Drugs and Agents Used in Neurolysis and Fluoroscopy
of neural transmission as a result of therapeutic application of a
chemical or physical destructive agent to a nerve, usually for pain
control purposes. Chemical neurolytic agents include alcohol, phenol,
glycerol, ammonium compounds, hypotonic or hypertonic solutions, and
alkyl tetracaine derivatives. Among these, alcohol and phenol have
remained the neurolytics of choice.
1931, which makes it, perhaps, the neurolytic agent that has been in
use the longest. Alcohol is a potent neurolytic agent that destroys
both spinal and peripheral nerves. It has a wide application, having
been used for trigeminal ganglion, subarachnoid, celiac plexus, and
lumbar sympathetic chain blockade.
extraction of phospholipids, cholesterol, and cerebrosides; and
precipitation of mucoproteins and lipoproteins. These actions result in
sclerosis and separation of the myelin sheath, edematous Schwann cells,
and axons. The basal lamina of the Schwann cell tube is often spared
and the axon can regenerate along the previous course; if the ganglion
is injected, it may produce cell destruction with no subsequent
Concentrations of at least 35% to 50% are needed to produce neurolysis.
There is a relationship between the concentration used and the degree
of block provided.
Ethanol 30% in the subarachnoid space temporarily destroys sensory but not motor function.
Concentrations below 50% produce no motor dysfunction.
Concentrations of 50% can produce neurolysis of C fibers.
Concentrations above 60% may produce paralysis for an unpredictable duration.
Alcohol of 75% concentration can produce neurolysis of sensory and C fibers.
At concentrations of 95% and above
(absolute alcohol), the destruction involves all fibers (sympathetic,
sensory, and motor), with a success rate up to 58%; injection of
absolute alcohol is followed by considerable fibrosis.
Subarachnoid block: Between a minimum of 0.3 mL to a maximum of 1.5 mL per segment. Generally, concentrations of 50% and 100% are preferred.
Celiac plexus and lumbar sympathetic blocks: 10 to 20 mL absolute alcohol bilaterally.
alcohol is usually 4 months or less. In animal models, topical
application of alcohol results in depression of action potentials
lasting for 8 weeks.
using alcohol as a neurolytic agent. It may cause pain that is worse
than the original pain. It follows an incomplete destruction of a
somatic nerve, more frequent during neurolysis of thoracic sympathetic
nerves. In most instances, the symptoms subside within a few weeks or a
month. Other complications/disadvantages of alcohol include:
Alcohol is an irritant for soft tissue,
and its injection is associated with an uncomfortable burning
dysesthesia, which requires prior or concomitant injection of local
Alcohol has a high solubility in body
fluids and spreads quickly from the injection site. This high
solubility makes it difficult for alcohol to reach its target tissue
and necessitates a larger volume, increasing the chance of damage to
tissue in the immediate vicinity.
Vasospasm accounts for the paraplegia
reported after celiac plexus block. Injection of alcohol triggers an
intense burning sensation along the target nerve tract, followed after
approximately 1 minute by a warm, numb sensation. Prior or concomitant
administration of local anesthetic has been used in practice.
Advantages of this technique include improved patient comfort and local
anesthetic effects in the area of distribution of target nerve with
confirmation of correct needle placement. An advantage of not using a
local anesthetic is that pain along the target nerve will confirm
correct needle placement. Denervation and pain relief occur over
approximately 1 week. If no pain relief has been accomplished after
this period, repeat neurolysis may be considered.
destruction in 1925. Putnam and Hampton were the first to report phenol
use for neurolysis in 1936. Nachaev reported its use as a local
anesthetic in 1933. Since 1959, phenol has been used as a neurolytic
agent for the treatment of both chronic pain and spasticity. The block
produced by phenol tends to be less profound and of shorter duration
than that produced by alcohol.
concentration: Protein denaturation occurs at concentrations less than
5%, and concentrations higher than 5% produce protein
nonspecific segmental demyelination, and orthograde degeneration (i.e.,
wallerian degeneration). Axons of all sizes are affected and appear
edematous; however, posterior root ganglia are unaffected by phenol. It
has been suggested that phenol has a greater affinity for vascular than
neuronal tissue (causing neuronal tissue damage by interfering with
blood flow), but this observation has not been supported by further
saline, Renografin (Bristol-Meyers Squibb, New York, NY), metrizamide,
and glycerin. The composition of phenol solution determines the
potency: Aqueous solutions are more potent than glycerin solutions. (Note:
Phenol is relatively insoluble in water, and aqueous solutions with
concentrations above 6.7% usually need additional glycerin.)
pharmaceutical compound; it should be prepared by the hospital
pharmacist. The most commonly used concentrations are between 6% and
8%. More recent studies have shown that 12% phenol in Renografin is a
better neurolytic agent than phenol in lesser concentrations. There is
also a gradation of intensity of the block according to the
Concentrations of 3.3% and below are ineffective.
Injection of the subarachnoid space with
concentrations of less than 5% produces mostly sensory blocks, whereas
concentrations above 5% produce motor blockade as well.
Pain transmission is blocked at concentrations of 5%.
Touch and proprioception are blocked at concentrations above 5%.
Concentrations between 5% and 6% produce destruction of nociceptive fibers with minimum side effects.
Concentrations higher than 6% may cause
axonal abnormalities, nerve root damage, spinal cord infarcts,
arachnoiditis, or meningitis. This may explain the long-lasting effects
of neurolytic blocks using 10% phenol in the sympathetic axis.
Phenol in glycerin at concentrations
varying between 6% and 12% can achieve a neurolytic blockade of motor,
sensory, and C fibers (success rate of 60%).
with cerebrospinal fluid. Also, they are very stable given the high
solubility of phenol in glycerin. The diffusion of phenol from the
solution is slow, with a limited spread and highly localized tissue
fixation. This is particularly important for intrathecal injections.
When mixed with glycerin, both phenol and glycerin should be totally
water-free; otherwise, the spread of the solution is unpredictable and
the narcotic effect much greater than anticipated. Because of their
high viscosity, glycerin solutions of phenol are difficult to inject
through smaller than 20-gauge needles.
clinically. It has an initial local anesthetic-like effect with
subjective warmth and numbness, which lasts for about 24 hours,
followed by neurolysis, with pain less intense than that caused by
alcohol. As with alcohol, the neurolytic effect should become
clinically evident after about 1 week. If neurolysis does not occur in
2 weeks, a repetition of the procedure may be considered. Neuritis is
less common with phenol injection than with alcohol. For this reason,
most physicians prefer phenol to treat neurolysis in patients with
unknown life expectancy, minimizing the chance of neuritis as a late
complication of the neurolysis.
concentrations between 1% and 10% (up to 1 g) are unlikely to cause
serious toxicity. Systemic doses of 8.5 g and above cause convulsions
followed by depression of the central nervous system and cardiovascular
collapse. A potency equivalence of 3% phenol and 40% alcohol has been
supported by studies.
neurolytic block; however, it is accepted that it is shorter than the
block provided by alcohol. Histopathologic studies have revealed that
the damage of perineural vascular elements reaches a maximum in 2
weeks, followed by maximum recovery in 14 weeks.
neurolytic agents for pain treatment. Some of the recommended
concentrations of alcohol and phenol solutions used for various
neurolytic blocks are as follows:
Intrathecal neurolytic blocks: Alcohol 100% or phenol 4% to 5% in glycerol.
Epidural neurolytic blocks: Alcohol 30% or 100%; phenol 10% in 10% glycerol or 7% in water.
Celiac plexus blocks: Alcohol 50%.
Sympathetic ganglion neurolytic block: Alcohol 100% or phenol 10% in 10% glycerol.
Pituitary gland block: Alcohol 100% or phenol 7% in water.
hypobaric, while phenol 4% to 5% is hyperbaric in relation to
cerebrospinal fluid. This is important for patient positioning. The
dorsal roots to be blocked should be in the most superior position when
alcohol is used as a neurolytic agent and in the most dependent
position when neurolysis is accomplished with phenol. Phenol is the
agent of choice for epidural neurolysis.
action of glycerol appears to affect primarily damaged myelinated
axons. Injection in the vicinity of the nerve causes perineural damage,
while intraneural injection results in Schwann cell edema, axonolysis,
and wallerian degeneration. Intraneural injection destroys all fibers.
with obliteration of C fibers and only a small effect on A fibers.
However, the degeneration is nonselective and may affect all types of
appears at concentrations of 10% and greater, with a success rate of
40% (a 10% concentration provides adequate analgesia and no motor
headache. Paresthesia and burning sensation occur in 30% of patients at
doses of 500 mg of ammonium salts, lasting 2 to 14 days.
a success rate of 30%. Normal saline is thought to act specifically on
C fibers, sparing larger fibers of sensory, motor, and autonomic
functions. Likewise, application of distilled water on the dorsal root
ganglia for 5 minutes produces a differential C-fiber block similar to
that seen with in vitro normal saline. The mechanism of action seems to
be an intrathecal shift of water with extracellular change in
saline injection. Complications consist of tachycardia, premature
ventricular contractions and myocardial infarction, localized paresis
(which may last for many hours), paresthesia (which may last for many
weeks), hemiplegia, pulmonary edema, pain in the ear, vestibular
disturbances, and loss of sphincter control with sacral anesthesia.
immediate progressive burning paresthesia that fades over several
hours. Although phenol may alleviate the pain, it may gradually return
in a few hours. These inconveniences led to the search for new
neurolytic agents, such as tetracaine derivatives. Derivatives of
tetracaine, such as N-alkyl tetracaine compounds, are being examined
for both their anesthetic and their neurolytic properties. N-butyl
tetracaine has both rapid-onset local anesthetic and neurolytic
properties, which may last several weeks.
derivatives is not known, it has already been shown that tetracaine is
neurotoxic and causes nerve damage when applied at high concentrations.
All derivatives are strong sodium channel blockers, more potent than
tetracaine. Neurolysis occurs as long as the compound can cross the
cell membrane and enter the cytoplasm; only derivatives having ≥ 3
carbons can cross the cell membrane and cause neurolysis. The longer
duration of alkylated tetracaine derivatives may be explained by their
permanent positive charge that causes compound to be trapped within the
cell; the alkylated derivatives of tetracaine display superior local
anesthetic properties compared with the original compound.
of tetracaine (like N-butyl tetracaine), apart from their neurolytic
properties, is a strong local anesthetic activity that prevents patient
discomfort at the time of injection.
neurolytic agents. At a concentration of 3%, metrizamide can provide a
block of C fibers.
is commonly used for identification of anatomic structures to be
injected subsequently with local anesthetics and antiinflammatory
drugs. Although our purpose is not to inject contrast media
intravascularly or intrathecally, these compounds still may
inadvertently reach the bloodstream or subarachnoid space. Concerning
allergic reactions, the dose of radio-opaque material used in this
medical field is usually not much, but that may not make a difference
in an already sensitized patient.
agents, besides avoiding compounds that the patient is allergic to, is
to make sure that any radio-opaque agent that may reach the epidural or
intrathecal space is nonionic. Serious adverse reactions have been
reported due to inadvertent intrathecal administration of iodinated
contrast media that are not indicated for intrathecal use. These
serious adverse reactions include: death, convulsions, cerebral
hemorrhage, coma, paralysis, arachnoiditis, acute renal failure,
cardiac arrest, seizures, rhabdomyolysis, hyperthermia, and brain edema.
nonionic and with low osmolality. The osmolality of a contrast medium
is classified as high (≈1.500 mOsm/kg) or low (≈350 to 600 mOsm/kg),
depending on the ionic content of the agent components.
Princeton, NJ) and iothalamate (Conray, Tyco, Pembroke, Bermuda) are
both ionic contrast media. Their use should be limited to peripheral
blockade (e.g., muscle injection, sacroiliac joint injection).
Metrizamide (Amipaque, Nycomed Amersham, Amersham, UK), iopamidol
(Isovue, Bracco Diagnostics, Princeton, NJ), and iohexol (Omnipaque,
Amersham Health, Princeton, NJ) are all nonionic compounds and
therefore may be used for central neural blockade.
following the use of nonionic than ionic contrast media. They are
usually mild and include a feeling of warmth, transient metallic taste,
gastrointestinal discomfort, hypersensitivity, vagal reactions
(hypotension, bradycardia), headache, hypertension, pyrexia, and iodism
(“iodine mumps”). Severe manifestations, such as laryngeal edema,
bronchospasm, or pulmonary edema, are very rare.
fetus are unknown, and they should be used during pregnancy only if
clearly needed. These agents may be excreted in breast milk. It is
recommended that bottle-feeding be substituted for breast-feeding for
24 hours postprocedure.
not absolutely contraindicate the use of a contrast agent when a
diagnostic procedure is thought essential, but caution should be
exercised and preparations should be made. A prophylactic regimen,
consisting of antihistamine medication and corticosteroids, may be
or intentionally), maintain the patient in the “head-up” position
during and after the procedure. Observe the patient for at least 30
minutes after contrast injection because the majority of side effects
occur within this period of time; however, delayed reactions may also
occur. If intrathecal injection is suspected, the patient should be
advised not to drive a car or use machines for the first 24 hours
of Drug and Contrast Media (1997–1998) and Commission of General and
Pediatric Radiology. Iodinated contrast media, 3rd ed.
GK, Vladimirov M, Shi H, et al. Structure–activity relation of N-alkyl
tetracaine derivatives as neurolytic agents for sciatic nerve lesions. Anesthesiology 1998;88:417–428.