|Year : 2015 | Volume
| Issue : 3 | Page : 370-374
Paraquat: A fatal poison
J Shashibhushan, K Venugopal, Mudegoudara Lingaraja, CP Patanjali, C Suresh, Vishwanath Huggi
Department of General Medicine, Vijayanagara Institute of Medical Sciences, Bellary, Karnataka, India
|Date of Web Publication||15-May-2015|
Department of General Medicine, Vijayanagara Institute of Medical Sciences, Bellary - 583 104, Karnataka
Source of Support: None, Conflict of Interest: None
Paraquat (1, 1'-dimethyl-4, 4'-dipyridylium) is a bipyridilium herbicide used widely in our country and is a highly toxic compound. This compound is very notorious to cause rapid development of renal, liver, and respiratory failure with very high mortality due to lack of specific antidote and dearth of high-quality evidence-based treatment. Respiratory system involvement is the most common cause of death in these people. We hereby report a fatal case of a 30-year-old male with a history of paraquat consumption. The patient developed oliguric renal failure, deterioration of liver function, and acute respiratory distress syndrome over next few days. Different treatment modalities were tried to manage patient's condition. In this case, none of the strategies worked well, and death ensued due to multi-organ dysfunction syndrome.
Keywords: Acute respiratory distress syndrome, cyclophosphamide, herbicide, methylprednisolone, N-acetyl cysteine
|How to cite this article:|
Shashibhushan J, Venugopal K, Lingaraja M, Patanjali C P, Suresh C, Huggi V. Paraquat: A fatal poison. Med J DY Patil Univ 2015;8:370-4
| Introduction|| |
Paraquat is a pungent smelling, bright green corrosive liquid. It is the second highest-selling weed killer globally and is available as 20% solution that needs to be diluted before agricultural use.  Usually, adult cases of intoxication are suicidal. The acute systemic effects are pulmonary edema, convulsions, cardiac, renal, and hepatic failure.  The lethal dose (LD50) in humans is approximately 35 mg/kg (10-15 ml of a 20% solution). This paper reports a case of fulminant paraquat poisoning and detailed review of the intoxication, histopathology and management.
| Case Report|| |
A 30-year-old male presented to the emergency department with alleged history of consumption of 600 ml of 24% w/w Gramoxone® (Paraquat, Syngenta India Limited, Plot No B-155/1, Bharuch, Gujarat, India) 3 days prior to admission. After ingestion, patient was taken to a nearby hospital; from there, patient was referred to our hospital. At the time of admission, patient had six episodes of vomiting. On examination, he was conscious, oriented; his vitals were normal and systemic examination revealed bilateral basal crepitation and diffused abdominal tenderness. Laboratory investigations showed raised blood urea, serum creatinine, and raised total bilirubin. Complete blood count, X-ray chest, ultrasonography abdomen, urine routine, and electrolytes were normal. Subsequent day's investigations are given in [Table 1].
Gastric lavage was done and started treatment with injection piperacillin-tazobactam 4.5 g TID, injection methylprednisolone 1 g OD for 3 days, N-acetyl cysteine (NAC) 600 mg TID, and other symptomatic treatment. On day-2, patient underwent hemodialysis for raised creatinine. On day-3, patient became restless and irritable, his saturation was 48% at room air, and patient was administered oxygen at 6 L/min through Hudson's mask. His saturation did not improve, in the view of falling saturation; he was intubated and put on synchronized intermittent mandatory ventilation. On day-5, his condition deteriorated and became hypotensive (systolic blood pressure -90 mmHg) with features of acute respiratory distress syndrome. His condition did not improve despite session of hemodialysis and ventilator support and patient expired on day-6. His body was autopsied; esophageal and gastric erosions were noted. Lung, liver, and kidney were biopsied, and histopathological findings are suggestive of diffuse alveolar hemorrhage, loss of centrilobular hepatocytes, and congestion of the renal parenchyma [Table 2]. Determination of the poison was not done in any organ.
| Discussion|| |
Paraquat is a contact herbicide, first synthesized in 1882 as a redox indicator. Its herbicidal property was recognized in the 1950s. It is produced commercially as a brownish concentrated liquid of the dichloride salt in 20% strength under the trade name of "Gramoxone®" and for horticultural use as brown granules called "Weedol®" (Syngenta India Limited, Plot No B-155/1, Bharuch, Gujarat, India) about 5% concentration. 
The most common route of poisoning is the ingestion. Dermal exposure also has been reported to result in severe paraquat poisoning, especially in the presence of preexisting skin lesions.  Inhalation of sprayed paraquat solution usually causes local irritation but rarely results in important systemic absorption. After ingestion, the gastrointestinal tract absorbs <20% of paraquat. The presence of ulcerated mucosa or an empty stomach increases the fraction of paraquat absorbed. Blood levels peak within a few hours after ingestion.
Paraquat is not actively metabolized in the body, and more than 90% is excreted unchanged by the kidneys. After absorption, paraquat is distributed to highly perfused organs such as the lungs, kidneys, liver, and muscles, and remains partly in the intravascular space.
Paraquat concentration in the lung parenchyma is very high because of active, energy-dependent uptake of paraquat by type 1 and type 2 alveolar epithelium, via the polyamine uptake pathway. 
Paraquat, during "redox-cycling-process" leads to the formation of superoxide anions from which more toxic reactive oxygen species (ROS) such as hydrogen peroxide and hydroxyl radicle are formed in the presence of NADPH and cytochrome P450 reductase.  If the protective mechanisms such as catalase and glutathione peroxidase are overwhelmed, the resultant oxidative stress will cause cellular damage. The hydroxyl radical, which is formed in the presence of iron, is a more potent oxidant and can induce lipid peroxidation which causes cell membrane damage and cell death[Figure 1],[Figure 2] and [Figure 3]. 
|Figure 1: Histopathology of lung (H and E, ×10). (a) Interstitial and intra-alveolar fi brin rich oedema. (b) Diffuse infiltration of interstitium and alveoli with lymphocytes and eosinophil. (c) Proliferation of type-2 pneumocytes. (d) Distended alveoli|
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|Figure 2: Arrow showing focal loss of centrilobular hepatocytes (H and E, ×20)|
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The clinical manifestations range from local irritation to multiple-organ failure and death. Systemic manifestations depend on the amount ingested, and patients can be classified into 3 categories [Table 3]. 
The diagnosis is usually from the accurate history of exposure. This can be difficult in children and case of homicide.  The urine dithionite test quickly confirms the presence of paraquat in urine. A paraquat blood level of >1.6 μg/mL 12 h after ingestion is universally lethal. 
Initial management focuses on prevention of further absorption and gastrointestinal decontamination. Adsorbents like activated charcoal (1-2 g/kg) and Fuller's earth (1-2 g/kg); given with a cathartic such as 70% sorbitol should be given as soon as possible. Hemoperfusion has been shown to decrease paraquat levels in humans if initiated within 4 h of ingestion, but there are insufficient data to support any survival benefit in humans.  There is no specific antidote. Paraquat is not removed by dialysis. Hemodialysis is used only as a supportive treatment for patients who develop kidney failure.  In a study by Afzali et al., the therapeutic effect has been reported with high dose cyclophosphamide and glucocorticoid where survival was about 75%.  This was further supported by Agarwal et al. , Since there is a lack of clear evidence-based therapy, different approaches have been tried for supportive management. Although high doses of cyclophosphamide and Dexamethasone treatments, including intravenous cyclophosphamide (5 mg/kg/d) and dexamethasone (24 mg/d) for 14 days have been correlated with 75% survival rate after poisoning,  a subsequent study  did not demonstrate the usefulness of this approach. A report  demonstrated that pulse therapy with cyclophosphamide and methyl prednisolone (MP) might be effective in preventing respiratory failure and reducing mortality in patients with moderate to severe poisoning. Pulse therapy with MP is known as a strong anti-inflammatory treatment in clinical practice,  suppressing ROS production by neutrophils and macrophages, and in the arachidonic acid cascade. 
It has been shown that desferrioxamine can exert its protective effects not only by iron chelating but also by blocking the uptake of paraquat by the alveolar type II cells.  Vitamin E (a-tocopherol) exerts its antioxidant effects by scavenging free radicals and stabilizing membranes containing polyunsaturated fatty acids,  which may prevent the cytotoxic effects of paraquat.
N-acetyl cysteine has also been used with success in massive paraquat poisoning.  It is an excellent source of sulfhydryl groups. NAC is indeed converted in the body into cysteine, the rate-limiting amino acid for glutathione synthesis, promoting detoxification, and acting directly as a free radical scavenger.  In addition, it delays inflammation. 
Other general supportive care includes fluid and electrolyte management and pain control. Oxygen supplementation should be avoided if possible because it can potentiate paraquat-induced lung injury. Oxygen is indicated when patient develops hypoxia. Limitations in the management are, not used all the treatment plans discussed above. Since there is no evidence-based standard protocol, and lack of specific antidote makes the management of paraquat poisoning difficult.
| Conclusion|| |
The lack of a specific antidote makes the treatment of parquet poisoning challenging. As there is no concrete proof regarding the efficacy of various modalities of treatment, further light needs to be thrown on this issue. This case report reiterates the need for early recognition and treatment of parquet poisoning which is a harbinger for multi-organ failure and even death, in severe cases.
| Acknowledgments|| |
We would like to thank Dr. Gadwalkar Srikant R, Professor and HOD, Department of Medicine for his support. The authors would like to thank Dr. Yogiraj, Professor of Forensic Medicine. Dr. Shanti, professor of pathology and Dr. Chandrashekar, Assistant Professor, Department of Pathology, Vims-Bellary, for his assistance in histopathological reporting and selecting appropriate images of the autopsied specimen of this patient.
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[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3]
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