Distribution of Bupivacaine in the Rabbit under Normal and Acidotic Conditions

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Abstract
SUMMARY: The tissue concentration of bupivacaine was determined under normal and acidotic conditions in ether‐anaesthetized rabbits by means of3H‐bupivacaine. The haematocrit in the blood of different organs and their blood volume were studied by a tracer technique, and the tissue concentration of bupivacaine was calculated after measurement of its concentration in arterial and mixed venous blood during infusion of3H‐bupivacaine. At the same dose rate the blood concentration in acidotic animals was significantly higher. The distribution of3H‐bupivacaine between plasma and erythrocytes was studiedin vivoand at a 200 times higher concentrationin vitro; the distribution coefficients were approximately 10 and 280, respectively. The results indicate that bupivacaine does not penetrate blood cells to any appreciable extent but thatin vivothe uptake of bupivacaine in the red blood cells is increased in acidosis. In rabbits with a normal pH the concentration of bupivacaine in the lung was 8 times, and in the liver and kidney 6 times that of the concentration in the blood, while the brain and heart showed the same concentration as in the blood. The excretion of bupivacaine in the bile was pronounced. Thin‐layer chromatography showed that the3H‐labelling was stable and that the3H‐excretion in the bile and urine emanated from3H‐bupivacaine. The lung tissue concentration decreased greatly within 20 min after termination of the infusion. In rabbits with acidosis higher bupivacaine concentration was noted in certain organs, especially the lung, where it was 5 times higher than in animals with a normal blood pH and about 25 times higher than the blood concentration in acidotic rabbits.—The uptake of bupivacaine is discussed from the aspects of nutritive flows, capillary permeability, dissociation form, tissue affinity and electrostatic forces as well as of the pH‐dependence of the tissue affinity.The importance of acidosis in the provocation of central‐nervous toxic reactions is discussed in the light of the dissociation of the bupivacaine molecule. From the results of this study it seems probable that the risk of complications in the use of local anaesthetics of the amide type increases in the presence of acidosis.