What is the toxic dose of lidocaine (local anesthetic) with and without epinephrine (adrenaline)?

Toxic Dose of Lidocaine With and Without Epinephrine

The maximum safe dose of lidocaine is 7 mg/kg (up to 500 mg) when combined with epinephrine, and 4.5 mg/kg (up to 300 mg) when used without epinephrine in adults. 1, 2, 3

Adult Dosing Guidelines

With Epinephrine (1:100,000 or 1:200,000)

• Maximum dose: 7 mg/kg, not to exceed 500 mg total 1, 2
• For a 70 kg adult, this allows up to 490 mg (49 mL of 1% lidocaine solution) 4
• Duration of action: 90-200 minutes 1, 4

Without Epinephrine

• Maximum dose: 4.5 mg/kg, not to exceed 300 mg total 1, 2, 3
• Duration of action: 60-90 minutes 2
• The lower maximum reflects faster systemic absorption without vasoconstriction 2

Pediatric Dosing Guidelines

With Epinephrine

• Maximum dose: 3.0-4.5 mg/kg 1, 2
• Doses should be reduced by 30% in infants younger than 6 months 1

Without Epinephrine

• Maximum dose: 1.5-2.0 mg/kg 2
• For children under 10 years, use standard pediatric formulas (e.g., Clark's rule) to calculate appropriate dosing 3

Critical Safety Considerations

Plasma Concentration Thresholds

• Toxic plasma levels begin at approximately 6 μg/mL 1, 5
• Serious toxicity (CNS depression, convulsions, hypotension) occurs at 9-10 μg/mL 1
• Research demonstrates that doses up to 28 mg/kg without epinephrine and 45 mg/kg with epinephrine (in tumescent technique) remain below toxic thresholds, though these higher doses are not recommended for standard infiltration 5

Important Caveat About Epinephrine

When lidocaine is administered intravascularly (accidental IV injection), epinephrine paradoxically decreases the toxic threshold and reduces time to seizure onset by 11-21%. 6, 7 This is the opposite effect compared to tissue infiltration, where epinephrine increases safety by slowing systemic absorption. This underscores the critical importance of aspirating before every injection. 1, 2

Duration-Dependent Toxicity Risk

• For infusions lasting >12 hours, lidocaine exhibits non-linear pharmacokinetics with prolonged half-life (3.22 hours vs. 100 minutes) 1
• After 24 hours of continuous infusion, reduce the rate by approximately 50% even in patients without organ dysfunction 1
• Plasma accumulation occurs with repeated epidural injections, with peak concentrations increasing from 2.30 μg/mL after the first dose to 4.11 μg/mL after the third dose 8

Patient-Specific Dose Reductions

Reduce doses in the following conditions:

• Hepatic dysfunction: Decreased lidocaine clearance requires dose reduction for repeated or continuous administration 1, 9
• Cardiac failure: Impaired hepatic blood flow reduces metabolism 1, 9
• Hypoalbuminemia: Increases free drug concentration in plasma 1
• Low body weight/reduced muscle mass: Less reservoir for local anesthetic storage 1
• Acidemia: Increases dissociation from plasma proteins 1
• Drug interactions: Beta-blockers and amiodarone reduce lidocaine metabolism and clearance 1

High BMI patients

• Calculate dose using ideal body weight, not actual weight, to avoid inadvertently higher plasma concentrations 1

Signs of Lidocaine Toxicity

Early CNS symptoms (in order of appearance):

• Circumoral numbness 4, 2
• Facial tingling 4, 2
• Metallic taste 4, 2
• Auditory changes 4, 2
• Slurred speech 4, 2

Advanced toxicity:

• Seizures 1, 2
• CNS depression 1, 2
• Cardiac arrest 2

Risk Mitigation Strategies

• Always aspirate before injection to avoid intravascular administration 1, 2
• Use the lowest effective dose and concentration 3, 9
• Inject slowly with frequent aspiration, especially in vascular tissues 1
• Monitor vital signs every 5 minutes when using high doses 1
• Have 20% lipid emulsion immediately available when using long-acting agents (bupivacaine, ropivacaine) in vascular areas 1
• Avoid cumulative dosing within 4 hours of other local anesthetic interventions 4
• Add epinephrine (2.5-5 μg/mL) when administering large doses, unless contraindicated 9

Common Pitfalls to Avoid

• Using actual body weight instead of ideal body weight in obese patients leads to overdosing 1
• Failing to account for cumulative doses from multiple injection sites 1
• Not reducing doses for prolonged infusions beyond 12-24 hours 1
• Ignoring drug interactions with beta-blockers, amiodarone, and CYP450 inhibitors 1
• Applying excessive topical doses to mucosal surfaces where systemic uptake is rapid 1