The Influence of a Right-to-left Cardiac Shunt on Lidocaine Pharmacokinetics

The pharmacokinetics of lidocaine were studied in 1-2-month-old lambs with surgically created, intracardiac right-to-left shunts (RLS) and in age-matched control lambs. Shunts were prepared by anastomosing the pulmonary artery to the left atrial appendage to achieve arterial oxygen saturation of 65-75%. Catheters were implanted both in the right atrium for drug infusion and in the ascending aorta for blood sampling. Lidocaine, 1 mg/kg, injected as a rapid bolus, or 12 mg/kg, injected as a continuous infusion over 15 min, was delivered into the right atrium. Serial samples of arterial blood were obtained every 2.5 s for 1 min following the bolus injection and up to 4 h following the continuous infusion. Samples were analyzed for lidocaine by gas chromatography. Peak arterial whole blood concentration of lidocaine in the shunted animals was 37.0 +/- 2.1 micrograms/ml compared to 21.1 +/- 0.1 microgram/ml in the control animals; P less than .01. The peak arterial concentrations during the lidocaine infusion were 12.6 +/- 3.5 micrograms/ml in the RLS and 5.8 +/- 1.5 micrograms/ml in the controls. Total body clearance of lidocaine was decreased in the shunted animals to 30.7 +/- 13.2 ml.kg-1.min-1 from 68.1 +/- 12.1 ml.kg-1.min-1 in the control animals; P less than .001. The steady-state volume of distribution was also decreased in the shunted animals, 1.0 +/- 0.2 l/kg versus 2.0 +/- 0.7 l/kg in the controls; P less than .02. To induce convulsions 4.75 +/- 0.46 mg/kg of lidocaine was required in the shunted animals and 7.37 +/- 0.44 mg/kg in the control animals (P less than .001).(ABSTRACT TRUNCATED AT 250 WORDS)