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.