Paraquat dichloride and diquat dibromide are dipyridyl herbicides used for weed control and as preharvest (desiccant) defoliants. Product formulations and concentrations differ by country. Concentrated solutions are highly toxic and caustic.

1. Paraquat and diquat are di-cations whose toxic effects are similar. Concentrated solutions (eg, >20%) may cause severe corrosive injury when ingested, injected, or applied to the skin, eyes, or mucous membranes. The dipyridyl herbicides are extremely potent systemic toxins and cause multiple-system organ damage. Engaging in a nicotinamide adenosine dinucleotide phosphate (NADPH)-powered reduction and oxidation cycle, dipyridyls spawn highly reactive free radicals, including superoxide and hydroxyl anions, leading to cell death and tissue destruction via lipid peroxidation. Renal failure is a common feature of both poisonings. Hepatic and cardiovascular failure may occur.
   1. In addition, paraquat is selectively taken up and concentrated by pulmonary alveolar cells, leading to cell necrosis followed (within days) by connective tissue proliferation and pulmonary fibrosis.
   2. Diquat is not taken up by pulmonary alveolar cells and does not cause pulmonary fibrosis, but it has been associated with CNS hemorrhagic infarctions.
2. Pharmacokinetics
   1. Absorption. Paraquat and diquat are rapidly (but incompletely) absorbed from the GI tract, and peak serum levels are reached within 2 hours of ingestion. The presence of food may reduce or delay absorption significantly. Although absorption is poor through intact skin, the dipyridyl herbicides can be taken up through abraded skin or after prolonged contact with concentrated solutions. Fatalities usually result from ingestion but have also been reported after intramuscular injection, vaginal and percutaneous exposure, and rarely after inhalation. Dipyridyls are contact herbicides not systemically incorporated into plants. Once applied to plants or soil, they are rapidly bound and unlikely to be toxic.
   2. Distribution. Paraquat has an apparent volume of distribution of 1.2-1.6 L/kg. It is taken up most avidly by lung, kidney, liver, and muscle tissue. In the lungs, paraquat is actively taken up against a concentration gradient.
   3. Elimination. Paraquat is eliminated renally, with more than 90% excreted unchanged within 12-24 hours if renal function is normal. Diquat is eliminated renally and via the GI tract.

Diquat is slightly less toxic than paraquat. However, both compounds are extremely poisonous.

1. Paraquat. Ingestion of as little as 2-4 g, or 10-20 mL, of concentrated 20% paraquat solution has resulted in death. The estimated lethal dose of 20% paraquat is 10-20 mL for adults and 4-5 mL for children. The mean oral 50% lethal dose (LD₅₀) in monkeys is approximately 50 mg/kg.
2. Diquat. Diquat deaths have been reported after ingestions of 15, 20, and 50 mL of 20% diquat, and after 30 mL of 14% diquat. The oral LD₅₀ in monkeys is approximately 100-300 mg/kg.

1. Paraquat. After ingestion of concentrated solutions, there is pain and swelling in the mouth and throat, and oral ulcerations may be visible. Nausea, vomiting, and abdominal pain are common. Severe gastroenteritis and GI fluid sequestration may cause massive fluid and electrolyte loss that contributes to renal failure. The severity and tempo of illness depend on the dose. Ingestion of more than 40 mg/kg (~14 mL of a 20% solution in an adult) leads to corrosive GI injury, rapid onset of renal failure, myonecrosis, shock, and death within hours to a few days. Ingestion of 20-40 mg/kg causes a more indolent course evolving over several days, with most patients dying of pulmonary fibrosis after days to weeks. Patients with ingestions of less than 20 mg/kg usually recover fully.
2. Diquat causes very similar initial symptoms but does not cause pulmonary fibrosis. Agitation, seizures, and coma have been described. Cerebral and brainstem hemorrhagic infarctions may occur.

Is based on a history of ingestion and the presence of oral burns, gastroenteritis, and multiple-organ system failure. Pulmonary fibrosis suggests paraquat poisoning and may be rapidly progressive or delayed.

1. Specific levels. The prognosis may be correlated with specific plasma levels, however levels are unlikely to be available in time to alter emergency management. Plasma and urine paraquat and diquat levels can be performed by Syngenta (US: 1-800-888-8372; Canada: 1-800-327-8633), although turnaround times may be very long. Plasma paraquat levels may be interpreted via the Hart nomogram or with assistance from a poison control center. A rapid qualitative test to detect paraquat or diquat adds sodium bicarbonate (2 g) and sodium dithionite (1 g) to 10 mL of the patient's urine. A blue or greenish grey color change is consistent with paraquat ingestion and a green color is seen with diquat ingestion.
2. Other useful laboratory studies include liver, renal and electrolyte studies, CBC, arterial blood gas, and upright chest radiography (for fibrosis, pneumomediastinum, or GI perforation). Rapid rise of creatinine (out of proportion to the BUN) has been seen.

1. Emergency and supportive measures. The Syngenta Agricultural Products Emergency Information Line (1-800-888-8372) is a resource for managing dipyridyl exposures and is available 24 hours a day, 7 days a week.
   1. Maintain an open airway and assist ventilation if needed.
   2. Treat fluid and electrolyte imbalance caused by GI losses and third spacing with IV crystalloid solutions.
   3. Avoid excessive oxygen administration, as oxygen is the substrate from which dipyridyls create harmful free radical species. Treat significant hypoxemia with supplemental oxygen, but use only the lowest amount needed to achieve a PO₂ of about 60 mm Hg.
   4. Treat pain due to corrosive injury with adequate doses of opioids.
2. Specific drugs and antidotes. A large number of studies have examined proposed treatments for dipyridyl poisoning, but at present, no specific antidote can be recommended. Treatment with cyclophosphamide and glucocorticoids has been effective for moderate-to-severe paraquat poisoning in a few small clinical trials but benefit has not been definitively proven.
3. Decontamination
   1. Skin and eyes. Remove all contaminated clothing and wash exposed skin with soap and water. Irrigate exposed eyes with copious saline or water.
   2. Ingestion. Immediate and aggressive GI decontamination is probably the only treatment that may affect the outcome significantly after paraquat or diquat ingestion.
      1. Prehospital. Prompt ingestion of food may provide some protection if charcoal is not immediately available.
      2. Hospital. Immediately administer 100 g of activated charcoal and repeat the dose in 1-2 hours. Gastric lavage may be helpful if performed within one hour of ingestion. Various clays, such as bentonite and fuller's earth, also adsorb paraquat and diquat but are probably no more effective than charcoal.
4. Enhanced elimination. The evidence supporting hemoperfusion is inconclusive. A limited number of studies suggest possible clinical benefit with early hemoperfusion (<4 hours) with and without concurrent continuous renal replacement therapy (CRRT). Hemodialysis and forced diuresis do not enhance elimination, although renal failure may necessitate hemodialysis.