In addition to host factors, neural blockade by local anesthetics is affected by the volume and concentration of local anesthetic injected, the absence or presence of vasoconstrictor additives, the site of injection, the addition of bicarbonate, and temperature of the local anesthetic.¹ Increasing the total milligrams of a local anesthetic dose shortens the onset and increases the duration of the local anesthetic. Epinephrine, norepinephrine, and phenylephrine are sometimes added to local anesthetics to reverse the intrinsic vasodilation effects of many of the local anesthetics and thereby reduce their systemic absorption. This increases the amount of local anesthetic available to block the nerve. More anesthetic means a quicker onset and longer duration. Application of the local anesthetic close to the nerve improves its ability to diffuse across the axon and block sodium channels. Highly vascular sites such as the intercostal nerve and caudal epidural space tend to result in slightly shorter duration of action. The addition of bicarbonate or CO₂ (700 mm Hg) to local anesthetics hasten their onset. Bicarbonate raises the pH and the amount of uncharged local anesthetic for diffusion through the nerve membrane. CO₂ will diffuse across the axonal membrane and lower the intracellular pH making more of the charged form of the local anesthetic available intracellularly to block the sodium channels. Temperature elevations decrease the pK_a of the local anesthetic and hasten the onset of action.

Individual Agents

Local anesthetics are administered in the intradermal, subcutaneous, intraarticular, intramuscular, perineural, and epidural spaces during pain management procedures. Injections into vascular regions such as the oral mucosa and epidural space may result in rapid absorption and higher systemic concentrations. Local anesthetics administered into or near the epidural space should be preservative free. Methylparaben is a common preservative in multidose vials and is also a common allergen.²

Lidocaine

Lidocaine is the most versatile and widely used of the local anesthetics. It has a short onset of action, 0.5 to 15 minutes, and short duration of action, typically 0.5 to 3 hours. The difference between the effective dose and the toxic does is wide, resulting in a high therapeutic index compared to other common local anesthetics. Maximum doses are variably reported in the range of 400 to 500 mg of lidocaine. Typical concentrations are 0.5% to 2%. Final concentration is often diluted by the addition of a corticosteroid.¹

Concentration percentages are easily converted to milligrams. For example, a 1% solution of lidocaine has 1 g of lidocaine in 100 mL of fluid. This is equivalent to 1000 mg/100 mL or 10 mg/mL. Volume of lidocaine injected varies widely with location and practitioner. Using the aforementioned guidelines, total injection of 1% lidocaine should remain below 40 mL (40 mL × 10 mg/mL = 400 mg).

Bupivicaine

Bupivacaine (Marcaine) is another widely used local anesthetic. Bupivacaine’s duration of action (2 to 5 hr) is longer than lidocaine’s as is its onset of action (5 to 20 min). Bupivacaine is commonly used in concentrations of 0.125% to 0.75%. Final concentrations are often diluted by 30% to 50% by the addition of a corticosteroid. The higher concentrations generally have a faster onset of action. Bupivacaine has more cardiotoxicity than lidocaine, especially if an injection is given intravenously inadvertently. The toxic dose of bupivacaine is only 80 mg (16 mL of a 0.5% solution) when given intravascularly, but may be up to 225 mg with an extravascular injection.¹

Toxicity

Action of local anesthetics is affected by numerous factors reviewed above. Location of injection plays a primary role in determining the onset, duration, and toxic dose of these agents (Table 2-1). Vasoconstrictors such as epinephrine reduce local bleeding and thereby prolong the onset and duration, but are generally not employed in a pain management practice.

Table 2-1 Classification and Uses of Local Anesthetics

Excess amounts of local anesthetics may cause CNS effects including confusion, convulsions, respiratory arrest, seizures, and even death. The risk for complications increases if the local anesthetics are given intravascularly. Other potential adverse reactions to local anesthetics include cardiodepression, anaphylaxis, and malignant hyperthermia. Patients with decreased renal function, hepatic function or plasma esterases eliminate local anesthetics more slowly and, therefore, have an increased risk of toxicity. Toxic blood levels of lidocaine are approximately 5 to 10 μg/mL, but adverse effects can be seen at lower blood levels.

Patients should be monitored for signs of toxicity including restlessness, anxiety, incoherent speech, lightheadedness, numbness, and tingling of the mouth and lips, blurred vision, tremors, twitching, depression or drowsiness. Injections into the head and neck area require the utmost care.³ Even small doses of local anesthetic may produce adverse reactions similar to systemic toxicity seen with unintentional intravascular injections of larger doses. Deaths have been reported.⁴

Resuscitative equipment and drugs should be immediately available when local anesthetics are used. Management of local anesthetic overdose begins with prevention by monitoring total dose administered, frequently aspirating for vascular uptake, and use of contrast to avoid vascular uptake when appropriate. Recognition of symptoms of toxicity and support of oxygenation with supplemental oxygen are keys to the initial management. Airway must be maintained and respiratory support should be provided as needed. Hypotension is the most common circulatory effect and should be treated with intravenous fluids and a vasopressor such as ephedrine in appropriate candidates. Convulsions persisting despite respiratory support are often treated with a benzodiazepine such as diazepam. If cardiac arrest occurs, standard cardiopulmonary resuscitative measures should be instituted.

Corticosteroids

Corticosteroids are administered in a pain practice for their potent antiinflammatory properties. These injections to relieve pain and inflammation work well temporarily, but questions remain regarding their role in the management of many chronic musculoskeletal conditions. Corticosteroids may result in significant side effects. The potential for these adverse effects, ranging from a relatively innocuous facial flushing effect to joint destroying avascular necrosis, must be weighed against potential benefits. Some locally injected corticosteroids are absorbed systemically and can produce transient systemic effects.

Corticosteroids can be helpful in a variety of conditions including rheumatoid arthritis, bursitis, tenosynovitis, entrapment neuropathies, crystal-induced arthropathies in patients who cannot tolerate systemic treatment well, radiculopathies, and at times, osteoarthritis (OA). Corticosteroids should never be injected directly into a tendon or nerve, subcutaneous fat, or an infected joint, bursa, or tendon (Table 2-2).

Table 2-2 Comparison of Commonly Used Glucocorticoid Steroids^∗

Mechanism of Action

All corticosteroids have both glucocorticoid, antiinflammatory, and mineralocorticoid activity. Agents with significant glucocorticoid and minimal mineralocorticoid activity include betamethasone (Celestone), dexamethasone (Decadron), methylprednisolone acetate (Depo-Medrol) and triamcinolone hexacetonide (Aristospan). Corticosteroids can be mixed in the same syringe with local anesthetics.

Corticosteroids produce both antiinflammatory and immunosuppressive effects in humans. The primary mechanism of action may be their ability to inhibit the release of cytokines by immune cells.⁵ The effects of corticosteroids are species specific.⁶ Lymphocytes in humans are much less sensitive to the effects of corticosteroids than lymphocytes in common laboratory animals including the mouse, rat, and rabbit. In humans, corticosteroids reduce the accumulation of lymphocytes at inflammatory sites by a migratory effect.⁷ In contrast to this lymphopenia, is the neutrophilia seen by demargination of neutrocytes from the endothelium and an accelerated rate of release from the bone marrow.⁸ A temporary rise in white blood cell count is commonly observed for this reason after a corticosteroid dose and in isolation does not mark a post injection infection.

The antiinflammatory effects of corticosteroid also occur at the microvascular level. They block the passage of immune complexes across the basement membrane, suppress superoxide radicals, and reduce capillary permeability and blood flow.⁹ Corticosteroids inhibit prostaglandin synthesis,¹⁰ decrease collagenase formation, and inhibit granulation tissue formation.

The immunosuppressant effects of corticosteroids are generally via effects on T cells. These effects are not the desired effect of corticosteroid used in pain management procedures and are not observed following epidural injections.¹¹ A review of these immunosuppressant effects can be found in other texts.¹¹^–¹⁴