1) Complex regional pain syndrome (CRPS) is a debilitating painful condition affecting a limb that is associated with sensory, motor, autonomic, skin and bone abnormalities. Pain is the leading symptom and is often out of proportion to the inciting event. 2) The pathophysiology of CRPS involves peripheral and central sensitization due to neurogenic inflammation, sympathetic dysfunction, and cortical reorganization. There are no definitive diagnostic tests and diagnosis is based on clinical criteria. 3) Treatment of CRPS is multidisciplinary and includes physical/occupational therapy, pharmacological management with NSAIDs, glucocorticoids, antidepressants/anticonvulsants, and interventional therapies like sympathetic blocks

1. COMPLEX REGIONAL PAIN
SYNDROME
Presenter: Dr. Darendrajit (Pain Medicine Fellow)
Moderator: Prof. Jyotsna Punj
AIIMS, New Delhi

2. INTRODUCTION
• Is a debilitating painful condition in a limb
• Associated with sensory, motor, autonomic, skin and bone
abnormalities
• PAIN is the leading symptom
• Often associated with limb dysfunction
• Psychological Distress

3. Definition (IASP,1994)
• A variety of painful conditions after injury with regional
distribution having a distal predominance of abnormal
findings, which exceed in intensity and duration of expected
clinical course of the inciting event resulting in significant
impairment of motor functions and showing variable
progress over time

4. INTRODUCTION
• Complex: Varied and dynamic clinical presentation
• Regional: Non-dermatomal distribution of symptoms
• Pain: Out of proportion to the inciting event
• Syndrome: Constellation of S/S

5. HISTORY
• 1872: During the civil war, Weir Mitchell observed chronic pain
syndromes in patients who suffered traumatic nerve injuries
• Symptoms included constant pain and significant trophic changes-spread
beyond the innervation territory of the injured peripheral nerve
• He described this syndrome using the term Causalgia
• Nerve lesions were always partial; complete transection did not cause
• He concluded that “in addition to disease of the nerve, some process in the
skin or other peripheral tissue was responsible for the pain”

6. HISTORY
• 1900: Sudek described regional demineralisation with post traumatic
pain
• After World War II, Leriche for the first time reported that
sympathectomy dramatically relieved causalgia

7. HISTORY
• 1950: John Bonica introduced the phrase reflex sympathetic
dystrophy (RSD)
• Vasomotor and sudomotor abnormalities are common
• Pain and swelling are often spatially remote from the inciting injury
• Patients typically obtain dramatic relief with sympathetic block
Clinical studies have not favored the term
• Some of the most intense cases exhibit skin vasodilation
• Microneurographic studies failed to demonstrate abnormalities in
sympathetic outflow in the affected limb
• Some patients with CRPS fail to experience relief of pain with
sympathetic blockade

8. HISTORY
• 1986: Roberts gave the term Sympathetically Maintained Pain SMP
• 1993: IASP introduced the term complex regional pain syndrome

9. MC GILL PAIN INDEX
AND CRPS

10. EPIDEMIOLOGY
• Incidence from two studies: 5.46 to 26.6/100,000 person-years
• Female : Male- 3:2 to 3:1
• Age: 9 to 85 years (median 42 yrs), Peak 55-70 yrs
• Fracture: most common precipitating factor (~40%)
• Minor trauma: 10%
• Spontaneously: 5% to 10%
• UL more common than LL (60% vs 40%)
• CRPS I (88%) more common than CRPS II (12%)

11. CLINICAL FEATURES
• Signs and symptoms of both conditions
• Are clinically indistinguishable
• Pain is the key feature for both CRPS 1 and 2
• 81% of patients have pain
• Typically out of proportion to the inciting event
• Characteristics: burning, deep-seated ache with a shooting quality and
associated allodynia or hyperalgesia
• Vasomotor abnormalities: 86.9%
• Sudomotor changes including hyperhidrosis/hypohidrosis: 52.9%
• Kinesiophobia and motor weakness: 74.6%
• Edema: 79.7%

12. Time Course
• CRPS mostly starts acutely, within hours or days
• Main symptoms at the onset: spontaneous pain, generalized swelling,
and difference in skin temperature → an early diagnosis of CRPS
• Physiologic diffuse post-traumatic reactions: tendency of symptoms
to generalize following trauma
• Disappear without any treatment
• Exact differentiation from the “real” CRPS not possible at present

13. Lankford and Evans Stages of RSD
Acute stage(0-3 mths)
• Warmth, coolness, burning
pain, edema
• ↑ sensitivity to touch,
hyperalgesia
• Accelerated hair / nail growth
• Tenderness or stiffness of
joints, spasm, bone changes on
X-ray
• ↓ sympathetic activity
Dystrophic phase (3-12
mths)
• Pain is constant – throbbing,
burning, aching, exaggerated by
stimuli
• May still have edema, cool,
mottled appearance
• Nails – brittle and ridged
• Pain and stiffness of joints
persist
• Muscles – tremors, wasting
• Psychological distress sets in
• Changes in body perception
(limbs)
• ↑ sympathetic activity
Atrophic stage(>12 mths)
• Typically the patient has had
CRPS for 3+ years
• Pain is still constant
• Skin is cool, thin and shiny
• Atrophy of limb – with
contractures of joints
• Muscle wasting
• ↑ osteoporosis
• Sympathetic blocks ±
• Features can extend beyond
the original region

14. Classification based on severity
Mild
No pain at rest and no
pain during movements
Moderate
No pain at rest, but pain
during movements
Severe
Intense pain at rest and
during movements
• Questionable whether staging of CRPS is appropriate
• One practical approach with direct therapeutic implications is to classify
into:

15. Psychology
• Most patients exhibit significant psychological distress-depression and
anxiety
• Pain in CRPS is the cause of psychiatric problems and not the
converse
• May develop maladaptive coping skills
• mostly the result of fear, regression, or misinformation
• No evidence to support the theory that CRPS is a psychogenic
condition
• Relaxation and antidepressive treatment are helpful
• Some patients with conversion disorders and factitious diseases have
been diagnosed incorrectly with CRPS

16. Genetics
• Clinical importance of genetic factors in CRPS is not clear
• Polymorphisms - genes encoding
• α1a adrenoceptors
• HLA system (HLA-DQ8, HLA-B62)
• Influences of the HLA system more prominent in patients with
dystonia

17. PATHOPHYSIOLOGY
• Debate continues vis-à-vis the pathophysiology of CRPS
• Existing framework focuses on the neurobiological changes,
peripherally and centrally
• Comparmentalization allows for examination of the
• Changes in cutaneous innervation, ensuing peripheral sensitization associated
with release of inflammatory mediators
• Involvement of the sympathetic system
• Central sensitization with cortical reorganization

18. PATHOPHYSIOLOGY
• Peripheral/afferent mechanisms
• Altered cutaneous innervation following injury
• Peripheral sensitization
• Central sensitization
• Sympathetically mediated pain
• Inflammatory mediators
• Cortical reorganization

19. PERIPHERAL/AFFERENT MECHANISMS
• Neurogenic inflammation plays an important role in
the elaboration and maintenance of CRPS
• ↑ levels of two neuropeptides associated with
inflammatory processes- CGRP and substance P

20. INFLAMMATORY MEDIATORS
• Release of proinflammatory cytokines
• Following tissue trauma (IL-1β, IL-2, IL-6, TNF-α) from mast cells and
lymphocytes
• Secondary to neurogenic inflammation causing the release of cytokines and
neuropeptides (substance P and CGRP)
• Neuropeptides: ↑tissue permeability →vasodilatation→“warm CRPS”
• Substance P and TNF-α: ↑osteoclastic activity
• CGRP: ↑hair growth and sudomotor activity

21. INFLAMMATORY MEDIATORS AND
PERIPHERAL SENSITIZATION
• Release of inflammatory cytokines
• Hypoxia
• Formation of free radicals
Nitric oxide
Endothelin 1
• Cytokine- induced inhibition of
endothelial nitric oxide
• Induction of the transcription
of preproendothelin-1
Serve as profound peripheral
nociceptive stimuli leading to
sensitization and sensory changes

22. Micromilieu of nociceptors

23. CENTRAL SENSITIZATION
• Nerve injury: Injured and non-injured sensory neurons fire
spontaneously
• Neuropeptide release within the dorsal horn
• Mediate central sensitisation through interaction with Neurokinin 1
(NK-1) and NMDA receptors.
• Exaggerated dorsal horn response to A-fibre input and thus allodynia.

24. ALTERED CUTANEOUS INNERVATION
FOLLOWING INJURY
• Persistent minimal distal nerve injury (MDNI), specifically distal
degeneration of small-diameter axons reported
• Significantly lower densities of epidermal neuritis (on average 29%
lower) observed
• Reduction in C and A-delta fiber density in the CRPS-affected limbs
• Abnormalities in the innervations around hair follicles and sweat
glands observed

25. CORTICAL REORGANIZATION
• Cortical reorganization in central somatosensory and
motor networks that may result in altered central
processing of tactile and nociceptive stimuli and cerebral
organization of movement have been reported
• Eg
• Reduced distance between thumb and little finger
representation in contralateral S1 cortex after tactile
stimulation of the affected hand
• Shift of the cortical S1 representation of the affected hand
toward the lip representation

26. SYMPATHETICALLY
MEDIATED PAIN
• Sympatho-afferent coupling
• Sympathetic Hyperactivity:
• Inflammatory mediators or nerve injury triggers sprouting
of new sympathetic nerves
• Increased sympathetic outflow provokes pain
• Adrenergic Hypersensitivity:
• Upregulation of adrenergic receptors
• Increase in nociceptor function
• Increased secretion of Nerve growth factor
• Spontaneous pain may also be relieved by an
infusion of the α-adrenergic blocker phentolamine

27. Model of interacting
CRPS mechanisms

28. Peripheral
Vs
central
pathophysiology

29. DIAGNOSIS
• Clinical – no diagnostic test considered to be a gold standard or
objective test that is specific for CRPS
• Differential diagnosis needs to be considered and excluded

30. 1994 IASP criteria (Orlando criteria)
CRPS type 1: Absence of major nerve damage
CRPS type 2: Presence of major nerve damage
Sensitivity= 1.00
Specificity=0.41

31. Budapest clinical diagnostic criteria
Decision rules Sensitivity Specificity
2+ symptoms and 2+ signs 0.94 0.36
3+ symptoms and 2+ signs 0.85 0.69
4+ symptoms and 2+ signs 0.70 0.94
2+ symptoms and 3+ signs 0.76 0.81
3+ symptoms and 3+ signs 0.70 0.83
4+ symptoms and 3+ signs 0.86 0.75
Clinical diagnosis
Research purposes

32. Investigations
• No specific test
• Main purpose: To exclude other diagnosis
• Lab: CBC, ESR, CRP to exclude infection/ rheumatologic
• Duplex ultrasound: to exclude peripheral vascular disease
• NCV studies: To exclude peripheral neuropathic disease
• Imaging: may demonstrate osteoporosis in affected limb (but no
diagnostic value)
• Other test:
• 3-Phase Bonescan, QST, AFT

34. Three-phase bone scintigraphy
Phase 1
Flow/Vascular:
• 60s dynamic
immediately post
injection
Phase 2
Soft-tissue/blood-pool:
• 5 min post injection
Phase 3
Delayed/bone phase:
• 2-3 hr post injection
Tc99m-MDP
• Homogeneous unilateral hyperperfusion in the perfusion and blood-pool phases are characteristic
• Increased unilateral periarticular tracer uptake at 3 hours after injection

35. Three-phase bone scintigraphy
• Pathologic uptake in the MCP or metacarpal bones thought to be
highly sensitive and specific for CRPS
• Shows significant changes only during the subacute period (≤1 year)
• Negative finding does not exclude the presence of CRPS
• High specificity (75% to 100%) but low sensitivity (31% to 69%), with
moderate interrater reliability
• Specific signs of CRPS (but positive only in chronic stages)
• Endosteal and intracortical excavation
• Subperiosteal and trabecular bone resorption
• Spotty and localized bone demineralization, and osteoporosis

36. QUANTITATIVE SENSORY TESTING
Test Sensory
modality
studied
Fibers studied
Von-Frey hairs,
Algometer
Mechanical Large and small myelinated,
unmyelinated axons
Thermostat Temperature Small myelinated and
unmyelinated sensory axons
Vibratometer Vibration Large myelinated sensory
axons

37. QUANTITATIVE SENSORY TESTING
• Static and dynamic allodynia
• Allodynia associated with pinprick
• Hyperalgesia related to mechanical and heat stimuli
• Temporal summation (increased pain to repeated stimuli)
• No sensory profile is characteristic for CRPS
• Assessment of the signs and changes over time may provide a tool to
track response to treatment
May be
abnormal

38. AUTONOMIC FUNCTION TESTS
• Includes
• Infrared thermometry and thermography
• Quantitative sudomotor axon reflex test (QSART)
• Thermoregulatory sweat test (TST)
• Laser doppler flowmetry
• Limitation
• Require special equipment and a setup that make
clinical applications less viable
• Specificity of abnormalities in these tests in the
diagnosis of CRPS or their role as predictors of
treatment success is unclear

39. TEMPERATURE MEASUREMENT
Infrared thermometry and infrared thermography
• Assess small skin temperature differences between the sides of the
body
• At resting state: Sensitivity: 32%, Specificity: 100%
• At controlled thermoregulation: Sensitivity: 76%, Specificity: 93%
• Temperature difference dependent on the duration of the disease
• Earlier in the disease process the affected limb may demonstrate elevated
temperatures
• while later on in the more chronic phase of the disease the affected side may
show lower temperature compared to the unaffected side

40. VASCULAR ABNORMALITIES

41. Relationship between vascular abnormalities
and duration of CRPS
Type of regulation Temperature Mean durartion of
disease
Range
Warm ≥35 ̊C 4 months 2 weeks to 15 months
Intermediate ~30 ̊C 15 months 2-48 months
Cold ≤25 ̊C 28 months 14-48 months

42. Differential Diagnosis of CRPS
Neuropathic pain syndromes
• Peripheral (poly)neuropathy
• Nerve entrapment
• Radiculopathy
• Postherpetic neuralgia
• Deafferentation pain after CVA
• Plexopathy
• Motor neuron disease
Vascular diseases
• Thrombosis
• Acrocyanosis
• Atherosclerosis
• Raynaud’s disease
• Erythromelalgia
Inflammation
• Erysipelas
• Inflammation NOS
• Bursitis
• Seronegative arthritis
• Rheumatologic diseases
Myofascial pain
• Overuse
• Disuse
• Tennis elbow
• Repetitive strain injury
Fibromyalgia
• Psychiatric problems
• Somatoform pain disorders
• Münchhausen syndrome

43. MANAGEMENT
• Patients seen by a host
of different specialists
• Important to create
awareness about CRPS
• Early recognition and
referral for appropriate
therapy improve
chances for better
management

44. 4 PILLARS OF Mx

45. TREATMENT OPTIONS

46. Physical/Occupational therapy

47. Approach to pharmacotherapy
Goals:
• To allow active participation in a rehabilitation regimen
• To restore movement and strength of the affected limb

48. Anti-inflammatory
• NSAIDs- used in the initial treatment
• Ibuprofen: 400 to 800 mg TID
• Naproxen: 250 to 500 mg BD for 2-4 weeks
• For patients who cannot tolerate nonselective NSAIDs, a selective
cyclooxygenase 2 (COX-2) inhibitor is an alternative option
• Currently there is no evidence supporting the use of NSAIDs for the
treatment of CRPS

49. Glucocorticoids
• Glucocorticoids effect on reducing inflammation
• However, the optimal dosage is not determined
• Their role in chronic CRPS in comparison with more acute cases is uncertain
• Not recommended that steroids be prescribed for long-term use because
of their complications
• Prednisolone: 30 mg/day for 4-6 weeks, Tapered over next weeks and continued
over a maximum of 12 weeks
• Dexamethasone: 8 mg OD for 7 days
• Methylprednisolone: 1000mg IV for 3-5 days

50. Glucocorticoids in CRPS
Study Drug Dosage Result
Christensen K et al (1981) Prednisone Oral, 10 mg TID X 12
weeks
More effective than placebo in
producing clinical improvement
Braus DF et al 1994 Methylprednisolone Oral, 32 mg x 14 days
followed by 14 days
taper
31 out of 36 patients being almost
asymptomatic within 10 days of
treatment
Grundberg A et al 1986 Depo-medrol IM, 80 mg fortnightly for
up to 4 inj
Improvement of limb mobility, pain,
swelling and strength
Bianchi C et al 2006 (case
series, 31 pts)
Prednisone Oral, 40-60 mg OD and
quick taper
Short- and long-term benefits across
various outcomes, such as pain,
swelling, mobility, strength and limb
functionality
Barbalinardo S et al 2016
(31 pts, Chronic CRPS
Prednisolone Oral, 60-100mg
day with a rapid taper-off
over 16-22 days
Reduction in average pain intensity
missed statistical significance, although
borderline

51. Adjuvant medications for neuropathic pain
• Rationale: neurogenic inflammation and changes in central pain
perception
• Anticonvulsants:
• Gabapentin
• Pregabalin
• Antidepressant: not specifically studied in CRPS
• Amitriptyline: 10 to 25 mg at bedtime or earlier
• SNRI

52. Bisphosphonates
• Can be considered for pain reduction in patients with early CRPS who
have abnormal uptake on bone scan
• Mechanism of analgesic effect: uncertain but is probably not related
to the antiresorptive properties of bisphosphonates
• Proposed mechanisms:
• decreased proton concentration in the bone microenvironment
• altering pain signal transduction via acid-sensitive ion channels
• decreased production of tumor necrosis factor and other proinflammatory
mediators

53. Neridronate
• IV, 100 mg, 4 times over 10
days

54. Alendronate
• Oral, 40 mg OD for 8 weeks
• At both 8 and 12 wks: VAS,
pressure tolerance, and
mobility scores better with
alendronate
• At study end: pain scores in
the alendronate group were
approximately one-third of
those in the placebo group

55. Clodronate
• IV, 300 mg daily for 10 days
• Adverse effects
• Transient hypocalcemia
• Flu-like symptoms (for IV infusions)
• Musculoskeletal pain
• Renal toxicity
• Ocular side effects
• Esophageal ulceration
• Osteonecrosis of the jaw

56. Topical creams
• Lodocaine, Capsaicin
• limited data suggest efficacy in CRPS
• probably best suited for patients with early
CRPS and mild to moderate pain
• Trial of 3 to 5 days may suffice to assess
effectiveness and tolerability of these
agents

57. Calcitonin
• Weak evidence for efficacy in CRPS
• An option in combination with PT for patients who have mild or
moderate symptoms
• Rationale for use: ability of calcitonin to retard bone resorption and a
putative analgesic effect
• Mechanism responsible for analgesia: uncertain
• optimal dose and duration of treatment in CRPS is uncertain
• Dose of 300 IU daily used in one positive RCT
• If pain and/or function improve during a two- to four-week trial period,
it can be continued for up to three months

58. Conflicting
evidence

59. Ketamine infusion
• Low to moderate quality evidence
• Treatment plan is individualized
• 0.25 to 0.5mg/kg diluted in 100 mL NS, infused over 1 to 4 hours
• IV Midazolam (0.5 to 2 mg) premedication to prevent acute side
effect
• Some patients may require antinausea medication before or during
the procedure
• Effect usually lasts for 4 to 12 weeks

60. Ketamine infusion
• Patients admitted for 5 days
• two iv lines one for drug infusion, and
the other for blood sampling
• Drug infusion rate started at 1.2
mcg/kg/min (or 5 mg/h for a 70-kg
patient) at 8 AM on day 1
• Titrated (max. thrice daily) to a max of
7.2 mcg/kg/min (or 30 mg/h for a 70-kg
patient)
• Infusion rate altered based on pain relief
and side effects
Low-quality evidence to suggest that a course of i.v.
ketamine may be effective for CRPS-related pain
O’Connell NE, Cochrane Database Syst Rev, 2013

61. OTHER POTENTIAL THERAPIES
Free radical scavengers
• Dimethylsulfoxide (DMSO)
• N-acetylcysteine (NAC)
• Mannitol
• IV Mg
DMSO 50% (5 times per day) Vs NAC (600 mg 3 times per day)
• DMSO more efficacious for warm CRPS 1 and for treating
dysfunctions of the lower extremity
• NAC more effective for cold CRPS 1

62. OTHER POTENTIAL THERAPIES
Immunoglobulin IV
• IVIG 0.5 g/kg or saline, separated by a washout period of greater than 28 days

63. Botulinum toxin

64. INTERVENTIONAL THERAPIES
Currently, two therapeutic techniques to block sympathetic activity are
used:
• Sympathetic ganglion blocks
• Regional intravenous application of guanethidine, bretylium, or reserpine
(which all deplete norepinephrine in the postganglionic axon) to an isolated
extremity blocked with a tourniquet (intravenous regional sympatholysis
[IVRS])

65. Sympathetic Nerve Blocks
• Utilized as a diagnostic tool to
determine if neuropathic pain is
SMP or SIP

66. Sympathetic Nerve Blocks
• Sympathetic block as a treatment for CRPS: conflicting evidence
• Small randomized trials comparing sympathetic block with
sham/placebo or other active comparators failed to show a difference
in short-term pain reduction

67. Stellate ganglion block

68. Stellate ganglion block

69. T2-T3 Sympathetic block

70. T2-T3 Sympathetic block

71. Lumbar sympathetic block

72. Lumbar sympathetic block

74. Intravenous Regional Anesthesia
• Agents: guanethidine, reserpine, droperidol, ketanserin, atropine, and
lidocaine-methylprednisolone
• Beneficial effects thought to occur through neuromodulation
• Does not support the use of IVRA for sympatholysis in CRPS
• To date, only bretylium has demonstrated benefits when added to a local
anesthetic agent for IVRB

75. Sympathetic block outcomes
• Retrospective review
• Sympathetic blocks in 255 pts
• Lumbar sympathetic (83%), stellate
ganglion (16%), and thoracic sympathetic
(<1%)
• 61% reported pain relief (>50 percent) of
whom the majority endorsed pain relief
for 1 to 4 weeks (71%) or longer (14%)

76. Intrathecal Baclofen
• Shown to be effective in CRPS
associated with dystonia
• ITB successfully used in patients with
CRPS refractory to other treatment
modalities
• Dose escalation: started @ 150 μg/d
and ↑ in 10% to 20% steps until
patients experienced a satisfactory
improvement of dystonia or dose-
limiting side effects occurred
• Long-term improvement in dystonia
observed

77. Neuromodulation
• Spinal cord stimulation
• Dorsal root ganglion stimulation
• Peripheral nerve stimulation
• Transcutaneous electrical nerve stimulation
• Non-Invasive brain stimulation
• Deep brain stimulation
• Graded Motor Imagery

78. Spinal cord stimulation
• Invasive neuromodulation strategy, helpful if traditional therapeutic
modalities fail
• In patients with disease limited to one extremity
• Effective for pain reduction (but not necessarily functional
improvement)
Marius A. Kemler

79. Dorsal root ganglion stimulation

80. Motor Imagery Program
• Incorporates recognition of the limb laterality, imagined movements,
and mirrored movements using a mirror box device

82. Psychotherapy
• Assist in the general rehabilitation of patients, particularly in children
• Techniques:
• Relaxation techniques
• Biofeedback
• Stress management
• Cognitive behavioral therapy
• “Graded Exposure” (GEXP) treatment has shown good evidence for
efficacy in CRPS

83. Amputation
• Rarely performed for severe, refractory cases of CRPS
• 66% experienced improvement in quality of life (QOL)
• Complications
• Phantom limb pain: 65%
• Recurrence of CRPS: 45%
• Stump pain: 30%

85. Michael D. Stanton-Hicks et al, Pain Practice,
Volume 2, Number 1, 2002 1–16

86. Summary of treatments

87. PROGNOSIS
• Uncertain prognosis, with highly variable rates of poor and favorable
outcomes in different studies
• Nevertheless, a substantial proportion of patients have some degree of
prolonged disability
• 102 CRPS patients assessed for
avg 5.8 years (range: 2.1 to 10.8)
since onset
• 16% reported the CRPS as still
progressive
• 31% were incapable of working

88. Risk of recurrence
• Recurrence of CRPS is not uncommon
• 10 to 30 percent, with the higher rates occurring in younger patients,
including children
• Can occur spontaneously or with cold exposure, triggered by trauma
or new surgery of the affected limb or of an unaffected remote site
and by emotional trauma

89. PREVENTION
Vitamin C
• Suggested as a low-risk intervention that might accelerate fracture healing
and limit excessive soft tissue injury via antioxidant mechanisms
• 416 older women with distal wrist fractures were randomly assigned to one of
three daily doses of vitamin C (200, 500, or 1500 mg) or placebo for 50 days
• Over a one-year follow-up period, CRPS was less prevalent in those who
received vitamin C(any dose versus placebo, 2.4 versus 10.1 percent)
VIT D Dose (Daily) Prevalence RR 95% CI
200 mg 4.2% (4 of 96 pt) 0.41 0.13 to 1.27
500 mg 1.8% (2 of 114 pts) 0.17 0.04 to 0.77
1500 mg 1.7% (2 of 118) 0.17 0.04 to 0.75

90. Vitamin C
• Vitamin C (500 mg daily) versus placebo in 336 adults with acute
distal radius fractures
• No difference between groups in the rate of CRPS (8% in both
groups), disability scores, and other functional outcomes at 6 weeks
and 1 year post-fracture

91. Vitamin C
• Meta-analysis of the three trials (n = 890) found a non-significant
trend towards benefit of vitamin C (risk ratio 0.45, 95% CI 0.18-1.13)
• Conclusion:
• Evidence for vitamin C to prevent CRPS in patients with distal radius fractures
is conflicting and fails to a statistically significant effect
• Overall quality of the evidence was low
• Results should be interpreted in the context of clinical expertise and patient
preferences
It is likely that oral administration of 500 mg of vitamin C per day
for 50 days from the date of the injury reduces the incidence of
CRPS-I in patients with wrist fractures (level 2: Zollinger et al. (A2),
Cazeneuve et al. (B))

92. Ischemic reperfusion injury
• Relates to the possible role of oxidative stress
• Minimizing ischemic reperfusion injury
• Eg. Duration of tourniquet

93. Emerging trend
• Naltrexone
• Tadalafil

94. Summary
• CRPS is clinically diagnosed
• No definitive diagnostic test is considered to be a gold standard
• Pathophysiology of CRPS still poorly understood- Peripheral and central
sensitization and neuroimmune mechanisms are thought to play essential
roles
• CRPS might appear as a complication of various malignancies in advanced
stages
• Management of CRPS depends on a multidisciplinary team approach, such
as pharmacologic, interventional and neuromodulation
• CRPS is continuously developing and evidence-based managements for
favorable results are insufficient
• Chronic pain and limb disability associated with CRPS may lead to
psychological stress and depression