Lecture 21: Poisoning Conference & Cases

The NPDS 2022 annual report documents approximately 40% of all human exposures occur in children ≤5 years. These are predominantly unintentional (exploratory) ingestions with relatively low fatality rates. In contrast, the majority of fatalities occur in adults, most often from intentional (self-harm) overdoses. Answer choices A and B underestimate pediatric exposure prevalence; D and E greatly overestimate it.

The NPDS 2022 fatality ranking: sedative/hypnotics (299) > APAP alone (270) > opioids (244) > alcohols (231). Note that "analgesics" is the #1 exposure category (11.5% of all calls) but APAP specifically is #2 in fatalities. Opioids are #3 in NPDS fatalities — though total opioid deaths nationally (CDC data) vastly exceed NPDS numbers because most opioid fatalities go directly to emergency services without a poison control call. Cleaning substances are a top exposure category in children but rarely fatal. Antidepressants (especially TCAs) are dangerous but rank lower in overall fatalities.

Bidirectional ventricular tachycardia (alternating QRS axis) is the hallmark EKG finding of digoxin toxicity. Bradycardia and varying degrees of AV block are also characteristic. The scenario of a child accessing a grandparent's "heart medication" and developing cardiac toxicity strongly suggests a cardiac glycoside (digoxin). Treatment: Digoxin-specific Fab antibody fragments. Aspirin causes metabolic acidosis/tinnitus, not bradycardia. Diphenhydramine causes anticholinergic toxidrome with tachycardia. Lisinopril causes hypotension but not this specific arrhythmia. Metformin can cause lactic acidosis in overdose.

In ALL intentional overdoses, serum acetaminophen and salicylate levels must be obtained regardless of the stated ingestion. Both are silent toxins with delayed presentations — APAP causes hepatotoxicity 24–72h later and salicylate causes mixed acid-base disorder. Patients with intentional overdose frequently minimize or misstate what they took. A normal appearing patient who "only took Benadryl" may have co-ingested APAP (commonly combined in products like NyQuil, Tylenol PM). Urine drug screen (C) alone is insufficient — it misses APAP and salicylates. D is reasonable but incomplete without the specific drug levels. E is dangerous — never send home an intentional OD without appropriate labs and psychiatric evaluation.

The classic CO poisoning presentation: multiple household members (including pets) with flu-like illness without fever in winter. Standard pulse oximetry is falsely normal because it cannot distinguish carboxyhemoglobin (COHb) from oxyhemoglobin — both absorb similarly at the measured wavelengths. Co-oximetry on ABG directly measures COHb. The family should be removed from the home immediately. Treatment: 100% O₂ via non-rebreather mask; hyperbaric O₂ for severe cases or pregnant patients. LP (A) and CT head (B) are premature without first confirming/ruling out CO. Blood cultures (E) are for suspected bacteremia with fever, not appropriate here.

Wide QRS (>120 ms) with hemodynamic instability in an overdose context strongly suggests TCA (tricyclic antidepressant) toxicity via sodium channel blockade. The treatment for TCA-induced wide QRS is sodium bicarbonate (1–2 mEq/kg IV) — the sodium load reverses the channel blockade AND alkalinization shifts the equilibrium away from channel binding. This narrows the QRS and can be life-saving. Amiodarone (A) is contraindicated in TCA OD as it can worsen QT prolongation and arrhythmias. Cardioversion (B) is not indicated for this wide complex tachycardia in TCA OD. Calcium (D) is for calcium channel blocker or hyperkalemia. Magnesium (E) treats QT-related torsades de pointes, not wide QRS.

For caustic ingestion (acid or alkali), dilution with a small amount of water or milk (120–240 mL) is appropriate. This reduces the concentration of the caustic agent at the mucosal surface. Never induce vomiting (A) — re-exposing damaged esophageal mucosa to caustic material causes additional necrosis and risks perforation. Never neutralize (D) — acid-base neutralization is exothermic and generates heat, causing thermal injury on top of chemical injury. Activated charcoal (C) is not indicated for caustic ingestion (interferes with endoscopy, no benefit). Doing nothing (E) misses the opportunity for immediate dilution.

At a salicylate level of 95 mg/dL with altered mental status and metabolic acidosis, hemodialysis is indicated. Hemodialysis indications for salicylate OD include: level >80–100 mg/dL, AMS, renal failure, pulmonary edema, or clinical deterioration. Urinary alkalinization (B) is a useful adjunct but insufficient alone at this level of toxicity. Urinary acidification (A) is actually harmful — it traps ionized salicylate in the blood, worsening toxicity. MDAC (D) can help reduce absorption but is not sufficient for severe toxicity. Hemoperfusion (E) is indicated for theophylline, not the first-line for salicylates.

Ethylene glycol is in the SLIME group dialyzable toxins: Salicylates, Lithium, Isopropanol, Methanol/Metformin, Ethylene glycol.
Why others are wrong: A — Digoxin is NOT effectively removed by HD (large Vd, tissue-bound; use Dig-Fab). B — Lithium is removed by HD, not MDAC (charcoal doesn't adsorb lithium). C — Methanol is removed by HD, not urinary alkalinization (urinary alkalinization works for weak acids like salicylates and phenobarbital, not alcohols). E — Phenobarbital is removed by MDAC (multiple-dose activated charcoal creates "gut dialysis") and urinary alkalinization, not hemodialysis primarily.

The opioid triad: AMS + miosis (3mm/pinpoint pupils) + respiratory depression. This patient has all three, plus hypotension — classic opioid overdose presentation. Naloxone (competitive μ-opioid antagonist) should be given immediately (IV, IM, or intranasal). While preparing naloxone, support ventilation with bag-mask if needed. NAC (A) is for APAP toxicity — no hepatotoxicity signs here. NaHCO₃ (B) is for TCA wide QRS. Flumazenil (D) would be for benzodiazepine reversal — benzodiazepines cause sedation but NOT miosis. Glucagon (E) is for beta-blocker toxicity.

A 4-hour serum APAP level of 210 mcg/mL falls in the "treatment line" on the Rumack-Matthew nomogram (the treatment threshold at 4h is approximately 150 mcg/mL). NAC should be started immediately — it is most effective within 8–10 hours of ingestion. Do NOT wait for symptoms or LFT elevation: APAP toxicity is clinically silent during the first 24 hours (Phase I). By the time symptoms appear (Phase II–III), significant hepatocellular necrosis may already be occurring. Discharging (A) or observing without treatment (B) would likely result in fulminant liver failure. Gastric lavage (D) is not indicated at 4 hours post-ingestion (beyond optimal window, and APAP is already absorbed). Liver biopsy (E) has no role in acute poisoning management.

Ethylene glycol itself is relatively nontoxic. Its toxicity comes from its metabolite: alcohol dehydrogenase (ADH) converts EG → glycolaldehyde → glycolic acid → oxalic acid. Oxalic acid then binds calcium → calcium oxalate crystals (deposit in renal tubules → acute tubular necrosis). Fomepizole (4-methylpyrazole, 4-MP) is a potent inhibitor of ADH — by blocking this enzyme, it prevents formation of the toxic metabolites. The parent compound (EG) is then eliminated unchanged by the kidneys and by hemodialysis. This same mechanism applies to methanol toxicity (ADH → formic acid → optic nerve damage/blindness).

This is organophosphate poisoning (pesticide exposure) causing a cholinergic toxidrome: SLUDGE (salivation, lacrimation, urination, defecation/cramping, emesis) + seizures. Treatment: (1) Atropine — competitive muscarinic antagonist; blocks excessive ACh at muscarinic receptors; give large doses (2–4 mg IV, repeat every 5–10 min) titrating to drying of secretions; (2) Pralidoxime (2-PAM) — reactivates acetylcholinesterase by cleaving the organophosphate-enzyme bond; must be given early before "aging"; also treats nicotinic effects (fasciculations, paralysis) that atropine cannot. Benzos treat seizures concurrently. Physostigmine (D) does the opposite of what is needed — it inhibits cholinesterase and would worsen the cholinergic crisis.

INH-induced seizures are characteristically refractory to benzodiazepines. The mechanism: INH inhibits pyridoxal kinase → depleted pyridoxal phosphate (active B6) → impaired glutamic acid decarboxylase → ↓ GABA synthesis → excitotoxic seizures. Benzodiazepines enhance GABA at GABA-A receptors but cannot work if GABA production is severely impaired. Pyridoxine (vitamin B6) restores GABA synthesis and terminates seizures. Dose: 5g IV empirically (or gram-for-gram the estimated INH dose). Phenytoin (A) is not effective for INH seizures and is actually not first-line for any toxin-induced seizures. NaHCO₃ (C) and NAC (D) target different toxins. Magnesium (E) is for eclampsia or torsades.

Hydroxocobalamin (Cyanokit) is the current first-line antidote for cyanide poisoning in the US. It directly binds cyanide (CN⁻) in a 1:1 molar ratio to form cyanocobalamin (vitamin B12), which is then excreted renally. Advantages: safe in fire victims who may also have CO poisoning (unlike the older nitrite-based regimen which induces methemoglobinemia — harmful in CO-poisoned patients). The older regimen (sodium nitrite + sodium thiosulfate) works by: nitrite → induces methemoglobinemia (Fe²⁺ → Fe³⁺) → CN⁻ preferentially binds methemoglobin; thiosulfate → donates sulfur to rhodanese enzyme → converts CN⁻ to thiocyanate (non-toxic, excreted). Methylene blue (A) treats methemoglobinemia, not cyanide. Deferoxamine (E) chelates iron.

Key discriminating features here: diaphoresis (wet skin) and hyperactive bowel sounds point to sympathomimetic toxidrome rather than anticholinergic (which shares tachycardia, hyperthermia, mydriasis, and agitation, but has dry skin and decreased bowel sounds). Cocaine and amphetamines (including MDMA/ecstasy) are common at raves. Treatment: benzodiazepines are first-line for agitation, tachycardia, hypertension, and hyperthermia. Avoid beta-blockers in cocaine OD (risk of unopposed alpha → severe vasoconstriction and rebound HTN). Note: Serotonin syndrome (D) is similar but characteristically includes hyperreflexia and clonus which are not mentioned here.

Classic opioid triad: AMS + miosis (pinpoint pupils) + respiratory depression. Bradycardia and hypothermia are also consistent. Naloxone (competitive μ-opioid antagonist) is the antidote. The dose range 0.4–2 mg is reasonable; in opioid-naive patients or for diagnostic purposes, 0.4 mg can be used; in severe overdose, 2 mg or more may be needed. If effective, pupils will dilate and respiratory rate improves within 1–2 minutes. Remember: naloxone's half-life is shorter than most opioids — re-sedation can occur; monitor closely and repeat or infuse as needed. Atropine (A) treats bradycardia from AV block (cholinergic/digoxin) but not opioids. NaHCO₃ (C) treats TCA wide QRS. Flumazenil (D) reverses benzodiazepines but NOT miosis. Physostigmine (E) would worsen bradycardia/bradypnea.

This is organophosphate poisoning (cholinergic toxidrome from gardening pesticide exposure). Organophosphates initially form a reversible covalent bond with the serine residue in acetylcholinesterase's active site. Over time — the speed depends on the specific organophosphate — this bond "ages" (undergoes dealkylation) into an irreversible form that pralidoxime cannot cleave. Once aging occurs, acetylcholinesterase is permanently inactivated and must be replaced by new enzyme synthesis (days). Pralidoxime works by nucleophilically attacking the phosphorylated enzyme, regenerating active acetylcholinesterase — but only before aging. Therefore, pralidoxime must be given early. Note: pralidoxime is typically not given for carbamate poisoning because carbamate-cholinesterase bonds are spontaneously reversible.