Maximum Safe Dose of Local Anesthetics When Used in Combination
When multiple local anesthetics are used in combination, the maximum safe dose should be calculated as a fraction of each drug's individual maximum allowable dose to prevent toxicity.
Understanding Local Anesthetic Toxicity Risk
Local anesthetics are cardiac depressants that can cause central nervous system effects ranging from excitation to depression. When using multiple local anesthetics simultaneously, their toxicity effects are additive, requiring dose adjustments to maintain safety.
Maximum Dose Guidelines for Individual Agents
According to the American Academy of Pediatrics guidelines 1, the maximum safe doses for commonly used local anesthetics are:
| Agent | Maximum Dose with Epinephrine | Maximum Dose without Epinephrine |
|---|---|---|
| Lidocaine | 7.0 mg/kg | 4.4 mg/kg |
| Bupivacaine | 3.0 mg/kg | 1.3-2.5 mg/kg |
| Ropivacaine | 3.0 mg/kg | 2.0 mg/kg |
| Mepivacaine | 7.0 mg/kg | 4.4-5.0 mg/kg |
Calculating Combined Maximum Doses
When using multiple local anesthetics together, their toxicity is additive. Therefore:
- Calculate the fraction of maximum dose for each agent
- Ensure the sum of these fractions does not exceed 1 (or 100%)
Formula for Combined Use
- Fraction of maximum dose = (Actual dose used ÷ Maximum allowable dose) for each agent
- Sum of all fractions should be ≤ 1
Example Calculation
If using lidocaine and bupivacaine together without epinephrine:
- Lidocaine used: 2 mg/kg (out of max 4.4 mg/kg) = 0.45 or 45% of max dose
- Bupivacaine used: 1 mg/kg (out of max 2.5 mg/kg) = 0.4 or 40% of max dose
- Total: 0.45 + 0.4 = 0.85 or 85% of combined maximum dose
Special Considerations
- Pediatric patients: Doses of amide local anesthetics should be decreased by 30% in infants younger than 6 months 1, 2
- Vascular areas: Lower doses should be used in highly vascular areas due to increased risk of systemic absorption 1, 2
- Enhanced sedative effects: There may be enhanced sedative effects when the highest recommended doses of local anesthetic drugs are used in combination with other sedatives or opioids 1
Safety Precautions
- Calculate maximum dose before administration to prevent toxicity
- Monitor for signs of toxicity:
- Early: circumoral numbness, facial tingling, slurred speech
- Progressive: seizures, CNS depression, cardiac depression
- Have resuscitation equipment readily available, including 20% lipid emulsion for treatment of local anesthetic toxicity 1
- Aspirate before injection to minimize risk of intravascular administration 3
Clinical Implications
Research comparing mixtures of local anesthetics (such as bupivacaine with lidocaine) shows that while combinations may provide faster onset of action, they do not necessarily provide better overall anesthesia 4, 5, 6. The primary benefit of combining agents is to balance onset time with duration of action, not to increase the total allowable dose.
The additive nature of local anesthetic toxicity means clinicians must be vigilant about calculating the fractional dose of each agent used and ensuring their sum remains within safe limits to prevent potentially life-threatening complications.