Paraquat toxicity

Background

• Paraquat is an herbicide that has a rapid and large distribution and can be fatal even with small ingestions. It has a high case-fatality rate (>50%) which makes it a frequent means of suicide in the developing world, as well as a dangerous accidental occupational exposure.
• Paraquat exerts its toxic effects via multiple proposed mechanisms, including lipid peroxidation and generation of reactive oxygen species, direct mitochondrial toxicity, and apoptosis.

Clinical Features

Paraquat Tongue (Credit: wikitox.org)

Overall, pulmonary and renal toxicities predominate and are the primary cause of mortality. GI toxicity is nearly universal and is probably an underrecognized cause of mortality secondary to erosion and perforation.

• Gastrointestinal: predominate early
  • Paraquat tongue
  • Esophageal and gastric erosion
  • Nausea and vomiting
• Pulmonary: occurs due to distribution to pneumocytes
  • Pneumonitis
  • Pulmonary fibrosis (delayed)
• Multiorgan failure
  • Acute renal failure
  • Hepatic necrosis
  • Myocardial necrosis
  • Internal bleeding

Differential Diagnosis

Toxic Ingestion

• Caustic Ingestion
• Toxic Alcohols
• Foreign Body Ingestion

Oral Burns/Mucositis

• Burns
• Infectious Causes
  • Aphthous Ulcer
  • Herpes simplex infection
  • Coxsackie virus
  • Tonsillitis
  • Methotrexate/chemotherapy toxicity

Acute Dyspnea

• Primary Lung
  • Pneumonia (bacterial and viral)
  • Pneumonitis
  • Pulmonary Embolism
  • Pneumothorax
  • Malignancy
  • Mucus plugging
  • Reactive airway disease
  • Aspiration
  • Pleural Effusion
• Primary Cardiac
  • Congestive Heart Failure
  • Myocardial infarction
  • Valvular disease
  • Aortic Stenosis or regurgitation
  • Pericardial Effusion
  • Myocarditis/Pericarditis
• Primary Metabolic
  • Sepsis
  • Metabolic Acidosis

Evaluation

Patients who present in extremis after an ingestion will not survive regardless of management and should be treated palliatively.

ABC's

• Airway: consider early aggressive intubation for any respiratory distress or large (>100mL) ingestions
• Breathing: CXR, O2. Avoid aggressive oxygen therapy if not necessary due to increased free radical production
• Circulation: may develop early shock and require aggressive inotropic support

Laboratory Evaluation

• CBC
• BMP
• LFTs and coagulation tests
• VBG or ABG
• UA: high concentrations of paraquat in the urine will cause it to appear blue
• Urine dithionate test:
  • Add 1cc of 1% sodium dithionate (hematology labs have this solution) to 10mL urine
  • Blue color change indicates presence of paraquat

Diagnostics

• CXR
• EKG
• consider CT if stable to evaluate for perforation/mediastinitis

Management

Decontamination

• Paraquat is absorbed transdermally. Unprotected first responders and healthcare workers are at risk
• Remove clothing and wash patient's skin if spillage or obvious skin involvement present
• Consider activated charcoal or Fuller's Earth if within 1-2 hrs of ingestion
• Consider NG tube for administration of AC
  • Must weigh risks as NGT placement can exacerbate caustic injury

Resuscitation

• Large >50mL ingestions of paraquat are universally fatal. Aggressive resuscitation is futile.
• ABCs as noted above; avoid supplemental O2 unless severe hypoxia present

Supportive Care

• IV fluids: patients often 2-3L fluid down
• Pain control

Antidotes/Additional Therapies

• Some centers administer glucocorticoids (typically dexamethasone 6mg-10mg IV q6h)
• Consider NAC, Vit C, other free radical scavengers in consultation with toxicologist or poison control
• No role for extracorporeal elimination (hemodialysis, hemoperfusion, CRRT)

Disposition

If small/trivial exposure and patient asymptomatic at 6 hours, unlikely to manifest a significant toxicity Any sympatomatic exposure requires admission for close hemodynamic monitoring and supportive care