Article Text
Abstract
The risk of accidental intravascular injection and consequent acute toxicity is ever-present with most neural blockade techniques. The severity of cardiovascular and central nervous system (respectively, CVS and CNS) toxicity is directly related to the local anesthetic potency, dose, and rate of administration. Nonetheless, although the anesthetic potency of ropivacaine and levobupivacaine is similar to that of bupivacaine, at usual clinical doses, ropivacaine and levobupivacaine are less likely than bupivacaine to cause convulsions or lethal dysrhythmias. Signs of CNS stimulation, ranging from tremors to convulsions and perhaps cardiac dysrhythmias, can be described in terms of a chaos-derived state change in which the local anesthetic appears to act as an initiator. Both CNS and CVS effects are rather poorly correlated with arterial drug concentrations but better correlated with concentrations in the respective regional venous drainage. Lung uptake reduces the maximum drug concentration by ˜40%. Prolonging intravenous administration from 1 to 3 minutes results in a similar decrease in maximum concentration. This is an underlying tenet of dose fractionation, but the main advantage of dose fractionation is that the anesthesiologist is able to cease administration with less of the dose given if signs or symptoms of toxicity occur. Overall, it appears that the gains in safety from ropivacaine and levobupivacaine are due more to favorable pharmacodynamic enantioselectivity than to pharmacokinetic factors. This essay presents some pharmacokinetic aspects relevant to acute toxicity of local anesthetics, mainly using data from the authors' studies in a sheep model of simulated accidental intravenous administration.
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Footnotes
See Editorial page 513