Complex Regional Pain Syndrome Type II (CRPS-II)

Miller's Anesthesia, 10th Edition — with supplemental coverage from Bradley and Daroff's Neurology in Clinical Practice

1. Nomenclature and Historical Background

2. Epidemiology

• Mean age of CRPS patients: 36–46 years
• Female predominance: 60–81% of cases
• Common precipitating injuries in CRPS overall:
  • Fracture: 16–46%
  • Strain/sprain: 10–29%
  • Post-surgical: 3–24%
  • Contusion/crush injury: 8–18%
• In CRPS-II specifically, a major nerve injury is the defining precipitant (e.g., median nerve, sciatic nerve)

3. Pathophysiology

a) Sympathetic Nervous System Dysfunction

• An abnormal reflex arc following the sympathetic nervous system, modulated by cortical centres, has been proposed
• Decreased sympathetic outflow to the affected limb is now understood to be the underlying mechanism — autonomic features previously ascribed to sympathetic overactivity are now thought to result from catecholamine hypersensitivity at peripheral receptors

b) Central Sensitization

• In Miller's framework of chronic pain neurophysiology, central sensitization — amplification of nociceptive signals in the dorsal horn — plays a critical role in maintaining and spreading CRPS pain beyond the original nerve distribution
• NMDA receptor upregulation, disinhibition, and cortical reorganization perpetuate pain

c) Peripheral Nerve Injury (Specific to CRPS-II)

• Unlike CRPS-I, CRPS-II requires a definable nerve lesion
• Axonal injury triggers ectopic discharge, upregulation of sodium channels, and abnormal sympatho-afferent coupling — injured afferents develop adrenoceptor sensitivity, so circulating catecholamines directly excite nociceptors

d) Psychosocial Factors

• Significant emotional disturbance at onset is present in many patients
• Stress may be a precipitating factor
• Miller's biopsychosocial model of chronic pain applies: biological injury, psychological (catastrophizing, fear-avoidance), and social reinforcement all perpetuate the syndrome — Miller's Anesthesia, 10th ed., p. 6835–6836

4. Clinical Features

Pain Characteristics

• Hyperalgesia: exaggerated pain response to a normally painful stimulus (e.g., pin prick)
• Mechanical allodynia: light touch perceived as severe, long-lasting pain
• Thermal allodynia: cooling stimuli (e.g., drop of alcohol) perceived as painful
• Pain severity is not proportional to the initial injury

Trophic and Autonomic Changes

• The affected area may be reddish, then turn blue, purple, or pale within minutes to hours
• Livedo reticularis (non-blanchable reticulated skin pattern) is common
• Temperature asymmetry between affected and unaffected sides may exceed 1°C

• ~60% of patients report excessive sweating in the affected limb

• Present in the majority; ranges from mild cellulitis-like swelling in early stages to severe edema requiring Doppler to exclude DVT in late stages

• Not required for diagnosis, but weakness, tremor, or dystonia may be present

• Waxy, shiny skin; brittle, ridged nails; muscle wasting; joint contractures

Skin Changes in CRPS: Shiny appearance of the right hand with discoloration. — Bradley and Daroff's Neurology in Clinical Practice

CRPS-I of the right foot and ankle with swelling and redness compared to the contralateral side. — Bradley and Daroff's Neurology in Clinical Practice

5. Clinical Staging

• CRPS can spread from one limb to others and, in severe cases, involve all four extremities with severe pain, edema, cold/cyanotic limbs, contractures, and atrophy

6. Diagnosis

• Diffuse, severe, nonsegmental pain
• Cyanosis or mottling, increased sweating, shiny skin
• Swollen non-articular tissue
• Coldness to touch
• History of a definable nerve injury (differentiating CRPS-II from CRPS-I)

Investigations

• Autonomic testing: Resting sweat output + quantitative sudomotor axon reflex test (QSART) together are 94% sensitive and 98% specific — excellent predictors of response to sympathetic block
• Bone scintigraphy: Most sensitive in Stage I; less useful in later stages
• Plain radiographs: Show severe bone demineralization in Stage III
• Sympathetic block: Serves both a diagnostic and therapeutic role — a positive response to stellate ganglion or lumbar sympathetic block supports the diagnosis

7. Management — Anesthetic Perspective

a) Pharmacological Treatment

b) Interventional/Regional Anesthetic Techniques

• Indicated for upper extremity CRPS (including CRPS-II)
• Sympathetically maintained pain may respond well — "sympathetically maintained pain syndrome" is a key indication
• Early stellate ganglion blocks may significantly decrease pain and hasten clinical recovery
• May also prevent recurrence of CRPS after reoperation of the affected extremity
• A Horner syndrome confirms correct placement; ultrasound guidance is preferred

• For lower extremity CRPS

• IVRB with bretylium provided significantly longer analgesia than lidocaine in a double-blind study

• Epidural clonidine and ketamine — good pain relief reported
• Epidural anesthesia facilitates physiotherapy and functional rehabilitation

• Perineural catheters reduce pain, facilitate physiotherapy, and are used for functional rehabilitation
• Reported effective in children with CRPS as well — Miller's Anesthesia, 10th ed., p. 10961

• Intrathecal baclofen and morphine — good pain relief reported in refractory cases

c) Spinal Cord Stimulation (SCS)

• SCS has gained interest; unblinded studies suggest selected CRPS patients may benefit
• An early study with 2-year follow-up reported long-term pain reduction and improved health-related quality of life with SCS
• However, a more recent RCT (Kemler et al., 2008) with 5-year follow-up found no extra benefit for SCS + physical therapy vs. physical therapy alone in terms of pain relief
• Miller's notes: SCS "may have difficulty stopping the spread of CRPS, and once CRPS spreads out of the area initially covered, pain is no longer under control" — Miller's Anesthesia, 10th ed., p. 6867

d) Surgical Sympathectomy

• Used for progressive disease in patients who have previously responded to sympathetic block
• Not first-line; evidence is limited

e) Psychological and Rehabilitative Approaches

• Miller's emphasizes the biopsychosocial model — monomodal therapy is insufficient
• Multimodal interdisciplinary programs simultaneously address physical, psychological, and social factors
• Functional rehabilitation is the primary goal of all interventions
• TENS and acupuncture may provide adjunctive benefit

8. CRPS-II vs. CRPS-I — Key Differences

9. Perioperative Considerations for CRPS Patients (Miller's)

• Central sensitization may cause increased and prolonged postoperative pain
• Higher analgesic requirements expected — titrate opioids starting at 2–4× the usual dose for opioid-naïve patients
• Maintain preoperative medications perioperatively (gabapentinoids, antidepressants, etc.) — abrupt discontinuation risks rebound hyperalgesia or seizures
• Regional anesthesia preferred where possible — prevents triggering/worsening CRPS
• Ketamine as adjunct: NMDA antagonism reduces central sensitization and opioid requirements
• Monitor for withdrawal in patients on chronic opioids: unexplained tachycardia, restlessness, sweating, hypertension
• Pain service consultation is recommended at discharge — Miller's Anesthesia, 10th ed., pp. 6867–6884

Summary

Autonomic and Peripheral Nerve Blocks

Miller's Anesthesia, 2-Volume Set, 10th Edition

Overarching Framework

"Nerve block therapy alone is usually not curative, but it can facilitate participation in rehabilitation and therefore may have a role in the management of chronic pain. Regardless which procedure is considered, a consensus decision on its use must be reached within the interdisciplinary team." — Miller's Anesthesia, 10e, p. 6864

1. Cervicothoracic (Stellate) Ganglion Block

Anatomy

• Anterolateral to the C7–T1 vertebral bodies
• Medial to the carotid sheath
• Anterior to the transverse processes and longus colli muscle
• Posterolateral to the trachea and esophagus

Technique

• Patient supine with neck slightly extended
• Longus colli muscle identified ultrasonographically — the key sonographic landmark
• Local anesthetic injected superior to the longus colli muscle
• Ultrasound guidance is strongly recommended — this is described as the contemporary standard in Miller's
• Horner syndrome (ptosis, miosis, anhidrosis, enophthalmos) = confirmation of correct sympathetic block

Indications (per Miller's 10e)

"Stellate ganglion block is a rather dangerous procedure with very few but very specific indications." — Miller's Anesthesia, 10e, Ch. 74 (p. 11047)

Complications

• Intravascular injection (vertebral artery, carotid artery) → seizures, cardiovascular collapse
• Pneumothorax (apex of lung is adjacent)
• Phrenic nerve block → unilateral diaphragm paralysis (bilateral stellate block is absolutely contraindicated)
• Recurrent laryngeal nerve block → hoarseness, dysphagia
• Brachial plexus block (unintended spread)
• Epidural or intrathecal injection with spinal spread
• Horner syndrome per se is an expected endpoint, not a complication

2. Semilunar (Gasserian) Ganglion Block

Anatomy

Miller's Context — Oculocardiac Reflex

"The pain, pressure or traction impulses are conducted by the ciliary nerves to the ciliary ganglion and then via the ophthalmic division of the trigeminal nerve to the Gasserian ganglion and the sensory nucleus of the trigeminal nerve." — Miller's Anesthesia, 10e, p. 4063

Indications

• Disabling trigeminal neuralgia (tic douloureux) — primary indication
• Head and neck cancer pain (neurolytic)
• When medical management (carbamazepine) has failed

Technique (Fluoroscopy-Guided — Hartel Approach)

"The most comprehensive block of the trigeminal nerve targets the central ganglion. This block is usually performed under fluoroscopic guidance to treat disabling trigeminal neuralgia. Few operating room anesthesiologists perform this technically challenging block." — Barash, Cullen and Stoelting, 9e, Ch. 36 (cross-referenced by Miller's)

1. Patient supine, mouth open
2. Skin entry point: lateral to the corner of the mouth, 2.5–3 cm
3. 20-gauge spinal needle directed toward the foramen ovale under AP and lateral fluoroscopy
4. Traverses infratemporal fossa → enters Meckel's cave through foramen ovale
5. Entry confirmed by CSF flow from the dural sleeve surrounding the ganglion
6. Inject local anesthetic / glycerol / or apply RF energy

Neurolytic Options at the Gasserian Ganglion (cited in Miller's)

Complications

• Corneal anesthesia → keratitis, corneal ulceration (most feared; V₁ injury)
• Masseter weakness (motor root at V₃)
• Anesthesia dolorosa — painful deafferentation state, more common with neurolytic agents
• Intracranial hemorrhage
• Carotid artery puncture
• CSF leak / meningitis
• Ipsilateral Horner syndrome (sympathetic fibres near ganglion)

3. Intercostal Nerve Block

Anatomy

"Intercostal nerves run along the lower border of each rib, within the intercostal space, a triangular space, with: (1) a medial border formed by the posterior intercostal and innermost intercostal muscles, endothoracic fascia, and parietal pleura; (2) a lateral border formed by the internal and external intercostal muscles and intercostal membrane; (3) a base formed by the lower rib." — Miller's Anesthesia, 10e, p. 11085

Technique

• Position: semi-prone at the midaxillary line — described as the safest approach in Miller's
• Needle: 22- or 20-gauge Tuohy needle (intradermal needles are explicitly stated as inappropriate)
• Guidance: In-plane ultrasound strongly preferred

1. Insert needle in-plane to contact rib
2. Redirect needle and walk off the rib caudally into the intercostal space

Miller's Anesthesia, 10e, Fig. 74.32 — (1) Insert needle in-plane to contact rib. (2) Redirect needle caudally off the rib into the intercostal space.

Catheter Technique

• A catheter may be placed for repeated reinjections
• Can also be inserted intraoperatively under direct surgical vision
• Large-volume injection can spread to distant intercostal spaces via the paravertebral space (even contralateral), and to the epidural space

"The safety of continuous techniques is questionable because of the high systemic uptake of local anesthetic." — Miller's Anesthesia, 10e, p. 11086

Indications

Safety Requirements — Explicit in Miller's

• Contraindicated in patients with impaired oxygenation or gas exchange
• Not suitable for outpatient surgery
• All patients must be kept under intensive medical observation — risk of clinically delayed pneumothorax
• Patients with catheters or large-volume injections should be admitted to ICU for monitoring of respiratory function and delayed pneumothorax

Complications

4. Celiac Plexus Block

Anatomy

• Greater splanchnic nerves (T5–T9) — preganglionic sympathetic
• Lesser splanchnic nerves (T10–T11)
• Least splanchnic nerve (T12)
• Parasympathetic fibres via the vagus nerve
• Visceral afferent pain fibres from upper abdominal viscera

"Sympathetic nerves to the kidney originate as preganglionic fibers from the eighth thoracic through the first lumbar segments and converge at the celiac plexus and aorticorenal ganglia. Postganglionic fibers to the kidney arise mainly from the celiac..." — Miller's Anesthesia, 10e, p. 984

Visceral Pain Coverage

Indications

Miller's cites the Cochrane Database Systematic Review on "Celiac plexus block for pancreatic cancer pain in adults" (2011) as the key evidence base. — Miller's Anesthesia, 10e, p. 6866

Techniques

• Patient prone
• Bilateral 20-gauge needles (15–20 cm) inserted at L1 level, angled toward the anterior surface of the L1 vertebral body
• Fluoroscopic or CT guidance; contrast injection to confirm pre-aortic spread
• Drug deposited anterior to the aorta / around the celiac axis

• Patient supine
• CT or ultrasound guided
• Single needle, transgastric or transhepatic path
• Preferred in patients who cannot lie prone or when posterior anatomy is distorted

• Direct injection at celiac axis at time of laparotomy or laparoscopy
• Increasingly used during pancreatic cancer resection

Drug Selection

Efficacy

• Pancreatic cancer: superior to systemic opioids alone; reduces opioid consumption and side effects; pain relief lasting weeks to months
• Miller's acknowledges celiac plexus block as one of the few interventional pain techniques with meaningful cancer pain evidence — p. 6866

Complications

Comparative Overview