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CHAPTER 2-6: ANESTHETICS, LOCAL

Neal L. Benowitz

INTRODUCTION

Local anesthetics are used widely to provide anesthesia via local subcutaneous (SC) injection; topical application to skin and mucous membranes; and epidural, spinal, and regional nerve blocks. In addition, lidocaine is used IV as an antiarrhythmic agent, and cocaine is a popular drug of abuse. Commonly used agents are divided into two chemical groups: ester-linked and amide-linked (Table II–2).

TABLE II–2.LOCAL ANESTHETICS
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TABLE II–2. LOCAL ANESTHETICS
Anesthetic Usual Half-life Maximum Adult Single Dosea (mg)
Ester-linked
 Benzocaineb   N/A
 Benzonatatec   200
 Butacaineb   N/A
 Butambenb   N/A
 Chloroprocaine 1.5–6 min 800
 Cocaineb 1–2.5 h N/A
 Hexylcaineb   N/A
 Procaine 7–8 min 600
 Proparacaineb   N/A
 Propoxycaine   75
 Tetracaine 5–10 min 15
Amide-linked
 Articaine 1–2 h 500
 Bupivacaine 2–5 h 400
 Dibucaine   10
 Etidocaine 1.5 h 400
 Levobupivacaine 1–3 h 300
 Lidocaine 1.2 h 300
 Lidocaine with epinephrine 2 h 500
 Mepivacaine   400
 Prilocaine   600
 Ropivacaine   225
Other (neither ester- nor amide-linked)
 Dyclonineb   N/A
 Pramoxineb   N/A

aMaximum single dose for subcutaneous infiltration. N/A, not applicable.

bUsed only for topical anesthesia.

cGiven orally as an antitussive.

Toxicity from local anesthetics (other than cocaine) is usually caused by therapeutic overdose (ie, excessive doses for local nerve blocks), inadvertent acceleration of IV infusions (lidocaine), or accidental injection of products meant for dilution (eg, 20% lidocaine) instead of those formulated for direct administration (2% solution). Acute injection of lidocaine has also been used as a method of homicide. To prolong the duration of effect, local anesthetics are often administered together with epinephrine, which can also cause toxicity.

MECHANISM OF TOXICITY

  1. Local anesthetics bind to sodium channels in nerve fibers, blocking the sodium current responsible for nerve conduction and thereby increasing the threshold for conduction and reversibly slowing or blocking impulse generation. In therapeutic concentrations, this results in local anesthesia. In high concentrations, such actions may result in CNS and cardiovascular toxicity.

  2. Bupivacaine is more cardiotoxic than other local anesthetics, with a very narrow toxic-to-therapeutic ratio and with numerous reports of rapid cardiovascular collapse and sometimes death. In addition to causing sodium channel blockade, bupivacaine inhibits carnitine acyltransferase, which is essential for fatty acid transport, resulting in mitochondrial dysfunction that is thought to contribute to cardiotoxicity.

  3. In addition, some local anesthetics (eg, benzocaine, prilocaine, lidocaine) can cause methemoglobinemia.

  4. Pharmacokinetics. With local subcutaneous injection, peak blood levels are reached in 10–60 minutes, depending on the vascularity of the tissue and whether a vasoconstrictor such as epinephrine has been added. Ester-type drugs are hydrolyzed rapidly by plasma cholinesterase and have short half-lives. Amide-type drugs are metabolized by the liver, have a longer duration of effect, and may accumulate after repeated doses in patients with hepatic insufficiency. For other kinetic values, see Table ...

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