Local anesthesia: neurologic complications

Neuropharmacology & Neurotherapeutics

Updated 01.15.2024
Released 12.14.1998
Expires For CME 01.15.2027

Local anesthesia: neurologic complications

Authors: Shilpi Mittal MBBS, Lori A Sheehan MD

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Editor: Matthew Lorincz MD PhD

Local anesthesia: neurologic complications

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Introduction

Overview

This article focuses on the neurologic complications of drugs used for local anesthesia as well as the procedures involved. Incidence of such complications is rare—less than 3%—but is important to understand for improved patient outcomes as there is rise in the number of outpatient procedures that utilize local anesthetics (15). One of the most common and potentially life threatening neurologic complications to local anesthetic agents are seizures. Sensorimotor neurologic deficits usually correspond to the blocked nerves. Such adverse effects may be transient or permanent. Adjuvant agents used for enhancing the effect of local anesthetics may also have neurotoxic effects. Suggestions are made for mitigating the neurologic complications of local anesthesia.

Key points

	• Local anesthetics may cause adverse effects either by action on the nerves and muscles or neurotoxicity following systemic absorption.
	• Iatrogenic injury of neural structures may result from procedures.
	• Seizures are a frequent adverse effect of local anesthetics, and principles of management are those applicable to drug-induced seizures.
	• Careful selection of the anesthetic agent and meticulous procedure for local anesthesia are important preventive measures.

Historical note and terminology

Local anesthetics are medications that produce a reversible loss of sensation or analgesia when applied to body tissues. This is achieved by interference with nerve conduction in the peripheral nerves.

Induction of analgesia by application of substances directly to the wound goes back to the dawn of medical history. About 1000 years ago, Arab physicians used opium as a local anesthetic in patients with dental pain, earache, or joint pain (03). Cocaine, isolated from the leaves of Erythroxylum coca in 1860, was the first modern local anesthetic. Its local anesthetic properties on the skin were described in 1880, and its usefulness as a topical anesthetic for the eye was demonstrated in 1884 (23). Various adverse effects of local anesthesia, such as syncope and seizures have been reported since the 1960s. Neurologic complications of cocaine have been well documented (20). Because of the abuse potential and neurotoxicity, cocaine use has declined as a local anesthetic. It is sometimes used in endonasal surgery because it is the only substance that has combined local anesthetic and vasoconstrictor effects. Safer local anesthetics are available as alternatives and can be combined with 1:1000 epinephrine for vasoconstrictor effect.

Use of local anesthetics is limited by their duration of action and the dose dependent adverse effects on the cardiac and central nervous systems. This article will primarily describe the neurologic adverse effects of local anesthetics; complications of anesthesia administration and other technical errors will also be mentioned. Regional anesthesia with the use of local anesthetics will be included in this discussion, except epidural anesthesia, which is the subject of a separate article. Local anesthetics include the following: lidocaine, ropivacaine, bupivacaine, mepivacaine, tetracaine, prilocaine, procaine, procainamide, and benzocaine. Articaine, a dental pain agent, and centbucridine are relatively newer local anesthetic agents with lower adverse effect profiles. Complications may occur due to use of adjuvant agents for potentiating the effect of local anesthetics by synergism or to prolong the duration of anesthesia and limit the cumulative dose required (43). Drugs used to potentiate the effect of local anesthetics include opioids, epinephrine, alpha-2 adrenergic antagonists, steroids, antiinflammatory drugs, midazolam, ketamine, remifentanil, and dexmedetomidine.

Local anesthesia is used widely in most branches of medicine and is generally considered to be safer than general anesthesia. However, rare but serious neurologic complications can occur.

Clinical manifestations

Presentation and course

	• Neurologic adverse effects of local anesthetics may be confined to peripheral or cranial nerves in proximity to the site of application.
	• Adverse effects may be due to direct CNS toxicity.
	• CNS adverse effects can also be caused by systemic toxicity involving other body systems.

Neurologic adverse effects of local anesthetics are shown in Table 1 and may be followed by involvement of the cardiovascular system. Other adverse effects, such as those involving the respiratory systems and allergic reactions, may occur concomitantly.

Table 1. Adverse Effects of Local Anesthetics Involving the Nervous System

• CNS excitation manifested by:
	- restlessness - tremors - light-headedness - syncope - tinnitus - nausea and vomiting - slurring of speech - muscular twitching and rigidity - visual changes such as oscillation of images (39) - agitation - irrational conversation
• Seizures – both generalized tonic clonic seizures and nonconvulsive status epilepticus—that may be followed by CNS depression • CNS depression manifested by:
	- drowsiness - respiratory arrest - coma
• Complications related to peripheral and cranial nerves:
	- numbness and tingling in the territories of the blocked nerves - phantom limb pain - peripheral nerve palsies - cranial nerve palsies
• Complications associated with spinal anesthesia:
	- irritation of spinal nerve roots - complications of leakage of cerebrospinal fluid - cauda equina syndrome - paraplegia due to toxic or ischemic myelopathy - meningitis - epidural hematoma
• Effect on muscles: myonecrosis following local injection into muscles • Neuroophthalmologic complications:
	- reduction of visual acuity following retrobulbar anesthesia - Horner syndrome - extraocular muscle palsies
• Neurologic manifestations of systemic toxicity of local anesthetics:
	- Hemispheric symptoms such as transient aphasia and neglect (41) - numbness of the tongue and perioral region - temporary blindness - tinnitus and hearing disorders - triggering of porphyria with progressive porphyric neuropathy - hypoglycemia with coma

Local manifestations related to cranial nerves. An analysis of 108 ophthalmologic complications following intraoral local anesthesia for dental procedures in 65 cases showed that the most common were those involving cranial nerves (49). The most common complication was diplopia (39.8%), mostly resulting from paralysis of the lateral rectus muscle; others were ptosis, dilated pupil, and loss of vision. Most of these resolved within a few hours as the effect of anesthetic wore off.

Temporary blindness has been reported after an inadvertent overdosage of lidocaine during a regional anesthetic procedure.

Diplopia, transient unilateral loss of vision, and strabismus due to paralysis of the extrinsic muscles of the eye have been reported following block of inferior dental nerve or posterior superior alveolar nerve with local anesthetic for dental procedures (01). The pathomechanism of visual loss due to oral nerve block is not known but there was partial recovery of visual function in a reported case (22). Transient blurred vision and diplopia has been reported following a Gow-Gates mandibular block injection in dentistry, and the possible mechanisms are inadvertent intravenous injection, or diffusion through tissue planes from the site of injection to the orbit (11).

Diplopia, loss of vision, or ophthalmoplegia can rarely occur following inferior alveolar nerve block, which is one of the common procedures in dentistry. Cases of drooping eyelid due to paralysis of the levator palpebrae superioris muscle with acute pain and numbness in the infraorbital area on the same side as infiltration of a local anesthetic in buccal vestibule have been explained by inadvertent injection of the anesthetic solutions in the extraosseous branch of posterior superior alveolar artery through to the infraorbital artery (38). In another case, transient diplopia was considered to be due to retro flow of local anesthetic agent through the inferior alveolar artery and indirectly to the ophthalmic artery paralyzing the lateral rectus muscle with recovery after 1 hour (37). In such cases recovery takes place spontaneously without any sequelae. Cranial nerve palsies can occur after procedures involving local anesthetic blocks, eg, of branches of trigeminal nerve. Ptosis has been reported after stellate ganglion block. Facial nerve paralysis has been reported after a superficial cervical plexus blocks.

Other cranial nerve manifestations that have been reported are facial nerve palsy, Horner syndrome (10), transient glossopharyngeal nerve palsy (34), and trigeminal neuralgia.

Local manifestations related to peripheral nerves. Phantom-limb pain can occur following a continuous popliteal nerve block after foot surgery with alleviation and recurrence corresponding to cessation and resumption of the local anesthetic infusion.

Carotid endarterectomy performed under local anesthesia may cause temporary ipsilateral vocal cord paralysis. There were no significant differences in operating time or volume or frequency of anesthetic administration in patients with temporary vocal cord paralysis compared with those without.

Though peripheral nerve injury/damage is rare due to nerve blocks and decreases over time, some blocks are relatively higher risk than others, such as interscalene block (25).

Effect of local anesthetics on muscles. Local anesthetics injections in muscles for relief of muscle pain have a detrimental effect on mesenchymal stem cells, which have an important role in the treatment of degenerative disorders of muscles (53). These were in vitro studies, and in vivo studies are needed to confirm these findings.

Manifestations of CNS toxicity of local anesthetics. Central nervous system symptoms are often part of local anesthetic systemic toxicity (LAST), which can lead to CNS toxicity besides cardiac toxicity. Initial symptoms of local anesthetic CNS toxicity are those of excitation, which may be manifested by restlessness and dizziness. Other manifestations are tremors, slurring of speech, and irrational conversation. This may proceed to a seizure or CNS depression. Ropivacaine is considered safer for the central nervous system, but a few published reports still implicate ropivacaine as being associated with convulsions.

Local anesthetics can lead to myotoxicity, which can be dose/concentration dependent and can worsen with longer exposure to anesthetic agent (56).

Seizures. Seizures are an adverse effect of an overdosage of local anesthetics and are likely to occur if the injection is made inadvertently into a blood vessel (08). Unfortunately, it can also lead to status epilepticus and nonconvulsive status epilepticus (04). Seizure activity following the administration of local anesthetic in pediatric dentistry is the most common adverse event, suggesting intravascular administration or a toxic dose, but there were no cases of permanent damage or fatal outcomes (45). A direct correlation exists between clinical symptoms and blood levels of lidocaine: as the level increases to 8 to 12 mg/L, the probability of seizure also increases. Central nervous system toxicity can develop even after accidental intraarterial injection of low concentrations of local anesthetics into peripheral arteries during peripheral nerve block. Convulsions have been reported after left superior laryngeal nerve block to facilitate endotracheal intubation. The possible cause may be accidental injection of the local anesthetic into the vertebral artery. Seizures may also occur as a complication of peripheral nerve block with a local anesthetic without inadvertent blood vessel puncture. Neonatal seizures have been reported following lidocaine administration for circumcision.

Apart from infiltration, local anesthetics may be given intravenously for regional anesthesia. According to a review of publications on intravenous regional anesthesia, the lowest dose of local anesthetic associated with a seizure is 1.4 mg/kg for lidocaine; 4 mg/kg for prilocaine, and 1.3 mg/kg for bupivacaine (16).

Miscellaneous manifestations. Initiation excitation may be followed by depression of the CNS with drowsiness, respiratory arrest, and coma. Concomitant myocardial depression may produce hypotension, disturbances of cardiac rhythm, and cardiac arrest. It can also cause DWI and FLAIR changes on MRI, which could mimic stroke, but no clear large vessel occlusion is identified (41).

Neurologic complications of spinal and epidural anesthesia. The most frequent complication of spinal anesthesia is spinal nerve root irritation. Cases have been reported of transient radicular irritation following intrathecal anesthesia with mepivacaine. This complication manifests from several hours to 1 day following the procedure and is characterized by sharp and bilateral radiating pain, usually involving the lower extremities. Usually no neurologic deficits arise, and the pain resolves within 1 week. Cauda equina syndrome is rare and is likely to occur with continuous spinal anesthesia through a microspinal catheter. Other complications of spinal anesthesia are due to leakage of spinal fluid through the lumbar puncture site with intracranial hypotension. These include headache, diplopia, and transient hearing loss. Sixth cranial nerve palsy may occur due to ischemic or traction injury (06). The risk of developing transient neurologic symptoms after spinal anesthesia with lidocaine is significantly higher than when bupivacaine, prilocaine, or procaine is used. Other complications may include lumbosacral radiculopathy, polyradiculopathy, and thoracic myelopathy after epidural injections (55).

Prognosis and complications

The prognosis of recovery from complications of local anesthesia is generally good. Recovery from seizures and transient neurologic deficits occurs within a matter of hours or days. Prognosis of neurologic deficits following spinal anesthesia is guarded, particularly in rare cases of paraplegia due to spinal cord ischemic infarction. Prompt identification and treatment can improve the prognosis in grave cases. Awareness about the myriad of neurologic symptoms among nurses and physicians can hopefully contribute to the timely diagnosis and treatment of such complications.

Biological basis

	• Peripheral nerves may be injured by the injection needle.
	• Systemic toxicity is due to absorption from subcutaneous tissues and mucous membranes or inadvertent direct introduction into a blood vessel and is dose related.
	• CNS is affected because the action of local anesthetics is through reversible binding at sodium channels.
	• Patients with a history of epilepsy are predisposed to seizures as an adverse effect of local anesthetics.
	• Size and angle of needle insertion during local anesthetic administration (40)

Etiology and pathogenesis

Neurologic complications have been reported with all currently used local anesthetics. Complications may result from the local effect on nerves, the neurotoxic effect of systemic absorption, overdosage, or inadvertent injection into the circulation. Some of the complications are due to injection, which may injure the nerve directly or compress it due to the formation of a hematoma. The causes of neurologic damage associated with spinal anesthesia include the following:

	• Trauma of lumbar puncture with subarachnoid hemorrhage.
	• Chemical and bacterial contamination of the local anesthetic solution.
	• Toxic reaction to the local anesthetic.

Because local anesthetics act through reversible binding at sodium channels, manifestations of toxicity include central nervous system as well as cardiovascular effects. Cumulative toxicity of local anesthetics depends directly on the concentration achieved in plasma, whereas CNS toxicity depends largely on the membrane-stabilizing effect of the drug. Factors affecting plasma concentration and, thus, toxicity, include the site and rate of injection, concentration and total administered dose, absorption, degree of tissue binding, and rate of metabolism and excretion. The extent of absorption depends on tissue vascularity, sites and techniques of application, and the patient's disease state. Lidocaine is eliminated mainly by the liver, and both the drug, as well as its toxic metabolite, can accumulate in congestive heart failure and liver disorders, producing neurotoxicity at low drug concentrations.

Absorption from mucous membranes is usually more rapid than from subcutaneous tissues. Seizures are associated with lidocaine after topical administration for airway anesthesia for bronchoscopy. Seizures have been reported following local application of lidocaine to the oropharyngeal region and following ureteral stone manipulation with lidocaine.

Complication of procedures. Examples of technical factors leading to neurologic complications are:

	• Accidental intrathecal injection of local anesthetic during trigger-point injection therapy, resulting in respiratory depression and hemiplegia.
	• Positioning of patients. Lithotomy position during hyperbaric spinal anesthesia predisposes to neurologic complications.
	• Paralysis of diaphragm, due to upward migration of local anesthetic after brachial block.

Risk factors. Patients with a history of epilepsy are predisposed to seizures as an adverse effect of local anesthetics. Patients with underlying mechanical, ischemic, or metabolic neurologic derangements are considered to be at increased risk of progressive neural injury following peripheral nerve block, but axillary blockade in patients with ulnar neuropathy undergoing ulnar nerve transposition is considered to be a safe procedure. Patients with prior nerve demyelination changes and prior existing neuropathies may be at relatively high risk for post nerve block peripheral nerve injuries (PNI). A retrospective study evaluated documented PNI in Charcot Marie Tooth neuropathy patients receiving peripheral nerve blocks but did not find any higher incidence of PNI in such patients. Age greater than 65 years could also be a patient-related risk factor (29).

Drug interactions. Complications of local anesthetics may be enhanced by interactions with other drugs. These interactions may be pharmacokinetic or pharmacodynamic. The following pharmacokinetic interactions increase the toxicity of local anesthetics:

	• Calcium antagonists reduce the protein binding and increase the free fraction of local anesthetics.
	• Beta blockers decrease clearance of local anesthetics.
	• Pethidine (meperidine) and phenytoin increase the free fraction of bupivacaine by displacing it from plasma proteins.
	• Cimetidine decreases the metabolism of lidocaine, thus, increases its toxicity.
	• Acetazolamide prolongs the half-life of procaine.
	• Drugs that have CYP3A4 enzyme enabled metabolism may have higher interaction with lidocaine

The following pharmacodynamic interactions increase the neurotoxicity of local anesthetics:

	• Baclofen lowers the threshold for seizures.
	• Flumazenil may increase the convulsive activity of bupivacaine.

Most of the studies reported in the literature have used lidocaine as the prototype for examining the effects of local anesthetics on the nervous system. The main action of local anesthetics on neural tissues is a depressant effect on the conduction of nerve impulse, due to the blocking of sodium channels. Lidocaine can also close the chloride channels at the synaptic cleft; the resultant chloride ion flow hyperpolarizes the membrane and enhances synaptic transmission.

Pathomechanism of local anesthetic-induced seizures. CNS toxicity of local anesthetics may be due to the depression of subcortical inhibitory control of gamma-aminobutyric acid over normally occurring excitatory activity. The convulsant effect of local anesthetics is due to an imbalance in brain activity because excitatory pathways are more resistant than are inhibitory pathways. The course of events, ie, initial excitation of the CNS followed by depression, is explained by selective blockade of inhibitory cortical synapses by local anesthetics.

One explanation of local anesthetic-induced seizures is blocking of sodium channels, which is for achieving local anesthesia, but can lead to neurotoxicity when spread to the systemic circulation and central nervous system, particularly in children (27). One theory of pathomechanisms of neurotoxicity of local anesthetics is based on Twik-related, pH-sensitive K+ channels, which generate neuronal potassium "leak" currents, membrane depolarization, and increased neuronal excitability (30). As these channels are expressed throughout the brain, this is the suggested mechanism for seizures in this setting.

Seizures have been reported after transversus abdominis plane block, which is commonly used for postcesarean section analgesia due to systemic absorption of the large amount of local anesthetic required for a successful block (51).

Pathomechanism of neurotoxicity. The toxic effect of local anesthetics on nerves has been studied. Local anesthetics precipitate nerve edema, increase endoneural nerve pressure, reduce nerve blood flow, and lead to nerve ischemia. Bupivacaine, ropivacaine, and mepivacaine are the least neurotoxic, whereas lidocaine is moderately toxic and procaine is the most damaging to the nerves. Increased caspase has been reported at molecular levels with local anesthetic agents, which may contribute to tissue damage (Verlinde at al 2016).

Ropivacaine promoted cell death in an in vitro study on PC12 cells as well as in animal spinal cords in a treatment group compared with a sham-operated group (42). This study showed that ropivacaine neurotoxicity in vivo and in vitro is mediated by the Akt (protein kinase B) signaling pathway and that may explain its adverse neurologic effects.

Amitriptyline, an antidepressant sodium ion channel blocker with prolonged local anesthetic effect, produces Wallerian degeneration with destruction of nerve fibers and a hyperalgesic pain state following application to peripheral nerves. In clinical use, it has no advantage over bupivacaine regarding efficacy and should not be used as a local anesthetic.

An overload of intracellular calcium is involved in the neurotoxic effect of some anesthetics. Results of a study suggest that T-type calcium channels, which lower the threshold of action potentials, may be involved in bupivacaine neurotoxicity, but specific subtypes of these channels have not yet been identified (52).

An experimental study on SH-SY5Y cells has shown that nicotinamide adenine dinucleotide (NAD+) depletion contributes to bupivacaine-induced neurotoxicity, which is attenuated by NAD+ repletion (58). An experimental study has shown that bupivacaine-induced neurotoxicity involves reactive oxygen species-induced mitochondrial damage and endoplasmic reticulum stress leading to apoptosis, which can be attenuated by ginkgolide B, an active component of Ginkgo biloba through its antioxidant property (26).

Epidemiology

	• It is difficult to determine the true incidence of adverse reactions to local anesthetics, but they are rare.
	• Seizures and syncope are the most frequent CNS complications, but incidence figures are not available.
	• Risks of permanent neurologic injury and systemic toxicity with local anesthesia are low.

The exact frequency of occurrence of adverse reactions to local anesthetics is difficult to determine, as only a small fraction of these are reported to health authorities. Those published are even fewer. Local anesthetics comprised 5% to 10% of the cases reported to the National Adverse Anesthetics Reactions Advisory Service in the United Kingdom. More than one fourth of all adverse reactions reported to the United Kingdom Medicines Control Agency were due to local anesthetics. An analysis of 1157 adverse reactions of local anesthetics in 721 patients, reported to the French Pharmacovigilance System, showed that 21.1% involved the nervous system (14). Seizures were the most frequent neurologic complications, leading to death in four cases.

In the United States, systemic toxicity from the injection or overdose of local anesthetics is a rare but potentially fatal complication that occurs in less than 1 in 1000 patients (50).

The reported risk of permanent neurologic injury with local anesthesia is less than 5 per 10,000 cases and systemic toxicity to 1 in 10,000 cases. The most common complication of procedures performed as outpatient with local anesthesia is syncope, which occurs in 1 in 160 patients.

Perineural catheters with administration of local anesthetics are used widely for the treatment of postoperative pain. If performed carefully, this procedure has a low rate of neurologic complications – less than 1 in 2000 cases.

A study found 7% risk of neurologic injury due to regional anesthesia in upper limb surgeries (02).

Prevention

	• The best approach to the management of local anesthetic complications is prevention.
	• A meticulous technique should be used to avoid injection injury, and the recommended dose of anesthetic should not be exceeded.
	• The use of epinephrine with local anesthetics decreases the rate of absorption, delays the onset of peak plasma concentrations and, thus, lowers the risk of neurotoxicity.
	• Concomitant use of drugs that may interact with local anesthetics should be avoided.
	• Ultrasound/electrostimulation-guided nerve blocks.

Use of local anesthetics with lower risk of CNS toxicity. Levobupivacaine has similar potency to bupivacaine, but a relatively lower risk of CNS complications. A prospective randomized study has shown that ropivacaine is an alternative for deep topical anesthesia, as it has a better safety margin and lesser toxicity effect than other comparable local anesthetic agents (21).

	• The use of cocaine-containing topical anesthetics is no longer recommended because of high cost and potential adverse effects; these should be replaced by noncocaine-containing topical anesthetics.
	• Transient neurologic symptoms commonly follow lidocaine spinal anesthesia, but are relatively uncommon with bupivacaine or tetracaine. The manufacturer of lidocaine recommends diluting lidocaine 5% with an equal amount of cerebrospinal fluid, and limiting the dose to a maximum of 100 mg.
	• Some of the complications of regional anesthesia for pain relief in children are procedural related to perineural infusion of local anesthetics. The success of nerve blocks can be improved and the risks reduced through the use of nerve mapping and ultrasound.
	• Neural injury during spinal injection of local anesthetic in the operating room can be minimized by careful patient positioning.
	• Following a procedure under spinal anesthetic, patients should be observed closely to detect potentially treatable neurologic complications such as expanding spinal hematoma.
	• Dexmedetomidine may lower the toxicity associated with lidocaine in cell studies (57).

Ultrasound-guided nerve blocks. It is generally recognized that real-time, needle-nerve visualization during ultrasound guided nerve block can prevent nerve injury. A review of cases of neuropathy as a complication of peripheral nerve block indicates that half of these complications can be prevented by use of ultrasound-guided nerve block (17). Despite this precaution, a severe brachial plexus injury has been reported after combined ultrasound and nerve stimulator-guided supraclavicular brachial plexus block (35). Intraneural injection during ultrasound-guided interscalene block resulted in a neurologic complication manifested by weakness and dysesthesias in the arm, which took 2 weeks to resolve (09). In a case of ultrasound-guided stellate ganglion block, inadvertent intra-arterial injection of a local anesthetic agent led to a tonic-clonic seizure, which could be minimized under the ultrasound guidance with various protective strategies, including the determination of any prior variation, optimizing the block route, maintaining a constant probe pressure, and using saline for the test dosage (28). This case resulted in the implementation of new protocols of the ultrasound-guided stellate ganglion block in the authors’ institution.

In an open study, for ultrasound-guided stellate ganglion block for patients with postherpetic neuralgia and complex regional pain syndrome of the upper extremity, a 2 mL dosage of 0.5% mepivacaine was found to be sufficient for block, which was as successful as that achieved by conventional larger volumes of local anesthetic, but produced fewer adverse effects such as dysphagia and upper arm weakness due to a less extensive spread of the anesthetic solution (24).

The American Society of Regional Anesthesia and Pain Medicine’s Practice Advisory on Neurologic Complications Associated with Regional Anesthesia and Pain Medicine offers recommendations to aid in the understanding and potential limitation of complications associated with mechanical, ischemic, or neurotoxic injury of the neuraxis or peripheral nervous system, which may arise during the practice of regional anesthesia and/or interventional pain medicine (33). It focuses on the preventive role of various monitoring technologies such as ultrasound guidance and injection pressure monitoring. New clinical recommendations focus on emerging concerns including nerve blocks in deeply sedated patients or those with preexisting neurologic disease, and inflammatory neuropathies.

A study by Xu and colleagues found that more experienced providers have lower risk of neurologic complications with peripheral nerve blocks in orthopedic surgeries (54).

Replacing general by local anesthesia for neurosurgical procedures. Several neurosurgical procedures such as craniotomies, laminectomies, and peripheral nerve procedures can now be done under local anesthesia. A retrospective study on 50 consecutive patients with single-level L5/S1 disc herniation underwent percutaneous endoscopic lumbar discectomy via the interlaminar approach under gradient local anesthesia to assess efficacy as well as safety as an alternative to general anesthesia because sinuvertebral nerve and the spinal nerve root can be irritated during shearing of the ligamentum flavum and manipulation of the annulus fibrosis, inducing intolerable back and leg pain (13). Different concentrations of local anesthetic compound were injected into different tissues inside and outside the ligamentum flavum to complete gradient local anesthesia. Results showed control of intraoperative pain. Gradient local anesthesia not only improved intraoperative satisfaction but also reduced local anesthesia-related adverse reactions and surgery-related complications.

Management

	• Control of seizures is the most important part of the neurologic management of adverse reactions to local anesthetics.
	• Systemic toxicity of local anesthetics and peripheral nerve injury may also require treatment.

Control of seizures is the most important part of the neurologic management of adverse reactions to local anesthetics.

The patient should receive 100% oxygen. Diazepam or barbiturates should be used for the control of seizures. Intravenous suxamethonium (succinylcholine) 2 mg/kg is used to facilitate intubation. Acidosis increases the amount of unbound drug, thus, increasing its toxicity. Hypoxia and hypercapnia increase cerebral blood flow and, therefore, carry more lidocaine to the brain. Correcting the acidosis and hypoxia in cases of lidocaine overdosage is important for seizure control. Although low-dose propofol has been recommended for the control of seizures, it should be noted that propofol has also been implicated in seizures due to general anesthetics. Lipid emulsions have been infused to reverse systemic toxicity, including seizures and cardiac arrest resulting from the administration of levobupivacaine, ropivacaine, bupivacaine, or mepivacaine. The optimal dose has not been established and risks of administering too high a dose are uncertain.

Neurologic and cardiovascular symptoms associated with systemic toxicity of local anesthetics usually resolves following infusion of a lipid emulsion. Intravenous lipid infusion was also used successfully with full recovery in a case of ropivacaine-induced neurotoxicity manifested by restlessness and limb-twitching during emergence from anesthesia (32). A metaanalysis showed improvement in perioperative peripheral nerve injuries with help of hyperbaric oxygen therapy (02).

Clinical trials have shown that phentolamine mesylate injection can accelerate reversal of soft-tissue anesthesia and the associated functional deficits resulting from an intraoral submucosal injection of a local anesthetic containing a vasoconstrictor used for dental procedures (18).

The American Society of Regional Anesthesia and Pain Medicine has updated its algorithm on management of systemic toxicity of local anesthetics and commented that lipid emulsions may currently be underutilized (47).

Special considerations

Local anesthesia in patients with neurologic disorders. Peripheral regional anesthesia can be safely used in patients with spinal cord injury, multiple sclerosis, Guillain-Barré disease, neurofibromatosis, diseases of the neuromuscular junction, and Charcot-Marie-Tooth disease without neurologic complications (31). In a single-blind study on patients undergoing transforaminal lumbar surgery, no significant difference in neurologic complications was observed between the epidural anesthesia and the local anesthesia groups (12).

A patient with postpolio syndrome developed cauda equina syndrome after combined spinal anesthesia and postoperative epidural analgesia (46). Needle- or catheter-induced trauma, spinal hematoma, spinal ischemia, intraneural anesthetic injection, or infection were ruled out, leading to suspicion of neurotoxicity of bupivacaine and ropivacaine. There has been successive use of local anesthesia in patients with amyotrophic lateral sclerosis based on a case report (36).

Pregnancy

Local anesthetics can cross the placenta by diffusion and may cause fetal CNS and respiratory depression. Hypotension due to spinal anesthesia for caesarian section may reduce the uteroplacental flow and contribute to fetal hypoxia. Generally, local and regional anesthesia in pregnancy is safe and has a good safety record. However, neonatal lidocaine intoxication, with manifestations including seizures, may occur following maternal pudendal block during delivery. No evidence shows that local anesthetics have any teratogenic effect when used during the first trimester of pregnancy.

Inadvertent intrathecal injection of local anesthetic has been reported in a patient undergoing epidural block for delivery and resulted in motor block of lower extremities and shortness of breath (44). This was successfully managed with cerebrospinal lavage using CSF exchange for an equal volume of normal saline resulting in successful delivery.

Immunocompromised patients. There may be enhanced risk of neurotoxicity in patients with underlying compromised immunity due to HIV, cancer, immunotherapy, or diabetes. There is increased incidence of meningitis and epidural abscess as complication of spinal anesthesia in patients with underlying compromised immunity. There is also a chance of worsened peripheral nerve injury due to preexisting neuropathy due to use of chemotherapy (19).

Pediatrics. Local anesthetic systemic toxicity has the highest incidence in infants less than 6 months of age and is associated with bolus dosing and penile nerve blocks (05). It is treated by securing the airway, control of seizure activity, and cardiopulmonary resuscitation if required. Administration of intralipid (intravenous lipid emulsion) should be started at the first sign of toxicity. In contrast to reports of adverse effects in individual pediatric patients, analysis of results of large series of cases has shown a level of safety in pediatric regional anesthesia that is comparable to that in adult patients and is a useful and safe modality (07).

Anesthesia

This article deals with complications of local anesthesia.

References

01: Aguado-Gil JM, Barona-Dorado C, Lillo-Rodríguez JC, De la Fuente-González DS, Martínez-González JM. Ocular complications following dental local anesthesia. Med Oral Patol Oral Cir Bucal 2011;16(5):e688-93. PMID 20711104
02: Albaum JM, Abdallah FW, Ahmed MM, Siddiqui U, Brull R. What is the risk of postoperative neurologic symptoms after regional anesthesia in upper extremity surgery? A systematic review and meta-analysis of randomized trials. Clin Orthop Relat Res 2022;480(12):2374-89. PMID 36083846
03: Al-Mazrooa AA, Abdel-Halim RE. Anesthesia 1000 years ago. In: Atkinson RS, Boulton TB, editors. The history of anaesthesia. International Congress and Symposium series number 134. London: The Parthenon Publishing Group, 1989:46-8.
04: Alsukhni RA, Ghoubari MS, Farfouti MT, Aboras YA. Status epilepticus following local anesthesia in a previously healthy adult. BMC Res Notes 2016;9:300. PMID 27287503
05: Boretsky KR. A review of regional anesthesia in infants. Paediatr Drugs 2019;21(6):439-49.** PMID 31628666
06: Cain RB, Patel NP, Hoxworth JM, Lal D. Abducens palsy after lumbar drain placement: a rare complication in endoscopic skull base surgery. Laryngoscope 2013;123(11):2633-8. PMID 23670572
07: Chun Y, Phillips M, Suresh S. Updates on neurologic complications in pediatric regional anesthesia. Minerva Anestesiol 2021;87(6):695-703.** PMID 32959634
08: Clark AT, Lacy AJ, Simpson MD, Lin SG, Jordano JO, Williams SR. Greater cervical nerve block with bupivacaine resulting in neurotoxicity: a case report. JEM Reports 2023;2(2).
09: Cohen JM, Gray AT. Functional deficits after intraneural injection during interscalene block. Reg Anesth Pain Med 2010;35(4):397-9. PMID 20607900
10: Crean SJ, Powis A. Neurological complications of local anaesthetics in dentistry. Dent Update 1999;26(8):344-9. PMID 10765749
11: Fa BA, Speaker SR, Budenz AW. Temporary diplopia after Gow-Gates injection: case report and review. Anesth Prog 2016;63(3):139-46. PMID 27585417
12: Fang G, Ding Z, Song Z. Comparison of the effects of epidural anesthesia and local anesthesia in lumbar transforaminal endoscopic surgery. Pain Physician 2016;19(7):E1001-4. PMID 27676669
13: Feng WL, Yang JS, Wei D, et al. Gradient local anesthesia for percutaneous endoscopic interlaminar discectomy at the L5/S1 level: a feasibility study. J Orthop Surg Res 2020;15(1):413.** PMID 32933553
14: Fuzier R, Lapeyre-Mestre M, Samii K, Montastruc JL; French Association of Regional Pharmacovigilance Centres. Adverse drug reactions to local anaesthetics: a review of the French pharmacovigilance database. Drug Saf 2009;32(4):345-56. PMID 19388725
15: Ghafoor H, Haroon S, Atique S, et al. Neurological complications of local anesthesia in dentistry: a review. Cureus 2023;15(12):e50790. PMID 38239523
16: Guay J. Adverse events associated with intravenous regional anesthesia (Bier block): a systematic review of complications. J Clin Anesth 2009;21(8):585-94. PMID 20122591
17: Hashimoto A, Ito H, Harato M, Fujiwara Y, Komatsu T. Complications of peripheral nerve block. [Article in Japanese] Masui 2011;60(1):111-9. PMID 21348262
18: Hersh EV, Moore PA, Papas AS, et al. Reversal of soft-tissue local anesthesia with phentolamine mesylate in adolescents and adults. J Am Dent Assoc 2008;139(8):1080-93. PMID 18682623
19: Horlocker TT, Wedel DJ. Regional anesthesia in the immunocompromised patient. Reg Anesth Pain Med 2006;31(4):334-45. PMID 16857553
20: Jain KK. Drug-induced neurological disorders. 4th ed. Cham (Switzerland): Springer, 2021.
21: Kashyap A, Varshney R, Titiyal GS, Sinha AK. Comparison between ropivacaine and bupivacaine in deep topical fornix nerve block anesthesia in patients undergoing cataract surgery by phacoemulsification. Indian J Ophthalmol 2018;66(9):1268-71. PMID 30127137
22: Ko IC, Park KS, Shin JM, Baik JS. Visual loss after intraoral local anesthesia for the removal of circumzygomatic and circum-mandibular wires: a case report. J Oral Maxillofac Surg 2015;73(10):1918. PMID 26215488
23: Koller C. Ueber die verwendung des cocain zur anesthesierung am auge. Wien Med Wochenschr 1884;34:1276-8.
24: Lee MH, Kim KY, Song JH, et al. Minimal volume of local anesthetic required for an ultrasound-guided SGB. Pain Med 2012;13(11):1381-8. PMID 23013477
25: Lemke E, Johnston DF, Behrens MB, et al. Neurological injury following peripheral nerve blocks: a narrative review of estimates of risks and the influence of ultrasound guidance. Reg Anesth Pain Med 2023. [Epub ahead of print] PMID 37940348
26: Li L, Zhang QG, Lai LY, et al. Neuroprotective effect of ginkgolide B on bupivacaine-induced apoptosis in SH-SY5Y cells. Oxid Med Cell Longev 2013;2013:159864. PMID 24228138
27: Lonnqvist PA. Toxicity of local anesthetic drugs: a pediatric perspective. Paediatr Anaesth 2012;22(1):39-43. PMID 21672079
28: Lu F, Tian J, Dong J, Zhang K. Tonic-clonic seizure during the ultrasound-guided stellate ganglion block because of an injection into an unrecognized variant vertebral artery: a case report. Medicine (Baltimore) 2019;98(48):e18168.** PMID 31770265
29: Macfarlane AJR, Gitman M, Bornstein KJ, El‐Boghdadly K, and Weinberg G. Updates in our understanding of local anaesthetic systemic toxicity: a narrative review. Anaesthesia 2021;76:27-39. PMID 33426662
30: Mahajan A, Derian A. Local anesthetic toxicity. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2019. PMID 29763139
31: McSwain JR, Doty JW, Wilson SH. Regional anesthesia in patients with pre-existing neurologic disease. Curr Opin Anaesthesiol 2014;27(5):538-43. PMID 25051260
32: Mizutani K, Oda Y, Sato H. Successful treatment of ropivacaine-induced central nervous system toxicity by use of lipid emulsion: effect on total and unbound plasma fractions. J Anesth 2011;25(3):442-5. PMID 21409350
33: Neal JM, Barrington MJ, Brull R, et al. The second ASRA practice advisory on neurologic complications associated with regional anesthesia and pain medicine: executive summary 2015. Reg Anesth Pain Med 2015;40(5):401-30. PMID 26288034
34: Papadopoulou M, Anastasakis S. Transient glossopharyngeal nerve palsy due to mandibular nerve block. BMJ Case Rep 2022;15(7):e251033. PMID 35878966
35: Reiss W, Kurapati S, Shariat A, Hadzic A. Nerve injury complicating ultrasound/electrostimulation-guided supraclavicular brachial plexus block. Reg Anesth Pain Med 2010;35(4):400-1. PMID 20607905
36: Samworth AG, Miller K, Haswah M, Tureanu L, Weeks J. Neuraxial and Regional Anesthesia in a Patient With Amyotrophic Lateral Sclerosis: A Case Report. Cureus. 2023 Apr 10;15(4):e37364. doi: 10.7759/cureus.37364. PMID: 37182071
37: Sargunam ED, Ganesan A, Chandrasekaran D, Siroraj PA. Transient diplopia: a loco regional complication of inferior alveolar nerve block. Indian J Dent Res 2019;30(4):639-42. PMID 31745066
38: Scarano A, Sinjari B, Lorusso F, Mortellaro C, D'Ovidio C, Carinci F. Intense, instantaneous, and shooting pain during local anesthesia for implant surgery. J Craniofac Surg 2018;29(8):2287-90.** PMID 29621089
39: Scott DB. Toxic effects of local anaesthetic agents on the central nervous system. Br J Anaesth 1986;58(7):732-5. PMID 3730224
40: Selander D, Dhunér KG, Lundborg G. Peripheral nerve injury due to injection needles used for regional anesthesia. An experimental study of the acute effects of needle point trauma. Acta Anaesthesiol Scand 1977;21(3):182-8. PMID 878831
41: Spitzer D, Wenger KJ, Neef V, et al. Local anesthetic-induced central nervous system toxicity during interscalene brachial plexus block: a case series study of three patients. J Clin Med 2021;10(5):1013.** PMID 33801401
42: Sun Z, Liu H, Guo Q, Xu X, Zhang Z, Wang N. In vivo and in vitro evidence of the neurotoxic effects of ropivacaine: the role of the Akt signaling pathway. Mol Med Rep 2012;6(6):1455-9. PMID 23027315
43: Swain A, Nag DS, Sahu S, Samaddar DP. Adjuvants to local anesthetics: current understanding and future trends. World J Clin Cases 2017;5(8):307-23. PMID 28868303
44: Ting HY, Tsui BC. Reversal of high spinal anesthesia with cerebrospinal lavage after inadvertent intrathecal injection of local anesthetic in an obstetric patient. Can J Anaesth 2014;61(11):1004-7. PMID 25125249
45: Townsend JA, Spiller H, Hammersmith K, Casamassimo PS. Dental local anesthesia-related pediatric cases reported to U.S. Poison Control Centers. Pediatr Dent 2020;42(2):116-22. PMID 32276677
46: Tseng WC, Wu ZF, Liaw WJ, Hwa SY, Hung NK. A patient with postpolio syndrome developed cauda equina syndrome after neuraxial anesthesia: a case report. J Clin Anesth 2017;37:49-51. PMID 28235527
47: Vasques F, Behr AU, Weinberg G, Ori C, Di Gregorio G. A review of local anesthetic systemic toxicity cases since publication of the American Society of Regional Anesthesia recommendations: to whom it may concern. Reg Anesth Pain Med 2015;40(6):698-705. PMID 26469367
48: Verlinde M, Hollmann MW, Stevens MF, Hermanns H, Werdehausen R, Lirk P. Local anesthetic-induced neurotoxicity. Int J Mol Sci 2016;17(3):339. PMID 26959012
49: von Arx T, Lozanoff S, Zinkernagel M. Ophthalmologic complications after intraoral local anesthesia. Swiss Dent J 2014;124(7-8):784-806. PMID 25120235
50: Wadlund DL. Local anesthetic systemic toxicity. AORN J 2017;106(5):367-77. PMID 29107256
51: Weiss E, Jolly C, Dumoulin JL, et al. Convulsions in 2 patients after bilateral ultrasound-guided transversus abdominis plane blocks for cesarean analgesia. Reg Anesth Pain Med 2014;39(3):248-51. PMID 24682078
52: Wen X, Xu S, Liu H, et al. Neurotoxicity induced by bupivacaine via T-type calcium channels in SH-SY5Y cells. PLoS One 2013;8(5):e62942. PMID 23658789
53: Wu T, Smith J, Nie H, et al. Cytotoxicity of local anesthetics in mesenchymal stem cells. Am J Phys Med Rehabil 2018;97(1):50-5. PMID 29252407
54: Xu AL, Lee RJ. Decrease in residual neurological symptoms after institutional changes in peripheral nerve block use for pediatric knee surgery. J Pediatr Orthop 2022;42(2):e138-e142. PMID 34995258
55: Yuen EC, Layzer RB, Weitz SR, Olney RK. Neurologic complications of lumbar epidural anesthesia and analgesia. Neurology 1995;45(10):1795-801. PMID 7477971
56: Zhang K, Li M, Yao W, Wan L. Cytotoxicity of local anesthetics on bone, joint, and muscle tissues: a narrative review of the current literature. J Pain Res 2023;16:611-621. PMID 36875687
57: Zheng LN, Guo FQ, Li ZS, et al. Dexmedetomidine protects against lidocaine-induced neurotoxicity through SIRT1 downregulation-mediated activation of FOXO3a. Hum Exp Toxicol 2020;39(9):1213-23. PMID 32228195
58: Zheng T, Xu SY, Zhou SQ, Lai LY, Li L. Nicotinamide adenine dinucleotide (NAD+) repletion attenuates bupivacaine-induced neurotoxicity. Neurochem Res 2013;38(9):1880-94. PMID 23817845

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All contributors' financial relationships have been reviewed and mitigated to ensure that this and every other article is free from commercial bias.

Authors

Shilpi Mittal MBBS

Dr. Mittal of Thomas Jefferson University Hospital has no relevant financial relationships to disclose.
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Lori A Sheehan MD

Dr. Sheehan of Thomas Jefferson University has no relevant financial relationships to disclose.
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Editor

Matthew Lorincz MD PhD

Dr. Lorincz of the University of Michigan has no relevant financial relationships to disclose.
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Former Authors

K K Jain MD†

Patient Profile

Age range of presentation: 0 month to 65+ years
Sex preponderance: male=female
Heredity: none
Population groups selectively affected: none selectively affected
Occupation groups selectively affected: none selectively affected

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Local anesthesia: neurologic complications

Differential Diagnosis

peripheral neuropathy
seizures
intracranial lesions
history of epilepsy
other drugs that may interact with local anesthetics to cause seizures
- cranial nerve lesions
- previous local anesthetic
- local anesthetic infiltration
- spinal anesthetic

Also Relevant

Drug-induced memory disturbance
Drug-induced neurologic disorders
Drug-induced seizures
Epidural anesthesia
General anesthesia: neurologic complications
- Horner syndrome
- Prognosis after cardiac arrest

	• Blood examination including levels of local anesthetics
	• ECG
	• EEG
	• Brain imaging such as MRI in some cases

Local anesthesia: neurologic complications

Local anesthesia: neurologic complications

Introduction

Overview

Key points

Historical note and terminology

Clinical manifestations

Presentation and course

Table 1. Adverse Effects of Local Anesthetics Involving the Nervous System

Prognosis and complications

Biological basis

Etiology and pathogenesis

Epidemiology

Prevention

Differential diagnosis

Confusing conditions

Associated or underlying disorders

Diagnostic workup

Management

Special considerations

Pregnancy

Anesthesia

References

Contributors

Authors

Editor

Former Authors

Patient Profile

This is an article preview.
Start a Free Account
to access the full version.

Questions or Comment?

Also in This Category

Brain death/death by neurologic criteria

Hepatic encephalopathy

Bowel dysfunction in neurologic disorders

Coma due to primary brainstem and diencephalic lesions

Transient visual loss

Neuroimaging in acute stroke

Sports activities: neurologic complications

Acupuncture

Local anesthesia: neurologic complications

Introduction

Overview

Key points

Historical note and terminology

Clinical manifestations

Presentation and course

Table 1. Adverse Effects of Local Anesthetics Involving the Nervous System

Prognosis and complications

Biological basis

Etiology and pathogenesis

Epidemiology

Prevention

Differential diagnosis

Confusing conditions

Associated or underlying disorders

Diagnostic workup

Management

Special considerations

Pregnancy

Anesthesia

References

Contributors

Authors

Editor

Former Authors

Patient Profile

This is an article preview. Start a Free Account to access the full version.

Questions or Comment?

Also in This Category

Brain death/death by neurologic criteria

Hepatic encephalopathy

Bowel dysfunction in neurologic disorders

Coma due to primary brainstem and diencephalic lesions

Transient visual loss

Neuroimaging in acute stroke

Sports activities: neurologic complications

Acupuncture

This is an article preview.
Start a Free Account
to access the full version.