Browse the corpus

Local anesthetics (LA) consist of amino amide and amino ester medications used for several medical purposes. This activity will cover the indications, mechanism of action, metabolism, adverse effects, and potential toxicity of local anesthetics used in children. It will also discuss the interprofessional team’s role in enhancing care for children who receive local anesthetics. Objectives: Outline indications for the use of local anesthetics. Review the mechanism of action of local anesthetics and discuss their metabolism. Explain the risks contributing to the adverse effects and toxicity of local anesthetics, and explain local anesthetic systemic toxicity (LAST) and its treatment. Identify the interprofessional team strategies for improving the care of and communication about local anesthetic administration and monitoring in children. Access free multiple choice questions on this topic.

The onset of LA toxicity can be variable ranging from immediate onset to delayed onset hours after the administration of the LA. There may be signs and symptoms that suggest impending LA toxicity, or systemic reactions may occur without forewarning. Peak absorption of LA is most rapid in intercostal block applications, followed by caudal/epidural uptake, then uptake in the brachial plexus, ending with the least rapid uptake from distal peripheral sites (sciatic/femoral) and topical administration.[3] The direct effect on the mitochondria is to inhibit metabolism and oxidative phosphorylation. Central nervous system (CNS) toxicity can result in seizures, while direct cardiac effects include impaired myocardial contractility and conduction disturbances.  Toxic signs and symptoms may vary from perioral tingling, confusion, dizziness, seizure, hypotension, and cardiac arrest.[1] A direct decrease in the rate of depolarization and increased duration of the action potential can result in cardiac arrhythmias and even cardiac arrest. The increased heart rate of neonates and infants makes them more susceptible to the cardiac effects of LA.[4] Hypotension and bradycardia are ominous signs. Low doses of LA are still used to treat epilepsy and convulsions in the pediatric population. However, the therapeutic index is narrow, and at toxic levels, LAs can cause seizures and coma.[4] Other neurologic signs and symptoms include tinnitus, perioral tingling, metallic taste, and agitation.[1][2] Prilocaine alone or as EMLA cream can cause methemoglobinemia, especially in neonates and infants less than 3 months old. The risk of methemoglobinemia is increased by concurrent medication use with medications such as dapsone, acetaminophen, trimethoprim-sulfamethoxazole, phenytoin, phenobarbital, and chloroquine. Treatment of methemoglobinemia is supportive with oxygen and intravenous fluids, and if needed, IV methylene blue 1 to 2 mg/kg infused over 5 minutes or ascorbic acid.[6][13] Methylene blue may be repeated every 30-60 minutes, not to exceed the maximum dose of 7 mg/kg.[13]

Prilocaine alone or as EMLA cream can cause methemoglobinemia, especially in neonates and infants less than 3 months old. The risk of methemoglobinemia is increased by concurrent medication use with medications such as dapsone, acetaminophen, trimethoprim-sulfamethoxazole, phenytoin, phenobarbital, and chloroquine. Treatment of methemoglobinemia is supportive with oxygen and intravenous fluids, and if needed, IV methylene blue 1 to 2 mg/kg infused over 5 minutes or ascorbic acid.[6][13] Methylene blue may be repeated every 30-60 minutes, not to exceed the maximum dose of 7 mg/kg.[13] Treatment of LA toxicity must prioritize securing the airway, oxygenation, and treatment of cardiac arrest and seizures. It is imperative to prevent acidosis, as this will exacerbate the toxic effects of LAs. A smartphone app developed by the American Society of Regional Anesthesia and Pain Medicine, ASRA LAST, guides and assists in the treatment of suspected or diagnosed LAST. In the treatment of LAST first stop the administration of all LAs. Then call for help, maintain ventilation and oxygenation while securing the airway, and consider early use of lipid emulsion therapy and consultation for extracorporeal membrane oxygenation. For CNS and cardiac toxicity, you must control seizures with benzodiazepines (i.e., diazepam 0.05 mg/kg IV bolus, may repeat once) and treat cardiac sequelae with Pediatric Advanced Life Support and Neonatal Resuscitation Program protocols. Care is necessary to know which medications to avoid: vasopressin, calcium channel and beta-adrenergic blockers, and local anesthetics. If epinephrine is used, the dose should be less than 1 microgram/kilogram.[1] Amiodarone is the preferred choice for ventricular arrhythmias caused by LA, but for bupivacaine-induced cardiac toxicity specifically, bretylium 5 mg/kg IV has been found to be effective (maximum dose of 30 mg/kg).[9][2]

In the treatment of LAST first stop the administration of all LAs. Then call for help, maintain ventilation and oxygenation while securing the airway, and consider early use of lipid emulsion therapy and consultation for extracorporeal membrane oxygenation. For CNS and cardiac toxicity, you must control seizures with benzodiazepines (i.e., diazepam 0.05 mg/kg IV bolus, may repeat once) and treat cardiac sequelae with Pediatric Advanced Life Support and Neonatal Resuscitation Program protocols. Care is necessary to know which medications to avoid: vasopressin, calcium channel and beta-adrenergic blockers, and local anesthetics. If epinephrine is used, the dose should be less than 1 microgram/kilogram.[1] Amiodarone is the preferred choice for ventricular arrhythmias caused by LA, but for bupivacaine-induced cardiac toxicity specifically, bretylium 5 mg/kg IV has been found to be effective (maximum dose of 30 mg/kg).[9][2] The gold standard for treatment of LAST is 20% lipid emulsion (20 grams in 100 mL or 0.2 g/mL). The recommended dose for pediatric patients begins with an initial bolus dose of 1.5 mL/kg (0.3 g/kg) followed by a continuous infusion of 0.25 mL/kg/min (0.05 g/kg/min), not to exceed 10 mL/kg (2 g/kg) in the first 30 minutes.[1][4] The role of lipid emulsion is to bind LA molecules and immediately increase the volume of distribution of the LA. Lipid emulsion also decreases the elimination of LA, so care is necessary to watch for recurrent toxic effects. Patients that have been stabilized after treatment for LAST need to be observed for at least 2 hours post-seizure and a minimum of 4 to 6 hours after recovery from cardiovascular instability. For those patients that survive cardiac arrest, the observation period needs to be determined on a case-by-case basis.[14]

The care of children receiving LA begins with the professional placing the LA, whether noninvasive, invasive, one-time dose or continuous infusion. Interprofessional communication is key in providing the first level of protection for children receiving LA. That begins with a minimum of two people checking the drug, dose, route, and site of administration, patient allergy profile, and patient weight. (see Tables 1-4) This could be the pharmacist and physician, the anesthesiologist and CRNA, or the nurse on the floor with a nursing colleague. This type of interprofessional teamwork enhances patient-centered care. [Level 5] Next, one must know the local anesthetic that has been given to appropriately monitor for adequate analgesic effect and maintain vigilance for signs and symptoms of adverse effects and LAST.  Institutions should develop a standard handoff that details the local anesthetic used, the method and timing of the administration of the local anesthetic, and the expected analgesic effect and duration. Signs and symptoms of toxicity should be reviewed. Prompt recognition and treatment of LAST can prevent potentiation of LAST. [Level 1] Monitoring provides the third level of protection for children receiving LA. Non-invasive blood pressure, pulse oximetry, and electrocardiogram are the minimum required mechanical monitors.[1] Vigilance in observation and communication with the child and family are of equal importance.  As a member of the care team, you must be knowledgeable of the normal use and effect of LA while also being informed of signs and symptoms of adverse effects and toxicity of LA.  If ever in doubt, seek advice and help from other care team members and proceed with emergency protocols as necessary. Early use of lipid emulsion and cardiopulmonary bypass/ECMO consult (both Level 2a) and immediate treatment of seizures (Level 1) improve patient outcomes.

Monitoring provides the third level of protection for children receiving LA. Non-invasive blood pressure, pulse oximetry, and electrocardiogram are the minimum required mechanical monitors.[1] Vigilance in observation and communication with the child and family are of equal importance.  As a member of the care team, you must be knowledgeable of the normal use and effect of LA while also being informed of signs and symptoms of adverse effects and toxicity of LA.  If ever in doubt, seek advice and help from other care team members and proceed with emergency protocols as necessary. Early use of lipid emulsion and cardiopulmonary bypass/ECMO consult (both Level 2a) and immediate treatment of seizures (Level 1) improve patient outcomes. The last level of protection for pediatric patients receiving LA is to implement an institutional, educational program that involves an annual review of local anesthetics, their effects, their potential adverse effects, and ultimately the treatment of LAST.  It would improve team performance to have a system for routine simulations that reviews the treatment and management of LAST in children. For example, vasopressin, beta-adrenergic blockers, and calcium channel blockers should be avoided in the treatment of cardiac arrest (Level 3).[14] These four strategies begin to ensure that the interprofessional team works collaboratively to enhance team performance and the outcomes of children receiving LA.