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The authors studied the effect of changes in arterial carbon dioxide tension on plasma lidocaine concentrations during a constant lidocaine infusion in eight healthy volunteers. With a PaCO2 of 41.4 +/- 0.9 mmHg (mean +/- SE), total plasma lidocaine concentrations were 3.97 +/- 0.20 microgram X ml-1. There was no significant change associated with hypercarbia (PaCO2 = 55.7 +/- 1.5 mmHg, lidocaine = 3.93 +/- 0.18 microgram X ml-1) or hypocarbia (PaCO2 = 19.5 +/- 1.4 mmHg, lidocaine = 4.29 +/- 0.25 microgram X ml-1), despite the known effects of changes in CO2 tension on hepatic blood flow and lidocaine protein binding. During hypercarbia, plasma lidocaine binding decreases while total plasma lidocaine remains essentially constant; therefore, increased CO2 tensions could cause toxicity if total lidocaine concentrations were in the high therapeutic range (5 micrograms X ml-1). Four subjects experienced transient symptoms of mild lidocaine toxicity during acute increases in carbon dioxide tension.

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