Local Anesthetic Toxicity in Older People - Symptoms, Management, and Prevention

What Is Local Anesthesia Systemic Toxicity?

Local anesthesia systemic toxicity is a life-threatening condition that may occur after the administration of local anesthesia drugs through various routes. This can occur as a result of inadvertent intravascular injection or dosing error, and this can also result if the administered dose is not given within the recommended dose range.

What Is the Mechanism of Local Anesthesia Systemic Toxicity?

Local anesthesia is generally effective and safe in therapeutic doses for fascial planes, infiltration, and near-nerve plexus. Supratherapeutic plasma levels of local anesthesia can result in local anesthesia systemic toxicity (LAST). The mechanism of local anesthesia systemic toxicity occurs due to the following factors:

1. Plasma Concentration Factors -

• High Plasma Concentrations of Local Anesthetics:

1. Intravascular injections.

2. Rapid vascular absorption from a highly vascularized injection site.

3. Partial venous or arterial injection.

2. Plasma Levels of Local Anesthesia: Rate of systemic absorption from the site of therapy.

• Rate of Absorption: This varies among tissues, depends on the size of the absorptive surface, and depends on the vascularization of tissues and injection made. Increased doses are equal to increased plasma levels of local anesthesia.

3. Mechanism of Local Anesthesia at the Cellular Level:

• Primary Therapeutic Agent: Voltage-gated sodium channel inhibition alters axons' sensory and motor signals transmission.

• Inhibitory Action: Nerve conduction by inhibiting the movement of ions through voltage-gated ionotropic channels at cell membrane levels.

• Local anesthesia inhibits voltage-gated Ca2+ channels, K+ channels, Na-K ATPase, other channels, and enzymes.

• Non-ionized Versus Ionized Molecules: Inhibition occurs from the intracellular side and requires local anesthesia to cross the lipid bilayer and unbound non-ionized free molecules.

• At Higher Concentrations: Local anesthesia inhibits other channels of enzymes and receptors, including the carnitine-acylcarnitine translocase in mitochondria.

• At Lower Concentrations: Local anesthesia block protein kinase signaling induced by TNF-alpha (tumor necrosis factor-alpha) protein.

What Are the Signs and Symptoms of Local Anesthesia Systemic Toxicity?

The symptoms of local anesthesia systemic toxicity are:

• Local anesthesia affects the balance between excitatory and inhibitory pathways in the CNS (central nervous system).

• Neurological signs and symptoms range between excitation and depression.

• CNS is more sensitive to local anesthesia toxicity than CVS. The CNS symptoms precede CVS symptoms.

• Seizures.

• Dysarthria.

• Loss of consciousness.

• Metallic taste.

• Perioral paresthesia.

• Tinnitus.

• Progression to cardiac arrest.

• Heart conduction.

• Decreased systemic vascular resistance.

• Decreased cardiac contractility.

• Tachyarrhythmias.

• Depression of spontaneous pacemaker activity.

• Refractory hypotension.

• Cardiogenic shock.

What Are the Risk Factors of LAST (Local Anesthetic Systemic Toxicity)?

The risk factors of local anesthesia systemic toxicity are:

• Hepatic Dysfunction: Clearance rate is most relevant if agents are slowly absorbed, that is, if provided as continuous infusion.

• Renal Dysfunction: Acidosis and uremia increase free drug levels.

• Cardiac Dysfunction: Reduced cardiac reserve may render LAST more dangerous.

• Low muscle mass.

• Pregnancy.

• Carnitine deficiency, mitochondrial disease.

Specific Risk Factors:

• Nerve Blocks:

  1. Placement of catheter for prolonged anesthesia infusion.

  2. Failure to use ultrasound guidance.

  3. Bupivacaine has a greater risk than lidocaine or ropivacaine.

• Intravenous Lidocaine Infusions: Prolonged high-dose infusion.

• A Less Common Cause of LAST: Mucosal administration or large volume of subcutaneous administration.

What Is the Treatment Provided For LAST?

The first and initial treatment provided for local anesthesia systemic toxicity is to stop further administration of the local anesthesia if it is still being infused.

Lipid Emulsion:

An antidote to LAST is a 20 percent lipid emulsion. Precise indications are unclear and include the following:

• Substantial neurologic toxicity.

• Rapid clinical deterioration.

• Substantial cardiovascular effects.

• Potential side effects of lipid emulsion are nausea and vomiting, pancreatitis, allergic reactions, clogging of ECMO, thrombocytopenia, or dialysis circuits.

Hemodynamic Management:

If arrhythmias occur, do not administer lidocaine or procainamide. Avoid beta-blockers and calcium channel blockers.

• Amiodarone is a front-line arrhythmic for ventricular arrhythmias.

• Vasopressin is generally avoided.

Airway Management:

• Hypercapnia and hypoxemia exacerbate LAST.

• There should be a relatively low threshold for intubation to secure the airway.

• Hypoventilation can lead to vicious spirals that may exacerbate LAST.

Seizures:

• First line of therapy with benzodiazepines lorazepam 0.1 mg/kg IV (intra-venous) and Midazolam 10 milligrams IV or IM 9intra-muscular).

• Use Propofol cautiously, as they promote cardiac collapse.

• Ketamine and Levetiracetam can be reasonable antiepileptic agents, but there is no high-level evidence.

• Convulsions may worsen acidosis. Paralysis would not protect the brain from ongoing seizures, and efforts are made to stop seizures.

• Avoid Phenytoin as they exert anti-sodium channel activity.

Cardiopulmonary Bypass or ECMO (extracorporeal membrane oxygenation):

• Prolonged CPR (cardiopulmonary resuscitation) is indicated.

• Toxicity may last for one to two hours.

• If cardiopulmonary bypass or ECMO are available, they are indicated for refractory LAST.

What Is the Differential Diagnosis of LAST?

Differential diagnoses due to procedure complications are as follows:

• Hemorrhage.

• Pneumothorax.

• Side effects from other medications that are co-administered to facilitate procedural sedation.

Differential diagnoses due to methemoglobinemia are as follows:

• This occurs with Lidocaine, Prilocaine, and Benzocaine.

• Methemoglobinemia presents initially with cyanosis and desaturation.

Anaphylaxis:

• Anaphylaxis with local anesthesia is very rare.

• Anaphylaxis is more common if other medications are co-administered.

How to Prevent Local Anesthetic Toxicity in Older Individuals?

Prevention is the best treatment for local anesthetic toxicity in older individuals. There is an increased risk of local anesthesia systemic toxicity in petite individuals with more age and pre-existing heart disease or carnitine deficiency.

• Half of the cases are atypical, with no signs of seizures. The incidence of toxicity increases in vascular areas with injections. It is highest in paravertebral injections, followed by upper and lower extremities.

• Prevention requires optimizing the complete system, individual selection, drug and dose, nerve block choice, and complete monitoring of the individual.

• Prevention includes awareness and educating non-anesthesiology with proper use of local anesthesias and risk.

Conclusion:

An anesthesiologist uses local anesthesia daily in many practices and various procedures. The sites where local anesthesia is used in potentially toxic doses should be equipped with basic resuscitation equipment and 20 percent lipid emulsion. Electronic decision support is proven to improve adherence to guidelines during the stimulation of management of LAST. Individuals can be saved in rare events that are properly managed and diagnosed by non-anesthesiologists or others.