Copper Poisoning

Copper poisoning is most often acute ingestion of copper sulfate (blue vitriol, used as a fungicide, algicide, in swimming pool treatments, in Bordeaux mixture sprays and sometimes in homicide or suicide, particularly in rural South Asia). Chronic toxicity arises from contaminated water (copper pipes and acidic water) or occupational exposure (vineyard sprayer's lung, metal fumes), and is distinct from Wilson disease, which is an inherited disorder of copper excretion.

Dose: ingestion of 1 to 2 g of copper sulfate causes severe gastrointestinal symptoms, and over 10 to 20 g (about 250 mg/kg) is often fatal. Mechanisms: free copper produces oxidative damage to red cell membranes and hemoglobin (hemolysis and methemoglobinemia), and injury to hepatocytes, renal tubules and the gastrointestinal mucosa through lipid peroxidation and protein binding.

Natural history is gastrointestinal injury in the first hours, then, over 24 to 96 hours, intravascular hemolysis, hepatic necrosis with jaundice, acute kidney injury, rhabdomyolysis, shock and multi-organ failure. Mortality is 15 to 25% in significant ingestion, and rises with a late presentation. Complications: esophageal and gastric ulceration with later stricture, cardiovascular collapse, hepatic failure, renal failure and death.

• Metallic taste, burning pain in the mouth and abdomen, persistent vomiting of blue-green material, hematemesis, diarrhea
• Hypotension and tachycardia from fluid loss, then shock
• Day 2 to 4: jaundice, dark urine (hemoglobinuria), oliguria, hepatomegaly, pallor, cyanosis from methemoglobin (a chocolate-brown blood)
• Rhabdomyolysis, seizures, confusion and coma in severe poisoning
• Red flags: hypotension, jaundice, oliguria, brown or black urine and a large ingested amount

1. Clinical diagnosis from the history, the blue-green vomit and the setting.
2. Serum copper (normal 11 to 22 micromol/L, or 70 to 140 micrograms/dL; levels over 24 micromol/L, and often over 100 micromol/L in severe poisoning) and ceruloplasmin (to exclude Wilson disease with a low value).
3. Full blood count with film (hemolysis, Heinz bodies, bite cells), reticulocytes, LDH, haptoglobin and free hemoglobin.
4. Methemoglobin level (co-oximetry), arterial blood gas and lactate.
5. Liver tests, coagulation, creatinine, urea, electrolytes, creatine kinase and urinalysis (hemoglobinuria).
6. Endoscopy within 12 to 24 hours for corrosive injury in those with persistent vomiting, hematemesis or severe pain.

Differentials: other corrosive ingestion, arsenic poisoning, paraquat poisoning, mushroom poisoning, Wilson disease crisis, other hemolytic anemias, hepatitis, sepsis.

1. No induced vomiting. Avoid activated charcoal (it does not bind copper well and obscures endoscopy), and avoid gastric lavage after the first hour.
2. Resuscitation: IV crystalloid 20 mL/kg initially and repeat, with a target urine output over 1 mL/kg/h to protect the kidneys from pigment injury, and blood transfusion for severe hemolysis.
3. Gastroprotection: omeprazole 40 mg IV twice daily, antiemetic (ondansetron 4 to 8 mg IV, with QT caution), and analgesia (morphine 0.05 to 0.1 mg/kg IV titrated).
4. Methemoglobinemia: methylene blue 1 to 2 mg/kg IV over 5 minutes, repeated once after 30 to 60 minutes if methemoglobin remains over 30% or symptoms persist (avoid if G6PD deficient, because it will fail and may worsen hemolysis). Use ascorbic acid 1 g IV every 6 hours if methylene blue is unsuitable.
5. Chelation (early, for severe poisoning):
   • Dimercaprol 3 to 5 mg/kg IM every 4 hours for 2 days, every 6 hours on day 3, then every 12 hours for up to 10 days, avoiding in peanut allergy.
   • D-penicillamine 250 mg orally four times daily (children 20 to 30 mg/kg a day in 3 to 4 divided doses, maximum 1 g a day) with pyridoxine 25 mg daily, once oral intake is possible. Adverse effects: rash, marrow suppression, proteinuria. Avoid in penicillin allergy.
   • Alternatives: succimer 10 mg/kg orally every 8 hours for 5 days, then every 12 hours for 14 days, or calcium disodium EDTA 1 g IV daily for 5 days in adults.
6. Hemolysis and renal failure: exchange transfusion or plasmapheresis for severe hemolysis, and haemodialysis for acute kidney injury (copper itself is poorly dialyzed).
7. Hepatic failure: standard supportive care, with N-acetylcysteine 150 mg/kg IV over 1 hour, then 50 mg/kg over 4 hours, then 100 mg/kg over 16 hours in selected patients, and transplant assessment for acute liver failure.
8. Late complications: esophageal dilatation for strictures after 3 weeks.

Follow-up: serum copper, liver tests and renal function weekly until normal, and endoscopy at 3 to 4 weeks for strictures. Counsel on safe storage of agricultural chemicals, avoiding copper vessels for acidic foods, and testing water in homes with copper plumbing.