Local Anesthetic Systemic Toxicity (LAST) is a rare but potentially life-threatening complication that can occur following the administration of local anesthetics. It occurs when local anesthetics reach supratherapeutic levels in systemic circulation, leading to adverse effects on the central nervous and cardiovascular systems. Clinical management of LAST relies on its rapid identification and a subsequent administration of lipid emulsion therapy.
The mechanism of LAST involves the interaction of local anesthetics with various targets including ionotropic and metabotropic receptors. In the brain, local anesthetics disrupt the balance between inhibitory and excitatory pathways, leading to neurological symptoms. At the cardiovascular level, they interfere with ion channels, particularly sodium channels, affecting cardiac conduction and contractility.
The hemodynamic effects of LAST can be severe and rapidly progressive. Early signs may include ECG changes such as prolonged PR and QTc intervals, QRS abnormalities, and ST segment changes. As toxicity progresses, patients may develop refractory brady- or tachyarrhythmias, high-degree AV blocks, or even asystole. Cardiogenic shock and refractory hypotension can occur due to decreased cardiac contractility. While the exact rates of morbidity and mortality associated with LAST are difficult to determine due to its rarity, it remains a significant concern in anesthesia practice.
The cornerstone of LAST clinical management is lipid emulsion therapy, also known as lipid rescue therapy (LRT). This involves the intravenous administration of a 20% lipid emulsion, which is thought to act as a “lipid sink,” extracting lipophilic local anesthetics from tissue. The American Society of Regional Anesthesia and Pain Medicine (ASRA) has published guidelines for LRT dosing and administration. Additional treatment for LAST includes supportive care, seizure management, and cardiovascular support. The prognosis for patients with LAST has improved significantly with the introduction of LRT, but outcomes depend on early recognition and prompt treatment.
Studies on lipid emulsion therapy have shown promising results in treating LAST. A systematic review and meta-analysis of 83 cases where lipid emulsion therapy was used for local anesthetic toxicity reported possible benefit in 71% of cases. Animal studies have demonstrated that lipid emulsion can increase the dosage of bupivacaine needed to produce asystole in rats and improve survival and hemodynamics in dogs with bupivacaine-induced cardiac toxicity. The binding capacity of lipid emulsions to local anesthetics has been found to correlate positively with the lipid solubility of the anesthetics, with bupivacaine showing the highest affinity. These findings support the “lipid sink” theory and provide a scientific basis for the efficacy of lipid emulsion therapy in the clinical management of LAST.
Prevention remains the best approach to managing LAST. This includes careful dosing of local anesthetics, use of ultrasound guidance for regional blocks, and aspiration before injection. Incremental injection techniques and the use of test doses can also help reduce the risk of intravascular injection. Ongoing education and the implementation of LAST treatment protocols in healthcare facilities are crucial for improving outcomes.
In conclusion, while LAST remains a serious complication of local anesthetic use, advances in understanding its mechanisms and the development of effective treatments have improved patient safety. Vigilance, proper technique, and preparedness for rapid intervention are key to managing this potentially life-threatening condition.
References
- Neal JM, Barrington MJ, Fettiplace MR, et al. The Third American Society of Regional Anesthesia and Pain Medicine Practice Advisory on Local Anesthetic Systemic Toxicity: Executive Summary 2017. Reg Anesth Pain Med. 2018;43(2):113-123. https://doi.org/10.1097/AAP.0000000000000720.
- Weinberg GL. Local Anesthetic Systemic Toxicity: A Historical Perspective. Reg Anesth Pain Med. 2010;35(2):162-166. https://doi.org/10.1097/AAP.0b013e3181d2306c.
- Di Gregorio G, Neal JM, Rosenquist RW, Weinberg GL. Clinical presentation of local anesthetic systemic toxicity: a review of published cases, 1979 to 2009. Reg Anesth Pain Med. 2010;35(2):181-187. https://doi.org/10.1097/AAP.0b013e3181d2310b.
- Sekimoto K, Tobe M, Saito S. Local anesthetic toxicity: acute and chronic management. Acute Med Surg. 2017;4(2):152-160. https://doi.org/10.1002/ams2.265.
- Neal JM, Woodward CM, Harrison TK. The American Society of Regional Anesthesia and Pain Medicine Checklist for Managing Local Anesthetic Systemic Toxicity: 2017 Version. Reg Anesth Pain Med. 2018;43(2):150-153. https://doi.org/10.1097/AAP.0000000000000726.
- Gitman M, Barrington MJ. Local Anesthetic Systemic Toxicity: A Review of Recent Case Reports and Registries. Reg Anesth Pain Med. 2018;43(2):124-130. https://doi.org/10.1097/AAP.0000000000000721.