CASE REPORT copper sulfate, ingestion; ingestion, copper sulfate; shock, refractory, copper sulfate ingestion

Refractory Shock Secondary to Copper Sulfate Ingestion

Earl Schwartz, MD, FACEP Eric Schmidt, MD

Winston-Salem, North Carolina

From the Section of Emergency Medicine, Department of Surgery, Wake Forest

Medical Center, Bowman Gray School of Medicine, Winston-Salem, North Carolina.

Received for publication November 1, 1985. Accepted for publication

January 8, 1986.

Address for reprints: Earl Schwartz, MD, FACEE Section of Emergency Medicine, Bowman Gray School of Medicine, 300 South Hawthorne Road, Winston-Salem,

North Carolina 27103.

Presented is the case of a 62-year-old man with refractory shock secondary to copper sulfate ingestion. The patient's history was complicated by the presence of peptic ulcer disease, myocardial disease, and a known abdomi- ned aortic aneurysm. Despite the presence of such characteristic signs and symptoms as hemorrhagic gastroenteritis, hemolytic anemia, and refractory hypotension, the diagnosis of copper sulfate ingestion was delayed for sever- al days after ingestion, when the family first volunteered that the patient had vomited blue-green material the day before his admission to the hospi- tal. This delay contributed significantly to the patient's ultimate demise. [Schwartz E, Schmidt E: Refractory shock secondary to copper sulfate inges- tion. Ann Emerg Med August 1986;15:952-954.]

I N T R O D U C T I O N The emergency physician frequently is faced with the evaluation of the

unconscious patient who is suspected of having ingested an unknown sub- stance.

We describe a case of lethal copper sulfate ingestion and review the signs and symptoms necessary for diagnosis and prompt initiation of possibly life- saving chelation therapy.

CASE REPORT A 62-year-old man was brought to the emergency department by am-

bulance. The patient's daughter told the paramedics that her father had been taking large amounts of aspirin, and that for two or three days he had had dark stools and had vomited coffee-ground-like material. He had become increasingly lethargic the day before and had been found unresponsive just before the paramedics were called. The paramedics found the patient to be unresponsive and cyanotic, with respirations of 20, a pulse of 110, and no measurable blood pressure. Ventilatory assistance with oxygen was provided, and two large-bore peripheral IV lines were established through which lac- tated Ringer's solution was run at a rapid rate. No change in mental status occurred following the IV administration of 50 mL 50% dextrose in water and a total of 2 mg naloxone.

By the time the patient arrived at the ED, he had become responsive and fairly alert, although he still was somewhat lethargic. His vital signs were as follows: blood pressure, unobtainable; pulse, 80; respirations, 24; and rectal temperature, 36 C. Further questioning of the family revealed that the pa- tient had a history of peptic ulcer disease, a myocardial infarction, and a small, 2.8-cm abdominal aortic aneurysm that was diagnosed several months earlier. His medications consisted of propranolol, 10 nag three times daily, oxazepam 30 mg three times daily, and nitroglycerin sublingually as needed. Family members did not think that the patient had been taking more of his medications, other than aspirin, than had been prescribed.

The patient's physical examination showed no marked abnormalities other than his obtundation and hypotension. His skin was somewhat cyanotic and cool. There was no dry blood in the nose or mouth. His neck was supple with no jugular venous distension. His heart and lungs were unremarkable. The patient had epigastric tenderness wi thout rebound, normal bowel sounds, and no palpable abdominal masses. His stool was melanotic and

140/952 Annals of Emergency Medicine 15:8 August 1986

positive for blood. He had bilateral femoral bruits of the inguinal area. There were no focal neurologic defi- cits.

A chest roentgenogram showed m- distinct interstitial markings consis- tent with early interstitial edema. The ECG showed a normal sinus rhythm, left ventricular hypertrophy, inferior infarct (age undetermined), ST depres- sion, and T-wave abnormalities some- what increased over previous ECGs. An abdominal ultrasonogram demon- strated an infrarenal abdominal aortic a n e u r y s m unchanged f r o m three months before and without evidence of a retroperitoneal hematoma.

In addition to the routine laboratory studies, a toxicologic screen and blood cultures were requested. The results were as follows: RBC, 4.72 x 106; he- moglobin, 13.9 gm/100 mL; hemato- crit, 41.9%; mean corpuscular volume, 88.8 ~m3; mean corpuscular hemo- globin, 29.4 pg; mean corpuscular he- moglobin concentration, 33.2 grn/100 mL; WBC, 13.2 x 103/mm 3, wi th 88% segmented cells, 7% banded cells, 2% lymphocytes, and 3% mono- cytes; sodium, 132 mEq/L; potassium, 4.1 mEq/L; chloride, 104 mEq/L; CO2, 20 mEq/L; BUN, 34 mg/100 mL; creatinine, 1.6 mg/100 mL; glucose be- fore es tab l i shment of IV lines, 92 mg/100 mL; and glucose after admin- istration of Dso , 324 rag/100 mL. Uri- nalysis revealed the following: pH, 6; protein, 30 rag/100 mL (heat + acid, 1+); glucose, none; ketones, none; bilirubin, none; blood, none; specific gravity, 1.022; urobilinogen, 1 EU/dL; hyaline casts, 0 to 3; RBC, 0 to 1; and WBC, 0 to 2.

Arterial blood gas values with the patient breathing 40% oxygen through a face shield were pH, 7.34; PCO2, 39 m m Hg; PO2, 182 m m Hg; HCO; , 21.9 m m Hg; oxygen saturation, 99%; carboxyhemoglobin, t.0; methemoglo-

bin, 0; and salicytate level, 12 mg/100 mL. The patient's central venous pres- sure gradually increased from 0 to 4 cm H20 to 14 cm H20 with the ad- ministration of 4 L to 5 L Ringer's lac- tate and two units of type-specific blood; however, he remained lethargic and markedly hypotensive with an ar- terial pressure of 80/40 m m Hg. Nasogastric aspiration revealed only small amounts of blood-tinged, coffee- ground-like aspirate, which quickly deared.

Because of the pe r s i s t en t unex- plained hypotension despite the in- creasing central venous pressure, a regimen of 1V dopamine was begun and the patient was admitted to the intensive care unit for Swan-Ganz and intraarterial monitoring. Medical and surgical consultations were obtained. The pa t i en t ' s blood pressure was maintained at 110/60 m m Hg by dopa- mine infusion. Despite his improved hemodynamic state, he became pro- gressively more obtunded, and it was decided to perform an exploratory laparotomy and concomitant intra- operative endoscopy.

Erosive esophagit is and gastri t is with gastric and duodenal ulcers were found. No intraabdominal bleeding was detected.

P os tope ra t i ve ly the pa t i en t re- mained very unstable, requiring dopa- mine to maintain his blood pressure. The family then for the first time vol- unteered that the patient had vomited large amounts of blue material onto his shirt the day before he was admit- ted. Family members were asked to obtain the shirt and anything from the medicine or cleaning cabinets that the patient might have taken. They re- turned with the blue-green stained shirt and a bottle of copper sulfate. By this time, however, the patient had de- veloped a hemolytic anemia, elevated liver enzymes, and increasing renal

failure, which did not respond when therapy with dimercaprol 4 mg/kg IM every four hours in oil (BAL) was be- gtm. He died on the second day after admission. Permission for autopsy was denied. Unfortunately, whole blood copper levels were never measured.

DISCUSSION Copper is an essential element in-

volved in the cytochrome system and the enzyme superoxide dismutase3 It is absorbed rapidly across the gastric mucosa and bound to various pro- teins; eventual ly the highest con- centrations are found in the liver, kid- neys, heart, and brain.t,2 Amounts of copper salts greater than trace are ex- tremely toxic, probably secondary to i n t e r a c t i o n s w i th the su l fhydro ! g r o u p s . 1

Copper poisoning has been known since people began smelting the metal and its alloys from ore on the island of Cyprus, from which the metal derives its name. The Egyptians probably made use of this toxicity in concoct- ing their antibiotic "green salve" from copper carbonate. 3 Cooking in copper or brass vessels may produce nausea and vomiting, but the toxic reaction is rarely lethal. 4 Copper toxicity in this country is related to exposure to cop- per salts, usually sulfate and oxide, that are found in fungicides, insec- ticides, and algicides) Copper sulfate accounts for a large number of poison- ings and suicides in India. 2

Topical exposure may result in se- vere skin or mucous membrane irrita- t i on : Ingestion of as little as 250 mg of copper sulfate may be toxic, result- ing in a prompt metal l ic taste fol- lowed by nausea and emesis of charac- teristic blue-green vomitus, usually within 15 minutes. It is for this reason that 1% CuSO 4 solution was used pre- viously as an emetic; 5 it now has been replaced by less toxic agents.

15:8 August 1986 Annals of Emergency Medicine 953/141

COPPER SULFATE INGESTION Schwartz & Schmidt

Copper sulfate produces mucosal erosions and a hemorrhagic gastroen- teritis, rarely accompanied by hemo- lytic anemia and methemoglobine- mia.l,Z, 4 Small amounts may produce refractory hypotension, coma, or sei- zures.l,2, 4 Renal sequelae, usually de- layed for one to two days, may include oiiguria, hemoglobinuria, or hematu- ria.l,2, 4 Two to three days after inges- tion of copper sulfate, centrilobular necrosis may result in hepatomegaly and jaundice.l,2,4, s Our patient had hemorrhagic gastroenteritis, refractory hypotension, and alteration in con- sciousness approximating coma.

The patient may complain of a me- tallic taste from the characteristic blue-green vomitus, or may be hypo- tensive and stuporous. Initial manage- ment involves securing the airway and treating the hypotension with crystal- loid solutions, plus dopamine or nor- epinephrine bi tar t rate if needed. 4 Emesis or lavage then should be initi- ated followed by activated charcoal and a cathartic. Baseline CBC counts and differential, renal and liver func- tion studies, and whole blood copper values should be obtained. A severe intoxication is indicated by a whole blood copper value of more than 500

mg/100 mL (normal, 50 to 120 mg/100 mL)3

Surgery for gastrointestinal hemor- rhage may be needed, but chelation therapy is the cornerstone of treat- ment.l,2, 4 While mammalian models suggest the superiority of some experi- menta l chelators, those available clinically are dimercaprol in oil and D-penicillamine.6, 7 Dimercaprol in oil is administered intramuscularly in 3- to 5-mg/kg doses every four hours for two days, every four to six hours for two days, and then every four to 12 hours for as many as seven additional days. D-penicillamine is given at 100 mg/kg/day in four divided doses for up to five days. Should renal failure ensue, either chelator can be removed by dialysis. 6

SUMMARY Copper sulfate ingestion is an un-

usual emergency department problem, one that requires prompt recognition of the significance of complaints of a metallic taste and blue-green vomitus, wi th or w i t h o u t gas t ro in tes t ina l bleeding. For the comatose patient, questioning of the family may elicit that history. Prompt in i t ia t ion of chelation therapy may ward off the

potentially fatal hepatic and renal se- quelae.

REFERENCES 1. Walsh FM, Crosson FJ, Bayley M, et al: Acute copper intoxication: Pathophys- iology and therapy with a case report. Am J Dis Child 1977;131:149-151.

2. Chuttani HK, Gupta PS, Gulati S, et al: Acute copper sulfate poisoning. Am l Med 1965;39:849-854.

3. Majno G: The Healing Hand. Man and Wound m the Ancient World. Cambridge, Massachusetts , Harvard University Press, 1975, pp 111-115.

4. Cohen SR: A review of the health haz- ards from copper exposure. J Occupa- tional Med 1974;16:621-624.

5. Stein RS, Jenkins D, Korns ME: Death after use of cupric sulfate as emetic (letter with case report). JAMA 1976;235:801.

6. Mitchell WM, Basinger MA, Jones MM: Antagonism of acute copper (II)-in- duced renal lesions by sodium 2, 3-dimer- captopropranesulfonate. Johns Hopkins Med ] 1982;15!:283-285.

7. Jones MM, Basinger MA, Tarka MP: The relative effectiveness of some chelat- ing agents in acute copper intoxication in the mouse. Res Commun Chem Pathol Pharmacol 1980;27:571-577.

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