Local anesthesia is the loss of sensation in a body part without the loss of consciousness or the impairment of central control of vital functions. It offers two major advantages. First, physiological perturbations associated with general anesthesia are avoided; second, neurophysiological responses to pain and stress can be modified beneficially. As already discussed, local anesthetics can potentially produce deleterious side effects. Proper choice of a local anesthetic and care in its use are the primary determinants in avoiding toxicity. There is a poor relationship between the amount of local anesthetic injected and peak plasma levels in adults. Furthermore, peak plasma levels vary widely depending on the area of injection. They are highest with interpleural or intercostal blocks and lowest with subcutaneous infiltration. Thus, recommended maximum doses serve only as general guidelines.
This discussion summarizes the pharmacological and physiological consequences of the use of local anesthetics categorized by method of administration. A more comprehensive discussion of their use and administration is presented in textbooks on regional anesthesia (e.g., Cousins et al., 2008).
Anesthesia of mucous membranes of the nose, mouth, throat, tracheobronchial tree, esophagus, and genitourinary tract can be produced by direct application of aqueous solutions of salts of many local anesthetics or by suspension of the poorly soluble local anesthetics. Tetracaine (2%), lidocaine (2-10%), and cocaine (1-4%) typically are used. Cocaine is used only in the nose, nasopharynx, mouth, throat, and ear, where it uniquely produces vasoconstriction as well as anesthesia. The shrinking of mucous membranes decreases operative bleeding while improving surgical visualization. Comparable vasoconstriction can be achieved with other local anesthetics by the addition of a low concentration of a vasoconstrictor such as phenylephrine (0.005%). Epinephrine, topically applied, has no significant local effect and does not prolong the duration of action of local anesthetics applied to mucous membranes because of poor penetration. Maximal safe total dosages for topical anesthesia in a healthy 70-kg adult are 300 mg for lidocaine, 150 mg for cocaine, and 50 mg for tetracaine.
Peak anesthetic effect following topical application of cocaine or lidocaine occurs within 2-5 minutes (3-8 minutes with tetracaine), and anesthesia lasts for 30-45 minutes (30-60 minutes with tetracaine). Anesthesia is entirely superficial; it does not extend to submucosal structures. This technique does not alleviate joint pain or discomfort from subdermal inflammation or injury.
Local anesthetics are absorbed rapidly into the circulation following topical application to mucous membranes or denuded skin. Thus, topical anesthesia always carries the risk of systemic toxic reactions. Systemic toxicity has occurred even following the use of local anesthetics to control discomfort associated with severe diaper rash in infants. Absorption is particularly rapid when local anesthetics are applied to the tracheobronchial tree. Concentrations in blood after instillation of local anesthetics into the airway are nearly the same as those following intravenous injection. Surface anesthetics for the skin and cornea have been described earlier in the chapter.
Use of eutectic mixtures of local anesthetics lidocaine (2.5%)/prilocaine (2.5%) (emla) and lidocaine (7%)/tetracaine (7%) (pliagis) bridges the gap between topical and infiltration anesthesia. The efficacy of each of these combinations lies in the fact that the mixture has a melting point less than that of either compound alone, existing at room temperature as an oil that can penetrate intact skin. These creams produce anesthesia to a maximum depth of 5 mm and are applied as a cream on intact skin under an occlusive dressing in advance (~30-60 min) of any procedure. These mixtures are effective for procedures involving skin and superficial subcutaneous structures (e.g., venipuncture and skin graft harvesting). The component local anesthetics will be absorbed into the systemic circulation, potentially producing toxic effects, as described earlier. Guidelines are available to calculate the maximum amount of cream that can be applied and area of skin covered. These mixtures must not be used on mucous membranes or abraded skin, as rapid absorption across these surfaces may result in systemic toxicity.
Infiltration anesthesia is the injection of local anesthetic directly into tissue without taking into consideration the course of cutaneous nerves. Infiltration anesthesia can be so superficial as to include only the skin. It also can include deeper structures, including intra-abdominal organs, when these too are infiltrated.
The duration of infiltration anesthesia can be approximately doubled by the addition of epinephrine (5 μg/mL) to the injection solution; epinephrine also decreases peak concentrations of local anesthetics in blood. Epinephrine-containing solutions should not, however, be injected into tissues supplied by end arteries—for example, fingers and toes, ears, the nose, and the penis. The resulting vasoconstriction may cause gangrene. For the same reason, epinephrine should be avoided in solutions injected intracutaneously. Since epinephrine also is absorbed into the circulation, its use should be avoided in those for whom adrenergic stimulation is undesirable.
The local anesthetics used most frequently for infiltration anesthesia are lidocaine (0.5-1%), procaine (0.5-1%), and bupivacaine (0.125-0.25%). When used without epinephrine, up to 4.5 mg/kg of lidocaine, 7 mg/kg of procaine, or 2 mg/kg of bupivacaine can be employed in adults. When epinephrine is added, these amounts can be increased by one-third.
The advantage of infiltration anesthesia and other regional anesthetic techniques is that it can provide satisfactory anesthesia without disrupting normal bodily functions. The chief disadvantage of infiltration anesthesia is that relatively large amounts of drug must be used to anesthetize relatively small areas. This is no problem with minor surgery. When major surgery is performed, however, the amount of local anesthetic that is required makes systemic toxic reactions likely. The amount of anesthetic required to anesthetize an area can be reduced significantly and the duration of anesthesia increased markedly by specifically blocking the nerves that innervate the area of interest. This can be done at one of several levels: subcutaneously, at major nerves, or at the level of the spinal roots.
Field block anesthesia is produced by subcutaneous injection of a solution of local anesthetic in order to anesthetize the region distal to the injection. For example, subcutaneous infiltration of the proximal portion of the volar surface of the forearm results in an extensive area of cutaneous anesthesia that starts 2-3 cm distal to the site of injection. The same principle can be applied with particular benefit to the scalp, the anterior abdominal wall, and the lower extremity.
The drugs, concentrations, and doses recommended are the same as for infiltration anesthesia. The advantage of field block anesthesia is that less drug can be used to provide a greater area of anesthesia than when infiltration anesthesia is used. Knowledge of the relevant neuroanatomy obviously is essential for successful field block anesthesia.
Injection of a solution of a local anesthetic into or about individual peripheral nerves or nerve plexuses produces even greater areas of anesthesia than do the techniques already described. Blockade of mixed peripheral nerves and nerve plexuses also usually anesthetizes somatic motor nerves, producing skeletal muscle relaxation, which is essential for some surgical procedures. The areas of sensory and motor block usually start several centimeters distal to the site of injection. Brachial plexus blocks are particularly useful for procedures on the upper extremity and shoulder. Intercostal nerve blocks are effective for anesthesia and relaxation of the anterior abdominal wall. Cervical plexus block is appropriate for surgery of the neck. Sciatic and femoral nerve blocks are useful for surgery distal to the knee. Other useful nerve blocks prior to surgical procedures include blocks of individual nerves at the wrist and at the ankle, blocks of individual nerves such as the median or ulnar at the elbow, and blocks of sensory cranial nerves.
There are four major determinants of the onset of sensory anesthesia following injection near a nerve:
proximity of the injection to the nerve
concentration and volume of drug
degree of ionization of the drug
Local anesthetic is never intentionally injected into the nerve, as this would be painful and could cause nerve damage. Instead, the anesthetic agent is deposited as close to the nerve as possible. Thus the local anesthetic must diffuse from the site of injection into the nerve, where it acts. The rate of diffusion is determined chiefly by the concentration of the drug, its degree of ionization (ionized local anesthetic diffuses more slowly), its hydrophobicity, and the physical characteristics of the tissue surrounding the nerve. Higher concentrations of local anesthetic will provide a more rapid onset of peripheral nerve block. The utility of higher concentrations, however, is limited by systemic toxicity and by direct neural toxicity of concentrated local anesthetic solutions. For a given concentration, local anesthetics with lower pKa values tend to have a more rapid onset of action because more drug is uncharged at neutral pH. For example, the onset of action of lidocaine occurs in ~3 minutes; 35% of lidocaine is in the basic form at pH 7.4. In contrast, the onset of action of bupivacaine requires ~15 minutes; only 5-10% of bupivacaine is uncharged at this pH. Increased hydrophobicity might be expected to speed onset by increased penetration into nerve tissue. However, it also will increase binding in tissue lipids. Furthermore, the more hydrophobic local anesthetics also are more potent (and toxic) and thus must be used at lower concentrations, decreasing the concentration gradient for diffusion. Tissue factors also play a role in determining the rate of onset of anesthetic effects. The amount of connective tissue that must be penetrated can be significant in a nerve plexus compared to isolated nerves and can slow or even prevent adequate diffusion of local anesthetic to the nerve fibers.
Duration of nerve block anesthesia depends on the physical characteristics of the local anesthetic used and the presence or absence of vasoconstrictors. Especially important physical characteristics are lipid solubility and protein binding. Local anesthetics can be broadly divided into three categories:
those with a short (20-45 minutes) duration of action in mixed peripheral nerves, such as procaine
those with an intermediate (60-120 minutes) duration of action, such as lidocaine and mepivacaine
those with a long (400-450 minutes) duration of action, such as bupivacaine, ropivacaine, and tetracaine
Block duration of the intermediate-acting local anesthetics such as lidocaine can be prolonged by the addition of epinephrine (5 μg/mL). The degree of block prolongation in peripheral nerves following the addition of epinephrine appears to be related to the intrinsic vasodilatory properties of the local anesthetic and thus is most pronounced with lidocaine.
The types of nerve fibers that are blocked when a local anesthetic is injected about a mixed peripheral nerve depend on the concentration of drug used, nerve-fiber size, internodal distance, and frequency and pattern of nerve-impulse transmission (see above, sections on Frequency and Voltage-Dependence and Differential Sensitivity). Anatomical factors are similarly important. A mixed peripheral nerve or nerve trunk consists of individual nerves surrounded by an investing epineurium. The vascular supply usually is centrally located. When a local anesthetic is deposited about a peripheral nerve, it diffuses from the outer surface toward the core along a concentration gradient (DeJong, 1994; Winnie et al., 1977). Consequently, nerves in the outer mantle of the mixed nerve are blocked first. These fibers usually are distributed to more proximal anatomical structures than are those situated near the core of the mixed nerve and often are motor. If the volume and concentration of local anesthetic solution deposited about the nerve are adequate, the local anesthetic eventually will diffuse inward in amounts adequate to block even the most centrally located fibers. Lesser amounts of drug will block only nerves in the mantle and the smaller and more sensitive central fibers. Furthermore, since removal of local anesthetics occurs primarily in the core of a mixed nerve or nerve trunk, where the vascular supply is located, the duration of blockade of centrally located nerves is shorter than that of more peripherally situated fibers.
The choice of local anesthetic and the amount and concentration administered are determined by the nerves and the types of fibers to be blocked, the required duration of anesthesia, and the size and health of the patient. For blocks of 2-4 hours, lidocaine (1-1.5%) can be used in the amounts recommended earlier (see "Infiltration Anesthesia"). Mepivacaine (up to 7 mg/kg of a 1-2% solution) provides anesthesia that lasts about as long as that from lidocaine. Bupivacaine (2-3 mg/kg of a 0.25-0.375% solution) can be used when a longer duration of action is required. Addition of 5 μg/mL epinephrine slows systemic absorption and therefore prolongs duration and lowers the plasma concentration of the intermediate-acting local anesthetics.
Peak plasma concentrations of local anesthetics depend on the amount injected, the physical characteristics of the local anesthetic, whether epinephrine is used, the rate of blood flow to the site of injection, and the surface area exposed to local anesthetic. This is of particular importance in the safe application of nerve block anesthesia, since the potential for systemic reactions is related to peak free serum concentrations. For example, peak concentrations of lidocaine in blood following injection of 400 mg without epinephrine for intercostal nerve blocks average 7 μg/mL; the same amount of lidocaine used for block of the brachial plexus results in peak concentrations in blood of ~3 μg/mL (Covino and Vassallo, 1976). Therefore, the amount of local anesthetic that can be injected must be adjusted according to the anatomical site of the nerve(s) to be blocked to minimize untoward effects. Addition of epinephrine can decrease peak plasma concentrations by 20-30%. Multiple nerve blocks (e.g., intercostal block) or blocks performed in vascular regions require reduction in the amount of anesthetic that can be given safely, because the surface area for absorption or the rate of absorption is increased.
Intravenous Regional Anesthesia (Bier's Block)
This technique relies on using the vasculature to bring the local anesthetic solution to the nerve trunks and endings. In this technique, an extremity is exsanguinated with an Esmarch (elastic) bandage, and a proximally located tourniquet is inflated to 100-150 mm Hg above the systolic blood pressure. The Esmarch bandage is removed, and the local anesthetic is injected into a previously cannulated vein. Typically, complete anesthesia of the limb ensues within 5-10 minutes. Pain from the tourniquet and the potential for ischemic nerve injury limits tourniquet inflation to 2 hours or less. However, the tourniquet should remain inflated for at least 15-30 minutes to prevent toxic amounts of local anesthetic from entering the circulation following deflation. Lidocaine, 40-50 mL (0.5 mL/kg in children) of a 0.5% solution without epinephrine is the drug of choice for this technique. For intravenous regional anesthesia in adults using a 0.5% solution without epinephrine, the dose administered should not exceed 4 mg/kg. A few clinicians prefer prilocaine (0.5%) over lidocaine because of its higher therapeutic index. The attractiveness of this technique lies in its simplicity. Its primary disadvantages are that it can be used only for a few anatomical regions, sensation (pain) returns quickly after tourniquet deflation, and premature release or failure of the tourniquet can produce toxic levels of local anesthetic (e.g., 50 mL of 0.5% lidocaine contains 250 mg of lidocaine). For the last reason and because its longer durations of action offer no advantage, the more cardiotoxic local anesthetic, bupivacaine, is not recommended for this technique. Intravenous regional anesthesia is used most often for surgery of the forearm and hand, but can be adapted for the foot and distal leg.
Spinal anesthesia follows the injection of local anesthetic into the cerebrospinal fluid (CSF) in the lumbar space. For a number of reasons, including the ability to produce anesthesia of a considerable fraction of the body with a dose of local anesthetic that produces negligible plasma levels, spinal anesthesia remains one of the most popular forms of anesthesia. In most adults, the spinal cord terminates above the second lumbar vertebra; between that point and the termination of the thecal sac in the sacrum, the lumbar and sacral roots are bathed in CSF. Thus, in this region there is a relatively large volume of CSF within which to inject drug, thereby minimizing the potential for direct nerve trauma.
A brief discussion of the physiological effects of spinal anesthesia relating to the pharmacology of the local anesthetics used is presented here. See more specialized texts (e.g., Cousins et al., 2008) for additional details.
Physiological Effects of Spinal Anesthesia. Most of the physiological side effects of spinal anesthesia are a consequence of the sympathetic blockade produced by local anesthetic block of the sympathetic fibers in the spinal nerve roots. A thorough understanding of these physiological effects is necessary for the safe and successful application of spinal anesthesia. Although some of them may be deleterious and require treatment, others can be beneficial for the patient or can improve operating conditions. Most sympathetic fibers leave the spinal cord between T1 and L2 (Chapter 8, Figure 8–1). Although local anesthetic is injected below these levels in the lumbar portion of the dural sac, cephalad spread of the local anesthetic occurs with all but the smallest volumes injected. This cephalad spread is of considerable importance in the practice of spinal anesthesia and potentially is under the control of numerous variables, of which patient position and baricity (density of the drug relative to the density of the CSF) are the most important (Greene, 1983). The degree of sympathetic block is related to the height of sensory anesthesia; often the level of sympathetic blockade is several spinal segments higher, since the preganglionic sympathetic fibers are more sensitive to low concentrations of local anesthetic. The effects of sympathetic blockade involve both the actions (now partially unopposed) of the parasympathetic nervous system and the response of the unblocked portion of the sympathetic nervous system. Thus, as the level of sympathetic block ascends, the actions of the parasympathetic nervous system are increasingly dominant, and the compensatory mechanisms of the unblocked sympathetic nervous system are diminished. As most sympathetic nerve fibers leave the cord at T1 or below, few additional effects of sympathetic blockade are seen with cervical levels of spinal anesthesia. The consequences of sympathetic blockade will vary among patients as a function of age, physical conditioning, and disease state. Interestingly, sympathetic blockade during spinal anesthesia appears to be minimal in healthy children.
Clinically, the most important effects of sympathetic blockade during spinal anesthesia are on the cardiovascular system. At all but the lowest levels of spinal blockade, some vasodilation will occur. Vasodilation is more marked on the venous than on the arterial side of the circulation, resulting in blood pooling in the venous capacitance vessels. This reduction in circulating blood volume is well tolerated at low levels of spinal anesthesia in healthy patients. With an increasing level of block, this effect becomes more marked and venous return becomes gravity-dependent. If venous return decreases too much, cardiac output and organ perfusion decline precipitously. Venous return can be increased by a modest (10-15 degree) head-down tilt or by elevating the legs. At high levels of spinal blockade, the cardiac accelerator fibers, which exit the spinal cord at T1-T4, will be blocked. This is detrimental in patients dependent on elevated sympathetic tone to maintain cardiac output (e.g., during congestive heart failure or hypovolemia), and it also removes one of the compensatory mechanisms available to maintain organ perfusion during vasodilation. Thus, as the level of spinal block ascends, the rate of cardiovascular compromise can accelerate if not carefully observed and treated. Sudden asystole also can occur, presumably because of loss of sympathetic innervation in the continued presence of parasympathetic activity at the sinoatrial node (Caplan et al., 1988). In the usual clinical situation, blood pressure serves as a surrogate marker for cardiac output and organ perfusion. Treatment of hypotension usually is warranted when the blood pressure decreases to ~30% of resting values. Therapy is aimed at maintaining brain and cardiac perfusion and oxygenation. To achieve these goals, administration of oxygen, fluid infusion, manipulation of patient position, and the administration of vasoactive drugs are all options. In practice, patients typically are administered a bolus (500-1000 mL) of fluid prior to the administration of spinal anesthesia in an attempt to prevent some of the deleterious effects of spinal blockade. Since the usual cause of hypotension is decreased venous return, possibly complicated by decreased heart rate, drugs with preferential venoconstrictive and chronotropic properties are preferred. For this reason, ephedrine, 5-10 mg intravenously, often is the drug of choice. In addition to the use of ephedrine to treat deleterious effects of sympathetic blockade, direct-acting α1 adrenergic receptor agonists such as phenylephrine (Chapter 12) can be administered either by bolus or continuous infusion.
A beneficial effect of spinal anesthesia partially mediated by the sympathetic nervous system is on the intestine. Sympathetic fibers originating from T5-L1 inhibit peristalsis; thus, their blockade produces a small, contracted intestine. This, together with a flaccid abdominal musculature, produces excellent operating conditions for some types of bowel surgery. The effects of spinal anesthesia on the respiratory system mostly are mediated by effects on the skeletal musculature. Paralysis of the intercostal muscles will reduce a patient's ability to cough and clear secretions, which may produce dyspnea in patients with bronchitis or emphysema. Respiratory arrest during spinal anesthesia is seldom due to paralysis of the phrenic nerves or to toxic levels of local anesthetic in the CSF of the fourth ventricle; it is much more likely to be due to medullary ischemia secondary to hypotension.
Pharmacology of Spinal Anesthesia. Currently in the U.S., the drugs most commonly used in spinal anesthesia are lidocaine, tetracaine, and bupivacaine. Procaine occasionally is used for diagnostic blocks when a short duration of action is desired. The choice of local anesthetic is primarily determined by the desired duration of anesthesia. General guidelines are to use lidocaine for short procedures, bupivacaine for intermediate to long procedures, and tetracaine for long procedures. As mentioned earlier, the factors contributing to the distribution of local anesthetics in the CSF have received much attention because of their importance in determining the height of block. The most important pharmacological factors include the amount, and possibly the volume, of drug injected and its baricity. The speed of injection of the local anesthesia solution also may affect the height of the block, just as the position of the patient can influence the rate of distribution of the anesthetic agent and the height of blockade achieved (described in the next section). For a given preparation of local anesthetic, administration of increasing amounts leads to a fairly predictable increase in the level of block attained. For example, 100 mg of lidocaine, 20 mg of bupivacaine, or 12 mg of tetracaine usually will result in a T4 sensory block. More complete tables of these relationships can be found in standard anesthesiology texts. Epinephrine often is added to spinal anesthetics to increase the duration or intensity of block. Epinephrine's effect on duration of block is dependent on the technique used to measure duration. A commonly used measure of block duration is the length of time it takes for the block to recede by two dermatomes from the maximum height of the block, while a second is the duration of block at some specified level, typically L1. In most studies, addition of 200 μg of epinephrine to tetracaine solutions prolongs the duration of block by both measures. However, addition of epinephrine to lidocaine or bupivacaine does not affect the first measure of duration, but does prolong the block at lower levels. In different clinical situations, one or the other measure of anesthesia duration may be more relevant, and this must be kept in mind when deciding whether to add epinephrine to spinal local anesthetics. The mechanism of action of vasoconstrictors in prolonging spinal anesthesia is uncertain. It has been hypothesized that these agents decrease spinal cord blood flow, decreasing clearance of local anesthetic from the CSF, but this has not been convincingly demonstrated. Epinephrine and other α-adrenergic agonists have been shown to decrease nociceptive transmission in the spinal cord, and studies in genetically modified mice suggest that α2A adrenergic receptors play a principal role in this response (Stone et al., 1997). Such actions may contribute to the beneficial effects of epinephrine, clonidine, and dexmedetomidine when these agents are added to spinal local anesthetics.
Drug Baricity and Patient Position. The baricity of the local anesthetic injected will determine the direction of migration within the dural sac. Hyperbaric solutions will tend to settle in the dependent portions of the sac, while hypobaric solutions will tend to migrate in the opposite direction. Isobaric solutions usually will stay in the vicinity where they were injected, diffusing slowly in all directions. Consideration of the patient position during and after the performance of the block and the choice of a local anesthetic of the appropriate baricity is crucial for a successful block during some surgical procedures. Lidocaine and bupivacaine are marketed in both isobaric and hyperbaric preparations, and if desired, can be diluted with sterile, preservative-free water to make them hypobaric.
Complications of Spinal Anesthesia. Persistent neurological deficits following spinal anesthesia are extremely rare. Thorough evaluation of a suspected deficit should be performed in collaboration with a neurologist. Neurological sequelae can be both immediate and late. Possible causes include introduction of foreign substances (such as disinfectants or talc) into the subarachnoid space, infection, hematoma, or direct mechanical trauma. Aside from drainage of an abscess or hematoma, treatment usually is ineffective; thus, avoidance and careful attention to detail while performing spinal anesthesia are necessary.
High concentrations of local anesthetic can cause irreversible block. After administration, local anesthetic solutions are diluted rapidly, quickly reaching nontoxic concentrations. However, there are several reports of transient or longer-lasting neurological deficits following lidocaine spinal anesthesia, particularly with 5% lidocaine (i.e., 180 mmol) in 7.5% glucose (Zaric and Pace, 2009). Spinal anesthesia sometimes is regarded as contraindicated in patients with pre-existing disease of the spinal cord. No experimental evidence exists to support this hypothesis. Nonetheless, it is prudent to avoid spinal anesthesia in patients with progressive diseases of the spinal cord. However, spinal anesthesia may be very useful in patients with fixed, chronic spinal cord injury.
A more common sequela following any lumbar puncture, including spinal anesthesia, is a postural headache with classic features. The incidence of headache decreases with increasing age of the patient and decreasing needle diameter. Headache following lumbar puncture must be thoroughly evaluated to exclude serious complications such as meningitis. Treatment usually is conservative, with bed rest and analgesics. If this approach fails, an epidural blood patch with the injection of autologous blood can be performed; this procedure usually is successful in alleviating postdural puncture headaches, although a second blood patch may be necessary. If two epidural blood patches are ineffective in relieving the headache, the diagnosis of postdural puncture headache should be reconsidered. Intravenous caffeine (500 mg as the benzoate salt administered over 4 hours) also has been advocated for the treatment of postdural puncture headache; however, the efficacy of caffeine is less than that of a blood patch, and relief usually is transient.
Evaluation of Spinal Anesthesia. Spinal anesthesia is a safe and effective technique, especially during surgery involving the lower abdomen, the lower extremities, and the perineum. It often is combined with intravenous medication to provide sedation and amnesia. The physiological perturbations associated with low spinal anesthesia often have less potential harm than those associated with general anesthesia. The same does not apply for high spinal anesthesia. The sympathetic blockade that accompanies levels of spinal anesthesia adequate for mid- or upper-abdominal surgery, coupled with the difficulty in achieving visceral analgesia, is such that equally satisfactory and safer operating conditions can be realized by combining the spinal anesthetic with a "light" general anesthetic or by the administration of a general anesthetic and a neuromuscular blocking agent.
Epidural anesthesia is administered by injecting local anesthetic into the epidural space—the space bounded by the ligamentum flavum posteriorly, the spinal periosteum laterally, and the dura anteriorly. Epidural anesthesia can be performed in the sacral hiatus (caudal anesthesia) or in the lumbar, thoracic, or cervical regions of the spine. Its current popularity arises from the development of catheters that can be placed into the epidural space, allowing either continuous infusions or repeated bolus administration of local anesthetics. The primary site of action of epidurally administered local anesthetics is on the spinal nerve roots. However, epidurally administered local anesthetics also may act on the spinal cord and on the paravertebral nerves.
The selection of drugs available for epidural anesthesia is similar to that for major nerve blocks. As for spinal anesthesia, the choice of drugs to be used during epidural anesthesia is dictated primarily by the duration of anesthesia desired. However, when an epidural catheter is placed, short-acting drugs can be administered repeatedly, providing more control over the duration of block. Bupivacaine, 0.5-0.75%, is used when a long duration of surgical block is desired. Due to enhanced cardiotoxicity in pregnant patients, the 0.75% solution is not approved for obstetrical use. Lower concentrations—0.25%, 0.125%, or 0.0625%—of bupivacaine, often with 2 μg/mL of fentanyl added, frequently are used to provide analgesia during labor. They also are useful preparations for providing postoperative analgesia in certain clinical situations. Lidocaine 2% is the most frequently used intermediate-acting epidural local anesthetic. Chloroprocaine, 2% or 3%, provides rapid onset and a very short duration of anesthetic action. However, its use in epidural anesthesia has been clouded by controversy regarding its potential ability to cause neurological complications if the drug is accidentally injected into the subarachnoid space (discussed earlier). The duration of action of epidurally administered local anesthetics frequently is prolonged, and systemic toxicity decreased, by addition of epinephrine. Addition of epinephrine also makes inadvertent intravascular injection easier to detect and modifies the effect of sympathetic blockade during epidural anesthesia.
For each anesthetic agent, a relationship exists between the volume of local anesthetic injected epidurally and the segmental level of anesthesia achieved. For example, in 20- to 40-year-old, healthy, nonpregnant patients, each 1-1.5 mL of 2% lidocaine will give an additional segment of anesthesia. The amount needed decreases with increasing age and also decreases during pregnancy and in children.
The concentration of local anesthetic used determines the type of nerve fibers blocked. The highest concentrations are used when sympathetic, somatic sensory, and somatic motor blockade are required. Intermediate concentrations allow somatic sensory anesthesia without muscle relaxation. Low concentrations will block only preganglionic sympathetic fibers. As an example, with bupivacaine these effects might be achieved with concentrations of 0.5%, 0.25%, and 0.0625%, respectively. The total amounts of drug that can be injected with safety at one time are approximately those mentioned earlier in the chapter under "Nerve Block Anesthesia" and "Infiltration Anesthesia." Performance of epidural anesthesia requires a greater degree of skill than does spinal anesthesia. The technique of epidural anesthesia and the volumes, concentrations, and types of drugs used are described in detail in standard texts on regional anesthesia (e.g., Cousins et al., 2008).
A significant difference between epidural and spinal anesthesia is that the dose of local anesthetic used can produce high concentrations in blood following absorption from the epidural space. Peak concentrations of lidocaine in blood following injection of 400 mg (without epinephrine) into the lumbar epidural space average 3-4 μg/mL; peak concentrations of bupivacaine in blood average 1 μg/mL after the lumbar epidural injection of 150 mg. Addition of epinephrine (5 μg/mL) decreases peak plasma concentrations by ~25%. Peak blood concentrations are a function of the total dose of drug administered rather than the concentration or volume of solution following epidural injection (Covino and Vassallo, 1976). The risk of inadvertent intravascular injection is increased in epidural anesthesia, as the epidural space contains a rich venous plexus.
Another major difference between epidural and spinal anesthesia is that there is no zone of differential sympathetic blockade with epidural anesthesia; thus, the level of sympathetic block is close to the level of sensory block. Because epidural anesthesia does not result in the zones of differential sympathetic blockade observed during spinal anesthesia, cardiovascular responses to epidural anesthesia might be expected to be less prominent. In practice this is not the case; the potential advantage of epidural anesthesia is offset by the cardiovascular responses to the high concentration of anesthetic in blood that occurs during epidural anesthesia. This is most apparent when, as is often the case, epinephrine is added to the epidural injection. The resulting concentration of epinephrine in blood is sufficient to produce significant β2 adrenergic receptor-mediated vasodilation. As a consequence, blood pressure decreases, even though cardiac output increases due to the positive inotropic and chronotropic effects of epinephrine (Chapter 12). The result is peripheral hyperperfusion and hypotension. Differences in cardiovascular responses to equal levels of spinal and epidural anesthesia also are observed when a local anesthetic such as lidocaine is used without epinephrine. This may be a consequence of the direct effects of high concentrations of lidocaine on vascular smooth muscle and the heart. The magnitude of the differences in responses to equal sensory levels of spinal and epidural anesthesia varies, however, with the local anesthetic used for the epidural injection (assuming no epinephrine is used). For example, local anesthetics such as bupivacaine, which are highly lipid soluble, are distributed less into the circulation than are less lipid-soluble agents such as lidocaine.
High concentrations of local anesthetics in blood during epidural anesthesia are especially important when this technique is used to control pain during labor and delivery. Local anesthetics cross the placenta, enter the fetal circulation, and at high concentrations may cause depression of the neonate. The extent to which they do so is determined by dosage, acid-base status, the level of protein binding in both maternal and fetal blood, placental blood flow, and solubility of the agent in fetal tissue. These concerns have been lessened by the trend toward using more dilute solutions of bupivacaine for labor analgesia.
Epidural and Intrathecal Opiate Analgesia. Small quantities of opioid injected intrathecally or epidurally produce segmental analgesia (Yaksh and Rudy, 1976). This observation led to the clinical use of spinal and epidural opioids during surgical procedures and for the relief of postoperative and chronic pain (Cousins and Mather, 1984). As with local anesthesia, analgesia is confined to sensory nerves that enter the spinal cord dorsal horn in the vicinity of the injection. Presynaptic opioid receptors inhibit the release of substance P and other neurotransmitters from primary afferents, while postsynaptic opioid receptors decrease the activity of certain dorsal horn neurons in the spinothalamic tracts (Willcockson et al., 1986; see also Chapters 8 and 18). Since conduction in autonomic, sensory, and motor nerves is not affected by the opioids, blood pressure, motor function, and non-nociceptive sensory perception typically are not influenced by spinal opioids. The volume-evoked micturition reflex is inhibited, as manifested by urinary retention. Other side effects include pruritus, nausea, and vomiting in susceptible individuals. Delayed respiratory depression and sedation, presumably from cephalad spread of opioid within the CSF, occur infrequently with the doses of opioids currently used.
Spinally administered opioids by themselves do not provide satisfactory anesthesia for surgical procedures. Thus, opioids have found the greatest use in the treatment of postoperative and chronic pain. In selected patients, spinal or epidural opioids can provide excellent analgesia following thoracic, abdominal, pelvic, or lower extremity surgery without the side effects associated with high doses of systemically administered opioids. For post-operative analgesia, spinally administered morphine, 0.2-0.5 mg, usually will provide 8-16 hours of analgesia. Placement of an epidural catheter and repeated boluses or an infusion of opioid permits an increased duration of analgesia. Many opioids have been used epidurally. Morphine, 2-6 mg, every 6 hours, commonly is used for bolus injections, while fentanyl, 20-50 μg/hour, often combined with bupivacaine, 5-20 mg/hour, is used for infusions. For cancer pain, repeated doses of epidural opioids can provide analgesia of several months' duration. The dose of epidural morphine, e.g., is far less than the dose of systemically administered morphine that would be required to provide similar analgesia. This reduces the complications that usually accompany the administration of high doses of systemic opioids, particularly sedation and constipation. Unfortunately, as with systemic opioids, tolerance will develop to the analgesic effects of epidural opioids, but this usually can be managed by increasing the dose.