This document discusses Paraquat poisoning. It begins by introducing Paraquat as a widely used herbicide that is highly toxic to humans. It then summarizes the pathophysiology of Paraquat poisoning as involving oxidative stress and free radical generation that causes damage to multiple organs, particularly the lungs and kidneys. The clinical presentation, diagnosis, and severity classification of Paraquat poisoning are outlined. Management is described as primarily supportive care, with early extracorporeal removal via hemodialysis or hemoperfusion considered for severe cases. However, the prognosis remains poor even with aggressive treatment.
Radiation Dosimetry Parameters and Isodose Curves.pptx
PARAQUAT POISONING: MANAGEMENT CHALLENGES
1. PARAQUAT POISONING
DR BODHISATWA CHOUDHURI
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 is a 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 stress and 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 but incomplete 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
• 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
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
• Plasma and 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 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
15. MANAGEMENT
• There is no 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%
16.
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 of type 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 a treatment 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, controlled interventional 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 with the 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: severe paraquat-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 to overcome 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 poisoning is 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 INFORMATION CENTRE
(NPIC)
Call 24 hours a day, 7 days a week, 365 days a year.
Toll Free No. - 1800 116 117
Tel No.- 26589391 , 26593677
