Local Anesthetic Systemic Toxicity: Symptoms, Types, Causes and Treatment

Local anesthetic systemic toxicity (LAST) is a rare but potentially life-threatening complication that can occur when local anesthetic agents enter the bloodstream in excessive amounts. For clinicians and patients alike, understanding the symptoms, types, causes, and treatments of LAST is essential for improving outcomes and ensuring safety during procedures involving local anesthetics. This article breaks down the latest knowledge on LAST, drawing on recent research and clinical recommendations.

Symptoms of Local Anesthetic Systemic Toxicity

When local anesthetics enter the systemic circulation in toxic concentrations, they can affect multiple organ systems—most notably the central nervous system (CNS) and the cardiovascular system. Recognizing the symptoms early is pivotal to prompt intervention and better outcomes.

Symptom Type	Description	Typical Progression	Sources
Neurologic	Perioral numbness, tinnitus, confusion, seizures	Early, often first	2 3 4 5
Cardiovascular	Arrhythmias, hypotension, cardiac arrest	May follow CNS or occur first	2 3 4 7 8
Atypical	Isolated cardiovascular collapse or delayed onset	Can occur without CNS symptoms	2 4 8

Table 1: Key Symptoms of LAST

Spectrum of Symptoms

LAST does not always follow a textbook pattern, but there are some classic presentations alongside atypical ones.

Classic Neurologic Presentation

• Early signs often include circumoral (around the mouth) numbness, metallic taste, tinnitus (ringing in the ears), lightheadedness, and confusion.
• Progression can include muscle twitching, agitation, and, at higher blood concentrations, seizures and CNS depression leading to coma 2 4 5.

Cardiovascular Manifestations

• Frequently, cardiovascular symptoms follow the CNS signs, manifesting as hypotension, arrhythmias, bradycardia, and ultimately, cardiac arrest 2 4 7.
• However, in up to 20% of cases, cardiovascular symptoms arise without preceding CNS involvement, particularly with certain agents or delayed absorption 2 4 8.

Atypical and Delayed Presentations

• Not all patients follow the typical progression. Some may exhibit isolated cardiovascular collapse or have a delayed onset of toxicity, especially with continuous infusions or depot formulations 2 4 8.
• Symptoms may be masked or confused with other perioperative events, making vigilance crucial 5.

Types of Local Anesthetic Systemic Toxicity

LAST is not a "one size fits all" phenomenon. The clinical presentations and underlying mechanisms vary depending on the local anesthetic agent, route, dose, and individual patient factors.

Type	Features	Associated Agents/Contexts	Sources
CNS Toxicity	Seizures, altered mental status, coma	Most local anesthetics	2 3 4 5
Cardiotoxicity	Arrhythmias, cardiac arrest, hypotension	Bupivacaine, ropivacaine (notably)	4 7 9
Delayed	Symptoms hours after administration	Depot injections, continuous infusions	8 5

Table 2: Types of LAST

CNS Toxicity

• Most common initial presentation: The majority of LAST cases begin with CNS symptoms, as the anesthetic disrupts sodium channels in neurons, impairing normal function and leading to excitatory symptoms and, eventually, CNS depression 2 3 4 5.
• Seizures are reported as the single most frequent sign, present in over half of documented cases 3 5.

Cardiotoxicity

• Potentially catastrophic: Cardiac toxicity can manifest as arrhythmias, profound hypotension, and even cardiac arrest. This risk is particularly high with long-acting, high-potency agents like bupivacaine and ropivacaine 4 7 9.
• Cardiotoxic symptoms may occur after, with, or even in the absence of neurological symptoms 2 4 7.

Delayed and Atypical Presentations

• With techniques like local infiltration or continuous infusions, peak plasma levels can occur hours after the initial injection, leading to delayed onset of toxicity 5 8.
• Some cases present solely with cardiovascular symptoms, highlighting the importance of considering LAST even in the absence of CNS involvement 2 4 8.

Causes of Local Anesthetic Systemic Toxicity

Understanding the root causes of LAST is crucial for prevention. Incidence rates have declined with improved techniques, but risk remains—especially in certain settings.

Cause/Factor	Mechanism/Description	Risk Context	Sources
Intravascular Injection	Accidental injection into a blood vessel	Nerve block procedures	1 4 5 8
Excess Dose	Exceeding recommended maximum dose	Large-volume or cumulative dosing	4 5 7
Rapid Absorption	High vascularity at injection site leads to faster uptake	Intercostal, epidural, caudal blocks	5 8 10
Patient Factors	Small size, age, comorbidities, liver dysfunction	Elderly, children, frail patients	4 8
Drug Potency	Certain agents more likely to cause toxicity	Bupivacaine, etidocaine	7 9

Table 3: Causes and Risk Factors for LAST

Intravascular Injection

• The most common cause of LAST is unintentional intravascular injection of anesthetic during regional block placement 1 4 5 8.
• Even with ultrasound guidance, this risk cannot be fully eliminated 1 8.

Excessive Dose or Cumulative Toxicity

• Overdosing—either by exceeding maximum recommended amounts or by repeated administration—raises plasma levels to toxic thresholds 4 5 7.
• Large-volume depots can slowly absorb and cause delayed toxicity 5.

Rapid Systemic Absorption

• Injection into highly vascular areas (e.g., intercostal spaces) leads to quicker systemic uptake and increased risk 5 8 10.

Patient-Related Risk Factors

• Children, elderly, and frail patients (e.g., those with sarcopenia or liver disease) are at higher risk due to reduced clearance and smaller volume of distribution 4 8.

Drug-Related Risks

• Some agents, especially bupivacaine and etidocaine, have a higher propensity for cardiotoxicity due to their strong sodium channel binding 7 9.

Treatment of Local Anesthetic Systemic Toxicity

Prompt, evidence-based treatment can dramatically improve survival and outcomes in LAST. Management protocols have evolved with new therapies and a deeper understanding of the underlying mechanisms.

Step	Intervention/Action	Notes	Sources
Airway & Oxygen	Secure airway, provide high-flow oxygen	Prevent hypoxia, hypercarbia	5 6 9 11
Seizure Control	Benzodiazepines preferred; avoid large-dose propofol	Control CNS excitation, avoid cardiac depression	5 6 11
Cardiovascular Support	Chest compressions, low-dose epinephrine, avoid vasopressin	Minimize arrhythmogenic risk	4 9 11
Lipid Emulsion	IV lipid therapy (bolus + infusion)	Start at first sign of serious toxicity	5 9 11
Perfusion Team	Prepare for possible cardiopulmonary bypass	For refractory cardiac arrest	11

Table 4: Treatment Steps for LAST

Immediate Supportive Measures

• Airway and Breathing: Secure the airway, provide supplemental oxygen, and ensure adequate ventilation to prevent hypoxia and hypercarbia, which can worsen toxicity 5 6 9 11.
• Seizure Suppression: Use benzodiazepines for seizures. Avoid large doses of propofol or other anesthetics that can suppress cardiac function 5 6 11.

Cardiovascular Management

• Basic Life Support: Initiate chest compressions if needed.
• Epinephrine: Use only small doses (e.g., <1 mcg/kg) to minimize arrhythmias. Avoid vasopressin entirely, as it may worsen outcomes 4 9 11.

Lipid Emulsion Therapy

• Lipid Rescue: Administer intravenous lipid emulsion at the first sign of serious systemic toxicity. For adults over 70 kg, an initial bolus of 100 mL; for adults under 70 kg and children, 1.5 mL/kg 5 9 11.
• Lipid therapy works by sequestering lipophilic anesthetics and improving cardiac function 8 9.

Advanced Interventions

• Perfusion Support: For cardiac arrest unresponsive to standard therapy, prepare for extracorporeal circulation or cardiopulmonary bypass 11.
• Be Prepared: Have LAST treatment algorithms and lipid emulsion readily available in all areas where local anesthetics are administered 5 10 11.

Conclusion

Local anesthetic systemic toxicity is a rare but serious risk associated with the use of local anesthetics. Vigilance, early recognition, and prompt evidence-based intervention are key to improving patient outcomes. Here’s what we’ve covered:

• Symptoms: LAST can present with neurologic (e.g., seizures, confusion) and cardiovascular (e.g., arrhythmias, hypotension) symptoms, sometimes in atypical patterns or with delayed onset.
• Types: Manifestations include classic CNS toxicity, cardiotoxicity, and delayed/atypical forms.
• Causes: Accidental intravascular injection, excessive dosing, rapid absorption, high-risk patient factors, and use of potent agents like bupivacaine are leading contributors.
• Treatment: Immediate airway management, seizure control, cautious cardiovascular support, and rapid administration of intravenous lipid emulsion are cornerstones of therapy.

Key points to remember:

• LAST is rare but potentially fatal—prevention and rapid response save lives.
• Symptoms may be neurologic, cardiovascular, or both, and can be delayed.
• Know the risk factors: agent, dose, patient, and technique.
• Lipid emulsion therapy has revolutionized LAST management; have it ready.
• Always follow updated protocols and maintain a high level of preparedness.

By staying informed and prepared, clinicians can minimize the risks of LAST and ensure safer outcomes for their patients.