Why can subcutaneous lidocaine cause seizures?

Why Subcutaneous Lidocaine Can Cause Seizures

Subcutaneous lidocaine causes seizures when excessive plasma concentrations reach the central nervous system, either from inadvertent intravascular injection, exceeding maximum safe doses, or rapid systemic absorption—resulting in direct neuronal excitation in the brain, particularly the amygdala. 1, 2

Mechanism of Seizure Induction

Lidocaine has a biphasic, concentration-dependent effect on the central nervous system 3:

• At therapeutic concentrations (1.5-5 mg/L): Lidocaine exhibits anticonvulsant properties by stabilizing neuronal membranes and inhibiting ionic fluxes required for impulse conduction 2
• At toxic concentrations (>6 mcg/mL free base): CNS excitation occurs, with objective adverse manifestations becoming increasingly apparent 2
• At concentrations >15 mcg/mL: Seizures frequently occur in both laboratory animals and humans 4, 3
• At arterial blood levels of 18-21 mcg/mL: Threshold for convulsive activity is reached (demonstrated in rhesus monkeys) 2

The seizures invariably originate in the amygdala in experimental models, though clinically they present as generalized tonic-clonic seizures without clear focal signs 3.

Routes to Toxic Plasma Levels from Subcutaneous Administration

1. Inadvertent Intravascular Injection

This is the most dangerous mechanism because it bypasses the slower absorption phase of subcutaneous tissue 5:

• Direct IV injection produces immediate peak plasma concentrations 5
• A case report documented acute mental status changes and generalized seizure immediately following lidocaine injection during a hematoma block, attributed to inadvertent intravascular administration 5
• Prevention: Always aspirate before each injection to avoid intravascular administration 6

2. Exceeding Maximum Safe Doses

The maximum safe dose for subcutaneous lidocaine is strictly weight-based 6, 7:

• Without epinephrine: 4.5 mg/kg maximum 6
• With epinephrine: 7.0 mg/kg maximum 6
• A pediatric case involved administering 38 mg/kg (nine times the recommended maximum of 4.5 mg/kg) over 90 minutes, resulting in toxic serum levels of 8.7 mg/L and grand mal seizures 8
• Another case involved a 4-year-old who ingested 20-25 cc of 2% lidocaine solution (400-500 mg), experiencing recurrent generalized tonic-clonic seizures 4

3. Rapid Systemic Absorption

Absorption rate varies significantly by injection site 2:

• Subcutaneous administration produces the lowest blood levels compared to other routes 2
• However, injection into highly vascular areas dramatically increases systemic absorption 6
• The presence of epinephrine reduces vascular absorption, allowing higher safe doses 6

Risk Factors That Lower the Seizure Threshold

Several patient-specific factors increase seizure risk even at lower lidocaine doses 1, 7:

• Age >70 years: Higher risk of lidocaine toxicity 1
• Cardiac conditions: Congestive heart failure, cardiogenic shock (half-life increases from 1-2 hours to >20 hours) 1
• Hepatic dysfunction: Lidocaine is metabolized almost exclusively by the liver; dysfunction prolongs half-life two-fold or more 2
• Acidemia: Lowers CNS threshold for lidocaine toxicity 2, 8
• Hypoalbuminemia: Increases free (unbound) lidocaine fraction, as 60-80% is normally protein-bound 2
• Hypercarbia: Lowers the seizure threshold to local anesthetics 8
• Concurrent CNS depressants or stimulants: Affect CNS levels required to produce systemic effects 2

Clinical Presentation of Lidocaine-Induced Seizures

CNS manifestations follow a predictable progression as plasma levels rise 1, 2:

Early Warning Signs (Lower Toxic Levels)

• Perioral numbness and facial tingling 6
• Metallic taste 1
• Lightheadedness, nervousness, apprehension 2
• Tinnitus 1
• Drowsiness (usually an early sign of high blood level) 1, 2

Progressive Toxicity (Higher Levels)

• Confusion, slurred speech 1, 7
• Blurred or double vision 2
• Muscle twitching, tremors 1, 2
• Seizures (generalized tonic-clonic) 2, 4, 5

Severe Toxicity

• Unconsciousness 2
• Respiratory depression and arrest 1, 2
• Cardiovascular collapse (bradycardia, hypotension, cardiac arrest) 2

Critical caveat: Excitatory manifestations may be very brief or absent, with drowsiness merging directly into unconsciousness and respiratory arrest 2.

Prevention Strategies

Calculate maximum allowable dose BEFORE starting the procedure 6, 7:

1. Use ideal body weight for dose calculations, not actual body weight (especially in obese patients) 1, 6
2. Reduce doses by 30% in infants <6 months 6
3. Aspirate before each injection to avoid intravascular administration 6
4. Use incremental injections rather than bolus dosing 6
5. Add epinephrine when appropriate to decrease systemic absorption and allow 55% higher safe doses 6
6. Avoid highly vascular areas or use reduced doses when injection into vascular tissue is unavoidable 6
7. Monitor continuously for early signs of toxicity (circumoral numbness, facial tingling, metallic taste) 6

Immediate Management of Lidocaine-Induced Seizures

The American Academy of Pediatrics recommends a three-step approach 7:

1. Immediately discontinue lidocaine administration 7
2. Airway management and ventilation with 100% oxygen 7
3. Seizure control with benzodiazepines: Intravenous midazolam 0.1-0.2 mg/kg 7

Conservative management is the best option for lidocaine-induced seizures 4. Multiple case reports document successful treatment with intravenous lipid emulsion for severe local anesthetic toxicity, including pediatric cases 1.

Common Pitfalls to Avoid

• Failing to convert concentrations correctly: 1% lidocaine = 10 mg/mL; 2% lidocaine = 20 mg/mL 6
• Using actual body weight instead of ideal body weight in dose calculations 1, 6
• Not tracking cumulative dose in prolonged or multistage procedures 6
• Exceeding maximum dose limits by not calculating total milligrams before starting 6, 7
• Ignoring early warning signs of toxicity (perioral numbness, tinnitus, drowsiness) 1
• Administering additional local anesthetics within 4 hours of lidocaine use without accounting for additive effects 6