Toxic Heavy Metals & Chelation Therapy
Comprehensive emergency evaluation and protocolized management of heavy metal poisonings: acute and chronic Lead poisoning (plumbism, microcytic anemia with basophilic stippling, lead colic, encephalopathy, and chelation protocols with Succimer/DMSA and Dimercaprol/EDTA); Iron overdose pathophysiological staging (5 clinical phases), abdominal KUB radiopacity, peak serum iron concentration thresholds (> 500 mcg/dL), and IV Deferoxamine therapy with 'vin rosé' urine monitoring; acute and chronic Arsenic toxicity (garlic breath odor, rice-water cholera-like diarrhea, Mee's lines, QTc prolongation, and BAL therapy); and Mercury toxicity (inhalation vs elemental vs organic, acrodynia, and erethism).
Resuscitation Quick Actions • First 2 Minutes
Lead Encephalopathy Rule
Administer Dimercaprol (BAL) 75 mg/m2 IM FIRST; wait 4 hours before starting Calcium Disodium EDTA (CaNa2EDTA) 1,500 mg/m2/day continuous IV infusion
Iron Overdose Toxic Dose
20-60 mg/kg elemental iron = Moderate GI toxicity; > 60 mg/kg = Severe, life-threatening mitochondrial toxicity and circulatory shock
Deferoxamine Indication
Serum Iron > 500 mcg/dL at 4-6 hours post-ingestion OR severe symptoms (shock, lethargy, refractory anion gap metabolic acidosis, KUB with radiopaque pills)
Deferoxamine Dosing
Infuse Deferoxamine at 15 mg/kg/hour IV (max 6 g/day); observe for 'vin rosé' (reddish-orange) urine confirming ferrioxamine chelation excretion
Arsenic Triad
Garlic breath odor + severe cholera-like watery/rice-water diarrhea + prolonged QTc/Torsades -> Chelate with Dimercaprol (BAL) or oral Succimer
Whole Bowel Irrigation (WBI)
For massive iron or lead foreign body ingestions seen on abdominal X-ray: Polyethylene glycol (GoLYTELY) 1-2 L/hr in adults (25-40 mL/kg/hr in kids) via NG tube
Bottom-Line Clinical Pearl
In heavy metal poisoning, antidote selection and sequencing are critical: in severe Lead Encephalopathy (blood lead level > 70-100 mcg/dL), ALWAYS administer Dimercaprol (BAL) FIRST before or concurrently with Calcium Disodium EDTA (CaNa2EDTA); giving EDTA alone mobilizes lead from bone stores directly into brain parenchyma, precipitating fatal cerebral edema and uncal herniation. In acute pediatric or adult Iron overdose, ingestions exceeding 60 mg/kg of elemental iron produce cellular mitochondrial poisoning and severe shock; initiate IV Deferoxamine (15 mg/kg/hr) for systemic toxicity, worsening metabolic acidosis, or serum iron levels > 500 mcg/dL.
Lead binds to sulfhydryl groups on critical cellular enzymes, inhibiting delta-aminolevulinic acid dehydratase (ALAD) and ferrochelatase in the heme synthesis pathway. This leads to erythrocyte microcytosis, hemolysis, and characteristic basophilic stippling (aggregates of precipitated ribosomal RNA). In the central nervous system, lead disrupts the blood-brain barrier, inhibits neurotransmission, and produces cerebral edema.
| Blood Lead Level (BLL) | Clinical Manifestations | Chelation Protocol & Antidote Sequencing |
|---|---|---|
| 5 to 44 mcg/dL (Subclinical to Mild) | Cognitive impairment, behavioral changes in children, ADHD-like symptoms, mild microcytic anemia. | Identify and remove environmental exposure source (lead paint abatement, contaminated water testing). Chelation is NOT indicated at this level. |
| 45 to 69 mcg/dL (Moderate Plumbism) | Colicky abdominal pain ('lead colic'), constipation, fatigue, arthralgias, peripheral neuropathy (wrist drop/foot drop from radial/peroneal motor axonopathy). | Oral Chelation with Succimer (DMSA): - 10 mg/kg PO every 8 hours for 5 days, then every 12 hours for 14 days (total 19 days). (Outpatient or inpatient depending on living environment safety). |
| >= 70 to 100 mcg/dL OR Severe Encephalopathy | Lead Encephalopathy: Lethargy, persistent projectile vomiting, ataxia, seizures, stupor, coma, increased intracranial pressure, papilledema, and brainstem herniation. | MANDATORY DUAL SEQUENCED CHELATION: 1. Dimercaprol (BAL) 75 mg/m2 IM every 4 hours. 2. WAIT 4 HOURS before starting Calcium Disodium EDTA (CaNa2EDTA) 1,500 mg/m2/day continuous IV infusion (or divided q4h). CRITICAL RULE: BAL crosses blood-brain barrier; giving EDTA alone mobilizes lead into the brain, precipitating fatal brain herniation! |
Elemental iron toxicity depends on the formulation (e.g., ferrous sulfate contains 20% elemental iron; ferrous fumarate contains 33%; ferrous gluconate contains 12%). Once transferrin binding is saturated, free circulating iron enters cells, catalyzing the Haber-Weiss and Fenton reactions to generate massive amounts of destructive hydroxyl free radicals, producing severe lipid peroxidation, cellular necrosis, and mitochondrial poisoning.
| Stage & Time Window | Clinical Features & Pathophysiology | Emergency Action & Findings |
|---|---|---|
| Stage 1: Gastrointestinal Phase (0.5 to 6 Hours) | Direct corrosive injury to gastric and duodenal mucosa: severe abdominal pain, nausea, vomiting, hematemesis, and explosive melena/bloody diarrhea. Shock may occur from volume loss. | Obtain stat Abdominal Radiograph (KUB): radiopaque iron tablets appear as dense radiopaque densities in stomach/bowel. Draw serum iron at 4 hours post-ingestion. |
| Stage 2: Latent/Quiescent Phase (6 to 24 Hours) | Apparent clinical improvement as GI mucosal bleeding subsides. A treacherous clinical trap! | Underlying cellular uptake of iron continues unabated: ongoing subclinical metabolic acidosis, hypoperfusion, and oliguria. Do NOT discharge the patient! |
| Stage 3: Systemic Shock & Metabolic Phase (12 to 48 Hours) | Catastrophic circulatory shock: profound vasodilation, myocardial depression, severe high anion gap metabolic acidosis with extreme hyperlactatemia, pulmonary edema, DIC, and coma. | Immediate resuscitation with IV crystalloids and vasopressors. Stat initiation of IV Deferoxamine continuous infusion. |
| Stage 4: Hepatotoxicity & Acute Liver Failure (2 to 4 Days) | Massive hepatic necrosis (iron concentrates in reticuloendothelial cells of the liver): jaundice, coagulopathy (INR > 5), hypoglycemia, hyperammonemia, and hepatic encephalopathy. | Transplant center consultation. Supportive ICU care. |
| Stage 5: Delayed Bowel Obstruction (2 to 6 Weeks) | Cicatricial healing and severe fibrosis of mucosal ulcerations leading to gastric outlet obstruction or small bowel strictures. | Presents weeks later with intractable postprandial vomiting; requires surgical pyloroplasty or bowel resection. |
| Clinical Intervention | Protocol & Dosing Details | Clinical Pearls & Endpoints |
|---|---|---|
| Gastrointestinal Decontamination | Activated Charcoal DOES NOT BIND IRON! Do not administer charcoal. Whole Bowel Irrigation (WBI) with Polyethylene Glycol (GoLYTELY) via nasogastric tube: - Children: 25 to 40 mL/kg/hour - Adults: 1.5 to 2.0 Liters/hour. Continue until rectal effluent is completely clear and repeat KUB shows disappearance of tablets. | Indicated when abdominal X-ray demonstrates significant radiopaque pill burden in the stomach or intestines. Avoid if bowel obstruction, perforation, or intractable shock is present. |
| Intravenous Deferoxamine Infusion (Desferal) | Specific iron chelator (binds ferric iron [Fe3+] to form water-soluble ferrioxamine, excreted by kidneys): - Starting dose: 15 mg/kg/hour continuous IV infusion (max 6 grams/24 hours). - Rate can be titrated down after 4-6 hours. | Observe urine color: formation of ferrioxamine complex produces a distinctive 'vin rosé' (orange-reddish) discoloration of the urine. (Note: absence of vin rosé does not rule out excretion). Stopping Criteria: 1. Resolution of metabolic acidosis 2. Clinical stability and resolution of symptoms 3. Serum iron level < 350 mcg/dL 4. Urine returns to normal color. |
| Toxin | Clinical Presentation & Triads | Specific Antidote Therapy |
|---|---|---|
| Arsenic (Acute Ingestion: pesticides, contaminated well water, wood preservatives) | 1. Garlic breath odor 2. Severe cholera-like, profuse 'rice-water' bloody diarrhea and vomiting 3. Cardiovascular collapse, prolonged QTc interval, and Torsades de Pointes 4. Late: Mee's lines (transverse white bands across fingernails), peripheral stocking-glove sensorimotor neuropathy. | 1. Aggressive IV crystalloid rehydration and ECG monitoring. 2. Dimercaprol (BAL) 3 to 5 mg/kg IM every 4 hours OR oral Succimer (DMSA) 10 mg/kg PO q8h for mild/subacute cases. (Hemodialysis removes free arsenic if acute renal failure develops). |
| Mercury (Elemental Inhalation vs. Organic vs. Inorganic) | 1. Inhaled Elemental Vapor (broken thermometer, smelting): Acute chemical pneumonitis, ARDS, non-cardiogenic pulmonary edema. 2. Inorganic Salts (corrosive): Corrosive gastroenteritis and acute tubular necrosis. 3. Organic/Methylmercury (Minamata disease, contaminated predatory fish): Neurotoxicity, ataxia, visual field constriction, acrodynia (pink disease: painful, red, desquamating palms/soles in children), erethism mercurialis (erethism: severe emotional lability, shyness, personality change). | 1. Succimer (DMSA) 10 mg/kg PO q8h (preferred first-line for elemental and organic mercury). 2. Dimercaprol (BAL) is effective for inorganic salts, but CONTRAINDICATED in elemental or methylmercury (BAL redistributes mercury to the brain!). |
The EDTA Encephalopathy Trap & The Latent Phase Iron Trap
In severe lead poisoning with encephalopathy, NEVER administer Calcium Disodium EDTA (CaNa2EDTA) as monotherapy or prior to Dimercaprol (BAL). EDTA chelates lead primarily in the extracellular fluid and skeletal compartment, but does not efficiently cross the blood-brain barrier; infusing EDTA alone creates a massive transcellular concentration gradient that drives free mobilized lead into the central nervous system, acutely worsening cerebral edema and causing fatal brain herniation. Always administer Dimercaprol (BAL) intramuscularly first and wait 4 hours before infusing EDTA. In acute iron overdose, beware Stage 2 (The Latent Phase): after several hours of vomiting, the patient's gastrointestinal symptoms often appear to resolve completely. Clinicians who mistake this temporary lull for clinical recovery and discharge the patient will find the patient dead 12 hours later from fulminant mitochondrial shock, refractory lactic acidosis, and liver failure. Any patient with significant iron ingestion (> 40-60 mg/kg) or an iron level > 500 mcg/dL must remain hospitalized for continuous IV Deferoxamine chelation.
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