Paraquat Poisoning

OVERVIEW

  • highly toxic herbicide
  • common agent in suicide in 3rd world, especially Asia (lethal in small amounts, cheap, available)
  • leading single agent causing death from pesticide poisoning in many countries including Sri Lanka
  • occurs sporadically elsewhere
  • >50% case fatality rate

MECHANISM

Toxicokinetics

  • Paraquat is rapidly but incompletely absorbed and then largely eliminated unchanged in urine within 12–24h
  • volume of distribution of 1.2–1.6 l kg−1
  • Kinetics of distribution into target tissues can be described by a two-compartment model with time-dependent elimination from the central compartment. The lungs may be considered a third compartment from which elimination is very slow.

Toxicodynamics

  • Paraquat generates reactive oxygen species which cause cellular damage via lipid peroxidation, activation of NF-κB, mitochondrial damage and apoptosis in many organs.
  • actively taken up against a concentration gradient into lung tissue leading to pneumonitis and lung fibrosis.
  • Paraquat also causes renal and liver injury.

CLINICAL FEATURES

Risk assessment

  • Ingestion of large amounts of liquid concentrate (>50–100 ml of 20% ion w/v) results in fulminant organ failure and death (hours to days)
  • Ingestion of smaller quantities usually leads to toxicity in the two key target organs (kidneys and lungs) developing over the next 2–6 days (still >50% mortality)

Clinical features

  • ulceration of the mucous membranes (paraquat tongue), esophageal perforation
  • nausea
  • sweating
  • vomiting
  • tremors
  • convulsions
  • pulmonary oedema
  • cardiovascular collapse
  • renal failure (early)
  • liver dysfunction with abnormal LFTs
  • acute alveolitis over 1–3 days followed by a secondary fibrosis (3-7 days) with death at up to 5 weeks

INVESTIGATIONS

As indicated

  • paraquat assay
  • sodium dithionite test on urine (if changes colour to blue -> confirms urine paraquat concentration >1 mg l−1,  indicates a very poor prognosis)
  • FBC, UEC, LFTs, lipase, coags (multi-organ dysfunction)
  • CT Chest
  • endoscopy

MANAGEMENT

  • Fullers earth (non-plastic clay): 30%, 250mL Q 4 hourly -> until comes out in stools
    OR
    Activated Charcoal
  • early NGT recommended (due to mucosal injury)
  • avoid gastric lavage (caustic injury, and unlikely to provide any benefit)
  • titrate O2 (can worsening pulmonary fibrosis, mild hypoxia is acceptable e.g. SpO2 >88%)
  • immediate plasma exchange or haemofiltration (not likely to change outcome – distribution to the lungs occurs <2h)
  • immune suppression with cyclophosphamide, MESNA, methylprednisolone and dexamethasone to dampen inflammatory reaction (unproven)
  • Antioxidants such as acetylcysteine and salicylate might be beneficial through free radical scavenging, anti-inflammatory and NF-κB inhibitory actions (no evidence)
  • patients in extremis should be palliated

References and Links

  • Gawarammana IB, Buckley NA. Medical management of paraquat ingestion. Br J Clin Pharmacol. 2011 Nov;72(5):745-57. PMC3243009.

CCC 700 6

Critical Care

Compendium

Chris is an Intensivist and ECMO specialist at the Alfred ICU in Melbourne. He is also the Innovation Lead for the Australian Centre for Health Innovation at Alfred Health and Clinical Adjunct Associate Professor at Monash University. He is a co-founder of the Australia and New Zealand Clinician Educator Network (ANZCEN) and is the Lead for the ANZCEN Clinician Educator Incubator programme. He is on the Board of Directors for the Intensive Care Foundation and is a First Part Examiner for the College of Intensive Care Medicine. He is an internationally recognised Clinician Educator with a passion for helping clinicians learn and for improving the clinical performance of individuals and collectives.

After finishing his medical degree at the University of Auckland, he continued post-graduate training in New Zealand as well as Australia’s Northern Territory, Perth and Melbourne. He has completed fellowship training in both intensive care medicine and emergency medicine, as well as post-graduate training in biochemistry, clinical toxicology, clinical epidemiology, and health professional education.

He is actively involved in in using translational simulation to improve patient care and the design of processes and systems at Alfred Health. He coordinates the Alfred ICU’s education and simulation programmes and runs the unit’s education website, INTENSIVE.  He created the ‘Critically Ill Airway’ course and teaches on numerous courses around the world. He is one of the founders of the FOAM movement (Free Open-Access Medical education) and is co-creator of litfl.com, the RAGE podcast, the Resuscitology course, and the SMACC conference.

His one great achievement is being the father of two amazing children.

On Twitter, he is @precordialthump.

| INTENSIVE | RAGE | Resuscitology | SMACC

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