Journal of Clinical Toxicology
Open Access
ISSN: 2161-0495
ISSN: 2161-0495
Research Article - (2022)
Background: Ingestion of copper sulphate is a common mode of poisoning in the Indian subcontinent. Cases are mainly suicidal in nature. The clinical course of the copper sulphate intoxicated patient is often complex involving intravascular hemolysis, jaundice and renal failure. The treatment is mainly supportive. Mortality is quite high in severe cases if treatment is not adequate and prompt.
Methods and materials: This cross sectional, observational, prospective study was conducted on 50 patients with acute copper sulphate poisoning attended in Medicine department of Khulna Medical College Hospital from January 2020 to June 2020.
Results: Almost all patients of copper sulphate poisoning, presented with gastrointestinal symptom like nausea 50 (100%), vomiting 49 (98%) and abdominal pain 26 (52%). Development of anemia 17 (34%) and signs of hepatotoxicity like jaundice 18 (36%), signs of dehydration 7 (14%), features of shock 8 (16%) and chest findings like tachypnoea, crepitations 9 (18%) were common. On investigation, Hemoglobin percentage below 10 gm/dl in 12 (24%), neutrophillic leukocytosis 18 (36%), Platelet count below 100000/cu mm blood in 3 (6%). features of hemolysis 16 (32%), haemoglobinuria 17 (34%) and haematuria 15 (30%), S. bilirubin was elevated in 23 (46%) of patients. Serum ALT level was elevated in 17 (34%) of patients of which 13 (26%) were found as moderate to severely raised both serum creatinine and blood urea were elevated in 16 (32%) of patients.
Conclusion: Acute copper sulphate poisoning is common in our country which is mainly suicidal in nature. As death occurs due to multi organ failure, while gastrointestinal, intravascular hemolysis, hepatic and renal toxicities significantly contribute to it. Management in high dependency unit is also required.
Intravascular hemolysis; Hepatotoxicity; Hemoglobinuria; Hematuria; Renal failure
Copper sulphate forms bright blue crystals containing five molecules of water (CuSO4. 5H2O). It is commonly known as "Blue Vitriol" or "Blue Stone". Usually the people of the southern region of Bangladesh uses copper sulphate as a fungicidal agent [1]. It is used chiefly for agricultural purposes as a pesticide and in leather industry. It was also being used as a precipitator in heavy metal poisoning and was used to treat gastric and topical exposure to phosphorous. It has a nauseous and metallic taste. Solutions are acid to litmus, freely soluble in water [2,3]. It is consumed mainly with suicidal intentions. Accidental poisonings have been reported from children as well [4,5].
Approximately 30% of ingested copper is absorbed from the gastrointestinal tract [6]. In blood, copper is initially albuminbound and transported via the hepatic portal circulation to the liver where it is incorporated into ceruloplasmin. Copper is present in serum in two forms; 93% is tightly bound to ceruloplasmin and 7% is loosely bound to albumin [7]. The copper-albumin complex represents the toxicological active portion of the serum copper [2]. Systemic transport of copper from liver is primarily as ceruloplasmin, which appears to donate copper to tissues. Copper is distributed to all tissues with the highest concentrations in liver, heart, brain, kidneys and muscle. Intracellular copper is predominantly bound to metallothionein. Fecal and biliary excretion accounts for 80% of excreted copper. Approximately 4% is excreted in the urine [6].
In acute poisoning, albumin, rather than ceruloplasmin, binds the excess copper. The liver is the major site of deposition of copper following large ingestion. Lethal dose is about 10 g-20 g [7]. The copper content in normal adults liver ranges from 18 to 45 mg/g dry weight. When the concentration of hepatic copper is greater than 50 mg/g dry weight, liver cell necrosis occurs with release of large amount of copper into the serum. This released copper is rapidly taken up by erythrocytes and results in oxidative damage and may result in hemolysis of RBCs [2]. It is proposed that free reduced copper in the cell binds to sulfhydryl groups and inactivates enzymes such as glucose-6-phosphate dehydrogenase and glutathione reductase [8]. Intravascular hemolysis appears 12 h-24 h following ingestion of copper sulphate.
Jaundice in copper sulphate poisoning is partly hepatic in origin in addition to hemolysis [9]. Jaundice appears on the 2nd or 3rd day following ingestion. Liver damage has been attributed to liver mitochondrial dysfunction due to oxidized state. Intravascular hemolysis plays a major role in the pathogenesis of renal failure [8,10]. The heam pigment released due to hemolysis and direct toxic effects of copper released from lysed red cells contribute to tubular epithelial damage of the kidney. Severe vomiting, diarrhoea, lack of replacement of fluid and gastrointestinal bleed, leading to hypotension could also contribute to renal failure [10]. Renal complications are usually seen on the third or the fourth day and onwards after the poisoning [11].
The incidence of copper sulphate poisoning varies at different geographical areas depending on the local use of copper sulphate and the availability of other suicidal poisons. Diagnosis is based on history of exposure. Mainstay of treatment is supportive, including careful fluid therapy and vasopressors as needed, blood transfusion if needed and methylene in symptomatic methemoglobinemia. Chelation therapy has given in most cases. The role of dialysis is limited to the management of associated renal failure. High mortality is noted in severe cases due to methemoglobinemea, hepatotoxicity and renal failure.
This cross sectional, observational, prospective study was carried out in medicine department of Khulna Medical College Hospital (KMCH) from Januray, 2020 to June 2020. Total 50 cases of acute copper sulphate poisoning were selected. Data were processed and analyzed using SPSS (Statistical Package for Social Science) 15.0.
Inclusion criteria
• All patients with acute copper sulphate poisoning admitted in Medicine wards of KMCH.
• Voluntarily given consent.
Exclusion criteria
• Not willing to give informed consent.
• Patient is suffering from Wilsons disease, chronic liver disease and chronic kidney disease.
Acute copper sulphate poisoning is a common mode of poisoning in southern region of Bangladesh which is mainly suicidal in nature [1]. Usually the people of this region use copper sulphate as a fungicidal agent. The incidence of acute copper sulphate poisoning varies at different geographical areas depending on the local use of copper sulphate and the availability of other suicidal poisons (Tables 1-5).
| Presenting feature | No. of patient | Percentage (%) |
|---|---|---|
| Nausea | 50 | 100 (%) |
| Vomiting | 49 | 98 (%) |
| Abdominal pain | 26 | 52 (%) |
| High coloured urine | 20 | 40 (%) |
| Jaundice | 8 | 16 (%) |
Table 1: Clinical presentation of the patients shows that almost all patients of copper sulphate poisoning, presented with gastrointestinal symptom like abdominal pain 26 (52%), nausea 50 (100%), and vomiting 49 (98%). A significant proportion of patients presented with high coloured urine 20 (40%) which developed initially and subsequently.
| Physical findings on subsequent days | No. of patients | Percentage (%) |
|---|---|---|
| Anemia | 17 | 34% |
| Jaundice | 18 | 36% |
| Signs of dehydration | 7 | 14% |
| Features of shock | 8 | 16% |
| Chest findings (e.g., crepitations) | 9 | 18% |
Table 2: Physical findings on subsequent days during hospital stay shows that anemia 17 (34%) and jaundice 18 (36%) developed on 2nd or 3rd day following copper sulphate poisoning. Development of signs of dehydration 7 (14%), features of shock 8 (16%) and chest findings like tachypnoea, crepitations 9 (18%) were not uncommon.
| Complete blood count | No. of patients | Percentage (%) | |
|---|---|---|---|
| Percentage of hemoglobin | <10 gm/dl | 12 | 24.00% |
| >10 gm/dl | 38 | 76.00% | |
| TC of WBC | >11000/cu mm | 18 | 36.00% |
| <11000/cu mm | 32 | 64.00% | |
| DC of WBC (Percentage of neutrophil) | >70% | 18 | 36.00% |
| <70% | 32 | 64.00% | |
| Platelet count | <100000/cu mm | 3 | 6.00% |
| >100000/cu mm | 47 | 94.00% | |
Table 3: Complete Blood Count among the patients shows that anemia is a common feature. Hemoglobin percentage was found below 10 gm/dl in 12 (24%) of patients. It is due to hemolysis or blood loss. Neutrophillicleucocytosis were found on 18 (36%) of patients. Platelet count was found below 100000/cu mm blood in a minority patient 3 (6%).
| PBF findings | Frequency | Percent |
|---|---|---|
| Features of hemolysis | 16 | 32.00% |
| Normal study | 34 | 68.00% |
| Total | 50 | 100.00% |
Table 4: Peripheral blood film among the patients shows that features of hemolysis was present on 16 (32%) of patient.
| Urine analysis | No. of patients | Percentage (%) | |
|---|---|---|---|
| Albuminuria | Present | 5 | 10.00% |
| Absent | 45 | 90.00% | |
| Hemoglobinuria | Present | 17 | 34.00% |
| Absent | 33 | 66.00% | |
| Hematuria | Present | 15 | 30.00% |
| Absent | 35 | 70.00% | |
Table 5: Urine Analysis among the patients shows that hemoglobinuria and hematuria developed in 17 (34%) and 15 (30%) of the patients respectively.
The lowest dose copper sulphate that is toxic when ingested is 11 mg/kg [12]. Akintonwa, et al. [13], claimed 10 gm-20 gm copper sulphate to be a “definitely fatal” dose. In a review of 123 cases Ahsan, et al. [1], observed an “unpredictable” outcome in those consuming less than 50 gm while 100 gm was “invariably” fatal.
Following ingestion of copper sulphate a gastrointestinal symptom appear first and is always present. In present study, gastrointestinal symptoms like nausea 50 (100%), and vomiting 49 (98%), abdominal pain 26 (52%) were observed in patients, which is consistent with the previous studies Mollick, et al. [14], Chowdhury, et al. [15], Singh, et al. [9], Chugh, et al. [10].
Jaundice developed on 2nd or 3rd day following ingestion of copper sulphate. Clinically it is detected in 36% patients (18 out of 50). Jaundice may be hemolytic or hepatocellular or mixed. Serum bilirubin was elevated in 23 (46%) of patients. In previous study, Wahal, et al. [16], jaundice was found on 36% of patient and Agarwal, et al. [17], jaundice was found 58% of patients. Serum ALT level was elevated in 17 (34%) of patients of which 13 were found as moderate to severely raised which is consistent [9,16,18]. In a study, Mollick, et al. [14], stated Serum ALT and serum bilirubin were elevated in 40% and 37% patients respectively. Among 13 patients of Moderate to severely raised (>80 u/l) serum ALT, 11 patients improved and 2 patients died. Among 4 patients with mildly raised (41-80 u/l) serum ALT and 33 patients with normal serum ALT, all of them (100%) had improved. There is statistically significant association (p-value=0.05) between raised serum ALT and outcome of patients in acute copper sulphate poisoning.
Intravascular hemolysis can start as early as within the first 24 hours since ingestion and is due to the direct oxidative damage to erythrocyte membranes. The hemolysis can be rapid and severe with drastic drops in the hemoglobin level. In this study, Hemoglobin percentage was found below 10 gm/dl in 12 (24%) of patients. Which may be due to copper induced hemolysis (increased total bilirubin and evidence from blood picture). A significant proportion of patients developed high coloured urine 20 (40%). which may be due to hemolysis or jaundice. Hemoglobinuria, hematuria and albuminuria were developed in 17 (34%), 15 (30%) and 5 (10%) of the patients respectively. In previous study, Chugh, et al. [14], and Agarwal, et al. [17], found intravascular hemolysis ranged from 47%-65% in two case series. Among 16 patients with features of haemolysis on peripheral blood film, 14 patients improved and 2 patients died. Among 34 patients of normal peripheral blood film, all of them (100%) improved. There is statistically significant association (p-value=0.035) between presence of features of haemolysis on peripheral blood film and outcome of patients in acute copper sulphate poisoning (Tables 6-10).
| Liver Function Test | No. of patients | Percentage (%) | |
|---|---|---|---|
| Serum bilirubin | Increased (>1.1 mg/dl) | 23 | 46 |
| Normal (upto 1.1 mg/dl) | 27 | 54 | |
| Serum Alanine Aminotransferase (ALT) | Moderate to severely raised (>80 u/l) | 13 | 26 |
| Mildly raised (41 u/l-80 u/l) | 4 | 8 | |
| Normal (upto 40 u/l) | 33 | 66 | |
Table 6: Liver Function Test (LFT) among the patients shows that serum bilirubin was elevated in 23 (46%) of patients. Serum ALT level was elevated in 17 (34%) of patients of which 26% were found as moderate to severely raised. LFT were done at the 4th day of copper sulphate ingestion.
| Renal Function Test | No. of patients | Percentage (%) | |
|---|---|---|---|
| Serum creatinine | Increased (>1.2 mg/dl) | 16 | 32.00% |
| Normal (upto 1.2 mg/dl) | 34 | 68.00% | |
| Blood urea | Increased (>1.2 mg/dl) | 16 | 32.00% |
| Normal (upto 1.2 mg/dl) | 34 | 68.00% | |
Table 7: Renal Function Test among the patients shows that both serum creatinine and blood urea were elevated in 16 (32%) of patients. RFT were done at the 4th day of copper sulphate ingestion.
| Serum creatinine | ||||
|---|---|---|---|---|
| Outcome of treatment of patient | Increased (>1.2 mg/dl) | Normal (upto 1.2 mg/dl) | Total | P-value |
| Improved | 14 | 34 | 48 | 0.035 |
| Death | 2 | 0 | 2 | |
| Total | 16 | 34 | 50 | |
Note: Chi-square (χ2) Test was employed to analyse the data. P-value <0.05 was considered statistically significant
Table 8: Co-relation between serum creatinine and outcome of treatment among 16 patients of raised serum creatinine, 14 patients improved and 2 patients died. Among 34 patients of normal serum creatinine, all of them (100%) improved. There is statistically significant association (p-value=0.035) between raised serum creatinine and outcome of treatment of patients in acute copper sulphate poisoning.
| Outcome of patient | ||||
|---|---|---|---|---|
| Serum Alanine Aminotransferase (ALT) | Improved | Death | Total | P-value |
| Moderate to severely raised (>80 u/l) | 11 | 2 | 13 | 0.05 |
| Mildly raised (41 u/l -80 u/l) | 4 | 0 | 4 | |
| Normal (upto 40u/l) | 33 | 0 | 33 | |
| Total | 48 | 2 | 50 | |
Note: Chi-square (χ2) Test was employed to analyse the data. P-value <0.05 was considered statistically significant.
Table 9: Co-relation between serum Alanine Aminotransferase (ALT) and outcome of treatment of patient among 13 patients of Moderate to severely raised (>80 u/l) serum ALT, 11 patients had improved and 2 patients had died. Among 4 patients of mildly raised (41 u/l -80 u/l) serum ALT and 33 patients of normal serum creatinine, all of them (100%) had improved. There is statistically significant association (p-value=0.05) between raised serum ALT and outcome of patients in acute copper sulphate poisoning.
| Outcome of patient | ||||
|---|---|---|---|---|
| Peripheral blood picture | Improved | Death | Total | P-value |
| Features of hemolysis | 14 | 2 | 16 | 0.035 |
| Normal study | 34 | 0 | 34 | |
| Total | 48 | 2 | 50 | |
Note: Chi-square (χ2) Test was employed to analyse the data. P-value <0.05 was considered statistically significant
Table 10: Co-relation between features on peripheral blood picture and outcome of patient among 16 patients with features of hemolysis on peripheral blood film, 14 patients improved and 2 patients died. Among 34 patients with normal peripheral blood film, all patients (100%) improved. There is statistically significant association (p-value=0.035) between presence of features of hemolysis on peripheral blood film and outcome of patients in acute copper sulphate poisoning.
Renal complications were observed usually after 48 h. The possible mechanisms of kidney damage include; pre-renal failure due to dehydration (vomiting, diarrhea, reduced fluid intake), hemoglobinuria, sepsis, rhabdomyolysis, direct copper toxicity on proximal tubules and secondary effects of multi organ dysfunction. In this study, serum creatinine and blood urea were elevated in 16 (32%) patients. High coloured urine developed in 20 (40%) patients (it may be due to hematuria and/or hemoglobinuria). Hemoglobinuria, hematuria and albuminuria developed in 17 (34%), 15 (30%) and 5 (10%) patients respectively.
In some previous studies, Dash, et al. [8], described that acute renal failure developed in 20%-40% of patients with acute copper sulphate poisoning and urinary abnormalities detected are oliguria, anuria, albuminuria, hemoglobinuria and hematuria [10,11]. Among 16 patients with raised serum creatinine, 14 patients improved and 2 patients died. Among 34 patients with normal serum creatinine, all of them (100%) improved. There is statistically significant association (p-value=0.035) between raised serum creatinine and outcome of patients in acute copper sulphate poisoning (Table 8).
Copper sulphate is a common form of suicidal agent with significant mortality. It is a readily available substance can be taken easily. Acute copper sulphate poisoning is a rare event and uncommon worldwide except Indian subcontinents. It is most prevalent in southern region of Bangladesh. Oral copper sulphate ingestion has significant effects on gastrointestinal, hematological, hepatic and renal system. Gastrointestinal symptoms like nausea, vomiting, abdominal pain frequently occurs and appears. Intravascular hemolysis usually developed within 12 h-24 h of ingestion. Appearance of jaundice is common. Most common renal toxicities are hematuria, hemoglobinuria, albuminuria, elevated blood urea, elevated serum creatinine level and acute renal failure. Although death occurs due to multi organ failure, gastrointestinal, intravascular hemolysis, hepatic and renal toxicities significantly contributes to it.
The sample size was relatively small. No follow-up could be carried out to repeat the investigations. Actual measurement of dose of copper sulphate is not possible. Advanced investigations facilities are limited. No advanced life supports were available.
None declared.
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Citation: Dutta D, Gomes RR, Hasan FMM, Saha S, Newaz M (2022) Correlation between Clinical Features and Laboratory Parameters and Outcome in Acute Copper Sulphate Poisoning: A Cross-Sectional Observational Study. J Clin Toxicol. S21:002.
Received: 01-Feb-2022, Manuscript No. JCT-22-16253; Editor assigned: 03-Feb-2022, Pre QC No. JCT-22-16253 (PQ); Reviewed: 17-Feb-2022, QC No. JCT-22-16253; Revised: 24-Feb-2022, Manuscript No. JCT-22-16253 (R); Published: 03-Mar-2022 , DOI: 10.35248/2161-0495-22.S21.002
Copyright: © 2022 Dutta D, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.