Maximum recommended doses of local anesthetics: A multifactorial concept

Abstract

The current recommendations regarding maximum doses of local anesthetics presented in textbooks, or by the responsible pharmaceutical companies, are not evidence based (ie, determined by randomized and controlled studies). Rather, decisions on recommending certain maximum local anesthetic doses have been made in part by 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 common occurrence of central nervous system toxicity symptoms when large lidocaine doses were used in infiltration anesthesia led to the recommendation of just 200 mg as the maximum dose, which has remained unchanged for more than 50 years. In most cases, there is no scientific justification for presenting exact milligram doses or mg/kg doses as maximum dose recommendations. Instead, only clinically adequate and safe doses (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 microg/mL should be added to the local anesthetic solution when large doses are administered, providing there are no contraindications for the use of epinephrine. As a rule, conditions (eg, end-stage pregnancy, high age in epidural, or spinal block) or diseases (uremia) that may increase the rate of the initial uptake of the local anesthetic are indications to reduce the dose in comparison to one normally used for young, healthy, and nonpregnant adults. On the other hand, the reduced clearance of local anesthetics associated with renal, hepatic, and cardiac diseases is the most important reason to reduce the dose for repeated or continuous administration. The magnitude of the reduction should be related to the expected influence of the pharmacodynamic or pharmacokinetic change.

Comparison of peri- and intraarticular analgesia with femoral nerve block after total knee arthroplasty: A randomized clinical trial

“…The addition of epinephrine helps to reduce the toxicity of the local anesthetic by reducing the rate the drug is released into the circulation. The maximum tolerated doses of local anesthetics with epinephrine administered intraarticularly or by infiltration are not properly established (Rosenberg et al 2004). Our patients received an initial dose of 300 mg ropivacaine followed by 2 bolus injections of 200 mg each.…”

A Comparative Study Between Bupivacaine with Adrenaline and Carbonated Bupivacaine with Adrenaline for Surgical Removal of Impacted Mandibular Third Molar

“…Maximum single dose of bupivacaine hydrochloride with epinephrine is 175 mg 50.00 % 50.00 % 100.00 % This shows the pain on injection (deposition of local anesthetic solution) for carbonated bupivacaine with adrenaline was significantly less than bupivacaine with adrenaline. This was found to be statistically significant using Chi square test * Statistically significant (Finland), 150 mg (Germany), 100 mg (Japan), 150 mg (Sweden), 175 mg (US) [25], that is maximum of 400 mg in 24 h. Incidence of pain in first 24 h after surgical removal of impacted tooth was 21 % [9]. Period of postsurgical pain was circumscribed [6] and its intensity was maximal at 3-5 h [7] and lasted for 8-12 h [6] following surgical removal of impacted mandibular third molar.…”

Local anesthetic systemic toxicity: Continuing Professional Development

“…Hepatic enzyme systems are also immature, and LA doses should therefore be reduced by 15% in babies less than four months old. 15 Although peak plasma concentrations and protein binding remain largely unchanged in elderly patients, clearance of LAs is reduced 16 due in part to reduced organ perfusion and metabolic function. Degenerative diseases and other comorbidities are more prevalent in the elderly, and this can increase their susceptibility to the systemic effects of LA.…”

“…Dose adjustment is unnecessary in cases of mildto-moderate heart failure where tissue perfusion is preserved, but it is encouraged in advanced heart failure. 16 Conduction disorders may predispose to CVS toxicity; therefore, the use of less-cardiotoxic LAs, such as ropivacaine or levobupivacaine, is recommended in conjunction with judicious drug dosing.…”