Acute ingestion of copper sulphate: A review on its clinical manifestations and management

Abstract

Ingestion of copper sulphate is an uncommon 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. In severe cases methemoglobinemia needs treatment. Mortality is quite high in severe cases. A comprehensive review of the clinical presentation and management of copper sulphate poisoning is done.

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Review Article
Acute ingestion of copper sulphate: A review on its
clinical manifestations and management
Kavitha Saravu, Jimmy Jose*, Mahadeva N. Bhat**, Beena Jimmy*, B. A. Shastry
Abstract
Ingestion of copper sulphate is an uncommon mode of poisoning in the Indian subcontinent. Cases are mainly sui-
cidal 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. In severe cases methemoglobinemia needs
treatment. Mortality is quite high in severe cases. A comprehensive review of the clinical presentation and manage-
ment of copper sulphate poisoning is done.
Key words: Acute ingestion, copper sulphate, poisoning
From:
Department of Medicine, Kasturba Medical College, Manipal, *Department
of Clinical Pharmacy, 4th Floor Shirdi Sai Baba Cancer Hospital, Kasturba
Hospital, Manipal, **Canara Health Centre, First Floor, Sheikh Hina Complex,
Anjuman Road, Udupi, India
For correspondence:
Dr. Kavitha Saravu, Department of Medicine, Kasturba Medical College,
Manipal University, Manipal - 576 104, India.
E-mail: kavithasaravu@yahoo.co.in
Introduction
Copper sulphate forms bright blue crystals containing
Þ ve molecules of water [CuSO4. 5H2O]. It is commonly
known as “Blue Vitriol” or “Blue Stone”. It is used chieß y
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.[1,2] It is consumed mainly with suicidal intentions.
Accidental poisonings have been reported from children
as well.[3-7]
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. Its incidence is reported to be 34% and 65%
of the total poisoning cases in two studies from Agra
and New Delhi in 1960’s. The mortality rates vary from
14-18.8%.[8,9] In another study from Aligarh in 1970’s, it
was the commonest mode of poisonings at that center
accounting to 118 cases over four and a half years.[10]
However, the incidence of copper sulphate poisoning is
declining in certain parts of India. Chugh et al., reported
a decrease in the number of cases of acute renal failure
attributed to intentional copper sulphate ingestion among
patients admitted to a renal unit in northern India over a
period of three decades from Þ ve per cent in the 1960s
to one per cent in the 1980s.[11] In another autopsy
series from north India, copper sulphate ingestion was
responsible for 22% of deaths due to poisoning from
1972 to 1977.[12,13] However, it declined to 3.85 and
3.33% between 1977-1982 and 1982-1987 respectively.
Pediatric cases of copper sulphate ingestion are rare, with
only few case reports available in literature.[4-7]
As some of the clinicians are faced with unfamiliarity
when challenged to manage the cases of copper sulphate
poisoning, we have attempted a comprehensive review
on the clinical manifestations and management of copper
sulphate poisoning.
Kinetics of Copper
The total body content of copper is 150 mg.[14]
Approximately 30% is absorbed from the gastrointestinal
tract.[15] In blood, copper is initially albumin-bound and
transported via the hepatic portal circulation to the liver
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where it is incorporated into ceruloplasmin (an alpha
globulin synthesized in hepatic microsomes). Copper is
present in serum in two forms; 93% is tightly bound to
ceruloplasmin and 7% is loosely bound to albumin.[14]
The copper-albumin complex represents the toxicological
active portion of the serum copper.[1] 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. Copper is found
extensively in red blood cells as erythrocuprein and other
proteins. Fecal and biliary excretion accounts for 80
percent of excreted copper. Approximately four percent
is excreted in the urine.[15] The average half-life of copper
in a healthy individual is estimated to be 26 days.[16]
The kinetics of copper during over dose differs from
that during the normal. The gastrointestinal absorption
varies with the copper intake and it can be as low as
12% in patients with high copper intake. However, in the
presence of damaged mucosa following acute overdose,
the fractional absorption is likely to be higher.[17] In acute
poisoning, albumin, rather than ceruloplasmin, binds the
excess copper. The liver is the major site of deposition of
copper following large ingestion, with most of the copper
bound to metallothionein. The copper content in normal
adult liver ranges from 18-45 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.[1]
This may account for the delayed secondary episode of
hemolysis that occurs in some copper sulphate poisoning
patients.[17]
Mechanism of Toxicity
Copper sulphate is a powerful oxidizing agent, which is
corrosive to mucous membranes. Concentrated solutions
are acidic with pH 4. Cellular damage and cell death may
result from excess copper accumulation. 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.[18]
In addition copper may interact with oxygen species (e.g.,
superoxide anions and hydrogen peroxide) and catalyze
the production of reactive toxic hydroxyl radicals. Lethal
dose is about 10-20 g.[14]
Pathology of Copper Sulphate Poisoning
Main brunt of copper toxicity is borne in the order
by the erythrocytes, the liver and then the kidneys.[19]
Intravascular hemolysis appears 12-24h following
ingestion of copper sulphate. Hemolytic anemia, is
caused either by direct red cell membrane damage
or indirectly as a result of the inactivation of enzymes
(including glutathione reductase) which protect against
oxidative stress.[2,20] Copper ions can oxidize hem iron
to form methaemoglobin. This blood loses its oxygen
carrying capacity. Clinically cyanosis and chocolate
brown blood may be seen.[21] Patients with cyanosis show
at least 1/3rd of the blood to be methemoglobin.
Jaundice in copper sulphate poisoning is partly hepatic
in origin in addition to hemolysis.[19] Jaundice appears on
the second or third day following ingestion. Liver damage
has been attributed to liver mitochondrial dysfunction
due to oxidized state.[22] Nature of liver damage is both
cell necrosis as well as obstruction. Obstructive factor
is seen predominantly as opposed to toxic hepatitis.[19]
Level of bilirubin is directly proportional to the severity of
the poisoning. Elevated levels of liver enzymes are seen
in all except mild cases of poisoning.[10,19,23] Liver biopsy
reveals centrilobular necrosis, mononuclear inÞ ltration
and biliary stasis.[9,24]
Intravascular hemolysis plays a major role in the
pathogenesis of renal failure.[18,25] The hem pigment
released due to hemolysis and direct toxic effect of copper
released from lysed red cells contribute to tubular epithelial
damage of the kidney. Severe vomiting, diarrhoea, lack of
replacement of ß uid and gastrointestinal bleed, leading
to hypotension could also contribute to renal failure.[25]
Renal complications are usually seen on the third or
the fourth day and onwards after the poisoning.[26] In
a report of acute renal failure manifestations following
copper sulphate poisoning, histology of kidney revealed
features of acute tubular necrosis in seven out of eight
kidney biopsies and tubules contained hemoglobin
casts. A single case of interstitial granuloma was also
reported.[25]
Copper sulphate being a corrosive acid, results in
caustic burns of the esophagus, superÞ cial and deep
ulcers in the stomach and the small intestine.[25] Changes
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of acute gastritis, hemorrhages in the intestinal mucosa,
necrosis of the intestinal mucosa and perforation have
been reported.[5,27,28]
Clinical Features
Gastrointestinal: The immediate symptoms following
ingestion of copper sulphate universally is gastrointestinal
in the form of nausea, vomiting and crampy abdominal
pain.[25] Vomiting usually occurs within 15 minutes of
ingestion. Vomitus is characteristically greenish-blue.
Hemorrhagic gastroenteritis associated with mucosal
erosions, a metallic taste, burning epigastric sensation
and diarrhea may occur.[9] In severe cases hemetenesis
and malena occur. In a case series including 19 patients
requiring hemodialysis after copper sulphate ingestion,
7(37%) developed gastrointestinal bleeding and in
5(26%) this was severe enough to cause signiÞ cant
hypotension.[29]
Cardiovascular: In cases with severe poisoning
cardiovascular collapse, hypotension and tachycardia can
occur early within a few hours of poisoning and may be
responsible for early fatalities or can occur late with other
complications.[9] Vomiting, diarrhea and GI blood loss are
the factors usually responsible for hypovolemia.[17] Severe
methemoglobinemia can result in cardiac dysryhtmia
and hypoxia which could contribute significantly to
cardiovascular collapse.[30] Other factors implicated are
direct effect of copper on vascular and cardiac cells and
sepsis due to transmucosal invasion.[7,17] In a series of
seven autopsies, Þ ve deaths occurred within an hour of
admission due to shock.[27] Four percent of patients in a
series of 50 cases by Wahal et al had early cardiovascular
collapse and succumbed within 10 hours of consumption
of the poison.[9]
Hematological: Intravascular hemolysis occurs12-
24h after ingestion. The discovery of significant
methemoglobinemia occurs early in the patient’s
clinical course and is rapidly followed by hemolysis.
Coagulopathy can occur due to liver injury or direct effect
of free copper ions on the coagulation cascade.[17] The
incidence of methemoglobinemia ranged from 3.4% to
42% and intravascular hemolysis ranged from 47-65%
in two case series.[25,29]
Hepatic: Jaundice appears after 24-48h in more severe
poisonings, which may be hemolytic or hepatocellular. It
may be associated with tender hepatomegaly. Jaundice
was seen in 11(58%) patients and 1(5%) patient died of
hepatic encephalopathy in one series.[29]
Renal: Renal complications are observed usually after
48h.[26] Acute renal failure developed in 20-40% of patients
with acute copper sulphate poisoning.[18,25] Urinary
abnormalities detected are oliguria, anuria, albuminuria,
hemoglobinuria and hematuria.[18,25,26]
Central nervous system: Central nervous system
depression ranging from lethargy to coma or seizure
are likely epiphenomenon related to other organ
involvement.[17]
Muscular: Rhabdomyolysis with high creatine phospho
kinase (CPK)>3000IU have been reported.[31,32] In one
case myoglobinuria was detected on the second day and
peak CPK level was observed on the sixth day.[27]
Clinical features in paediatric patients
From the limited case reports available in paediatric
patients, the clinical features in paediatric group
resembles that of adults with early gastrointestinal feature
and hemolysis usually occurring after 24h. Hepatic and
renal toxicities develop one to two days after ingestion
as in adults.[4]
Cardiac abnormalities was reported with multiple
ventricular extrasystloes, tachycardia and occasional
unifocal bigeminy in a two-year-old boy who ingested 30
ml of a super-saturated copper sulphate solution (10 gm
of copper sulphate).[7]
Investigations
Baseline hemoglobin, liver function, renal function and
electrolyte levels should be obtained and monitored as
clinically indicated until symptoms abate. Hemoglobin
should be monitored as clinically indicated to guide the
need for blood transfusion. Monitoring renal functions
and electrolytes is required to assess the ß uid status and
extent of renal failure and the renal toxicity of chelating
agents like penicillamine. In patients with hepatitis and
bleeding manifestations, coagulation parameters have
to be monitored. Methemoglobin level is to be monitored
in cyanotic patients to assess the need for methylene
blue.[33] In one series where biochemical changes in blood
were studied in copper sulphate poisoning, the authors
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suggested a prognostic signiÞ cance for estimation of
levels of serum transaminases along with blood urea
estimations with higher levels seen in more seriously ill
patients.[19] However the signiÞ cance of this observation
was not statistically tested. Urine examination is required
for evidence of hemoglobinuria and hematuria.
For diagnostic purpose, if the history is not clear,
serum and whole blood copper estimation on a sample
collected early in the course may be of help.[17,19] Serum
copper concentrations normally range from 10.5 to
23 micromoles/liter.[16] However it is not mandatory
if the diagnosis is obvious by history and clinical
examination.
No correlation was found between plasma copper
concentrations and prognosis in a study by Wahal et al.[23]
In a study by Singh, an increase in serum copper was
found within three hours of ingestion of copper sulphate
and after reaching peak values within 48h it showed
a gradual fall and attained normal levels within 17h to
7 days. The fall in blood copper levels was attributed
to an increase in concentration of copper in tissues
especially liver and the kidneys.[19] Although serum
ceruloplasmin levels rise in patients with acute copper
poisoning, because of increased hepatic synthesis, the
ceruloplasmin cannot be used to deÞ ne the patients’
prognosis.[17,34]
Treatment
A) Decreasing absorption
After acute ingestion of copper sulphate, in the
prehospital setup, immediate dilution with water or
milk is advisable. The same action is extrapolated
from recommendations for management of corrosive
ingestions.[35-37] In corrosive ingestion one should avoid
emesis and should begin early dilutional therapy. Water
may be used initially to dislodge adherent solid particles,
as well as to dilute the caustic ingestion. It is important
not to be excessively aggressive with dilution, as this may
cause nausea, vomiting and possible aspiration.
Emesis should be avoided to prevent reexposure of the
esophagus to the corrosive agent.[37] In copper sulphate
poisoning vomiting is likely to occur spontaneously
and hence patient may require antiemetic therapy.[17] In
corrosive acid ingestion, there is a risk of perforation if
blind gastric lavage is attempted, however in patients with
large intentional ingestion of acid who presents within 30
min, consideration can be given to cautious placement
of a narrow nasogastric tube suction to remove the
remaining acid in the gut.[37]
Activated charcoal administration should be considered
after a potentially dangerous ingestion.[38] A dose of
oral activated charcoal, while of unproved beneÞ t, is
unlikely to be harmful and may have potential adsorptive
capacity for copper.[17] Usual dose is 25 to 100 gm in
adults and adolescents and 25 to 50 gm in children aged
1 to 12 years (or 0.5 to 1 gram/kilogram body weight).
Administer charcoal as aqueous slurry; most effective
when administered within one hour of ingestion. Use a
minimum of 240 ml of water per 30 gm charcoal.[39]
B) Supportive measures
1) Management of corrosive burns:
If corrosive oesophageal or gastric damage is
suspected upper GI endoscopy should be carried out,
ideally within 12-24h, to gauge the severity of injury.[40-43]
This recommendation is extrapolated from experience
with ingestion of acids and /or alkaline corrosives.
Endoscopic procedures done during the early period
after corrosive ingestion has shown to be relatively
safe without any complications. In a series of 94
patients with corrosive ingestion, GI endoscopy was
performed in 81 patients within 24h and in 12 patients
within 48h. The procedure was not associated with any
complications.[42] Similarly, in another series of 16 patients
with corrosive acid ingestion, Þ breoptic endoscopy was
done in 13 patients within 24h. The authors concluded
that endoscopy did not give rise to any complications
and it helped in grading the injury caused by corrosive
acids, planning the management of patients and also in
predicting the prognosis.[43]
The period of wound softening starts on the second
or third day post-injury and last for roughly two weeks
during which time there is an increased risk of perforation
if endoscopy is performed.[37] An early surgical opinion
should be sought if there is any suspicion of pending
gastrointestinal perforation or where endoscopy reveals
evidence of grade III burns.
Sucralfate may help to relieve the symptoms of mucosal
injury.[44] Adequate human data regarding role of steroid
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in caustic burn is yet to be generated. The most suitable
group to receive corticosteroid (with antibiotic) is probably
the patients with grade IIb injuries (submucosal lesions,
ulcerations and exudates with near circumferential
injuries). In patients with grade III ulcers (deep ulcers and
necrosis into periesophageal tissues) stricture formation
occurs, irrespective of steroid administration. Moreover,
steroids may mask or worsen the complications of
corrosives in grade III patients and hence steroids are
contraindicated.[41]
Considering the experience with the use of steroid in
copper sulphate poisoning, in a study of copper sulphate
poisoning by Gupta et al., the mortality was lower in a
group of 26 patients treated with steroids as compared
to those without steroids.[2] However, this was not a
randomized-controlled study. The role of steroid has not
been tested in any other controlled studies to strongly
recommend this therapeutic intervention.
2) Methemoglobinemia:
Patients with symptomatic methemoglobinemia should
be treated with methylene blue. This usually occurs
at methemoglobin levels above 20 to 30 percent, but
may occur at lower methemoglobin levels in patients
with anemia or underlying pulmonary or cardiovascular
disorders. Administer oxygen while preparing for
methylene blue therapy.
Methylene blue enhances the conversion of
methemoglobin to hemoglobin by increasing the activity of
the enzyme methemoglobin reductase. Initial dose is 1-2
mg/kg/dose (0.1 to 0.2 ml/kg of 1% solution) intravenously
over 5 minutes. The dose may be repeated if cyanosis
does not disappear within one hour.[45] At high levels of
methemoglobin (>70%), methylene blue reduces the half
life from an average of 15-20 hours to 40-90 min. Hence,
improvement from methylene blue therapy should be
observed within one hour of administration.
Failure of methylene blue therapy suggests inadequate
dose of methylene blue, inadequate decontamination,
G-6-PD deÞ ciency, NADPH dependent methemoglobin
reductase deÞ ciency.[45] Further, methylene blue action
requires intact erythrocytes and hence if hemolysis
is severe, it may be ineffective in copper sulphate
poisoning.[17] Large doses of methylene blue itself may
cause methemoglobinemia or hemolysis and the same
needs to be considered while administering this agent.[33]
It is contraindicated in G-6-PD deÞ cient patients in whom
it may cause hemolysis. Exchange transfusion and/or
the transfusion of packed red blood cells may be useful
for methylene blue failures or for patients with G6PD or
NADPH methaemoglobin reductase deÞ ciency. (Nitrates,
Nitrites and methaemoglobinemia.[45] Hyperbaric oxygen
may be beneÞ cial if methylene blue is ineffective.[34]
Hyperbaric oxygen increases the dissolved oxygen
which can protect the patient while the body reduces
methaemoglobin.[34] Another alternative to methylene
blue is the reducing agent ascorbic acid which can be
administered 100-500 mg twice daily either orally or
intravenously. But, this agent probably has a minor effect
on increasing methemoglobin reduction and the clinical
experience with the use of this agent is limited.[45]
3) Hypotensive episode:
Hypotensive episode should be treated with ß uids,
dopamine and noradrenaline
4) Rhabdomyolysis:
Early judicious ß uid replacement of 4-6L/day with careful
monitoring for ß uid overload, mannitol (100 mg/day) and
urine alkalinization are suggested early in the course,
but deÞ nite evidence for the efÞ cacy of these measures
is lacking.[46]
C) Chelation therapy
There is little clinical experience with the use of
chelators for acute copper sulphate intoxication. Data
on efÞ cacy is derived from patients with chronic copper
intoxication (Wilson’s disease, Indian childhood cirrhosis)
and experimental animal studies. British anti Lewisite
(BAL), D-penicillamine, 2, 3-dimercapto-1-propane
sulfonate, Na+ (DMPS) and ethylene diamine tetra
acetate (EDTA) have been used. In severely poisoned
patients the presence of acute renal failure often limits
the potential for antidotes.
1) Penicillamine:
D-penicillamine has been used to treat acute
copper intoxication, but data regarding efficacy are
lacking.[32,33,47,48]
Adult dose: 1000 to 1500 mg/day divided every six to
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12h, before meals.
Pediatric dose: Initially 10 mg/kg/day, gradually
increase to 30 mg/kg/day divided in two or three doses
as tolerated. Doses up to 100 mg/kg/day in four divided
doses; maximum one gram/day may be used depending
on the severity of poisoning and adverse effects.[49]
Avoid in patients with penicillin allergy. Proteinuria,
hematuria, renal failure, bone marrow suppression and
hepatotoxicity are the common adverse effects.
2) Dimercaprol / BAL:
Intramuscular BAL is probably appropriate in patients in
whom vomiting and gastrointestinal injury prevents oral
D-penicillamine administration. BAL- copper complex
primarily undergoes biliary elimination and hence it is
useful in patients with renal failure. However, BAL may
be less effective than D-penicillamine and hence, when
tolerated, D-penicillamine therapy should be started
simultaneously or shortly after the initiation of therapy
with BAL.[17]
Dose: 3 to 5 mg/kg/dose deep intramuscularly every
four hours for two days, every four to six hours for an
additional two days, then every four to 12h for up to seven
additional days.[6,31,47,50] Adverse reactions are urticaria
and persistent hyperpyrexia.
3) Edetate calcium disodium
The dose of this agent is 75 mg/kg/day deep
intramuscularly or slow intravenous infusion given in
three to six divided doses for up to Þ ve days; may be
repeated for a second course after a minimum of two
days; each course should not exceed a total of 500 mg/kg.
Complications include renal tubular necrosis.[6]
D) Enhanced elimination
Hemodialysis to remove copper is ineffective, but may
be indicated in patients with renal failure secondary to
copper poisoning.[33,51]
Peritoneal dialysis with salt-poor albumin resulted in
extraction of more copper than dialysate without albumin.
However, the amount of copper removed by peritoneal
dialysis was very small.[7] There is insufÞ cient evidence
regarding any role of hemoperfusion and hemodiaÞ ltration
for copper elimination.[31]
Conclusion
Copper sulphate poisoning, which is mostly suicidal,
is associated with high mortality in severe cases due
to methemoglobinemea, hepatotoxicity and renal
failure. Mainstay of treatment is supportive, including
careful fluid therapy and methylene in symptomatic
methemoglobinemia. Chelation therapy though tried
in many cases, their beneÞ ts are not established in
controlled trials. The role of dialysis is limited to the
management of associated renal failure.
References
Barceloux DG. Copper. J Toxicol Clin Toxicol 1999;37:217-30.
Gupta PS, Bhargava SP, Sharma ML. Acute copper sulphate poi-
soning with special reference to its management with corticosteroid
therapy. J Assoc Physicians India 1962;10:287-92.
Sharma NL, Singh RN, Natu NK. Accidental poisoning in infancy
and childhood. J Indian Med Assoc 1967;48:20-5.
Blundell S, Curtin J, Fitzgerald D. Blue lips, coma and haemolysis.
J Paediatr Child Health 2003;39:67-8.
James LP, Stowe CD, Argao E. Gastric injury following copper
sulphate ingestion. Pediatr Emerg Care 1999;15:429-31.
Walsh FM, Crosson FJ, Bayley M. Acute copper intoxication. Am
J Dis Child 1977;131:149-51.
Cole DE, Lirenman DS. Role of albumin-enriched peritoneal dialy-
sate in acute copper poisoning. J Pediatr 1978;92:955-7.
Chuttani HK, Gupta PS, Gulati S, Gupta DN. Acute copper sulfate
poisoning. Am J Med 1965;39:849-54.
Wahal PK, Lahiri B, Mathur KS, Kehar U, Wahi PN. Acute copper
sulphate poisoning. J Assoc Physicians India 1963;11:93-103.
Ashraf I. Hepatic derangements (biochemical) in acute copper
sulphate poisoning. J Indian Med Assoc 1970;55:341-2
Chugh KS, Sakhuja V, Malhotra HS, Pereira BJ. Changing trends
in acute renal ailure in Third-world countries - Chandigarh study.
Q J Med 1989;73:1117-23.
Singh D, Jit I, Tyagi S. Changing trends in acute poisoning in
Chandigarh zone: A 25 year autopsy experience from a ter-
tiary care hospital in northern India. Am J Forensic Med Pathol
1999;20:203-10.
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. J Clin Forensic Med
2003;10:145-52.
Metals and Related Compounds. In: Ellenhorn MJ. Ellenhorn’s
Medical Toxicology: Diagnosis and treatment of human poisoning.
2nd ed. Williams and Wilkins: Maryland; 1997. p. 1554-6.
Dowdy RP. Copper metabolism. Am J Clin Nutr 1969;22:887-92.
Bentur Y, Koren G, McGuigan M. An unusual skin exposure
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
[Downloaded free from http://www.ijccm.org on Friday, October 17, 2008]

80
Indian J Crit Care Med Apr-Jun 2007 Vol 11 Issue 2
This PDF is available for free download from
a site hosted by Medknow Publications (www.
medknow.com).
to copper: Clinical and pharmacokinetic evalution. Clin Toxicol
1988;26:371-80.
Nelson LS. Copper. In: Goldfrank LR, Flomenbaum NE, Lewin NA,
editors. Goldfrank’s toxicologic emergencies, 7th ed. McGraw-Hill:
New York; 2002. p. 1262-71.
Dash SC. Copper sulphate poisoning and acute renal failure. Int J
Artif Organs 1989;12:610.
Singh M, Singh G. Biochemical changes in Blood in cases of acute
copper sulphate poisoning. J Indian Med Assoc 1968;50:549-54.
Mital VP, Wahal PK, Bansal OP. A study of erythrocytic glutathi-
one in acute copper sulphate poisoning. Indian J Pathol Bacteriol
1966;9:155-62.
Patel KC, Kulkarni BS, Acharya VN. Acute Renal Failure and Me-
thaemoglobinaemia due to copper sulphate poisoning. J Postgrad
Med 1976;22:180-4.
Nakatani T, Spolter L, Kobayashi K. Redox state in liver mitochon-
dria in acute copper sulfate poisoning. Life Sci 1994;54:967-74.
Wahal PK, Mehrotra MP, Kishore B, Patney NL, Mital VP, Hazra
DK, et al. Study of whole blood, red cell and plasma copper levels in
acute copper sulphate poisoning and their relationship with compli-
cations and prognosis. J Assoc Physicians India 1976;24:153-8.
Kurisaki E, Kuroda Y, Sato M. Copper-binding protein in acute
copper poisoning. Forens Sci Int 1988;38:3-11.
Chugh KS, Sharma BK, Singhal PC. Acute renal failure following
copper sulphate intoxication. Postgrad Med J 1977;53:18-23.
Mehta A, Patney NL, Bhati DP, Singh SP. Copper sulphate poison-
ing - Its impact on Kidneys. J Indian Med Assoc 1985;83:108-10.
Deodhar LP, Deshpande CK. Acute copper sulphate poisoning. J
Postgrad Med 1968;14:38-41.
Papodayanakis N, Katsilambros N, Patsourakos B. Acute copper
sulfate poisoning with jaundice. J Ir Med assoc 1969;62:99-100.
Agarwal SK, Tiwari SC, Dash SC. Spectrum of poisoning requiring
haemodialysis in tertiary care hospital in India. Int J Artif Organs
1993;16:20-2.
Price D. Methaemoglobinemia. In: Goldfrank LR, Flomenbaum
NE, Lewin NA, editors. Goldfrank’s toxicologic emergencies, 7th
ed. McGraw-Hill: New York; 2002. p. 1438-49.
Takeda T, Yukioka T, Shimazaki S. Cupric sulfate intoxication with
rhabdomyolysis, treated with chelating agents and blood puriÞ ca-
tion. Intern Med 2000;39:253-5.
Jantsch W, Kulig K, Rumack BH. Massive copper sulfate ingestion
resulting in hepatotoxicity. J Toxicol Clin Toxicol 1985;22:585-8.
Howland MA. Methylene Blue. In: Goldfrank LR, Flomenbaum NE,
Lewin NA, editors. Goldfrank‘s toxicologic emergencies, 7th ed.
McGraw-Hill: New York, USA; 2002. p. 1450-1.
Wahal PK, Mehotra MP, Kishore B, Goyal SP, Gupta MC, Patney
NL, et al. A study of serum ceruloplasmin levels in acute copper
17.
18.
19.
20.
21.
22.
23.
24.
25.
26.
27.
28.
29.
30.
31.
32.
33.
34.
sulphate poisonings. J Assoc Physicians India 1978;26:983-7.
Friedman FM, Lovejoy FH Jr. The emergency management of
caustic ingestions. Emerg Med Clin North Am 1984;2:77-86.
Homan CS, Maitra SR, Labe BP, Thode HC Jr, Davidson L.
Histopathologic evaluation of the therapeutic efÞ cacy of water
and milk dilution for esophageal acid injury. Acad Emerg Med
1995;2:587-91.
Rao RB, Hoffman RS. Caustics and batteries. In: Goldfrank LR,
Flomenbaum NE, Lewin NA, editors. Goldfrank’s toxicologic emer-
gencies, 7th ed. McGraw-Hill: New York; 2002. p. 1326.
Chyka PA, Seger D. Position statement: Single-dose activated
charcoal. American Academy of Clinical Toxicology; European As-
sociation of Poisons Centres and Clinical Toxicologists. J Toxicol
Clin Toxicol 1997;35:721-41.
FDA. Poison treatment drug product for over-the-counter human use:
Tentative Þ nal monograph. FDA: Fed Register 1985;50:2244-62.
Crain EF, Gershel JC, Mezey AP. Caustic ingestions: Symptoms as
predictors of esophageal injury. Am J Dis Child 1984;138:863-5.
Gupta SK, CrofÞ e JM, Fitzgerald JF. Is esophagogastroduodenos-
copy necessary in all caustic ingestions? J Pediatr Gastroenterol
Nutr 2001;32:50-3.
Di Costanzo J, Norclerc M, Jouglard J, EscofÞ er JM, Cano N,
Martin J, et al. New therapeutic approach to corrosive burns of the
gastrointestinal tract. Gut 1980;21:370-5.
Dilawari JB, Singh S, Rao PN, Anand BS. Corrosive acid ingestion
in man - a clinical and endoscopic study. Gut 1984;25:183-7.
Mittal PK, Gulati R, Sibia SS, Jain P. Sucralfate therapy for acid-
induced upper gastrointestinal tract injury. Am J Gastroenterol
1989;84:204-5.
Nitrates, Nitrites and methaemoglobinemia. In: Ellenhorn MJ.
Ellenhorn’s Medical Toxicology: Diagnosis and treatment of hu-
man poisoning. 2nd ed. Williams and Wilkins: Maryland; 1997. p.
1496-9.
Hellmann DB, Stone JH. Arthritis and musculoskeletal disorders. In:
Tierney LM, Mc Phee SJ, Papadakis MA, editors. Current medical
diagnosis and treatment. 45th ed. McGraw Hill’s: New York; 2006.
p. 843-4.
Hantson P, Lievens M, Mahieu P. Accidental ingestion of a zinc and
copper sulfate preparation. J Toxicol Clin Toxicol 1996;34:724-30.
Holtzman NA, Haslam RH. Elevation of serum copper following
copper sulfate as an emetic. Pediatrics 1968;42:189-93.
Benitz WE, Tatro DS. The Pediatric Drug Handbook, 3rd ed. Mosby-
Year Book Inc: St. Louis, MO; 1995.
Fairbanks VF. Copper sulfate-induced hemolytic anemia. Inhibition
of glucose-6-phosphate dehydrogenase and other possible etiologic
mechanisms. Arch Intern Med 1967;120:428-32.
Agarwal BN, Bray SH, Bercz P, Plotzker R, Labovitz E. Ineffec-
tiveness of hemodialysis in copper sulphate poisoning. Nephron
1975;15:74-7.
35.
36.
37.
38.
39.
40.
41.
42.
43.
44.
45.
46.
47.
48.
49.
50.
51.
Source of Support: Nil, Confl ict of Interest: None declared
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