LETTER TO THE EDITOR
Year : 2011 | Volume
: 22 | Issue : 6 | Page : 1240--1242
Copper sulphate poisoning and exchange transfusion
Muneeba Malik, Abeera Mansur
Nephrology Division, Doctors Hospital and Medical Center, Lahore, Pakistan
Nephrology Division, Doctors Hospital and Medical Center, Lahore
|How to cite this article:|
Malik M, Mansur A. Copper sulphate poisoning and exchange transfusion.Saudi J Kidney Dis Transpl 2011;22:1240-1242
|How to cite this URL:|
Malik M, Mansur A. Copper sulphate poisoning and exchange transfusion. Saudi J Kidney Dis Transpl [serial online] 2011 [cited 2020 Jul 10 ];22:1240-1242
Available from: http://www.sjkdt.org/text.asp?2011/22/6/1240/87244
To the Editor,
Copper sulphate ingestion is a rare mode of poisoning except in India and Pakistan, where the cases are mainly suicidal in nature  . Its clinical course involves intravascular hemolysis, jaundice and renal failure. Amongst the patients who develop renal failure, mortality is high.  Here, we describe the clinical presentation of a 20-year-old girl who took copper sulphate crystals for suicidal purpose.
She presented to us six days after the copper sulphate ingestion. She complained of anuria, mild drowsiness, irritability, and gastritis associated with hemetemesis. Initially, oliguria was accompanied with hematuria. She was hemodynamically stable, but had pallor, cyanosis, and jaundice. She was fluid over loaded and had epigastric tenderness. On admission, her blood urea nitrogen (BUN) was 200 mg/dL, serum creatinine (SCr) 16 mg/dL, serum potassium (K+) was 2.5 mmol/L. Hemoglobin (Hb) was markedly reduced to 6.3 mg/dL, reticulocyte count was 3.8%. She had a total leukocyte count (TLC) of 22.6 × 10 9 /L and lactate dehydrogenase (LDH) level was found to be 2479 U/L. Liver enzymes were deranged with serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT), which were elevated to 790 U/L and 270 U/L, respectively.
She was initially given treatment with 1% methylene blue at a dose 2 mg/kg for methemoglobinemia. But she had no improvement of her cyanosis. Subsequently, hemodialysis was done along with exchange transfusion. Her mental status improved significantly after the first HD and exchange transfusion. Exchange transfusions were done twice with three units of blood each time. She was discharged seven days post admission. A total of four sessions of HD were done. Her urine output gradually improved and she also had complete recovery of hemolysis. Six weeks post ingestion; she had a SCr of 0.9 mg/dL and was in good health.
Copper sulphate is used in fungicides, insecticides, white washing, and leather manufacturing. Toxic dose is considered to be 10-20 gm. In acute poisoning, copper is bound to albumin and is also taken up by the liver, kidneys, brain, and red blood cells (RBCs). The clinical course of such patients is complicated by intravascular hemolysis, jaundice, renal failure, methemoglobinemia and central nervous system (CNS) symptoms.
Amongst poisons that cause renal failure and need dialysis, copper sulphate was the second most common and was one of the major fatal poisons in India.  However, the incidence is showing a declining trend.  Mortality can be as high as 24.9%. 
Hemolytic anemia is caused by increased red cell membrane permeability or as a result of inactivation of enzymes including glutathione reductase and glucose-6-phosphate dehydrogenase, which protect against oxidative stress. Copper is an oxidizing agent and inactivates these enzymes. In addition, copper ions oxidize oxyhemoglobin from the ferrous to the ferric form resulting in methemoglobinemia and therefore reducing oxygen binding capacity, leading to cyanosis.
Intravascular hemolysis occurs almost 12-24 hours following copper sulphate ingestion. Jaundice can be secondary to hepatic necrosis and hemolysis. Liver damage is due to cell necrosis as well as obstruction.  Renal impairment is mainly due to intravascular hemolysis. Heme pigment released due to hemolysis and direct toxic effects of copper from lysed red cells contribute to acute tubular necrosis. Volume depletion and shock could also contribute to renal failure. Kidney biopsies in these patients has revealed features of acute tubular necrosis and tubules contained hemoglobin casts. 
Renal complications become manifested usually after 48h and include hemoglobinuria and hematuria, oliguria, and eventually anuria.  Renal failure develops in almost 38% of patients.  In one report of 66 patients requiring dialysis for acute poisoning, 18 cases were due to ingestion of copper sulphate. Mortality was 30% in patients with copper sulphate poisoning who needed dialysis.  In another series, the mortality was more than 60% in patients who needed dialysis.  Thus, renal failure is frequent in copper sulphate poisoning with high mortality rate in those patients who require dialysis.
Several methods of treatment of copper sulphate poisoning have been described. Chelation therapy with dimercaperol and pencillamine has been tried which showed some success, including patients with renal failure. ,, Methylene blue is an effective antidote for most patients with methemoglobinemia. The dose is 1 to 2 mg/kg infused intravenously over three to five minutes which may be repeated. Methylene blue should reduce methemoglobin levels significantly in less than an hour. It does this by acting as a co-factor to increase the activity of NADPH-methemoglobin reductase. Acquired methemoglobinemia is also seen secondary to aniline dyes, nitrites, dapsone, and benzocaine, etc.
For severe life-threatening methemoglobinemia, when the patient responds poorly to methylene blue therapy, when the patient has G6PD deficiency or when there is severe hemolysis (for methylene blue to work, intact RBCs are needed), clinicians have tried various treatment alternatives. , One treatment option in these patients is exchange transfusion. In one case report, with the use of organic copper fungicide, failure of methylene blue was followed by successful use of BAL and plasma exchange.  Furthermore, exchange transfusion has been used to remove other poisons. Exchange transfusion refers to removal of around 100 mL of blood from the poisoned patient each time and its replacement with an identical quantity of whole blood. This patient had severe hemolysis. Thus, in our case, we used exchange transfusion twice in her course of treatment. This proved to have effective results and to the best of our knowledge, this is only the second reported case of using exchange transfusion for copper sulphate poisoning.
Hemodialysis is not very helpful for the removal of copper. In a case of parenteral copper poisoning, there was no significant change in either blood or dialysate copper post dialysis.  In another case of fatal copper sulphate poisoning, during autopsy, a significant amount of copper was found in the brain, heart, liver, kidney, spleen, and adrenals. This patient had undergone dialysis for 13 hours post ingestion.  This indicates that probably hemodialysis is useful in the removal of copper only during the time period that it is still present in the circulation as free copper. However, in some patients, hemodialysis may be required subsequently as supportive treatment for the renal failure often associated with this poisoning.
In summary, copper sulphate is a very toxic and lethal compound. Although mortality is high, especially in patients with renal failure, our patient recovered completely. Treatment is mainly supportive, but almost always requires methylene blue; chelating agents can be useful. Hemodialysis, although may not contribute much in the removal of copper, it may be required for acute kidney injury and its complications. Exchange transfusion, a simple procedure, can be beneficial, as seen in this patient. Mortality can be reduced if the above measures are undertaken without delay.
|1||Saravu K, Jose J, Bhat MN, Jimmy B, 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.|
|2||Chugh KS, Sharma BK, Singhal PC, Das KC, Datta BN. Acute renal failure following copper intoxication. Postgrad Med J 1977;53(615):18-23.|
|3||Agarwal SK, Tiwari SC, Dash SC. Spectrum of poisoning requiring haemodialysis in a tertiary care hospital in India. Int J Art Organs 1993; 16(1):20-2.|
|4||Singh D, Dewan I, Pandey AN, Tyagi S. Spectrum of unnatural fatalities in the Chandigarh zone of north-west India-a 25 year autopsy study from a tertiary care hospital. Clin Forensic Med 2003;10(3):145-52.|
|5||Ahasan HA, Chowdhury MA, Azhar MA, Rafiqueddin AK. Copper sulphate poisoning. Trop Doct 1994;24(2):52-3.|
|6||Oldenquist G, Salem M. Parenteral copper sulphate poisoning causing acute renal failure. Nephrol Dial Transplant 1999;14:441-3.|
|7||Franchitto N, Gandia-Mailly P, Georges B, et al. Acute copper sulphate poisoning: a case report and literature review. Resuscitation 2008;78(1): 92-6|
|8||Bradberry SM. Occupational methaemoglobinaemia. Mechanisms of production, features, diagnosis and management including the use of methylene blue. Toxicol Rev 2003;22(1):13-27.|
|9||Agency for toxic substances and disease registry, Case Studies in Environmental Medicine (CSEM): Nitrate/nitrite toxicity how should patients exposed to nitrates/nitrites be treated and managed?|
|10||Yang CC, Wu ML, Deng JF. Prolonged hemolysis and methemoglobinemia following organic copper fungicide ingestion. Vet Hum Toxicol 2004;46(6):321-3.|
|11||Agarwal BN, Bray SH, Bercz P, Plotzker R, Labovitz E. Ineffectiveness of hemodialysis in copper sulphate poisoning. Nephron 1975;15 (1):74-7.|