Local Anesthetic (LA): a short introduction

Overview: 

Local anesthetics are agents that produce a reversible blockade of neural transmission in autonomic, sensory and motor nerve fibers.

Mechanism of action:

  • Reversibly inhibits nerve transmission by binding voltage-gated sodium channels (Nav) located on the plasma membrane of the nerve.
  • LA binds to Nav making the channels impermeable to Na+ thus preventing action potential initiation and propagation.
  • Onset and duration are both dependent on the type of LA used (discussed in Table 1)
Clinical Use: 
  1. Neuraxial anesthesia 
    • Spinal anesthesia
    • Epidural anesthesia
  2. Peripheral nerve block
  3. Intravenous regional anesthesia
  4. Subcutaneous infiltration
  5. Topical agent (skin, mucous membrane)
  6. Systemic Analgesic (IV lidocaine)
  7. Antiarrhythmic (lidocaine)

Local Anesthetic Pharmacodynamics:

Potency

  • Associated with lipid solubility
    • Greater lipid solubility increases LA ability to permeate nerve membranes therefore increasing potency 
  • ↑ Molecular Weight = ↑ Lipid Solubility 
  • ↑ Lipid Solubility = ↑  Protein Binding

 

Speed of onset

  • Dependent on LA physiochemical properties, LA concentration & site of injection
  • ↑ Concentration = Shorter time of onset
  • ↑ Lipid Solubility = Longer time of onset
  • Site of injection (in order of increasing time of onset)

   Subcutaneous > Intrathecal > Epidural > Peripheral Nerve (also depends on how far LA is deposited from nerve)

pKa

  • The pKa describes the pH at which the ratio of ionized to non-ionized molecules is 1:1
  • All local anesthetics have a pKa above physiologic pH therefore <50% of the drug is in the nonionized (lipid soluble) state
  • LA with pKa closer to physiologic pH will have a faster onset time (as they get faster into the nerve)
  • In regions of local acidosis (infection sites), LA is less effective because the high degree of ionization prevents LA from moving into the nerve

Duration

Elimination

  • Duration of LA is determined by removal from their site of action by vascular uptake and metabolism
  • Highly lipid soluble LA have a longer duration because they diffuse slowly from neural tissue

Alkalinization

  • Alkalinization with sodium bicarbonate can increase LA speed of onset 
  • Usually with LA solutions pre-mixed with epinephrine
  • Not used with bupivacaine* or ropivacaine as (fails to increase time of onset)

   *Bupivacaine can also easily precipitate when alkalized

Combination of Local Anesthetics

  • Mixed results in clinical trials with some studies demonstrating no difference in onset while others reporting faster speed of onset than use of longer acting agent alone
  • Usually, the speed of onset is somewhere between the longer and shorter acting agents

 

Local Anesthetic Dosing

Spinal Anesthesia: Commonly Used Local Anesthetics

Local Anesthetic

Concentration %

Baricity

Dose 

Duration (Min)

Ropivacaine

0.5

Isobaric

15-20 mg

75-120

Bupivacaine

0.5

Isobaric

5-15 mg

75-120

Bupivacaine

0.75%

Hyperbaric

6-15 mg

90-150

 

Spinal: Other Local Anesthetics

Local Anesthetic

Concentration %

Baricity

Dose

Duration (Min)

Lidocaine

2

Isobaric

40-80 mg

45-75

Chloroprocaine

3

Isobaric

40-50 mg

30-50

 

Epidural: Commonly Used Local Anesthetic

Local Anesthetic 

Concentration

Onset

Ropivacaine

0.1%

20-30 min

Bupivacaine

0.06%

20-30 min
  • Routinely followed by a continuous epidural infusion following placement of an epidural catheter

 

Peripheral Nerve Blocks: Commonly Used Local Anesthetics

Local Anesthetic

Onset (min)

Duration of Anesthesia (hours)

Duration of Analgesia (hours)

Max Dose (mg/kg)

Max Dose (mg/kg) with Epinephrine

0.2% Ropivacaine

15-30

4-12

5-16

3

3.5

0.5% Ropivacaine

15-30

4-12

5-16

3

3.5

0.2% Bupivacaine

15-30

5-15

5-26

2.5

3

0.5% Bupivacaine

15-30

5-15

6-30

2.5

3

2% Lidocaine

10-20

2-5

3-8

4.5

7

2% Mepivacaine

10-20

2-5

3-10

5

7

3% Chloroprocaine

6-12

60

60

11

14

Adapted from: Gadsen J. Local Anesthetics: Clinical Pharmacology and Rational Selection. The New York School of Regional Anesthesia website

Duration of onset, anesthesia and analgesia vary widely by site of injection and amount of LA injected.

Epinephrine

  • Used as an adjuvant to prolong the effects of LA
  • In addition to its vasoconstrictive actions, it also seems to have anti-nociceptive properties mediated by alpha 2-adrenoreceptor activation

Liposomal Bupivacaine (Exparel)

Extended release formulation of bupivacaine: bupivacaine that is stored in a depofoam molecule is injected into tissue. The depofoam disintegrates over time releasing bupivacaine over up to 72 hours. 

The injection can be done

  • into an incision (infiltration anesthesia)
  • into a fascial plane (such as a TAP block)
  • next to a nerve or plexus (peripheral nerve block)

The use of Exparel is highly controversial. It is an expensive drug and systematic reviews showed no benefits over plain bupivacaine:  its use at UCSF is limited to trials in selected cases only

Intravenous Regional Anesthesia

  • Lidocaine most commonly used
  • 1- 2 mg/kg/hour IV
  • Monitor for signs of local anesthetic toxicity especially with longer infusions
  • UCSF – maximal infusion duration is 48 hr for pain
References: 

John F Butterworth, IV, MD. Clinical use of local anesthetics in anesthesia. In: UpToDate, Post TW (Ed), UpToDate, Waltham, MA. (Accessed on December 04, 2021.)

Peck, T., & Hill, S. (2014). Pharmacology for Anaesthesia and Intensive Care (4th ed.). Cambridge: Cambridge University Press. doi:10.1017/CBO9781107477605

Sulyok, I., Camponovo, C., Zotti, O. et al. A randomised, non-inferiority study of chloroprocaine 2% and ropivacaine 0.75% in ultrasound-guided axillary block. Sci Rep 11, 10035 (2021). https://doi.org/10.1038/s41598-021-89483-y

Enneking, F. Kayser MD Local Anesthetics and Additives, Anesthesia & Analgesia: March 2001 - Volume 92 - Issue 3 - p 32-36

doi: 10.1097/00000539-200103001-00006

Salazar F, Bogdanovich A, Adalia R, Chabás E, Gomar C. Transient neurologic symptoms after spinal anaesthesia using isobaric 2% mepivacaine and isobaric 2% lidocaine. Acta Anaesthesiol Scand. 2001 Feb;45(2):240-5. doi: 10.1034/j.1399-6576.2001.450216.x. Erratum in: Acta Anaesthesiol Scand. 2003 May-Jun;28(3):257. PMID: 11167171.

Gadsden J, Hadzic A, Gandhi K, Shariat A, Xu D, Maliakal T, Patel V. The effect of mixing 1.5% mepivacaine and 0.5% bupivacaine on duration of analgesia and latency of block onset in ultrasound-guided interscalene block. Anesth Analg. 2011 Feb;112(2):471-6. doi: 10.1213/ANE.0b013e3182042f7f. Epub 2010 Dec 14. PMID: 21156983.

Author: 
Mae Yap