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![CLINICAL PRESENTATION
• GI Tract:
• Local irritation – nausea, vomiting
• Caustic – Ulceration of tongue & mouth [Paraquat tongue], sloughing of
oropharyngeal mucosa, dysphagia
• Severe – perforation of esophagus, mediastinitis, surgical emphysema,
pneumothorax, pleural effusion
• Jaundice, hepatomegaly, hepatitis, pancreatitis – pain abdomen
• Renal:
• Oliguric or non-oliguric failure – mostly due to ATN – becomes evident in 1-2
days
• Hematuria, proteinuria, glycosuria, excessive leakage of Na & urate](https://image.slidesharecdn.com/paraquatpoisoning-drbchoudhuri-230604165312-517a0a25/75/Paraquat-Poisoning-Clinical-Insights-Management-and-Challenges-by-Dr-Bodhisatwa-Choudhuri-8-2048.jpg)
![SEVERITY INDEX OF PARAQUAT POISONING
(SIPP SCORE)
• Best predictor of survival after self-poisoning
• SIPP Score: The time from paraquat ingestion (to intensive treatment) [in hours] x
Serum paraquat levels at admission [mg/dl]
• Score <10 – survival is likely
• Useful in planning treatment, determining the prognosis and studying the
pathology of acute paraquat poisoning
• Also effective in comparing therapeutic results at different stages of treatment
and in evaluating new therapeutic methods
• Challenges: imprecise time of exposure, paraquat assay within relevant time
frame](https://image.slidesharecdn.com/paraquatpoisoning-drbchoudhuri-230604165312-517a0a25/75/Paraquat-Poisoning-Clinical-Insights-Management-and-Challenges-by-Dr-Bodhisatwa-Choudhuri-14-2048.jpg)
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"Paraquat Poisoning: Clinical Insights, Management, and Challenges" - by Dr Bodhisatwa Choudhuri
- 1. PARAQUAT POISONING DR BODHISATWACHOUDHURI MBBS, MD(Med), MRCEM(UK), MEM(GWU-USA), MRCP Acute Medicine(UK), Dip Rheumatology(UK), FCCS, CCEBDM, Dip Echo(IAE) Consultant & In-Charge, Emergency & Critical Care, Medicine & Rheumatology, Parkview Super-specialty Hospital, Saltlake, Kolkata Secretary, SEMI West Bengal Chapter
- 2. INTRODUCTION • Paraquat isa highly toxic & widely used bipiridyl compound • Was discovered in 1950s and found its way into agricultural use by 1962 • Primarily used for weed and grass control, but due to its highly poisonous nature was soon categorized as a “restricted-use” herbicide • However, as it is cheap and effective, its unregulated use in developing countries like India has made it a commonly used pesticide • It is exceedingly toxic to humans, and a minimal ingestion of 10–20 mL of 20% paraquat (around a mouthful) is lethal • Concentrated solutions are known to corrode even mild steel and aluminum
- 3. INCIDENCE • Global problem •Trinidad, Tobago, Samoa – reported around 63-76% suicidal deaths on late nineties – due to Paraquat self-poisoning • England & Wales – reported 56% deaths due to paraquat use out of all pesticide ingestion between 1945-1989 • USA – Paraquat was responsible or greater number of deaths than any other pesticide in 2008 • The case fatality rate in paraquat is as high as 70% • Almost all European countries have banned paraquat due to high mortality
- 4. PATHOPHYSIOLOGY • Oxidative stressand Generation of free radicals: • Redox cycling - Generates Reactive oxygen species (ROS) like – NADPH, NADH- Ubiquinone oxidoreductase, cytochrome P450 reductase, NO synthase, xanthine oxidase • Further generates superoxide (O2 -) inside cell • NO combines with superoxide to produce Peroxynitrite (ONOO-), a very strong oxidant • This strongly active oxygen & nitrite species is highly toxic majority of organs • Effects of Oxidative stress: • Lipid peroxidation • Mitochondrial toxicity • Oxidation of NADPH • Activation of NF-kB • Apoptosis
- 5. MECHANISM OF TOXICITY •Multiple synergistic mechanisms – usually occurs simultaneously • The principal target organ for paraquat poisoning is the lung and kidney • Lungs: Major impact – alveolar epithelium remains the most affected part in lungs • Acute alveolitis, diffuse alveolar collapse, congested vessels, apoptosis, attachment of PMLs & activated platelets to vascular endothelium • 3 overlapping phases: acute destructive phase, proliferative phase, lung fibrosis • Kidney: Paraquat is actively secreted by the kidney – its accumulation in the proximal tubular epithelial cells at higher concentrations – causes vacuolation in the cells of the PCT – causing renal tubular necrosis • Liver: Hepatocellular injury occurs secondary to mitochondrial damage and endoplasmic reticulum degranulation
- 6. TOXICOKINETICS • Rapid butincomplete absorption in gut upon ingestion • Rapidly distributed to highly vascular organs – lung, liver, kidney, muscle • Within 12-24 hours, kidneys excrete majority of the absorbed paraquat rapidly • But in severe poisoning, renal clearance declines rapidly after few hours – leads to slow clearance of paraquat distributed to deeper compartments – over days to weeks • Type II pneumocytes take up paraquat against concentration gradient – behaves like a third ‘toxic effect’ compartment – has even slower elimination rate than other deeper compartments
- 7. CLINICAL PRESENTATION • Pulmonary: •Paraquat concentration in the lung is 10–20 times greater than in the plasma due to the energy-dependent uptake of the poison by the alveoli, which persists despite decreasing paraquat levels in the blood • Involvement of the lung in the form of diffuse alveolitis (over 1–3 days) and subsequent pulmonary fibrosis is the hallmark of paraquat poisoning • Symptoms – cough, hemoptysis, dyspnoea • Rarely, pneumothorax, pleural effusion and pulmonary edema • ARDS sets in after 24–48 hours of exposure • Skin: Erythema, eruptions, ulceration of skin may occur • Eyes: inflammation, ulceration of conjunctive, cornea, diminution of vision – healing is slow with complete recovery
- 8. CLINICAL PRESENTATION • GITract: • Local irritation – nausea, vomiting • Caustic – Ulceration of tongue & mouth [Paraquat tongue], sloughing of oropharyngeal mucosa, dysphagia • Severe – perforation of esophagus, mediastinitis, surgical emphysema, pneumothorax, pleural effusion • Jaundice, hepatomegaly, hepatitis, pancreatitis – pain abdomen • Renal: • Oliguric or non-oliguric failure – mostly due to ATN – becomes evident in 1-2 days • Hematuria, proteinuria, glycosuria, excessive leakage of Na & urate
- 9. PARAQUAT TONGUE Multiple erosionsand superficial ulcers over tongue covered with yellowish necrotic debris
- 10. CLINICAL PRESENTATION • CVS: •Initially sinus tachycardia • Lately, Myocarditis, VT, non-specific ST-T changes, intraventriclar conduction defects • Terminal – hypotension, sinus bradycardia • Neurological: cerebral edema – ataxia, convulsion, facial paresis, finally coma • Endocrine: adrenal cortical necrosis
- 11.
- 12. DIAGNOSIS & INVESTIGATIONS •Mainstay is circumstantial history - history of exposure, evidence of paraquat exposure and the amount of poison ingested • ABG – respiratory/metabolic acidosis • Routine labs: deranged based on organ involvement – regular monitoring of KFT, LFT, Electrolytes, Lactate, CBC • Serum Cr: Rate of increase correlates with survival – <0.034mg/dl/hr over 5 hours – survival; >0.049mg/dl/hr over 6 hours – death • Chest X-ray: useful in detecting early insult to the lungs (alveolitis), pulmonary fibrosis, ARDS, and rarer complications like pneumomediastinum or pneumothorax • ECG • Amylase, Lipase – to rule out toxin-induced pancreatitis
- 13. SPECIFIC INVESTIGATIONS • Plasmaand urine sodium dithionate tests - simple, bedside methods to assess systemic paraquat toxicity • In an alkaline medium, dithionate reduces paraquat to a blue radical (if urine paraquat concentration >1 mg/L or plasma paraquat concentration >2 mg/L) • Darker the colour, more the concentration • Helps in predicting prognosis in paraquat poisoning – positive test ~40% mortality, negative test ~100% survival • Qualitative assessment of paraquat poisoning • Measurement of Paraquat concentration in plasma and urine - quantitative assessment of paraquat poisoning, but not commonly available and the results are often delayed
- 14. SEVERITY INDEX OFPARAQUAT POISONING (SIPP SCORE) • Best predictor of survival after self-poisoning • SIPP Score: The time from paraquat ingestion (to intensive treatment) [in hours] x Serum paraquat levels at admission [mg/dl] • Score <10 – survival is likely • Useful in planning treatment, determining the prognosis and studying the pathology of acute paraquat poisoning • Also effective in comparing therapeutic results at different stages of treatment and in evaluating new therapeutic methods • Challenges: imprecise time of exposure, paraquat assay within relevant time frame
- 15. MANAGEMENT • There isno accepted & effective treatment guideline for paraquat poisoning • Most of the treatment options are extrapolated from small, uncontrolled animal studies • Treatment given is either supportive care alone or combinations of various supportive measures • Even the best centers have an overall mortality greater than 50%
- 17. AIRWAY MANAGEMENT AND DECONTAMINATION •Patient is conscious with no vomiting - consider gastric lavage with activated charcoal (1–2 g/kg) or Fuller’s earth (1–2 g/kg) - aids in gastric decontamination and prevents further absorption • Supplemental oxygen is not advocated - as the oxygen free radical-mediated cytotoxic injury causes rapid worsening of pulmonary alveolar infiltrates, leading to the ARDS and subsequent pulmonary fibrosis if the patient survives the acute phase • Corrosive poison - so early insertion of a nasogastric tube - to maintain nutrition; may be very challenging due to severe ulcerations and friable mucosa, which may lead to complications including perforation • Keep NPM in the early phase • Oral lesions can be very painful - may need anticholinergic agents such as diphenhydramine; an anesthetic, such as viscous lidocaine; and an antacid or mucosal coating agent, such as magnesium or aluminum hydroxide, kaolin, or sucralfate • Antibiotics may be used for supervening infections
- 18. VENTILATION • Development oftype 2 respiratory failure may be an early predictor of ARDS in patients - worse outcome • Management of oxygenation and ventilation is identical to ARDS due to any other etiology (ARDS protocol, lung protective strategy) • Limit FiO2 to minimum to maintain PaO2 of about 60–65 mm Hg or SpO2 88–90% • Usually patients who get intubated for respiratory failure have a stormy course and deteriorate rapidly in few hours to days • Experimental: addition of NO (25 ppm) to inhaled gas
- 19. HAEMODIALYSIS AND HAEMOFILTRATION •Initial management includes rehydration with IV fluids • Target UOP 1-2 ml/kg body wt/hr • In all cases of paraquat poisoning (significant ingestion), hemoperfusion is the first and the earliest modality of treatment of removal of paraquat • Clinical benefit only when initiated within 2 hours post-ingestion • Initiating HD/HP 2-4 hours after ingestion can reduce plasma paraquat concentration, but those taken up by lungs gets reduced negligibly, thus unlikely to change overall outcome
- 20. • Proposed atreatment strategy - • to use up to seven hemoperfusion sessions (6–8 hours duration) • to be started within 4 hours of ingestion • maintained until plasma paraquat levels would be <0.2 mg/L
- 21. • Prospective, controlledinterventional study over 4 years • Recruited patients admitted to Shanghai Tenth People's Hospital within 48 hours after paraquat ingestion • Concluded that treatment with combined continuous venovenous hemofiltration and hemoperfusion significantly improved 90-day survival rates in paraquat poisoning
- 22. IMMUNOSUPPRESSANTS • Interferes withthe acute inflammatory response causing alveolitis and lung fibrosis • Options: Cyclophosphamide, Methylprednisolone pulse, Dexamethasone • Dexamethasone has shown to cause significantly reduced paraquat accumulation in lung tissues • No mode of treatment is shown to be effective in preventing lung injury or fibrosis once it is established • But some degree of benefit is seen when given early in course of treatment
- 23. • Target: severeparaquat-poisoned patients with >50% to <90% predictive mortality • Initial pulse therapy with methylprednisolone (1 g/day for 3 days) and cyclophosphamide (15 mg/kg/day for 2 days), followed by dexamethasone 20 mg/day until Pao2 was >11.5 kPa (80 mm Hg) • Repeated pulse therapy with methylprednisolone (1 g/day for 3 days) and cyclophosphamide (15 mg/kg/day for 1 day), if Pao2 was <8.64 kPa (60 mm Hg) • The mortality rate (85.7%) of the control group was higher than that of the study group (31.3%; p = .0272)
- 24. ANTIOXIDANTS • Tried toovercome circulatory shock due to reactive oxygen species, causing lactic acidosis, lung & renal injury • N-Acetyl cysteine: found to increase the level of glutathione (antioxidant) by suppressing the superoxide production - 150 mg/kg over 3 hours; 300 mg/kg over 24 hours for up to 3 weeks • Vitamin C: can donate electrons to free radicals and hence neutralize them • High doses of vitamin C (300 mg twice daily orally) reduced mortality in a case series of 10 patients • Vitamin E: acts by membrane stabilization, oxygen free radical scavenging, inhibiting activation of NF-kB • Deferoxamine: chelate iron that acts as a catalyst in the production of hydroxyl radicals (100 mg/kg over 24 hours) • Salicylic Acid: Anti-inflammatory, anti-oxidant, hydroxyl radical scavenger, inhibits activation of NF-kB & lipid peroxidation
- 25. NOVEL THERAPIES • Edaravone:free radical-scavenging antioxidant, which also has antiapoptotic, necrotic, and anti-inflammatory effects – beneficial for protecting the kidneys and liver from paraquat poisoning, but did not reduce pulmonary fibrosis , only delayed it • Anti-C5a Antibodies: anti-inflammatory • Lung irradiation: proposed for inhibiting fibroblastic proliferation • Lung transplantation • ECMO: as a bridge to sequential bilateral lung transplantation
- 26. CONCLUSION • Paraquat poisoningis a leading cause of death from pesticide poisoning with mortality of >70% • The literature on paraquat poisoning in India is sparse and the evidence on management is vague and lacks proven survival benefit • Though India is among the highest users of this herbicide worldwide, we are yet to equip ourselves with evidence-based treatment to successfully manage paraquat poisoning • Lungs are affected the most – as they take up the poison against a concentration gradient • No proven treatment or antidote • Oxygen supplementation may further worsen oxidative stress, so should be avoided in mild to moderate hypoxia • Extracorporeal elimination by HD/HP should be considered early – within 1-2 hours post- ingestion
- 27. NATIONAL POISONS INFORMATIONCENTRE (NPIC) Call 24 hours a day, 7 days a week, 365 days a year. Toll Free No. - 1800 116 117 Tel No.- 26589391 , 26593677
- 28.
- 29. THANK YOU Any questions?? Contact:9830636315 E-mail: [email protected]