The influence of acidosis on the distribution of lidocaine and bupivacaine into the myocardium and brain of the sheep

To test the hypothesis that acidosis can increase the toxicity of bupivacaine more than that of lidocaine by increasing the distribution into the brain, myocardium, or both, studies were performed to measure the in vivo tissue:blood partition coefficients during continuous steady state intravenous infusions of these agents in anesthetized sheep during normal acid-base status and during combined respiratory-metabolic acidosis. Acidosis decreased the partition coefficient of both agents into the myocardium and that of bupivacaine into the brain but did not systematically change that of either agent into skeletal muscle or fat. Total body and hepatic drug clearances were not affected systematically, but plasma binding of both agents was decreased. Thus predictions based on the pH partition hypothesis about the effects of acidosis on myocardial:blood partition coefficients being a basis for explaining the relative toxicity of these agents were not supported.