Local anesthetics may be injected or topically applied to skin and mucosal membranes.

Topical application usually results in a more rapid and potent analgesic response when applied to mucous membranes -which are more permeable to drug absorption - when compared to intact skin (Butterworth et eds). The state of the chosen site also influences serum drug concentration. Tissue characteristics such blood supply (increased vascularity) and integrity of surface epithelium (if disrupted) can increase systemic uptake of local agents and lower the maximum safe dosage (Butterworth et eds, Catterall & Mackie, Schwartz & Kaufman, Rosenberg et al).

Vasoconstricting agents are often included with both topical (e.g. nasal spray, 4% lidocaine with 1% phenylephrine) and injectable (e.g. 1% lidocaine with 1:100,000 epinephrine) anesthetics.

The maximum safe dosage of local anesthetics, whether topical or injected, is generally increased when used in combination with a vasoconstricting agent. Serum concentration increases at a slower rate when blood flow is diminished at the site of treatment as the anesthetic is sequestered. This same process will increase the duration of analgesic effect for a given anesthetic when administered along with a vasoconstrictor (Berde & Strichartz, Catterall & Mackie, Drasner, Hilal-Dandan & Brunton, Schwartz & Kaufman).

Due to concern of ischemia and necrosis, use of local anesthetic-vasoconstrictor combination solutions is generally discouraged in areas with limited blood supply with reports indicating these areas may include the digits, penis, tip of the nose, and earlobe (McGee, Nolan).

Other factors to be considered prior to administering local anesthesia include the age of the patient and conditions such as renal dysfunction, hepatic dysfunction, heart failure, and pregnancy. The metabolism and excretion of local anesthetics plays a major role in determining serum drug concentrations -- any factor that modifies these parameters will also influence appropriate drug dosing for these patients (Rosenberg et al).

Local anesthetics can be classified as either amide (e.g. lidocaine) or ester (e.g. tetracaine). 

Primary systemic toxicities of local anesthetics are central nervous system (CNS) dysfunction  which is initially CNS stimulation manifesting as tremors and/or convulsions. Subsequently CNS depression may occur with respiratory failure and cardiovascular disturbances (Catterall & Mackie, Curtis et al).

If ingested orally, ester-type anesthetics may initially cause gastric irritation and related symptoms of vomiting and abdominal pain (Curtis et al). Methemoglobinemia can occur as a more delayed presentation (Curtis et al).

Sedative effects of local anesthetics may be synergistically increased when using these drugs in combination with narcotics.

Common Maximum Recommended Doses

A compilation from references: AAP, AAPD, Cote, Wilson, & Work Group on Sedation; Access Pharmacy drug monographs; Berde & Strichartz; Butterworth, Mackey, & Wasnick (eds.); Catterall & Mackie; Cousins & Bridenbaugh (eds.) 2009; Dorian 2015; Drasner; Hilal-Dandan & Brunton (eds.); Keddis; Micromedex; Rosenberg, Veering, & Urmey 2004; Schwartz & Kaufman 2015; Williams & Walker 2014.

The values cited below include all consistent recommended values from the above sources, with the exception of: maximum values recommended by Butterworth et eds for procaine alone (12 mg/kg) and bupivacaine alone (3 mg/kg); by Berde & Strichartz for total dose of procaine alone (500 mg) and total procaine with epi (600 mg).

These doses are based on risk for systemic toxicity and possible death. Maximum values to avoid local toxicity may be much lower.

Anesthetic route of administration	Maximum single dose without vasoconstrictor (mg/kg)	Maximum single dose with vasoconstrictor (mg/kg)	Onset of action (min)	Duration of action in isolation (min) [w/ vasoconstrictor, if available]
Esters
Procaine infiltration, subcutaneous	7-10 - not to exceed 1000 mg total	10		20-30 [30-45 w/ epinephrine]
Chloroprocaine infiltration, subcutaneous	10-12 - not to exceed 800 mg per dose	14 - not to exceed 1000 mg per dose	6-12	30-60 [60-90 w/ epinephrine]
Tetracaine topical, skin & mucous membranes infiltration, subcutaneous	1-3 - topical skin, adults: 7g/24h - topical skin, children: 2g/24h - topical mucous membranes: 20 mg/dose - infiltration, subcutaneous: 3 mg/kg per dose	1.5	3-8	120-180
Amides
Lidocaine topical, skin & mucous membranes infiltration, subcutaneous	3-4.5 - topical skin: 4.5 mg/kg per dose, not to exceed 300 mg - topical mucous membranes: 4.5 mg/kg per dose, not to exceed 300 mg per dose, maximum 2400 mg/24h - infiltration, subcutaneous: 4.5 mg/kg per dose	6-7 (infiltration) - not to exceed 500 mg per dose	- infiltration 1-3 - topical skin 3-5	30-120 [120-240 w/ epinephrine]
Mepivacaine infiltration, subcutaneous	4.5-5 - not to exceed 400 mg per dose - maximum 1000 mg/24h	6.6 - not to exceed 400 mg per dose if with levonordefrin - not to exceed 500 mg per dose if with epinephrine	3-20	45-90 [60-330 w/ levonordefrin, 120 w/ epinephrine]
Bupivacaine infiltration, subcutaneous	2-2.5 - not to exceed 175 mg per dose - maximum 400 mg/24h	2.5-3 - not to exceed 225 mg per dose - maximum dose 400 mg/24h	2-10	120-175 [180-480 w/ epinephrine]
Levobupivacaine infiltration, subcutaneous	2 - not to exceed 150 mg per dose	3		180-360
Ropivacaine infiltration, subcutaneous	2-3 - not to exceed 225 mg per dose	3-4 - not to exceed 225 mg per dose	3-15	120-240 [180-480 w/ epinephrine]
Articaine infiltration, subcutaneous	n/a	7	1-9	[60-230 w/ epinephrine]

Calculation of Maximum Recommended Dosage:

1. The concentration of the local anesthetic should be known.

   • Percent concentration must be converted to concentration of drug (mg/mL) as follows (table modeled from AAP, AAPD, CJ Cote, S Wilson, Work Group on Sedation)

   • Concentration %	mg/mL
     4	40
     3	30
     2.5	25
     2	20
     1	10
     0.5	5
     0.25	2.5
     0.125	1.25

2. The weight of the patient should be known.

Average Weight of Pediatric Patients 

Adapted from the Centers for Disease Control and Prevention Clinical Growth Charts 2001.

Boys:

Age (year)	Mean (kg)	Range - 3% to 97% (kg)
1	10.3	8.4 - 12.7
2	12.7	10.4 - 15.6
3	14.3	11.8 - 17.9
4	16	13 - 21
5	18.5	15 - 24.5
6	21	16.5 - 28
7	23	18 - 31.8
8	25.5	20 - 37
9	28.5	22 - 43
10	32	24 - 49
11	36	26.5 - 56
12	40.5	29 - 63
13	45.5	32.5 - 70
14	51	37 - 76.5
15	56	41.3 - 83
16	61	45.5 - 88.5
17	64.5	49 - 93.5

Girls:

Age (year)	Mean (kg)	Range - 3% to 97% (kg)
1	9.5	7.8 - 11.7
2	12	10.0 - 15.0
3	13.9	11.3 - 17.9
4	16	13 - 21
5	18	14 - 25
6	20	16 - 28.5
7	22.5	17.5 - 33
8	25.5	19.5 - 38.5
9	29	21.5 - 44.5
10	33	24 - 51
11	37	26.5 - 58.5
12	41.5	30 - 65.5
13	46	33 - 72
14	49	36.5 - 77.5
15	52	39.5 - 81.5
16	54	42 - 84.5
17	55	43 - 86

Example calculation - Lidocaine

• Total dose that can be used
  • Maximum dose of lidocaine (plain, without vasoconstrictor)  is 4.5 mg/kg (not to exceed 300 mg)
  • Example patient weight - 10 kg
  • Total dose that can be used for this patient = 4.5 mg/kg x 10 kg = 45 mg
• Maximum volume of lidocaine administered
  • Depends on concentration (see conversion table above)
  • E.g. for 1% lidocaine: contains 10 mg of lidocaine per 1 mL
  • Max volume of 1% lidocaine that can be administered to a 10 kg patient  = 45 mg / 10mg/mL = 4.5 mL

References

Access Pharmacy drug monographs - all drugs in table except procaine, levobupivacaine

American Academy of Pediatrics, American Academy of Pediatric Dentistry, Cote CJ, Wilson S, Work Group on Sedation. Guidelines for monitoring and management of pediatric patients during and after sedation for diagnostic and therapeutic procedures: an update. Pediatrics. 2006 Dec;118(6):2587-602.

Antonio Hernandez and Edward R. Sherwood:  Anesthesiology Principles, Pain Management, and Conscious Sedation Sabiston Textbook of Surgery, Chapter 14, 360-392 Twentieth Edition Copyright © 2017 by Elsevier, Inc

Berde CB and Strichartz GR. Miller's anesthesia. 4th ed. Amsterdam (Netherlands): Elsevier Academic Press; c2015. Chapter 36: Local anesthetics; p. 1028-1054.

Catterall WA, Mackie K. Local Anesthetics. In: Brunton LL, Hilal-Dandan R, Knollmann BC. eds. Goodman & Gilman's: The Pharmacological Basis of Therapeutics, 13e New York, NY: McGraw-Hill.

Curtis LA, Dolan TS, and Seibert HE. Are One or Two Dangerous? Lidocaine and Topical Anesthetic Exposures in Children. The Journal of Emergency Medicine vol 37, No.1, pp 32-9, 2009

Dorian RS. Anesthesia for the Surgical Patient. In: Brunicardi F, Andersen DK, Billiar TR, Dunn DL, Hunter JG, Matthews JB, Pollock RE. eds. Schwartz's Principles of Surgery, 10e New York, NY: McGraw-Hill; 2015.

Drasner K. Local Anesthetics. In: Katzung BG. eds. Basic & Clinical Pharmacology, 14e New York, NY: McGraw-Hill.

Keddis, RN. Chapter 120: Local Anesthetics and Adjuvants. In: Atchabahian A, Gupta R. The Anesthesia Guide, 1e New York, NY: McGraw-Hill.

Local Anesthetics. In: Butterworth IV JF, Mackey DC, Wasnick JD. eds. Morgan & Mikhail's Clinical Anesthesiology, 6e New York, NY: McGraw-Hill.

Local Anesthetics. In: Hilal-Dandan R, Brunton LL. eds. Goodman and Gilman's Manual of Pharmacology and Therapeutics, 2e New York, NY: McGraw-Hill.

McGee, DL. Local and topical anesthesia. In: Roberts JR, Custalow CB, Thomsen TW, eds. Roberts and Hedges' Clinical Procedures in Emergency Medicine and Acute Care. 7th ed. Amsterdam (Netherlands): Elsevier Academic Press; 2019. https://www-clinicalkey-com.proxy.lib.uiowa.edu/#!/content/book/3-s2.0-B.... Accessed November 29, 2018.

Micromedex - all drugs in table except levobupivacaine, articaine

Nolan, JP. Anaesthesia and neuromuscular block. In: Brown MJ, Sharma P, Mir FA, Bennett PN, eds. Clinical Pharmacology. 12th ed. Amsterdam (Netherlands): Elsevier Academic Press; 2019. https://www-clinicalkey-com.proxy.lib.uiowa.edu/#!/content/book/3-s2.0-B.... Accessed November 29, 2018.

Properties, absorption, and disposition of local anesthetic agents. In: Cousins MJ, Bridenbaugh PO, eds. Cousins and Bridenbaugh’s Neural Blockade in Clinical Anesthesia and Pain Medicine. 4th ed. Philadelphia: Lippincott Williams & Wilkins; 2009:49.

Rosenberg PH, Veering BT, Urmey WF. Maximum recommended doses of local anesthetics: a multifactorial concept. Reg Anesth Pain Med. Nov 2004; 29;564-575.

Schwartz DR, Kaufman B. Local Anesthetics. In: Hoffman RS, Howland M, Lewin NA, Nelson LS, Goldfrank LR. eds. Goldfrank's Toxicologic Emergencies, 10e New York, NY: McGraw-Hill; 2015.

Williams DJ, Walker JD. A nomogram for calculating the maximum dose of local anaesthetic. Anaesthesia. 12 May 2014; 69:847-853.

Wolfe J.W., Adams J.M., Ehrenfeld J.M. (2016) Pharmacology of Local Anesthetics. In: Ehrenfeld J., Urman R., Segal S. (eds) Anesthesia Student Survival Guide. Springer, Cham