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Cryoneurolysis
Dr .Moallemy
Historical Considerations
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Cryoanalgesia is a technique in which cold is applied to
produce pain relief.
The analgesic effect of cold has been known to humans
for more than 2 millennia. Hippocrates (460–377 bc)
provided the first written record of the use of ice and
snow packs applied before surgery as a local painrelieving technique.
Early physicians, such as Avicenna of Persia (980–1070
ad) and Severino of Naples (1580–1656) recorded using
cold for preoperative analgesia.
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In 1812, Napoleon's surgeon general, Baron Dominique
Jean Larrey, recognized that the limbs of soldiers frozen
in the Prussian snow could be amputated relatively
painlessly.
Contemporary interest in cryoanalgesia was sparked in
1961, after Cooper described a cryotherapy unit in
which liquid nitrogen was circulated through a hollow
metal probe that was vacuum insulated except at the
tip.
The coldest temperature used today is approximately
−70°C.
Physics of Cryoanalgesia
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The working principle of a cryoprobe is that compressed gas
(nitrous oxide or carbon dioxide) expands.
The cryoprobe consists of an outer tube and a smaller inner
tube that terminates in a fine nozzle High-pressure gas (650 to
800 psi) is passed between the two tubes and is released
through a small orifice into a chamber at the tip of the probe. In
the chamber, the gas expands, and the substantial reduction in
pressure (80 to 100 psi) results in a rapid decrease in
temperature and cooling of the probe tip.
Absorption of heat from surrounding tissues accompanies
expansion of any gas, according to the principles of the general
gas law; this is the adiabatic principle of gas cooling and heat
extraction, also known as the Joule-Thomson effect.
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The sealed construction of the cryoprobe ensures that no gas
escapes from the probe tip, handle, or hose.
The rapid cooling of the cryoprobe produces a tip surface
temperature of approximately −70°C (–94°F)
Tissue in contact with the tip cools rapidly and forms an ice ball.
The ice ball varies in size, depending on probe size, freeze time,
tissue permeability to water, and the presence of vascular
structures (heat sink). The ice ball typically measures 3.5 to 5.5
mm in diameter.
Precise levels of gas flow through the cryoprobe are essential for
maximum efficiency. Inadequate gas flow does not freeze tissue.
Excessive gas flow results in freezing down the stem of the probe
and the associated risk of cold skin burns.
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The application of cold to peripheral nerves, whether by direct
cooling of localized segments or complete immersion of tissue in
a cold medium, induces reversible conduction block. The extent
and duration of the effect depend on the temperature attained
in the tissues and the duration of exposure.
In practice, a freeze of 2 to 3 minutes' duration produces a
good result.
Histologically, the axons and myelin sheaths degenerate after
cryolesioning (wallerian degeneration), but the epineurium and
perineurium remain intact, thus allowing subsequent nerve
regeneration. The duration of the block is a function of the rate
of axonal regeneration after cryolesioning, which is reported to
be 1 to 3 mm/day
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The absence of external damage to the nerve and the minimal
inflammatory reaction to freezing ensure that regeneration is
exact. The regenerating axons are unlikely to form painful
neuromas. (Surgical and thermal lesions interrupt perineurium
and epineurium.) Other neurolytic techniques (alcohol, phenol)
potentially can produce painful neuromas because the
epineurium and perineurium are disrupted.
Clinically, a cryoblock lasts weeks to months.
The analgesia often lasts longer than the time required for
axons to regenerate. The reasons are still a matter of
speculation, but it is obvious that cryoanalgesia is more than
just a temporary disruption of axons. Possibly, sustained
blockade of afferent input to the central nervous system (CNS)
has an effect on CNS windup.
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One report suggested that cryolesions release sequestered
tissue protein or facilitate changes in protein antigenic
properties.
Perhaps immune mechanisms play a role in the analgesic
response after cryoablation.
Indications and Contraindications
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Cryoanalgesia is best suited for clinical situations when analgesia is
required for weeks or months. Permanent blockade does not usually
occur because the cryoinjured axons regenerate .
Cryoanalgesia is suited for painful conditions that originate from small,
well-localized lesions of peripheral nerves (e.g., neuromas, entrapment
neuropathies, and postoperative pain).
Cryoablative procedures can be open or closed (percutaneous),
depending on the clinical setting. Most often, open procedures are
performed as part of postoperative analgesia.
The cryoprobe is withdrawn only after the tissue thaws because
removing it earlier can tear tissue.
Percutaneous (closed) cryoablation is the technique of choice for
outpatient chronic pain management.
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Patients should be fully aware that a cryoanalgesia procedure
usually is not a permanent solution. It can ameliorate
symptoms, however, and can allow the patient to participate in
physical therapy more fully.
Cryoanalgesia for chronic pain syndromes always should be
preceded by diagnostic or prognostic local anesthetic injections.
After a test block with local anesthetic, the examiner should
inquire about the patient's tolerance to the numbness and the
extent of pain reduction.
If the patient's response to the test injections is inadequate,
the patient will not have a good response to cryodenervation.
Patients also should be aware that numbness can replace pain,
and small areas of skin depigmentation can occur if the ice ball
frosts skin because the probe is not deep enough or is
inadequately insulated from tissues.
All procedures are performed with appropriate sterile
preparation. As a general rule, infected areas are avoided.
TECHNIQE
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The cryolesion is attempted only after successful temporary
reduction of symptoms by a diagnostic block .
Localization is facilitated with stimulation between 50 and 100
Hz at less than 0.5 V for sensory nerves or at 2 to 5 Hz for
motor nerves.
Two or three 2-minute cycles are usually sufficient.
During the freezing, care is taken to prevent frostbite if the
probe comes in direct contact with the skin. Continuous
irrigation with 0.9% saline solution at room temperature
reduces the possibility of skin injury.
Clinical Pearls and Tricks of theTrade
1.Postoperative Pain Management
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At many institutions, cryoanalgesia is reserved for patients with
special analgesia needs and patients at high risk who cannot
receive standard postoperative treatment
Cryoanalgesia procedures are provided intra-operatively by
surgeons who have access to involved peripheral nerve and pain
management specialists participating in the operative procedure.
At times, pain specialists are called on to provide cryoanalgesia
postoperatively, in which case they must decide whether some
other alternative is more suitable than open or closed
cryodenervation.
Popular Cryodenervation Techniques
for Postoperative Pain Management
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Post-thoracotomy pain:
Post-thoracotomy cryoanalgesia is most effective for treating
incisional pain, but it is ineffective for pain from visceral pleura
supplied by autonomic fibers or for ligament pain of the chest
secondary to rib retraction. Post-thoracotomy cryoanalgesia
often has little effect on chest tube pain, for the same reasons.
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For effective intra-operative cryoneurolysis, intercostal nerves
on each side of the thoracotomy incision are lesioned. If a rib is
removed, that intercostal nerve also undergoes cryolesioning.
The intercostal nerves are best cryoablated just lateral to the
transverse process, before the collateral intercostal nerve
branches
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A comparison of epidural analgesia and intercostal nerve
cryoanalgesia for post-thoracotomy pain as part of a
randomized control study cast some doubt on the long-term
utility of cryoanalgesia for post-thoracotomy pain.
Both thoracic epidural analgesia and intercostal nerve
cryoanalgesia produced satisfactory analgesia for postthoracotomy acute pain. The incidence of post-thoracotomy
chronic pain is high. Cryoanalgesia may be a factor that
increases the incidence of neuropathic pain.
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Postherniorrhaphy pain:
A cryolesion of the ilioinguinal nerve reduced analgesic
requirements during the postoperative period.
After repair of the internal ring, posterior wall of the inguinal
canal, and internal oblique muscle, the ilioinguinal nerve on the
surface of the muscle is identified and mobilized. The surgeon
elevates the nerve above the muscle, and an assistant performs
the cryoablation.
the technique is not widely used.
Given its effectiveness and freedom from side effects, it is ideal
for ambulatory surgery.
Chronic Pain Management
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For management of chronic pain, open cryoablation is avoided
whenever the procedure can be performed effectively
percutaneously.
Before committing to cryoablation, the provider must perform a
series of test blocks to determine presence of a consistent
analgesic response. A favorable response before cryoablation
occurs when the local anesthetic injection decreases pain, and
the numbness that replaces the pain is tolerated by the patient.
Care always must be taken to ensure correct positioning of the
needles. When necessary, fluoroscopic guidance should be used.
Many patients with chronic pain have suffered for a long time
and are hopeful that the next procedure is going to be the longawaited successful treatment. These patients are responsive to
suggestion and placebo effect. To identify such effects, the first
test injection is done with lidocaine and the second with
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For patients who do not have the desired response to
bupivacaine or lidocaine, further testing is necessary,
including differential blockade with local anesthetics and
normal saline solution and consideration of consultation
with a clinical psychologist.
Bending the probe during percutaneous introduction can
distort the lumen of the low-pressure outer tube, increase
the resistance pressure to the expanding nitrous oxide gas,
and convert a low-pressure exhaust system to one of
higher pressure.
To maintain the integrity of the cryoprobe, the probe
should be placed through an introducer.
The operator always should check to see that the
cryoprobe fits through the lumen of the catheter.
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Careful palpation with a small blunt instrument, such
as a felt-tipped pen, can help to localize a soft tissue
neuroma or another palpable pain generator.
An image intensifier (fluoroscopy) can identify bony
landmarks.
Contrast medium improves definition of tissue
planes, capsules, and spaces. (Nonionic contrast
medium should be used in areas close to neural
tissue.)
The nerve stimulator at the tip of the cryoprobe is
used to produce a muscle twitch in a mixed nerve.
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The operator freezes the nerve for 2 to 3 minutes. Often, the
patient has discomfort initially as cooling begins, but it should
dissipate quickly. If significant pain persists beyond 30 seconds,
the operator should investigate whether the ice ball is in the
proper position.
In general, with closed procedures, two freeze cycles of 2
minutes each, followed by thaw cycles, are sufficient. In areas
with a large vascular heat sink, longer periods of cryotherapy
are necessary. Pain relief should be immediate and should be
assessed subjectively and by physical examination while the
patient is on the procedure table .
Intercostal neuralgia
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Percutaneous cryolesions of the intercostal nerves can be
offered for various pain syndromes, including post-thoracotomy
pain, traumatic intercostal neuralgia, rib fracture pain, and
occasionally postherpetic neuropathy.
For each of these conditions, a meticulous series of local
anesthetic blocks is performed before consideration is given to
cryoablation.
The volume of local anesthetic should be kept to less than 3 to
4 mL to prevent tracking back into the epidural space. In
addition, only two or three levels should be injected at any one
time because systemic absorption could confound interpretation
of the patient's response.
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Because the intercostal nerve runs with a large arterial and
venous heat source, the use of two 4-minute cryolesions at
each level is suggested.
After the procedure, a chest film is obtained to check for
pneumothorax.
Effective blockade in some patients with postherpetic
neuropathy suggests that this pain is sometimes related to
peripheral afferent input, as opposed to being strictly a central
neuropathy.
Neuromas
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Typically, painful neuromas are associated with lancinating or
shooting pain that is aggravated by movement or deformation
of nearby soft tissues.
First-line therapy should include empirical trials of
anticonvulsants, tricyclic antidepressants, steroids, and local
anesthetics, including a topical local anesthetic cream or patch.
Cryoablation seems most effective when the volume of local
anesthetic necessary to produce analgesia is 1 mL or less. After
the block with lidocaine, the patient's response and its duration
are recorded. If initial blockade is successful in decreasing the
patient's symptoms, it should be followed by at least one more
injection with bupivacaine.
Iliac crest bone harvest
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The pain associated with the harvest of iliac crest bone for
fusion often responds to cryoablation when more conservative
therapies have failed.
Such pain often is associated with deep, lancinating pain and
often is attributed to periosteal neuromas.
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Cryoablation of an anterior iliac crest bone harvest site. (From
Waldman SD: Cryoneurolysis in clinical practice. In
Interventional pain management, ed 2, Philadelphia, 2001,
Saunders.)
Biomechanical spine pain
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Cryolesions have been used effectively for cervical and lumbar
facet syndromes and for pain from the interspinous ligaments
For biomechanical pain of lumbar facet origin, the patient
typically has pain that is exacerbated by hyperextension of the
lumbar spine .
A fluoroscopically guided diagnostic intra-articular facet block
can be performed in patients who fulfill the aforementioned
criteria.
The levels chosen for injection are determined by bone scan,
computed tomography, plain films, and, most important,
physical examination findings.
To confirm a facet pain generator, repeat blockade of the facet
nerves can be done next. If the result is similar, it is reasonable
to consider ablation.
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In patients who continue to be responsive, improvement is
observed on physical examination, especially with lumbar
hyperextension. For these patients, a cryoablative procedure
can be considered
A 12-gauge introducer catheter is introduced to the junction of
the transverse process and the pedicle, the Scottie dog's eye. At
this point, the cryoprobe is inserted into the introducer catheter.
The nerve stimulator is used to locate the sensory branch.
When pain is reproduced or the patient feels dysesthesia
overlapping the region of the pain, motor testing is in order to
ensure that the ice ball is not near a motor nerve.
Two cryolesions are made, each of 2 minutes' duration.
The patient is expected to have some postprocedure discomfort,
but should notice improvement.
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In the recovery room, ice can be applied to the operative site
for 30 minutes for local postoperative irritation and swelling.
Application of ice may decrease swelling and facilitate
mobilization
The patient should continue with outpatient lumbar
strengthening programs. If the musculature is significantly
deconditioned, it may be better to restart the program in water.
After muscle condition improves, the patient should begin a
supervised industrial rehabilitation program that offers
vocational retraining and job placement.
One publication demonstrated that the evidence-based
information available for cryodenervation in facet denervation is
indeterminate.
Cervical facet syndrome
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Patients with cervical facet syndrome typically present with
severe posterior neck pain and muscle spasm.
If these patients fail to respond to conservative therapy, a
diagnostic series of injections with fluoroscopic guidance is
considered. To patients who respond to local anesthetic
injections with reduction in pain, cryodenervations can be
offered as an adjunct to comprehensive physical therapy and
rehabilitation.
One study concluded that with intra-articular facet joint
injections, the evidence for short- and long-term pain relief is
limited for cervical pain and moderate for lumbar pain. For
medial branch blocks, the evidence is moderate for short- and
long-term pain relief. For medial branch neurotomy, the
evidence is moderate for short- and long-term pain relief.
Interspinous ligament pain
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Interspinous ligament pain is common after a spine operation
(lumbar, thoracic, or cervical). Pain impulses from interspinous
ligaments are carried by the medial branch of the posterior
ramus Patients report severe movement-related spine pain,
identified to the midline, which is worsened with hyperextension
and relieved by small volumes of local anesthetic injected into
the intraspinous ligament.
Cryodenervation can
responsive patients
be
considered
in
local
anesthetic–
Coccygodynia
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When coccygodynia has failed to respond to conservative
therapy, including the patient's use of a donut pillow, NSAIDs,
and local steroid injections, consideration can be given to
coccygeal neural blockade as the coccygeal nerve exits from the
sacral canal at the level of the cornu
Perineal pain
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Pain over the dorsal surface of the scrotum, perineum, and anus
that has not responded to conservative management at times
can be managed effectively with cryodenervation from inside
the sacral canal with bilateral S4 lesions. Test local anesthetic
injections should produce a positive response before
cryoablations are performed bilaterally at S4.
Ilioinguinal, iliohypogastric, and
genitofemoral neuropathies
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Ilioinguinal, iliohypogastric, and genitofemoral neuropathies
often complicate herniorrhaphy, general abdominal surgery, and
cesarean section. Patients present with sharp, lancinating to dull
pain radiating into the lower abdomen or groin.
The pain is exacerbated by lifting and defecating.
If the patient is responsive to a series of low-volume test
injections, consideration can be given to cryodenervation of the
appropriate nerve. Significant care and time must be spent
localizing the nerve with the sensory nerve stimulator.
The patient may help to localize the pain generator by pointing
with one finger to the point of maximum tenderness
Lower Extremity Pain
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Neuralgia resulting from irritation of the infrapatellar branch of
the saphenous nerve develops weeks to years after blunt injury
to the tibial plateau or after knee replacement
Neuralgia secondary to irritation of the deep and superficial
peroneal and intermediate dorsal cutaneous nerves can be seen
weeks to years after injury to the foot and ankle.
Neuralgia resulting from irritation of the superior gluteal branch
of the sciatic nerve is common after injury to the lower back
and hip sustained while lifting.
The clinical presentation consists of sharp pain in the lower
back, dull pain in the buttock, and vague pain to the popliteal
fossa
Craniofacial Pain
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Craniofacial nerves can be cryolesioned with a percutaneous or
open technique.
Entrapment neuropathies and neuromas are more responsive
to local anesthetic and cryodenervations than are neuropathies
of medical causes. Meticulous diagnostic injection ensures the
best outcome with cryoablation
A nerve stimulator is used to localize the nerve. Because these
areas are relatively densely vascular, injecting a few milliliters of
saline
solution
containing
1:100,000
epinephrine
is
recommended before inserting the cryoprobe introducer
cannula. A postprocedural ice pack applied for 30 minutes
reduces pain and swelling.
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Irritative neuropathy of the supraorbital nerve often occurs at
the supraorbital notch.Vulnerable to blunt trauma, this nerve
often is injured by deceleration against an automobile
windshield. Commonly confused with migraine and frontal
sinusitis, the pain of supraorbital neuralgia often manifests as a
throbbing frontal headache
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This neuralgia often worsens over time, perhaps owing to scar
formation around the nerve.
Neuropathic pain in the distribution of the supraorbital nerve
can be addressed with an open or closed cryoablative procedure
as long as appropriate conservative therapy has failed and the
pain responds to a series of test local anesthetic injections
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The infraorbital nerve (see Fig. 179.12) is the termination of the
second division of the trigeminal nerve. Irritative neuropathy
can occur at the infraorbital foramen secondary to blunt trauma
or fracture of the zygoma with entrapment of the nerve in the
bony callus .
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Cryoablation can be accomplished by an open or closed
technique. The closed technique can be performed from inside
the mouth through the superior buccolabial fold. In both
operations, the probe is advanced until it lies over the
infraorbital foramen
The mandibular nerve can be irritated at many locations along
its path.
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Injury to the mental nerve, the terminal portion of the
mandibular nerve, frequently occurs in edentulous patients. Pain
can be reproduced easily with palpation
The auriculotemporal nerve can be irritated at many sites
Patients often present with temporal pain associated with retroorbital pain. Pain often is referred to the teeth.
Posterior auricular neuralgia often follows blunt injury to the
mastoid area. It is common in abused women and usually
involves the left side owing to the preponderance of righthanded abusers. The clinical presentation consists of pain in the
ear associated with a feeling of “fullness” and tenderness. This
syndrome often is misdiagnosed as a chronic ear infection. The
posterior auricular
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nerve
runs
along
the
posterior
border
of
the
sternocleidomastoid muscle, superficially and immediately
posterior to the mastoid.
The glossopharyngeal nerve lies immediately subjacent to the
tonsillar fossa
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Many other common peripheral nerve injuries are amenable to
cryodenervation, including most cutaneous branches and the
occipital, suprascapular, superficial radial, and anterior
penetrating branches of the intercostal nerves.