Drugs and Agents Used in Neurolysis and Fluoroscopy

Victor Andrei Georgescu

Drugs Used in Neurolysis

Neurolysis is the long-lasting or permanent interruption 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.

Alcohol (Ethyl Alcohol)

Doglioti first used alcohol for neurolytic purposes in 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.

Mechanism

The mechanisms of action of alcohol include dehydration; 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 regeneration.

Concentration and Use

The usual concentrations are 50%, 75%, and 100%. 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.

Doses

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.

Prior to injection, alcohol 100% may be diluted 1:1 with local anesthetic for better patient tolerance.

Duration

Effective duration of neurolysis with intrathecal alcohol is usually 4 months or less. In animal models, topical application of alcohol results in depression of action potentials lasting for 8 weeks.

Complications and Disadvantages

Neuritis has been defined as “the great disadvantage” of 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 anesthetic.
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.

Phenol

Doppler first used phenol for deliberate nerve 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.

Mechanism

The mechanism of action of phenol depends on its concentration: Protein denaturation occurs at concentrations less than 5%, and concentrations higher than 5% produce protein
coagulation, 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 studies.

Concentration and Use

Phenol has been prepared in sterile water, normal 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.)

Phenol is not available in a “ready-to-use” 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 concentration used.