A Case Report of Acute Paraquat Poisoning

INTRODUCTION: Paraquat (1,1’-dimethyl, 4,4’-bipyridinium dichloride; PQ) is one of the most widely used herbicides, poses a significant risk of mortality. Paraquat can be rapidly absorbed through inhalation, ingestion and damaged skin. The toxic effects of paraquat are at the cellular level, which generate intracellular reactive oxygen species (ROS) through redox cycling and disrupt the mitochondrial electron transport chain, which leads to significant mitochondrial damage and lipid peroxidation. Its bioavailability ranges from 0.3% to 10%. With a large volume of distribution (1.2–1.6 l/kg), it is distributed to all organs, particularly the liver, kidneys and lungs. The mean elimination half-life of paraquat is 84 hours. Paraquat is not metabolized but is reduced to an unstable free radicle, which is then reoxidized to reform a superoxide anion, It is excreted unchanged in the urine. Paraquat poisoning mortality rates ranging from 33.0% to 91.7%, primarily due to multiple organ failure and pulmonary fibrosis.(1–4) CASE REPORT: A 22 year old male, referred from local hospital with history of alleged consumption of paraquat dichloride solution 24% W/V, 30 ml at his residence, a day prior to admission. On the day of ingestion, he had multiple episodes of vomiting (blood tinged), difficulty in swallowing and reduced urine output. There was no remarkable history of cough, abdominal distension. He was primarily treated at local hospital with intravenous fluids, proton pump inhibitors bolus dose and then transferred to the quaternary care center for further treatment. On admission in the ICU, his Glasgow coma score was 15/15, afebrile, mildly tachycardic, mildly tachypneic, blood pressure readings were normal and was maintaining oxygen saturation 94% on room air. On general examination skin turgor, dry tongue, mild jaundice and oral mucosal erosions were noted. Chest was clear on auscultation. Abdominal examination showed unremarkable findings. He had indwelling urinary catheter with small quantity of urine in the urobag Initially resuscitated with intravenous normal saline and proton pump inhibitor therapy. Laboratory assessment revealed leucocytosis, raised serum creatinine levels (8.3 mg%) and impaired liver function parameter. Urine analysis showed protein 1 + with few granular cast with 4 to 6 pus cells. Chest X-ray showed prominence in bronchovascular markings, CT chest was suggestive of subpleural ground glass opacity with minimal pleural effusion. Ultrasound abdomen revealed raised cortical echotexture in bilateral kidneys As history and Clinico-laboratory evaluation was suggestive of Acute paraquat poisoning with early involvement of liver, kidneys, lungs and gastrointestinal mucosa. On the same day, hemodialysis catheter was inserted in right Internal jugular vein and initiated with hemoperfusion with HA 230 cartridge for 4 hrs with ultrafiltration of 1 litre. Initially he was kept nil by mouth as couldn't swallow clear liquids due to painful ulcers, Nasogastric tube was not placed considering the risk of bleeding from oropharyngeal erosions. Eventually on day 3, total parenteral nutrition was started in anticipation with delayed enteral feeding Intravenous Proton pump inhibitor infusion continued for 48 hours, N- acetyl cysteine infusion was continued for 24 hrs. Also administered with IV Cyclophosphamide 500 mg once daily for three days, Methylprednisolone 500 mg once daily for 3 days, Vitamin C 1 gm for 5 days He had persistent nausea and vomiting, was not able to swallow saliva for initial 5--6 days and also developed one episode of melena. Oropharyngeal, gastric ulcer bleed was suspected, although there was no significant drop in hemoglobin. GI endoscopy was deferred in view of erosion of the gastrointestinal tract due to paraquat ingestion. Although patient remained hemodynamically stable except oliguria, was maintaining oxygen saturation with supplemental oxygen 5 lit per minute by mask. After 5–6 days, vomiting reduced, was able to swallow and tolerate clear liquids. Although had increase in trend of liver enzymes for 8--10 days. His interval CT chest showed increase in ground glass opacites. On day 8, patient was shifted to high dependency unit, his oral intake improved and able to tolerate liquids to semisolid food. Sessions of hemodialysis were continued daily for 10 days Gradually his renal and hepatic functions improved, urine output improved, HD catheter and urinary catheter were removed, his oxygen requirement was reduced to 2 litre per minute with nasal prongs, On day 15, he was shifted to wards. He was monitored in the ward for few days, was started on oral diuretics, oral steroids--Wysolone 60 mg once daily and supportive treatment was continued. On day 20, he was discharged to home in stable condition, maintaining oxygen saturation on room air.(5–10) Patient is being followed up in OPD regularly since more than a year post-discharge. Barrium swallow was done one month post-discharge showed no evidence of significant filling defect or narrowing or dilatation. CT Thorax which was done 6 months post-discharge showed Multiple subcentimetric lymph nodes in pretracheal, paratracheal, precarinal, subcarinal and prevascular regions with Multiple resolving ground glass opacities with interstitial septal thickening seen in subpleural locations with Multiple fibrotic strands seen in bilateral lungs and ground glass opacities were reduced in density and number. Spirometry showed mild restriction with obstruction with significant reversibility. Although patient is stable to manage routine work and lifestyle, but has features of lung fibrosis, develops symptoms of dyspnea and dry cough on and off with moderate exertion.(6–13) DISCUSSIONS: Diagnosis of paraquat poisoning is commonly predicated on circumstantial evidence and clinical manifestations. Diagnostic indicators includes the patient's history of paraquat exposure, the presence of empty pesticide containers, suggestive residues, distinctive odours or anomalous colouring. Maximum tissue levels achieved within 6 hours, high concentration in liver, lungs, kidneys, muscle. Its excreted by kidneys by 24 hours, but once kidneys get affected, elimination can exceed 100 hours. Strengh and dose are important, amount > 30 ml with 20% paraquat can be lethal. Paraquat poisoning can manifest as acute and chronic toxicity. The major acute effects can result in both local and systemic manifestations. Local effects include ulceration of the skin, lips, tongue, pharynx, and esophagus. Systemic effects involve multiple organ failure, including liver insufficiency, acute kidney injury, respiratory failure, and convulsions. Acute tubular necrosis suggest significant poisoning and increased risk of mortality. Usually develops diffuse alveolar infiltrates and then progressive fibrosis within 1 to 2 weeks. The severity of paraquat poisoning is classified into three categories: mild, moderate to severe, and fulminant. Mild poisoning is characterized by minor gastrointestinal tract disorders. Moderate-to severe poisoning often leads to acute renal failure, acute hepatitis, acute lung injury and progressive pulmonary fibrosis. Fulminant poisoning results in multiple organ failure and death within a few days. Kidney failure, acute liver dysfunction may resolves within 2–3 weeks. Urine paraquat level can be monitored, urine paraquat (dithionate) positive, carries 40% mortality. Early hemoperfusion (within 4 hrs of ingestion), hemodialysis, immunosuppressant, N-acetylcysteine and vitamin C is the mainstay of treatment. The unavailability of a specific antidote and lack of definitive treatment for paraquat toxicity have led to a high case fatality rate of around 50–90%. Gastric decontamination (activated charcoal) is beneficial in those who present within 1–2 hrs of ingestion. Gastric lavage is contraindicated due to its corrosive nature of paraquat. In a study by Lin et al., pulse therapy with Cyclophosphamide and Methylprednisolone has shown effective in preventing respiratory failure and reducing mortality by 25%Pulse therapy, along with antioxidants such as N-acetyl-cysteine and vitamin C has shown efficacy in preventing ongoing inflammation and pulmonary fibrosis.(14–17) CONCLUSION: Paraquat poisoning causes detrimental effects on multiple system and the lack of a specific treatment makes it challenging. Symptoms of parquat ingestion are usually dose-dependent, The focus should be on preventive measures and in case of exposure, prompt decontamination, hemodynamic stabilization, immunosuppressive therapy, antioxidants is the mainstay. If patient presents early, the therapeutic interventions with hemoperfusion and dialysis is recommended to prevent pulmonary and multi-organ failure The data on paraquat poisoning from our country is scanty, since there is lack of clear evidence-based therapy for paraquat intoxication, different approaches have been tried for supportive management. In the present case, our therapeutic strategy has improved clinical outcome.