ACMT Toxicology Visual Pearls: Blue Urine

Answer: 4
Paraquat – causes urine to turn blue with the urinary dithionite test

What is Paraquat?

Paraquat is a bipyridal herbicide that is extremely toxic to humans in small amounts. An ingestion of 5 mL of 20% paraquat can result in death in more than 50% of patients. Although paraquat is heavily restricted in the United States and the United Kingdom, it remains a commonly used suicide agent in the developing world.

From “Redox Cycling” to Respiratory Failure

The toxicity of paraquat is complex. Ingestion causes formation of free radicals that have a predilection for pneumocytes. These free radicals then react with oxygen to create superoxide and further hydroxyl free radicals. This vicious cycle is called “redox cycling” and ultimately causes respiratory failure, the most common cause of mortality following paraquat ingestion. Paraquat also causes damage to lipid containing cell membranes and is thought to produce direct damage to mitochondria.

Paraquat Toxicity: Clinical Manifestations

Clinical manifestations are dependent on the route and amount of exposure. The most common route of exposure is oral ingestion. Gastrointestinal symptoms such as nausea, vomiting, and abdominal pain are seen early. Due to corrosive nature of paraquat, patients can develop necrosis of their mucous membranes, ulcerations, and even esophageal rupture. Respiratory symptoms are common and acute respiratory distress syndrome (ARDS) can develop. Given the damage done to pneumocytes, patients that survive the acute toxicity often die weeks to months after an ingestion from pulmonary fibrosis.

Potential Diagnostics

Diagnostic testing is a challenge as plasma levels are not readily available in most clinical settings. Several nomograms have been created with the aim of predicting outcomes based on the paraquat concentration versus time from ingestion. The nomograms have been found to be better at predicting death than survival when examining plasma concentrations of paraquat between 4-24 hours after ingestion. However, all of the nomograms were found to underestimate mortality and therefore are not fully reliable to be used to predict outcomes.

A bedside test, the urinary dithionite test, can confirm paraquat ingestion, and is available in countries where paraquat ingestion is more common. This test is performed by adding 1 gram of sodium dithionite and 1 gram of sodium bicarbonate or 2M sodium hydroxide to 10 mL of patient urine. If paraquat was ingested, the urine will turn blue. Higher concentrations produce a deeper color. If no color change has occurred by 6 hours post ingestion, paraquat exposure is excluded.

One study showed that 68% of patients with an equivocal or negative dithionite test survived to discharge and that 100% of patients with a positive dithionite test died secondary to multi-organ failure. While this test is not difficult to perform in the laboratory, there are still limitations as often labs are unfamiliar with the test if paraquat toxicity is not endemic in their society.

Potential Treatments

Treatment is focused on:

• Decontamination: Activated charcoal or Fuller’s Earth is recommended for gastrointestinal decontamination.
• Prevention of further absorption: Extracorporeal removal has been suggested to possibly assist in the removal of paraquat, however mortality benefit has not been proven.
• Supportive care

Note that supplemental oxygen should be used judiciously as additional oxygen promotes further free radical formation.

Experimental Treatments

Other unproven treatments focus on reducing the inflammatory response and other processes that result in pulmonary fibrosis and delayed mortality. High dose immunosuppression with cyclophosphamide or steroids has been studied with variable results. Other experimental treatment options include acetylsalicylate, acetylcysteine, deferoxamine, and vitamin E.

Bedside Pearls

• Urine dithionite test can confirm the presence of paraquat (blue urine).
• Early recognition, clinical toxicology consultation, and confirmation of paraquat ingestion are key.
• The darker the color change, the higher the concentration of paraquat.
• If the urine does not show color change at 6 hours post ingestion, the patient is safe for discharge home.
• An ingestion of 5 mL of paraquat 20% concentrated solution can result in death in more than 50% of patients.
• Treatment is focused on decontamination and supportive care.
• Supplemental oxygen can worsen toxicity.