Toxicology and Overdose Management — Part 4: Toxic Alcohols, Metals, Organophosphates, Environmental & Chemical Poisonings
Complete management of methanol and ethylene glycol poisoning (fomepizole, hemodialysis), carbon monoxide, cyanide, organophosphates and nerve agents, iron poisoning, caustic ingestions, local anesthetic systemic toxicity (LAST), sympathomimetic toxicity, and enhanced elimination techniques including urinary alkalinization and EXTRIP hemodialysis indications.
1. Methanol Poisoning
1.1 Sources and Mechanism
Methanol (wood alcohol) is found in windshield washer fluid, antifreeze formulations, industrial solvents, and illicitly produced spirits. Methanol itself has relatively low toxicity; the danger lies in its metabolites. Alcohol dehydrogenase (ADH) converts methanol to formaldehyde, which is then rapidly converted to formic acid by aldehyde dehydrogenase. Formic acid inhibits cytochrome oxidase (complex IV of the mitochondrial electron transport chain), producing cellular hypoxia, lactic acidosis, and selective damage to the optic nerve and basal ganglia.1 2
1.2 Lethal Dose
The minimum lethal dose is approximately 1 mL/kg of pure methanol (about 60–240 mL in adults), though as little as 15 mL has been reported to cause blindness and 30 mL has caused death.
1.3 Clinical Presentation
| Phase | Time | Features |
|---|---|---|
| Early | 0–12 hours | Inebriation similar to ethanol; headache; nausea; GI distress. May be asymptomatic during this “latent period” while methanol is being metabolized. |
| Latent period | 12–24 hours | Relative improvement; methanol being converted to formic acid |
| Late/Toxic | 18–48 hours | Severe metabolic acidosis (elevated anion gap); visual disturbances (“snowfield” vision, blurred vision, photophobia, blindness); Kussmaul respirations; altered mental status → coma → death |
1.4 Diagnostic Evaluation
| Test | Finding |
|---|---|
| Osmol gap | Elevated early (methanol contributes to osmol gap) |
| Anion gap | Elevated late (formic acid accumulation); inversely related to osmol gap over time |
| Methanol level | Confirm diagnosis; level > 20 mg/dL generally warrants treatment; > 50 mg/dL is severe |
| Lactate | Elevated (formic acid inhibits oxidative metabolism) |
| ABG/VBG | Severe metabolic acidosis with respiratory compensation |
| Fundoscopy | Optic disc hyperemia, papilledema (if visual toxicity) |
1.5 Management
1.5.1 Fomepizole (4-Methylpyrazole) — Antidote of Choice
Fomepizole competitively inhibits alcohol dehydrogenase, blocking conversion of methanol to formaldehyde. It is the preferred antidote due to predictable pharmacokinetics, ease of dosing, and lack of CNS depression.1 3
| Component | Protocol |
|---|---|
| Loading dose | 15 mg/kg IV in 100 mL NS over 30 minutes |
| Maintenance | 10 mg/kg IV every 12 hours for 4 doses |
| After 48 hours | Increase to 15 mg/kg every 12 hours (fomepizole induces its own metabolism) |
| During hemodialysis | Dose every 4 hours (fomepizole is dialyzable) |
| Continue until | Methanol level < 20 mg/dL AND acidosis resolved AND patient clinically improved |
Indications for fomepizole:
- Methanol level > 20 mg/dL
- Strong clinical suspicion of methanol ingestion with osmol gap > 10 or anion gap metabolic acidosis
- History of methanol ingestion with any visual symptoms
Ethanol (as ADH inhibitor) may be used when fomepizole is unavailable:
- Loading dose: 0.8 g/kg IV (10% ethanol in D5W) or orally
- Target serum ethanol: 100–150 mg/dL
- Disadvantages: CNS depression, hypoglycemia, difficulty maintaining target level, requires ICU monitoring
1.5.2 Hemodialysis
Hemodialysis is the definitive treatment for removing methanol and its toxic metabolites. Recommendations from the extracorporeal treatments workgroup:4
| Indication | Recommendation |
|---|---|
| Methanol level > 50 mg/dL | Hemodialysis recommended |
| Severe metabolic acidosis (pH < 7.15) | Hemodialysis recommended |
| Visual disturbances | Hemodialysis recommended |
| Renal failure (inability to clear methanol/formate) | Hemodialysis recommended |
| Clinical deterioration despite antidote therapy | Hemodialysis recommended |
| Methanol level > 20 mg/dL with acidosis or symptoms | Hemodialysis strongly suggested |
Continue hemodialysis until: methanol level < 20 mg/dL, acidosis resolved, and clinical improvement.
1.5.3 Adjunctive Therapy
| Agent | Rationale | Dose |
|---|---|---|
| Folic acid (folinic acid/leucovorin preferred) | Enhances formic acid metabolism to CO₂ and water | 50 mg IV every 6 hours for 24 hours (or folic acid 50 mg IV q6h) |
| Sodium bicarbonate | Treat severe acidosis; maintain pH > 7.20 | 1–2 mEq/kg IV bolus; infusion as needed |
2. Ethylene Glycol Poisoning
2.1 Sources and Mechanism
Ethylene glycol is found in automotive antifreeze, de-icing solutions, and industrial coolants. It is metabolized by ADH to glycoaldehyde, then to glycolic acid (the primary source of the anion gap), then to glyoxylic acid, and finally to oxalic acid. Oxalic acid chelates calcium, forming calcium oxalate crystals that deposit in renal tubules and other tissues, causing acute kidney injury.1 2 5
2.2 Lethal Dose
The minimum lethal dose is approximately 1–1.5 mL/kg (roughly 100 mL in adults), though survival has been reported with much larger ingestions when treated early.
2.3 Clinical Stages
| Stage | Time | Features |
|---|---|---|
| Stage 1 — CNS | 0.5–12 hours | Inebriation (without ethanol odor), nausea, vomiting; may appear “drunk” without smelling of alcohol; elevated osmol gap; mild acidosis developing |
| Stage 2 — Cardiopulmonary | 12–36 hours | Severe anion gap metabolic acidosis; tachycardia; hypertension → hypotension; pulmonary edema; multiorgan failure; hypocalcemia (calcium chelated by oxalate); QTc prolongation |
| Stage 3 — Renal | 24–72 hours | Oliguric or anuric renal failure; flank pain; calcium oxalate crystalluria (envelope-shaped or needle-shaped crystals on urinalysis under polarized light); hematuria |
2.4 Diagnostic Clues
| Finding | Significance |
|---|---|
| Elevated osmol gap (early) → Elevated anion gap (late) | Characteristic temporal pattern |
| Calcium oxalate crystals on urinalysis | Highly suggestive (envelope/octahedral = monohydrate; needle-shaped = dihydrate); NOT always present |
| Hypocalcemia | Calcium chelation by oxalic acid; can cause tetany, QTc prolongation, cardiac arrhythmias |
| Fluorescence of urine under Wood lamp | Unreliable; sodium fluorescein is an additive in some but not all antifreeze products |
| Ethylene glycol level | Confirmatory; > 20 mg/dL warrants treatment |
2.5 Management
Treatment mirrors methanol poisoning with the following key differences:1 3 5
2.5.1 Fomepizole
Protocol is identical to methanol (see Section 1.5.1). Fomepizole blocks the initial metabolism step, preventing formation of toxic metabolites.
2.5.2 Hemodialysis
Recommendations from the extracorporeal treatments workgroup:6
| Indication | Recommendation |
|---|---|
| Ethylene glycol level > 50 mg/dL | Hemodialysis recommended |
| Severe metabolic acidosis (pH < 7.30) | Hemodialysis recommended |
| Acute kidney injury | Hemodialysis recommended |
| Deterioration despite fomepizole therapy | Hemodialysis recommended |
| Level > 20 mg/dL with acidosis or renal injury | Strongly consider hemodialysis |
Note on modern approach: If fomepizole is administered early (before significant metabolite accumulation), and the patient has normal renal function and no significant acidosis, hemodialysis may potentially be avoided even with moderately elevated ethylene glycol levels. The kidneys will gradually eliminate the parent compound while fomepizole prevents toxic metabolite formation. However, this strategy requires careful monitoring and toxicology consultation.3
2.5.3 Adjunctive Therapy
| Agent | Rationale | Dose |
|---|---|---|
| Thiamine (vitamin B₁) | Cofactor for metabolism of glyoxylic acid to non-toxic α-hydroxy-β-ketoadipic acid | 100 mg IV every 6 hours |
| Pyridoxine (vitamin B₆) | Cofactor for metabolism of glyoxylic acid to glycine (non-toxic) | 50 mg IV every 6 hours |
| Calcium | For symptomatic hypocalcemia (tetany, QTc prolongation) | Calcium gluconate 1–2 g IV; monitor ionized calcium |
| Sodium bicarbonate | For severe acidosis | 1–2 mEq/kg bolus; infusion as needed |
3. Carbon Monoxide (CO) Poisoning
3.1 Sources and Mechanism
Carbon monoxide is a colorless, odorless gas produced by incomplete combustion. Sources include house fires, motor vehicle exhaust, gas heaters, charcoal grills, and generators used indoors. CO binds hemoglobin with approximately 200–250 times the affinity of oxygen, forming carboxyhemoglobin (COHb), which shifts the oxyhemoglobin dissociation curve to the left and impairs oxygen delivery to tissues. CO also binds cytochrome oxidase, disrupting cellular respiration, and triggers inflammatory cascades via oxidative stress and lipid peroxidation.7
3.2 Clinical Presentation
| COHb Level | Symptoms (Non-Smoker) |
|---|---|
| < 10% | May be asymptomatic; mild headache |
| 10–20% | Headache, nausea, dizziness, exertional dyspnea |
| 20–30% | Severe headache, impaired judgment, visual disturbances, fatigue |
| 30–40% | Confusion, syncope, tachycardia, tachypnea |
| 40–50% | Coma, seizures, cardiovascular instability |
| > 50% | Cardiopulmonary failure, death |
Important caveats:
- Pulse oximetry is unreliable — standard pulse oximeters cannot distinguish COHb from oxyhemoglobin and will read falsely normal
- Diagnosis requires co-oximetry (measured on ABG/VBG)
- “Cherry red” skin color is a late/postmortem finding and is unreliable
- Levels poorly correlate with severity — a patient with COHb of 15% may be sicker than one at 25% depending on exposure duration
3.3 CO Half-Life by Oxygen Therapy
| Oxygen Therapy | Approximate CO Half-Life |
|---|---|
| Room air (21% O₂) | 320 minutes (approximately 5–6 hours) |
| 100% O₂ via non-rebreather mask | 60–90 minutes |
| Hyperbaric oxygen (HBO) at 2.5–3 ATA | 20–30 minutes |
3.4 Management
| Intervention | Details |
|---|---|
| Remove from exposure | Immediate; ensure scene safety for responders |
| 100% oxygen via non-rebreather mask (NRB) | Start immediately; continue until COHb < 5% and symptoms resolve (typically 6–8 hours of high-flow O₂) |
| Intubation | For coma, respiratory failure, or airway compromise |
| IV fluids | As needed for hypotension |
| Cardiac monitoring | CO poisoning can cause myocardial injury; obtain troponin and ECG |
| Hyperbaric oxygen | See Section 3.5 |
3.5 Hyperbaric Oxygen (HBO) — Indications
The role of HBO in CO poisoning remains debated, but it is generally recommended for the following indications:7 8
| Indication | Details |
|---|---|
| Loss of consciousness (at any point during exposure) | Strongest indication |
| COHb level > 25% (> 15–20% in pregnancy) | Level-based criterion |
| Cardiac ischemia or arrhythmia | CO-related myocardial injury |
| Severe metabolic acidosis | pH < 7.10 |
| Persistent neurologic symptoms despite 4–6 hours of NRB oxygen | Ongoing CNS effects |
| Pregnancy with COHb > 15–20% or any symptoms | Fetal hemoglobin has higher CO affinity; lower threshold |
Practical consideration: HBO requires transfer to a facility with a hyperbaric chamber. If transfer time exceeds 4–6 hours, the benefit may diminish. Continue 100% NRB oxygen during transport.
3.6 Delayed Neurologic Sequelae (DNS)
- Occurs in 10–30% of significantly poisoned patients
- Onset: days to weeks after exposure (classically 2–40 days)
- Features: cognitive deficits, personality changes, parkinsonism, memory impairment, dementia
- Risk factors: loss of consciousness, prolonged exposure, age > 36, COHb > 25%
- HBO may reduce the incidence of DNS (based on the Weaver et al. randomized trial), though evidence remains mixed8
4. Cyanide Poisoning
4.1 Sources
- House fires (combustion of synthetic materials — polyurethane, nylon, wool, silk produces hydrogen cyanide)
- Industrial exposure (metal plating, mining, chemical manufacturing)
- Ingestion (cyanide salts, acetonitrile-based nail polish removers, bitter almond extract)
- Iatrogenic (prolonged/high-dose nitroprusside infusion)
- Plants (amygdalin in bitter almonds, apricot/peach pits, cassava)
4.2 Mechanism
Cyanide binds to cytochrome oxidase (complex IV), halting aerobic metabolism. Cells switch entirely to anaerobic glycolysis, producing profound lactic acidosis. The brain and heart are most vulnerable due to high oxygen demand.9
4.3 Clinical Presentation
- Early: Headache, anxiety, confusion, tachycardia, tachypnea, hypertension
- Progressive: Bradycardia, hypotension, seizures, coma, apnea, cardiovascular collapse
- Classic finding: Lactic acidosis with high mixed venous oxygen saturation (cells cannot utilize oxygen; venous blood remains oxygenated) — “arterialization” of venous blood
- Bitter almond odor: Present in only 40–60% of the population (genetic ability to detect)
4.4 Cyanide Antidote Kits
4.4.1 Hydroxocobalamin (Cyanokit) — Preferred First-Line Antidote
Hydroxocobalamin (vitamin B12a) directly binds cyanide to form cyanocobalamin (vitamin B12), which is non-toxic and renally excreted.9 10
| Component | Protocol |
|---|---|
| Adult dose | 5 g IV over 15 minutes |
| Pediatric dose | 70 mg/kg IV (max 5 g) over 15 minutes |
| Repeat dose | May give a second 5 g dose if inadequate response |
| Advantages | Safe in smoke inhalation (no methemoglobin formation); can be given empirically; rapid onset; safe even if cyanide is NOT the cause |
| Side effects | Red discoloration of skin, urine, and mucous membranes (lasts 2–3 days); may interfere with colorimetric laboratory assays (CO-oximetry, lactate, creatinine, glucose) for 24–48 hours |
4.4.2 Sodium Thiosulfate
Acts as a sulfur donor for rhodanese-mediated conversion of cyanide to non-toxic thiocyanate.9
| Component | Protocol |
|---|---|
| Adult dose | 12.5 g IV (50 mL of 25% solution) over 10–20 minutes |
| Pediatric dose | 400 mg/kg IV (max 12.5 g) |
| Onset | Slow (30–60 minutes); often used as adjunct to hydroxocobalamin |
4.4.3 Nitrite-Based Cyanide Antidote Kit (Traditional)
The traditional kit (Taylor Pharmaceuticals) contains amyl nitrite pearls, sodium nitrite, and sodium thiosulfate. Nitrites generate methemoglobin, which preferentially binds cyanide (forming cyanmethemoglobin).9
| Agent | Dose | Limitation |
|---|---|---|
| Amyl nitrite (inhaled) | Crush pearl, inhale for 30 sec of each minute | Temporizing measure only; hypotension risk |
| Sodium nitrite (3%, 10 mL) | 300 mg IV (10 mL) over 5 minutes (adult); pediatric: 0.2 mL/kg (max 10 mL) | Contraindicated in smoke inhalation (concurrent COHb + MetHb = severe oxygen-carrying deficit); causes hypotension |
| Sodium thiosulfate | As above | Adjunct |
In fire-related cyanide exposure: Use hydroxocobalamin (not nitrites) because patients likely have concurrent CO poisoning, and inducing methemoglobinemia in a patient with elevated COHb is dangerous.
5. Organophosphate and Nerve Agent Poisoning
5.1 Mechanism
Organophosphates (OPs) and nerve agents irreversibly inhibit acetylcholinesterase (AChE), causing accumulation of acetylcholine at muscarinic and nicotinic receptors and in the CNS. “Aging” occurs when the OP-enzyme bond becomes permanent (timing varies by agent: soman ages within minutes; most agricultural OPs age over 24–48 hours).11 12
5.2 Clinical Features — SLUDGE/DUMBBBELS + Nicotinic + CNS
| Receptor Type | Mnemonic | Features |
|---|---|---|
| Muscarinic | DUMBBBELS | Diarrhea, Urination, Miosis, Bronchospasm, Bronchorrhea, Bradycardia, Emesis, Lacrimation, Salivation |
| Nicotinic | — | Fasciculations, muscle weakness, paralysis (including diaphragm), tachycardia, hypertension, mydriasis |
| CNS | — | Seizures, coma, respiratory depression |
The primary cause of death is respiratory failure from bronchorrhea, bronchospasm, and diaphragmatic paralysis.
5.3 Decontamination
- Remove all clothing
- Wash skin with soap and copious water (dilute hypochlorite for nerve agents)
- Protect healthcare workers with appropriate PPE (gown, gloves, respiratory protection)
- Activated charcoal for oral ingestion if within 1 hour (OP adsorption is variable)
5.4 Pharmacologic Management
5.4.1 Atropine — Muscarinic Antagonist (Primary Treatment)
| Component | Protocol |
|---|---|
| Initial dose | 2 mg IV (adult); pediatric: 0.05 mg/kg (minimum 0.1 mg) |
| Titration | Double the dose every 5 minutes until secretions dry (2 mg → 4 mg → 8 mg → 16 mg → 32 mg…) |
| Endpoint | Drying of bronchial secretions (the most important endpoint); clearing of bronchospasm; heart rate is NOT the endpoint |
| Massive exposure | May require tens to hundreds of milligrams of atropine over the first 24 hours |
| Infusion | 10–20% of loading dose per hour once stabilized |
| DO NOT | Atropine does NOT reverse nicotinic effects (weakness, fasciculations, paralysis) |
5.4.2 Pralidoxime (2-PAM) — Oxime Reactivator
Pralidoxime reactivates AChE before aging occurs, restoring function at nicotinic junctions (muscle strength, diaphragm function).11 12
| Component | Protocol |
|---|---|
| Loading dose | 1–2 g IV over 15–30 minutes (adult); pediatric: 25–50 mg/kg (max 1 g) |
| Infusion | 500 mg/hour (adult) continuous; pediatric: 10–20 mg/kg/hour |
| Continue | For at least 24 hours after atropine is no longer needed and patient has clinical improvement |
| Timing | Most effective if given within 24–48 hours of exposure (before aging occurs) |
| Side effects | Hypertension, tachycardia, muscle rigidity (if infused too rapidly), headache |
5.4.3 Seizure Management
| Agent | Dose |
|---|---|
| Benzodiazepines (first-line) | Diazepam 5–10 mg IV or midazolam 5–10 mg IM |
| Repeat as needed | Every 5–10 minutes |
| Avoid phenytoin | Ineffective for OP-induced seizures |
| Military autoinjectors | Diazepam 10 mg IM available in military MARK I/DuoDote kits |
5.5 Intermediate Syndrome
Occurs 24–96 hours after exposure; characterized by proximal muscle weakness, cranial nerve palsies, and respiratory failure. Requires continued respiratory support and pralidoxime. Not prevented by atropine.11
6. Iron Poisoning
6.1 Toxic Doses
| Dose (mg/kg of elemental iron) | Expected Severity |
|---|---|
| < 20 mg/kg | Non-toxic |
| 20–60 mg/kg | Mild to moderate toxicity |
| > 60 mg/kg | Severe toxicity |
| > 120 mg/kg | Potentially lethal |
Elemental iron content by salt:
| Iron Salt | % Elemental Iron |
|---|---|
| Ferrous sulfate | 20% |
| Ferrous gluconate | 12% |
| Ferrous fumarate | 33% |
6.2 Clinical Stages
| Stage | Time | Features |
|---|---|---|
| Stage 1 | 0–6 hours | GI toxicity: vomiting, diarrhea (may be hemorrhagic), abdominal pain |
| Stage 2 | 6–24 hours | Apparent improvement (“quiescent phase”); patient may seem to improve while systemic iron absorption continues |
| Stage 3 | 12–48 hours | Systemic toxicity: shock, metabolic acidosis (AGMA), hepatic failure, coagulopathy, renal failure |
| Stage 4 | 2–5 days | Hepatic necrosis (if it occurs) |
| Stage 5 | 2–6 weeks | GI scarring and strictures (pyloric/gastric outlet obstruction) |
6.3 Diagnostic Evaluation
| Test | Interpretation |
|---|---|
| Serum iron level (4–6 hours post-ingestion) | < 300 mcg/dL: unlikely significant toxicity; 300–500 mcg/dL: moderate toxicity; > 500 mcg/dL: severe toxicity; > 1,000 mcg/dL: potentially lethal |
| Abdominal radiograph | Iron tablets are radiopaque; can confirm ingestion and monitor decontamination |
| Total iron binding capacity (TIBC) | NOT reliable in acute overdose (falsely elevated); do NOT use the “serum iron > TIBC” rule |
| WBC > 15,000 or glucose > 150 mg/dL | Predictive of iron level > 300 mcg/dL (screening tool) |
6.4 Management
| Intervention | Details |
|---|---|
| Activated charcoal | NOT effective (iron is not adsorbed) |
| Whole bowel irrigation | Recommended for significant iron ingestion; PEG-ELS until rectal effluent is clear and tablets no longer visible on radiograph |
| Deferoxamine | See Section 6.5 |
| IV fluids | Aggressive resuscitation for hypovolemia and shock |
| Vasopressors | For refractory shock |
6.5 Deferoxamine — Iron Chelation Therapy
Deferoxamine chelates free iron, forming ferrioxamine (water-soluble, renally excreted, producing “vin rose” or pinkish-orange urine).13
| Component | Protocol |
|---|---|
| Dose | 15 mg/kg/hour IV continuous infusion |
| Maximum rate | 15 mg/kg/hour (higher rates associated with hypotension) |
| Maximum duration | 24 hours (longer infusions associated with ARDS) |
| Endpoint | Resolution of clinical toxicity, clearing of “vin rose” urine, declining iron levels, resolution of acidosis |
| Side effects | Hypotension (rate-related), ARDS (prolonged infusion > 24h), Yersinia enterocolitica sepsis (iron-dependent organism), urine discoloration |
Indications for deferoxamine:
- Serum iron level > 500 mcg/dL
- Severe clinical toxicity (shock, metabolic acidosis, altered mental status) at any level
- Serum iron > 350 mcg/dL with significant symptoms
7. Caustic Ingestions (Acids and Alkalis)
7.1 Mechanisms
| Type | Common Agents | Injury Pattern |
|---|---|---|
| Alkali (base) | Drain cleaners (NaOH, KOH), oven cleaners, bleach (concentrated), button batteries | Liquefactive necrosis — deep, penetrating injury; esophageal injury predominates; higher risk of perforation |
| Acid | Toilet bowl cleaners (HCl), battery acid (H₂SO₄), rust removers | Coagulation necrosis — superficial coagulum may limit initial depth (but does NOT prevent full-thickness injury with strong acids); gastric injury often predominates (pylorospasm traps acid) |
7.2 Management
| Intervention | Details |
|---|---|
| DO NOT induce vomiting | Risk of re-exposure of esophagus to caustic |
| DO NOT give activated charcoal | Not effective; obscures endoscopy; risk of vomiting |
| DO NOT attempt neutralization (acid for base or vice versa) | Exothermic reaction causes thermal injury |
| DO NOT place NGT blindly | Risk of perforation |
| NPO status | Until evaluation complete |
| IV fluids | Resuscitation as needed |
| Airway assessment | Stridor, voice changes, drooling suggest airway edema; early intubation if any concern (direct laryngoscopy preferred; small ETT may be needed) |
| CT of neck/chest/abdomen | May identify perforation, mediastinitis, or full-thickness injury |
| Endoscopy | Within 12–24 hours (optimally within 24 hours; avoid after 48 hours due to increased perforation risk during healing phase) |
7.3 Endoscopic Grading (Zargar Classification)
| Grade | Endoscopic Findings | Prognosis |
|---|---|---|
| 0 | Normal | No injury |
| 1 | Edema, erythema of mucosa | Excellent; no stricture risk |
| 2A | Superficial ulceration, friability, hemorrhage, exudates | Low stricture risk (< 5%) |
| 2B | Deep discrete or circumferential ulceration | Moderate stricture risk (up to 50%) |
| 3A | Focal necrosis (small areas) | High stricture risk (> 65%); perforation risk |
| 3B | Extensive necrosis | Perforation likely; may require surgery; high mortality |
7.4 Button Battery Ingestion
Requires special mention as a unique caustic emergency, particularly in pediatric patients:
- Esophageal impaction is a surgical emergency — lithium button batteries generate hydroxide ions via electrolysis, causing alkali burns that can perforate within 2 hours
- Obtain chest/abdominal radiograph immediately to locate the battery
- If lodged in esophagus: immediate endoscopic removal (within 2 hours)
- Pre-removal: honey (10 mL every 10 minutes if > 12 months old and able to swallow) or sucralfate to mitigate ongoing tissue injury while awaiting removal
- If past the esophagus: most will pass spontaneously; follow with serial radiographs; surgery only if symptomatic or not progressing
8. Local Anesthetic Systemic Toxicity (LAST)
8.1 Mechanism
Local anesthetic systemic toxicity occurs when plasma levels of local anesthetics exceed a toxic threshold, typically from accidental intravascular injection, excessive dosing, or rapid absorption. Local anesthetics block sodium channels in the CNS and cardiovascular system.14
8.2 Clinical Presentation
Toxicity progresses through CNS then cardiovascular stages:
| Phase | Features |
|---|---|
| CNS excitation (early) | Perioral numbness, metallic taste, tinnitus, agitation, tremor, dizziness |
| CNS depression | Seizures → CNS depression → coma → respiratory arrest |
| Cardiovascular | Hypertension and tachycardia (early) → bradycardia → conduction blocks → wide-complex arrhythmias → asystole |
Bupivacaine is the most cardiotoxic local anesthetic (high affinity for cardiac sodium channels, slow dissociation).
8.3 Intravenous Lipid Emulsion (ILE) Protocol — LAST Treatment
The lipid emulsion protocol for LAST is the most well-established indication for ILE therapy in toxicology.14 15
Protocol (20% Lipid Emulsion — e.g., Intralipid 20%)
| Step | Protocol |
|---|---|
| Bolus | 1.5 mL/kg of 20% lipid emulsion IV over 2–3 minutes |
| Infusion | 0.25 mL/kg/min for 30–60 minutes |
| Repeat bolus | If cardiovascular instability persists, may repeat bolus (1.5 mL/kg) one or two times at 5-minute intervals |
| Increase infusion | May double infusion rate to 0.5 mL/kg/min if blood pressure remains low |
| Maximum dose | Approximately 12 mL/kg total (over first 30 minutes) |
Mechanism of ILE: Creates a “lipid sink” that sequesters lipophilic local anesthetic molecules from tissue binding sites, and may provide a direct myocardial energy substrate.
Additional LAST Management
| Intervention | Details |
|---|---|
| Airway management | Intubate for seizures or respiratory failure |
| Seizures | Benzodiazepines first-line; small doses of propofol acceptable; avoid large propofol doses (additional cardiac depression) |
| Epinephrine | Use reduced doses (≤ 1 mcg/kg); standard ACLS doses of epinephrine may worsen toxicity |
| AVOID | Vasopressin, calcium channel blockers, beta-blockers, lidocaine (additional sodium channel blockade), and local anesthetics of any kind |
| CPR | Prolonged resuscitation may be warranted — patients can recover even after prolonged arrest if ILE is administered |
| ECMO/bypass | For refractory cardiac arrest |
9. Sympathomimetic Toxicity (Cocaine and Methamphetamine)
9.1 Clinical Presentation
Cocaine and amphetamines produce a sympathomimetic toxidrome through different mechanisms (cocaine: reuptake inhibition and sodium channel blockade; amphetamines: increased monoamine release and reuptake inhibition).16
| Feature | Details |
|---|---|
| Cardiovascular | Hypertension, tachycardia, acute coronary syndrome (vasospasm + thrombosis), aortic dissection, arrhythmias |
| CNS | Agitation, psychosis, seizures, intracranial hemorrhage, hyperthermia |
| Other | Rhabdomyolysis, disseminated intravascular coagulation, mesenteric ischemia |
9.2 Management Principles
| Intervention | Details |
|---|---|
| Benzodiazepines | First-line for ALL sympathomimetic emergencies: agitation, hypertension, tachycardia, seizures, chest pain. Diazepam 5–10 mg IV or midazolam 5 mg IV/IM; repeat as needed |
| Active cooling | For hyperthermia; target core temperature < 39°C |
| Nitroglycerin | For cocaine-associated chest pain/ACS |
| Phentolamine | Alpha-blocker; 5 mg IV for refractory hypertension |
| AVOID beta-blockers | Contraindicated in cocaine toxicity — “unopposed alpha stimulation” may worsen hypertension and coronary vasospasm. This applies to all beta-blockers including labetalol (its alpha-blocking component is insufficient to prevent the phenomenon) |
| Sodium bicarbonate | For cocaine-induced QRS widening (sodium channel blockade effect) |
| IV fluids | Aggressive hydration for rhabdomyolysis |
10. Enhanced Elimination Techniques
10.1 Urinary Alkalinization — Complete Protocol
Urinary alkalinization (formerly “alkaline diuresis”) enhances renal excretion of weak acids by ion trapping in the renal tubule.17
Solution: 150 mEq NaHCO₃ (three 50-mEq ampules) + 40 mEq KCl in 1 L D5W
Rate: 250 mL/hour initially; titrate to urine output 2–3 mL/kg/hour and urine pH 7.5–8.0
Monitoring:
- Urine pH every 1–2 hours (goal: 7.5–8.0)
- Serum pH every 2–4 hours (goal: 7.45–7.55; do NOT exceed 7.60)
- Serum potassium every 2 hours (goal: ≥ 4.0 mEq/L; hypokalemia is the most common reason for failure to alkalinize urine)
- Fluid balance, electrolytes, clinical status
Indications:
| Agent | Notes |
|---|---|
| Salicylates | Primary indication; significantly enhances renal clearance |
| Phenobarbital | Alternative to MDAC or hemodialysis for mild-moderate cases |
| Chlorpropamide | Enhances elimination |
| Methotrexate | Prevents crystalluria and enhances elimination |
| Chlorophenoxyacetic acid herbicides (e.g., 2,4-D) | Significantly enhances elimination |
10.2 Hemodialysis in Poisoning — EXTRIP Recommendations
The following table summarizes the key recommendations from the extracorporeal treatments in poisoning (EXTRIP) workgroup for the most clinically relevant toxins:4 6 18 19 20 21 22
| Substance | Hemodialysis Recommended When | EXTRIP Recommendation Strength |
|---|---|---|
| Methanol | Level > 50 mg/dL; visual symptoms; severe acidosis (pH < 7.15); renal failure | Strong |
| Ethylene glycol | Level > 50 mg/dL; severe acidosis (pH < 7.30); acute kidney injury | Strong |
| Salicylate | Level > 100 mg/dL; altered mental status; pulmonary edema; severe acidosis (pH < 7.20); renal failure | Strong |
| Lithium | Level > 4.0 mEq/L; significant neurologic symptoms; renal failure; level > 2.5 with renal impairment | Strong |
| Phenobarbital | Prolonged coma expected; hemodynamic instability despite supportive care | Strong |
| Theophylline | Acute level > 100 mg/L; chronic level > 60 mg/L; seizures; life-threatening arrhythmia; rising level despite MDAC | Strong |
| Valproic acid | Level > 900 mg/L; cerebral edema; hemodynamic instability; level > 1,300 mg/L in acute ingestion | Strong |
| Metformin | Lactate > 20 mmol/L; pH ≤ 7.0; refractory shock; failure of standard measures | Strong |
| Carbamazepine | Refractory seizures; life-threatening arrhythmia; prolonged coma despite MDAC | Conditional |
| Acetaminophen | Level > 900 mcg/mL with acidosis; mitochondrial dysfunction (early elevated lactate and acidosis with very high levels) | Conditional |
| Dabigatran | Life-threatening bleeding when idarucizumab unavailable | Conditional |
| Isopropanol | Refractory hypotension; level > 400 mg/dL with clinical deterioration | Conditional |
10.3 Continuous Renal Replacement Therapy (CRRT)
CRRT (CVVH, CVVHD, CVVHDF) provides lower clearance rates than intermittent hemodialysis but may be useful when:18
- Patient is hemodynamically unstable and cannot tolerate intermittent HD
- Substance has significant rebound (lithium, metformin) — CRRT may be continued after intermittent HD to prevent rebound
- Intermittent HD is unavailable
CRRT alone is generally NOT the preferred modality — intermittent hemodialysis provides far superior clearance for most dialyzable toxins.
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