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Table of Contents
CASE REPORT
Year : 2022  |  Volume : 8  |  Issue : 1  |  Page : 73-76

Paraquat-induced lung fibrosis and multiorgan failure: A case report from North India


Department of General Medicine, Government Medical College and Hospital, Chandigarh, India

Date of Submission27-May-2021
Date of Acceptance21-Oct-2021
Date of Web Publication30-Jun-2022

Correspondence Address:
Jyoti Aggarwal
Department of General Medicine, Government Medical College and Hospital, Level 4 D Block, Sector 32, Chandigarh - 160 030
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijcfm.ijcfm_38_21

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  Abstract 


Paraquat is a herbicide which is widely used by agricultural communities worldwide. It is extremely toxic for humans and ingestion of as less as 30 mL of 20%–24% concentration is usually lethal. The lack of an effective antidote is a concern due to the fatal outcomes associated with ingestion of paraquat. Herein, we are presenting a case of fatal paraquat poisoning in a young male from a center in India. The clinical course was complicated by liver, renal, and lung injury. We also describe its mechanism of toxicity, clinical features, and newer strategies being tried for treatment.

Keywords: Fibrosis, herbicide, kidneys, lungs, paraquat, poisoning


How to cite this article:
Aggarwal J, Lamba AS, Gaba S, Gupta M. Paraquat-induced lung fibrosis and multiorgan failure: A case report from North India. Indian J Community Fam Med 2022;8:73-6

How to cite this URL:
Aggarwal J, Lamba AS, Gaba S, Gupta M. Paraquat-induced lung fibrosis and multiorgan failure: A case report from North India. Indian J Community Fam Med [serial online] 2022 [cited 2022 Nov 27];8:73-6. Available from: https://www.ijcfm.org/text.asp?2022/8/1/73/349381




  Introduction Top


Ingestion of pesticides with an intent of deliberate self-harm is prevalent in the rural parts of South Asia due to their easy availability and lack of strict regulatory laws. The consumption of organophosphorus compounds, celphos (aluminum phosphide), and paraquat account for majority of the suicide cases.[1] Paraquat (dimethyl bipyridylium dichloride) poisoning is particularly concerning due to its widespread use, low fatal dose, high mortality, and lack of an effective antidote. It is a herbicide and inhibits the growth of a wide variety of weeds on direct contact.[2] The lethal dose has been estimated to be 150 mg/kg of bodyweight. Therefore, the ingestion of more than 30 mL of the commercially available 20%–24% solution is lethal, and lesser quantities can also result in significant damage.[3] Here, we present a case of fulminant paraquat poisoning with discussion regarding pathophysiology, clinical presentation, and various novel treatment strategies.


  Case Report Top


A 25-year-old male was brought to the casualty with a history of ingestion of around 50 mL of paraquat 3 days earlier with suicidal intent. He was previously healthy and had no significant past medical or surgical history. He developed epigastric pain and several episodes of vomiting for which he was admitted to a primary care center where gastric lavage was done 3 h after ingestion. He was managed conservatively for 2 days and kept nil per os. He was referred to our hospital in view of progressive dyspnea and jaundice. At presentation, the patient was icteric and in respiratory distress but well oriented to time, place, and person. He was already on oxygen therapy and any attempt to step down the oxygen support led to worsening of dyspnea with desaturation. His oral mucosa was edematous and ulcerated [Figure 1]. Bilateral fine-end inspiratory crepitations were noted on auscultation. The rest of the systemic examination was unremarkable.
Figure 1: Ulcerations on the tongue

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The important investigations are depicted in [Table 1]. The clinical course was marked by progressive renal, hepatic, and pulmonary dysfunction. The kidney injury was nonoliguric and creatinine rose to 5.5 g/dL. The bilirubin rose to 12 mg/dL and transaminases to 500 IU/L. The blood culture was sterile and he tested negative for viral markers. No abnormality was noted on the ultrasound of the abdomen and urinalysis. The patient was treated with intravenous dexamethasone (8 mg IV TDS), ceftriaxone (1 g IV BD), pantoprazole (40 mg IV OD), Vitamin C (500 mg PO BD), Vitamin E (600 mg PO OD), and intravenous fluids. Gel-containing benzalkonium chloride (antiseptic) and choline salicylate (analgesic) were applied to the oral mucosal lesions. Mild hyperkalemia occurred that was medically managed by the use of nebulized salbutamol and infusions of dextrose with insulin. The hypoxia gradually worsened and oxygen therapy had to be stepped up. Chest radiograph that was done on the fourth day of poisoning showed bilateral haziness and reticulations [Figure 2]. He was placed on nonrebreathing mask and a high-resolution computed tomography scan of the chest was done 2 days later [Figure 3], which revealed changes consistent with pneumonitis. In view of respiratory failure, rapid sequence intubation was performed, and mechanical ventilation was instituted. He died on the tenth day of poisoning due to severe acute respiratory distress syndrome (ARDS) and progressive multiple organ dysfunction syndrome. Due to the clear-cut chronological history, clinical features and investigations, other differential diagnoses such as sepsis, viral pneumonia, and acute interstitial pneumonia were not considered.
Table 1: Serial laboratory investigations and clinical observations

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Figure 2: Chest radiograph showing diffuse confluent areas of ground-glass haziness and interspersed areas of reticular opacities in bilateral lung fields

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Figure 3: Axial section of high-resolution computed tomography scan of the chest at the level of lower lobes showing bilateral areas of ground-glass attenuation (red arrows), interlobular septal thickening (blue arrow heads), and consolidation (yellow arrows)

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  Discussion Top


Paraquat toxicity is caused by the generation of superoxide radicals and other highly reactive oxygen species that lead to exhaustion of reduced nicotinamide adenine dinucleotide phosphate and subsequent damage to body cells through lipid peroxidation.[4] The organs most commonly affected are those with high perfusion and oxygen requirement, chiefly the lungs, kidneys, and liver.[5] Paraquat is preferentially concentrated to more than ten times the plasma value in the lung parenchyma by uptake through the alveolar epithelium by the activity of polyamine transport system. Damage to lungs occurs in two phases. First, the destructive phase which manifests as swelling and fragmentation of the alveolar epithelium, and second, the proliferative phase which is characterized by alveolar edema and appearance of an acute inflammatory exudate. This can progress to pulmonary fibrosis.

The clinical course can be classified into mild, moderate to severe and acute fulminant.[2] The manifestations depend on the amount ingested.[2] In the mild form, patients experience only gastrointestinal discomfort and recover completely, while the severe form shows multi-organ involvement and relentlessly progressive lung fibrosis, culminating in death within 2–3 weeks of poisoning. Death in fulminant poisoning occurs within a few hours to days. Serum and urine paraquat levels can be measured to confirm diagnosis when in doubt and higher levels are associated with increased mortality. These tests are not essential and have no role in guiding the management.

A study comprising of 14 fatal cases of paraquat poisoning from South India by Kanchan et al. in 2015 reported a survival duration ranging from 10 h to 25 days after ingestion.[6] Acute kidney injury occurred in 10 patients, multi-organ failure in five, ARDS in six, acute liver failure in three, and nosocomial pneumonia in one patient. Im et al. described radiological findings in 42 patients of paraquat ingestion. Twenty-six manifested diffuse consolidation; 15 developed pneumomediastinum with or without pneumothorax, and eight exhibited cardiomegaly with superior mediastinal widening.[7]

Nonavailability of a specific antidote makes supportive management the current mainstay of treatment of paraquat poisoning. Initial measures include gastric lavage and use of adsorbents such as activated charcoal and Fuller's earth within 1 h of ingestion to reduce the absorption.[5] Possible role of antioxidants such as Vitamin C and E and free radical scavengers such as N-acetyl cysteine has also been studied with unconvincing results. The data are available from animal studies or uncontrolled human studies with very small sample sizes. Hemoperfusion is reserved for patients who develop acute kidney injury and, if done within the first 4 h of ingestion, is known to decrease the systemic levels of paraquat.[8] Oxygen therapy acts as a double-edged sword as higher partial pressure of oxygen has been shown to enhance the oxidation of paraquat which increases its toxicity; hence, the use of oxygen therapy is recommended only in the presence of significant hypoxia.[9]

Various studies worldwide have also studied the role of immunosuppressive agents. In a Cochrane systematic review of three randomized controlled trials with a total of 164 patients of moderate or severe paraquat poisoning, the mortality was lower in the subset of patients who received glucocorticoids and cyclophosphamide in addition to the conventional management.[10] Pirfenidone, an antifibrotic drug currently approved for the treatment of idiopathic pulmonary fibrosis, has also been seen to reduce the production of reactive oxygen species; however, its role in the treatment of poisoning in humans is yet to be investigated.[11] Resveratrol, an antioxidant that is currently being explored for its anti-aging and anti-cancer properties, has been shown to reduce paraquat-induced damage to hepatocytes in rats by depleting the excess free radicals generated.[12]

A systematic review studying the use of immunosuppressive pulse therapy in the treatment of paraquat poisoning which included 7 trials enrolling 426 patients over a period of 23 years concluded a 21.7% reduction in mortality when patients were treated with immunosuppressive pulse therapy. However, patients with hypoxia did not achieve remission during hospitalization suggesting that methylprednisolone and cyclophosphamide might have little effect on hypoxia caused by early acute inflammation.[13]

Another meta-analysis evaluating the efficacy of immunosuppressive therapy in the management of lung injury due to paraquat poisoning included 12 studies between 1980 and 2006, suggested that immunosuppressive therapy with glucocorticoids and cyclophosphamide is efficacious in the management of lung injury in patients with severe paraquat poisoning and is likely to decrease the mortality in this group of patients.[14]

The use of paraquat as a herbicide is common in rural India. Intake of paraquat with suicidal intent carries with it a high risk of morbidity and mortality even when consumed in small amount due to its low lethal dose. Primary health care centers in India are mostly ill-equipped to manage paraquat poisoning cases as they rapidly progress to respiratory and multi organ failure. Such patients often have delayed contact with a tertiary health care facility leading to high mortality rates. The absence of a specific antidote makes its management even more challenging as the available supportive therapies have no definitive mortality benefit. In many countries (Sri Lanka and South Korea), paraquat has been banned which has led to reduction in pesticide-associated mortality rates.[15]


  Conclusion Top


Suicidal poisoning with herbicides is a common yet neglected cause of mortality in South Asia. This case report highlights the clinical features and outcomes following paraquat poisoning. It also outlines the various treatment strategies that have been devised in the management of paraquat poisoning and are under research currently. We hope that this report will help clinicians in the prompt management of paraquat poisoning. Lungs, kidneys, and liver are the most severely affected organs. Research is underway to develop the treatments to halt organ damage with little success so far.

Declaration of patient consent

The authors certify that they have obtained the appropriate patient consent form. In the form, the patients' relative (father) has given consent for patient's images and other clinical information to be reported in the journal. The relative understands that the patients' name and initials will not be published, and due efforts will be made to conceal the identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Dawson AH, Eddleston M, Senarathna L, Mohamed F, Gawarammana I, Bowe SJ, et al. Acute human lethal toxicity of agricultural pesticides: A prospective cohort study. PLoS Med 2010;7:e1000357.  Back to cited text no. 1
    
2.
Vale JA, Meredith TJ, Buckley BM. Paraquat poisoning: Clinical features and immediate general management. Hum Toxicol 1987;6:41-7.  Back to cited text no. 2
    
3.
Wilks MF, Tomenson JA, Fernando R, Ariyananda PL, Berry DJ, Buckley NA, et al. Formulation changes and time trends in outcome following paraquat ingestion in Sri Lanka. Clin Toxicol (Phila) 2011;49:21-8.  Back to cited text no. 3
    
4.
Suntres ZE. Role of antioxidants in paraquat toxicity. Toxicology 2002;180:65-77.  Back to cited text no. 4
    
5.
Gawarammana IB, Buckley NA. Medical management of paraquat ingestion. Br J Clin Pharmacol 2011;72:745-57.  Back to cited text no. 5
    
6.
Kanchan T, Bakkannavar SM, Acharya PR. Paraquat poisoning: Analysis of an uncommon cause of fatal poisoning from Manipal, South India. Toxicol Int 2015;22:30-4.  Back to cited text no. 6
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7.
Im JG, Lee KS, Han MC, Kim SJ, Kim IO. Paraquat poisoning: Findings on chest radiography and CT in 42 patients. AJR Am J Roentgenol 1991;157:697-701.  Back to cited text no. 7
    
8.
Hampson EC, Pond SM. Failure of haemoperfusion and haemodialysis to prevent death in paraquat poisoning. A retrospective review of 42 patients. Med Toxicol Adverse Drug Exp 1988;3:64-71.  Back to cited text no. 8
    
9.
Hoet PH, Demedts M, Nemery B. Effects of oxygen pressure and medium volume on the toxicity of paraquat in rat and human type II pneumocytes. Hum Exp Toxicol 1997;16:305-10.  Back to cited text no. 9
    
10.
Li LR, Sydenham E, Chaudhary B, You C. Glucocorticoid with cyclophosphamide for paraquat-induced lung fibrosis. Cochrane Database Syst Rev 2010;6:1465-858.  Back to cited text no. 10
    
11.
Seifirad S, Keshavarz A, Taslimi S, Aran S, Abbasi H, Ghaffari A. Effect of pirfenidone on pulmonary fibrosis due to paraquat poisoning in rats. Clin Toxicol (Phila) 2012;50:754-8.  Back to cited text no. 11
    
12.
Elgizawy HA, Ali AA, Hussein MA. Resveratrol: Isolation, and its nanostructured lipid carriers, inhibits cell proliferation, induces cell apoptosis in certain human cell lines carcinoma and exerts protective effect against paraquat-induced hepatotoxicity. J Med Food 2021;24:89-100.  Back to cited text no. 12
    
13.
Xu YG, Lu YQ. Systematic review and meta-analysis of the efficacy and safety of immunosuppressive pulse therapy in the treatment of paraquat poisoning. J Zhejiang Univ Sci B 2019;20:588-97.  Back to cited text no. 13
    
14.
Agarwal R, Srinivas R, Aggarwal AN, Gupta D. Immunosuppressive therapy in lung injury due to paraquat poisoning: A meta-analysis. Singapore Med J 2007;48:1000-5.  Back to cited text no. 14
    
15.
Ravichandran R, Amalnath D, Shaha KK, Srinivas BH. Paraquat poisoning: A retrospective study of 55 patients from a tertiary care center in southern India. Indian J Crit Care Med 2020;24:155-9.  Back to cited text no. 15
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

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