Copper toxicity: Difference between revisions
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==Management== | ==Management== | ||
===Supportive care=== | |||
*Antiemetics | |||
*Fluid and electrolyte repletion | |||
*GI decontamination unlikely to benefit | |||
*Activated charcoal contraindicated | |||
===Chelation=== | |||
*Recommended in cases with hematologic or hepatic complications | |||
*Most commonly used are BAL and D-penicillamine | |||
*British anti-Lewisite (BAL) | |||
**Beneficial in patients with vomiting who are unable to take D-penicillamine | |||
**Useful in those with renal failure | |||
*D-penicillamine | |||
**Should be started as soon as able to tolerate PO | |||
**Begin simultaneously with BAL or soon after | |||
**Prevents copper induced hemolysis in patients with wilson disease | |||
**Undergoes renal clearance | |||
**'''1.0-1.5 g/d given PO in 4 divided doses''' | |||
**Can be used for acute and chronic copper poisoning | |||
**Complications | |||
***Worsening of neurologic findings | |||
***Aplastic anemia | |||
***Agranulocytosis | |||
***Renal and pulmonary disease | |||
***Hypersensitivity reactions in 25% of patients with pencillin allergies | |||
***Congenital abnormaliies in pregnenancy | |||
*CaNa<sub>2</sub>EDTA | |||
**Will reduce oxidative damage | |||
**Does not enhance elimination | |||
*[[Succimer]] | |||
**Ineffective copper chelator | |||
**Does increase copper elimination in murine models | |||
**Dose is the same as lead dosing | |||
*DMPS | |||
**Not recommended for treatment of copper poisoning | |||
**Can worsen copper induced hemolysis | |||
*Trientine | |||
**Second line chelator for wilson disease | |||
**No reports in acute copper poisoning | |||
*Tetrathiomolybdate | |||
**FDA chelating agent with orphan drug status | |||
**No human studies but showed benefits in animal models | |||
===Extracorporeal Elimination=== | |||
*Unlikely to benefit | |||
*Exchange transfustion | |||
**Limited benefit | |||
*Hemodialysis | |||
**Not recommended | |||
**Membranes allow copper ions to cross | |||
**Unlikely to be clinnicall useful | |||
**May also lyse erythrocytes release stored copper causing worsening toxicity | |||
*Molecular adsorbents recirculating system (MARS) and Single Pass Albumin Dialysis (SPAD) | |||
**Rapidly and substantially lower serum copper concentraions | |||
**Risk of hemolysis | |||
*Plasma Exchange | |||
**Enhanced elimination of copper by 3-12 mg | |||
**Unclear if benficial after large ingestions | |||
**Risk of hemolysis | |||
*Peritoneal Dialysis | |||
**Not useful | |||
==Disposition== | ==Disposition== |
Revision as of 20:33, 12 August 2018
Background
- Widely available metal
- Obtained from various foods including nuts, fish, and green vegetables
- Numerous poisonings from copper pipes
- Occurs from storage of acidic substances (lemon/orange juice), pipes exposed to carbon dioxide from carbonation process, stagnant, and hot water which leach out copper from pipes
Copper Uses
- Pipes
- Cookware
- Electrical wire
- Medical devices (copper IUD)
- Dietary supplements
- Bordeaux solution (used as a pesticide)
Toxicokinetics
- Absorbed in the GI tract
- Bound by ceruoplasmin
- Elimination via biliary system
- Minimal renal elimination
- VD : 2L/kg
- Copper sulfate
- Most common acute poisoning
- Lethal dose is 0.15-0.3g/kg
- Toxicity is caused through redox reactions
- Fenton reaction
- Haber-Weiss cycle
- Generates oxidative stress, inhibiting key metabolic enzymes, particularly in cell membranes and mitochondria
- Organ specific damage
- Erythrocytes
- Membran dysfunction resulting in hemolysis
- Occurs within the first 24 hours
- Hepatic
- Excess copper not bound by metallothionein participates in redox reactions and cause lipid peroxidation
- Centrilobular necrosis
- After necrosis there is a release of massive amounts of copper into the blood causing a secondary hemolysis
- Renal
- ATN with hemoglobin casts, likely from hemolysis
- Erythrocytes
Clinical Features
Acute
- GI irritation
- Emesis (may be blue based on copper compound, but is not pathognomonic)
- Abdominal pain
- Gastroduodenal hemorrhage, ulceration, and perforation
- Metallic taste
- Hepatic
- Jaundice
- Hematologic
- Hemolysis
- May see methemoglobinemia
- Renal
- Renal failure uncommon
- Hypotension and cardiovascular collapse
- Likely multifactorial
Chronic
- Wilson disease
- CNS
- Ataxia
- Tremor
- Parkinsonism
- Dysphagia
- Dystonia
- Behavioral
- Mood changes
- Occular
- Kayser-Fleischer rings
Differential Diagnosis
Also seen in Wilson disease
Heavy metal toxicity
- Aluminum toxicity
- Antimony toxicity
- Arsenic toxicity
- Barium toxicity
- Bismuth toxicity
- Cadmium toxicity
- Chromium toxicity
- Cobalt toxicity
- Copper toxicity
- Gold toxicity
- Iron toxicity
- Lead toxicity
- Lithium toxicity
- Manganese toxicity
- Mercury toxicity
- Nickel toxicity
- Phosphorous toxicity
- Platinum toxicity
- Selenium toxicity
- Silver toxicity
- Thallium toxicity
- Tin toxicity
- Zinc toxicity
Evaluation
Clinical diagnosis, as copper levels will likely take days to result
- BMP
- Hepatic function tests
- CBC
- PT/PTT/INR\
- Copper and ceruloplasmin level
- Abdominal films to assess for foreign bodies
Copper level
No set number that establishes a prognosis [1]
- Whole blood = 70–140 μg/dL (11–22 μmol/L)
- Total serum = 120–145 μg/dL (18.8–22.8 μmol/L)
- Free serum = 4–7 μg/dL (0.63–1.1 μmol/L)
- Ceruloplasmin = 25–50 μg/dL (3.9–7.8 μmol/L)
- Urine = 5–25 μg/24 h (.078–3.9 nmol/L)
Management
Supportive care
- Antiemetics
- Fluid and electrolyte repletion
- GI decontamination unlikely to benefit
- Activated charcoal contraindicated
Chelation
- Recommended in cases with hematologic or hepatic complications
- Most commonly used are BAL and D-penicillamine
- British anti-Lewisite (BAL)
- Beneficial in patients with vomiting who are unable to take D-penicillamine
- Useful in those with renal failure
- D-penicillamine
- Should be started as soon as able to tolerate PO
- Begin simultaneously with BAL or soon after
- Prevents copper induced hemolysis in patients with wilson disease
- Undergoes renal clearance
- 1.0-1.5 g/d given PO in 4 divided doses
- Can be used for acute and chronic copper poisoning
- Complications
- Worsening of neurologic findings
- Aplastic anemia
- Agranulocytosis
- Renal and pulmonary disease
- Hypersensitivity reactions in 25% of patients with pencillin allergies
- Congenital abnormaliies in pregnenancy
- CaNa2EDTA
- Will reduce oxidative damage
- Does not enhance elimination
- Succimer
- Ineffective copper chelator
- Does increase copper elimination in murine models
- Dose is the same as lead dosing
- DMPS
- Not recommended for treatment of copper poisoning
- Can worsen copper induced hemolysis
- Trientine
- Second line chelator for wilson disease
- No reports in acute copper poisoning
- Tetrathiomolybdate
- FDA chelating agent with orphan drug status
- No human studies but showed benefits in animal models
Extracorporeal Elimination
- Unlikely to benefit
- Exchange transfustion
- Limited benefit
- Hemodialysis
- Not recommended
- Membranes allow copper ions to cross
- Unlikely to be clinnicall useful
- May also lyse erythrocytes release stored copper causing worsening toxicity
- Molecular adsorbents recirculating system (MARS) and Single Pass Albumin Dialysis (SPAD)
- Rapidly and substantially lower serum copper concentraions
- Risk of hemolysis
- Plasma Exchange
- Enhanced elimination of copper by 3-12 mg
- Unclear if benficial after large ingestions
- Risk of hemolysis
- Peritoneal Dialysis
- Not useful
Disposition
- Consult Toxicology or Poison Control Center
References
- ↑ Gulliver JM. A fatal copper sulfate poisoning. J Anal Toxicol. 1991;15: 341-342.
Nelson, L. Copper. In: Goldfrank's Toxicologic Emergencies. 9th Ed. New York: McGraw-Hill; 2011: 1256-1265