Herbicides

Introduction

Acute poisonings with herbicides constitute a significant problem in developing countries; although uncommon in Australia, it can cause life-threatening toxicity. Herbicides encompass a broad group of poisons, with differing mechanisms and manifestations of toxicity.

Paraquat (Bipyridyl herbicide)

Paraquat is a non-selective contact herbicide. It is extremely toxic when ingested and there are no effective treatments available. This is reflected in the very high mortality rate in poisoning, between 50% and 90%. Therefore access to paraquat is heavily regulated in Australia, but it continues to be an important cause of death in a number of countries throughout Asia. There is minimal absorption with inhalation or through intact skin, and systemic poisoning is not expected via these routes.

Diquat is another bipyridyl herbicide that is more widely available in Australasia. The clinical manifestations and management are summarised in Table 25.15.3 .

Mechanism of toxicity

Paraquat is rapidly but incompletely absorbed. It is distributed to all tissues but concentrates in the lungs and kidneys owing to active uptake in type II pneumocytes and renal tubular cells. Paraquat toxicity results from the production of free oxygen radicals, which cause oxidative stress leading to lipid peroxidation of cell membranes, mitochondrial toxicity and cellular death.

Clinical features

Paraquat is corrosive, and gastrointestinal toxicity occurs with all oral exposures. Vomiting and diarrhoea occur initially, then ulceration of the oral mucosa follows about 12 hours after ingestion. In severe cases, oesophageal perforation can occur. Patients ingesting more than 20 mL are likely to develop severe toxicity with multi-system involvement and death within 48 hours. The sequelae manifest as pneumonitis, hypotension, hepatitis, acute kidney injury and severe gastrointestinal toxicity. Patients ingesting less than 20 mL are still at risk of death, but this is more likely to be delayed by weeks or months post-ingestion. The primary mechanism of death is respiratory failure due to pulmonary fibrosis, with varying degrees of hepatic and kidney impairment. Acute kidney injury usually recovers within 2 to 3 weeks in survivors.

Diquat does not concentrate in the pneumocytes as readily as paraquat and delayed pulmonary fibrosis is less likely to occur.

Clinical investigations

Exposure can be confirmed by a urinary dithionite test. This involves the addition of 1 g of sodium dithionite solution and 1 g of sodium bicarbonate (or 1 to 2 mL of 1% sodium dithionite in 1 to 2 M of sodium hydroxide) to 10 mL of urine. A blue colour change indicates paraquat ingestion and a green colour change indicates diquat ingestion. The darker the colour change, the higher the paraquat concentration. If the test is negative on urine passed 6 hours after ingestion, a significant exposure is unlikely. A commercial kit is now available for this test.

How to perform the urinary diothonite testIt is useful to confirm that an exposure to paraquat is significant because this will guide subsequent management. The easiest method to do this is by the dithionite urine test using the test that is distributed by Syngenta in Australia and many other countries free-of-charge. A blue colour change indicates paraquat ingestion and green colour change indicates diquat ingestion. The darker the colour change, the higher the concentration. If the test is negative on urine passed 6 h after ingestion, a significant exposure is unlikely.

Further investigations should focus on specific organ injury, monitoring deterioration and recovery. These include serial measurements of electrolytes, kidney and liver function, as well as serial blood gases and chest x-ray to quantify pulmonary injury. Computed tomography (CT) of the chest can define pulmonary fibrosis. Paraquat concentrations can confirm exposure and estimate prognosis but are not widely available in a clinically useful time frame.

Differential diagnosis

Acute paraquat poisoning may resemble sepsis or poisoning with another cellular poison, such as phosphine (aluminium or zinc phosphides), colchicine or iron. Oropharyngeal necrosis is more marked in paraquat poisoning.

Treatment

All patients with paraquat ingestions should be observed in hospital for at least 12 hours post-ingestion because of the potential for severe toxicity. Standard resuscitative principles apply except that mild to moderate hypoxia should not be treated routinely with oxygen because it will exacerbate oxidative stress. Adequate hydration is important to optimize renal function and promote paraquat clearance.

Patients who present within 24 hours with severe systemic toxicity (e.g. hypotension, hypoxia, acidosis or low Glasgow Coma Scale [GCS] score) have no realistic chance of survival and early palliation should be instituted.

Current treatment options for paraquat poisoning include decontamination, immunosuppression, the provision of antioxidants and enhanced elimination.