Rapid estimation of unbound lidocaine clearance in cardiac patients: implications for reducing toxicity.
The clearance (CL), volume of distribution (Vd) and elimination half-life (t1/2), based on unbound and total concentration-time data, were estimated using two serum lidocaine concentrations drawn approximately 6 and 12 hours after the initiation of continuous intravenous lidocaine therapy in nine patients with myocardial infarction (MI) (in the immediate postinfarct period) and in 12 patients with ventricular arrhythmias. No significant intergroup differences were found for any of the parameters based on unbound or total lidocaine concentration-time data. A significant (P less than .01) correlation was found between measured unbound lidocaine and unbound lidocaine concentrations predicted using alpha-1-acid glycoprotein (AAGP) and total serum lidocaine concentrations. However, the predicted values were significantly lower than the measured values for both groups (P less than .001). Significant correlations were found between total and unbound volumes of distribution and between total and unbound clearances. Coefficients of determination (r2) for these correlations were 0.6906 and 0.9178 respectively. The relationship between total and unbound clearance allows rapid estimation of unbound clearance from two total serum lidocaine concentrations. Unbound clearance can then be used to determine patient-specific maximum infusion rates and reduce the risk of central nervous system toxicity from lidocaine.