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CASE REPORT Table of Contents  
Ahead of print publication
Fulminant paraquat poisoning leading to spontaneous pneumomediastinum: A rare but catastrophic complication


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

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Date of Submission12-Dec-2021
Date of Decision12-Dec-2021
Date of Acceptance22-Dec-2021
Date of Web Publication25-Jun-2022
 

  Abstract 


Paraquat (PQ) is a liquid herbicide commercially traded under the name “Gramoxone.” Human ingestion is uncommon but often fatal. Toxicity of PQ is mediated by the generation of reactive oxygen species which damages cell membranes. Apart from local corrosive damage to the gastrointestinal system, the lungs, liver, and kidneys bear the maximum damage. Rarely, PQ may present as spontaneous pneumothorax or pneumomediastinum or both. Herein, we present a case of fatal PQ poisoning where the patient developed pneumomediastinum on the 9th day with multiorgan dysfunction leading to his demise on 12th day. We also take this opportunity to briefly describe the pathogenesis of lung toxicity, the clinical manifestations, and various treatment strategies being explored in the different parts of the world, as no specific antidote is available till date.

Keywords: Paraquat, pneumomediastinum, poisoning, pulmonary fibrosis


How to cite this URL:
Aggarwal J, Lamba AS, Gaba S, Gupta M, Jindal M. Fulminant paraquat poisoning leading to spontaneous pneumomediastinum: A rare but catastrophic complication. APIK J Int Med [Epub ahead of print] [cited 2022 Oct 6]. Available from: https://www.ajim.in/preprintarticle.asp?id=348290





  Introduction Top


The problem of pesticide poisoning is rampant in the rural parts of Asia due to the easy availability of a variety of highly hazardous pesticides. Paraquat (PQ) is an herbicide used widely in agricultural communities worldwide. Ingestion of more than 30 mL PQ preparation with a concentration of 20%–24% proves lethal, and even 10 ml may cause significant damage.[1] PQ is1,1-dimethyl-4, 4-bipyridylium dichloride, a yellow salt having ammoniacal odor. It is commercially traded under the name “MILQUAT” (Milquat, Insecticides India Limited, Delhi, India). Toxicity is mediated by the release of highly reactive oxygen species (ROS) in organs having high perfusion and oxygen requirements, chiefly the lungs, kidneys, and liver.[2] PQ ingestion is becoming an important etiology for spontaneous pneumothorax in medical emergencies and critical care units and is now known to develop in about 20% cases but spontaneous pneumomediastinum is rare.[3]


  Case Report Top


A 25-year-old healthy male was brought in with a history of suicidal ingestion of an unknown quantity of PQ 12 h before admission. At presentation, his vital parameters were normal, and he was conscious and oriented. He had oral ulcerations and mucosal erythema and erosions over lips, tongue, and palate. Both lung fields were clear on auscultation and systemic examination was unremarkable. There was no significant past history or any history of addictions. The serial day wise investigations are summarized in [Table 1]. The blood culture was sterile and urinalysis was normal. Abdominal ultrasonography and chest radiograph revealed no abnormality. As is obvious from the table, the patient developed progressive respiratory failure, acute kidney injury, and acute liver injury.
Table 1: Serial laboratory investigations

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Medical management was carried out with 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. Nebulized salbutamol and infusions of dextrose with insulin were administered on the development of hyperkalemia. He complained of progressive difficulty in breathing and required increasing support of supplemental oxygen from day 4 onward. Hemodialysis sessions were conducted for 2 h each on days 9 and 10 of poisoning. On the 9th day of admission, he developed subcutaneous emphysema in the neck and chest area, and pneumomediastinum without pneumothorax was seen on contrast-enhanced computed tomography (CT) scan of the neck and chest [Figure 1]. Esophageal perforation was deemed unlikely as it was not seen on the CT scan and the patient was taking drugs and meals orally. Upper gastrointestinal endoscopy for better visualization could not be done due to poor general condition. Continuation of the medical management alone was advised on review by cardiothoracic surgeon. He was placed on mechanical ventilation due to increasing hypoxia. The patient continued to deteriorate and died on the 12th day of poisoning due to progressive lung fibrosis.
Figure 1: Contrast enhanced computed tomography neck and chest on 9th day of poisoning revealed subcutaneous emphysema, multiple air foci in superior and inferior mediastinum, suggestive of pneumomediastinum, diffuse ground glass haze in bilateral lung fields with interlobular septal thickening in bilateral upper lobes

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Informed consent was obtained from the patient's father after explaining him in his vernacular language.


  Discussion Top


Two mechanisms have been proposed to explain PQ-induced pneumomediastinum and pneumothorax.[3] ROS destroy type I and II pneumocytes which leads to acute lung injury (ALI). Damage to type I pneumocytes impair the effective gas exchange at alveolar level and injury to type II pneumocytes limit the production of surfactant causing increase in surface tension within alveoli leading to pulling of fluid from capillaries to produce edema. PQ induced ALI leads to increased production of chemokines and increased deposition of collagen in the lung which can occur as early as 3 days after ingestion of PQ. Increased deposition of collagen, secondary pulmonary hypertension leads to development of pneumothorax and pneumomediastinum due to increasing alveolar pressures. This is known as “Daisley Barton syndrome” and has been recently highlighted by Chaudhuri et al. in a young male after ingestion of about 50 ml PQ on 2nd day of admission who later succumbed to the illness.[4] Sahoo et al. has reported a similar case of bilateral pneumothorax and pneumomediastinum with diffuse subcutaneous emphysema over the neck and chest.[5]

Zhao et al. described radiological (CT) findings in 146 patients of PQ poisoning. The Ct findings varied depending upon severity and stage of disease; however, the presence of ground-glass opacity, interstitial pulmonary fibrosis, and mediastinal emphysema predicted mortality.[6] Zhou et al. looked for prognostic value of pneumomediastinum following PQ ingestion and found that the early development of pneumomediastinum (within 8 days of poisoning) is a specific predictor of mortality.[7] Pneumomediastinum results most commonly from esophageal erosion and perforation due to the corrosive effect.[7] This necessitates surgical management by thoracotomy. Other postulated mechanisms are increased shear force due to fibrosis leading to leakage of air from the ruptured alveoli, repeated gastric lavage, esophageal damage from severe vomiting, or ventilator-induced airway damage.

There is no specific antidote against PQ poisoning. Initial measures such as gastric lavage, use of adsorbents, anti-oxidants such as Vitamin C and E, and free radical scavengers such as N-acetyl cysteine have been tried. Hemodialysis is reserved for patients who develop acute kidney injury. Liberal oxygen therapy acts as a double-edged sword as higher partial pressure of oxygen has been shown to enhance the oxidation of PQ which increases its toxicity; hence, the use of oxygen therapy is recommended only in the presence of significant hypoxia.[8]

Various studies worldwide have also studied the role of immunosuppressive agents. A Cochrane systematic review of 164 patients with moderate or severe PQ poisoning, illustrated that the mortality was lower in the subset of patients who received glucocorticoids and cyclophosphamide in addition to the conventional management.[9] However, there exists a lacunae regarding the optimal timing of these interventions, although these are usually administered within 24–48 h of hospitalization. Other complications such as aspiration pneumonia, hospital-acquired infections, and sepsis may be observed during the initial phase of alveolitis.

One of the primary causes of morbidity and mortality in these patients is pulmonary fibrosis. Pirfenidone used to treat mild or moderate cases of idiopathic pulmonary fibrosis has shown to be beneficial at tissue metabolic level in rat models.[10] Its role in the treatment of PQ poisoning in humans is yet to be studied. Recently, Imrecoxib, a cyclooxygenase-2 inhibitor has been found to alleviate PQ-induced pulmonary fibrosis through the NF-κB/snail signal pathway in mice model.[11] In a systemic review of preclinical studies, mesenchymal stem cells have shown anti-fibrotic therapeutic effects on lung injury caused by PQ poisoning by reducing oxidative stress and inflammatory cytokine levels.[12]

A protective effect has also been attributed to atorvastatin and heparin in reducing ALI. High doses of atorvastatin attenuate serum levels of malondialdehyde and tissue hydroxyproline.[13] Anticoagulation therapy may benefit the cytokine-mediated hyper-coagulation state.[14] Lung protective strategies of ventilation have been proposed to treat ALI in PQ toxicity, which advocates tidal volumes of 6–8 ml/kg, permissive hypercapnia, and appropriate positive end-expiratory pressure.[15] Further animal experiments and clinical practice are needed to fill the gaps in our existing literature for the optimal management of PQ poisoning.


  Conclusion Top


PQ poisoning has been an emerging concern due to its easy availability, low fatal dose, high mortality, and lack of an effective antidote. Lungs, kidneys, and liver are most severely affected. Pneumothorax and pneumomediastinum are catastrophic complications with high mortality; hence, high index of clinical suspicion is required for timely intervention. Extensive research is required to develop an antidote and an effective treatment to stop organ damage and decrease mortality.

Declaration of patient consent

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

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Sukumar CA, Shanbhag V, Shastry AB. Paraquat: The poison potion. Indian J Crit Care Med 2019;23:S263-6.  Back to cited text no. 1
    
2.
Sharma DS, Prajapati AM, Shah DM. Review of a case of paraquat poisoning in a tertiary care rural-based ICU. Indian J Crit Care Med 2019;23:284-6.  Back to cited text no. 2
    
3.
James N, Bakshi R, Rudresh SS, Kaushik K, Ghumaan KS, Pannu AK. Pneumoperitoneum from pneumomediastinum in paraquat poisoning. Trop Doct 2021;51:241-2.  Back to cited text no. 3
    
4.
Chaudhuri S, Sagar MS, Ravindranath S, Reddy V. Paraquat poisoning presenting as the “Daisley Barton syndrome”. Indian J Respir Care 2020;9:110-2.  Back to cited text no. 4
  [Full text]  
5.
Sahoo D, Kar N, Devi S, Dey A, Das DS. A case of paraquat poisoning presenting with spontaneous pneumothorax and pneumomediastinum. Cureus 2020;12:e11943.  Back to cited text no. 5
    
6.
Zhao Y, Tian ZG, Xu T, Gao FH, Guo YY, Wang GJ, et al. CT manifestations and prognosis of acute paraquat induced lung injury. Chin J Ind Hyg Occup Dis 2020;38:140-4.  Back to cited text no. 6
    
7.
Zhou CY, Kang X, Li CB, Li XH, Liu Y, Wang Z, et al. Pneumomediastinum predicts early mortality in acute paraquat poisoning. Clin Toxicol (Phila) 2015;53:551-6.  Back to cited text no. 7
    
8.
Lin XH, Pan HY, Cheng FJ, Huang KC, Li CJ, Chen CC, et al. Association between liberal oxygen therapy and mortality in patients with paraquat poisoning: A multi-center retrospective cohort study. PLoS One 2021;16:e0245363.  Back to cited text no. 8
    
9.
Li LR, Sydenham E, Chaudhary B, Beecher D, You C. Glucocorticoid with cyclophosphamide for paraquat-induced lung fibrosis. Cochrane Database of Systematic Reviews 2014, Issue 8. Art. No.: CD008084. DOI: 10.1002/14651858.CD008084.pub4. Accessed 02 March 2022.  Back to cited text no. 9
    
10.
Ma J, Sun F, Chen B, Tu X, Peng X, Wen C, et al. Tissue metabolic changes for effects of pirfenidone in rats of acute paraquat poisoning by GC-MS. Toxicol Ind Health 2017;33:887-900.  Back to cited text no. 10
    
11.
Jin H. Imrecoxib inhibits paraquat-induced pulmonary fibrosis through the NF-κB/snail signaling pathway. Comput Math Methods Med 2020;2020:6374014.  Back to cited text no. 11
    
12.
He F, Zhou A, Feng S, Li Y, Liu T. Mesenchymal stem cell therapy for paraquat poisoning: A systematic review and meta-analysis of preclinical studies. PLoS One 2018;13:e0194748.  Back to cited text no. 12
    
13.
Khodayar MJ, Kiani M, Hemmati AA, Rezaie A, Zerafatfard MR, Rashidi Nooshabadi MR, et al. The preventive effect of atorvastatin on paraquat-induced pulmonary fibrosis in the rats. Adv Pharm Bull 2014;4:345-9.  Back to cited text no. 13
    
14.
Montoya-Giraldo MA, Díaz LF, Gómez UE, Quintero J, Zuluaga AF. Use of low-molecular-weight heparin in severe paraquat poisoning: A case report. J Med Case Rep 2020;14:240.  Back to cited text no. 14
    
15.
Lan C, Wang J, Li L, Li H, Li L, Su Q, et al. Effects of different tidal volume ventilation on paraquat-induced acute lung injury in piglets. Med Sci Monit 2015;21:452-8.  Back to cited text no. 15
    

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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/ajim.ajim_127_21



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