Why does oral lidocaine (local anesthetic) injection cause systemic jitters?

Why Oral Lidocaine Injection Causes Systemic Jitters

Systemic jitters from oral lidocaine injection occur due to central nervous system (CNS) toxicity when plasma levels exceed therapeutic thresholds, resulting from either inadvertent intravascular injection, excessive dosing, or rapid systemic absorption from highly vascular oral tissues. 1

Mechanism of CNS Toxicity

Lidocaine has an extremely narrow therapeutic window, with CNS toxicity beginning at plasma levels only slightly above therapeutic concentrations. 1 The drug affects multiple receptor systems in a concentration-dependent manner:

• At therapeutic concentrations, lidocaine blocks muscarinic (M1, M3) and NMDA receptors 1
• At near-toxic concentrations, many additional receptor types become affected including Nav1.8/1.7, nicotinic cholinergic receptors, voltage-gated calcium channels, and others 1
• The correlation between plasma levels and toxicity symptoms is not linear, making toxicity unpredictable even with appropriate dosing 1

Why Oral Injections Are High-Risk

The oral cavity presents unique risks for systemic absorption:

• Highly vascular tissues in the oral mucosa allow rapid systemic absorption 2
• Inadvertent intravascular injection can occur during oral procedures, leading to immediate toxic plasma levels 1
• Systemic absorption is an inherent risk with oral infiltration techniques that are not standardized 1

Clinical Presentation of Early CNS Toxicity

Early neurologic symptoms of lidocaine toxicity include:

• Lightheadedness and dizziness 1
• Perioral numbness 2
• Tinnitus (ringing in ears) 2, 3
• Metallic taste 2
• Visual disturbances 1, 2
• Confusion and disorientation 1

These symptoms represent the initial manifestations before progression to more severe toxicity including seizures and cardiovascular collapse. 2, 4

Critical Dosing Considerations

• Maximum recommended dose is approximately 4.5 mg/kg to avoid toxicity 5
• CNS toxicity starts at plasma levels above 6.0 mcg/mL free base, with objective adverse manifestations becoming increasingly apparent 6
• Convulsive threshold in primates occurs at arterial blood levels of 18-21 mcg/mL 6
• Even doses as low as 1 mg/kg IV have been reported to cause convulsions in susceptible patients 4

Patient-Specific Risk Factors

Certain conditions dramatically increase toxicity risk by impairing lidocaine clearance:

• Congestive heart failure 7
• Hepatic dysfunction (prolongs half-life two-fold or more) 6, 7
• Renal dysfunction (increases metabolite accumulation) 6
• Low body mass index 8
• Concurrent use of medications interfering with hepatic metabolism 8
• Acidosis 6

Common Pitfalls to Avoid

The most dangerous scenario is inadvertent intravascular injection during oral procedures, which delivers the entire dose directly into systemic circulation, bypassing first-pass metabolism and immediately achieving toxic plasma levels. 1 This has been documented with:

• Tachycardia occurring in 1 out of 25 patients during glossopharyngeal nerve blocks 1
• Cardiac arrhythmias in 6 out of 30 patients receiving bupivacaine infiltration (similar mechanism) 1

Always aspirate before injection and use the lowest effective dose, as the therapeutic index is inherently low regardless of technique. 1

Immediate Management

Lipid emulsion 20% should be readily available wherever lidocaine is used, and all staff must know its location for immediate treatment of systemic toxicity. 1