Unintended Systemic Absorption of Local Anesthesia

Local anesthetics (LAs) are commonly administered by a variety of medical professionals, including anesthesia clinicians, surgeons, emergency department providers, dentists, and others. In general, LAs are safe and have minimal side effects. However, it is important to note that local anesthetic systemic toxicity (LAST), in which there is systemic absorption of local anesthesia, is a rare but severe complication that can occur with any type of local anesthetic and via any route of administration.

The reported incidence of major LAST events associated with regional anesthesia is very low. Data on LAST incidence mainly comes from registry studies and retrospective reviews of many regional anesthetics, with few reported events. The adoption of more advanced guidance for injecting local anesthesia and the increased use of novel blocks are likely to affect how often systemic absorption due to imperfect injections occurs. In a study of 238,437 patients undergoing peripheral nerve blocks for total joint arthroplasty from 2006 to 2014, the overall LAST incidence was 1.8 per 1000. Over this period, outcomes declined (from 8.2 per 1000 in 2006 to 2.5 per 1000 in 2014), while lipid emulsion use increased (from 0.2 to 2.6 per 1000).

As traditionally outlined in literature and older research, LAST typically manifests shortly after the injection of LA. It progresses through stages of central nervous system (CNS) excitation, followed by CNS inhibition, cardiovascular excitation, and in severe cases, cardiovascular inhibition and arrest. Risk factors for LAST include patient-related factors that elevate the free plasma drug concentration or increase sensitivity to LA. The potential for systemic absorption is heightened at highly vascular block sites, irrespective of the local anesthesia drug or dose administered. Alongside the total dose per body weight, patient and procedural factors can significantly impact plasma levels in adults, thereby impacting the risk of toxicity.

Low alpha 1 acid glycoprotein (AAG) levels can increase free plasma LA concentrations, particularly in infants under four months with immature hepatic clearance, necessitating a 15% dose reduction in repeat or continuous administration compared to standard doses. Infants and young children are at increased risk of LAST due to their small size, especially with topical administration. The FDA warns against using viscous lidocaine 2% in young children due to the risk of severe LAST or death. In older adults, deteriorating hepatic function and perfusion reduce LA clearance, increasing LAST risk with repeated or continuous dosing. Additionally, nerves are more sensitive to LAs in older adults, often requiring lower doses for effective blocks than in younger patients.

Various strategies can mitigate the risk of LAST. These include administering the lowest effective dose, employing safe injection practices, using ultrasound guidance, and avoiding heavy sedation. The total local anesthetic dose should be the minimum necessary for the desired block extent and duration. It is noteworthy that systemic toxicity can arise within recommended dose ranges, while exceeding maximum recommended doses has been done without toxicity. Safe injection practices, such as slow incremental injection, aspiration before injection, and ultrasound guidance, can further reduce LAST risk.

Swift recognition and management in the event of systemic absorption of local anesthesia is essential for protecting patient safety and must focus on preventing hypoxia and acidosis, suppressing seizures, and providing cardiovascular support. For patients showing seizures or signs of cardiovascular toxicity (e.g., arrhythmias, severe hypotension, or cardiac arrest), intravenous lipid emulsion (ILE) along with advanced life support is recommended. Although the mechanism and optimal dose of lipid rescue are still unclear, LAST can be fatal, and adverse effects of lipid emulsion are rare.

References

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Mörwald EE, Zubizarreta N, Cozowicz C, Poeran J, Memtsoudis SG. Incidence of Local Anesthetic Systemic Toxicity in Orthopedic Patients Receiving Peripheral Nerve Blocks. Reg Anesth Pain Med. 2017 Jul/Aug;42(4):442-445. doi: 10.1097/AAP.0000000000000544. PMID: 28079735.

Rubin DS, Matsumoto MM, Weinberg G, Roth S. Local Anesthetic Systemic Toxicity in Total Joint Arthroplasty: Incidence and Risk Factors in the United States From the National Inpatient Sample 1998-2013. Reg Anesth Pain Med. 2018 Feb;43(2):131-137. doi: 10.1097/AAP.0000000000000684. PMID: 29280923; PMCID: PMC5777869.

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