PHARMACOKINETICS

The concentration of local anesthetics in blood is determined by the amount injected, the rate of absorption from the site of injection, the rate of tissue distribution, and the rate of biotransformation and excretion of the specific drug. Patient-related factors such as age, cardiovascular status, and hepatic function influence the physiologic disposition and the resultant blood concentration of local anesthetics.

Absorption

The systemic absorption of local anesthetics is determined by the site of injection, the dosage and volume, the addition of a vasoconstrictor agent, and the pharmacologic profile of the agent itself. A comparison of the blood concentration of local anesthetics after various routes of administration reveals that the anesthetic drug level is highest after intercostal nerve blockade, followed in order of decreasing concentration by injection into the caudal epidural space, lumbar epidural space, brachial plexus, and subcutaneous tissue.^[98] When a local anesthetic solution is distributed to an area of greater vascularity, a greater rate and degree of absorption occur. This relationship is of clinical significance because the use of a fixed dose of a local anesthetic may be potentially toxic in one area of administration but not in others. For example, the use of 400 mg of lidocaine without epinephrine for an intercostal nerve block results in an average peak venous plasma level of approximately 7 µg/mL, which is sufficiently high to cause symptoms of central nervous system (CNS) toxicity in some patients.^[98] By comparison, this same dose of lidocaine used for brachial plexus block yields a mean maximum blood level of approximately 3 µg/mL, which is rarely associated with signs of toxicity.

The maximum blood level of local anesthetics is related to the total dose of drug administered for any particular site of administration. For most drugs, a proportionality exists between the amount of drug administered and the resultant peak anesthetic blood levels.^[99] Higher blood levels also follow from the administration of larger volumes of a correspondingly dilute solution than from the same dose in a smaller volume.

Local anesthetic solutions frequently contain a vasoconstrictor, usually epinephrine, in concentrations varying from 5 to 20 µg/mL. Epinephrine decreases the rate of vascular absorption of certain drugs from various sites of administration and thus lowers their potential systemic toxicity. A 5-µg/mL dose of epinephrine (1:200,000) significantly reduces the peak blood levels of lidocaine and mepivacaine, irrespective of the site of administration. Peak blood levels of bupivacaine and etidocaine are minimally influenced by the addition of a vasoconstrictor after injection into the lumbar epidural space.^[100] However, epinephrine will significantly reduce the rate of vascular absorption of these drugs when used for peripheral nerve blocks such as brachial plexus blockade. ^[101]

Differences also exist in the rate of absorption of various local anesthetics. For example, a comparison of drugs

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