Anesthesia

  • Local anesthetics are classified into 2 groups: the ester group and the amide group. The classification is based on the chemical structure of the intermediate chain. This structural difference affects the pathway by which local anesthetics are metabolized and the allergic potential.
  • Ester anesthetics are listed in the Table below. They are metabolized by hydrolysis, which depends on the plasma enzyme pseudocholinesterase. Some patients have a rare genetic defect in the structure of this enzyme and may be unable to metabolize ester-type anesthetics; this inability increases the possibility of their having toxic reactions and elevated levels of anesthetics in the blood. In addition, 1 of the metabolic products generated by hydrolysis is PABA, which inhibits the action of sulfonamides and is a known allergen. In patients with a known allergy to an ester anesthetic, the use of all other ester-type anesthetic agents should be avoided.
  • Amide-type local anesthetics (see Table below) are metabolized by microsomal enzymes located in the liver. The specific microsomal enzyme responsible for the elimination of lidocaine is cytochrome P-450 3A4. Therefore, amide-type anesthetics should be used with care in patients with severe liver disease and patients taking medications that interfere with the metabolism of the anesthetic, and the patients should be carefully monitored for signs of toxicity.
  • Cytochrome P-4503A4 is present in the small bowel and the liver. Commonly used medications known to inhibit cytochrome P-4503A4 are listed below (adapted from Klein and Kassarjdian).Specific potent inhibitors of cytochrome P-4503A4 that have been associated with clinically relevant interactions include itraconazole, ketoconazole (azole antifungals), erythromycin, clarithromycin, cyclosporin (macrolides), amprenavir, indinavir, nelfinavir, ritonavir (HIV protease inhibitors), diltiazem, mibefradil (calcium channel blockers), and nefazodone. Grapefruit juice is also a potent inhibitor of P-4503A4 but appears to affect only the enteric enzyme, which does not play a role in the metabolism of local anesthetics.
  • If the enzyme is inhibited because of the concurrent use of medications, it is unavailable to metabolize the anesthetic and potentially toxic levels of the anesthetic can occur. In addition, beta-blockers may decrease blood flow to the liver; therefore, they may also decrease the metabolism of amide-type anesthetics and may cause serum levels of the anesthetic to increase.
  • Antiarrhythmic agents
    • Amiodarone
    • Quinidine
  • Antibiotic agents
    • Chloramphenicol
    • Clarithromycin
    • Erythromycin
    • Tetracycline
    • Metronidazole
  • Antidepressant agents
    • Citalopram
    • Fluoxetine
    • Paroxetine
    • Sertraline
  • Antiepileptic agents
    • Carbamazepine
    • Valproic acid
  • Antifungal agents
    • Fluconazole
    • Itraconazole
    • Ketoconazole
  • Antitubercular agents - Isoniazid
  • Antiulcer agents - Cimetidine
  • Benzodiazepines
    • Midazolam
    • Triazolam
  • Beta-blockers
  • Calcium channel blockers
    • Diltiazem
    • Nicardipine
    • Nifedipine
    • Verapamil
  • Immunosuppressants
    • Cyclosporin
    • Dexamethasone
    • Methylprednisolone

Common Local Anesthetics*

Table
Anesthetic

 

Duration Without Epinephrine,

min

 

Duration With Epinephrine,

min

 

Maximum Dose Without Epinephrine,

mg/kg

 

Maximum Dose With Epinephrine,

mg/kg

 

Esters

 

Cocaine

 

45

 

-

 

2.8

 

-

 

Procaine

 

15-30

 

30-90

 

7.1

 

8.5

 

Chloroprocaine

 

30-60

 

-

 

11.4

 

14.2

 

Tetracaine

 

120-240

 

240-480

 

1.4

 

-

 

Amides

 

Lidocaine

 

30-120

 

60-400

 

4.5

 

7

 

Mepivacaine

 

30-120

 

30-120

 

4.5

 

7

 

Bupivacaine

 

120-240

 

240-480

 

2.5

 

3.2

 

Etidocaine

 

200

 

240-360

 

4.2

 

5.7

 

Prilocaine

 

30-120

 

60-400

 

5.7

 

8.5

 

Anesthetic

 

Duration Without Epinephrine,

min

 

Duration With Epinephrine,

min

 

Maximum Dose Without Epinephrine,

mg/kg

 

Maximum Dose With Epinephrine,

mg/kg

 

Esters

 

Cocaine

 

45

 

-

 

2.8

 

-

 

Procaine

 

15-30

 

30-90

 

7.1

 

8.5

 

Chloroprocaine

 

30-60

 

-

 

11.4

 

14.2

 

Tetracaine

 

120-240

 

240-480

 

1.4

 

-

 

Amides

 

Lidocaine

 

30-120

 

60-400

 

4.5

 

7

 

Mepivacaine

 

30-120

 

30-120

 

4.5

 

7

 

Bupivacaine

 

120-240

 

240-480

 

2.5

 

3.2

 

Etidocaine

 

200

 

240-360

 

4.2

 

5.7

 

Prilocaine

 

30-120

 

60-400

 

5.7

 

8.5

 

*Adapted from Dinehart.

Future of Anesthetics

Tumescent anesthesia

  • In 1987, Jeffery Klein, a dermatologist, first created the technique of tumescent anesthesia in liposuction procedures.Tumescent anesthesia is based on the use of dilute solutions of lidocaine (0.05-0.1%) in large volumes to provide superior anesthesia. Epinephrine (1:1,000,000) is added for hemostasis, and the solution is buffered with sodium bicarbonate to decrease injection discomfort. Concentrations as high as 55 mg/kg have been used safely with the tumescent technique.
  • The use of such high total doses of anesthetic without systemic toxicity is understood. The absorption kinetics of lidocaine change when high-volume, low-concentration solutions are used. Decreased concentrations of lidocaine also result in slower plasma absorption with decreased peak plasma levels. The development of this anesthetic delivery system has revolutionized the surgical technique of liposuction.
  • Source Emedicine.medscape.com

     

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