Local anesthetic agents

Last updated: September 11, 2023

Summarytoggle arrow icon

Local anesthetics (LAs) are drugs that block the sensation of pain in the region where they are administered. LAs act by reversibly blocking the sodium channels of nerve fibers, thereby inhibiting the conduction of nerve impulses. Nerve fibers that carry pain sensation have the smallest diameter and are the first to be blocked by LAs. Loss of motor function and sensation of touch and pressure follow, depending on the duration of action and dose of the LA used. LAs can be infiltrated into skin/subcutaneous tissues to achieve local anesthesia or into the epidural/subarachnoid space to achieve regional anesthesia (e.g., spinal anesthesia, epidural anesthesia). Some LAs (lidocaine, prilocaine, tetracaine) are effective on topical application and are used before minor invasive procedures (venipuncture, bladder catheterization, endoscopy/laryngoscopy). LAs are divided into two groups based on their chemical structure. The amide group (lidocaine, prilocaine, mepivacaine, etc.) is safer and, hence, more commonly used in clinical practice. The ester group (procaine, tetracaine) has a higher risk of causing allergic reactions or systemic toxicity and is therefore reserved for patients with known allergies to drugs of the amide group. Local anesthetic systemic toxicity may result from intravascular injection or administration of LA that exceeds the maximum recommended local anesthetic dose. Toxicity may affect the CNS (e.g., tinnitus, seizures) or cardiovascular system (e.g., arrhythmias, cardiac arrest).

See “Local anesthesia,” and ” Regional anesthesia” for the clinical applications of these agents.

Overviewtoggle arrow icon

Comparison of local anesthetic agents [1][2]
Ester group anesthetics Amide group anesthetics
Short-acting Long-acting Intermediate-acting Long-acting
Common agents
  • Procaine
  • Chloroprocaine
  • Benzocaine
  • Tetracaine
  • Lidocaine
  • Prilocaine
  • Mepivacaine
  • Bupivacaine
  • Etidocaine
  • Ropivacaine
  • Metabolized in the serum by esterases
  • Metabolized in the liver
Safety profile
  • Generally safer than the ester agents

Amide LAs (e.g., lidocaine, bupivacaine) contain an "i" in their name preceding “-caine.” Ester LAs do not.

Pharmacodynamicstoggle arrow icon

  • Pain pathway: thermal, mechanical, or chemical stimuli nociceptor stimulation → conversion of stimulus to an electric signal (action potential) → neural conduction of electric signal to the CNS → perception of pain
  • LAs bind to the inner portion of voltage-gated sodium channels of the nerve fibers; reversible blockage of sodium channels inhibition of nerve excitation and impulse conduction (pain signals) local anesthesia in the area supplied by the nerve
  • LAs with 3° amine structure infiltrate membranes in their uncharged form, then bind to ion channels in their charged form.
  • The susceptibility of nerve fibers to LA depends on their firing rate, size, and myelination.
    • Rapidly firing neurons are blocked more effectively than slow-firing neurons.
    • Small diameter nerves are the first to be anesthetized.
    • Myelinated nerves are blocked faster than unmyelinated nerves.
    • Because size is thought to outweigh myelination, nerve fibers are blocked in the following order:
      1. Small myelinated fibers
      2. Small unmyelinated fibers
      3. Large myelinated fibers
      4. Large unmyelinated fibers
    • Loss of sensation occurs in the following order:
      1. Pain
      2. Temperature
      3. Touch
      4. Pressure
  • Factors that affect the efficacy of LA
    • Use of vasoconstrictors (e.g., epinephrine) reduces bleeding and systemic absorption of LAs, leading to a prolonged anesthetic effect.
    • Inflamed/infected tissue: decreased efficacy of LAs
      • LAs are composed of a lipophilic group and a hydrophilic group, and permeability depends on which group is predominant.
      • Because inflamed tissue has an acidic environment, alkaline anesthetics are charged; and the hydrophilic group predominates → ↓ ability to penetrate the nerve cell membranes → efficacy


Adverse effectstoggle arrow icon

Complications are generally uncommon.

Local anesthetic systemic toxicity (LAST) [8][9][10]

LAST is a potentially fatal adverse event caused by dose-dependent LA blockade of sodium channels in the CNS and cardiovascular system (CVS). [8][9]


Clinical features [8][9]

Be vigilant for symptoms of LAST when administering moderate to large doses of local anesthetics. [9]

Management [9][12][15]

Consider lipid emulsion therapy early for all patients with LAST.

Intravenous lipid emulsion therapy [15][17]

  • Indications
    • LAST
    • Life-threatening, refractory toxicity from other lipid-soluble drugs
  • Contraindications: known egg allergy, chronic liver disease, fat metabolism disorders
  • Administration protocol
    • Lipid emulsion 20% bolus followed by lipid emulsion 20% infusion [15][17][18]
    • Consider a repeat bolus and doubling the infusion if the patient remains unstable after 5 minutes. [12]
    • Continue lipid emulsion infusion for ≥ 15 minutes once hemodynamically stable.
    • Maximum lipid dose: 12 mL/kg

Prevention [9]

Aspirate the syringe prior to each injection to avoid intravascular injection.

Maximum local anesthetic doses [10]
Local anesthetic Without epinephrine With epinephrine
Lidocaine 3–5 mg/kg 7 mg/kg
Mepivacaine 5 mg/kg 7 mg/kg
Bupivacaine 2 mg/kg 3 mg/kg
Ropivacaine 3 mg/kg 3 mg/kg

Other adverse effects

We list the most important adverse effects. The selection is not exhaustive.

Acute management checklist for local anesthetic systemic toxicitytoggle arrow icon

Referencestoggle arrow icon

  1. Becker DE, Reed KL. Local anesthetics: review of pharmacological considerations. Anesth Prog. 2012; 59 (2): p.90-102.doi: 10.2344/0003-3006-59.2.90 . | Open in Read by QxMD
  2. Christie LE, Picard J, Weinberg GL. Local anaesthetic systemic toxicity. Contin Educ Anaesth Crit Care Pain. 2015; 15 (3): p.136-142.doi: 10.1093/bjaceaccp/mku027 . | Open in Read by QxMD
  3. $An introduction to pain pathways and mechanisms.
  4. Dubin AE, Patapoutian A. Nociceptors: the sensors of the pain pathway. J Clin Invest. 2010; 120 (11): p.3760-3772.doi: 10.1172/JCI42843 . | Open in Read by QxMD
  5. Local Anesthetics: Clinical Pharmacology and Rational Selection. Updated: October 14, 2013. Accessed: February 19, 2017.
  6. Becker DE, Reed KL. Essentials of local anesthetic pharmacology. Anesth Prog. 2006; 53 (3): p.98-108.doi: 10.2344/0003-3006(2006)53[98:EOLAP]2.0.CO;2 . | Open in Read by QxMD
  7. Hsu DC. Subcutaneous Infiltration of Local Anesthetics. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. Last updated: January 3, 2017. Accessed: February 19, 2017.
  8. Walls R, Hockberger R, Gausche-Hill M, Erickson TB, Wilcox SR. Rosen's Emergency Medicine 10th edition- Concepts and Clinical Practice E-Book. Elsevier Health Sciences ; 2022
  9. Neal JM, Bernards CM, Butterworth JF, et al. ASRA Practice Advisory on Local Anesthetic Systemic Toxicity. Reg Anesth Pain Med. 2010; 35 (2): p.152-161.doi: 10.1097/aap.0b013e3181d22fcd . | Open in Read by QxMD
  10. El-Boghdadly K, Pawa A, Chin KJ. Local anesthetic systemic toxicity: current perspectives. Local Reg Anesth. 2018; Volume 11: p.35-44.doi: 10.2147/lra.s154512 . | Open in Read by QxMD
  11. Local Anesthetic Systemic Toxicity (LAST) Revisited: A Paradigm in Evolution. Updated: February 1, 2020. Accessed: October 19, 2022.
  12. Safety Committee of Japanese Society of Anesthesiologists. Practical guide for the management of systemic toxicity caused by local anesthetics. J Anesth. 2018; 33 (1): p.1-8.doi: 10.1007/s00540-018-2542-4 . | Open in Read by QxMD
  13. Gitman M, Barrington MJ. Local Anesthetic Systemic Toxicity. Reg Anesth Pain Med. 2018: p.1.doi: 10.1097/aap.0000000000000721 . | Open in Read by QxMD
  14. 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. Reg Anesth Pain Med. 2015; 40 (6): p.698-705.doi: 10.1097/aap.0000000000000320 . | Open in Read by QxMD
  15. Neal JM, Neal EJ, Weinberg GL. American Society of Regional Anesthesia and Pain Medicine Local Anesthetic Systemic Toxicity checklist: 2020 version. Reg Anesth Pain Med. 2020; 46 (1): p.81-82.doi: 10.1136/rapm-2020-101986 . | Open in Read by QxMD
  16. Panchal AR, Bartos JA, Cabañas JG, et al. Part 3: Adult Basic and Advanced Life Support: 2020 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2020; 142 (16_suppl_2).doi: 10.1161/cir.0000000000000916 . | Open in Read by QxMD
  17. Gosselin S, Hoegberg LCG, Hoffman RS, et al. Evidence-based recommendations on the use of intravenous lipid emulsion therapy in poisoning. Clin Toxicol. 2016; 54 (10): p.899-923.doi: 10.1080/15563650.2016.1214275 . | Open in Read by QxMD
  18. Smollin CG. Toxicology: Pearls and Pitfalls in the Use of Antidotes. Emerg Med Clin North Am. 2010; 28 (1): p.149-161.doi: 10.1016/j.emc.2009.09.009 . | Open in Read by QxMD
  19. Guay J. Methemoglobinemia related to local anesthetics: a summary of 242 episodes. Anesth Analg. 2009; 108 (3): p.837-845.doi: 10.1213/ane.0b013e318187c4b1 . | Open in Read by QxMD
  20. Cefalu JN, Joshi TV, Spalitta MJ, et al. Methemoglobinemia in the Operating Room and Intensive Care Unit: Early Recognition, Pathophysiology, and Management. Adv Ther. 2020; 37 (5): p.1714-1723.doi: 10.1007/s12325-020-01282-5 . | Open in Read by QxMD
  21. Kouba DJ, LoPiccolo MC, Alam M, et al. Guidelines for the use of local anesthesia in office-based dermatologic surgery. J Am Acad Dermatol. 2016; 74 (6): p.1201-1219.doi: 10.1016/j.jaad.2016.01.022 . | Open in Read by QxMD
  22. Prabhakar H, Rath S, Kalaivani M, Bhanderi N. Adrenaline with lidocaine for digital nerve blocks. Cochrane Database Syst Rev. 2015; 2020 (11).doi: 10.1002/14651858.cd010645.pub2 . | Open in Read by QxMD
  23. $Chapter 3: Local Anesthetics.

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