Topical, Local, and Regional Anesthesia and Anesthetics

Earn CME/CE in your profession:

Continuing Education Activity

Nerve impulse transmission occurs when voltage-gated sodium channels on the neuronal membrane open, allowing a massive influx of sodium. This causes membrane depolarization and propagation of the impulse. Local anesthetics block nerve impulse transmission in the peripheral and central nervous system without causing central nervous system depression or altered mental status. The block generally occurs in a stepwise sequence depending on the concentration and volume of the local anesthetic, with autonomic impulses blocked first, then sensory impulses, and finally, motor impulses. Local anesthetics are used to anesthetize skin, subcutaneous tissue, and peripheral nerves for invasive or surgical procedures. This activity outlines the indications, mechanism of action, administration methods, significant adverse effects, contraindications, toxicity, and monitoring, of topical, local, and regional anesthetic agents so providers can direct patient therapy when indicated as part of the interprofessional team.


  • Describe the various mechanisms of action of the most common topical and local anesthetic agents.
  • Identify the various indications for employing local or topical anesthetics.
  • Review the contraindications and adverse events of various topical or local anesthetics.
  • Explain the importance of improving care coordination among the interprofessional team to enhance care delivery for patients who can benefit from therapy with topical and local/regional anesthesia.


Nerve impulse transmission occurs when voltage-gated sodium channels on the neuronal membrane open, allowing a massive influx of sodium. This results in membrane depolarization and propagation of the nerve impulse. Local anesthetics block nerve impulse transmission in the peripheral and central nervous systems without causing central nervous system depression or altered mental status. The block generally occurs in a stepwise sequence depending on the concentration and volume of the local anesthetic, with autonomic impulses blocked first, then sensory impulses, and finally, motor impulses.

Local anesthetics work to anesthetize skin, subcutaneous tissue, and peripheral nerves for invasive or surgical procedures. The duration of action of local anesthetics can range from 30 minutes to 12 hours or more. The range depends on the location of the block (e.g., high blood supply equals shorter duration), the specific local anesthetic used, and its preparation (liposomal preparations create extended-release drugs).

Commonly used local anesthetics in clinical practice include the following:

Amino Amides

  • Mepivacaine
  • Lidocaine
  • Etidocaine
  • Bupivacaine
  • Levobupivacaine
  • Ropivacaine

Amino Esters

  • Procaine
  • Cocaine
  • Chloroprocaine
  • Tetracaine
  • Benzocaine

Because of the variable pharmacodynamics, pharmacokinetics, and toxicity profile of the various local anesthesia agents, the intended procedure will dictate the agent used.

Recently the FDA approved liposomal bupivacaine for postoperative analgesia. Hopefully, this formulation will decrease the reliance on opiates in the post-surgical period.[1]

Several reports indicate that lidocaine may also function as a tinnitus suppressing agent. The drug requires intravenous injection, but the risk of systemic toxicity remains a significant concern.[2][3][4][5]

Mechanism of Action

Local anesthetics block voltage-gated sodium channels, which prevents sodium influx into the cell and blocks impulse transmission. Local anesthetics are also class I antiarrhythmic drugs due to the blockade of cardiac sodium channels, with lidocaine being the class IB prototype. They selectively block channels that are frequently depolarizing (as occurs in tachyarrhythmias) and, therefore, slow transmission.[6]

Two subclasses of local anesthetics categorize according to the location where metabolism occurs. The amino amides such as bupivacaine, ropivacaine, and lidocaine, are hydrolyzed in the liver, whereas plasma cholinesterases metabolize the amino-esters such as procaine, chloroprocaine, and tetracaine. 

Amino amides are stable in solution, whereas the amino esters are unstable. Allergic or hypersensitivity reactions are more likely to occur with amino esters than amino amides.

Local anesthetics work in the nonionic form. In the presence of a low pH, the ionized form is dominant; this can delay the onset of action; this also explains why local anesthetics are not effective in sites of inflammation, where an acidic environment is common. Thus, many clinicians add sodium bicarbonate to overcome the tissue acidity and increase the local anesthetic efficacy.

Epinephrine is often added to a local anesthetic solution, which allows the clinician to use a lower dose of the anesthetic and improve safety. Further, epinephrine acts as a vasoconstrictor and delays absorption of the anesthetic into the peripheral arteriole, thus increasing the duration of action. The addition of epinephrine can also improve hemostasis by inducing vasoconstriction in the surgical field.

However, the dose of epinephrine used should not be more than a 1 to 100,000 concentration. In certain patients, the drug can cause arrhythmias, especially for patients receiving halothane. Epinephrine can also compromise flap viability, so the surgeon must account for this when determining whether to use it and at what dose. Finally, the patient should not use epinephrine on the nose, ear, or penis.


Local anesthetics can be applied topically and subcutaneously to anesthetize local tissues. Topical use for some agents (e.g., viscous lidocaine) can include oral ingestion with swish and spit, as well as gargling and swallowing for pharyngeal anesthesia effects. Oral applications can also include agents such as benzocaine applied to the gums or aphthous stomatitis. These local anesthetic agents can also be administered around peripheral nerves and in the neuraxial space to anesthetize larger nerves or dermatomal distributions. Lidocaine is also administered intravenously to provide surgical anesthesia for an extremity, such as Bier block, or as a cardiac antiarrhythmic.[7][8]

Adverse Effects

Local anesthetics have a significant risk of systemic toxicity when administered intravascularly or orally in excessive dosages. Symptoms usually manifest in the central nervous system first (metallic taste, auditory changes, circumoral numbness, blurred vision, agitation, seizures), followed by cardiovascular effects (hypotension, decreased cardiac contractility, dysrhythmias, complete heart block, cardiovascular collapse). Bupivacaine is particularly cardiotoxic, and there have been reports of cardiovascular collapse in the absence of antecedent neurologic symptoms. Cardiopulmonary bypass or extracorporeal membrane oxygenation is still useful in refractory cases.[9][10][11]


Allergic or hypersensitivity reactions to local anesthetics are rare. In most cases, the hypersensitive response is not to the anesthetic itself but the preservative solution. The risk of an allergic reaction is higher with the ester group than with the amides. The cause of the hypersensitivity reaction appears to be para-aminobenzoic acid, which is a breakdown product generated by the actions of the pseudocholinesterase enzyme. Para-aminobenzoic acid is considered extremely antigenic and rapidly sensitizes lymphocytes.

More commonly, reactions to a local anesthetic arise from apprehension, anxiety, and phobia about needles. These feelings may result in a vasovagal response, a panic attack, or a syncopal episode.

If a patient develops a hypersensitive reaction to one anesthetic in the ester group, they will generally also be sensitive to all other anesthetics in the same class. Thus, it is better to use an amino group anesthetic in such scenarios.


Allergies have been reported for each class of local anesthetics, but crossover sensitivity does not occur. Ester local anesthetics are metabolized to a para-aminobenzoic acid-like compound, and anaphylaxis has been reported. Amide local anesthetics sometimes contain the preservative methylparaben, which has also been reported to cause severe allergic reactions.

It is essential to know which class of local anesthetic caused the reaction and avoid that class in the future. Some pathological states, including decreased cardiac output, renal pathology, severe hepatic disease, cholinesterase activity, fetal acidosis, sepsis, can alter the pharmacodynamics and pharmacokinetics of specific local anesthetics. For example, patients with depressed hepatic function may experience a prolonged duration of action or a higher risk of toxicity with amides. Patients with a cholinesterase deficiency may have prolonged effects of esters.[12]


Recommended maximum dosages for local anesthetics are widely available. Still, practitioners should always use the lowest dose necessary to achieve the desired result due to the significant risk of systemic toxicity. All local anesthetics are vasodilators, except cocaine. Cocaine is a norepinephrine reuptake inhibitor, thus potentiating sympathetic stimulation and causing hypertension and ventricular irritability. 


Local and topical anesthetics are generally safe when dosed properly, and they remain confined to the site of administration, such as a nerve plexus or infiltrated tissue. However, if large quantities of local anesthetic enter the systemic circulation, toxicity can result from supratherapeutic drug levels.

Patients with a suspected local anesthetic overdose should be treated immediately with intravenous lipid emulsion 20% at 1.5 mL/kg (lean body mass) given over 1 minute, followed by a 0.25 mL/kg/minute infusion. The bolus may be repeated up to two times for refractory cardiovascular compromise. The infusion can be increased to 0.5 mL/kg/minute if the patient has the return of cardiac function but remains hypotensive. The maximum recommended dose is 10 mL/kg over the first 30 minutes (per the American Society of Regional Anesthesia and Pain Medicine 2011 Consensus Statement).

Enhancing Healthcare Team Outcomes

Local anesthetics are used by many healthcare professionals, including anesthesiologists, nurse anesthetists, nurse practitioners and PAs, primary care providers, emergency department physicians, surgeons, nursing staff, and pharmacists. These various disciplines must coordinate as an interprofessional team must each contribute from their area of expertise to optimize the therapeutic effect of these drugs and minimize adverse events, particularly potential systemic adverse events. [Level 5]

It is essential for health care team members to know about the toxicity of these agents and always use the lowest dose possible. When injecting these agents parenterally, resuscitative equipment must be in the room. Countless litigation cases have resulted simply due to a failure to even have a bag valve mask in the room.



8/28/2023 9:16:14 PM



Litman RS. Anesthetic and Analgesic Drug Products Advisory Committee Activity and Decisions in the Opioid-crisis Era. Anesthesiology. 2020 Oct 1:133(4):740-749. doi: 10.1097/ALN.0000000000003485. Epub     [PubMed PMID: 32773684]


Olawin AM, M Das J. Spinal Anesthesia. StatPearls. 2023 Jan:():     [PubMed PMID: 30725984]


Shah J, Votta-Velis EG, Borgeat A. New local anesthetics. Best practice & research. Clinical anaesthesiology. 2018 Jun:32(2):179-185. doi: 10.1016/j.bpa.2018.06.010. Epub 2018 Jul 3     [PubMed PMID: 30322458]


Wu S, Tang KC. Advanced Subconjunctival Anesthesia for Cataract Surgery. Asia-Pacific journal of ophthalmology (Philadelphia, Pa.). 2018 Sep-Oct:7(5):296-300. doi: 10.22608/APO.2018231. Epub 2018 Sep 28     [PubMed PMID: 30264551]


Frattinger C, Grange I, Line Cavalie M, Rouhana K, Dziadzko M. [Topical application of analgesic cream for spinal anaesthesia in elective orthopaedic surgery]. Soins; la revue de reference infirmiere. 2018 Sep:63(828):14-17. doi: 10.1016/j.soin.2018.06.005. Epub     [PubMed PMID: 30213307]


Földi MC, Pesti K, Zboray K, Toth AV, Hegedűs T, Málnási-Csizmadia A, Lukacs P, Mike A. The mechanism of non-blocking inhibition of sodium channels revealed by conformation-selective photolabeling. British journal of pharmacology. 2021 Mar:178(5):1200-1217. doi: 10.1111/bph.15365. Epub 2021 Feb 1     [PubMed PMID: 33450052]


Mankowitz SL. Laceration Management. The Journal of emergency medicine. 2017 Sep:53(3):369-382. doi: 10.1016/j.jemermed.2017.05.026. Epub 2017 Aug 25     [PubMed PMID: 28847677]


Dias R, Dave N, Tullu MS, Deshmukh CT. Local anaesthetic systemic toxicity following oral ingestion in a child: Revisiting dibucaine. Indian journal of anaesthesia. 2017 Jul:61(7):587-589. doi: 10.4103/ija.IJA_166_17. Epub     [PubMed PMID: 28794532]


Yang Y, Liu Z, Wei Q, Cao D, Yang L, Zhu Y, Wei X, Tang Z, Liu L, Han P. The Efficiency and Safety of Intrarectal Topical Anesthesia for Transrectal Ultrasound-Guided Prostate Biopsy: A Systematic Review and Meta-Analysis. Urologia internationalis. 2017:99(4):373-383. doi: 10.1159/000481830. Epub 2017 Oct 30     [PubMed PMID: 29084411]

Level 1 (high-level) evidence


Hung MH, Chen JS, Cheng YJ. Precise anesthesia in thoracoscopic operations. Current opinion in anaesthesiology. 2019 Feb:32(1):39-43. doi: 10.1097/ACO.0000000000000680. Epub     [PubMed PMID: 30540577]

Level 3 (low-level) evidence


Boyce RA, Kirpalani T, Mohan N. Updates of Topical and Local Anesthesia Agents. Dental clinics of North America. 2016 Apr:60(2):445-71. doi: 10.1016/j.cden.2015.12.001. Epub     [PubMed PMID: 27040295]


Šimurina T, Mraović B, Župčić M, Graf Župčić S, Vulin M. LOCAL ANESTHETICS AND STEROIDS: CONTRAINDICATIONS AND COMPLICATIONS - CLINICAL UPDATE. Acta clinica Croatica. 2019 Jun:58(Suppl 1):53-61. doi: 10.20471/acc.2019.58.s1.08. Epub     [PubMed PMID: 31741560]