Paraquat Poisoning

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

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

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

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

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

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

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)

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

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

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

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.

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.

Diagnosis

h/o ingestion/exposure

Physical examination-oropharyngeal burns etc

Subsequent development of: AKI, metabolic

acidosis, or ARDS

Lab confirmation-urine dithionite test

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

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.

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.

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

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.

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.

Antinflammatory and immunosuppressive therapy:

Cyclophosphamide+glucocorticoid- not validated

by studies

Antioxidant therapy-acetylcysteine, sodium

salicylate, deferoxamine, vitamin C, vitamin E.

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

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

Thankyou