Clinical and pathological profile of paraquat poisoning cases - A cross-sectional study in Odisha, India

Introduction    

Agriculture is the primary occupation of the people of Odisha with majority of population involved in it. This leads to wide and rampant use of chemical pesticides and herbicides which are easily available in the market. Paraquat (PQ) is N, N’-dimethyl-4, 4′-bipyridinium dichloride, a synthetic quaternary nitrogenous organic compound.^[1]  Its oxidative reactions were known and used in various chemical reactions. The herbicidal properties were not recognized until 1955 and then marketed in early 1962 under the name ‘Gramoxone’, and is today amongst the most commonly used herbicides.^[2] It is a broad spectrum nonselective herbicide which acts on contact, destroys the unwanted green plants by the formation of superoxide anion during photosynthesis.^[3] Paraquat dichloride of 24% SL strength is registered in India with the Central Insecticide Board and Registration Committee (CIBRC).^[4] Paraquat is a pungent corrosive liquid available in market commonly as ‘All Quit’, ‘Finish’, ‘Gramex’, ‘Gramo’, ‘Gramoxone’, etc. in India.^[5] Ingestion of PQ irrespective of the quantity could be fatal with life-threatening effects on the gastrointestinal (GI) tract, kidney, liver, lungs and other organs.^[6] Death is usually associated with respiratory insufficiency due to an oxidative insult to the Type-II alveolar epithelium with subsequent fibrosis.^[7] There are no specific antidotes and none of the current treatments have proven successful in acute fulminant PQ poisoning.^[8] Several studies have been done on PQ poisoning globally.^[9], ^[10], ^[11], ^[12], ^[13], ^[14] So far original articles with large sample sizes explaining various clinical scenarios along with autopsy findings in India are rare or absent. Literature survey shows in the form of a case report with one or two cases revealing a wide range of initial symptomatic presentation with initial hospitalization and early discharge followed by other complication with various lag times leading to rehospitalization, thus creating a confusing clinical scenario affecting the management and outcome of the patients due to incidence of occasional poisoning. In this study we have tried to analyze the clinic-pathological profile of all the cases of paraquat poisoning presented to AIIMS, Bhubaneswar during the study period along with their specific autopsy findings and histopathological examination.

Materials and Methods

This is an observational study in which the poisoning cases with a history of paraquat ingestion, admitted to the Trauma and Emergency Department of AIIMS, Bhubaneswar from July, 2020 to November, 2020. The clinic-pathological findings observed during the hospital stays were documented in a proper preformed format designed for poisoning cases after a proper written informed consent. All the fatal cases were subjected to postmortem examination which was done in the Department of Forensic Medicine & Toxicology, which are also evaluated.

Results

There were 12 patients with a history of PQ ingestion were admitted during the study period. The diagnosis was based on the history, verification of the ingested herbicide, clinical findings and positive report from the Forensic Science Laboratory. All patients were included in the study. Their characteristics are summarized in the table. Most of the patients were treated symptomatically and used steroids for suppressing the inflammation.

Cause of Death

Respiratory system was the most commonly affected system followed by gastro intestinal tract and kidneys. Respiratory failure and multi-organ failure were the main causes of death. All fatal cases were subjected to postmortem examination and the findings were also tabulated ([Table 1] ).

S.No.

Age (in years)

Gender

Manner

Amount

Time duration between consumption and admission

Organ System Involvement

Outcome

Time duration between consumption and death/ discharge

Cause of death

GI

Liver

Respiratory

Renal

1

28

Male

Suicidal

15 - 30ml

3 days

Yes

Yes

Yes

Yes

Death

27 days

Multi Organ failure

2

22

Male

Suicidal

15 - 30ml

2 days

Yes

Yes

Yes

Yes

Death

17 days

Multi Organ failure

3

18

Male

Suicidal

15 - 30ml

5 days

No

Yes

Yes

Yes

Death

13 days

Respiratory failure

4

22

Female

Suicidal

Around 20 ml

1 day

Yes

No

Yes

Yes

Death

8 days

Respiratory failure

5

20

Female

Suicidal

Unknown diluted with water

18 hrs

No

No

No

No

Discharged

2 days

NA-

6

30

Female

Suicidal

Around 20 ml diluted with cocunut water

2 days

Yes

No

Yes

No

Death

7 days

Respiratory failure

7

41

Male

Suicidal

15 - 20 ml

12 hrs

No

Yes

Yes

Yes

Death

15 days

Multi Organ failure

8

37

Female

Suicidal

Around 15 ml

20 hrs

Yes

No

Yes

Yes

Death

7 days

Respiratory failure

9

42

Male

Suicidal

15 - 20 ml

1 day

Yes

No

Yes

Yes

Death

10 days

Respiratory failure

10

23

Male

Suicidal

Around 15 ml

1 day

Yes

Yes

Yes

Yes

Death

15 days

Multi Organ failure

11

34

Male

Suicidal

Around 30 ml

1 day

Yes

Yes

Yes

Yes

Death

8 days

Respiratory failure

12

29

Female

Suicidal

Around 20 ml

2 days

Yes

Yes

Yes

Yes

Death

10 days

Respiratory failure

Table 1 Brief summary of the cases

Discussion

Majority of the population in Odisha and its bordering districts in Chhattisgarh are dependent on agriculture. Crop failures and family disturbances often drive people to look for poison to commit suicide. Nastaran Eizadi Mood et al. (2013) studied on 42 PQ poisoning cases mostly in male and third decade of life with the mortality rate 47%.^[9] Rukhsana Parvin et al. (2016) reported a case of 15 years old girl who consumed 20 ml of PQ died on the 4^th day even after aggressive treatment.^[10] Hsiao-Hui Chen et al. (2013) reported that corrosive action PQ is greater than the Glyphosate weedicide and systemic toxicity occurred with rapid development of hypoxia, hepatitis, and renal failure in many cases.^[11] Hsieh YW et al. (2013) observed in six pediatric patients with 33.3% mortality.^[12] Ja-Liang Lin et al. (2006) in a randomized control trial observed the mortality rate of the study group (five of 16, 31.3%) was lower than that of the control group (six of seven, 85.7%) with repeated pulse of methylprednisolone and cyclophosphamide with continuous dexamethasone therapy for patients with severe PQ poisoning.^[13] Chen and colleagues successfully treated a case of severe PQ poisoning using repeated pulse therapy of methylprednisolone.^[14] It is observed that one tertiary healthcare Centre in Western Odisha registered more than 90% deaths in PQ poisoning.^[15] PQ is highly toxic to human and has a high case fatality rate due to a lack of specific antidotes.^[14] It is still widely used in many countries in the world because of its low cost and high efficacy.^[16] It has low environmental toxicity due to rapid deactivation upon soil contact.^[17] The routes of poisoning are ingestion and direct contact with the skin.^[18] Direct contact of PQ with skin causes burns and dermatitis.^[19] Contact with the eye may irritate, burn, corneal damage, and scarring.^[20]

Lethality of PQ depends on the quantity ingested. A patient who has ingested a large amount (>40 ml) of PQ, generally presents with multi-organ dysfunction syndrome, pulmonary edema, cardiac, renal, and hepatic failure along with central nervous system involvement with seizure and have a higher chance of death.^[21] Patients, who ingested smaller quantities, presented with predominant involvement of two organs namely kidney and lungs, mortality in these groups also more than 50%.^[22] The lethal dose in humans is approximately 35mg/kg body weight (10ml - 15ml of a 20% solution).^[23] Clinical features depend upon the amount of ingested poison. After ingestion, it causes a burning sensation in the mouth, throat, abdominal pain, nausea, vomiting, and diarrhea. Severe oral ulcers may develop within a few days.^[24] The tongue may be coated and inflamed with ulceration called ‘Paraquat tongue’ which was observed in six of our cases after third days of ingestion. It is poorly absorbed by oral route (about 10 – 30%), around 1% to 5% of an oral dose is absorbed in the intestine.^[25] It is rapidly distributed in most tissues including lung and kidney.^[26] It is rapidly eliminated via the kidney (90% eliminated within 12 to 24 hours).^[27] Once absorbed, it rapidly distributes the tissue such as the liver, kidney, and lungs. After ingestion, the greatest PQ concentration is found in the lungs, and the concentration peak in 5 to 7 hours.^[15] In lungs it causes pulmonary congestion, edema, hemorrhage, diffuse alveolitis, and extensive pulmonary fibrosis. Acute respiratory distress may occur after 24 to 48 hours after ingestion. PQ selectively accumulates in the capillary endothelial and epithelial cells of the lung and causes diffuse alveolitis followed by extensive pulmonary fibrosis in about 3-14 days. Lungs were usually affected in all the fatal cases with features of pulmonary edema and lung fibrosis. After absorption, its accumulation in the liver cause hepatic injury. PQ is eliminated mainly by the kidney and acute kidney failure is a recognized complication of its poisoning, with reports of oliguric and non-oliguric cases. PQ causes renal failure by causing hypovolemia, circulatory failure, septicemia, and direct toxicity. Multiple systems are involved but pulmonary features are predominant and are the usual cause of death. Late referral to the hospital, the severity of poisoning, and involvement of the kidney, liver, and lungs leading to multi-organ failure are the main cause of increased mortality in our study. The mainstay of treatment is supportive. Despite advances in treatment and supportive care, the mortality rate remains more than 90%. A very high case fatality of PQ is due to its inherent toxicity and lack of definitive treatment.

Source of Funding

None.

Conflict of Interest

The authors declare no conflict of interest.