DESCRIPTION

Paraquat and diquat are herbicides used in commercial applications.

FORMS AND USES

• Paraquat is used as a desiccant, a contact herbicide, defoliant, and plant growth regulator.
• It is a restricted herbicide in the United States and therefore not widely available.
• Paraquat-based substances include Gramoxone (S, D, W), Gramonol, Gramixel, Gramuron, Actor, Dextrone, Dexuron, Esgram, Goldquat, Herbaxon, Herboxone, Para-col, Pathelion, Pillarquat, Pillarxone, Preglone, Priglone, Sweep, Terraklene, Total, Totacol, Toxer, Toxer Total, Viologen, and Weedol.
• Diquat is a structurally similar herbicide that produces similar toxicity, except for lung injury.

TOXIC DOSE

• Death occurs in most patients who ingest 20 to 40 mg/kg of paraquat; this may be just one swallow of more concentrated forms.
• Diquat is slightly less toxic, but 25 ml of concentrated solution is estimated as a lethal dose.

PATHOPHYSIOLOGY

• Paraquat is rapidly absorbed after gastrointestinal or dermal exposure.
• Pulmonary absorption is small because aerosol droplets are too large to reach the alveolus.
• After absorption, paraquat is actively taken up by type 1 and type 2 pulmonary epithelial cells, the principal target organ for toxicity.
• Paraquat is enzymatically reduced to an unstable free radical that is then reoxidized to produce a superoxide radical, causing direct free radical cell injury to the lung.

EPIDEMIOLOGY

• Poisoning is uncommon.
• Toxic effects are typically severe, with death occurring in most patients who ingest a gulp or more.

CAUSES

• Toxic ingestion is usually intentional.
• Dermal exposure is typically occupational.
• Child abuse must be considered if the patient is less than 1 year of age; suicide attempt if the patient is over 6 years of age.

PREGNANCY AND LACTATION

• Paraquat is concentrated in the fetus.
• The value of emergent cesarean section is unproven; no fetus has ever survived.

WORKPLACE STANDARDS

Paraquat

• OSHA. PEL TWA is 0.5 mg/m³.
• NIOSH. Not listed.
• ACGIH. TLV TWA is 0.5 mg/m³ for total particulate.

Section Outline:

• DESCRIPTION
• FORMS AND USES
• TOXIC DOSE
• PATHOPHYSIOLOGY
• EPIDEMIOLOGY
• CAUSES
• PREGNANCY AND LACTATION
• WORKPLACE STANDARDS
  • Paraquat

DIFFERENTIAL DIAGNOSIS

• Caustic injury to mucosa and oropharyngeal membranes may be mistaken for diphtheria or ingestion of caustic agents.
• The rapid progression of multiorgan failure following serious paraquat ingestion may resemble several clinical conditions, such as sepsis, cardiogenic shock, or severe salicylate toxicity.
• Pulmonary fibrosis and restrictive lung disease may resemble silicosis, asbestosis, and sarcoidosis; however, the rapid progression of severe pulmonary fibrosis is highly characteristic of paraquat ingestion.

SIGNS AND SYMPTOMS

• Paraquat. The initial effects are caustic burns to the gastrointestinal tract or skin, depending on exposure; after a day or two, pulmonary complaints and rapidly progressive pulmonary injury develop in serious cases.
• Diquat. Symptoms begin with gastrointestinal effects similar to paraquat, but diquat does not produce pulmonary injury.

Vital Signs

• Tachycardia and hypotension may occur due to gastrointestinal toxicity.
• Tachypnea develops in patients who develop pulmonary injury.

HEENT

• Splash injuries may result in severe conjunctival and corneal lesions or uveitis from paraquat or diquat.
• Oropharyngeal burns may result from ingesting paraquat or diquat.

Dermatologic

Concentrated paraquat or diquat solutions may cause dermal burns that enhance absorption.

Cardiovascular

• Cardiovascular collapse may occur rapidly following large ingestions of paraquat or diquat.
• Myocarditis may occur with large ingestions of paraquat.

Pulmonary

• Death due to pulmonary fibrosis is common with paraquat.
• Progression of pulmonary fibrosis is refractory to treatment.

Gastrointestinal

Both diquat and paraquat produce marked gastrointestinal effects: nausea, vomiting, abdominal pain and diarrhea, followed by perforation and hemorrhage within a few days in some severe cases.

Hepatic

• Moderate centrilobular hepatocellular necrosis may occur within a few days with paraquat.
• Intrahepatic cholestasis is common.
• Diquat produces minor injury.

Renal

• Renal tubular injury evolves over a few days for both paraquat and diquat.
• Renal failure may resolve if the patient survives.

Fluids and Electrolytes

Fluid losses may be severe due to gastrointestinal burns or hemorrhage.

Musculoskeletal

Muscular necrosis has occurred after ingestion.

Neurologic

• Cerebral edema, lethargy, and coma occur in severe cases with either paraquat or diquat.
• Pontine purpura and brainstem infarct have occurred with diquat.

Endocrine

Adrenal necrosis may occur with massive ingestion.

PROCEDURES AND LABORATORY TESTS

Emergency information and analysis for paraquat:

• United States: Zeneca Inc. Agricultural Products, Wilmington, DE 19897; Telephone 1-800-327-8633 (24-hour emergency line)
• Canada: ICI Chipman, Stoney Creek, Ontario L8G 3G1; Telephone 1-800-561-3636 (24-hour emergency line)
• United Kingdom: Zeneca Agrochemicals, Femhurst, Haslemere, Surrey GU27 3JE, England; Telephone (0622) 814777 (24-hour emergency line)
• Australia: ICI Crop Care, Melbourne, Victoria 3001; Telephone 008-033-111 (24-hour emergency line)

Essential Tests

• Serum electrolytes, glucose, BUN, creatinine, and urinalysis to assess renal injury and guide replacement therapy in patients with fluid losses; paraquat may cause hypokalemia, which indicates a poor prognosis.
• Aspartate aminotransferase, alanine aminotransferase, lactic dehydrogenase, bilirubin, prothrombin time/international normalized ratio, and partial thromboplastin time are used to monitor for the development of hepatic injury.

Recommended Tests

• Serum creatine kinase assesses muscle injury.
• Serum amylase assesses pancreatic injury.
• Arterial blood gases are used to monitor the progression and treatment of pulmonary injury.
• Paraquat levels in urine and serum are possibly helpful in predicting severity of poisoning, but they are not typically available (see emergency numbers above).
• Quantitative tests are predictive of prognosis; plasma levels greater than 2 mg/L at 4 hours and greater than 0.1 mg/L at 24 hours usually indicate a fatal outcome.
• Chest radiograph may be normal initially, but bilateral massive infiltrates develop in severe cases.
• Pulmonary function tests. Impairment of diffusion and decrease in pulmonary compliance as fibrosis develops.
• Endoscopy. The presence of gastric or esophageal ulcers indicate a poor prognosis; endoscopy is also used to identify ulcerations at risk of perforation.

Section Outline:

• DIFFERENTIAL DIAGNOSIS
• SIGNS AND SYMPTOMS
  • Vital Signs
  • HEENT
  • Dermatologic
  • Cardiovascular
  • Pulmonary
  • Gastrointestinal
  • Hepatic
  • Renal
  • Fluids and Electrolytes
  • Musculoskeletal
  • Neurologic
  • Endocrine
• PROCEDURES AND LABORATORY TESTS
  • Essential Tests
  • Recommended Tests

• Initial treatment for diquat or paraquat exposure should focus on decontamination and supportive care.
• Supportive care with appropriate airway management is vital.
• Name, amount, concentration, and time of exposure should be determined for all substances involved.

DIRECTING PATIENT COURSE

The health-care professional should call the poison control center when history of paraquat or diquat exposure is obtained.

The patient should be referred to a health-care facility when:

• History of paraquat or diquat exposure is obtained.
• Patient or caregiver seems unreliable.
• Toxic effects develop.

Admission Considerations

Inpatient management is warranted for all patients who have ingested paraquat or diquat or have signs that suggest potential paraquat toxicity.

DECONTAMINATION

Out of Hospital

• Emesis should not be induced due to caustic effects.
• If delay in reaching medical care is expected, the patient should be instructed to eat 1 to 2 handfuls of dirt, food, or activated charcoal immediately in order to decrease gastrointestinal absorption as much as possible.
• Exposed skin should be irrigated with soap and water; scrubbing may enhance absorption and is not recommended.

In Hospital

• Gastric lavage is not recommended due to caustic hazard.
• Cautious aspiration with nasogastric tube for patient presenting soon after ingestion of paraquat or diquat may be reasonable due to extreme potential toxicity.
• Activated charcoal (1-2 g/kg) should be administered without a cathartic if an ingestion has occurred within the previous few hours; a second dose can be given after 4 hours.
• Both fuller's earth (1-2 g/kg of a 15% aqueous suspension) and bentonite (1-2 g/kg of a 7% aqueous slurry) have been advocated to absorb paraquat after ingestion; these are often not available and have no clear advantage over activated charcoal.
• Exposed skin should be irrigated with soap and water; scrubbing should be avoided.

ANTIDOTES

There is no specific antidote for paraquat or diquat poisoning.

ADJUNCTIVE TREATMENT

Hemodialysis is used for renal failure, but is not effective for paraquat pulmonary toxicity. The following therapies are not recommended for either paraquat or diquat toxicity:

• Hemoperfusion is not effective.
• Lung transplantation has been attempted; there have been no long-term survivors due to paraquat injury to the transplanted lung.
• Urinary alkalinization has no proven benefit.
• Whole-bowel irrigation has no proven benefit.
• None of the following therapies have yet been found effective: cyclophosphamide, D-propranolol, vitamin E, deferoxamine, selenium, superoxide dismutase, ascorbic acid (vitamin C), N-acetylcysteine, fibrinolytic agents, colchicine, radiotherapy, and dexamethasone.

Section Outline:

• DIRECTING PATIENT COURSE
  • Admission Considerations
• DECONTAMINATION
  • Out of Hospital
  • In Hospital
• ANTIDOTES
• ADJUNCTIVE TREATMENT

PATIENT MONITORING

• Continuous cardiac and pulmonary monitoring should be performed on all patients.
• Patients should be monitored for the development of pulmonary fibrosis even after other systemic effects have resolved.

EXPECTED COURSE AND PROGNOSIS

• Large (>40 mg/kg) paraquat ingestion (more than 15 ml of 20% liquid concentrate in adult) typically causes death from multiorgan failure within a few days.
• Ingestion of 20 to 40 mg/kg (e.g., more than one sachet of 2.5% Weedol or less than 15 ml of 20% concentrate in adult). Initial gastrointestinal toxicity is followed by systemic toxicity, which may include reversible renal failure or hepatic failure, followed by death from pulmonary failure within 3 to 20 days.
• Ingestion of less than 20 mg/kg (e.g., less than one sachet of 2.5% Weedol). Patient is asymptomatic or develops some gastrointestinal effects; transient impairment of lung function may occur, but patient recovers.
• Fatal pulmonary fibrosis may occur even in patients who recover from initial toxic effects.
• Esophageal perforation and possibly mediastinitis may occur following ingestion.

DISCHARGE CRITERIA/INSTRUCTIONS

• From the emergency department. Patients with paraquat or diquat exposure should not be discharged.
• From the hospital. Asymptomatic patients may be discharged if toxic effects do not develop within a few days of exposure.

Section Outline:

• PATIENT MONITORING
• EXPECTED COURSE AND PROGNOSIS
• DISCHARGE CRITERIA/INSTRUCTIONS

DIAGNOSIS

Smoking of paraquat-treated marijuana has not been documented to cause significant toxicity; pyrolysis inactivates the paraquat.

TREATMENT

Administration of activated charcoal should not be delayed while waiting for endoscopy to be performed.

FOLLOW-UP

Patients may recover from early gastrointestinal, renal, and other effects only to develop fatal pulmonary fibrosis later.

Section Outline:

• DIAGNOSIS
• TREATMENT
• FOLLOW-UP

Toxic effect of other substances, chiefly nonmedicinal as to source.

RECOMMENDED READING

Ellenhorn MJ. Paraquat. Ellenhorn's medical toxicology, 2nd ed. Baltimore: Williams & Wilkins, 1997:1631-1637.

POISINDEX Editorial Staff. Paraquat. In: Rumack BH, Sayre NK, Gelman CR, eds. POISINDEX system. Englewood, CO: Micromedex Inc. (edition expires May 31, 1998).

Authors: Lada Kokan and Gerald F. O'Malley

Reviewer: Richard C. Dart