Paraquat poisoning results from ingestion of the herbicide paraquat. It causes multi-organ damage through generation of reactive oxygen species. Clinical features include mouth ulcers, renal failure, liver damage, and pulmonary fibrosis. Diagnosis is confirmed by urine or blood tests detecting paraquat. Management focuses on decontamination, supportive care, and immunosuppression to reduce lung fibrosis. Prognosis is poor, even with treatment, due to progressive pulmonary damage.

1. Paraquat Poisoning

2. • Introduction
• Methods of poisoning
• Kinetics
• Pharmacology and cellular toxicity
• Clinical feature
• Diagnosis
• Management
• Prognosis

3. Introduction
• Incidence of paraquat poisoning is 3.8/1,00,000 in a year
• A Bipyridyl compound, rapidly acting nonselective herbicide
• Mechanism of toxicity to plants includes inhibition of photosynthesis,
respiration, protein synthesis, growth stimulation
• Manufactured as liquid granules / aerosols
• Combined with Diquat – contains dye, emetic, stenching agent (to
reduce toxicity on ingestion)

4. • Mortality rates of 72.7% in a study conducted in 55 people
• 3,00,000 occur in Asian-pacific region due to paraquat poisoning

5. Methods of poisoning
• Ingestion – responsible for majority of deaths
• Transdermal absorption is minimal in the absence of skin lesions, but
deaths have been reported
• Inhalation / exposure to sprays – irritate conjunctiva and airway,
unlikely to cause systemic toxicity

6. Kinetics
• Highly polar and corrosive
• Not absorbed in significant amounts across intact skin or inhaled
droplets
• Rapidly but incompletely absorbed from gut (jejunum - 17.6%).

7. • Lethal oral dose of 20% concentrate solution is about
: 10-20 ml in adult
: 4-5 ml in children
• Plasma concentration peaks with in 2 hours of ingestion
• Tissue concentration peaks by 6 hours
• Elimination is mainly by kidneys unchanged form, most ingested
paraquat appears in the urine with in 24 hours in minor poisoning

8. • In severe poisoning kidney function is greatly reduced leading to
much slower elimination

9. Pharmacology and cellular toxicology
• Actively accumulate in many cells where it under goes redox cycling
and form superoxide radical, a highly reactive oxygen spices
• Superoxide causes direct cellular damage or react further to form
other ROS and nitrite radicals
• Redox cycling consumes NADPH (anti-oxidant)

10. • The resultant oxidative stress created by production of free radicals
and depletion of NADPH causes cell damage (lipid peroxidation,
mitochondrial dysfunction, necrosis and apoptosis) and triggers
secondary inflammation
• Over a period of hours to days these process lead to multiorgan
dysfunction

11. • Most organs affected are those with high blood flow and oxygen
tension and energy requirements – lungs, heart, kidneys and liver
• Brain is uncommonly affected as it doesn’t cross BBB

12. • Lung injury has two phases
• Initial destruction phase – loss of type 1 and 2 alveolar cells, infiltration
by inflammatory cells, haemorrhage. Changes are reversible
• Later proliferative phase – fibrosis of interstitium and alveolar spaces
• Paraquat and oxygen enhance each other toxicity sustaining redox cycle
• Myocardial injury and necrosis of adrenal gland

13. Clinical features
• Depends on quantity, route of exposure
• Skin exposure causes local skin irritation and ulceration of epithelial
surfaces due to severe caustic
• Eye exposure causes corneal injury due to severe corrosive action
• Upper respiratory tract exposure causes mucosal injury and epistaxis
due to corrosive action

14. • Inhalation – cough, dyspnoea, chest pain
• Ingestion – GI irritation and mucosal damage with ulceration, painful
mouth and pain with swallowing, nausea, vomiting and abdominal
pain

15. On examination
• Mouth and pharynx charred, ulcers
• Tongue dry due to vomiting, poor oral intake due to odynophagia
• Tachypnoea, tachycardia, hypotension
• Bilateral crepitation due to alveolitis
• Subcutaneous emphysema indicating mediastinitis
• Diffuse abdominal tenderness

16. Paraquat tongue early lesion, within 24
hours after ingestion
Paraquat tongue late lesion, 2 weeks after
ingestion with extensive ulceration

17. Classification based on clinical features
• Mild
• Severe
• Fulminant

18. Mild Asymptomatic
Nausea, vomiting, diarrhoea
Renal and hepatic injury
minimal/absent
Reduced pulmonary diffusion
capacity
Complete recovery expected
<20mg/kg
Or
<7.5ml of 20% concentration
solution in adult
Severe Initially nausea, vomiting,
diarrhoea
Abdominal pain
Mouth and throat ulcers
Positive colorimetric test for
paraquat in urine
1-4 days, renal failure, hepatic
impairment, hypotension
1-2 weeks cough, haemoptysis,
pleural fibrosis
Majority die within 2-3 weeks due
to pulmonary failure
20-40mg/kg
Or
7.5-15ml of 20% concentration in
adult

19. Fulminant Initially nausea, vomiting,
diarrhoea
Pain abdomen
Rapid development of renal and
hepatic failure
GI ulcers
Pancreatitis
Toxic myocarditis
Refractory hypotension
Convulsions
Coma
Death due to cardiogenic shock
and multiorgan failure with in 1-4
days
>40-50mg/kg
Or
>15-20ml of 20% concentration
solution

20. • Multisystem effects include GI tract corrosion, acute renal failure,
cardiac failure, hepatic failure, extensive pulmonary injury few hours
after ingestion
• Renal failure and hepatic cellular necrosis develop between 2nd – 5th day
• Progressive pulmonary fibrosis leading to refractory hypoxemia occur 5
days to several weeks
• Metabolic acidosis common due to hypoxia combined with multisystem
failure

21. Investigations
• Electrolytes
• RFT – acute kidney injury due to acute tubular necrosis, volume
depletion. Most commonly used to asses kidney function are
Creatinine and Cystatin C
• Rate of serum creatinine correlates with survival
• Amylase and lipase – acute pancreatitis in case patient develops pain
abdomen

22. • Increase in S . Creatinine
- <0.034mg/dL/hr over 5 hours – recovery expected
- >0.045mg/dL/hr over 6 hours
or
- increase in serum cystatin concentration of >0.09mg/L
over 6 hours – death
• Creatinine also increases due to muscle oxidative stress
• Therefore is not a marker of GFR in paraquat poisoning

23. • Alkalosis due to excessive vomiting
• Acidosis - respiratory acidosis (alveolitis or aspiration pneumonia) and
metabolic acidosis (diarrhoea, AKI, mitochondrial toxicity, hypotension)
• Lactic acidosis in severe poisoning due to multiorgan dysfunction,
hypotension, hypoxic acute respiratory distress syndrome
• Serum lactate above 4.4mmol/L or 3.35mmol/L associated with fatal
outcome ( sensitivity 82% and 74%, specificity 88% and 91%) and hence
aid in prognosis

24. • Chest X-Ray - diffuse pulmonary infiltrates bilaterally due to poison,
local infiltrates due to aspiration (more on the right)
pneumomediastinum, pneumothorax due to corrosive action

25. • Urinary dithionate test – in alkaline medium sodium dithionate
reduces paraquat to blue radical. Test should performed on fresh
urine sample around 6 hours after ingestion detect paraquat within
few hours after ingestion, semiquantitative test
• If urine paraquat concentration is more than 1mg/L the urine will turn
blue in the test (poor prognosis)

26. • The addition of sodium bicarbonate and sodium dithionite to
urine specimens containing decreasing concentrations of
paraquat shows characteristic color changes.
• Each number represents decreasing concentrations of
paraquat.

27. • Paraquat detection kits – 10ml urine to collected in a clear container,
add sachet A containing sodium bicarbonate, shake. Add sachet B
containing sodium dithionate wait for effervescence to subside and
shake again.

28. • Once mixture settled, view against white background for blue or
greenish grey colour change, which indicates paraquat poisoning

29. • Serum paraquat concentration – serum concentration levels to time
of poisoning predicts likelihood of death. A fatal outcome is likely if
the plasma concentration lies
above any line. (Sample to be drawn
at least after 4 hours of ingestion)

30. • Qualitative serum testing – conduct dithionate test in plasma with
positive urinary dithionate test. Equivocal colour change associated
with 50% mortality, definitive colour change associated with 100%
mortality

31. HRCT one year following a paraquat ingestion,
showing pulmonary fibrosis, more in the left lung.

32. Diagnosis
• History of ingestion
• Oropharyngeal burns and subsequent development of AKI, metabolic
acidosis, ARDS
• Confirmed with urinary or blood dithionate test

33. Management
• Survival rate is about 13% with no treatment and increases to 73% with
active treatment
• Resuscitation – assessment of airway, breathing and circulation
• Airway compromised due to mucosal damage or presence of vomitus
• Tachypnoea and/or hypoxia due to metabolic acidosis, aspiration, acute
alveolitis
• Mild to moderate hypoxia should not be treated with oxygen as worsens
oxidative stress

34. • Hypotension to be treated with crystalloids 15-20ml/kg over 15-30
minutes
• Maintaining high urine out put is desirable (how much?)
• Impaired consciousness indicates severe toxicity resulting in altered
consciousness from hypoxia, hypotension and severe acidosis or
co-ingestion of other agents like ethanol – intubated the patient

35. • Decontamination - gastric lavage with in 2 – 4hours, followed by
activated charcoal or Fuller’s earth. Lavage not indicated in as it is
contraindicated in caustic injury
• Nasogastric tube – pharyngeal or oesophageal burns, painful
swallowing
• IVF – hypotension
• Acute renal failure – daily fluid balance to be maintained with
ensuring good urine output

36. • Pain relief and sedation – opioids and benzodiazepines
• Hemoperfusion/haemodialysis – if presents wit in 2 hours of
ingestion in case of AKI without pneumonitis.
- Benefits are limited, endogenous clearance is high in first 6-12
hours and additional amount eliminated will be relatively modest.
- Subsequent elimination of accumulated paraquat from the lungs
is minimally dependent on plasma concentration

37. • Immunosuppression – suppressing acute inflammatory response, thus
reducing chances of lung fibrosis and death
- Cyclophosphamide, MESNA, Methylprednisolone and Dexamethasone
- Dexamethasone increases the expression of P-glycoprotein
- Significant reduction of paraquat accumulation in the lungs and increase
faecal excretion
- Has also shown to ameliorate histological and biochemical changes and
reduce lipid perioxidation

38. • 1g of cyclophosphamide daily for 2 days and 1g of
methylprednisolone daily for 3 days

39. Study Description Treatment Mortality
Addo & Poon-King [84] Uncontrolled 72
patients
CP, Dex, MP, vitamin B,
vitamin C
28%
Afzali & Gholyaf [87] RCT 20 patients CP, Dex, MP vs. conventional
treatment
33% vs. 81%
Perriens et al. [89] Uncontrolled 47 patients CP, Dex vs. conventional treatment 63% vs 61%
Lin et al. [86] RCT 23 patients CP, Dex, MP vs. conventional
treatment
31% vs 86%
Lin et al. [80] RCT 50 patients CP, Dex, MP vs. conventional
treatment
68% vs 82%
Lin et al. [85] 16 patients 17 historic
controls
CP, Dex, MP 25% vs 70%
Yasaka et al. [28] Uncontrolled 9 patients Vitamin E 100–4000 mg/day 78%
Hong et al. [99] Uncontrolled 5 patients Vitamin C escalating doses 0%

40. • Anti-oxidants
• Vitamin E – vitamin E stabilises membrane and scavenges ROS.
- Vitamin E deficiency rats had lower lethal dose and shorter
survival time, vitamin E treated rat lungs after 24 hours of exposure
showed less peroxidation
- human study only 2/9 patients survived
- 200-400mg/day

41. • Vitamin C – donate electron to free radicals and neutralise. Study
done on 10 patients, positive urine dithionate test and stable vitals
high dose of vitamin c and other oxidants were given, increased anti-
oxidants in the body
• N-acetylcysteine – replenishes cysteine, rate limiting in synthesis of
glutathione. Reduced paraquat induced apoptosis and inflammatory
response
- S - carboxymethycysteine 1500mg/day

42. • Deferoxamine – iron contributes to generation of free radicals by
Fenton’s reaction. Iron chelator used with no survival benefits
• Salicylic acid – inhibits cyclo-oxygenase. Scavenges hydroxyl radicals
and inhibit their production by Fenton’s reaction
- reduces inflammatory mediators IL4, oxidative stress, NF, lipid
peroxidation, platelet activation and histological lung damage
- single dose of salicylic acid 200mg/kg, showed no deaths when
compared to control group

43. Prognosis
• Details of exposure including time, route, accidental/intentional,
amount, concentration
• Quantity related to outcome
• >50 years and H/O renal disease worst prognosis
• S. Lactate aid prognosis

44. Thank you