Epidemiology of Substance Poisoning (Updated)

• Local anesthetics are frequent pharmaceutical exposures; lidocaine is among the most reported.

• Serious outcomes are uncommon but cluster with infant/child ingestions, large intentional overdoses, or repeated/stacked dosing.

• The FDA (2014) warns against using 2% viscous lidocaine for infant teething due to seizures, severe CNS depression, and deaths after small volumes.

Pharmacokinetics

Absorption and Peak Concentration

• Rapid oropharyngeal/mucosal absorption (partly bypasses first-pass metabolism).

• GI absorption is variable; Tmax ~30–60 min after ingestion; mucosal effects can start in 15–30 min.

• Oropharyngeal anesthesia transiently increases aspiration risk.

Metabolism

• Hepatic (CYP1A2, CYP3A4) → active metabolites MEGX (monoethylglycinexylidide) and GX (glycinexylidide).

Half-Life

• Adults: ~1.5–2 h (prolonged with hepatic disease/heart failure).

• Neonates/infants: longer (~3–5+ h).

Excretion

• Renal as metabolites; <10% excreted unchanged.

Bioavailability

• Oral ≈ 35% (first-pass). Mucosal absorption can produce higher, faster systemic exposure.

Mechanisms of Toxicity

• Voltage-gated sodium channel blockade → CNS excitation (tinnitus, perioral numbness, metallic taste) → CNS depression (seizures, coma).

• Cardiac: conduction slowing (PR/QRS prolongation), myocardial depression, ventricular dysrhythmias, hypotension (vasodilation + negative inotropy).

• Methemoglobinemia: very rare with lidocaine (far more common with benzocaine/prilocaine) but possible at high doses.

• Risk amplified by acidosis, hypercarbia, hypoxia, low α1-acid glycoprotein (infants), and CYP inhibitors.

Toxic Dose (Triage Thresholds for ED Referral)

2% = 20 mg/mL • 5 mL (1 tsp) = 100 mg • 15 mL (1 Tbsp) = 300 mg
Quick check: mg/kg = 20 × mL ingested ÷ weight (kg)

Refer to ED if ≥ any of the following (these are conservative triage cutoffs, not toxicity guarantees):

• Infants (<12 months): ≥1.5 mg/kg (≈ 0.075 mL/kg) or any non-therapeutic exposure.

• Children: ≥3 mg/kg (≈ 0.15 mL/kg) or any symptoms.

• Adults: ≥4.5 mg/kg (≈ 0.225 mL/kg), unknown amount, or any symptoms.

Examples

• 10-kg toddler @ 3 mg/kg → 30 mg ≈ 1.5 mL

• 20-kg child @ 3 mg/kg → 60 mg ≈ 3 mL

• 70-kg adult @ 4.5 mg/kg → 315 mg ≈ 16 mL

Higher risk at lower doses with: hepatic/cardiac disease, pregnancy, low body mass, CYP inhibitors (e.g., amiodarone, cimetidine, clarithromycin, fluoxetine, itraconazole, verapamil), or co-exposure to other local anesthetics.

Sources

• Prescription 2% viscous lidocaine (mouth/throat/esophageal analgesia).

• Other forms: dermal gels/sprays/patches, dental preparations, infiltration/nerve block solutions, IV antiarrhythmic (additive exposure risk).

Therapeutic and Toxic Serum Concentrations

• Therapeutic (antiarrhythmic): 1.5–5 µg/mL (mg/L)

• Early neurotoxicity: >5 µg/mL

• Seizures: ~8–12 µg/mL

• Severe cardiotoxicity/collapse: >20 µg/mL
  Levels are rarely timely and do not guide initial triage/management.

Clinical Presentation and Signs & Symptoms

Mild

• Perioral/tongue numbness, metallic taste, tinnitus, dizziness, visual blurring, nausea/vomiting, mild anxiety/drowsiness.

• Oropharyngeal anesthesia → aspiration risk.

Moderate

• Agitation, confusion, tremor, seizure, ataxia.

• Vitals: hypotension or tachycardia. ECG: PR/QRS prolongation, AV block.

Severe

• Refractory seizures/status epilepticus, coma.

• Ventricular dysrhythmias, profound hypotension, bradycardia/asystole, cardiovascular collapse.

• Methemoglobinemia (rare): cyanosis with normal PaO₂, chocolate-colored blood, low pulse oximetry unresponsive to O₂.
  Infants may present without a classic excitation prodrome—apnea or seizure can be the first sign.

Management of Toxicity (By Severity)

Immediate Priorities (all patients)

• ABCs, high-flow oxygen, IV access, continuous ECG + pulse oximetry; consider capnography.

• Check glucose early; correct hypoglycemia.

• NPO until gag returns (≈ 60 min after oropharyngeal anesthesia).

• Decontamination: No emesis. Activated charcoal only for large, early (<1–2 h) ingestions if airway is protected (intubated) due to aspiration risk.

Conduction delay & acidosis

• Optimize ventilation to correct hypercarbia/acidosis.

• If marked QRS widening from Na⁺ channel blockade, consider sodium bicarbonate 1–2 mEq/kg IV (bolus), especially with associated acidosis.

Mild

• Cardiac monitoring; antiemetics as needed.

• If asymptomatic after a small exposure: observe 4–6 h (children ≥6 h).

Moderate

• Seizures: Benzodiazepines first-line

  • Adults: lorazepam 0.1 mg/kg IV (max 4 mg) or diazepam 0.15–0.2 mg/kg IV.

  • Children: lorazepam 0.1 mg/kg IV (max 4 mg) or midazolam 0.1 mg/kg IV/IM.

  • Avoid phenytoin/fosphenytoin (Na⁺ channel blockers) in LAST.

• Hypotension: isotonic fluids → small epinephrine boluses (10–100 µg IV) if needed.

• Avoid vasopressin and avoid additional local anesthetics (e.g., do not use lidocaine as an antiarrhythmic).

Severe (LAST – Local Anesthetic Systemic Toxicity)

• 20% Intravenous Lipid Emulsion (ILE) – initiate early

  • Bolus: 1.5 mL/kg IV over ~1 min.

  • Infusion: 0.25 mL/kg/min.

  • If instability persists: repeat 1.5 mL/kg bolus up to 2–3× and increase infusion to 0.5 mL/kg/min.

  • Continue infusion ≥10 min after hemodynamic stability.

  • Upper limit: about 10–12 mL/kg in the first 30 min.

• ACLS with LAST modifications

  • Prefer amiodarone for ventricular dysrhythmias.

  • Keep epinephrine doses small; avoid vasopressin.

  • Avoid large doses of propofol in hemodynamically unstable patients.

• Airway control early for recurrent seizures/AMS (consider non-depolarizing NMBs if needed).

• Methemoglobinemia: Methylene blue 1–2 mg/kg IV over 5 min; may repeat once at 30–60 min. Use caution in G6PD deficiency.

• Hemodialysis is not useful (large Vd, protein binding, lipophilicity).

• Post-ILE caveat: lipemia may interfere with some lab assays and extracorporeal circuits.

Antidote

• 20% Intravenous Lipid Emulsion is the preferred “antidotal” therapy for severe LAST.

• Methylene blue is the antidote for clinically significant methemoglobinemia.

Observation Criteria

Children

• ED referral: any symptoms; any infant exposure beyond prescribed use; or ≥3 mg/kg (≈ 0.15 mL/kg of 2%).

• Monitoring: ≥6 h after last symptom; longer for large doses, hepatic disease, or interacting meds.

• Discharge: asymptomatic with normal ECG for ≥6 h and reliable caregivers.

Adults

• Home observation (with poison center guidance) may be acceptable if asymptomatic, <4.5 mg/kg by reliable history (e.g., <15–16 mL for a 70-kg adult), no risk factors/interactions, and ready access to care.

• ED referral: any symptoms, large/unknown amount, hepatic/cardiac disease, pregnancy, significant CYP inhibitors, or co-exposures to other local anesthetics.

• Monitoring: 4–6 h if asymptomatic; ≥6–8 h if symptomatic/high-risk; longer if ILE given.

Prevention and Public Health Measures

• Do not use viscous lidocaine for infant teething.

• Store in child-resistant containers; avoid bedside storage.

• Use measuring devices; avoid “sips/swigs”.

• Prefer swish-and-spit when appropriate; if swallowing is prescribed (e.g., esophageal pain), enforce strict dose limits and spacing (no redosing for several hours).

• Avoid eating/drinking for ~60 min after oropharyngeal application.

• Screen for CYP interactions; avoid stacking multiple local anesthetics.