert Opinion on Pharmacotherapy, 2019

• Duong, S et al. Treatment of complex regional pain syndrome: an updated systematic review and narrative synthesis. CJA, 2018

Pharmacotherapy• No FDA/HC approved treatment• No clear evidence for neuropathic pain

medications in CRPS, despite widespread use:– Gabapentinoids + (SNRI or TCA)– Cannabinoids

• Need to taper off meds if no benefit – Opioids lowest dose, short duration, may

need to facilitate rehabilatation

Anti-inflammatory medications• NSAIDs: no clear evidence of benefit

• Steroids:– Prednisolone 40mg per day for 2 weeks

then gradual taper over 2 months– Some evidence of benefit for early CRPS,

does NOT appear helpful if duration is greater than 3 months.

Bisphosphonates• Off label use (except Italy, neridronate)• Concern

– Osteonecrosis jaw (cancer patients, periodontal disease/osteomyelitis, high dose IV)

– Esophagitis (oral alendronate)– Need to check calcium levels, renal

function

Pharmacology of bisphosphonates in pain

Tzschentke, T. British Journal of Pharmacology, First published: 25 July 2019

Bisphosphonates• Mechanism of action:

– Analgesic effect extends beyond osteoclast inhibition: reduce inflammation, inhibit bone marrow cell growth/migration, reduce acidity of bone microenvironment, reduce macrophage activation

– Especially if warm CRPS, early, fracture• Evidence:

– Decreased VAS pain scores, improved function at 2-3mos

– No serious side effects reported but need more data on dose/drug/duration

Ketamine

Ketamine

Ketamine• For CRPS, there is moderate evidence supporting

ketamine infusions (22 mg/h for 4 days or 0.35 mg/kg per hour over 4 hours daily for 10 days) to provide improvements in pain for up to 12 weeks (grade B recommendation, low to moderate level of certainty).

• Reasonable duration of benefit should be considered 3 weeks for a single outpatient infusion, 6 weeks for a series of infusions/inpatient

Cohen, SP et al.Reg Anesth Pain Med 2018;43: 521–546)

Ketamine • Short term infusion = short term effect• Adverse effects are common• Need to titrate and individualize the

dose administered• Placebo control studies are difficult• Effects may last up to 12 weeks with

longer infusion administration• Need for more research

Kamp et al, Expert Opin Drug Metab &Toxicology 2019

Topical Analgesia• Topical Ketamine 10%

– 2009, Finch et al. short term benefit of 30min

• Topical DMSO 50% (free radical scavenger). No definitive evidence (no RCT since 2009).

• Topical clonidine 0.2%, capsaicin, prazosin 1%, lidocaine 5-10% uncertain effects

Antihypertensives• Oral nifedipine

– 10mg po tid then increase to 20mg po tid after 2 days

– Side effect: headaches• Oral phenoxybenzamine

– 10mg at nite, may increase to 30mg qid– Side effects: GI, orthostatic intolerance,

male impotence

Vitamin C: for Prevention Unclear, conflicting evidence for benefit and not clear that its use can reduce the incidence CRPS after surgery/trauma

Low risk and low cost intervention • 1000mg vitamin C per day • May reduce CRPS after distal radius

fracture, foot ankle surgery.

Intravenous Immunoglobulin (IVIG)• Improvement in CRPS in some patients noted

serendipitously: decreases glia-mediated neuro-immune activation

• ? Autoimmune neuropathy due to cross-reactivity with prior infections and self-antigens (chylamydia, parvovirus, Campylobacter)

• Animal studies lend evidence for autoimmune mechanisms

• Future : use of immune modulators / IVIG still under investigation. Evidence is modest/conflicting.

Other possible treatments:Botulinum toxin A:- Decrease peripheral sensitization- Administered SC 5U / 0.1cc over 10-40 sitesIntravenous Regional Analgesia (IVRA)Intrathecal/Epidural neuraxial therapyPlexus nerve cathetersLow dose naltrexone (2 case reports)Oral tadalafil



Stellate ganglion blocks

Samer Narouze

SYMPATHETIC NERVE BLOCKS

Lumbar sympathetic block

- No good evidence to support or refute (Cochrane review 2016)

- Lots of anecdotes. Care reports- Postive responder achieves

analgesia far outlasting the duration of local anesthesia

- if positive response then engage in series of 6 neve blocks spaced one week apart

- Couple with active physical therapy modalities same day or next day

Spinal Cord Stimulation Systematic Review:

– Significant benefits: Pain relief/pain scores, QOL, satisfaction

– Inconclusive: functional status, psychological effects, analgesia-sparing

Visnjevac, O et al. Pain Practice 2017 April

Conclusion:Can be very effective for analgesia, but is an expensive limited option. Need for more research.

CRPS Treatment:

Putting it all together


12 weeks ago• Now taking gabapentin,

duloxetine, topical compounded cream.

• Does physical therapy measures with immediate release opioid, is doing home desensitization

Bruehl, BMJ 2015

www.crpsnetworkuk.org

Ballantyne, Jane C.,Fishman, Scott M.,Rathmell, James P.. Bonica's Management of Pain

SUMMARY• CRPS is a complex, multi-

factorial, biopsychosocial condition

• Early recognition and treatment: up to 75% of cases will resolve or be manageable

• There is an urgent need for more research:

Some patients will improve with no specific treatment plan whereas others will not improve despite all aggressive measures

SUMMARY• Consider adverse effects of

any treatment offered• Follow evidence-based

guidelines and expert advice• No easy treatment option for

patients with chronic CRPS

Other websites to visit:• www.ninds.nih.gov• Reflex Sympathetic Dystrophy

Syndrome Association (RSDSA)

http://www.ninds.nih.gov/

Documents

Toronto Physical Medicine & Rehabilitation Conference - …torontopmrconference.com/2019/wp-content/uploads/2019/11/... · 2019-11-03 · • For CRPS, there is moderate evidence