Drugs

Not all procedures and physicians are created equal, at least regarding the amount of time needed to complete an operation. If anesthesiologists are to use regional techniques effectively, they must be able to choose a local anesthetic that lasts the right amount of time. To do this, they understand the local anesthetic timeline from the shorter-acting to the longer-acting agents (Fig. 1-1).

Figure 1-1. Local anesthetic timeline (length in minutes of surgical anesthesia).

All local anesthetics share the basic structure of aromatic end, intermediate chain, and amine end (Fig. 1-2). This basic structure is subdivided clinically into two classes of drugs, the amino esters and the amino amides. The amino esters possess an ester linkage between the aromatic end and the intermediate chain. These drugs include cocaine, procaine, 2-chloroprocaine, and tetracaine (Figs. 1-3 and 1-4). The amino amides contain an amide link between the aromatic end and the intermediate chain. These drugs include lidocaine, prilocaine, etidocaine, mepivacaine, bupivacaine, and ropivacaine (see Figs. 1-3 and 1-4).

Figure 1-2. Basic local anesthetic structure.

Figure 1-3. Local anesthetics commonly used in the United States. A, Amides. B, Esters.

Figure 1-4. Chemical structure of commonly used amino ester and amino amide local anesthetics.

Amino Esters

Cocaine was the first local anesthetic used clinically, and it is used today primarily for topical airway anesthesia. It is unique among the local anesthetics in that it is a vasoconstrictor rather than a vasodilator. Some anesthesia departments have limited the availability of cocaine because of fears of its abuse potential. In those institutions, mixtures of lidocaine and phenylephrine rather than cocaine are used to anesthetize the airway mucosa and shrink the mucous membranes.

Procaine was synthesized in 1904 by Einhorn, who was looking for a drug that was superior to cocaine and other solutions in use. Currently, procaine is seldom used for peripheral nerve or epidural blocks because of its low potency, slow onset, short duration of action, and limited power of tissue penetration. It is an excellent local anesthetic for skin infiltration, and its 10% form can be used as a short-acting (i.e., lasting <1 hour) spinal anesthetic.

Chloroprocaine has a rapid onset and a short duration of action. Its principal use is in producing epidural anesthesia for short procedures (i.e., lasting <1 hour). Its use declined during the early 1980s after reports of prolonged sensory and motor deficits resulting from unintentional subarachnoid administration of an intended epidural dose. Since that time, the drug formulation has changed. Short-lived yet annoying back pain may develop after large (>30 mL) epidural doses of 3% chloroprocaine.

Tetracaine, first synthesized in 1931, has become widely used in the United States for spinal anesthesia. It may be used as an isobaric, hypobaric, or hyperbaric solution for spinal anesthesia. Without epinephrine it typically lasts 1.5 to 2.5 hours, and with the addition of epinephrine it may last up to 4 hours for lower extremity procedures. Tetracaine is also an effective topical airway anesthetic, although caution must be used because of the potential for systemic side effects. Tetracaine is available as a 1% solution for intrathecal use or as anhydrous crystals that are reconstituted as tetracaine solution by adding sterile water immediately before use. Tetracaine is not as stable as procaine or lidocaine in solution, and the crystals also undergo deterioration over time. Nevertheless, when a tetracaine spinal anesthetic is ineffective, one should question technique before “blaming” the drug.

Amino Amides

Lidocaine was the first clinically used amide local anesthetic, having been introduced by Lofgren in 1948. Lidocaine has become the most widely used local anesthetic in the world because of its inherent potency, rapid onset, tissue penetration, and effectiveness during infiltration, peripheral nerve block, and both epidural and spinal blocks. During peripheral nerve block, a 1% to 1.5% solution is often effective in producing an acceptable motor blockade, whereas during epidural block, a 2% solution seems most effective. In spinal anesthesia, a 5% solution in dextrose is most commonly used, although it may also be used as a 0.5% hypobaric solution in a volume of 6 to 8 mL. Others use lidocaine as a short-acting 2% solution in a volume of 2 to 3 mL. The suggestion that lidocaine causes an unacceptable frequency of neurotoxicity with spinal use needs to be balanced against its long history of use. I believe that the basic science research may not completely reflect the typical clinical situation. In any event, I have reduced the total dose of subarachnoid lidocaine I administer to less than 75 mg per spinal procedure, inject it more rapidly than in the past, and no longer use it for continuous subarachnoid techniques. Patients often report that lidocaine causes the most common local anesthetic allergies. However, many of these reported allergies are simply epinephrine reactions resulting from intravascular injection of the local anesthetic epinephrine mixture, often during dental injection.

Prilocaine is structurally related to lidocaine, although it causes significantly less vasodilation than lidocaine and thus can be used without epinephrine. Prilocaine is formulated for infiltration, peripheral nerve block, and epidural anesthesia. Its anesthetic profile is similar to that of lidocaine, although in addition to producing less vasodilation, it has less potential for systemic toxicity in equal doses. This attribute makes it particularly useful for intravenous regional anesthesia. Prilocaine is not more widely used because, when metabolized, it can produce both orthotoluidine and nitrotoluidine, agents in methemoglobin formation.

Etidocaine is chemically related to lidocaine and is a long-acting amide local anesthetic. Etidocaine is associated with profound motor blockade and is best used when this attribute can be of clinical advantage. It has a more rapid onset of action than bupivacaine but is used less frequently. Those clinicians using etidocaine often use it for the initial epidural dose and then use bupivacaine for subsequent epidural injections.

Mepivacaine is structurally related to lidocaine and the two drugs have similar actions. Overall, mepivacaine is slightly longer acting than lidocaine, and this difference in duration is accentuated when epinephrine is added to the solutions.

Bupivacaine is a long-acting local anesthetic that can be used for infiltration, peripheral nerve block, and epidural and spinal anesthesia. Useful concentrations of the drug range from 0.125% to 0.75%. By altering the concentration of bupivacaine, sensory and motor blockade can be separated. Lower concentrations provide sensory blockade principally, and as the concentration is increased, the effectiveness of motor blockade increases with it. If an anesthesiologist had to select a single drug and a single drug concentration, 0.5% bupivacaine would be a logical choice because at that concentration it is useful for peripheral nerve block, subarachnoid block, and epidural block. Cardiotoxicity during systemic toxic reactions with bupivacaine became a concern in the 1980s. Although it is clear that bupivacaine alters myocardial conduction more dramatically than lidocaine, the need for appropriate and rapid resuscitation during any systemic toxic reaction cannot be overemphasized. Levobupivacaine is the single enantiomer (l-isomer) of bupivacaine and appears to have a systemic toxicity profile similar to that of ropivacaine, and clinically it has effects similar to those of racemic bupivacaine.

Ropivacaine is another long-acting local anesthetic, similar to bupivacaine; it was introduced in the United States in 1996. It may offer an advantage over bupivacaine because experimentally it appears to be less cardiotoxic. Whether that experimental advantage is borne out clinically remains to be seen. Initial studies also suggest that ropivacaine may produce less motor block than that produced by bupivacaine, with similar analgesia. Ropivacaine may also be slightly shorter acting than bupivacaine, with useful drug concentrations ranging from 0.25% to 1%. Many practitioners believe that ropivacaine may offer particular advantages for postoperative analgesic infusions and obstetric analgesia.

Vasoconstrictors

Vasoconstrictors are often added to local anesthetics to prolong the duration of action and improve the quality of the local anesthetic block. Although it is still unclear whether vasoconstrictors actually allow local anesthetics to have a longer duration of block or are effective because they produce additional antinociception through α-adrenergic action, their clinical effect is not in question.

Epinephrine

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