Episode 229: Iron Poisoning

Podcast Video

Show Notes

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Iron Poisoning Stages at a Glance

The Case

• 31M w/ hx depression, anxiety; found minimally responsive at home by family
• EMS: HR 67, SpO2 96% on 2 L NC, BP 46/21; withdraws to pain, not opening eyes → 2 L IVF + push-dose epi en route
• ED: BP ↑ to 90/61, other VS unchanged; dried vomit on lips/shirt; breathing comfortably, protecting airway
• POC VBG: pH 7.24, pCO2 33, pO2 25, HCO3 14, lactate 2.5
• ECG: NSR, otherwise unremarkable → get an ECG in any possible toxic ingestion
• Additional 30 mL/kg bolus + norepi gtt
• Family arrives → bottle of iron pills under the pt’s bed

Pathophysiology

• Free iron = multisystem oxidative injury
• Primary mechanism: free radical generation + lipid peroxidation → damages cellular and mitochondrial membranes throughout the body
• Profound metabolic acidosis via 2 routes: uncoupled oxidative phosphorylation → anaerobic metabolism → lactate; Fe³⁺ reacts w/ water → releases 3 H⁺ → excess acid
• Direct mucosal necrosis in the gut (corrosive injury)
• Negative inotrope on the myocardium → hypotension, cardiogenic shock in large ingestions

Clinical Stages

• Classic progression after large ingestions; stages overlap and pts can present anywhere along the timeline
• Stage 1, GI (30 min–6 h): direct GI tract injury; abd pain, vomiting. Persistent vomiting = very sensitive indicator of a serious ingestion
• Stage 2, latent (6–24 h): GI sx improve, but iron is redistributing into the tissues → ongoing damage
• The latent-phase trap: pts look like they’re turning the corner right before they crump. Contrast: pts never symptomatic >6 h after ingestion are unlikely to develop toxicity (AAPCC 2005); GI sx that improve ≠ never symptomatic
• Stage 3, shock (6–72 h): tissue iron → profound acidosis → shock, MSOF
• Stage 4, hepatotoxicity (12–96 h): hepatotoxicity → fulminant liver failure
• Stage 5, GI scarring (2–8 wks): gastric outlet obstruction, GI tract scarring from the initial corrosive injury

Diagnosis / Workup

Imaging

• Emergent plain-film abd XR in any suspected iron ingestion → intact adult iron tabs are radiopaque
• Confirms pills still in the stomach/GI tract → helps decide on WBI
• Negative XR ≠ no ingestion: chewables, liquid formulations and already-dissolved tabs often don’t show up

Serum Iron

• Draw 4–6 h post-ingestion for regular formulations, ~8 h for extended release
• Often hard to interpret → time of ingestion and formulation frequently unknown
• >500 mcg/dL → serious systemic toxicity
• >1,000 mcg/dL → very significant mortality

Elemental Iron Math

• Toxicity tracks the elemental iron dose, not the mass of the pill

• <20 mg/kg elemental Fe → usually asymptomatic
• 20–60 mg/kg → GI sx likely; systemic toxicity possible, esp. at the upper end
• >60 mg/kg → threshold for serious toxicity, possible death
• AAPCC out-of-hospital guideline: refer to an ED for ≥40 mg/kg elemental Fe (adult ferrous salt formulations) or severe/persistent sx; any self-harm ingestion → ED regardless of amount (Manoguerra 2005)
• AAPCC: children’s chewable vitamins w/ iron, and unintentional carbonyl iron or polysaccharide-iron complex ingestions → home obs w/ f/u

Management

Decontamination

• Activated charcoal: no role. Iron is a metal → doesn’t bind; ↑ aspiration and other complications
• Whole bowel irrigation (WBI) = main decontamination strategy, esp. w/ pills on XR → flush tablets before further GI injury and systemic absorption
• PEG-ELS (polyethylene glycol electrolyte solution) until rectal effluent is clear; large volume → often via NG tube
• PEG-ELS rates: 1.5–2 L/h adolescents/adults (as on air); peds 500 mL/h (9 mo–6 y), 1 L/h (6–12 y) (AACT/EAPCCT 1997)
• AACT/EAPCCT: consider WBI after substantial iron ingestions; contraindicated w/ bowel obstruction, perforation, ileus, hemodynamic instability or a compromised unprotected airway (Thanacoody 2015)
• Gastric lavage: generally not used unless a large pill burden remains in the stomach → aspiration, direct GI injury; ED unfamiliarity ↑ complications
• Get toxicology and your local poison center on the line early

Deferoxamine (DFO)

• Mechanism: chelator isolated from bacteria → binds iron in the blood (ferrioxamine) → renal excretion in the urine
• Indications: shock · AMS · profound metabolic acidosis · persistent GI sx (persistent vomiting) · serum iron >500 mcg/dL · predicted severe ingestion (>60 mg/kg elemental Fe) in a symptomatic pt
• Reported dose >60 mg/kg in a pt w/o sx or acidosis → discuss w/ toxicology/poison center rather than chelating on pill count alone
• Dosing: start 5 mg/kg/h IV → titrate to ~15 mg/kg/h. Some protocols go higher, up to ~30 mg/kg/h in the first 24 h.
• Watch for hypotension: DFO can worsen existing hypotension.
• FDA label: IV only for cardiovascular collapse, by slow infusion; ≤15 mg/kg/h initially; max 6 g/24 h; ARDS reported w/ excessively high IV doses; ↑ risk of Yersinia infxn.
• Urine: classic “vin rosé” (red-orange) urine = ferrioxamine being excreted → helpful but not quantitative. Its absence doesn’t exclude significant toxicity or effective chelation; don’t use urine color to guide duration.
• Stop when the pt is clinically well and the anion gap acidosis has resolved.

Pitfalls

• Waiting for a level → a level that hasn’t peaked or looks low doesn’t exclude toxicity in a sick pt
• Being reassured by GI improvement in the latent phase
• Being reassured by a negative XR (chewables, liquids, dissolved tabs)
• Dosing by tablet weight instead of elemental iron
• Giving activated charcoal
• Using urine color (or its absence) to decide when to stop DFO

Take-Home Points

1. Treat the patient, not the number. Shock or profound metabolic acidosis → start DFO even if the serum iron hasn’t peaked or is lower than expected; very little harm in starting it, other than hypotension
2. Calculate elemental iron. Formulations differ in elemental content → helps predict whether the dose is toxic
3. Get an X-ray. Plain film confirms tablets and guides the decision on WBI
4. Beware the latent phase. GI improvement ≠ toxicity over → often precedes cardiovascular collapse and shock as iron moves into the tissues

Links & References

Guidelines

• Manoguerra AS, et al. Iron ingestion: an evidence-based consensus guideline for out-of-hospital management. Clin Toxicol (Phila). 2005;43(6):553–570. — DOI (AAPCC)
• Dart RC, et al. Expert consensus guidelines for stocking of antidotes in hospitals that provide emergency care. Ann Emerg Med. 2018;71(3):314–325.e1. — DOI

Decontamination Position Statements (AACT/EAPCCT)

• Tenenbein M. Position statement: whole bowel irrigation. American Academy of Clinical Toxicology; European Association of Poisons Centres and Clinical Toxicologists. J Toxicol Clin Toxicol. 1997;35(7):753–762. — DOI
• Thanacoody R, et al. Position paper update: whole bowel irrigation for gastrointestinal decontamination of overdose patients. Clin Toxicol (Phila). 2015;53(1):5–12. — DOI
• Chyka PA, et al. Position paper: single-dose activated charcoal. Clin Toxicol (Phila). 2005;43(2):61–87. — DOI
• Benson BE, et al. Position paper update: gastric lavage for gastrointestinal decontamination. Clin Toxicol (Phila). 2013;51(3):140–146. — DOI

Poison Center

• Poison Help line (US): 1-800-222-1222

Music

• Outro music: “Metalmania” Kevin MacLeod (incompetech.com). Licensed under Creative Commons: By Attribution 4.0 License