Pharmacology

Useful Drugs

Successful choice of drug for epidural anesthesia (see Chapter 14 ) requires an understanding of the local anesthetic's potency and duration, as well as an estimation of surgical requirements and duration and postoperative analgesia requirements. As with any regional anesthetic, the surgeon, anesthesiologist, procedure, and anesthetic technique must all be included in the drug-choice equation.

Drugs available for epidural use can be categorized as short-, intermediate-, and long-acting local anesthetics, and with the addition of epinephrine to these agents, surgical anesthesia ranging from 45 to 240 minutes is possible ( Table 43-8 ). Chloroprocaine, an ester local anesthetic, is a short-acting agent that was associated with neurotoxicity (i.e., adhesive arachnoiditis) when unintentionally injected in large volumes subarachnoid before a formulation change.^{[143] [144]} Since 1985, reduced bisulfate concentrations have been available; since 1987, bisulfate-free 2-chloroprocaine has been available; and since 1996, preservative-free 2-chloroprocaine has been available. Since these formulation changes, there have not been reports of neurotoxicity attributable to 2-chloroprocaine until recently. Winnie and Nader^[145] highlighted that in this era of increasing drug costs, some hospitals are substituting generic formulations of anesthetic drugs, and in one situation, metabisulfite-containing 2-chloroprocaine was returned to anesthesia stock without knowledge of the physicians. We all must be aware of the solutions we are using, because this type of substitution is likely to increase.

In the era of ever-increasing numbers of surgical outpatients, combining 2-chloroprocaine and a catheter technique allows an efficient matching of surgical procedure and duration of epidural analgesia and enables patients to spend a minimal recovery time in the facility. It is available in 2% and 3% concentrations, with the latter preferable for

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There is evidence that back pain developing after larger volumes (>25 mL) of 2-chloroprocaine was related to the EDTA used as a preservative in the chloroprocaine.^[146] It appears that the preservative-free chloroprocaine is not associated with back pain in larger doses at the same frequency.

Lidocaine is the prototypical amide local anesthetic and is used epidurally in 1.5% to 2% concentrations. Mepivacaine is similar to lidocaine in the concentrations necessary for epidural anesthesia and lasts 15 to 30 minutes longer. Epinephrine prolongs the duration of surgical anesthesia by approximately 50% with lidocaine and mepivacaine.^[111] Another additive to these drugs that may influence clinical use is fentanyl, an intermediate-acting, amide drug for epidural use. When fentanyl was added to mepivacaine, it accelerated the onset of analgesia and enhanced the analgesic effect during epidural anesthesia. ^[147] One technique receiving more attention to minimize length of an epidural motor block after surgery is completed is the use of saline in 15 to 30 mL volumes through the epidural catheter before it is removed. ^[148]

Bupivacaine is the most widely used long-acting local anesthetic; it is used in 0.5% and 0.75% concentrations for surgical anesthesia. Analgesic techniques can be performed with concentrations from 0.125% to 0.25%. Its duration of action is less consistently prolonged by addition of epinephrine, although up to 240 minutes of surgical anesthesia can be obtained when epinephrine is added. In 1983, the FDA stated that 0.75% bupivacaine was no longer recommended in obstetric anesthesia as a result of a perception that systemic toxicity with that concentration resulted in more difficult resuscitations than occurred with the lower concentrations. The evidence for this action remains controversial, although it does appear that bupivacaine and etidocaine are more likely to impair myocardial performance and conduction than other local anesthetics when systemic toxicity occurs.^{[149] [150]}

Ropivacaine is increasing in use as an epidural agent. It is used in 0.5% to 1.0% concentrations for surgical anesthesia and 0.1% to 0.3% concentrations for analgesia. Animal evidence supports the concept that ropivacaine has less impact on cardiac conduction and arrhythmia frequency with blood levels found during local anesthetic-induced systemic toxicity.^[151] In an individual patient, the clinical effect of ropivacaine is difficult to separate from a similar effect from bupivacaine, although it appears to produce less motor block and has a slightly shorter duration of action than bupivacaine.^[152] However, it is the only local anesthetic still in use that has a vasoconstrictive property at clinically used concentrations.

Levobupivacaine is also used as an epidural local anesthetic in 0.5% to 0.75% concentrations for surgical anesthesia, and analgesic techniques can be performed with concentrations from 0.125% to 0.25%. In an individual patient, the clinical anesthetic effect from the drug is indistinguishable from racemic bupivacaine. ^[153] Similar to ropivacaine, animal evidence supports the concept that levobupivacaine has less impact on cardiac conduction and arrhythmia frequency with blood levels found during local anesthetic-induced systemic toxicity.

Etidocaine is an infrequently used epidural anesthetic, principally because of the perception and some data supporting that motor block is more profound than sensory block with the drug.^[154] The reason for this may be that etidocaine is less effective than bupivacaine in producing small-fiber blockade.^[155]

Additives

Some investigators advocate combining agents with local anesthetics to make epidural anesthesia last longer, to improve the quality of blockade, or to accelerate onset of block. Epinephrine increases the duration of useful anesthesia with all the agents, although the proportional effect is greatest with lidocaine, mepivacaine, and 2-chloroprocaine; shows a lesser effect with bupivacaine, levobupivacaine, and etidocaine; and has a limited effect with ropivacaine (see Table 43-8 ). Phenylephrine has been used in epidural anesthesia less widely than in spinal anesthesia, perhaps because it does not reduce peak blood levels of local anesthetic as effectively as epinephrine during epidural use.^[156]

Carbonation of the local anesthetic solution has been suggested as a means of increasing speed of onset and quality of block by producing more rapid intraneural diffusion and more rapid penetration of connective tissue surrounding the nerve trunk.^{[157] [158]} Some data suggest that there are no clinical advantages for carbonated solutions, ^[159] and some disadvantages may occur more rapidly because peak blood levels of the drug are higher after carbonation of the local anesthetic and blood pressure decreases^{[160] [161]} (see Chapter 14 ).

The addition of bicarbonate has also been suggested as a means of increasing the pH of local anesthetic solution, increasing the concentration of nonionized free base, which theoretically increases the rate of diffusion of the drug and speed onset of block. Clinically, the addition of 1 mEq of sodium bicarbonate to each 10 mL of commercially prepared 1.5% lidocaine solution produces a significantly faster onset of anesthesia and more rapid spread of sensory block.^[162] In addition to speeding the onset of the block, there is evidence that a more complete block may be produced.^[163] The clinical applicability of this modification should be considered individually on its merits by each institution's anesthesia group.

Another alteration of drugs for epidural use involves combining long- and short-acting drugs, theoretically to gain the benefits of each. This practice does not seem necessary or prudent because familiarity with the local anesthetics and additives available allows a spectrum of block lengths to be produced. Moreover, the purported advantage of faster onset with the combinations of local anesthetics seems clinically inconsequential.