What are the presentations of Local Anesthetic Systemic Toxicity (LAST)?

From the Guidelines

Local anesthetic systemic toxicity (LAST) typically presents with a constellation of CNS and cardiovascular symptoms, including seizures, agitation, syncope, obtundation, dizziness, and life-threatening cardiovascular toxicity such as asystole, ventricular fibrillation, or ventricular tachycardia, as reported in the most recent guidelines 1. The presentation of LAST can vary depending on the potency of the local anesthetic used, with more potent agents like bupivacaine being more likely to cause severe cardiovascular toxicity 1. Key symptoms of LAST include:

• CNS toxicity, which occurs in 77%–89% of patients, and can manifest as seizures, agitation, syncope, obtundation, and dizziness
• Cardiovascular toxicity, which occurs in 32%–55% of patients, and can be life-threatening, with symptoms such as asystole, ventricular fibrillation, or ventricular tachycardia The variability in presentation and severity of LAST highlights the importance of prompt recognition and treatment to minimize morbidity and mortality. According to the most recent guidelines, the optimal treatment for LAST is not well understood, but it is crucial to prioritize airway management, seizure suppression, and cardiovascular support to prevent long-term sequelae and improve quality of life 1. In terms of specific treatment, the use of 20% lipid emulsion therapy may be recommended for significant cardiovascular toxicity, as it can create a "lipid sink" that extracts local anesthetic from tissues and provides a direct cardiotonic effect, although this is not explicitly stated in the most recent guidelines 1. It is essential to note that the treatment of LAST should be guided by the most recent and highest-quality evidence, and clinicians should be mindful of the potential for toxicity and take steps to ensure patient safety, including the use of ultrasonographic guidance and intravascular markers to avoid introducing the drug directly into a vessel 1.

From the Research

Presentation of Local Anesthetic Systemic Toxicity

• Initial symptoms are characterized by central nervous system signs such as excitation, convulsions, followed by loss of consciousness and respiratory arrest 2
• These symptoms are often accompanied with cardiovascular signs such as hypertension, tachycardia and premature ventricular contractions 2
• Further increase of plasma concentration of local anesthetic induces bradycardia, conduction disturbances, circulatory collapse and asystole 2
• Neurological presentation is most common, but LAST often presents atypically, and one-fifth of the reported cases present with isolated cardiovascular disturbance 3
• Clinical presentation can be highly variable, however, and atypical presentations are not uncommon 4

Risk Factors

• Infants, patients with decreased liver function and low cardiac output are vulnerable to systemic toxicity 2
• Patients at extremes of age or with organ dysfunction are at higher risk 5
• Inadvertent intra-arterial or intravenous injection, as well as repeated doses and higher doses of local anesthetics are associated with greater risk of developing LAST 5

Mechanisms

• Systemic toxicity of local anesthetic is induced by an increase of its protein-unbound plasma concentration 2
• The underlying mechanisms of LAST are multifactorial, with diverse cellular effects in the central nervous system and cardiovascular system 3
• Local anesthetic cardiotoxicity primarily arises from a blockade of sodium channels 6

Prevention and Treatment

• Prevention of local anesthetic systemic toxicity can be achieved by careful choice and dosing of drugs, aspiration before injection, dose fractionation, use of intravascular markers and ultrasound guidance 4
• Management of LAST includes adequate oxygenation and ventilation, seizure termination, maintenance of circulation, and intravenous lipid emulsion therapy 4
• Early recognition and intervention, including supportive care and intravenous lipid emulsion 20%, are the mainstays of treatment 5
• Lipid emulsion therapy should be a primary element in the treatment of cardiovascular LAST 6