This column supports excellence in perioperative nursing by addressing key clinical issues and best practices, with this inaugural column focusing on local anesthetic systemic toxicity (LAST). Perioperative nurses administer or assist with procedures that involve local anesthetics, including topical, infiltrative, and regional techniques, and should therefore be informed about LAST to ensure patient safety, particularly in outpatient and office-based environments where emergency resources may be limited. Early recognition of LAST and immediate treatment, especially lipid emulsion therapy, can be lifesaving. Ongoing education and preparation reduce the risk of severe complications and align with best practices in perioperative nursing care. DEFINITION Local anesthetic systemic toxicity (LAST) is a rare but potentially life-threatening complication that can occur after administration of local anesthetics. It may result from inadvertent intravascular injection, topical application (eg, oropharyngeal spray), or overdose. Most cases are associated with accidental intravascular injection or absorption of excessive doses. LAST may occur during peripheral nerve blocks in highly vascular areas, including interscalene, supraclavicular, and femoral regions, as well as with epidural or spinal anesthesia, field blocks, local infiltration, and tumescent anesthesia used in liposuction when large volumes of dilute lidocaine are applied.1 Local anesthetics act by blocking sodium channels, preventing nerve signal transmission. When absorbed systemically in large amounts, they interfere with neural and cardiac conduction, leading to the signs and symptoms of LAST. EPIDEMIOLOGY The true frequency of LAST is difficult to determine because of the widespread use of local anesthetics, underreporting, and the fact that many cases involve only minor symptoms. LAST has been estimated to occur in 0.03% of peripheral nerve blocks or 0.27 episodes per 1000 blocks.2 Importantly, LAST is not limited to regional anesthesia. Case series have shown that up to 20% of incidents occur during simple tissue infiltration with local anesthetics.3–5 SIGNS AND SYMPTOMS LAST is often underrecognized and underreported. Its presentation usually progresses through 3 phases: initial, excitation, and depression, which reflect the effects of local anesthetics on the central nervous system (CNS) and cardiovascular system over time.1 Symptoms usually appear within 1 to 5 minutes of administration but can occur as early as 30 seconds or as late as 60 minutes after exposure.6 In the initial phase, local anesthetics disrupt inhibitory neurons, which normally slow neural activity. This disruption causes early sensory and neurologic symptoms, which may be masked under general anesthesia. In the excitation phase, unchecked activity of excitatory neurons causes CNS hyperactivity, which increases signal transmission and responsiveness. In the depression phase, systemic anesthetic levels suppress both CNS and cardiovascular function, leading to arrhythmias, widened QRS complexes, PR prolongation, and possible cardiovascular collapse (Table 1). Table 1 - Phases of local anesthetic systemic toxicity (LAST) and associated signs/symptoms. Phase Signs and symptoms Initial Metallic taste Perioral numbness (eg, tongue, lips) Auditory changes (eg, tinnitus) Dizziness Diplopia Dysarthria (eg, slurred speech) Tachycardia/hypertension Excitation Agitation Shivering Tremors Delirium Seizures Bradycardia/hypotension Depression Syncope Respiratory arrest Coma Ventricular arrhythmias (eg, ventricular tachycardia, Torsades de Pointes, ventricular fibrillation, asystole) Recent studies demonstrate that atypical presentations, including isolated cardiovascular dysfunction or subtle CNS signs, may account for nearly half of all LAST cases. Delayed onset, defined as greater than 5 minutes and up to 1 hour after injection, is increasingly recognized.6 Nurses and other health care professionals should differentiate LAST from other complications, including vasovagal reactions, allergic responses, or seizure disorders unrelated to anesthetic use. Maintaining a high index of suspicion and rapid assessment supports accurate diagnosis and prompt treatment. MANAGEMENT The American Society of Regional Anesthesia and Pain Medicine (ASRA) LAST Checklist provides an evidence-based protocol for recognizing and managing LAST7 (Fig. 1). Critical interventions include airway support, seizure control, and rapid administration of intravenous lipid emulsion therapy.Figure 1.: Local Anesthetic Systemic Toxicity Checklist. ACLS = Advanced Cardiac Life Support; LAST = local anesthetic systemic toxicity. Reprinted with permission from Neal et al. 7 Copyright 2020 by the American Society of Regional Anesthesia and Pain Medicine.Nurses should act quickly by notifying anesthesia providers and surgical team members, stopping further administration of anesthetic, and supporting the airway and ventilation with 100% oxygen. Anesthesia providers should begin lipid emulsion therapy using a 20% solution (eg, Intralipid 20%, Fresenius Kabi USA, LLC), which binds lipophilic anesthetics, including lidocaine and bupivacaine, to reduce toxicity. Providers should treat seizures with intravenous benzodiazepines, including midazolam or diazepam. Vasopressors may be required for hemodynamic support, and large doses of propofol should be avoided because of negative cardiac effects in unstable patients.1 Nurses should prepare for advanced cardiac life support and assist with resuscitation if necessary. Nurses must carefully document all vitals, treatments, and time points. Timely recognition and rapid action are critical for survival. Events should be reported to risk management or institutional safety databases to support quality improvement. TOXICITY OF LOCAL ANESTHETICS No dose of local anesthetic is completely safe if administered incorrectly.8 Toxicity depends on the plasma concentration and rate of absorption. Intra-arterial injections are more dangerous than intravenous ones. Bupivacaine, levobupivacaine, and ropivacaine are more cardiotoxic than lidocaine or prilocaine. Understanding the pharmacokinetics of each agent, including lipid solubility, protein binding, and clearance, is essential when selecting a local anesthetic, especially for high-risk patients or procedures involving large volumes. Table 2 outlines the maximum recommended doses and durations of amide local anesthetics. Table 2 - Maximum recommended doses and durations of amide local anesthetics. Agent Route Onset (min) Max dose without epi Duration (min) Max dose with epi Duration (min) Bupivacaine Infiltration, subcutaneous (SC) 2–10 2–2.5 mg/kg(max 175 mg)Max 400 mg per 24 h 120–175 2.5–3 mg/kg (max 225 mg)Max 400 mg/24h 180–480 Levobupivacaine Infiltration, SC Not specified 2 mg/kg(max 150 mg) 180–360 3 mg/kg Not specified Lidocaine Topical—Skin 3–5 4.5 mg/kg(max 300 mg) 30–120 — — Topical—Mucous Mem. Not specified 4.5 mg/kg (max 300 mg/dose)Max 2400 mg per 24 h Not specified — — Infiltration, SC 1–3 4.5 mg/kg(max 300 mg) 30–120 6–7 mg/kg(max 500 mg) 120–240 Mepivacaine Infiltration, SC 3–20 4.5–5 mg/kg(max 400 mg)Max 1000 mg per 24 h 45–90 6.6 mg/kg(max 500 mg) 120–330 Ropivacaine Infiltration, SC 3–15 2–3 mg/kg(max 225 mg) 120–240 3–4 mg/kg(max 225 mg) 180–480 Reference: University of Iowa Health Care, Department of Anesthesia.9 PATIENT RISK FOR LAST Certain patient factors and comorbidities increase the risk of LAST. Procedures performed in highly vascular areas, including paravertebral, intercostal, and fascial plane blocks, carry a higher risk because of increased systemic absorption.10 These techniques often require larger anesthetic doses to reach target nerves and may involve multiple nerves in a single block. Patients at the extremes of age are also at increased risk because of lower muscle mass available to absorb and metabolize the anesthetic.6 Individuals with chronic cardiac or renal disease are particularly vulnerable. In patients with reduced ejection fraction, local anesthetics circulate more slowly, delaying uptake by the liver and muscles. Patients with coronary artery disease are more susceptible to ischemia, and those with preexisting arrhythmias may develop anesthetic-induced rhythm disturbances more readily.10 Local anesthetics bind to alpha-1 acid glycoprotein in the bloodstream. Infants and pregnant women often have lower levels of this protein, which increases their risk for LAST because more unbound, active drug remains in circulation.11 Special consideration should be given to patients receiving compounded12 or topical13 anesthetics for cosmetic procedures, as absorption rates vary, and systemic toxicity has been reported. PROGNOSIS With prompt treatment and supportive care, including oxygenation, ventilation, and adequate cardiac output, most patients recover fully. Without intervention, LAST can cause seizures, respiratory and cardiac arrest, and death.14 In 2022, poison control centers reported 895 lidocaine exposures. Most resulted in no or minor effects, but 38 caused major outcomes, and 4 resulted in death.15 PREVENTION No single measure eliminates the risk of LAST, but multiple strategies can reduce it significantly. Providers should use the lowest effective dose, inject incrementally, and aspirate before each injection. They should account for the additive effects of multiple anesthetics, use ultrasound guidance when available, and include dosing in the preoperative briefing. A LAST rescue kit should be available and include 1 L of 20% lipid emulsion, an intravenous infusion set, two 60 mL syringes, large-bore needles, and the ASRA LAST Checklist7 as a cognitive aid. A typical 70 kg (154 pounds) adult requires 105 mL of lipid emulsion administered rapidly, which underscores the importance of keeping these tools accessible.1 Rescue kits should be stored wherever local anesthetics are administered. Ultrasound use reduces the risk of LAST by 65%.16 Small doses of epinephrine (10–15 mcg/mL) can help detect intravascular injection through heart rate increases.6 Even with ultrasound, nurses should aspirate and inject small aliquots slowly. In patients with low cardiac output or during distal extremity injections, providers should wait 15 to 30 seconds between aliquots.10 Patients should be monitored for 30 to 45 minutes after procedures to detect delayed toxicity. Informed consent should include a discussion of the risks, signs, and interventions for LAST, especially in outpatient settings. Personnel who may be first responders should be educated and trained to recognize LAST, use rescue kits, and activate emergency protocols. This education and training is particularly important in nonhospital environments where anesthesia personnel may not be present. PATIENT MONITORING AFTER LAST The ASRA LAST Checklist recommends monitoring for 4 to 6 hours after a cardiovascular event and at least 2 hours after a CNS event because symptoms can recur.7 ROLE OF HUMAN FACTORS Human factors (eg, environment, workflow, communication, cognitive load) play a significant role in LAST risk. These factors contribute to both the occurrence and delayed recognition of events. Common issues include insufficient monitoring, medication errors, and lapses in safety protocols, including skipping aspiration, test dosing, or incremental injection.17 Teams can mitigate these risks by maintaining consistent neurologic and cardiovascular monitoring, following standardized safety protocols, using low-dose epinephrine to detect intravascular injection, and conducting regular simulations and debriefings. Nurses should ensure immediate access to lipid rescue kits, dosing guides, and cognitive aids.17 By addressing human factors through structured education, system improvements, and a culture of safety, perioperative teams can reduce the risk of LAST and improve patient outcomes. Conflicts of interest statement The authors have no conflicts of interest to disclose. Funding source None. Nursing Continuing Professional Development Please be sure to visit http://www.cc-institute.org/Additional-Points-Activities for a free points activity related to this topic.
Sharon Ann Van Wicklin (Fri,) studied this question.