Seizure and Convulsion After Subcutaneous Lidocaine: Mechanism
The seizure occurred due to local anesthetic systemic toxicity (LAST), where lidocaine reached toxic plasma concentrations and caused central nervous system excitation by blocking inhibitory pathways in the brain before affecting excitatory pathways. 1
Mechanism of CNS Toxicity
Lidocaine causes seizures through a concentration-dependent effect on the central nervous system. At toxic plasma concentrations (typically >5-10 μg/mL), lidocaine preferentially blocks inhibitory neurons in the cerebral cortex before affecting excitatory pathways, resulting in unopposed excitatory activity that manifests as seizures. 1, 2
The FDA drug label confirms that lidocaine stabilizes neuronal membranes by inhibiting ionic fluxes required for impulse conduction, but at excessive blood levels, CNS manifestations become excitatory and may be characterized by twitching, tremors, and convulsions. 2 Research demonstrates that concentrations above 15 μg/mL frequently result in seizures in both laboratory animals and humans. 3
How Subcutaneous Administration Led to Toxicity
Even with subcutaneous administration, several factors can cause toxic plasma levels:
Dose-Related Factors
- Excessive total dose administered - The maximum safe dose without epinephrine is 4.5 mg/kg in adults. 4
- Rapid absorption from the subcutaneous site - While subcutaneous administration typically produces the lowest blood levels compared to other routes, absorption can be unpredictable, especially in highly vascular areas. 4, 2
- Inadvertent intravascular injection - Even partial intravascular injection during subcutaneous administration can cause immediate toxic levels. 2
Patient-Specific Risk Factors
The Association of Anaesthetists identifies critical patient factors that predispose to toxicity even at therapeutic doses: 1
- Hepatic dysfunction - Reduces lidocaine clearance and prolongs half-life
- Cardiac failure - Extends half-life to >4 hours (normal is 1.5-2 hours)
- Low body weight (<40 kg) - Increases plasma concentration per mg administered
- Acidemia - Increases free (unbound) lidocaine concentration
- Hypoalbuminemia - Increases free drug in plasma
- Advanced age (>70 years) - Reduced clearance
Timing of Toxicity
Lidocaine toxicity can develop rapidly within minutes after administration or may occur in a delayed fashion up to 3.5 hours later, depending on absorption kinetics and patient factors. 5 The case report literature confirms that seizures typically occur 30 minutes to 3 hours after exposure. 3
Clinical Progression of Toxicity
The Association of Anaesthetists describes a predictable progression of symptoms correlating with plasma concentrations: 1
Early signs (5-7 μg/mL):
- Perioral numbness and tingling of tongue/lips
- Tinnitus
- Light-headedness
- Slurred speech
Intermediate signs (7-10 μg/mL):
- Muscle twitching (critical warning sign)
- Confusion
- Drowsiness
Severe toxicity (>10 μg/mL):
- Seizures and convulsions
- Loss of consciousness
- Respiratory arrest
- Cardiac arrhythmias and cardiovascular collapse
Critical Clinical Pitfall
A particularly important caveat: toxicity can occur even with therapeutic dosages and undetectable serum lidocaine levels in some patients. 6 A 2024 case report documented a patient who developed perioral numbness, seizure-like activity, and confusion after a therapeutic lumbar injection despite an undetectable serum lidocaine concentration, requiring lipid emulsion therapy. 6 This demonstrates that the correlation between plasma levels and symptoms is not always linear and reflects unpredictable interactions between patient factors and drug pharmacokinetics. 7
Why Seizures Occur Before Cardiac Toxicity
Neurological symptoms appear at lower plasma concentrations than cardiovascular symptoms because lidocaine affects inhibitory CNS pathways at lower concentrations than it affects cardiac conduction. 7 This makes CNS signs the critical early warning system - muscle twitching should prompt immediate discontinuation before progression to seizures or cardiovascular collapse. 5
The FDA label confirms that excitatory CNS manifestations may be very brief or may not occur at all, in which case the first manifestation of toxicity may be drowsiness merging into unconsciousness and respiratory arrest. 2 This biphasic response explains why some patients progress directly to CNS depression without the excitatory phase.