Modification of lidocaine protein binding with CO2

Area of Science:

• Biochemistry
• Pharmacology
• Clinical Chemistry

Background:

• Lidocaine is a common local anesthetic and antiarrhythmic drug.
• The binding of lidocaine to plasma proteins influences its distribution and toxicity.
• Hypercarbia, or elevated carbon dioxide levels, is known to increase the risk of lidocaine toxicity.

Purpose of the Study:

• To investigate the effect of varying carbon dioxide tension (pCO2) on the fractional binding of lidocaine to human plasma proteins.
• To determine the relationship between pCO2 and unbound lidocaine concentration at both therapeutic and toxic levels.

Main Methods:

• Utilized specially designed ultrafiltration devices for sample separation.
• Employed an enzyme immunoassay technique for quantifying lidocaine.
• Tonometered human serum samples at 37°C across a range of CO2 tensions (0.13–10.7 kPa).

Main Results:

• A linear correlation was observed between increasing pCO2 and the fraction of unbound lidocaine (r = 0.93, p < 0.001).
• This effect was consistent across both therapeutic (2.2 µg/mL) and toxic (6.8 µg/mL) lidocaine concentrations.
• The fraction of unbound lidocaine increased significantly with elevated CO2 levels.

Conclusions:

• Elevated carbon dioxide tension directly increases the unbound fraction of lidocaine in human plasma.
• This mechanism provides a biochemical explanation for the enhanced central nervous system toxicity of lidocaine observed in patients with hypercarbia.
• Understanding this interaction is crucial for managing lidocaine therapy, especially in conditions involving respiratory compromise.