Greenish-blue gastric content: literature review and case report on acute copper sulfate poisoning.
TABLE OF CONTENTS INTRODUCTION The Essential Function of Copper in the Human Body as a Trace Dietary Element Copper Sulfate in Its Available Forms The Everyday Practices of Copper Sulfate Pentahydrate in Agriculture, Industry, and Religion The Use of Copper Sulfate in Medical Science Copper Sulfate Poisoning--General Information I. METHODOLOGY II. RESULTS A. Incidence and Trends Over the Years B. Sociodemographic Variables C. Mortality Rates D. Fatal Dose in Relation to the Method of Intake III. DISCUSSION A. Physiology of Copper B. Pathology, Mechanism of Toxicity, and Clinical Expression C. Complications D. Clinical Course in Pediatric Cases E. Diagnosis and Prognostic Indicators F. Management and Treatment IV. CASE PRESENTATION Background--Clinical Management A. Postmortem Examination--External Forensic Examination Findings B. Autopsy Findings C. Histopathological Findings D. Toxicological Examination F. Case Study CONCLUSION ACKNOWLEDGMENTS REFERENCES ABOUT THE AUTHORS
The Essential Function of Copper in the Human Body as a Trace Dietary Element
Copper is essential in the human body as a trace dietary element. It is an ingredient of certain enzymes including cytochrome c oxidase, catalase, tyrosinase, peroxidase, and uricase, functioning as a cofactor that participates in several enzyme reactions . Its presence is also necessary in mediating the absorption of iron from the gastrointestinal tract.
Copper Sulfate in Its Available Forms
Copper sulfate--also known as cupric sulfate--is considered to be the most important of copper salts. This salt exists in various forms that differ in their degree of hydration. The anhydrous form has the appearance of a pale greenish powder, while the pentahydrate (CuS[O.sub.4] x 5[H.sub.2]O) is a bright blue crystalline material that contains five molecules of water. Copper sulfate pentahydrate (CSP) is colloquially called "blue vitriol" or "bluestone," while in Asia, it is also known as "Neela Thotha" .
The Everyday Practices of Copper Sulfate Pentahydrate in Agriculture, Industry, and Religion
Burning copper sulfate is a common domestic practice among Buddhists and Hindus for religious activities as a good luck charm. However, children find the marine blue color of copper sulfate crystals attractive, which sometimes results in unintentional poisoning [27,63].
CSP is widely applied in agriculture and industry, which makes it an easily available chemical compound for some professionals in everyday life. It is frequently used as a fungicide, herbicide, and pesticide in common agricultural practice as well as an algaecide in swimming pools, also inhibiting bacterial growth (e.g., Escherichia coli) [26,27,55,63]. Copper sulfate has multiple applications in industry, including photography and printing (as a component of binding pastes, glues, and dyes in order to prevent insect bites of paper) and in construction (as an additive to concrete for water resistance and sterilization) [27,63].
The Use of Copper Sulfate in Medical Science
In medicine, copper sulfate was once used as an emetic, antifungal, and anthelmintic agent. It was withdrawn, however, when fatal incidents were reported implicating emetic drugs containing copper sulfate. Several chemical tests also utilize copper sulfate, including anemia blood tests, Fehling and Benedict's solutions to test for reducing sugars, and the Biuret reagent used in the Biuret protein assay, which is a colorimetric test determining protein concentration by UV/VIS spectroscopy at a wavelength of 565 nm [38,59].
Copper Sulfate Poisoning--General Information
Copper sulfate poisoning may occur by accident, due to suicide attempts, or after chronic exposure. It is reported that chronic occupational exposure to copper sulfate may cause liver disease after 3 to 15 years [60,63]. Animal research has revealed adverse effects on sperm quality, teratogenicity, and carcinogenicity [2,10,50]. Poisoning due to chronic exposure to copper sulfate is outside of the scope of the present paper and will not be discussed further. Acute copper sulfate poisoning due to suicidal or accidental intake is considered to be a rarity throughout international medical literature of developed countries. As some clinicians unfamiliar with such cases, a review of the clinical manifestations and management of copper sulfate poisoning is warranted.
This paper updates and summarizes the relevant literature on copper sulfate poisoning, and reports a new case of suicide by deliberate CSP consumption. A systematic review was carried out on copper sulfate poisoning incidents by searching the electronic data bases of PubMed, Google search, Google Scholar, Heal Link, EMBASE, Scopus, and Cochrane Library up to January 2016. The search terms were: "copper sulfate poisoning", "cupric sulfate poisoning", "pesticide poisoning", "suicide with copper sulfate", "bluestone poisoning", "blue vitriol poisoning", and "bluestone suicide". No language restriction was applied. All the articles have been evaluated and supplemented by searches of the bibliographies of key papers. The studies were reviewed in order to investigate the incidence, cause, sociodemographic variables of the patients, pathophysiology, symptomatology, prognosis, treatment, complications, and therapeutic outcome of copper sulfate poisoning. In addition, the following case study is written in compliance with the Helsinki Declaration of 1975, as revised in 1983. Complete patient anonymity has been assured.
A. Incidence and Trends Over the Years
Pesticides are the principal cause of poisoning. According to World Health Organization (WHO) estimates, approximately 3 million pesticide poisoning incidents occur annually worldwide, causing more than 220 thousand deaths . Copper sulfate poisoning incidence varies in different regions depending on safety rules and availability. It is very rare in western countries, while it is more common in South Asian countries, especially India [3,44,51,63]. Specifically, its incidence was reported to be 34% and 65%, respectively, among the total poisoning cases in two studies from Agra and New Delhi conducted in the decade of the 1960s [16,51,66]. In another study from Aligarh in 1970, it was the most frequent poisoning agent, accounting for 118 incidents over a period of 4.5 years [6,51]. However, in the following years the incidence of poisoning by copper sulfate has followed a downward trend in some parts of India. Between 1972 and 1977, copper sulfate ingestion was responsible for 22% of deaths due to poisoning. However, death rates due to copper sulfate declined to 3.85% and 3.33% between 1977-1982 and 1982-1987, respectively [14,51,53,54].
B. Sociodemographic Variables
Among thoroughly described case reports throughout relevant literature, it was observed that the majority of acute copper sulfate poisoning incidents involve males (62.5%). The patients' ages range from 18 to 87 years, while their mean age is 37.9. According to the data (diverse individual case reports worldwide) discussed in this meta-analysis (n = 16), the prevalence of copper sulfate poisoning is observed to be high (62.5%) among people aged 18 to 35. More specifically, the highest prevalence (37.5%) is found in the age subgroup of 26-35 years, followed by 25.0% in the age subgroup of 16-25 years and 18.8% in the age sub-group of 46-55 years. Copper sulfate intake is often a suicidal gesture among adults; 93.75% of the cases are intentional (see Table 1) [12,26,27,30,34,35,37,39,40,43,46,49,55,68].
Among 48 cases of acute copper sulfate poisoning, which were studied in 1961 by Chuttani, it was noted that 70.7% of the cases were ages 16-25 years. Two-thirds of the patients were male and one-third were female . According to the data (several individual case reports) discussed in this paper (n = 16), the age distribution of copper sulfate poisoning incidence differentiates from the findings of Chuttani and his colleagues (n = 48). The divergence from Chuttani's findings (n = 48) is attributable to the cultural backgrounds and religious practices of a particular social group. In addition, in western countries, this substance is only available to professional agricultural workers for safety reasons and not widely used in the domestic environment. Therefore, copper sulfate is unavailable to minors. However, the present sample is not adequately large and, thus, the authors are unable to draw strong statistical inferences with regard to the exact age distribution of copper sulfate poisoning.
Kanchan et al. conducted a statistical study on the fatal incidents (762 cases) that were autopsied in Nepal from 2000 to 2004. Fatalities due to suicidal poisoning constituted 17.9% of all autopsy cases, while a downward trend in total suicidal poisoning mortalities was noted during the four-year period. Males outnumbered female victims, accounting for 73.7% of the suicidal poisoning victims. Both males and females were most prone to suicidal poisoning during the third decade of their lives. The propensity to suicidal poisoning was detected at a younger age among women compared to men. Adolescent females as well as elderly males constituted the most susceptible groups. The study also showed that tendencies concerning time of day differed between genders. Males tended to commit suicide by poisoning during late evening and night, while females tended to commit suicide by poisoning during the morning and afternoon. Seasonal asymmetry was also noticed, as most male deaths occurred during the premonsoon period and most female deaths occurred in summer months . Naha et al. conducted a retrospective analysis of 35 patients presenting with copper sulfate poisoning in a period of 10 years from 2001 to 2010. The number of cases was markedly lower than previous studies and the demographics differed: 65.7% of total cases involved females and the patients' mean age was 29.2 [+ or -] 10.78 years .
To the contrary, pediatric cases involved accidental copper sulfate ingestion were very rare, with only a few case reports available in literature [11,18,31,51,67].
C. Mortality Rates
In the case reports available throughout international literature, 37.5% of the patients passed away within a few hours, although the average hospitalization time is more than 20 days (see Table 1) [12,26,27,30,34,35,37,39,40,43,46,49,55,68]. Acute copper sulfate poisoning is associated with high mortality rates (14-24.9%) in comparison to other types of poisoning [4,39,44]. Mortality in copper sulfate poisoning is variable, however, as it depends on the severity of poisoning and whether multiple organ dysfunctions are induced . Agarwal et al. reported that among 19 cases of acute copper sulfate poisoning, 7 patients eventually passed away (36%) [3,51].
D. Fatal Dose in Relation to the Method of Intake
The lethal dose of ingested copper is considered to be 10-20 g  although reports vary with higher or lower values, but the lowest toxic dose of copper in humans is considered to be 11 mg/kg [44,59,60]. Intake of small doses of copper between 15 mg and 1 g causes predominantly gastrointestinal symptoms . This is only a rough threshold for toxicity, however, as it depends on individual idiosyncratic factors. Mortality in cases of severe poisoning is high. Individuals with glucose-6-phosphate dehydrogenase deficiency are more susceptible to the toxic effects of copper . Chuttani et al. reported a number of deaths after copper sulfate ingestion. Thirteen out of 53 patients (24.5%) died after the oral intake of copper sulfate at a dosage ranging from 6-637 mg/kg . Furthermore, Akintonwa et al. reported deaths after the ingestion of "spiritual green water", containing more than 100 mg/L of copper sulfate . In 87.5% of reported incidents, copper sulfate involved ingestion and absorption through the gastrointestinal tract [12,26,27,30,34,35,37,39,40,43,46,49,55,68]. Few studies, however, have reported parenteral copper sulfate poisoning (6.25%) [7,9]. Oldenquist et al. reported a case of deliberate intravenous and subcutaneous copper sulfate injection at a dosage of 50 mg with a suicidal intent . In addition, an unusual fatal case of copper sulfate poisoning has been reported involving a 29-yearold woman, who inserted an unknown quantity of copper sulfate vaginally in order to terminate an unwanted pregnancy. She died of a septic abortion and hepatorenal failure .
A. Physiology of Copper
Normally, the total body content of copper is 50-150 mg. It is an essential trace element and the recommended daily dietary intake is approximately 2 mg. About 30% of copper is absorbed through the gastrointestinal tract, predominantly through the stomach and duodenum. Its transport is very fast, as peak serum copper levels are reached in the following 1-3 h. Once entering circulation, copper is originally albumin-bound and transported to the liver, where it is incorporated into ceruloplasmin. Therefore, in serum, 93% of copper gets tightly bound to ceruloplasmin and 7% is loosely bound to albumin. Copper is distributed by ceruloplasmin to all tissues. Its highest concentrations are in the liver, heart, brain, kidneys, and muscles. Normally, the liver of an adult contains copper amounts that range from 18-45 mg/g dry weight. Intracellular copper is principally bound to metallothionein. It is also largely found in red blood cells as erythrocuprein. Copper has an enterohepatic circle; 80% of the copper excretion occurs through the fecal matter and bile, whereas approximately 4% of copper is excreted in the urine. The bile and pancreatic secretions are reabsorbed by the duodenum, indicating the complexity of analysis of copper bioavailability. The average half-life of copper in a healthy individual is estimated to be 26 days [8,21,22,26,27,51].
In cases of acute overdose, copper kinetics differs from the aforementioned and the transport mechanisms are reversed. The gastrointestinal absorption may fall to even 12% in patients with high copper intake. In areas of damaged gastric mucosa, however, the fractional absorption is likely to be higher. In acute poisoning, excess copper binds to albumin, rather than ceruloplasmin. This protein-metal complex is the toxic part of serum copper. The major site of copper deposition is the liver, with most of the copper bound to metallothionein. When the concentration of hepatic copper exceeds 50 mg/g dry weight, liver cell necrosis occurs with release of large amounts of copper into the serum. Released copper is rapidly taken up by erythrocytes, resulting in oxidative damage, which in turn may induce hemolysis [27,45,51].
B. Pathology, Mechanism of Toxicity, and Clinical Expression
Copper sulfate poisoning is responsible for oxidant injury in various tissues and dysfunction of several organs including the gastrointestinal tract, liver, and kidneys, whereas the cardiovascular, central nervous, and endocrine systems, as well as the pancreas, are rarely directly affected. Therefore, the clinical course of copper sulfate poisoning includes erosive gastropathy, intravascular hemolysis, methemoglobinemia, hepatitis, acute kidney injury, and rhabdomyolysis. Arrhythmias and seizures are also reported due to the secondary involvement of other organ systems [27,51,56].
The mechanism by which copper acts upon cells, accumulates in the cell nucleus, and induces direct injury is not clear. Although a number of studies have investigated copper toxicity in animals (rats, monkeys, dogs), it is not known whether animals are a good model regarding the description of copper toxicity in humans. At a cellular level, excessive copper putatively results in oxidative damage, involving lipid peroxidation. It has been theorized that the production of free oxygen radicals induces cytoplasmic injury and cell death. Another putative mechanism may involve the inactivation of certain cellular enzymes due to excessive copper. Copper is particularly toxic against the red blood cells, hepatocytes, and myocytes. Sokol et al. suggested that oxidant injury toward hepatocyte mitochondria may be an inducing factor in hepatic cell damage [27,51,56].
Corrosive gastrointestinal injury is a common aftermath of copper sulfate poisoning [27,31,38,51,55,69]. Orally obtained copper is primarily absorbed through the stomach and duodenum. Gastrointestinal symptoms are the first to appear, including metallic taste in the mouth, epigastric pain, nausea, vomiting, diarrhea, gastrointestinal hemorrhage, hematemesis, and melena. Copper sulfate toxicity due to oral ingestion results in acute irritation and erosion of gastrointestinal epithelium. Due to gastric irritation, vomiting is automatically triggered immediately after intake, which may reduce the amount of copper that would otherwise be absorbed through the gastrointestinal tract. In a case series of 19 patients requiring hemodialysis after copper sulfate oral intake, 7 (37%) developed gastrointestinal bleeding and in 5 (26%) gastrointestinal bleeding was severe enough to cause significant hypotension . Gastrointestinal symptoms, however, may also appear in parenteral poisoning, indicating that the toxic effects of copper sulfate putatively stem from systemic toxicity beyond its direct toxicity to the gastrointestinal tract [7,9,27,46,51].
As mentioned above, absorbed copper is tightly bound to ceruloplasmin in serum and, transported via the hepatic portal circulation, is finally deposited in liver by metallothionein. Hepatotoxicity and acute liver failure following tissue necrosis occurs at early stages of poisoning due to direct copper toxicity on hepatocytes. Acute liver failure following massive or submassive hepatic necrosis is usually seen in cases of copper sulfate poisoning [27,51,52]. Centrolobular hepatic necrosis can cause the release of stored copper from the hepatocytes into the plasma. The clinical presentation of acute liver failure includes hepatic dysfunction (jaundice, hepatomegaly), abnormal liver biochemical values (increased serum transaminases), coagulopathy (prolongation of prothrombin time), and progressive encephalopathy. Furthermore, patients with acute liver failure after copper sulfate poisoning have an increased risk for sepsis and multiple organ dysfunction syndrome [25,27,51,61].
Jaundice is a symptom that has been reported among several patients with copper sulfate poisoning [27,40,41,47,51,52,64]. It manifests itself on the second or third day after intake mainly due to liver failure or hemolysis . The jaundice may result from hepatocellular, hemolytic, or cholestatic mechanisms, or some combination thereof . Elevated levels of liver enzymes and bilirubin are observed in the majority of copper sulfate poisoning incidents [6,54]. Mollick et al. reported that blood chemistries performed on the third day after copper sulfate ingestion showed elevations of serum glutamic oxaloacetic transaminase and serum bilirubin of 40% and 37%, respectively . In addition, Agarwal et al. reported that jaundice was noted in 58% of patients, while one individual (5%) died of hepatic encephalopathy .
Intravascular hemolysis and methemoglobinemia are the most serious hematological manifestations of copper sulfate poisoning [4,24,27,34,51,62]. Methemoglobinemia is an additional hematological manifestation of copper sulfate poisoning, the reported incidence of which varies from 3.4% to 42% in the international literature [3,13,14,27,35,46,51,52,55]. The mechanism through which copper sulfate poisoning may cause methemoglobinemia is dictated by the capacity of the [Cu.sup.+2] ion to oxidize the ferrous ion ([Fe.sup.2+]) of the heme group of the hemoglobin molecule into the ferric state ([Fe.sup.3+]). This mechanism converts hemoglobin to methemoglobin, resulting in reduced oxygen-binding capacity. The binding of oxygen to methemoglobin, however, results in an increased affinity of oxygen to the three other heme sites leading to increased oxygen-binding affinity of other subunits in the same hemoglobin molecule, which in turn leads to a deficiency of oxygen release to the tissues, and thus, hypoxia. The transformation of hemoglobin into methemoglobin results in the manifestation of several characteristic clinical symptoms including cyanosis (bluish coloring of the skin), chocolate-brown coloration of arterial blood, and hypoxic shock symptomatology (dyspnea, tachycardia) [27,48,51]. Symptoms of methemoglobinemia were not obvious when blood methemoglobin levels were below 3%. Cyanosis appears when values exceed 15%, while chocolate-brown colored blood is usually indicative of values between 15% and 30%. The risk of morbidity increases even further when methemoglobin levels exceed 50%, resulting in arrhythmias, acidosis, coma, and death [27,43,51].
Intravascular hemolysis occurs approximately between 12 and 24 h after intake and results from direct damage of red cell membranes or the deactivation of major enzymes. The intracellular concentration of copper inhibits the function of glucose-6-phosphate dehydrogenase (G6PD) and glutathione reductase in red blood cells. The aforementioned enzymes are vital for the protection of red blood cells from oxidative stress. In addition, Fairbanks et al. reported that copper sulfate accelerates the oxidation of reduced nicotinamide adenine dinucleotide phosphate (NADP) inside cells . Furthermore, copper inhibits [Na.sup.+]/[K.sup.+] ATPase pumps and increases the cell membrane permeability . Intravascular hemolysis results in hemoglobinemia, as the amount of hemoglobin released into the plasma exceeds the binding capacity of haptoglobin. The unbound hemoglobin is filtered in the urine and reabsorbed by the renal tubules. When the absorptive capacity is exceeded, hemoglobinuria is induced. Intravascular hemolysis is one of the main factors leading to acute renal failure [9,13,15,27,34,51,57]. Chugh et al. reported a total of 29 patients suffering from acute copper sulfate poisoning. Among all patients (n = 29), 17 developed hemolysis. Among these 17 patients, 11 (64.7%) developed renal failure, while none of the nonhemolytic patients (n = 12) experienced acute renal failure [13,15].
Acute renal failure is the cardinal consequence of severe poisoning due to copper sulfate intake and its frequency ranges from 35% to 60% [13,15,19,27,42,46, 51]. Chugh et al. reported that in a series of 29 patients suffering from acute copper sulfate poisoning, 11 (37.8%) had developed acute renal failure [13,15]. Besides intravascular hemolysis, several putative mechanisms may explain the causation of acute renal failure, including direct renal copper toxicity due to copper, dehydration or hypovolemia, rhabdomyolysis, and myoglobinuria as well as sepsis. In particular, copper released from hemolyzed red cells is involved in the injury of proximal convoluted tubules and renal tubular epithelial cells. Furthermore, hypovolemia in cases of copper sulfate poisoning may be induced due to blood loss or loss of body fluids. Fluid imbalance may result from gastrointestinal bleeding, severe vomiting, or diarrhea. Insufficient restoration of the fluid balance results in hypovolemia, which in turn may lead to renal failure. The renal symptomatology in cases of acute copper sulfate poisoning includes oliguria, anuria, hematuria, hemoglobinuria, albuminuria, and myoglobinuria [13,15,63]. Mollick et al. reported that the renal complications manifested in a series 40 cases of acute copper sulfate poisoning included oliguria (25%), albuminuria (30%), hematuria (32.5%) and renal dysfunction (30%) . Histologic examination of kidney specimens in cases of acute renal failure due to copper sulfate poisoning has revealed the histological image of acute tubular necrosis [13,15,34]. Furthermore, Chugh et al. reported that kidney histology in seven of the eight kidney biopsies with acute renal failure revealed acute tubular necrosis (87.5%). Loss of the epithelial lining (cellular apoptosis), interstitial edema, and the presence of inflammatory cells were detected in the renal tubules [13,15]. In addition, Bhowmik et al. reported a case of parenteral copper sulfate poisoning that led to irreversible chronic tubulointerstitial nephritis .
Rhabdomyolysis in cases of acute copper sulfate poisoning has rarely been reported [20,27,32,51,61]. Coppertoxicity on muscle cells may cause rhabdomyolysis followed by high levels of creatine phosphokinase and myoglobinuria. Few cases of rhabdomyolysis and simultaneous presence of acute renal failure have been reported regarding copper sulfate poisoning [27,51,61].
Pancreatitis has also been a very rarely reported manifestation in cases of copper sulfate poisoning. It has been theorized that elevated serum amylase levels do not result from copper toxicity effect on pancreas, as there is no putative explanatory mechanism. Levels of serum amylase are believed to increase in a nonspecific manner due to acute renal failure. In addition, due to the restrictive presence of renal failure, the performance of imaging examinations (computed tomography scan or magnetic resonance imaging) is often difficult to confirm the diagnosis of pancreatitis without the usage of a contrast agent [36,57,63].
Complications due to recurrent vomiting, aspiration pneumonia, or chemical pneumonitis should be anticipated and the patient is very likely to need mechanical ventilation. Copper sulfate poisoning may develop several severe complications and escalate into the multiple organ dysfunction syndrome (MODS) due to systematic inflammatory response and sepsis. Specifically, early mortality of acute copper sulfate poisoning is usually induced by severe shock or cardiovascular collapse, while late mortality usually results from either hepatic, renal, or MODS [7,28]. In particular, Wahal et al. reported that 4% of patients had developed early cardiovascular collapse and consequently passed away within 10 h of copper sulfate consumption .
D. Clinical Course in Pediatric Cases
From the limited available literature, clinical features among pediatric patients are similar to the aforementioned symptoms among adults with acute appearance of gastrointestinal symptoms and hemolysis usually occurring after 24 h. Hepatic and renal pathology develops 1 or 2 days after intake, similarly to adults. Cardiac abnormalities have been reported with multiple ventricular extrasystoles, tachycardia, and occasional unifocal bigeminy in a two-year-old male who swallowed 30 mL of a supersaturated copper sulfate solution, containing 10 g of copper sulfate [11,18,31,51,67].
E. Diagnosis and Prognostic Indicators
Timely diagnosis in cases of copper sulfate poisoning is crucial and often it is primarily based on history taking and clinical examination. The clinical indicators suggesting copper sulfate are bluish-green vomit and occurrence of intravascular hemolysis. Bluish-green vomit in emergency departments may be indicative of three possible diagnoses; copper sulfate, boric acid, or paraquat poisoning [27,51,68].
If the patient's history is doubtful, the assessment of serum copper levels or whole blood copper concentrations may also be indicative. Elevated serum copper levels and whole blood copper concentrations have been reported in cases of deliberate oral intake of copper sulfate ranging from 1-30 g. The association between copper levels in blood and the severity of symptoms has not been ascertained. Chuttani et al. in a research study found no credible association between serum copper levels and the severity of toxicity symptoms [16,27,51]. Furthermore, Wahal et al. noted no prognostic value of plasma copper concentrations. There is no linear relationship between serum copper values and the clinical expression, partly due to the rapid uptake of copper into the red blood cells. Notwithstanding, whole blood copper levels seemed to correlate positively with the severity of symptoms and, thus, they may be a more accurate indicator of the patients' prognosis [16,27,51,64,65].
F. Management and Treatment
Treatment in all cases of copper sulfate poisoning (oral or parenteral) is primarily symptomatic and supportive. It focuses on four specific key principles --absorption reduction, close observation for complications, supportive therapy, and chelation therapy --to remove active copper from the body [27,51].
An ABC approach has to be followed initially in order to ensure the airway patency, adequate ventilation, and circulation. In cases of acute oral poisoning, the primary objective is to minimize the corrosive contact damage of the gastrointestinal mucosa by ministering large quantities of milk and water, as dilution reduces the direct mucosal injury. In addition, activated carbon may be administered in order to delay the absorption of copper; a usual dose is from 25 mg to 100 mg in adults, but it is of unproven benefit . Among studies, judgments regarding the use of active carbon are divided due to the fact that copper sulfate is already an emetic agent and, thus, it may be more useful to avoid gastric lavage in order not to injure or perforate the already eroded mucosa [27,51]. Patients may need an antiemetic management with omeprazole or ranitidine in order to prevent reexposure of the esophagus to the corrosive substance. In 1962, Gupta et al. published a study supportive of corticosteroid administration for the management of gastrointestinal injuries in cases of acute copper sulfate poisoning . The exact extent of the gastrointestinal damage can be revealed by performing a gastroduodenal endoscopy. Endoscopy carried out at the early stage of poisoning has not been associated with any complications [27,51].
Where methemoglobinemia occurs and methemoglobin levels exceed 30% of the hemoglobin levels, treatment with methylene blue is required [27,43,51]. Methylene blue interacts with nicotinamide adenine dinucleotide phosphate-oxidase (NADPH) producing leukomethylene blue, which in turn reduces methemoglobin to hemoglobin. Methylene blue is contraindicated in case of G6PD deficiency. Unless methemoglobinemia responds effectively to methylene blue administration, exchange transfusion is an alternative therapeutic option [27,39,51,69]. In severe cases of methemoglobinemia, alternative treatments have also included administration of ascorbic acid or hyperbaric oxygen [23,27,46,51,64,65].
The treatment of choice for copper sulfate poisoning is chelation therapy, which is based on Wilson's disease treatment. Chelation therapy removes heavy metals from the body. A variety of chelating agents have been recommended in copper sulfate poisoning including D-penicillamine, 2,3-dimercapto-1-propanesulfonic acid (DMPS), British anti-Lewisite or dimercaprol, and ethylenediaminetetraacetic acid. Chelating agents bind to copper and form ringlike complex structures that are removed from intracellular or extracellular parts in order to be easily excreted. Although there are no controlled studies regarding the effectiveness of specific chelating agents in cases of acute copper sulfate poisoning, administration of DMPS has proved to be the most helpful among chelating agents [27,51,55]. The side effects accompanying the administration of chelating agents are a serious concern regarding their medical use in copper sulfate poisoning. Their principal toxic effect occurs to the detriment of the renal function due to the large quantities of chelated metals that pass through the renal tubules in a relatively short time. Therefore, chelation therapy should be administered prudently in cases of copper sulfate poisoning and concurrent severe acute renal failure. In comparison to other chelating agents, treatment with DMPS precipitates less severe side effects, involving elevated levels of liver enzymes, abdominal disturbances, and anaphylactic reactions [27,51].
Hemodialysis, on the other hand, appears to be ineffective in the removal of copper from the body, as copper is excreted through the bile [1,27,39,46,51]. Therefore, Agarwal et al. have suggested that hemodialysis may prove useful only at early stages of poisoning, while the metal is still in the circulation as free copper and it is possible to be removed. Hemodialysis, hemoperfusion, or hemodiafiltration can be administered as a part of supportive treatment in patients who experience acute renal failure . Given that copper binds to serum and tissue proteins, Takeda et al. proposed a combined treatment with chelating agents and blood purification (hemodialysis or hemoperfusion), during which the chelated copper may be removed through diuresis and dialysis . Interestingly, in Table 1 it is observed that in those cases that acute renal failure was managed with a combined treatment of chelation therapy and hemodialysis, all the patients survived.
IV. CASE PRESENTATION
An 87-year-old man ingested an unknown amount of a pesticide consisting of highly concentrated copper sulfate. He was found lethargic at his home by his son with a 2-h history of vomiting and diarrhea. His family suspected deliberate poisoning because he had suffered from bipolar disorder and he had recurrently expressed his desire to commit suicide (active suicidal ideation). The previous day, he had just been diagnosed with pleural effusion, which caused discomfort and feelings of depression and worthlessness. Neither the exact time of poisoning nor the quantity of intake could be determined. He was immediately transferred to the University General Hospital by ambulance. On admission, clinical findings including dyspnea, wheezing, nausea, abdominal pain, and vomiting of blue gastric content were detected. He was tachycardic with 112 beats per minute heart rate and sinus rhythm as indicated by the electrocardiogram (ECG). His blood pressure was within normal values (145/85 mmHg), body temperature 36.3[degrees]C, respiration rate 16 breaths per minute, and oxygen saturation by pulse oxymetry 90%. Laboratory findings on admission are summarized in Tables 2 and 3.
The patient suffered from diagnosed bipolar disorder for which he received carbamazepine 400 mg daily. He also had a known history of anemia and coronary disease. For the later, he was under daily treatment with acenocoumarol and diltiazem. Furthermore, he had been hospitalized recently for atelectasis and pleural effusion, for which he had been under treatment with antibiotics. He had been discharged one day prior to his suicidal attempt.
Poison control center guidelines indicated that nasogastric intubation and gastric lavage were contraindicated; instead they instructed the administration of antiemetic drugs, administration of 200 mL water or milk, constant vital signs monitoring, renal function monitoring, overnight otolaryngological examination, and continuation of patient's monitoring for 2 to 3 days in the absence of complications. They also recommended fluid replacement. Moreover, the patient was treated with omeprazole for gastritis, paracetamol, and diuretics (furosemide). However, 4 h after his admission the patient's condition suddenly deteriorated and he died. The treating physicians were falsely reassured by the patient's relatively normal laboratory values (which did not initially suggest severe renal or hepatic impairment), their lack of familiarity with such cases, and the seeming authority of the Poison Control Center instructions. Moreover, it was known that the patient suffered from anemia and respiratory distress. No treatment with chelating agents or methylene blue was administered to the patient. All the aforementioned putatively led to poor management of the incident.
A. Postmortem Examination--External Forensic Examination Findings
The external postmortem examination revealed the body of an elderly, moderately nourished male adult. He was wearing an adult diaper for incontinence containing greenish blue excrement. The lips and nail beds in the upper extremities of the deceased were cyanotic (Figure 1). Multiple ecchymoses were present over his entire body. A left temporal injury with a maximum diameter of 1.5 cm was noted from the patient's fall to the ground when his consciousness level declined.
B. Autopsy Findings
Autopsy dissection revealed congestion of his visceral organs. After removal of the calvarium, cerebral edema was observed. In the thoracic cavity, multiple pleural adhesions were present, while signs of chronic respiratory distress were observed in the lungs. The heart was enlarged and weighed 540 g, coronary arteries bore severe atherosclerotic lesions causing severe localized stenoses of their walls (approximately 75%). The stomach revealed flattened mucosal folds and erosive gastritis and contained a bluish watery material (Figures 2 and 3). The intestine was also full of a bluish watery content. The macroscopic appearance of the liver indicated focal necrosis of the liver parenchyma. In addition, both kidneys demonstrated granular external surfaces with focal subcapsular hemorrhages.
C. Histopathological Findings
Tissue sections were obtained from the lung, liver, spleen, stomach, kidneys, and myocardium of the deceased. Histopathological examination of the liver tissue sections indicated submassive hepatic necrosis, while histopathological examination of both kidneys revealed features of acute tubular necrosis.
The histopathological examination of the pulmonary tissue sections revealed lung-nodule features with extensive hyaline degeneration and multiple deposits of soot granules.
D. Toxicological Examination
Blood, urine, gall bladder, and gastric content samples were obtained for toxicology. The toxicological analysis revealed a blood copper concentration of 24 mg/L, whereas the values were negative for other heavy metals or drugs.
E. Case Study
This case demonstrates consistencies and inconsistencies with the relevant literature. The gender of the patient and the use of copper sulfate as a suicide method are as typically found in the literature. In contrast, an intoxication in an elderly patient is a rarity, and this patient (age 87) is the oldest reported in the literature to date (see Table 1).The primary clinical symptoms were consistent with those reported in the literature: erosive gastritis, recurrent bluish vomiting, dyspnea, tachycardia, cyanosis, hepatotoxicity, acute tubular necrosis, and increased serum amylase [27,51,56,57]. As acute kidney injury is associated with a rise in serum amylase, the latter cannot be attributed to pancreatitis; a computed tomography scan would have been a useful examination in this regard [36,57,63].
The patient in the present case report suffered submassive hepatic necrosis, as found in the postmortem examination. As the majority of absorbed copper is deposited in the liver after being delivered from the portal circulation, severe hepatotoxicity and subsequently acute liver failure are predictable consequences. Elderly people are at an even higher risk of hepatic injury due to decreased clearance, reduced hepatic blood flow, variation in copper binding, and relatively lower hepatic volume. In addition, poor diet, infections, and multiple hospitalizations make patients more susceptible to copper-induced liver injury [27,51].
Notwithstanding the foregoing, laboratory findings --though inadequate--were not indicative of severe hepatic or renal damage, which in association to the physicians' inexperience in similar incidents, misled them as to the gravity of the clinical expression. The main diagnostic indicator was the bluish vomiting, while cyanosis was a significant symptom and prognostic indicator [16,27,51].
With regard to the therapeutic approach, omeprazole is the treatment of choice for the management of erosive gastritis; it was administered in the present case, whereas in four cases of the literature (4/16) copper absorption was decreased with gastric lavage, which is not recommended (see Table 1) [27,51]. As mentioned above, hemodialysis seems to be beneficial in cases of acute renal failure only at early stages--when copper is still in circulation . Table 1 also suggests that in the cases in which a combined treatment of chelation therapy and hemodialysis was administered for the management of acute renal failure, all the patients survived. However, the patient of the present case study died without having been provided this kind of treatment. Furthermore, neither blood transfusion nor chelating agents nor methylene blue was administered to the patient, in contrast to accepted practice. The patient passed away due to multiple organ dysfunction within 6 h of poisoning, which is consistent with the literature of fatal cases ([less than or equal to] 10 h) (see Tables 1 and 4).
The clinical expression (symptomatology and clinical chemistries) of poisoning by copper sulfate vary significantly. Due to the sparse literature and lack of detailed reporting of blood chemistries, no reliable statistical analysis can be accomplished. The key take-home message of this paper is that copper sulfate poisoning is very serious and this seriousness is not adequately revealed through laboratory testing. The amount of the ingested substance may not seem alarming. The vigilance of the medical personnel as well as the general condition of the patient's health (age and comorbidity) play important roles in the therapeutic outcome.
In conclusion, acute copper sulfate poisoning may be a severe life-threatening condition. Copper sulfate poisoning incidence and age distribution vary by geographic region, safety regulations, and availability. It is a rarity in western countries, while it is very common in South Asian countries--although its incidence has fallen in recent years. The majority of copper sulfate poisonings is seen in rural populations. Patients are typically males in their third decade of life. The lethal dose of ingested copper is considered to be 10-20 g; 14-36% of the patients die within a few hours of ingestion, while the average hospitalization time is more than 20 days. Common clinical signs suggesting copper sulfate poisoning include bluish-green emesis, and intravascular hemolysis. The timely identification of the condition and a stepwise approach are important for proper management. The clinical course of copper sulfate poisoning includes erosive gastropathy, intravascular hemolysis, methemoglobinemia, hepatitis, acute kidney injury and rhabdomyolysis. The therapeutic management should focuses on absorption reduction, chelation therapy, supportive therapy, and close observation, particularly for renal and hepatic complications.
The heterogeneity of symptoms, the absence of a direct correlation of laboratory measurements with the prognosis and therapeutic outcome, as well as the lack of familiarity of physicians of the western world with such cases, are risk factors which negatively affect health care quality. There is a strong need for detailed recording and presentation of cases of poisoning by copper sulfate so that medical practice can be improved through experience. This study should add to that experience and hopefully guide others to allow the creation of a statistically valuable database from which clinical practice can draw insight.
We would like to express deep gratitude to the technicians of the Laboratory of the Forensic Sciences, A. Papadoudis and K. Lazaridou, for their valuable help.
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Evangelos Nastoulis obtained a medical degree (M.D.) and license to practice from the National Kapodistrian University of Athens (Athens, Greece). Dr. Nastoulis is currently a specialized forensic pathologist and doctoral student in the Department of Anatomy at Democritus University of Thrace (Alexandroupolis, Greece). His research interests focus on clinical-surgical anatomy and forensic medicine.
Maria-Valeria Karakasi obtained a medical degree (M.D.) and license to practice from the Democritus University of Thrace. Dr. Karakasi is currently a doctoral student in the Laboratory of Forensic Sciences at Democritus University of Thrace and a resident psychiatrist in Papanikolaou General Hospital of Thessaloniki (Thessaloniki, Greece). Her research interests focus on forensic psychiatry, issues of autonomy, suicidal behavior, sexual homicide, homicide, antisocial behavior, puerperal mental disorders, and drug abuse disorder from a psychodynamic perspective.
Constantinos (Michael) Couvaris obtained a medical degree (M.D.) and license to practice from the University of Crete (Heraklion, Greece). Dr. Couvaris is currently a doctoral student at the First Pathology Laboratory in the Medical School of the National and Kapodistrian University of Athens.
Dr. Couvaris is a specialized forensic pathologist. He holds the post of Pro Bono Forensic Anthropologist for the Forensic Service of Athens and he is a forensic consultant to the International Committee of the Red Cross (ICRC) for Greece. His research interests focus on forensic anthropology and examination of skeletal remains.
Stylianos (Nicolaos) Kapetanakis obtained a medical degree (M.D.) and Ph.D. from the School of Medicine, Democritus University of Thrace. Dr. Kapetanakis is currently an assistant professor of anatomy in the School of Medicine, Democritus University of Thrace.
Dr. Kapetanakis is a specialized orthopedic and spine surgeon. He also holds the post of director of the South East Endoscopic Spinal Center in European Interbalkan Medical Hospital (Thessaloniki, Greece).
Aliki Fiska obtained a medical degree (M.D.) and Ph.D. from the School of Medicine, Democritus University of Thrace (Alexandroupolis, Greece). Dr. Fiska is currently an assistant professor of anatomy in the School of Medicine, Democritus University of Thrace. She also holds the post of director of the Laboratories of Anatomy and Clinical Anatomy in the School of Medical, Democritus University of Thrace.
Dr. Fiska is a specialized pathologist. Her research interests focus on anatomy, clinical-surgical anatomy, anatomical pathology, electron microscopy, and history of medicine.
Pavlos Pavlidis obtained a medical degree (M.D.) from the Faculty of Medicine, Trakia University (Stara Zagora, Bulgaria) and a Ph.D. from the Faculty of Medicine, Aristotle University of Thessaloniki (Thessaloniki, Greece). Dr. Pavlidis is currently an assistant professor of forensic medicine at the Democritus University of Thrace, School of Medicine.
Dr. Pavlidis is a licensed forensic pathologist and a court-appointed expert in matters relating to homicide, suicide, occupational accidents, rape, child abuse, domestic violence, (migration) border-related deaths, and toxicology. He is a frequent consultant to the national media and international press involving numerous newspaper articles and international documentaries. His published work includes a monograph: Pavlidis P: Elements of Medical Law, Ethics and Problematic; Publications Utopia: Athens, Greece; 2008.
E. Nastoulis (1), M.-V. Karakasi (1,2), C. M. Couvaris (1), S. Kapetanakis (3), A. Fiska (3), P. Pavlidis (1)
(1) Laboratory of Forensic Sciences School of Medicine Democritus University of Thrace Alexandroupolis, Greece
(2) Adult Psychiatry Psychiatric Department G. Papanikolaou General Hospital of Thessaloniki Thessaloniki, Greece
(3) Department of Anatomy School of Medicine Democritus University of Thrace Alexandroupolis, Greece
* Corresponding author: Dr. Pavlos Pavlidis, Laboratory of Forensic Sciences, School of Medicine, Democritus University of Thrace, Dragana GR68100, Alexandroupolis, Evros Prefecture, Greece; + 30 25513 53822 (voice); pavlidi@,med.duth.gr.
Caption: Figure 1: Cyanotic nail beds (postmortem external examination).
Caption: Figure 2: Hemorrhagic, greenish-blue stained mucosa of stomach (autopsy findings).
Caption: Figure 3: Greenish-blue stained mucosa of esophagus (autopsy findings).
Table 1. Appendix detailing all acute poisoning incidents by copper sulfate reported throughout international literature (n = 16) (a) Gender Cause of Method of Time of Quantity /age poisoning intake intake M/58 Suicidal Per os Found dead Unknown M/47 Suicidal IV, SC 3 days 50 mg M/55 Suicidal Per os 7 h 1/2 spoon M/29 Suicidal-- Per os 1 day Unknown psychosis F/33 Suicidal Per os 5 h Unknown M/22 Accidental Per os 3 h One cup M/26 Suicidal Per os 48 h 30 g M/45 Suicidal Per os 2 h 50 g F/20 Suicidal Per os 6 days Unknown F/30 Suicidal/ Per os Few h Unknown Pregnancy F/55 Suicidal Per os 1 day Unknown M/22 Suicidal-- Per os Found Unknown Erratic per- unconscious sonality F/29 Pregnancy-- Vaginal 2 h Unknown abortion M/18 Suicidal Per os Unknown ~20 g F/30 Suicidal-- Per os Unknown ~30-40 g Previous attempts M/87 Suicidal-- Per os 2 h Unknown Bipolar affective disorder Gender Absorption IV hemolysis Chelation /age regulation/ management therapy erosive methemoglobinemia gastropathy management M/58 -- -- -- M/47 Not required Transfusion: Penicillamine packed red (40 mg/kg IM); blood cell & BAL (5 mg/kg fresh frozen IM) plasma (3 units each) M/55 Gastric lavage Transfusion: Penicillamine red cell (9 (900 mg/day) units) M/29 Omeprazole (40 Transfusion: Edetate calcium mg/day); red cell (4 disodium (1 g/ amoxicillinclavulanic units) 12 h) in 5% DW acid (2 g); levofloxacin (500 mg) F/33 Gastric lavage Methylene blue DMPS (25 mg/ with activated (2 mg/kg); 4 h IV) carbon; fluid transfusion: replacement; packed red bicarbonate; blood cell, dopamine (10 fresh frozen [micro]g/kg/ plasma, human min); albumin ranitidine; meropenem (1 g/8 h); hydrocortisone (100 mg/6 h) M/22 Antiemetics Methylene blue Penicillamine (IV) (1 mg/ kg); (1 g/day); BAL exchange (3 mg/kg/4 h transfusion: IM) packed red cell M/26 Omeprazole (4 Transfusions: Penicillamine days IV); no red cell (3 (500 mg/6 h) gastric lavage units); methylene blue (2 mg/kg) in 5% DW M/45 Omeprazole Transfusion: Penicillamine (IV); no red cell (500 mg/6 h) gastric lavage F/20 No gastric 1% methylene Not required lavage blue (2 mg/kg); hemodialysis with exchange transfusion F/30 Not available Not available Not available F/55 Broad spectrum 5% Methylene Penicillamine antibiotics blue in DW IV (500 mg/6 h) (2x 2 mg/kg) M/22 Gastric lavage; 5% Methylene DMPS (250 fluid replacement; blue in DW IV mg/4 h IV) vasoactive (1x 1-2 mg/kg); drugs; transfusion: ranitidine; red cell (1x 10 furosemide mL/kg) F/29 Ringers lactate No blood No (1 L); face transfusion mask oxygen; available; cefotaxime (1 g methylene blue IV); not available metronidazole (500 mg/8 h IV); 5% lactate (1 L) in DW with simultaneous ringers lactate bolus (1 L) M/18 Gastric lavage Not required Penicillamine with activated (500 mg/6 h) carbon; proton pump inhibitor; meropenam (1 g/ 8 h IV) F/30 Not available Not available Not available M/87 5% DW/12 h (1 No No L); omeprazole (1 amp/12 h); paracetamol Gender Renal failure Hospitalization /age management M/58 -- -- M/47 Hemodialysis Unknown M/55 Hemodialysis 30 days (20 days) M/29 Not required 9 days F/33 Furosemide (IV); 35 days venovenous hemodiafiltration: intermittent dialysis M/22 Hemodialysis 14 days M/26 Hemodialysis 38 days (4 weeks) M/45 Hemodialysis 25 days (10 days) F/20 Not required 7 days F/30 Not available 48 h F/55 -- 4 days M/22 No 6 h F/29 No 22 h M/18 No 10 days F/30 Hemodialysis 14 days M/87 Fourosemide 4 h Gender Outcome Ref. /age M/58 Died  M/47 Survived  M/55 Survived  M/29 Survived  F/33 Survived  M/22 Survived  M/26 Survived  M/45 Survived  F/20 Survived  F/30 Died (b)  F/55 Died  M/22 Died  F/29 Died  (hypoxia, MODS) M/18 Survived  F/30 Survived  M/87 Died This case study (a) Abbreviations: BAL: dimercaprol, also called British anti-Lewisite; DMPS: dimercaptopropane sulfonate; DW: dextrose in water--intravenous sugar solution; IM: intramuscularly; IV: intravenously; MODS: multiple organ dysfunction syndrome; per os: oral administration; SC: subcutaneously. (b) Hepatorenal failure; septic abortion. Table 2. Hematological laboratory findings upon admission Measurement Finding (a) Hematocrit (HCT) 35.4% Hemoglobin (HGB) ([??]) 12.4 g/dL Red blood cells (RBC) 4.19 M/[micro]L Mean corpuscular volume (MCV) 84.5 fl Mean corpuscular hemoglobin (MCH) 29.6 pg White blood cells (WBC) 8.86 K/[micro]L Platelets (PLT) 355 K/[micro]L (a) ([??]): Pathological value lower than normal range. Table 3. Blood chemistry findings upon admission Test item Finding (a) Glucose ([??]) 194 mg/dL Urea 47 mg/dL Creatinine ([??]) 1.5 mg/dL Sodium 139 mmol/L Potassium 4.6 mmol/L Calcium 9.2 mg/dL Aspartase aminotransferase AST (GOT) ([??]) 56 U/L Alanine aminotransferase ALT (GPT) 9 U/L Alkaline phosphatase (ALP) ([??]) 158 U/L Lactate dehydrogenase (LDH) 217 U/L Creatine phospokinase (CPK) 38 U/L Gamma gloutamyl transferase (y-GT) ([??]) 152 U/L Amylase ([??]) 191 U/L Total bilirubin ([??]) 1.5 mg/dL Conjugated bilirubin ([??]) 0.6 mg/dL C-Reactive protein (CRP) ([??]) 12.1 mg/dL (a) ([??]): Pathological value higher than normal range. Table 4. Comparing of overall medical findings in the present case study with the data available throughout international literature Patient and findings Literature cases Present case study Sociodemographic data Gender Male prevalence Male Age 16-35 87 Most common causation Self-harm Self-harm Psychiatric disorder (Often not diagnosed) Present case study Hours of death after within 10 (among 6 poisoning fatal cases) Findings Clinical Common symptom Erosive gastropathy Not defined Metallic taste Not defined Epigastric pain Yes Nausea Yes Vomiting Yes (a) Diarrhea Yes (b) Gastrointestinal No hemorrhage Hematemesis No Melena No Hepatotoxicity Yes (incipient) (c) Jaundice No (e) Hepatomegaly No Abnormal liver Yes (c) biochemical values Coagulopathy Not diagnosed (f) Encephalopathy -- Septic phenomena Yes (h) Methemoglobinemia Yes Cyanosis Yes Chocolate brown Not defined coloration of arterial blood Dyspnea Yes (wheezing) (j) Tachycardia Yes (112 bpm) Arrhythmia No Acidosis Not defined (k) Seizures Not defined (l) Level of consciousness Not defined (l) drop/coma Intravascular hemolysis No Hemoglobinemia No (n) Acute renal failure Yes (incipient) (b) Hypovolemia No Oliguria/anuria No Hematuria Not defined (p) Hemoglobinuria Not defined (p) Albuminuria Not defined (p) Myoglobinuria Not defined (p) Acute tubular -- necrosis (ATN) Rhabdomyolysis No (r) Elevated serum Yes (191 U/L) amylase levels Chemical pneumonitis No Aspiration pneumonia No Multiple organ -- dysfunction syndrome Whole blood copper Not defined (s) concentration Patient and findings Literature cases Present case study Sociodemographic data Gender Male prevalence Age 16-35 Most common causation Self-harm Psychiatric disorder (Often not diagnosed) Hours of death after within 10 (among poisoning fatal cases) Findings Autopsy Common symptom Erosive gastropathy Yes Metallic taste -- Epigastric pain -- Nausea -- Vomiting -- Diarrhea -- Gastrointestinal No hemorrhage Hematemesis -- Melena -- Hepatotoxicity Yes (d) Jaundice -- Hepatomegaly No Abnormal liver Yes biochemical values Coagulopathy Yes (g) Encephalopathy Cerebral edema Septic phenomena Yes (i) Methemoglobinemia -- Cyanosis Yes Chocolate brown -- coloration of arterial blood Dyspnea -- Tachycardia -- Arrhythmia -- Acidosis -- Seizures -- Level of consciousness -- drop/coma Intravascular hemolysis -- (g) Hemoglobinemia -- Acute renal failure Yes (q) Hypovolemia -- Oliguria/anuria -- Hematuria -- Hemoglobinuria -- Albuminuria -- Myoglobinuria -- Acute tubular Yes (q) necrosis (ATN) Rhabdomyolysis -- Elevated serum -- amylase levels Chemical pneumonitis No Aspiration pneumonia No Multiple organ Yes dysfunction syndrome Whole blood copper 24 mg/L concentration (a) Blue gastric content. (b) Greenish blue coloration. (c) Slightly elevated hepatic enzymes. (d) Sub-massive hepatic necrosis (revealed by macroscopic and histopathological examination). (e) Slightly elevated bilirubin. (f) Platelets within normal values; no other coagulation tests conducted (e.g., prothrombin time). (g) Multiple ecchymotic lesions (disperse). (h) Elevated C-reactive protein value; normal whilte blood cells value. (i) Edematous viscera. (j) Blood oxygen saturation level 90% (justified by chronic obstructive pulmonary disease); arterial blood gases tests not conducted. (k) Arterial blood gases tests not conducted. (l) Unspecified in medical record. (m) May be covered up by anemia. (n) Urea within normal values; elevated creatinine value. (o) Sub-capsular hemorrhagic foci. (p) No urine tests conducted. (q) Indicated by histological examination. (r) Creatine phospokinase within normal values. (s) No measurement available.
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|Author:||Nastoulis, E.; Karakasi, M.-V.; Couvaris, C.M.; Kapetanakis, S.; Fiska, A.; Pavlidis, P.|
|Publication:||Forensic Science Review|
|Date:||Jan 1, 2017|
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