Hydrazine toxicity

Background

• Clear, colorless liquid that has an ammonia-like odor
• Powerful reducing agent that is highly reactive
• Exposure to metal oxides makes it highly exothermic and combustible
• Used in rocket fuels, missile fuels, aircraft emergency power unit fuel (notably the F-16)
• Used in chemical manufacturing (intermediate for insecticides/herbicides/dyes, polymerization catalyst for making plastics, used to manufacture sodium azide [air bag propellant], used to make isoniazid and fluconazole

Toxic Dose

• OSHA limit 1 ppm in air for 8-hour workday
• NIOSH recommends 0.03 ppm in air for 2-hour period
• Odor threshold 3.7 ppm in air

Routes of Exposure

• Inhalation
• Skin contact / absorption (rapid within 30 seconds of contact)
• Ingestion

Mechanism of Action

• Hydrazine + ketone/aldehyde = hydrazones + B6 = hydrazones of pryidoxine
  • "consumes" B6 in body
  • functional B6 deficiency results
• Metabolism of hydrazine produces free radical intermediates
• Inhibits pryidoxine kinase as well as glutamic acid decarboxylase which results in decrease production of GABA neurotransmitter

Clinical Features

Health Effects

• Short term inhalation exposure may cause coughing, irritation of throat/lungs, development of pulmonary edema, central nervous system depression, convulsions, tremors, or seizures
• Long term inhalation exposure may cause liver and kidney damage
• Ingestion may cause nausea, vomiting, uncontrolled shaking, inflammation of nerves, drowsiness, coma
• Short term contact exposure may cause dermatitis and/or chemical burn, can also lead to hemolytic anemia once absorbed

Signs and Symptoms

• Dizziness, nausea, itching, skin burning, tearing, coughing, excitement, tremors, polyneuritis, impaired cognition, lethargy, convulsions

Evaluation

• Monitor vital signs and mental status
• Examination with emphasis on skin, lungs, central nervous system
• Labs - serum electrolytes, renal function, urine analysis, complete blood count, liver function test, pH, lactate level, monitor methemoglobin levels
• Ancillary testing - chest x-ray and pulmonary function testing if inhalation exposure or patient has pulmonary symptoms

Management

• Mild to Moderate Exposure
  • Ensure patient has been decontaminated
  • Irrigate eyes with normal saline or water if exposed
  • Treat chemical burns if present
  • Monitor pulmonary status
  • Monitor for development of methhemoglobinemia
• Severe Exposure
  • Seizures - pyridoxine 25 mg/kg IM or IV up to 5 grams plus benzodiazepine
  • Respiratory distress - secure airway and assist ventilation
  • Methemoglobinemia - initiate oxygen therapy, give methylene blue if patient is symptomatic; Methylene blue dose 1 mg/kg IV over 5 to 30 minutes repeat dose may be given 1 hour after first if symptoms persist
  • Consider hemodialysis and acidification of urine if member has severe CNS depression
  • Hypoglycemia treat with D10 and thiamine

Disposition

• Home in cases of mild skin exposure without burns
• Observation for patients with inhalational or ingestion exposure for at least 12 hours to ensure no serious symptoms develop
• Admit patients with CNS symptoms or persistent pulmonary/gastrointestinal symptoms

See Also

Pyridoxine

Methylene blue