CONTENTS

• Epidemiology
• Presentation
• Differential diagnosis
• Treatment
• Podcast
• Questions & discussion
• Pitfalls

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epidemiology

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patient-dependent risk factors

• Hepatic dysfunction: Most anesthetics are hepatically cleared. Clearance rate is most relevant if the agent is slowly absorbed, administered in multiple doses, or provided as a continuous infusion.
• Cardiac dysfunction: Reduced cardiac reserve function may render LAST more dangerous (e.g., patients with severe chronic systolic heart failure or underlying conduction disease).
• Renal dysfunction: Uremia and acidosis may increase free drug levels, exacerbating toxicity.(33426662)
• Low muscle mass (e.g., older age, cachexia).
• Pregnancy (hyperdynamic circulation may accelerate systemic absorption following nerve blocks; reduced concentration of alpha-1 acid glycoprotein leads to higher free drug levels).
• Mitochondrial diseases, carnitine deficiency.

specific risk factors

• Nerve blocks:
  • High-volume blocks, with doses approaching the maximal safe dose range (see table below).
  • Placement of catheter for prolonged anesthetic infusion.
  • Failure to use ultrasound guidance. (29356773)
  • Bupivacaine has greater risks than ropivacaine or lidocaine. (29356773)
• Intravenous lidocaine infusions:
  • Prolonged, high-dose infusions.
• Less common causes of LAST:
  • Mucosal administration (e.g., bronchoscopy or awake intubation).
  • Large-volume, subcutaneous administration (e.g., to facilitate liposuction).

incidence of LAST following nerve blocks

• LAST has an incidence of roughly one per thousand nerve blocks.(33426662) This creates an interesting duality:
  • Overall, nerve blocks are a very safe procedure (often safer than the use of systemic analgesics).
  • At a large center which performs lots of nerve blocks, LAST is an event which will occasionally occur.

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presentation

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timing

• LAST can occur within minutes of local anesthetic administration (due to inadvertent intravenous administration).
• LAST can occur in a delayed fashion:
  • i) Due to gradual systemic absorption, following a single administration of local anesthetic. This may occur several hours after administration.
  • ii) Due to accumulation following a continuous infusion of local or systemic medication (e.g., intravenous lidocaine infusion).
• Delayed-onset LAST may be harder to diagnose because it's not obviously temporally linked to anesthetic administration and clinically it may evolve in a more gradual fashion.(31461049)

LAST typically begins with CNS symptoms

• Early symptoms may include:
  • Sensory abnormalities: auditory changes, tinnitus, metallic taste, circumoral numbness, visual disturbance (e.g., blurred vision), or dizziness.
  • Delirium, dysarthria, tremor, or anxiety.
  • Ideally patients would be diagnosed early, based on mild symptoms. Unfortunately, sedation may mask these initial features.
• 💡 Seizure was the most common presentation in one literature review.(31461049)
• Increasing drug levels may eventually cause somnolence, coma, and respiratory suppression.

cardiovascular symptoms usually occur second

• 🔑 Neurologic symptoms usually occur first, but a fifth of patients may initially present with cardiovascular abnormalities.(30122981)
• Initial features may include sympathetic activation (e.g., tachycardia, hypertension, diaphoresis).
• Later features may vary, including:
  • Bradycardia and AV block, widened QRS complexes.
  • Reduced contractility, which may manifest predominantly as hypotension.
• Ultimately, any form of cardiac arrest can occur (ventricular tachycardia, ventricular fibrillation, PEA, or asystole).
• Lidocaine tends to reduce contractility more, whereas bupivacaine and ropivacaine tend to cause more arrhythmias.

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differential diagnosis

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procedural complication (if nerve block is done to facilitate a procedure)

• Pneumothorax.
• Hemorrhage.
• Side effects from other medications which were co-administered to facilitate procedural sedation.

methemoglobinemia

• This may occur with benzocaine, lidocaine, or prilocaine.
• Typically, methemoglobinemia presents initially with desaturation and cyanosis.
• More on methemoglobinemia here.

anaphylaxis

• Anaphylaxis due to local anesthetics is very rare.
• Anaphylaxis is more likely if other medications are co-administered (e.g., antibiotic).
• More on anaphylaxis here.

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treatment

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stop further administration

• If anesthetic is being infused, stop it.

lipid emulsion

• The antidote to LAST is 20% lipid emulsion (e.g., Nutrilipid, Intralipid, or Liposyn III 20%).
• Precise indications are unclear, but may include:
  • Substantial neurologic toxicity (e.g., seizures).
  • Substantial cardiovascular effects (e.g., arrhythmias, hypotension, or cardiac arrest).
  • Rapid clinical deterioration.
• Optimal dosing isn't well defined. Dosing below is based on consensus guidelines, but may require titration to effect.
• Initial bolus:
  • >70 kg ideal body weight: Give 100 ml.
  • < 70 kg: Give 1.5 ml/kg ideal body weight.
  • May repeat bolus if needed.
• Infusion:
  • >70 kg: ~600-1,000 ml/hour.
  • <70 kg: 15 ml/kg/hour (0.25 ml/kg/minute) using ideal body weight.
  • For ongoing cardiovascular instability, re-bolus and double the infusion rate.
  • Continue the infusion for at least ten minutes after hemodynamic stability is achieved (usually for a total duration of 30-60 minutes).
• Dosing upper limit: Avoid a cumulative dose above:
  • > 84 kg: ~1 liter.
  • < 84 kg: 12 ml/kg ideal body weight.
  • Wean down the infusion rate over time to avoid going over this cumulative dose, if possible.
• Potential side effects of lipid emulsion include allergic reactions, nausea, vomiting, pancreatitis, thrombocytopenia, and clogging of ECMO or dialysis circuits.(31461049) Lipid interferes with measurement of laboratory tests, although this might be minimized by centrifuging the blood followed by removal of the lipid component.

airway management

• Hypoxemia and hypercapnia may both exacerbate LAST.
  • ⚠️ Hypoventilation may lead to a vicious spiral that exacerbates LAST.
• There should be a relatively low threshold for intubation to secure the airway.

hemodynamic management

• If arrhythmias occur:
  • Don't give lidocaine or procainamide!
  • Avoid pure beta-blockers or calcium channel blockers, which may exacerbate hypotension.
  • Amiodarone is the front-line antiarrhythmic for ventricular arrhythmias.(29356773)
• If epinephrine is required (e.g., for PEA arrest), it should be dose-reduced by a factor of about ten to avoid arrhythmia:
  • Instead of 1 mg doses, 1 microgram/kilogram doses are recommended.(29356773)
• Vasopressin is generally avoided (the primary problem is cardiogenic failure, so increasing the afterload may merely exacerbate that).(33426662)

seizures

• First-line therapy is with benzodiazepines; for example, beginning with an initial dose of:
  • Lorazepam 0.1 mg/kg IV.
  • Midazolam 10 mg IV or IM.
• Use propofol cautiously, as this may promote cardiac collapse.
• ⚠️ Avoid phenytoin, because phenytoin exerts anti-sodium channel activity.
• Ketamine and/or levetiracetam could be reasonable antiepileptic agents in this context, but no high-level evidence exists.
• Convulsions may worsen acidosis and thereby exacerbate the overall LAST toxicity. If seizures are resistant to benzodiazepine and intubation (with ketamine and/or propofol), neuromuscular paralysis might be an acceptable therapy to avoid muscular exertion that causes acidosis.(29356773) However, paralysis will not protect the brain from ongoing seizure activity, so simultaneous and aggressive efforts must be made to stop the seizures (e.g., including placement of video EEG monitoring and administration of additional antiepileptic medications).
• More on the management of status epilepticus here.

cardiopulmonary bypass or ECMO

• Toxicity can last 1-2 hours.
• Prolonged CPR may be indicated.
• If cardiopulmonary bypass or ECMO are available, these are indicated for refractory LAST.

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podcast

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questions & discussion

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To keep this page small and fast, questions & discussion about this post can be found on another page here.

• Nerve blocks are increasingly being performed by clinicians throughout the hospital (and even at outpatient clinics). Staff in any location where nerve blocks are being performed should be prepared to manage LAST.
• LAST may occur in a delayed fashion following large-volume blocks or indwelling catheters that infuse local anesthetic. Such cases may evolve gradually and be less obvious than reactions which occur immediately after anesthetic administration.

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