Continuing Education Activity

It was not until 1926 that the use of phenol as a neurolytic agent was described by Doppler et al., followed by a description of intrathecal injection of phenol in 1955. In 1959, Nathan et al. and Kelly et al. described the earliest use of phenol for spasticity and reported relief following intrathecal injections. Phenol is a chemical composite agent that is comprised of carbolic acid, phenic acid, phenylic acid, phenyl hydroxide, hydroxybenzene, and oxybenzone. It denatures protein readily and may cause denervation when injected near neural structures, leading to loss of cellular fatty content, separation of the myelin sheath from the axon, and axonal edema. This activity reviews the role of phenol to denervate nerves, its indications, contraindications and highlights the role of the interprofessional team in the management of patients with chronic pain.

Objectives:

• Describe the mode of action of phenol.
• Describe the indications for phenol nerve block.
• Summarize the complications of a phenol nerve block.
• Outline interprofessional team strategies for improving care of patients withe chronic pain who undergo a phenol nerve block.

Introduction

Neurolysis is the temporary denervation of a targeted nerve or nerve plexus by directed infiltration of chemicals, obliteration from cryotherapy, or radiofrequency ablation. The first report of chemical neurolysis for the treatment of pain was made in 1863 by Luton who administered irritant chemicals subcutaneously into painful body areas and claimed substantial benefit to those with sciatic neuralgia. It was not until 1926 that the use of phenol as a neurolytic agent was described by Doppler et al., followed by a description of intrathecal injection of phenol in 1955.[1] In 1959, Nathan et al. and Kelly et al. described the earliest use of phenol for spasticity and reported relief following intrathecal injections.[2],[3]

Phenol is a chemical composite agent that is comprised of carbolic acid, phenic acid, phenylic acid, phenyl hydroxide, hydroxybenzene, and oxybenzone. It denatures protein readily and may cause denervation when injected near neural structures, leading to loss of cellular fatty content, separation of the myelin sheath from the axon, and axonal edema. Phenol’s effects may be a combination of both neurotoxicity and ischemia. Histologic specimens have demonstrated non-selective nerve destruction, muscle atrophy, and necrosis with phenol injections.[4],[5]

Currently, neurolysis is most often performed with ethanol and phenol, although hypertonic saline, glycerol, ammonium salt solutions, and chlorocresol have also been used in the past.[6]

Anatomy and Physiology

Anatomy is dependent on the planned procedure as phenol neurolysis may be performed in various peripheral nerves and nerve plexuses. Neuraxial drug administration is infrequently performed. Careful advancement of the needle should be taken to localize the desired nerve target with high fidelity, utilizing the guidance of ultrasonography, fluoroscopy, and/or nerve stimulation.

Indications

While no consensus guidelines or indications exist, phenol neurolytic injections may be utilized for persistent and intractable pain conditions. Careful patient selection is crucial, and it should be established that the patient has trialed other modalities of pain control prior to pursuing neurolysis. Psychological evaluation is also important before determining candidacy for neurolysis. Due to the adverse effects, extensive communication and a thorough informed consent process should be undertaken to describe the risks, benefits, and alternatives. While most patients have failed prior therapy, neurolysis should still be used in conjunction with other therapeutic regimens including pharmacotherapy, psychologic counseling, and physical therapy. Diagnostic local anesthetic blocks should also be employed prior to neurolysis in the desired target nerve, allowing the provider to predict a successful outcome of neurolysis. Furthermore, a trial of a local anesthetic block may also confirm the anatomic nature of the pain and allow the patient to experience short-term clinical effects similar to a neurolytic block but without the same adverse effect profile of neurolytic agents. If short-term pain relief is experienced, the patient may be a good candidate for successful neurolysis.

Targets for chemical neurolysis may include peripheral nerves, saddle blockade, lumbar sympathetic blocks, the celiac plexus, and the neuraxis. General indications include management of chronic and intractable pain unresponsive to other modalities, treatment of cancer pain in patients with a short life expectancy, and alternative management of spasticity to improve functional status including balance, gait, and self-care. While the indications for neurolysis may be broadly applicable to various neurolytic agents, phenol is a widely instilled agent to treat severe spasticity as direct injection near a motor nerve can selectively reduce hypertonicity.[7] Moreover, intrathecal phenol has also been utilized to treat spasticity of spinal cord etiology and intractable pain disorders such as end-stage cancer of the abdomen or pelvis. Furthermore, phenol infiltration along the paravertebral and perivascular sympathetic fibers can be used to establish a sympathectomy for the treatment of peripheral vascular disease.[8] An important difference between neurolytic blocks for pain relief versus spasticity is that motor or mixed nerves are targeted preferentially in the management of spastic disorders.

Contraindications

Contraindications include patient refusal, active infection, tumor involvement at the needle entry site (for non-malignant pain or spasticity disorders), and bleeding disorders or use of anticoagulant therapy when injection will occur at a high-risk site, for example, neuraxis.

Equipment

A small-gauge needle, typically a 25-gauge needle, is used for local anesthetic infiltration of skin. Localization of the desired nerve may be guided by the use of fluoroscopy, ultrasound, and/or nerve stimulators. If a neuraxial approach is being performed, spinal or epidural needle characteristics are dependent on patient body habitus, age, provider preference, and other factors. If peripheral nerve neurolysis is being performed, needle length and gauge depend on the depth of the target nerve, provider preference, use of a peripheral nerve stimulator, and other factors.

Preparation

Phenol is available in an 89% solution and must be prepared by the hospital pharmacy. It is unstable at room temperature and oxidizes in the presence of air and light, changing to red. Depending on the desired pharmacokinetic and therapeutic effect, phenol may be prepared in an aqueous, glycerin, or lipid solution and diluted to the desired concentration, typically 2% to 3%. Phenol mixed with glycerin causes the phenol to diffuse slowly, resulting in a very limited spread pattern maintained at the site of injection. This viscous preparation of phenol diluted with glycerin is hyperbaric in relation to cerebrospinal fluid (CSF). Aqueous preparations of phenol are more potent neurolytic agents with a wider spread. Contrast may also be mixed to aid in visualization during fluoroscopy.

Although the ideal concentration of phenol for neurolysis is not well-studied, studies report an ideal range from 3% to 12%.[9] Dilute concentrations less than 5% result in protein denaturation of axons and blood vessels, while concentrations greater than 5% may produce protein coagulation and nonselective segmental demyelination. The maximum daily dose is 1 gram, and caution must be taken in patients with advanced liver disease given that the liver metabolizes phenol.

The performing provider must appropriately obtain informed consent. Patient positioning depends on which nerve is targeted. Minimal or no sedation is typically required, as injection with phenol is painless due to its immediate local anesthetic properties. This is in contrast to alcohol, which may be intensely painful upon injection. Aseptic technique must be employed.

Technique or Treatment

Under aseptic precaution and occasionally with mild sedation, the desired target nerve is first identified via ultrasound, nerve stimulation, or fluoroscopy. A local anesthetic may be infiltrated at the skin. Then, the needle is advanced until it is near the target nerve, which is again confirmed via the modalities above of ultrasound, nerve stimulation, or fluoroscopy, often with contrast administration. If the nerve stimulation approach is performed, advancement of the needle and current reduction are continued until the desired motor response is achieved with a current of 0.2 to 0.5 mA at 0.1-millisecond stimulus duration. Once a proper motor response is obtained with a current of 0.2 to 0.5 mA from the nerve stimulator, the needle should be in the correct position. After a preliminary aspiration, a diagnostic block with a local anesthetic may be used to confirm the correct position of the needle. The prepared phenol solution may then be injected. Because phenol has immediate local anesthetic effects, injection is typically painless. Other immediate effects include the abolition of contractions and a reduction in the degree of spasticity. Cardiovascular monitoring during and after the procedure with resuscitative backup is important in preventing and treating adverse outcomes. Due to its immediate selective effect on smaller nerve fibers, phenol has an immediate local anesthetic effect. Thus, it is crucial to remember that the therapeutic effect from phenol neurolysis cannot be evaluated until after 24 to 48 hours after resolution of its local anesthetic effect, and often the neurolytic effect may not be clinically evident for 3 to 7 days.

Complications

As with other interventional procedures, common complications include pain on injection, bleeding, and infection. There may be damage to skin and necrosis of surrounding muscles, blood vessels, and soft tissues. An accidental intravascular injection may cause tinnitus and flushing. Neuritis may manifest after partial destruction of a somatic nerve with subsequent regeneration; the dysesthesia or hyperesthesia that results may be worse than the original pain. Other especially concerning complications include prolonged motor paralysis from motor nerve denervation or vascular injury, as well as bowel and bladder dysfunction and sexual dysfunction. Phenol is metabolized in the liver via conjugation and oxidation and excreted by the kidney. Thus, it is typically avoided in patients with advanced hepatic disease. Chronic exposure to phenol may also lead to renal toxicity, skin lesions, and gastrointestinal effects. Systemic side effects include nausea and vomiting, central nervous system (CNS) stimulation, and cardiovascular depression. Due to this side effect profile, Boas et al. recommends avoidance of phenol for celiac plexus block and sparing use for splanchnic nerve block due to the proximity to major blood vessels. Side effects are uncommon if systemic doses are less than 100 mg.

Clinical Significance

No large-scale controlled studies are available on the use of phenol neurolysis, and thus the literature only consists of small retrospective studies, case series and reports, observations, and book chapters reflecting opinions from experienced clinicians. Chemical neurolysis with phenol or other agents like alcohol) is typically a therapy of last resort and reserved for end-stage therapy.

When used for the treatment of acquired muscle spasticity, phenol nerve injection can provide a temporary motor nerve blockade lasting weeks or months, which may improve physical functioning and gait. Spasticity is typically associated with neurological diagnoses of stroke, traumatic brain injury, and spinal cord injury. Depending on the pattern and location of spasticity, phenol neurolysis can target various peripheral nerves in the upper and lower extremities. In a retrospective analysis of 185 patients who underwent phenol neurolysis for spasticity, the most commonly injected nerve was the obturator nerve in 35.8% of cases and the sciatic branches to the hamstrings and adductor magnus in 27.0% of cases.[10] Duration of therapeutic effect for decreased pain or spasticity has been reported to be between 2 months and t2o years, irrespective of the underlying disorder.[5][11] During this period, passive limb mobilization can also be performed to prevent fixed soft tissue contractures.[12]

Neuraxial administration of phenol has fallen out of favor due to potential side effects and is mostly described in the literature in the end-stage cancer population.[12] For instance, neuraxial neurolysis may provide an improvement in pain symptoms and quality of life in patients with cancer in the abdomen or pelvis, although this modality will often lead to loss of bowel and bladder function and lower extremity weakness.[13] Only a small percentage of cancer patients are suitable candidates for this type of neurolytic blockade, which should be considered as a last resort option. Cancer pain may manifest as visceral, somatic, or neuropathic pain. Intrathecal neuraxial neurolysis is likely most effective in treating somatic and occasionally a visceral pain, but less effective for neuropathic pain states.[13]

Regarding pain control, while phenol neuroablation is widely known in chronic malignant pain, Weksler et al. explored its benefits in 42 patients with refractory chronic non-malignant pain. The interventions for phenol neurolysis in this study were diverse, comprising lumbar sympathectomy, medial branch destruction, sacroiliac joint injections, intercostal neurolysis, greater occipital nerve destruction, genitofemoral neuroablation, and paracoccygeal infiltration. The use of 4% phenol in aqueous solution was effective and safe for neurolysis in these patients with no major complications reported. However, due to the risk for flaccid paralysis, phenol use should still be reserved for selected cases of non-malignant pain, far removed from motor nerves and the spinal cord.

Finally, studies have compared the efficacy and adverse effects of different types of neurolytic agents, most commonly between alcohol and phenol. Moller et al. described phenol as being more potent than alcohol, stating that 5% phenol is equivalent to 40% alcohol in neurolytic potency.[14] However, most providers agree that phenol leads to a shorter duration and less intense neurolytic block with more systemic side effects compared to alcohol, although some studies report no difference. For instance, in a randomized controlled pilot study on 20 patients with hemiplegic stroke, it was observed that both phenol and alcohol were equally effective in reducing spasticity, though the use of 50% alcohol in the management of ankle plantar flexor spasticity appears to be a longer lasting modality.[15] Furthermore, a non-randomized trial of 57 cancer patients by Shah et al. showed a greater incidence of systemic side effects with phenol compared to alcohol, including nausea, hypotension, and bradycardia.

Phenol is a well-recognized neurolytic agent that may serve as another useful tool in the pain specialist’s armamentarium. Data for its use are quite limited but are most encouraging for spasticity and end-stage cancer. Future large-scale trials should focus on the role of phenol neurolysis in spasticity management, and also investigate its cost-effectiveness compared to other available treatment options.

Enhancing Healthcare Team Outcomes

Phenol was once widely used for pain control. However, with the availability of better and safer agents, its use has declined. Phenol is primarily used by the pain specialist, anesthesiologist, and the radiologist. If phenol is used, the interprofessional team of the clinician, nurse, and pharmacist must be aware of the correct dosing and expected toxicity. The nurse must monitor the patient during injection and post-procedure. The pharmacist must confirm correct dosing. If there are complications, the interprofessional clinical team needs to be made aware of concerns quickly. While phenol is safe, there are reports about paralysis, hypotension, and apnea following the injection. Its efficacy as a pain-relieving agent also varies depending on the concentration used and volume. As such, for the best outcomes, an interprofessional team approach will lead to the best outcomes.