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Paraquat – boon or bane? A retrospective study of paraquat poisoning and outcomes in a tertiary care center in South India


1 Department of Medicine, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, Karnataka, India
2 Indian Institute of Public Health, Shillong, Meghalaya, India

Date of Submission30-Oct-2021
Date of Decision30-Dec-2021
Date of Acceptance02-Mar-2022

Correspondence Address:
Kusugodlu Ramamoorthi,
Department of Medicine, Kasturba Medical College, Manipal Academy of Higher Education, Manipal - 576 104, Karnataka
India
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/mjdrdypu.mjdrdypu_859_21

  Abstract 


Setting: Paraquat is a highly toxic, herbicide, extensively used in various parts of India. There is no effective treatment for paraquat poison and carries a very high mortality. In India, this compound can be misused for harmful purposes. Objective: A retrospective time-bound descriptive study of paraquat-consumed patients was conducted at Kasturba Hospital, Manipal, from January 1, 2014 to January 31, 2016. Materials and Methods: All the data were analyzed using the SPSS version 16. All the categorical data are expressed in terms of frequency and percentage. Continuous normal variables were expressed in terms of mean ± standard deviation, and skewed variables were expressed in terms of median and quartiles. Chi-square test was used to find the association between the categorical independent variables across the outcome in survivors, nonsurvivors, and those patients who were discharged from the hospital against medical advice. Similarly, Fisher's exact test was performed for those variables, for which 20% of the expected cell count was <5%. Kruskal–Wallis test was used to compare the relationship between the continuous skewed variables across the outcome. Results: A total of 55 paraquat-consumed patients were admitted, out of which 67.27% (n = 37) of patients were men. Only 32.7% (n = 18) of patients were farmers. Oral ulcers were seen in 43.6% (n = 24) of patients. About 65.5% (n = 36) of patients underwent hemoperfusion, 27.3% (n = 15) of patients survived, 47.3% (n = 26) of patients expired, and 25.5% (n = 14) of patients were discharged against medical advice in a critical condition. The presence of respiratory failure, hypotension, need for ventilator supportive therapy, the elevation of levels of blood urea, serum creatinine, and liver enzymes AST and ALT levels were statistically significant in three groups (P < 0.001). Conclusion: Paraquat poisoning is highly fatal. Treatment is expensive and available only in tertiary care hospitals in India. Central and state governments should ensure that it should not be readily accessible to ordinary people and it should be banned progressively.

Keywords: Hemoperfusion, herbicide, multi-organ failure, paraquat, pesticide



How to cite this URL:
Ramamoorthi K, Acharya V, Lewis MG. Paraquat – boon or bane? A retrospective study of paraquat poisoning and outcomes in a tertiary care center in South India. Med J DY Patil Vidyapeeth [Epub ahead of print] [cited 2022 Dec 1]. Available from: https://www.mjdrdypv.org/preprintarticle.asp?id=339952




  Introduction Top


Paraquat is a nonselective, highly toxic, herbicide used in many countries as a weed killer including India.[1] This herbicide was first discovered in 1882 and first entered the market in 1962.[2] This weed killer when consumed, causes various organ failure, respiratory distress, life-threatening acidosis, kidney injury, shock, ulcerations of the gastrointestinal tract, and liver dysfunction, leading to the death of patients.[1],[2],[3] Various treatment options such as hemoperfusion, antioxidant agents, and cytotoxic drugs are being tried. However, the mortality rate is very high in all published articles.[4] These cases are being treated in well-equipped tertiary care centers such as medical college hospitals and other hospitals where highly skilled specialized care is available.[5] Till now, many paraquat poisoning cases were reported from various parts of India.[1],[2],[3],[4],[5],[6],[7],[8],[9],[10],[11],[12],[13],[14]


  Materials and Methods Top


A time-bound retrospective descriptive study was conducted in Kasturba Medical Hospital, Manipal, from January 1, 2014 to January 31, 2016 based on patients' case records, after getting the approval from an Ethical Committee of Kasturba Hospital. No personal identification data were collected, and all other information was kept confidential.

Inclusion criteria

We included the patients above 18 years of age, with alleged consumption of paraquat, admitted in emergency medical intensive care wards.

Exclusion criteria

Patients with a history of consumption of other poisons were excluded from the study.

Procedure

All data were collected manually from the patients' hospital records. The patients' information such as age, gender, occupation, time since ingestion of paraquat to hospital admission, the quantity of poison consumed, symptoms, laboratory reports on the date of admission, treatment received, and outcomes were collected.

Statistical analysis

All the data were analyzed using the SPSS version 16 (Chicago II, USA). All the categorical data were expressed in terms of frequency and percentage. Continuous normal variables were expressed in terms of mean ± standard deviation, and skewed variables were expressed in terms of median and quartiles. Chi-square test was used to find the association between the categorical independent variables across the outcome in survivors, non-survivors, and those patients who were discharged from the hospital against medical advice. Similarly, Fisher's exact test was performed for those variables, for which 20% of the expected cell count was <5%. Kruskal–Wallis test was used to compare the relationship between the continuous skewed variables across the outcome.


  Results Top


A total of 55 patients were included in this study, out of which 37 were males, and 18 were females. The age range of the study patients ranged from 18 to 45 years. The mean age of males was 26.86 ± 6.39, and that of females was 25.56 ± 7.28. Out of the total patients, 18 patients (32.7%) were agriculturists, 10 (18.2%) were housewives, 9 (16.4%) were laborers, 9 (16.4%) were students, 2 (3.6%) were college lecturers, and 1 (1.8%) were each a shopkeeper, painter, driver, welder, supervisor, businessman, and a priest. Oral ulcers were the most common presenting complaint seen among 24 (43.6%) patients. This was followed by vomiting among 17 (30.9%), retrosternal pain among 11 (20%) patients, odynophagia among 6 (10.9%), and breathlessness among 11 (20.4%). One patient (1.8%) was admitted to the hospital within 4 h of consumption of paraquat. Twenty-one (38%) patients were admitted between 4 and 12 h, 11 (19.91%) patients between 12 and 24 h, 6 (10.86%) between 24 and 48 h, and 16 (28.96%) after 48 h of paraquat consumption. The renal function test and liver function tests report at the time of admission are shown [Table 1]. The majority of the patients were found to have abnormal values of serum creatinine, aspartate aminotransferase (AST), and alanine transaminase (ALT).
Table 1: Renal function and liver function tests of the patients reported at the time of admission

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Out of the total 55 patients, urine paraquat test was done only in 40 (72.7%) patients and was positive among 25 (62.5%) patients. Thirty-one (55.4%) patients had respiratory failure and 28 (50.9%) patients received ventilator support; Twenty-four (43.6%) patients had hypotension on inotropic support. Twenty-seven (49.1%) received antioxidant therapy, 36 (65.5%) patients received hemoperfusion, and 17 (30.9%) received immunosuppressive therapy. Fifteen (27.3%) patients survived, 26 (47.3%) patients expired, and 14 (25.5%) patients were discharged against medical advice in a very critical condition.

The clinical symptoms such as vomiting, retrosternal pain, odynophagia, breathlessness at the time of admission, and the signs such as oral ulcers, respiratory failure, hypotension, positive urine paraquat test, ventilator support, and different modes of treatment were compared with the outcomes. An alpha level of 0.05 was considered statistically significant [Table 2]. Chi-square test revealed that the presence of hypotension, respiratory failure, and the need for supportive ventilator therapy were significantly associated with the outcomes (P < 0.001). Furthermore, Fisher's exact test revealed that the presence of vomiting (P = 0.04) and immunosuppressive therapy (P = 0.03) have statistical significance as shown in [Table 2].
Table 2: Signs, symptoms and different modes of treatment among the patients across different groups of patients

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When the lab investigation parameters were compared between the three groups at the time of admission, we observed that Blood urea, serum creatinine, AST, and ALT levels were high in patients' groups, who expired and were discharged against advice than those who survived (P < 0.001) [Table 3]”. Kruskal–Wallis test showed that there was a statistically significant difference in serum creatinine, blood urea, ALT, and AST between the survived, discharged against advice, and expired (P < 0.001).
Table 3: Details of lab investigation parameters with the outcome at the level of admission to the hospital

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  Discussion Top


Paraquat is a very fast-acting, nonselective herbicide, widely used in India because of its easy availability and low price.[1],[10] This weed killer undergoes oxidation–reduction cycling, producing superoxide anion, and other highly reactive-free radicles. These may be responsible for the cellular depletion of NADPH leading to mitochondrial damage, lipid peroxidation of cell membranes, and cell death leading to multi-organ failure.[1],[4],[7],[15]

Paraquat is quickly, but only 18% of it gets absorbed by the jejunum in the gastrointestinal tract and does not undergo metabolism.[4],[16],[17] It is rapidly distributed to major organs such as lungs, kidneys, muscles, and liver leading to multiple organ failures.[16],[17] Paraquat toxicity is very severe in the lungs resulting in respiratory distress, leading to a drop in oxygen saturation, requiring mechanical ventilation, because of the destruction of alveolar epithelial cells, and later leading to pulmonary fibrosis in those patients.[2],[3],[17],[18] The majority (90%) of absorbed paraquat is excreted in the urine in an unchanged form within 12–24 h of ingestion.[4],[14],[16] However, after a few hours, renal clearance of paraquat decreases rapidly in severe poisoning due to tubular necrosis. In those patients with severe poisoning, after 1 day of ingestion of the poison, the approximate elimination half-life may exceed up to 96 h. Because of the progressive worsening of renal function, the elimination of paraquat is delayed over many days to weeks.[4],[17] Paraquat is a very corrosive poison, which causes severe inflammation, necrosis, and ulceration of the skin, oral cavity, pharynx, larynx, and esophagus.[1],[6],[14]

There is no specific antidote and no effective treatment for this poison.[2],[4],[19] The present treatments are nonspecific and aimed at preventing secondary pathological pathways such as inflammation in target organs.[4] Several published papers revealed that currently practiced therapies for paraquat poisoning cases are very disappointing.[4],[19],[20],[21] The treatment comprises intensive care unit admission, gastric lavage, and decontamination with activated charcoal and judicious use of oxygen.[1],[2],[4],[14] Since multi-organ dysfunction is due to oxygen-derived free radicles, immunosuppressive therapy and antioxidant agents are being tried. Parenteral methylprednisolone 15 mg/kg/day for consecutive 3 days along with intravenous cyclophosphamide 15 mg/kg/day for 2 consecutive days, followed by injection dexamethasone 4 mg three times a day till recovery or death. Various antioxidants such as Vitamin E, Vitamin C, and n-acetylcysteine are also being used.[4],[6] Hemoperfusion and hemodialysis are used to enhance the elimination of paraquat. However, this treatment is very expensive.[4],[17] In severe cases with multi-organ dysfunction with circulatory failure, advanced life supports such as ventilator therapy, and inotropic supports and hemodialysis are required.[1],[2],[4],[6]

In India, critical care is available only in tertiary care centers such as medical college hospitals and other urban tertiary care hospitals.[5] There are some reports of favorable outcomes if the patient undergoes hemoperfusion within 4 h of consumption of paraquat.[2],[22] However, in most circumstances, patients reach the tertiary care hospital beyond that period either due to delay in transport or late referrals.[8],[10] In our study, only one patient came to the hospital within 4 h and all the patients consumed paraquat intentionally to commit suicide. They would have consumed the poison by impulsive behavior, either due to a brief period of anger or grief, without knowing the very lethal nature of the poison.[23]

About 90.9% (n = 50) of patients in this study are in the young productive age group of 18–35 years. In the other studies from Iran, the majority of patients were in the age group of 15–30 years, which is comparable to our studies.[20],[24],[25] The death of these young people is very catastrophic to the family as well as to society.[20]

In the current study, only 32.7% (n = 18) of patients were farmers, and the majority of patients were of other occupations. This observation reflects that paraquat is very readily available to ordinary people in India. Hence, this can be misused for a harmful purpose.[10] In India, the general public and farmers are not aware of the very lethal nature of paraquat. Dileep Kumar A. D. (2015) in his study revealed the use and hazards of paraquat in the agriculture sector across six states in India.[26] The lethal dose of paraquat is approximately 30 mg/kg body weight, which is equivalent to 10–20 ml of 20% of liquid paraquat. Even 5 ml of paraquat consumption produces enough severe illness.[1],[9],[13],[17],[20] A urine dithionite test is used to confirm the paraquat presence in the urine. The usually light blue color of urine indicates mild poisoning, and the very dark blue color of urine indicates moderate-to-severe poisoning. However, in the presence of renal failure, this test may be a false negative.[5] Previous studies showed that the presence of respiratory failure, severe hepatic failure, metabolic acidosis following the circulatory collapse, the very high plasma concentration of paraquat, and poisoning with suicidal intention lead to very high mortality.[21],[24],[25] In our study also the presence of hypotension, respiratory failure and need for ventilator support, severe hepatic, and renal dysfunction indicate a very grave prognosis (P < 0.001) in paraquat-consumed patients.

In the present study, the symptom vomiting and the treatment with immunosuppressive therapy showed statistical significance (P < 0.05). However, the previous studies showed that early presentation of vomiting is not associated with a bad prognosis.[20] Immunosuppressive therapy is not proved to be effective in the treatment of paraquat poisoning.[4] However, large trials are required to demonstrate the effectiveness of chemotherapy with immunosuppressive drugs.[4]

The mortality rate is very high (47.3%) in our study. However, in previous studies, the mortality has been reported to be ranging from 50% to 90%. In other studies from Korea, the death rate was 62% and 70.7%.[20],[27] In our study, 25.5% of patients were discharged against medical advice in a very critical state after knowing the prognosis. Even though their final fate is not known, we can assume the prognosis, based on the very lethal nature of the poison. Only 27.3% of patients survived in our study which is comparable with another study from Korea, where the survival was reported to be 19%.[27] The European Union, including in Switzerland where the paraquat is manufactured, has entirely banned this herbicide.[28] The United States and China restricted paraquat use. In India, the Kerala state banned paraquat in 2011. However, in other parts of India, this herbicide is easily available and extensively used.[29]


  Conclusions Top


Paraquat is widely used as a herbicide for agricultural purposes, readily available to ordinary people in India, which can be used for harmful purposes. Till now, there is no specific antidote to this poison and the mortality rate is very high. Treatment of this lethal poison is very disappointing and expensive, available only in tertiary care centers. Central and state governments should ensure that it should not be readily accessible to ordinary people and it should be banned progressively.

Limitations

This is a retrospective study based on hospital records of patients. Urine paraquat tests are not done in some patients. Blood paraquat levels are not measured in patients, as this test is not available in our hospital. The sample size is also small as this study is time-bound, and the exact quantity of paraquat consumed by patients is not available in all patients.

Acknowledgment

We are grateful to Medical Superintendent, Kasturba Hospital, Manipal, for permitting us to carry out the study.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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    Tables

  [Table 1], [Table 2], [Table 3]



 

 
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