Effects of pronounced haemodilution on the plasma protein binding of lidocaine

The effects of pronounced haemodilution on the protein binding of lidocaine was investigated in vitro in plasma from five healthy adult volunteers. The plasma was diluted with a phosphate buffer to reach a plasma protein concentration normally seen during paediatric cardiopulmonary bypass (CPB) and protein binding was determined at a low (1.5 micrograms/ml) and a moderate (4 micrograms/ml) total plasma concentration of lidocaine. The effects of different haematocrits on plasma protein binding was also determined over the haematocrit range 20-60%. The binding of lidocaine was found to be inversely related to the degree of dilution, i.e. the free fraction increased significantly with increasing dilution (p < 0.0001). Furthermore, the binding was dependent on the total plasma concentration of lidocaine, since a significantly higher percentage of free drug was found at the higher total lidocaine level (4 micrograms/ml) compared with the lower level (1.5 micrograms/ml) (p < 0.05). No significant difference in the free fraction of lidocaine could be found over the studied haematocrit range. The results of the present study indicate that plasma protein levels commonly associated with CPB in neonates and infants are associated with a significant increase in the free, unbound and pharmacologically active fraction of lidocaine compared with normal conditions. The use of commonly recommended dosages of lidocaine might result in toxic-free concentration in this setting.