Neurolytic therapy remains a therapy of last resort. However, for the appropriate patient, it can result in significant improvement of quality of life and possibly improved function. Few other interventional pain therapies have such extreme risk/benefit profiles requiring targeted patient selection and meticulous procedural technique. Evaluating neurolysis as a therapeutic option is usually reserved for end-stage therapy, primarily patients with refractory cancer pain resulting from the significant possibility of severe side effects. For instance, neuraxial neurolysis can provide profound pain relief for patients with pain related to invasive tumors involving the pelvis, but this approach often also leads to loss of bowel or bladder function and may well also produce weakness in the lower extremities. It should also be emphasized that relief from neurolytic blocks is usually not complete, as most patients with cancer pain have multiple sources of their pain. Although this therapeutic modality is no longer novel in development or application, neuraxial neurolysis is an important treatment modality for patients in extremis . Neurolytic agents available in the United States for common use in the neuraxis include ethanol and phenol. The five criteria for neurolysis are (1) the presence of severe pain, (2) the failure of less invasive techniques to relieve the pain, (3) the presence of well-localized pain, (4) the relief of pain with diagnostic local anesthetic blocks, and (5) the absence of undesirable effects after diagnostic blocks ( Box 58.1 ).
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Pain is severe and unremitting
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Pain is unresponsive to medical management
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Pain is relieved with diagnostic blocks using local anesthetic
- •
No undesirable effects appear during local anesthetic blocks
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Pain is well localized
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Pain affects the patient’s function
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Patient is not a candidate for neuraxial medication delivery systems
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Patient has failed neuraxial medication delivery
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The patient is able perform informed consent or has appropriate advance directive
Neurolytic blocks can be peripheral, neuraxial, or visceral. Of the three, visceral blocks are most commonly performed (this subject will be covered in Chapter 60 ), whereas neuraxial and peripheral neurolytic blocks are performed less frequently for many reasons. In the case of peripheral neurolytic nerve blocks, blocking mixed motor and sensory nerves can cause motor deficit leading to loss of functionality for the patient. In addition, peripheral neuritis and deafferentation pain are potential painful consequences, whereas the block itself is not predictably permanent. Finally, the patient may also be dissatisfied with the subsequent numbness of the area and complain of symptoms of anesthesia dolorosa . Neuraxial neurolytic blocks, including both intrathecal and epidural alcohol or phenol neurolytic blocks, are rarely used today because neuraxial analgesics including opioids, local anesthetics, and clonidine can effectively and safely be used to treat cancer pain. Where an intrathecal drug delivery system can provide widespread pain relief that can be adjusted to accommodate many scenarios, a successful neurolytic block may have to be repeated with changes in pain pathology, such as the presence of new metastatic lesions. In such cases, it is impractical to perform subsequent subarachnoid neurolytic injections because of their attendant risks, whereas an indwelling intrathecal (and occasionally epidural) drug delivery system will cover new areas of pain and continue to be useful. This chapter reviews the technical approaches and pharmacological agents used for neurolytic blocks.
Neurolytic Agents ( Table 58.1 )
Alcohol
Ethyl alcohol (ethanol) is the classic neurolytic agent first reported by Dogliotti in 1931 for intrathecal injection. Anhydrous ethanol is commercially available undiluted (100% concentration) but will absorb a small amount of water from the air upon exposure to the atmosphere. Although neurolytic blocks have been shown to require a concentration of 33% or greater to effect neurolysis, the most common concentrations used are ≥80% when diluted with contrast medium or local anesthetic. The neurolytic action of alcohol is produced by the extraction of neural cholesterol, phospholipids, and cerebrosides, and the precipitation of mucopeptides. These actions result in sclerosis of the nerve fibers and myelin sheath, leading to demyelination. The basal lamina of the Schwann cell sheath remains intact, allowing for new Schwann cell growth, thereby providing the framework for subsequent nerve fiber growth. This framework encourages the regeneration of axons, but only if the cell bodies of these nerves are not completely destroyed. The pathway of degeneration is nonselective and can be observed in peripheral nerves and spinal nerve roots following intrathecal injection. Areas of demyelination can be seen in posterior columns, Lissauer’s tract, and the dorsal root, followed by Wallerian degeneration to the dorsal horn. Intrathecal alcohol injection results in rapid uptake of alcohol and variable injury to the surface of the spinal cord.
| Alcohol | Phenol | |
|---|---|---|
| Physical properties | Low water solubility | Absorbs water on air exposure |
| Stability at room temperature | Unstable | Stable |
| Concentration | 100% | 4%-8% |
| Diluent | None | Glycerin |
| Relative to CSF | Hypobaric | Hyperbaric |
| Injection sensation | Burning pain | Painless, warm feeling |
| Onset of neurolysis | Immediate | Delayed (15 min) |
| CSF uptake ends | 30 minutes | 15 minutes |
| Full effect of neurolysis | 3-5 days | 1 day |
Ethanol is quickly absorbed from the cerebrospinal fluid (CSF) so that only 10% of the initial dose remains in the CSF after 10 minutes and only 4% after 30 minutes. The rapid spread from the injection site means larger volumes are required than for phenol, which in turn may result in local tissue damage. In the case of celiac plexus blocks, alcohol is rapidly absorbed into the bloodstream. It has been shown that serum ethanol levels up to 54 mg/dL can occur after a celiac plexus block. However, following the intrathecal administration of alcohol, it is unlikely that there will be significant vascular uptake. Ethanol has a specific gravity of less than 0.8, and CSF has a specific gravity of slightly greater than 1. Within the CSF, alcohol is hypobaric and will move against gravity, “floating” upward. Therefore, positioning of the patient is an extremely important factor to consider when planning the procedure.
The use of ethanol as a neurolytic agent has been associated with a disulfram-like effect, acetaldehyde syndrome. Case reports include patients taking moxalactam, a beta lactam antibiotic that inhibits aldehyde dehydrogenase, documented disulfram-like effects, and another taking 1-hexyl carbamoyl-5-fluorouracil, an anticancer drug, experienced similar symptoms. The patients experienced flushing, hypotension, tachycardia, and diaphoresis within 15 minutes of alcohol administration. The symptoms resolved 4 to 6 hours later, and efforts were undertaken to stabilize hemodynamics. Both cases occurred after celiac plexus blocks. It is important for the pain practitioner to recognize medications that may cause disulfram-like effects, such as chloramphenicol, beta-lactams, metronidazole, tolbutamide, chlorpropamide, and disulfram, after peripheral neurolytic blocks with alcohol.
Perineural administration of ethanol is associated with burning dysesthesias in the distribution of the nerve. This sensation is often extremely unpleasant for the patient and can last from a few minutes to a few weeks. To alleviate this outcome, local anesthetic is administered prior to the use of ethyl alcohol. The use of this initial dose of local anesthetic can also provide diagnostic guidance on the correct location for the neurolytic that has enormous importance. The administration of ethanol for the purpose of neurolysis can have catastrophic consequences. It has been associated with both transient and permanent paraplegia in both celiac plexus and intrathecal blocks. It has been postulated that these effects are secondary to vasospasm of the spinal arteries by the direct action of alcohol or direct damage to the spinal motor nerves.
Phenol
Phenol is a benzene ring with one hydroxyl group substituted for a hydrogen atom. It is usually prepared by the hospital pharmacy because it is not commercially available in premixed liquid form. Phenol is poorly soluble in water and, at room temperature, forms only a 6.7% aqueous solution. It has a shelf life of approximately 1 year if refrigerated and shielded from light exposure. When phenol is exposed to room air, it oxidizes and turns a reddish color. Phenol is frequently prepared with contrast and sterile water, sterile saline, or glycerin. When it is prepared with glycerin, it has limited anatomic spread, and, hence, injections are well localized. In rats, the aqueous solution of phenol has greater ability to penetrate the perineurium and produce greater endoneurial damage than glycerin preparations, but there is no difference in results following intraneural injection. Unlike alcohol, phenol injection has an initial local anesthetic effect. It is not associated with localized burning but instead creates a sensation of warmth for a short time after injection. The distribution of this sensation can help the practitioner verify proper needle placement similar to a diagnostic local anesthetic injection. Concentrations of 4% to 10% are typically used for neurolysis. When phenol is prepared in glycerin, it has a specific gravity of 1.25, making it hyperbaric. Preparations of phenol in glycerin are highly viscous, which may make administration through a small (22 or 25 gauge) spinal needle difficult.
Putnam and Hampton first used phenol as a neurolytic agent in 1936. Mandl used it for a sympathetic ganglion block in animals in 1947. Phenol was first used as a medication in an intrathecal injection in humans in 1955. It was once believed that phenol’s neurolytic effects might be due to local ischemia because of its greater affinity for vascular tissue compared to neural tissue. Racz found that unlike epidural injection, tissue destruction resulted after intrathecal injection even though the vasculature was intact in the areas of spinal cord destruction. This finding points toward direct neurotoxic effects rather than effects secondary to local ischemia. Phenol’s effects may be a combination of direct neurotoxic and ischemic effects. Originally, it was surmised that phenol had a selective effect on small-diameter, unmyelinated nerve fibers, such as C-fiber afferents and lightly myelinated A-δ afferents. Subsequent studies have shown that phenol concentrations determine the type and extent of nerve disruption. Dilute intrathecal phenol can produce a transient local anesthetic blockade, whereas increased concentrations can produce significant neural damage. At concentrations less than 5%, phenol results in protein denaturation of axons and surrounding blood vessels. At concentrations >5%, phenol can produce protein coagulation and nonselective segmental demyelination. Nathan confirmed the nonselective effects of phenol using histologic studies combined with evidence of electrophysiologic changes to Aα and Aβ fibers. Smith showed that intrathecal phenol injections in cats and humans primarily destroyed axons in dorsal rootlets and in the dorsal columns of the spinal cord. It was also noted to exert some effects on the ventral root axons. Maher and Mehta noted that motor blocks by phenol were possible at concentrations greater than 5%, whereas intrathecal injections of less than 5% produced mostly sensory blocks. At higher concentrations, the extent of damage can increase significantly, with the potential of axonal nerve root damage and spinal cord infarcts. Injections of high-concentration phenol have also been associated with arachnoiditis and meningitis.
Systemic doses of phenol in excess of 8.5% are associated with toxic side effects. These effects initially are convulsions, followed by central nervous system depression, and, finally, cardiovascular collapse. Chronic long-term exposure may be associated with renal toxicity, skin lesions, and gastrointestinal effects. However, phenol is not classically used in long-term settings, and the customary doses of less than 100 mg are unlikely to produce any systemic effects.
When compared to alcohol, phenol seems to facilitate axonal regeneration in a shorter period of time. Electrophysiologic studies comparing peripheral nerve destruction in cats showed that those injected with phenol had returned to normal by 2 months, whereas at the end of the same time period, those injected with alcohol still demonstrated depression of compound action potentials.
Glycerol
Glycerol is a colorless, odorless, viscous, liquid, polyol compound. It has three hydroxyl groups that result in high water solubility and it is hygroscopic in nature. The glycerol backbone is central to all lipids known as triglycerides. When placed on nervous tissue, myelin disintegration and axonolysis occur in both myelinated and unmyelinated fibers. In the uninjured nerve, the c-fiber and lightly myelinated fibers are the most sensitive to neurolysis, requiring higher concentrations to destroy the heavily myelinated fibers. However, this order is altered in the injured nerve; the heavily myelinated fibers become very sensitive to the neurolytic properties of glycerol. In 1981, Hakanson was the first to use glycerol for neurolysis of the trigeminal ganglion. The success is most likely related to a combination of the viscous nature of glycerol and resultant lack of spread into other sensitive structures, the low concentration required to destroy the abnormally firing myelinated fibers while preserving the uninjured sensory afferents. The use of glycerol for neurolysis is now primarily restricted to the neurolysis of the Gasserian ganglion.
Neurolytic Blocks
Neurolytic agents can be injected surrounding peripheral nerves, along the neuraxis within the intrathecal or epidural spaces, or adjacent to visceral sympathetic nerves. Each of these sites of injection is associated with specific benefits, risks, and complications. Peripheral neurolysis can include injection into the trigeminal ganglion, truncal, upper, and lower extremities.
Head and Neck
Gasserian Ganglion Neurolysis
Peripheral nerves in the head and neck are destroyed for a variety of reasons. These include blockade of the trigeminal ganglion for trigeminal neuralgia that is not responsive to medical management and for relief of cancer pain secondary to invasive tumors of the orbit, maxillary sinus, and mandible; and blockade of individual peripheral nerves in the head.
The gasserian ganglion is formed from two trigeminal roots that exit the ventral surface of the brainstem at the midpontine level. The roots pass forward and in a lateral direction, in the posterior fossa of the cranium, across the border of the petrous temporal bone. It then enters the Meckel’s cave in the middle cranial fossa. The gasserian ganglion contains the ophthalmic, maxillary, and mandibular divisions. A smaller motor root joins the mandibular division as it exits the foramen ovale. It should be noted that a dural pouch, the trigeminal cistern, lies behind the trigeminal ganglion. In gasserian ganglion block, the needle is inserted approximately 2.5 cm lateral to the side of the mouth and advanced, perpendicular to the middle of the eye (with the eye in the midposition), in a cephalad direction toward the auditory meatus. When contact is made with the base of the skull, the needle is withdrawn and “walked” posteriorly toward the foramen ovale ( Fig. 58.1 ). A free flow of CSF is usually noted, and fluoroscopy is then used to confirm correct needle placement. Very small amounts (i.e., 0.1-mL increments) of local anesthetic or neurolytic agent (commonly glycerol) are injected to a total of 0.4 to 0.5 mL. Because of their different baricity, the patient remains supine if alcohol is used but placed in a sitting position with the chin on the chest prior to the injection of phenol. This maneuver localizes the phenol around the maxillary and mandibular divisions of the trigeminal nerve, avoiding the ophthalmic division and the risk of keratitis from loss of the conjunctival reflex. If glycerol is used, the patient is kept in a “seated”/head-up position. The pterygopalatine space is highly vascular, and significant hematoma of the face and subscleral hematoma of the eye can occur. Veins in the subtemporal region can be punctured, causing hemorrhage in the temporal fossa. Local anesthetic injection can lead to spinal anesthesia because the ganglion lies within the cerebrospinal fluid. Blockade of the motor fibers of the trigeminal nerve can interfere with mastication. Oculomotor palsy, which results in diplopia and strabismus, is usually temporary. Abducens palsy is also temporary, although cases of permanent lateral rectus palsy have been reported. Spread of the neurolytic agent into the facial nerve results in paralysis of the facial muscles and inability of the eyelid to close, resulting in keratitis or corneal ulceration. Blockade of the greater superficial petrosal nerve may result in lack of tear formation and conjunctivitis. Blockade of the acoustic nerve may result in deafness or dizziness. The delayed effects of gasserian ganglion neurolytic block include trophic problems such as keratitis, ulcerations in the nose, and erosions in the mouth. These disturbances usually occur after trauma to the area. Another delayed complication is anesthesia dolorosa seen more commonly with alcohol and phenol neurolysis. Because the neurolytic block of the gasserian ganglion is associated with myriad devastating complications, many neurosurgeons and pain medicine physicians choose to perform radiofrequency rhizotomy of the ganglion instead. The technical difficulty and complications associated with gasserian ganglion block led some investigators to perform peripheral branch (supraorbital, infraorbital, and mandibular nerves) injections with 10% phenol to relieve the pain of tic douloureux.
Other Neurolytic Blocks of the Head and Neck
Neurolytic blocks of individual cranial nerves and their branches have also been performed, and complications are related to nerve location and the tissues it innervates. Neurolytic block of the maxillary nerve at the foramen rotundum or of the infraorbital nerve may cause ulceration and sloughing of the alar of the nose and the cheek, ischemic necrosis of the palate, or sloughing of the posterior portion of the superior ridge of the maxilla. Blockade of the mandibular nerve at the foramen ovale may result in weakness of the muscles of mastication in the blocked side, whereas blockade of the facial nerve causes weakness or paralysis of the facial muscles. Blockade of the glossopharyngeal nerve is rarely performed because of the proximity of the nerve to the vagus, spinal accessory, and hypoglossal nerves. The close location of the other nerves led investigators to recommend blockade of the glossopharyngeal nerve under fluoroscopic control or to use radiofrequency rhizotomy. The sensory area of innervation of the glossopharyngeal nerve includes the nasopharynx, eustachian tube, uvula, tonsil, soft palate, base of the tongue, and part of the external auditory canal. Paralysis of the pharyngeal muscles is a consequence of blockade of the glossopharyngeal nerve. The authors do not recommend any of these neurolytic procedures for use by pain physicians.
Paravertebral Sympathetic Neurolysis
Stellate Ganglion Neurolysis
The cervical sympathetic trunk contains the superior, middle, and inferior cervical ganglia. In 80% of the population, the lowest cervical ganglion is fused with the first thoracic ganglion, forming the cervicothoracic (stellate) ganglion. The cervical sympathetic chain lies anterior to the prevertebral fascia, which encloses the prevertebral muscle. The sympathetic chain is enclosed within the alar fascia, a thin fascia that separates the cervical sympathetic chain from the retropharyngeal space. The carotid sheath is connected to the alar fascia by a mesothelium-like fascia. The fascial plane that encloses the sympathetic chain may be in direct communication with several spaces and structures, including the brachial plexus, vertebral artery, endothoracic fascia, and the thoracic wall muscle at T1-T2. At the C6 level, the cervical sympathetic trunk is located posterolaterally to the prevertebral fascia on the surface of the longus colli muscle. The carotid vessels are anterior, whereas the nerve roots that contribute to the inferior portion of the brachial plexus are lateral to the ganglion. The vertebral artery passes over the ganglion and enters the vertebral foramen posterior to the anterior tubercle of C6. The communications of the fascia covering the stellate ganglion with several structures, as noted previously, and the proximity of the stellate ganglion to the vertebral and carotid vessels, phrenic nerve, and the recurrent laryngeal nerve explain some of the potential complications of the stellate ganglion block ( Fig. 58.2 ).
Several techniques of stellate ganglion block have been described. These include insertion of the needle at the level of C6, placement of the needle at C7, and the posterior thoracic approach. With C6 placement, the needle is placed in contact with either the C6 tubercle or the junction between the C6 vertebral body and the tubercle. The needle is withdrawn 1 to 2 mm and an initial test dose of 0.5 to 1 mL is injected, or volumes of 5 to 10 mL can be injected. If the patient is positioned in reverse Trendelenburg, the injectate travels caudad and reaches the stellate ganglion and the upper thoracic sympathetic ganglia. A smaller volume of drug is adequate when the needle is placed at the level of C7. However, there is increased incidence of vertebral artery injection with this approach because the artery lies anterior to the C7 transverse process. There is also an increased risk of pneumothorax because the dome of the lung is closer to the injection site. These risks are reduced when an oblique approach aiming at the uncinate process of C7 is taken. The posterior thoracic approach requires fluoroscopic guidance to identify the lamina of T1 or T2, and dye injection is recommended to document the spread of the drug. In this approach, the needle contacts the lamina of T1 or T2, is moved laterally off the lamina, and is advanced to pass the costotransverse ligament at a depth of 2 cm beyond the lamina. Either loss of resistance is used or dye is injected to confirm proper needle placement.
Kapral developed a technique, involving the use of ultrasound, to visualize the stellate ganglion. Since the initial technique was developed, many modifications have been made to increase the safety, efficacy, and speed of the block. The patient is positioned supine with the neck slightly hyperextended, and an ultrasound probe is placed at the level of C6, providing a cross section of the anatomy at this level. Visible are the trachea, esophagus, thyroid gland, carotid artery, jugular vein, longus colli muscle, and transverse process of C6. A 22G × 2-inch needle can be advanced in plane with the ultrasound probe paratracheally toward the longus colli muscle, while avoiding the other structures, and stopping once the tip reaches the prevertebral fascia. At this point, 5 to 10 mL of local anesthetic is deposited under direct visualization and can be seen spreading along the prevertebral fascia.
The complications of an intravascular injection of local anesthetic are well known. These include loss of consciousness, apnea, hypotension, and seizures. Local anesthetic blocks of the stellate ganglion have been performed for complex regional pain syndrome, vascular insufficiency of the upper extremities, and hyperhidrosis of the face and upper extremities. Neurolytic blockade of the stellate ganglion has been performed for complex regional pain syndrome when there is consistent relief after diagnostic block with local anesthetic and without prolongation of the duration of pain relief. The overall incidence of complications is 0.17%. The exact incidence of pneumothorax is not known. Aside from Horner’s syndrome, hoarseness, blockade of the brachial plexus, subarachnoid and epidural spread, and cord infarction have been reported. Brachial plexus block is secondary to the needle being inserted too lateral or from the spread of the drug along the prevertebral fascia. Ptosis can be corrected by suspension operation of the upper eyelid. Additionally, retropharyngeal hematomas have been reported, ranging from minimal patient discomfort to complete loss of airway. An unusual reported complication is transient locked-in syndrome, in which the patient is paralyzed and cannot breathe or speak, but can only move his or her eyes due to accidental intravascular anesthetic injection. These complications led other investigators to use alternative techniques to cervicothoracic sympathectomy, including radiofrequency rhizotomy and thoracoscopic sympathectomy.
Lumbar Sympathetic Neurolysis
Paravertebral sympathetic blocks are performed for the treatment of complex regional pain syndromes, vascular insufficiencies of the lower extremities, phantom limb pain, and other conditions such as hyperhidrosis. Percutaneous thoracic paravertebral sympathetic neurolysis is rarely performed because of the high incidence of pneumothorax. A thoracic surgeon who does a surgical sympathectomy under direct vision usually performs treatment of this region. Lumbar paravertebral sympathetic neurolysis can be more safely performed. In this technique, the needles are placed in the anterolateral surface of L2 or L3. Fluoroscopy is used to confirm vertebral level of placement, correct position of the needle tip, and adequate spread of the dye along the anterolateral aspect of the vertebral bodies. Although a single needle technique can be used, two needles (one at L2 and the other at L3) are recommended for chemical neurolysis so that a smaller volume can be injected per needle. One to 2 mL of local anesthetic is injected, and if it is followed by a temperature increase, 3 to 4 mL of 6% to 10% phenol is injected per needle. The reported complications of the block include subarachnoid injection secondary to injection near the dural cuff at the intervertebral foramen, sensory and motor block resulting from nerve root injury, paresthesias, and backache. The ureter can be injured from the needle or from phenol-induced thrombosis of the branch of the ovarian artery supplying the ureter. Genitofemoral neuralgia occurs in 7% to 20% of patients and may last 4 to 5 weeks. Postsympathectomy dysesthesias result in numbness and pain in the thigh and may last several months. The use of guidance (fluoroscopy, computed tomography [CT], or ultrasound) is mandatory when neurolytic block of the sympathetic chain is performed. Alternate nonchemical neurolytic techniques, including radiofrequency rhizotomy of the lumbar sympathetic nerves, have been employed to avoid the complications from spillage of the neurolytic agent; however, this technique did not result in long-term relief, although other studies have found benefit. Compared with phenol neurolysis, incomplete neurolysis appears to be more common with radiofrequency rhizotomy, but the incidence of postsympathectomy neuralgia was higher in the phenol group (33% versus 11%).
Neurolytic Blocks of the Trunk and Extremities
Intercostal Neurolysis
Peripheral neurolysis is a controversial subject. Although some argue that it has no real use in pain management, it has found a role in intercostal neurolytic blocks for the management of malignant chest wall pain. The use of peripheral neurolysis follows successful diagnostic blocks using local anesthetics. Peripheral neurolytic blocks are frequently associated with neuritis and deafferentation pain, in addition to postinjection dysesthesias ( Box 58.2 ). Although these complications are unpleasant, they may be preferable to the patient’s current pain, or the patient may succumb to his or her primary disease before these complications fully manifest themselves. Intercostal blocks are used in the treatment of thoracic or abdominal wall pain and as adjunct in surgery. Complications include pneumothorax, intravascular injection, intrapulmonary injection with consequent bronchospasm, and neuraxial spread ( Table 58.2 ). The incidence of pneumothorax detected by radiograph is 0.082 to 2%. Clinically significant pneumothorax occurs at a low rate and chest tube insertion is rarely required. Another reported complication is total spinal anesthesia after intraoperative intrathoracic injection. The intrathoracic injection at a medial location resulted in the injection of the local anesthetic into a dural cuff or into the nerve itself, with proximal spread of the drug. Bronchospasm from intrapulmonary injection of phenol has been reported. Persistent paraplegia from intercostal block with 7.5% phenol has additionally been reported, with the authors suspecting the damage occurred via spread of phenol through the intervertebral foramen and subsequent destruction of motor and sensory nerve roots. Similar to the advantages of its use in other peripheral nerve blocks, ultrasound has made intercostal nerve block a safer technique in that the pleura is visualized, preventing its puncture and avoiding pneumothorax.
