Surviving accidental paraquat ingestion: a limited evidence zone

A 17-year-old youth accidentally ingested paraquat, a herbicide which is an uncommon but potentially highly lethal cause of poisoning. He was initially managed at a regional hospital where, upon advice from a Victorian Poisons Information Centre toxicologist, he was commenced on dexamethasone, continuous venovenous haemodiafiltration (CVVHDF), and N-acetyl cysteine (NAC) and sodium salicylate infusions. He was transferred to a transplant centre for consideration of lung transplantation where he was maintained on CVVHDF, dexamethasone and NAC for 2 weeks. Fortunately, despite ingestion of a potentially lethal dose of paraquat at 36.48 mg/kg, he recovered with mild restrictive respiratory deficits, steroid side effects, and oropharyngeal burns as sequelae.

Paraquat toxicity primarily damages the respiratory and renal systems. In the alveolar epithelium, absorbed paraquat concentrations can be up to 10–20 times the serum paraquat levels.1 Here it undergoes oxidation to form superoxide radicals leading to progressive pulmonary fibrosis. In the kidneys, paraquat induces acute tubular necrosis, which impairs its elimination and further increases lung concentrations. The ingestion of greater than 20 mg/kg of paraquat, which represents only 10–20 mL of a 20% w/w solution typically leads to acute kidney injury (AKI) and progressive pulmonary fibrosis causing death in 1–3 weeks.2

The diagnosis of paraquat poisoning may be made urgently by the semiquantitative urinary dithionite spot test. Knowing the serum paraquat concentration is useful for prognostication purposes, and five nomograms predicting outcome from 4 to 200 hours postingestion are available for use.3 However, none of these as yet alter clinical management.

The optimal management of paraquat poisoning, as with most pesticide poisonings, remains unclear. The patient in this report developed rapid AKI with creatinine levels increasing from a baseline of 90 μmol/L to 239 μmol/L within 28 hours of ingestion. For this, he was maintained on CVVHDF for 2 weeks, although the benefit of this treatment is unclear. Haemoperfusion, as opposed to continuous haemofiltration, is more efficacious at removing paraquat from the serum, and despite widespread clinical use the evidence for its use is mostly limited to animal studies.4 Paraquat induces an intense inflammatory reaction, so other treatment modalities have focused on immunosuppressive and antioxidant therapies. Small, underpowered studies have previously used pulsed methylprednisolone and cyclophosphamide followed by 2 weeks of dexamethasone, although cyclophosphamide has been shown to have little efficacy in small randomised controlled trials.5 Sodium salicylate and NAC both act in an anti-inflammatory manner, although the data are again mostly limited to animal studies.3

Paraquat toxicity remains an uncommon event in Australia. When paraquat poisoning is suspected, the involvement of a specialist toxicology service accessible through avenues such as the Poisons Information Australia provides an indispensable avenue for expertise to manage this limited evidence zone.