9.2 Pediatric Toxicology, Toxidromes & Emergency Antidotes

9.2 Pediatric Toxicology, Toxidromes & Emergency Antidotes

Pediatric toxicologic emergencies represent a major cause of emergency department admissions, ranging from exploratory ingestions in toddlers to intentional self-poisoning in adolescents. The pediatric emergency nurse must rapidly recognize clinical toxidromes, initiate decontamination when indicated, interpret diagnostic nomograms, and administer life-saving antidotes.

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Acetaminophen (APAP) Toxicity & N-Acetylcysteine (NAC)

Acetaminophen (APAP) is the most common pediatric medication overdose. In acute ingestions, a dose exceeding 150 mg/kg in pediatric patients (or >7.5 to 10 grams in adults) is potentially hepatotoxic.

Pathophysiology of APAP Toxicity

At therapeutic doses, acetaminophen is metabolized by hepatic glucuronidation and sulfation. In overdose, these primary metabolic pathways become saturated, forcing excess APAP through the cytochrome P450 (CYP2E1) system. This generates the highly reactive, toxic intermediate N-acetyl-p-benzoquinone imine (NAPQI). NAPQI rapidly depletes hepatic glutathione stores. Once glutathione levels fall below 30% of normal, NAPQI binds covalently to hepatic parenchymal proteins, causing acute centrilobular hepatic necrosis.

Four Clinical Stages of Acetaminophen Toxicity

Diagnostic Management & The Rumack-Matthew Nomogram

• Serum APAP Level: Drawn at 4 hours post-ingestion (levels drawn prior to 4 hours cannot be plotted accurately due to ongoing GI absorption).
• Rumack-Matthew Nomogram: Used exclusively for single acute ingestions with a known time of ingestion between 4 and 24 hours. If the 4-hour serum APAP level plots at or above the treatment line (150 mcg/mL at 4 hours), antidote therapy must be initiated immediately.

       APAP SERUM CONCENTRATION (mcg/mL)
        400 ┬──────────────────────────────────────────┐
            │                     \                    │
        200 ┼───────────────────────\  [TREATMENT LINE]│  <-- Start NAC if at or
            │                        \                 │      above this line!
        100 ┼─────────────────────────\                │
            │                          \               │
          0 ┴───┬───────┬───────┬───────┬──────────────┘
                4       8      12      16   TIME (Hours)

Antidote Protocol: N-Acetylcysteine (NAC)

N-Acetylcysteine (NAC) acts as a glutathione precursor, directly detoxifying NAPQI and restoring hepatic glutathione reserves. NAC is virtually 100% effective in preventing severe liver injury when administered within 8 hours of acute ingestion.

• Intravenous NAC Protocol (Acetadote): Total 300 mg/kg IV infused over 21 hours in 3 distinct steps:
  1. Loading Dose: 150 mg/kg IV in 5% dextrose over 1 hour.
  2. Second Dose: 50 mg/kg IV over 4 hours.
  3. Third Dose: 100 mg/kg IV over 16 hours.
• Oral NAC Protocol: 140 mg/kg loading dose PO/NG, followed by 70 mg/kg PO every 4 hours for 17 additional doses (72-hour total regimen).

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Opioid Toxidrome & Naloxone (Narcan) Dosing Protocols

Opioid toxicity results from accidental ingestion of prescription analgesics (e.g., methadone, oxycodone, fentanyl patches) or illicit substance exposure.

Opioid Toxidrome Clinical Triad

1. Miosis (Pinpoint Pupils): Constricted, poorly reactive pupils (exceptions: meperidine, propoxyphene, or severe hypoxic brain injury causing mydriasis).
2. Central Nervous System Depression: Depressed level of consciousness ranging from lethargy to profound coma.
3. Respiratory Depression: Bradypnea, shallow hypopnea, hypoxemia, or complete apnea.

• Associated Findings: Hypothermia, bradycardia, hypotension, hyporeflexia, and decreased bowel sounds.

Emergency Management & Naloxone Administration

• Airway Priority: The emergency nurse's immediate priority is establishing an open airway and performing bag-valve-mask (BVM) ventilation with 100% oxygen before administering antidote therapy.
• Naloxone (Narcan) Dosing:
  • Pediatric Dose: 0.01 mg/kg IV/IO/IM/IN (up to 0.1 mg/kg in pediatric arrest or severe depression; maximum initial dose 2 mg). Repeat every 2 to 3 minutes as needed.
  • Therapeutic Goal: The goal of naloxone administration is restoration of adequate spontaneous ventilation and oxygenation, NOT full behavioral arousal. Over-dosing naloxone triggers acute opioid withdrawal, severe agitation, pulmonary edema, and projectile emesis (endangering the un-intubated airway).
  • Continuous Infusion: Because the half-life of naloxone (30 to 90 minutes) is shorter than most opioids (especially methadone or extended-release formulations), recurrent respiratory depression is common. Prepare a continuous IV naloxone infusion calculated at two-thirds of the initial successful reversal dose per hour.

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Anticholinergic vs. Cholinergic Toxidromes

Distinguishing between anticholinergic and cholinergic toxidromes is a high-yield CPEN exam requirement.

Toxidrome Comparison Matrix

Clinical Details & Antidote Safety Rules

• Anticholinergic Mnemonic: "Mad as a hatter (delirium), Blind as a bat (mydriasis), Red as a beet (flushed skin), Hot as a hare (hyperthermia), Dry as a bone (anhidrosis), Full as a flask (urinary retention)."
  • Physostigmine Rule: Physostigmine (10 to 30 mcg/kg IV over 5 minutes) reverses central anticholinergic delirium. However, physostigmine is STRICTLY CONTRAINDICATED if tricyclic antidepressant (TCA) ingestion is suspected or if the ECG shows QRS widening (>100 ms), as it can precipitate fatal asystole and intractable seizures.
• Cholinergic Mnemonic: "SLUDGEM" (Salivation, Lacrimation, Urination, Defecation, GI distress, Emesis, Miosis) and "DUMBELS" (Diarrhea, Urination, Miosis, Bradycardia/Bronchospasm, Emesis, Lacrimation, Salivation).
  • Atropine Titration: Administer IV Atropine (0.02 to 0.05 mg/kg IV, doubled every 3 to 5 minutes) rapidly. Titrate atropine until bronchial secretions dry and wheezing clears. Heart rate and pupil size are not the endpoint titrating parameters!
  • Pralidoxime (2-PAM): 20 to 50 mg/kg IV infused over 30 minutes to reactivate acetylcholinesterase before irreversible enzyme "aging" occurs.

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Iron Ingestion & Deferoxamine Chelation

Iron overdoses (e.g., pediatric ingestion of prenatal vitamins or iron supplements) are potent cellular toxins. Elemental iron doses >20 mg/kg produce local toxicity, while doses >60 mg/kg cause severe systemic toxicity and shock.

Clinical Phases of Iron Poisoning

1. Phase 1 (0.5 to 6 Hours): Severe hemorrhagic gastroenteritis, abdominal pain, hematemesis, melena, and hypovolemic shock due to direct corrosive destruction of the GI mucosa.
2. Phase 2 (6 to 24 Hours): Apparent latent recovery period; GI symptoms abate, but systemic cellular absorption continues.
3. Phase 3 (12 to 48 Hours): Severe Systemic Toxicity. Metabolic acidosis, uncoupled oxidative phosphorylation, distributive/cardiogenic shock, acute liver failure, hypoglycemia, and coagulopathy.
4. Phase 4 (2 to 4 Weeks): Late scarring phase resulting in gastric outlet obstruction, pyloric stenosis, and intestinal strictures.

Radiographs & Deferoxamine Chelation

• Abdominal X-ray: Iron tablets are radiopaque and readily visible on abdominal radiographs to confirm ingestion magnitude.
• Antidote (Deferoxamine Mesylate): IV chelation therapy indicated for serum iron levels >350 to 500 mcg/dL, severe symptoms, or metabolic acidosis. Deferoxamine binds free ferric iron to form ferrioxamine, excreted renally. Successful chelation produces a pathognomonic "vin-rosé" (reddish-pink) discoloration of the urine.

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Foreign Body Emergencies: Button Batteries & Magnets

Button Battery Ingestion

• Pathophysiology: A button battery lodged in the esophagus creates an electrical circuit with mucosal tissue, generating hydroxide ions that cause severe liquefaction necrosis and esophageal perforation within 2 hours.
• Pre-Hospital Mitigation: In children >1 year old with ingestion <2 hours prior, administer commercial honey or sucralfate (10 mL PO every 10 minutes, up to 6 doses) prior to hospital arrival to coat the battery and buffer tissue pH.
• Emergency Action: Immediate, emergency endoscopic retrieval. Do NOT induce emesis or administer activated charcoal.

Magnet Ingestion

• Ingestion of multiple magnets (or one magnet plus a metallic object) leads to magnetic attraction across adjacent loops of bowel. This entraps intestinal tissue, causing pressure necrosis, ischemia, bowel perforation, volvulus, fistula formation, and peritonitis. Urgent pediatric surgical or endoscopic intervention is required.

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Activated Charcoal Indications & Contraindications

Single-Dose Activated Charcoal (SDAC; dose 1 g/kg, max 50 g) adsorbs toxins in the GI tract when administered within 1 hour of ingestion.

The "PHAILS" Contraindication Mnemonic

Activated charcoal is ineffective and CONTRAINDICATED for substances that are poorly adsorbed or present high aspiration risk, summarized by the "PHAILS" mnemonic:

• P: Pesticides & Petroleum Hydrocarbons (aspiration pneumonitis risk)
• H: Heavy metals (Iron, Lead, Mercury)
• A: Alcohols (Ethanol, Methanol, Ethylene Glycol)
• I: Iron
• L: Lithium
• S: Salts / Small Molecules & Corrosives (Strong acids and alkalis)