Local Anesthetics
Local and Regional Anesthesia
Some surgical procedures can be performed under regional anesthesia (anesthesia selective for part of the body, such as the area near the surgical site) rather than general anesthesia (total body anesthesia with the patient rendered unconscious). Epidural, spinal (intrathecal), IV regional, peripheral nerve block, topical, or local infiltration anesthesia can be chosen, depending on the location of the surgical site, extent of the surgery, patient health and physical characteristics, coagulation status, duration of surgery, and the desires and cooperativeness of the patient. For epidural anesthesia, the local anesthetic is administered into the epidural space, which is located between the dura and the ligament covering the spinal vertebral bodies and disks. To provide spinal anesthesia, the local anesthetic is injected into the cerebrospinal fluid within the subarachnoid (intrathecal) space. By injecting a local anesthetic in the tissue near a specific nerve or nerve plexus, anesthesia can be provided for a carotid endarterectomy (cervical plexus), upper extremity surgery (brachial plexus), or hand surgery (ulnar, median and/or radial nerve). Regional anesthesia can be selected to reduce or avoid the likelihood of complications such as postoperative pain, nausea, vomiting, and laryngeal irritation, or dental complications, all of which are associated with general anesthesia. Peripheral nerve block may be selected over general, spinal, or epidural anesthesia because it is not associated with bowel obstruction or urinary retention, and it provides postoperative analgesia (particularly when long-acting local anesthetics are used).80 Potential advantages of spinal or epidural anesthesia include reduction of the stress response to surgery, improvement in cardiac function in patients with ischemic heart disease, fewer postoperative pulmonary complications, potentially favorable effects on coagulation (lower risk of venous thrombosis), and the ability to continue epidural analgesia into the postoperative period.81 Disadvantages of spinal, epidural, or peripheral nerve block include the additional time and manipulations required to perform it, possible complications or pain from invasive catheter placements or injections, slow onset of effect, possible failure of technique, and toxicity from absorption of the drugs administered. Local infiltration anesthesia can be used to provide localized anesthesia to allow a minor procedure (e.g., a deep laceration repair) to be performed.
| Table 9-11 Clinical Uses of Local Anesthetic Agents | ||||||||||||||||||||||||||||
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Uses of Local Anesthetic Agents
Local anesthetics are a mainstay of analgesia because they prevent the initiation or propagation of the electrical impulses required for peripheral and spinal nerve conduction. These agents can be administered by all routes previously discussed, depending on the drug chosen. Table 9-11 lists the common uses of currently available local anesthetics.82,83 Local anesthetics are often given in combination with other agents, such as sodium bicarbonate (to increase the speed of onset and reduce pain on local infiltration), epinephrine (to prolong the duration of action and to delay vascular absorption of the local anesthetic, thereby minimizing plasma concentration and systemic toxicity), or opioids (to provide analgesia by a different mechanism of action).
Mechanism of Action
The two structural classes of local anesthetics are characterized by the linkage between the molecule's lipophilic aromatic group and hydrophilic amine group: amides and esters. Both amide and ester classes provide anesthesia and analgesia by reversibly binding to and blocking the sodium channels in nerve membranes, thereby decreasing the rate of rise of the action potential such that threshold potential is not reached. As a result, propagation of the electrical impulses required for nerve conduction is prevented. The axonal membrane blockade that results is selective depending on the drug, the concentration and volume administered, and the depth of nerve penetration.
C fibers (pain transmission and autonomic activity) appear to be the most easily blocked, followed by fibers responsible for touch and pressure sensation (A-α, A-β, and A-Δ), and finally, those responsible for motor function (A-α and A-β). At the most commonly used doses and concentrations, some non–pain-transmitting nerve fibers are also blocked. The blockade of sensory, motor, or autonomic (sympathetic, parasympathetic) fibers may result in adverse effects such as paresthesia, numbness and inability to move extremities, hypotension, and urinary retention. Systemic effects (e.g., seizures or cardiac arrhythmias) are related to the inherent cardiac and CNS safety margins of these drugs.82,83
Ropivacaine, like bupivacaine, has a long duration of action. Higher plasma concentrations of ropivacaine are required to produce mild CNS toxicity (lightheadedness, tinnitus, numbness of the tongue) in volunteers, when compared with bupivacaine. In animal studies, ropivacaine was found to be less cardiotoxic than bupivacaine. In addition, ropivacaine may produce less motor blockade than bupivacaine.84 As a result, some anesthesia providers believe ropivacaine is safer than bupivacaine. However, inadvertent intravascular administration of ropivacaine can produce significant CNS toxicity (seizures), emphasizing the importance of ensuring appropriate placement of the local anesthetic solution by the anesthesia provider.
Allergic Reaction
Most adverse effects to local anesthetics are manifestations of excessive plasma concentration (systemic toxicity) of the local anesthetic. Localized hypersensitivity reactions (e.g., local erythema, edema, dermatitis) to local anesthetics are rare. Ester-type local anesthetic agents (benzocaine, procaine, tetracaine) produce most of the allergic reactions, which is probably caused by their metabolite, para-aminobenzoic acid (PABA). True (systemic) allergy to amide-type local anesthetics is extremely rare and may be due to the preservative (methylparaben or other substances that are structurally similar to PABA) or to accidental intravascular injection of an epinephrine-containing local anesthetic. Because amide-type local anesthetics do not undergo metabolism to a PABA metabolite, a patient with a known allergy to an ester-type local anesthetic can safely receive an amide-type agent.82,83,85 It is best to administer a preservative-free, epinephrine-free preparation to a patient with a known allergy to a local anesthetic.
Toxicity
Factors that influence the toxicity of local anesthetics include the total amount of drug administered, presence or absence of epinephrine, vascularity of the injection site, type of local anesthetic used, rate of destruction of the drug, age and physical status of the patient, and interactions with other drugs. Systemic absorption of the local anesthetic is positively correlated with the vascularity of the injection site (IV > epidural > brachial plexus > subcutaneous). End-stage pregnancy, older age (e.g., the elderly), significant hepatic/renal dysfunction, and advanced heart failure can result in either higher peak levels or accumulation of local anesthetic with continued or repeat dosing. In general, local anesthetic doses should be reduced in patients with these conditions.86
Toxic levels of local anesthetics are most often achieved by unintentional intravascular injection, which result in excessive plasma concentrations. Systemic toxicity of local anesthetics involves the CNS and cardiovascular system. Patients may initially complain of tinnitus, lightheadedness, metallic taste in their mouth, tingling, numbness, and dizziness. Hypotension may occur. These symptoms can quickly be followed by tremors, seizures, arrhythmias, unconsciousness, and cardiac/respiratory arrest as plasma levels rise.82,87
Physicochemical Properties Affecting Action
The potency of a local anesthetic is primarily determined by the degree of lipid solubility. Local anesthetics such as bupivacaine are highly lipid soluble and can be given in concentrations of 0.25% to 0.5%. Less lipid-soluble agents, such as lidocaine, require concentrations of 1% to 2% for many anesthetic techniques.
Amide-type local anesthetics are metabolized primarily by microsomal enzymes in the liver. The cytochrome P450 enzyme system is involved in the metabolism of lidocaine (CYP3A4), levobupivacaine (CYP3A4, CYP1A2), and ropivacaine (CYP3A2, CYP3A4, and CYP1A2). Agents that induce or inhibit these enzymes could affect the metabolism, and therefore the plasma concentration, of these drugs. Ester-type local anesthetics are hydrolyzed by plasma cholinesterase and, to a lesser extent, cholinesterase in the liver.82,83
Differences in the clinical activity of local anesthetics are explained by other physicochemical properties such as protein binding and pKa (the pH at which 50% of the drug is present in the unionized form and 50% in the ionized form). Agents that are highly protein bound typically have a longer duration of action. Agents with a lower pKa typically have a faster onset of action.83
Choice of local anesthetic is based on the duration of the surgical procedure (e.g., the duration of analgesia required). Usually, a local anesthetic that will, at least minimally, outlast the duration of surgery with a single injection is chosen; a continuous infusion can also be administered for titration of effect with shorter-acting agents. Important physicochemical and pharmacokinetic properties of local anesthetics are shown in Table 9-12.82,83
Regional Anesthesia in High-Risk Patients
13. M.S., a 52-year-old, 5′9′′, 105-kg black man, is undergoing an emergent minor hand repair procedure after a fall-related injury. His medical history is positive for type 1 diabetes mellitus for 41 years, angina, and hypertension. On OR admission, laboratory values of note are plasma glucose, 240 mg/dL, and BP, 145/92 mmHg. His sister tells the anesthesia provider that he has been having increasing difficulty walking up stairs and, of late, is often short of breath. The anesthesia provider chooses to provide regional anesthesia via an axillary block; the anticipated duration of surgery is 2 hours. M.S. agrees with this plan. Why is this a good plan for M.S., and which local anesthetic should be chosen?
[SI unit: glucose, 13.3 mmol/L]
With his medical conditions of diabetes, angina, and hypertension, M.S. is at risk for complications from genera anesthesia. General anesthesia is not absolutely necessary in this localized surgery. Regional anesthesia would be beneficial in M.S. because it does not disrupt autonomic function. In addition, his diabetes and obesity, and possibly full stomach (emergency surgery, diabetic gastroparesis), place him at significant risk for aspiration during induction or emergence from general anesthesia. An axillary block with a local anesthetic could provide M.S. with adequate anesthesia and analgesia during and after his procedure.
The local anesthetic of choice is one with a duration at least that of the anticipated surgery and with a good safety profile should systemic absorption inadvertently occur. A local anesthetic containing epinephrine would increase the agent's duration of action and reduce the systemic absorption; however, such an agent is not indicated in M.S. because of his diabetes (peripheral vascular effects) and hypertension (added effect from catecholamine administration). Lidocaine as a single injection without epinephrine has a duration of action that may be too short for M.S.'s procedure. Mepivacaine, an intermediate-acting local anesthetic, or bupivacaine, a long-acting agent, would be appropriate choices to use in M.S.
Alkalinization of Local Anesthetics
15. T.F., a 22-year-old man, is scheduled for a hernia repair. He has never undergone surgery and is very anxious. In the preoperative area, the nurse chooses to locally infiltrate 1% lidocaine to reduce the pain and discomfort from IV catheter placement. She injects a small amount of lidocaine under the skin. T.F. flinches and complains of pain from the injection. Can anything be done to speed the onset and reduce the pain from injection of lidocaine?
The onset of action of local anesthetics depends on their pKa. Drugs with pKas closest to body pH (7.4) will have the fastest onset because a high percentage of the local anesthetic molecules will be unionized and therefore able to cross the nerve membranes to their intracellular site of action. Local anesthetics are formulated in solutions with acidic pHs to optimize their shelf-lives. When sodium bicarbonate is added to local anesthetic solutions, the pH is increased, the percentage of unionized drug is increased, and the onset of local anesthetic action can be shortened considerably. The amount of bicarbonate added to the solution depends on the pH of the local anesthetic agent. Because too much sodium bicarbonate will precipitate the local anesthetic, a dose of 0.1 mEq (0.1 mL of a 1 mEq/mL concentration) of sodium bicarbonate is added to 10 mL of bupivacaine, whereas 1 mEq (1 mL of a 1 mEq/mL concentration) is added to 10 mL of lidocaine. Furthermore, alkalinized lidocaine can be significantly less painful for subcutaneous injection before IV catheter placement when compared with lidocaine at pH 5 (its pH in the commercially available vial).88
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