Paraquat poisoning causes severe oxidative stress and multi-organ failure. Ingestion has a high fatality rate. It is rapidly absorbed and concentrated in lungs, liver, and kidneys, causing cellular damage through redox cycling. Clinical features include oropharyngeal burns, respiratory distress, and acute kidney injury. Diagnosis is confirmed by positive urine dithionite test showing blue color change. Prognosis is poor for those with serum paraquat levels above the Sipp score threshold or rapidly increasing creatinine. Early extracorporeal removal within 4 hours may help severe cases, but long-term outcomes are generally poor with progressive lung fibrosis. Management focuses on supportive care, though antioxidants have been tried with

1. Paraquat Poisoning

2. Introduction
 Paraquat is a rapidly acting, non selective
herbicide ; inexpensive
 Dermal /spray exposure(inhalation)-limited
localised injury
 Ingestion-high case fatality rate
 Diquat is a related herbicide-similar mechanism,
clinical features, treatment
 Coformulated with an antiemetic/alginate to reduce
absorption

3. Pharmacology and cellullar
toxocology
 Chemically- bi pyridyl compounds
 Absorption..concentrated inside cells..redox
cycling( repetitive enzyme mediated cycling
between paraquat and its radicals)
 Byproduct- superoxide radical
 Redox cycling –consumes NADPH(antioxidant)
 Oxidative stress-cellullar damage
 Secondary inflammatory response
 Multiorgan failure-organs with high blood
flow,oxygen tension and energy requirements-
lungs/heart/kidneys/liver

4. Kinetics
 Highly polar and corrosive
 Ingestion ..rapid absorption..rapid distribution
 Max tissue levels..6hrs
 Active uptake by cell membrane transporters(eg:
spermidine/putrescine)
 High conc: in liver, lungs, kidney,muscle
 No significant phase 1/phase 2 biotransformation
 Elimination –kidneys
 Minor-most ingested will appear in urine by 24 hrs
 Severe-kidney function impaired..elimination
delayed..elimination half life can exceed 100 hrs

5. Clinical features:
History
 Formulation , strength and dose are important-
>30ml of 20% paraquat can be lethal.
 Kidney disease and age>50yrs- bad prognosis
 Time of ingestion
 Painful mouth, difficulty in swallowing, nausea,
vomiting , abdominal pain
 Burning skin sensation
 Respiratory complaints-systemic poisoning

6. Physical examination and basic
monitoring
 Mouth,pharynx- necrosis, inflammation, ulceration-
maybe delayed to upto 12 hours, peak severity in
some days later
 Dehydration(vomiting)
 Monitor respiratory rate, pulse oximetry- O2 only if
SpO2<90%
 Heart rate, BP- progressive refractory hypotension
 Chest-dyspnoeic, tachypnoeic, crackles
(alveolitis).subcutaneous emphysema-
mediastinitis
 Abdominal pain, diffuse tenderness
 Topical contact- corneal ulceration, non specific
dermatitis

7. Lab evaluation
 General testing:
 Blood tests- on admission, every 6 to 12th hourly for
first 48 hours, then based on clinical severity-
vomiting, diarrhea, kidney injury.
 If prognosis is poor - palliative measures

8.  Serum electrolytes- may be altered due to
vomiting, diarrhea, acute kidney injury and multi
organ dysfunction.
 Renal function-
◦ AKI suggests significant poisoning-acute tubular
necrosis/volume depletion-increased mortality
◦ Serum creatinine-rate of increase correlates with survival -
<0.034mg% per hr over 5 hrs(survival); >0.049mg% per hr
over 6hrs(death)
◦ Serum cystatin C- >0.009mg/L per hr over 6 hrs (death)

9.  Blood gas-
◦ Alkalemia-vomiting, early in the course
◦ Acidemia- respiratory acidosis( alveolitis,
pneumonitis) and metabolic acidosis( diarrhea,
AKI, mitochondrial toxicity, hypotension)
 Respiratory index >1.5(death)
 Arterial Lactate- MODS, hypotension, ARDS.
Lactate concentration >40mg%-fatal outcome-
helps determine prognosis

10.  Chest radiograph- for assessing acute lung injury(
hypoxia/hyperventilation/crackles)-direct effect of
paraquat(bilateral) / aspiration( focal-mostly right
lung).
 early phase(1-2 weeks)-diffuse alveolar
infiltrates-ARDS
 late phase-reticulointerstitial infiltrates-
progressive fibrosis
 Toxicology screen- for patients in altered mental
status-usually not caused by paraquat- but by
acetaminophen exposure etc

11.  Specific testing:
 Urine paraquat- inexpensive; based on color
change after addition of dithionite soln to urine-
positive within 6 hrs after large ingestion,remains
positive for several days.
 Positive test-40% mortality. Negative- 100 %
survival
 Methods : 100mg sod.dithionite to 10ml of 2M
sodium hydroxide- 200ul of this to 2ml urine-
blue(paraquat), green(diquat)- darker the color,
more the concentration

12.  Serum paraquat- nomograms –correlate serum
paraquat concentration with mortality risk
 The proudfoot nomogram, best cut off for the
Severity in Paraquat Poisoning(Sipp)
 Sipp score-paraquat concentration(mg/dl) x time
since poisoning(hrs)..score <10 survival is likely.
 Challenges –imprecise time of exposure, paraquat
assay within a relevant time frame.

13.  Qualitative serum paraquat- in patients with
positive urinary dithionite test
 soln prepared as before.. But added to 2ml of
plasma instead of urine- equivocal color change-
50% mortality, definitive color change-100 %
mortality
 Topical exposure-no need of investigations.
 If in doubt- urinary dithionite at 6 and 12 hrs for
reassurance.

14. Diagnosis
 h/o ingestion/exposure
 Physical examination-oropharyngeal burns etc
 Subsequent development of: AKI, metabolic
acidosis, or ARDS
 Lab confirmation-urine dithionite test

15. Differential diagnosis
 No other pesticide makes such severe oral burns
 Most corrosives do not cause acute systemic
toxicity
 Previously was mistaken for HIV related infections-
oral candidiasis/Pneumocystis jiroveci pneumonia

16. Management -overview
 Determined on an individual basis based on
amount ingested, time elapsed since exposure
 None of the current treatments are effective in
severe poisoning
 Symptoms/signs manifest in 6 to 12 hrs- need
monitoring atleast for this duration.
 Negative urinary dithionite test at 6 hrs- minimal
exposure.

17.  GI decontamination to limit systemic exposure
 Hemoperfusion followed by
hemodiafiltration/repeated hemoperfusion may be
beneficial if commenced within 4 hrs of exposure
 Antedotes- antiflammatory and antioxidant
therapies- limited data to support efficacy.
 For severe poisoning- better approach may be
palliative care.
 Titrated fentanyl/morphine.

18. Initial resuscitation
 Follows standard guidelines??
 O2 should not be administered unless SpO2 <90%.
 Hydration -2 to 3 L of isotonic crystalloids or more
 Continuous pulse oximetry
 For severe systemic illness- active management
may be futile.but decision can be taken based on
history/prognostic tests/clinical signs

19.  Gastro intestinal decontamination:
◦ If presented within 2 hrs of exposure: Activated
charcoal 1g/kg in water, max dose 50g ; per oral or via NG
tube
◦ Gastric lavage and forced emesis are contraindicated- caustic
injury
◦ NG tube aspiration prior to charcoal administration
 Topical/inhalational exposure:
◦ Wash with soap and water for 15 mins.
◦ Staff should use universal precautions
◦ Ocular exposure- standard treatment for corrosive exposure??-
rinsing for 30 mins then standard protocol??
 Monitoring: pulse oximetry.

20. Specific treatments and
antidotal therapy:
 Indications for extracorporeal therapies:
◦ Hemoperfusion for 4 hrs if initiated within 4 hrs of ingestion.
◦ Haemodialysis/hemofiltration may be used –paraquat has
less protein binding.??; can also be used in AKI as renal
replacement therapy.
◦ Rebound in plasma paraquat following hemoperfusion can
be minimised with continuous extracorporeal technique.

21.  Antinflammatory and immunosuppressive therapy:
 Cyclophosphamide+glucocorticoid- not validated
by studies
 Antioxidant therapy-acetylcysteine, sodium
salicylate, deferoxamine, vitamin C, vitamin E.

22. Ongoing management
 Avoid O2 unless hypoxic
 Correct electrolyte abnormalities
 Monitor blood lactate concentrations, renal function
 Acute hepatic injury/pancreatitis- do not influence
prognosis
 The likely outcome is generally apparent within a
day or two:
◦ Either critically ill with severe poisoning
◦ Mild to moderate poisoning but adequately compensated
without intervention
◦ Asymptomatic

23.  Renal failure resolves in weeks
 Lung injury becomes progressively more severe for
several weeks.
◦ Lung transplant ineffective- paraquat injures the allograft
 Diquat- may be associated with MODS and rapid
death similar to paraquat.
◦ But survivors are most likely to recover and not experience
delayed or progressive respiratory failure

24.  Thankyou