Lidocaine - maximum dose
Fråga: A doctor lecturing at the university has compared the British National Formulary (BNF) with the Norwegian Felleskatalog (FK) regarding lidocaine for skin infiltration. BNF states that the maximum dose for adults is 200 mg without epinephrine (adrenaline) and 500 mg with epinephrine. For children between 1 and 12 years recommended dose is 3mg/kg without epinephrine, but it is unclear what to do with epinephrine. According to FK, themaximum dose for adults is 400 mg without epinephrine and 400mg with epinephrine, for children - 5mg/kg without epinephrine and 7 mg/kg with epinephrine. The doctor is particularly worried about the paediatric dose without epinephrine, and refers to an article from 2003: http://emj.bmj.com/content/21/2/249.full. The doses are different in each country. What would RELIS recommend for adult and children, for both preparations?
Svar: According to Summary of Product Characteristics for lidocaine-only products marketed in Norway, the maximum dose for children <12 years is 5 mg/kg. The dose must not be repeated more than four times within 24 hours (1). Miromedex refers to product information stating that in children over 3 years of age with normal lean body mass and body development, the maximum dose is determined by age and weight (3.3 to 4.4 mg/kg) (2). According to WHO, the maximum cumulative safe doses of lidocaine for both adults and children (1-12 years) are 4 mg/kg, and 7 mg/kg with epinephrine (3).
We have in identified different recommended maximum doses in product summaries and formularies (1,2,3), but we have been unable to find any scientific justification to limit the paediatric dosing to 3 or 5 mg/kg.
Recommendations on maximum local anesthetic doses have been based on extrapolations from animal experiments, clinical experiences from the use of various doses and measurement of blood concentrations, case reports of local anesthetic toxicity, and pharmacokinetic results (). The recommendation of just 200 mg as the maximum dose has remained unchanged for more than 50 years. According to a review, there is no scientific justification for presenting exact milligram doses or mg/kg doses as maximum dose recommendations. Clinically adequate and safe dose ranges that are block specific are justified, taking into consideration the site of local anesthetic injection and patient-related factors such as age, organ dysfunctions, and pregnancy, which may influence the effect and the pharmacokinetics of the local anesthetic. Epinephrine in concentrations of 2.5 to 5 µg/mL should be added to the local anesthetic solution when large doses are administered, providing there are no contraindications for the use of epinephrine (4).
The referenced article is based on a British case report of a 7 weeks old infant that developed a series of generalised seizures 20–30 minutes after a dorsal penile nerve block were 6,7 mg/kg lidocaine had been administered. The occasion was a circumcision performed by a family general practitioner. A paramedic crew administered oxygen and intravenous benzodiazepines at the appropriate dose, and the patient recovered without complications. It was assumed that lidocaine was the triggering factor. The authors state that the maximum safe dose of lidocaine is 3 mg/kg, but without giving any reference for this statement (5).
Arrhythmias, cardiac arrest, and transient neuropathic symptoms have been reported in children using local anaestethics (5). Even toxic effects in children of topical lidocaine preparations have been reported, among them seven deaths in children younger than six years old (6).
Conclusion
It is probable that lidocaine can cause severe toxic effects, including death in children. However, although lidocaine is widely used, these are extremely rare events. Also serious allergic reactions due to lidocaine occur very rarely.
There is insufficient evidence to conclude that a maximum lidocaine dosing of 3 mg/kg is more adequate than 5 mg/kg in children. We therefore find it acceptable to follow the 5 mg/kg as maximum recommendation in line with the Norwegian SPCs.
Lidocaine should be considered a safe local anaesthetic in children when used correctly. However, since serious toxic and even lethal effects in paediatric patients cannot be excluded, it is important that doses are kept at the lowest possible level. To reduce the risk of accidental excess dosing, the equivalent maximum dose in milliliters should be calculated in each case. Special attention should be paid to the lidocaine concentration in the vial, since this might vary.
In infiltration anaesthesia, epinephrine seems to limit the toxicity of lidocaine. We recommend the use of lidocaine-epinephrine combinations whenever possible.
Our best advice is to keep doses for both children and adults below the maximum given in the SPCs approved by The Norwegian Medicines Agency.
- Statens legemiddelverk. Preparatomtale (SPC) Xylocain. http://www.legemiddelverket.no/legemiddelsok (Sist oppdatert: 20.08.2014).
- Micromedex® 2.0 (online). Lidocaine hydrochloride (Drugdex System). http://www.helsebiblioteket.no/ (Sist oppdatert: 09. november 2015).
- WHO. WHO Model Prescribing Information: Drugs Used in Anaesthesia. Lidocaine. http://apps.who.int/medicinedocs/en/d/Jh2929e/5.2.html (03.11.2015).
- Rosenberg PH, Veering BT etal. Maximum Recommended Doses of Local Anesthetics: A Multifactorial Concept. Reg Anesth Pain Med 2004; 29(6): 564-75.
- Donald MJ, Derbyshire S. Lignocaine toxicity; a complication of local anaesthesia administered in the community. Emerg Med J 2004; 21(2), 249-50.
- Curtis LA, Dolan TS et al. Are one or two dangerous? Lidocaine and topical anesthetic exposures in children. J Emerg Med 2009; 37(1): 32-9.