DESCRIPTION

Copper is a reddish-brown metal. Copper sulfate is caustic salt composed of blue crystals or liquid.

FORMS AND USES

• Substances covered in this chapter include metallic copper, copper sulfate (cupric sulfate), cupric oxide, cuprous oxide, cupric acetate, cupric acetoarsenate, cupric arsenite, cupric carbonate, cupric chloride, cupric chromate, cuprous cyanide, cupric tungstate, cupric hydroxide, cupric nitrate, and cupric selenide.
• Copper is used in battery work, electroplating, fungicides and insecticides, plumbing, soldering, welding, ceramics, paints, pigments, pyrotechnics, photography, water purification, animal foods, petroleum distillation, and pharmaceuticals.
• Copper sulfate may be found in children's chemistry sets and crystal gardens and in Clinitest tablets.

TOXIC DOSE

• Copper sulfate is the most toxic form. Renal failure and death have been reported after ingestion of 1 g of copper sulfate.
• Death has occurred after a few swallows of water (29 µg/ml copper sulfate) from a crystal garden.

PATHOPHYSIOLOGY

• Chronic exposure to copper sulfate during spraying has been associated with interstitial pulmonary granulomas and fibrohyaline scars that contain large amounts of copper.
• Copper sulfate has caused alkaline corrosive mucosal injury after ingestion.
• Copper inhibits sulfhydryl enzymes, allowing production of free radicals and increasing susceptibility to lipid peroxidation, thereby causing hemolysis, hepatotoxicity, and nephrotoxicity

EPIDEMIOLOGY

• Poisoning is uncommon.
• Toxic effects during chronic exposure are mild.
• Death may occur after ingestion of copper sulfate in high concentration.
• Carcinogenesis. The risk of adenocarcinoma is increased after chronic exposure to copper sulfate spray, believed to be due to arsenite contaminant.

CAUSES

• Chronic exposure is usually occupational.
• Acute exposure is usually from accidental ingestion.
• Child neglect or abuse should be considered if the patient is less than 1 year of age, suicide attempt if the patient is over 6 years of age.

WORKPLACE STANDARDS

Metallic copper

• ACGIH. TLV TWA is 0.2 mg/m³ (fumes).
• OSHA. PEL TWA is 0.1 mg/m³ (fumes); 1 mg/m³ (dusts and mists).
• NIOSH.
  • REL TWA is 0.2 mg/m³ (fumes); 1 mg/m³ (dusts and mists).
  • IDLH is 100 mg/m³.

Section Outline:

• DESCRIPTION
• FORMS AND USES
• TOXIC DOSE
• PATHOPHYSIOLOGY
• EPIDEMIOLOGY
• CAUSES
• WORKPLACE STANDARDS

DIFFERENTIAL DIAGNOSIS

• Toxicologic causes of acute gastrointestinal caustic effect include alkaline or acid solutions, phenol, several of the inorganic metal salts, and hydrogen peroxide, among others.
• Toxicologic causes of hepatic necrosis and renal failure include Amanita phalloides mushroom, acetaminophen, and carbon tetrachloride, among others.
• Toxicologic causes of interstitial lung disease include chronic exposure to beryllium, cobalt, coal mining, or multiple allergens (e.g., farmer's lung).
• Other causes of gastrointestinal effects include esophagitis, gastritis, peptic or duodenal ulcers, and perforated ulcer.

SIGNS AND SYMPTOMS

• Copper sulfate ingestion causes initial vomiting, diarrhea, abdominal pain, and corrosive injury leading to bleeding, perforation, shock, hemolysis, and renal and hepatic failure in severe cases.
• Chronic occupational exposure rarely causes serious illness.
• Metal fume fever may develop with exposure to copper fumes.

Vital Signs

Hypotension and tachycardia occur after copper sulfate ingestion.

HEENT

• Copper sulfate crystals have caused severe corneal injury.
• Oral burns may develop after copper sulfate ingestion.

Dermatologic

• Copper sulfate can cause dermal irritation.
• Chronic copper exposure can cause blue-green discoloration of skin and hair.

Cardiovascular

Cardiovascular collapse and ventricular dysrhythmias may develop after severe copper sulfate ingestion.

Pulmonary

• Chronic exposure to copper sulfate spray is associated with interstitial disease with granulomas and fibrohyaline scars.
• Some patients progress to pulmonary fibrosis.

Gastrointestinal

Early effects of copper sulfate ingestion include vomiting, diarrhea (may be blue-green), and abdominal pain, with corrosive gastrointestinal injury, hemorrhage, and perforation in severe cases.

Hepatic

Copper sulfate may cause centrilobular hepatic necrosis with elevated liver function tests and jaundice after 2 to 3 days, which may progress to hepatic failure.

Renal

• Copper sulfate may cause hematuria or hemoglobinuria from hemolysis.
• Acute renal failure may occur after severe poisoning.

Fluids and Electrolytes

Fluid and electrolyte disturbances and metabolic acidosis from severe vomiting and diarrhea may occur after copper sulfate ingestion.

Musculoskeletal

Rhabdomyolysis develops rarely after copper sulfate ingestion.

Neurologic

Coma and hepatic encephalopathy may occur after severe ingestion.

PROCEDURES AND LABORATORY TESTS

Essential Tests

No tests may be needed in asymptomatic patients.

Recommended Tests

• Complete blood count with peripheral smear may be performed to assess hemolysis.
• Serum electrolytes, BUN, and creatinine are measured in symptomatic patients to assess electrolyte disturbance or metabolic acidosis.
• Prothrombin time and liver function tests may be elevated in acute liver injury.
• Serum copper levels may be measured in symptomatic patients.
  • Normal serum copper is 1 µg/ml.
  • Greater than 5 µg/ml is considered toxic.
• ECG, serum acetaminophen, and aspirin levels may be performed in an overdose setting to detect occult overdose.
• Chest radiograph may be performed in symptomatic patients; copper salts may be radiopaque.
• Abdominal radiography may be useful to assess adequacy of decontamination.
• Gastrointestinal endoscopy is performed within 24 hours of ingestion of corrosive copper salt for patients with stridor, drooling, or vomiting or for adults with suicidal or large ingestions to assess extent of mucosal injury.

Section Outline:

• DIFFERENTIAL DIAGNOSIS
• SIGNS AND SYMPTOMS
  • Vital Signs
  • HEENT
  • Dermatologic
  • Cardiovascular
  • Pulmonary
  • Gastrointestinal
  • Hepatic
  • Renal
  • Fluids and Electrolytes
  • Musculoskeletal
  • Neurologic
• PROCEDURES AND LABORATORY TESTS
  • Essential Tests
  • Recommended Tests

• Treatment should focus on replacing gastrointestinal losses of fluid and blood, assessing gastrointestinal burns, and evaluating hemolysis, renal, and hepatic injury.
• Dose and time of exposure should be determined for all substances involved.
• Consultation with a medical toxicologist and other specialists, such as a gastroenterologist, is highly recommended.
• Patients with corneal burns should immediately be referred to an ophthalmologist.

DIRECTING PATIENT COURSE

The health-care professional should call the poison control center when:

• History of ingestion of copper sulfate is obtained.
• Toxic effects are not consistent with copper poisoning.
• Coingestant, drug interaction, or underlying disease presents an unusual problem.

Patients should be referred to a health-care facility when:

• History of ingestion of copper sulfate is obtained.
• Attempted suicide or homicide is possible.
• Patient or caregiver seems unreliable.
• Coingestant, drug interaction, or underlying disease presents an unusual problem.

Admission Considerations

Inpatient management in an intensive care setting is warranted when the patient has symptoms after ingestion of corrosive copper salt.

DECONTAMINATION

Out of Hospital

• Emesis should not be induced.
• Stomach contents should be diluted (by encouraging the patient to drink) with a small amount (4 ounces) of milk or water.
• Exposed eyes and skin should be irrigated with water.

In Hospital

• Stomach contents should be diluted (by encouraging the patient to drink) with a small amount (4 ounces) of milk or water.
• Gastric aspiration with a flexible tube should be performed in patients who have not already had repeated emesis within 1 hour of ingestion of a corrosive copper salt.
• Gastric lavage is not recommended because there is some risk of perforation during lavage after corrosive ingestion.
• Copper will adhere somewhat to activated charcoal, and if a noncorrosive form of copper is ingested, then one dose of activated charcoal (1-2 g/kg) should be administered without a cathartic.
• Exposed eyes should be irrigated with copious amounts of water, and a slit-lamp examination should be performed.
• Exposed skin should be irrigated with copious amounts of water and washed with soap.

ANTIDOTES

• Copper is bound to metal chelators, but there is little experience with chelation after acute copper intoxication.
• It is generally used for serious exposures, but the efficacy of this practice is unknown.
• Consultation with a medical toxicologist is advised.
• d-penicillamine
  • Indication. Symptomatic, acute copper sulfate ingestion or chronic intoxication (Wilson's disease).
  • Contraindications. Allergy to penicillin or penicillamine.
  • Dose. 20 to 30 mg/kg orally, divided into four doses daily.
  • Potential adverse effects
    • Rash, fever, leukopenia, thrombocytopenia, eosinophilia, and hemolytic anemia may occur.
    • The antidote may be difficult to administer due to vomiting.
  • Other chelating agents. Ethylenediaminetetraacetic acid (EDTA) and British anti-Lewisite (dimercaprol) also have been used for copper intoxication.

ADJUNCTIVE TREATMENT

Hypotension

• The patient should be given 10 to 20 ml/kg 0.9% saline intravenously and placed in the Trendelenburg position.
• Further fluid therapy should be guided by central pressure monitoring to avoid volume overload.
• If hypotension is unresponsive, a vasopressor should be administered. Dopamine is preferred, and norepinephrine is added for refractory hypotension.

Steroids

• Studies suggest that steroids reduce stricture formation after alkaline-induced esophageal burns, but no data are available for copper sulfate burns.
• Steroids should be considered for patients with grade 2 burns.

Surgery

If the patient has Grade III esophageal injury or perforation, consider surgical consultation to assess the extent of gastric or duodenal burns.

Section Outline:

• DIRECTING PATIENT COURSE
  • Admission Considerations
• DECONTAMINATION
  • Out of Hospital
  • In Hospital
• ANTIDOTES
• ADJUNCTIVE TREATMENT
  • Hypotension
  • Steroids
  • Surgery

PATIENT MONITORING

Patients who are symptomatic after ingestion of copper salt should be monitored in an intensive care unit.

EXPECTED COURSE AND PROGNOSIS

• Patients who survive the first 24 hours after copper sulfate ingestion generally recover.
• Renal insufficiency, sequelae of prolonged hypotension, and esophageal strictures may persist.

DISCHARGE CRITERIA/INSTRUCTIONS

• From the emergency department. Asymptomatic patients may be discharged after 6 hours of observation, gastrointestinal decontamination, and psychiatric evaluation, if needed.
• From the hospital. Patients may be discharged when hemolysis and gastrointestinal bleeding are controlled, renal function is stable, hepatic function is improving, and adequate nutrition has been established.

Section Outline:

• PATIENT MONITORING
• EXPECTED COURSE AND PROGNOSIS
• DISCHARGE CRITERIA/INSTRUCTIONS

Grade II or III esophageal burns require a follow-up upper gastrointestinal series to detect strictures.

Toxic effect of other metals: other specified metals.

See Also: SECTION II, Hypotension and Metal Fume Fever chapters; SECTION III, British Anti-Lewisite, Ethylenediaminetetraacetic Acid (EDTA), and Penicillamine chapters; and SECTION IV, Caustics—Basic chapter.

RECOMMENDED READING

Jantsch W, Kulig K, Rumack BH. Massive copper sulfate ingestion resulting in hepatotoxicity. J Toxicol Clin Toxicol 1984;22:585-588.

Schwartz E, Schmidt E. Refractory shock secondary to copper sulfate ingestion. Ann Emerg Med 1986;15:952-954.

Author: Scott D. Phillips

Reviewer: Katherine M. Hurlbut