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Iron Poisoning, Emergency Medicine

Basics

Description

- Classically divided into 5 stages: - Stage 1: GI (0.5-6 hr): - Abdominal pain - Vomiting - Diarrhea - Hematemesis - Hematochezia

- Stage 3: Shock and organ failure (6-72 hr): - Hypoperfusion - Metabolic acidosis - Coma - Coagulopathy

- Stage 4: Hepatic failure (2-3 days): - Coagulopathy - Hypoglycemia - Jaundice - Elevated LFTs (transaminases) and bilirubin

- Electrolytes, BUN/creatinine, glucose: - Anion gap metabolic acidosis - Hyperglycemia early - Hypoglycemia late

- Tablets (childrens chewables rarely visible) - Absence of pill fragment interpretation: - Patient did not ingest iron - Iron was in solution or has already dissolved - Patient ingested pediatric multivitamin product - Absence of radiopacities does not rule out significant or lethal ingestion

- ABCs: - Intubate if profoundly unstable - Venous access and fluids for hypotension - Cardiac monitor and pulse oximetry

- Decontamination: - Poorly adsorbed by activated charcoal - Gastric lavage has not been shown to change outcome - NaHCO3, phospho soda, and oral deferoxamine are not recommended - If pill fragments are visualized on x-ray, or history of significant ingestion: - Consider whole bowel irrigation (with NG GoLytely: Peds: 10-15 mL/kg/h; adult: 1-2 L/h) while monitoring progression with radiograph (KUB). - Caution with GI bleed

- Administration techniques: - Increase IV infusion rate to 15 mg/kg/h over 20 min, monitoring for hypotension - Decrease infusion rate if hypotension - Infusion rates as high as 45 mg/kg/h have been tolerated - Disregard manufacturers recommendation of max. daily doses of 6 g in serious iron exposures

- IM DFO challenge test is not advocated - Interpret serum levels cautiously: - Time since ingestion must be considered: Treatment may be indicated in patient who presents late, after distribution stage (>8 hr postingestion), with serum iron level <350 mg/dL

- If serum iron levels are not readily available, base treatment decisions on clinical status - Length of infusion (controversial): - DFO-iron complex causes urine to turn vin rose color; this suggests continuing infusion until urine returns to normal - Resolution of signs and symptoms of significant toxicity is criterion for discontinuing DFO - Prolonged DFO therapy >24-48 hr may precipitate adult respiratory distress syndrome - In severe cases with continued signs and symptoms, infusion may be continued cautiously at lower dose

- Controversies: - Safety of DFO infusions given for >24 hr - Maximal infusion rates and total amount - Serum iron concentration warranting treatment - Endpoint of treatment (best endpoint is resolution of poisoning, i.e., acidemia) - Role of extracorporeal elimination

  • Peak concentrations are 2-4 hr postingestion
  • Serum concentrations not reliable if obtained >4-6 hr after ingestion:Enteric coated or sustained release-warrants serial levels
  • Postabsorption: Iron redistributes into tissues, and fall in serum iron occurs as free iron shifts intracellularly resulting in cellular injury
  • Injury patterns:Corrosive injury to intestinal mucosa may result in profound fluid loss (shock), hemorrhage, and perforationLiver receives largest load of iron because of portal venous circulation-(hemorrhagic periportal necrosis)
  • Free iron:Concentrates in mitochondria, disrupting oxidative phosphorylation; catalyzes lipid peroxidation and free radical formation, resulting in cell death; increases anaerobic metabolism and acidosisCauses myocardial depression, venodilation, and cerebral edema
  • Hydration of ferric form liberates 3 protons, resulting in acidemia

Etiology

Elemental iron ingestion:

  • Nontoxic <20 mg/kg
  • Moderate to severe >40 mg/kg
  • Lethality possible >60 mg/kg
  • Elemental iron equivalents:Ferrous sulfate, 20% (325 mg = 65 mg Fe)Ferrous gluconate, 12%Ferrous fumarate, 33%
  • Prenatal vitamins vary from 60-90 mg elemental iron per tablet
  • Childrens vitamins may contain 5-18 mg elemental iron per tablet
  • Historically notorious for the highest mortality rate among pediatric accidental exposures (adult iron products)
  • Children's chewable iron products have been shown to be safe

Diagnosis

Signs and Symptoms

  • Classically divided into 5 stages:Stage 1: GI (0.5-6 hr):Abdominal painVomitingDiarrheaHematemesisHematocheziaStage 2: Latent/quiescent (6-24 hr):Resolution of GI symptomsDeceptive phase (ongoing injury?)Possible hypotension and acidosisStage 3: Shock and organ failure (6-72 hr):HypoperfusionMetabolic acidosisComaCoagulopathyStage 4: Hepatic failure (2-3 days):CoagulopathyHypoglycemiaJaundiceElevated LFTs (transaminases) and bilirubinStage 5: Obstruction (2-4 wk):Gastric outlet and small bowel obstructionAbdominal pain, vomiting
  • Patient may present in or skip any of the 5 stages
  • If onset of stage 1 does not occur within 6 hr, likely not significant ingestion

Essential Workup

Acute iron poisoning is a clinical diagnosis, regardless of lab results

Diagnosis Tests & Interpretation

Lab

  • Serum iron levels (mg/dL):Peak absorption 2-6 hr4 hr is most common time for peakDelayed peak with enteric coated/sustained release
  • Electrolytes, BUN/creatinine, glucose:Anion gap metabolic acidosisHyperglycemia earlyHypoglycemia late
  • Arterial blood gas:
  • CBC:Anemia with significant hemorrhageLeukocytosis
  • Liver function
  • Coagulation profile
  • Lactate
  • Type and screen if hemorrhage
  • Total iron-binding capacity is not useful and not recommended

Imaging

Abdominal radiograph check for:

  • Tablets (childrens chewables rarely visible)
  • Absence of pill fragment interpretation:Patient did not ingest ironIron was in solution or has already dissolvedPatient ingested pediatric multivitamin productAbsence of radiopacities does not rule out significant or lethal ingestion
  • Perforation

Differential Diagnosis

  • Sepsis
  • Acetaminophen toxicity
  • Toxic ingestions causing anion gap acidosis:SalicylateCyanideMethanolEthylene glycol
  • Mushrooms
  • Heavy metals
  • Theophylline toxicity
  • GI bleed from other causes (alcoholic liver disease)

Treatment

Pre-Hospital

Collect prescription bottles/medications for identification in the ED

Initial Stabilization/Therapy

  • ABCs:Intubate if profoundly unstableVenous access and fluids for hypotensionCardiac monitor and pulse oximetry
  • Naloxone, thiamine, dextrose (or Accu-Chek) as indicated for altered mental status

Ed Treatment/Procedures

  • Decontamination:Poorly adsorbed by activated charcoalGastric lavage has not been shown to change outcomeNaHCO3, phospho soda, and oral deferoxamine are not recommendedIf pill fragments are visualized on x-ray, or history of significant ingestion:Consider whole bowel irrigation (with NG GoLytely: Peds: 10-15 mL/kg/h; adult: 1-2 L/h) while monitoring progression with radiograph (KUB).Caution with GI bleedEndoscopy or gastrotomy can remove bezoar formation after massive ingestions (>240 mg/kg)
  • Chelation with deferoxamine (DFO):DFO is a highly specific chelator of parenteral ironIV infusion results in more constant DFO levels and is route of choice:Administer as soon as possible (<24 hr)Administration techniques:Increase IV infusion rate to 15 mg/kg/h over 20 min, monitoring for hypotensionDecrease infusion rate if hypotensionInfusion rates as high as 45 mg/kg/h have been toleratedDisregard manufacturers recommendation of max. daily doses of 6 g in serious iron exposuresIM DFO challenge test is not advocatedInterpret serum levels cautiously:Time since ingestion must be considered: Treatment may be indicated in patient who presents late, after distribution stage (>8 hr postingestion), with serum iron level <350 mg/dLIf serum iron levels are not readily available, base treatment decisions on clinical statusLength of infusion (controversial):DFO-iron complex causes urine to turn vin rose color; this suggests continuing infusion until urine returns to normalResolution of signs and symptoms of significant toxicity is criterion for discontinuing DFOProlonged DFO therapy >24-48 hr may precipitate adult respiratory distress syndromeIn severe cases with continued signs and symptoms, infusion may be continued cautiously at lower doseControversies:Safety of DFO infusions given for >24 hrMaximal infusion rates and total amountSerum iron concentration warranting treatmentEndpoint of treatment (best endpoint is resolution of poisoning, i.e., acidemia)Role of extracorporeal eliminationContact regional poison center for moderate to severe iron exposures

Medication

  • Dextrose: D50W 1 amp (50 mL or 25 g; peds: D25W 2-4 mL/kg) IV
  • Naloxone (Narcan): 2 mg (peds: 0.1 mg/kg) IV or IM initial dose
  • Thiamine (vitamin B1): 100 mg (peds: 50 mg) IV or IM

Follow-Up

Disposition

Admission Criteria

  • GI symptoms or dehydration
  • Altered mental status
  • Hypotension, lethargy, metabolic acidosis, or shock
  • Serum iron >500 mg/dL
  • Serum iron >350 mg/dL and pills seen on KUB
  • Rising serum iron levels
  • Patients treated with deferoxamine
  • ICU admission for coma, shock, metabolic acidosis, or iron levels >1,000 mg/dL

Discharge Criteria

  • Asymptomatic with negative radiograph
  • Minimal to no symptoms after 6-hr observation
  • Mild GI symptoms that have resolved without evidence of metabolic acidosis and serum iron <350 mg/dL

Issues for Referral

Contact regional poison center for mild to moderate toxicity

Follow-Up Recommendations

  • Follow-up after discharge may be indicated in patients who are at risk of developing gastric outlet obstruction
  • Psychiatric referral for patients with intentional overdose

Pearls and Pitfalls

  • DFO may be indicated in patients who present late, after distribution stage (>8 hr postingestion), or with serum iron level <350 mg/dL and signs of intracellular poisoning (e.g., anion gap metabolic acidosis)
  • Resolution of GI symptoms does not indicate that there is no ongoing toxicity that may progress over time

Additional Reading

  • Bryant SM, Leikin J. Iron. In: Brent J, Wallace KL, Burkhart KK, et al., eds. Critical Care Toxicology. St. Louis, MO: Mosby; 2005.
  • Chang TP, Rangan C. Iron poisoning: A literature-based review of epidemiology, diagnosis, and management. Pediatr Emerg Care. 2011;27:978-985.
  • Tenenbein M. Unit-dose packaging of iron supplements and reduction of iron poisoning in young children. Arch Pediatr Adolesc Med. 2005;159:557-560.

Codes

ICD9

964.0 Poisoning by iron and its compounds

ICD10

  • T45.4X1A Poisoning by iron and its compounds, accidental, init
  • T45.4X4A Poisoning by iron and its compounds, undetermined, init

SNOMED

  • 445902007 Poisoning by iron (disorder)
  • 216802005 Accidental poisoning by iron compounds (disorder)