Acute Copper Sulfate Poisoning

Michael L. Sternberg, MD
David G. Nesbitt, MD
Volume 56 - Issue 2 - February 2016

A 61-year-old man presented to the emergency department with a 1-day history of burning abdominal pain, nausea, and 11 episodes of nonbloody emesis.

History. The patient reported ingesting over a 2-day period “7 rocks of blue stone” (Figure 1), a commercially available pond and swimming pool algaecide whose active ingredient is 99% copper sulfate. He did this upon the advice of friends in an effort to treat a “black tongue.” This tongue discoloration had been present for 2 months and had not resolved despite a 1-month course of fluconazole and a 1-week trial of prednisone prescribed by his primary care physician.

His past medical history was significant for hypertension, noninsulin-dependent diabetes, depression, and gastroesophageal reflux disease, for which he was taking lisinopril/hydrochlorothiazide, metformin, buspirone, and omeprazole, respectively. Social history included daily use of smokeless snuff tobacco and beer and occasional use of marijuana and crack cocaine.

Physical examination. Aside from tachycardia (heart rate of 132 beats/min) associated with hypotension (blood pressure of 95/70 mm Hg), physical examination findings were remarkable only for midepigastric abdominal tenderness, and a darkly mottled tongue showing papillary atrophy and fissuring (Figure 2).

Diagnostic tests. An electrocardiogram showed sinus tachycardia with right bundle branch block and left anterior fascicular block. Chest and abdominal radiographs were normal. Laboratory testing with a complete blood count, comprehensive metabolic panel, urinalysis, serum creatine kinase (CK), lactate, cardiac enzymes, a drug and alcohol screen, HIV testing, and serum copper and ceruloplasmin levels were obtained. Significant among laboratory test findings were elevations in blood urea nitrogen (45 mg/dL), creatinine (2.1 mg/dL), aspartate aminotransferase (AST, 90 U/L), alanine aminotransferase (ALT, 187 U/L), and serum CK (458 U/L).

Outcome of the case. The patient was admitted for therapy of acute copper sulfate ingestion. His hypotension, nausea, vomiting, and abdominal pain were managed with intravenous hydration, antiemetics, and a proton-pump inhibitor. Chelation therapy was instituted with intramuscular injections of dimercaprol (2.5 mg/kg every 6 h for 48 h, then every 12 h for 24 h), as well as oral zinc sulfate (220 mg twice daily).

Over the course of his hospitalization, the patient’s symptoms abated, and renal function and blood pressure improved. On hospital day 2, the serum copper level was 185 µg/dL (reference range, 70-140 µg/dL), and the ceruloplasmin level was 68 mg/dL (reference range, 17-54 mg/dL). During the course of stay, the AST level peaked at 136 U/L (reference range, 15-37 U/L), and the ALT level peaked at 215 U/L (reference range, 30-65 U/L).

After a 4-day hospital stay, the patient was discharged to complete a 2-week course of zinc sulfate therapy. He remained well at follow-up.

Discussion. Black discoloration of the tongue has been linked with poor oral hygiene as well as a number of direct toxic exposures and physiologic diseases (eg, adrenal insufficiency, acanthosis nigricans, Peutz-Jeghers syndrome, melanoma, postradiation syndrome).1 It has been associated with the use of crack cocaine and many medications, including corticosteroids, tricyclic antidepressants, and proton-pump inhibitors.2 The most common causes are staining from food products (eg, coffee, tea), bismuth, and tobacco product use, and from an overgrowth of chromogenic bacteria in response to the use of systemic antibiotics.1,3

Copper sulfate poisoning is rare in the Western world. Copper sulfate is a corrosive acid used as a pesticide in agriculture, a preservative in the lumber industry, and as an algaecide.4,5 It is available as a bright blue crystal that is commonly referred to as blue stone or blue vitriol.5

Clinically significant ingestion is facilitated by its relatively innocuous smell and taste.4 Erosive gastropathy evidenced by repeated and often bloody emesis can occur with ingestions of as little as 250 mg, and blue-green vomitus is characteristic.6 The oxidative stress on intracellular glutathione, hemoglobin, and nicotinamide adenine dinucleotide phosphate, as well as inhibition of glucose-6-phosphate and glycolytic enzymes, leads to cell wall damage.4 Erythrocytes rapidly absorb copper and are particularly susceptible to hemolysis and methemoglobinemia.5,6 Myoglobinuria from rhabdomyolysis as well as hemoglobinuria and hypovolemia combine to induce acute tubular necrosis, with renal failure usually seen by 48 hours after ingestion.5 Rapid copper absorption by the liver can induce centrilobular necrosis and hepatotoxicity by 72 hours.5,7

Minimum toxic levels of copper sulfate ingestion have been estimated at 1 g, whereas amounts of more than 10 to 20 g have been linked to lethality, predominantly from these hepatic and renal effects.6,7

The diagnosis of copper sulfate toxicity is based on history and clinical findings. Ceruloplasmin level and serum copper concentrations do not correlate with the degree of clinical symptoms; however, whole blood copper levels may.4,7 Peak serum levels of ALT (> 55 U/L) and AST (> 234 U/L) have been linked with higher mortality.4

Therapy is largely supportive, with maintenance of fluid volume essential. Early gastric lavage is indicated, although it often is precluded by copper’s emetic effects, but activated charcoal is unproven.4,7 Hemodialysis is ineffective at removing copper but commonly is employed to treat associated acute renal failure.4,7 Chelation therapy, usually with a 5- to 7-day course of d-Penicillamine, dimercaprol, or edetic acid, has limited efficacy on intrahepatic copper stores and is complicated in practice by renal injury.5 Copper usually is cleared in bile, but once chelated, it is excreted renally.7 The use of elemental zinc (150 mg/d in 3 divided doses) commonly is employed in the management of Wilson disease to block gastrointestinal absorption of copper and induce metallothionein, a protein and endogenous metal chelator.8 The benefit of the use of zinc in the acute toxic setting still is unclear.

References:

  1. D’Alessandro DM, D’Alessandro MP. What causes a black colored tongue? PediatricEducation.org. http://pediatriceducation.org/2011/12/19/what-causes-a-black-colored-tongue/. Published December 19, 2011. Accessed February 3, 2016.
  2. Jover-Diaz F, Cuadrado-Pastor JM, Talents-Bolos A, Martin-Gonzalez C. Black tongue associated with linezolid. Am J Ther. 2010;17(4):e115-e117.
  3. Allen CM, Camisa C. Oral disease. In: Bolognia JL, Jorizzo JL, Schaffer JV, eds. Dermatology. Vol 1. 3rd ed. Philadelphia, PA: Elsevier Saunders; 2012:1149-1170.
  4. Naha K, Saravu K, Shastry BA. Blue vitriol poisoning: a 10-year experience in a tertiary care hospital. Clin Toxicol (Phila). 2012;50(3):197-201.
  5. Saravu K, Jose J, Bhat MN, Beena J, Shastry BA. Acute ingestion of copper sulphate: a review on its clinical manifestations and management. Indian J Crit Care Med. 2007;11(2):74-80.
  6. Gamakaranage CSSK, Rodrigo C, Weerasinghe S, Gnanathasan A, Puvanaraj V, Fernando H. Complications and management of acute copper sulphate poisoning; a case discussion. J Occup Med Toxicol. 2011;6(1):34-38.
  7. Franchitto N, Gandia-Mailly P, Georges B, et al. Acute copper sulphate poisoning: a case report and literature review. Resuscitation. 2008;78(1):92-96.
  8. Roberts EA, Schilsky ML. Diagnosis and treatment of Wilson disease: an update. Hepatology. 2008;47(6):2089-2111.