No abstract

Local anesthetics can be administered by local or regional injection to provide anesthesia during surgery. Regional injection of local anesthetics is used for major nerve block and for spinal (subarachnoid) or epidural block. Although local anesthetics are among the most widely used anesthetic agents and have a good record of clinical safety, questions about their toxicity have recently been raised.The amide local anesthetics (lidocaine, mepivacaine, and bupivacaine) have replaced the esters (e.g., procaine) because of their stability and the fact that they do not cause allergic reactions. Because of its high lipid solubility and high affinity for nonspecific protein-binding sites, bupivacaine has a much longer duration of action than the other amides. However, the avid binding of bupivacaine to nonspecific cardiac protein-binding sites after an unintentional intravenous injection may lead to profound myocardial depression and intractable cardiac arrest. With other amides, such as lidocaine, central nervous system effects after an excessive dose or an unintended intravenous injection occur at a much lower blood level (8 to 10 m g per milliliter) than that associated with cardiovascular toxic effects (20 m g per milliliter). Central nervous system toxic effects caused by local anesthetics can be controlled with the intravenous administration of benzodiazepines (midazolam or diazepam) or thiobarbiturates (thiopental) and protection of the patient's airway and management of ventilation. Toxic effects in the central nervous system and cardiovascular system occur at the same blood level of bupivacaine (3 to 5 m g per milliliter). Prolonged resuscitation and repeated administration of epinephrine may not restore cardiac function. Reports of profound cardiovascular depression have been associated, for the most part, with the use of a higher concentration of bupivacaine (0.75 percent). Consequently, this concentration is not recommended for routine use.Ropivacaine is a new amide local anesthetic with a duration of action similar to that of bupivacaine. 101 Its pharmacokinetic properties are also similar to those of bupivacaine, 102 although ropivacaine is less lipid-soluble and therefore less potent. Stereoisomerism is not present with ropivacaine but is present with bupivacaine. The R (rectus) isomer of bupivacaine stays in the sodium channel for a prolonged period, which may result in cardiotoxic effects. 103 The S (sinister) isomer of bupivacaine stays in the cardiac sodium channel for a shorter period. Thus, it is hypothesized that ropivacaine has clinical pharmacologic characteristics similar to those of bupivacaine but without cardiotoxic effects. This hypothesis is supported by studies of isolated perfused rabbit hearts, which have shown that bupivacaine has stronger cardiodepressant and arrhythmogenic effects than either lidocaine or ropivacaine. 104 Lidocaine has been used for spinal and epidural anesthesia for decades because of the rapid onset and predictable duration of its action. Recent modifications of t...