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Hydrazines are a generic group of structurally related chemicals with numerous commercial uses. Different kinds of hydrazine compounds include hydrazines, hydrazones, 1,1-dimethylhydrazine, and 1,2-dimethylhydrazine. Most hydrazines are manufactured as an intermediate during agricultural chemicals and plastics production, a component of rocket propellant and fuels, water treatments, and a metabolite of the gyromitra mushroom and anti-tuberculosis drug isoniazid. Hydrazine exposure has toxic effects on multiple organ systems, including the neurological, hematological, pulmonary, dermatologic, and hepatic systems. Hydrazines produce a functional pyridoxine deficiency by inhibiting its synthesis by deactivating key coenzymes. Management involves aggressive supportive care and the administration of pyridoxine (vitamin B6) for refractory seizures. This activity reviews the history, potential for exposure, pathophysiology, evaluation, and management of hydrazine toxicity. The role of the interprofessional team in evaluating and managing patients exposed to this chemical compound is highlighted. Objectives: Understand the pathophysiology of hydrazine toxicity depending on the route of exposure and the system involved. Recognize occupational and environmental risk factors commonly associated with exposure to hydrazine and its derivatives. Implement effective diagnostic processes involving the interprofessional team. Apply best practices to treat hydrazine toxicity, including decontamination, supportive care, and administration of pyridoxine for neurological sequelae. Access free multiple choice questions on this topic.

Hydrazines (R2N−NR2) are a class of chemical compounds with 2 nitrogen atoms linked by a single covalent bond and may carry up to four alkyl substituents.[1][2] Organohydrazine compounds and their derivatives produce significant toxicity in human exposures.[3] Commonly encountered examples include hydrazine, hydrazones, 1,1-dimethylhydrazine, 1,2-dimethylhydrazine, and monomethylhydrazine (MMH). In its pure form, hydrazine (H2N-NH2) is a clear, colorless liquid chemical with an ammonia-like odor.[4] Throughout this activity, the word "hydrazines" refers to hydrazine, 1,1-dimethylhydrazine, 1,2-dimethylhydrazine, and monomethylhydrazine.

Hydrazine and its derivatives have numerous industrial, military, and medical applications.[3][5] Due to its high heat of combustion and highly exothermic reaction in the presence of oxygen, German scientists first developed hydrazine as the principal component of rocket fuel during World War II.[6] Postwar, hydrazines became widely adopted as a powerful and reliable propellant with liquid properties like water.[7] From the 1970s to today, they can be found in thruster fuel for spacecraft and as a propellant for missiles. Because hydrazines possess strong reducing properties, they are commonly used as a starting or intermediate reactant during the production of foaming or blowing agents for plastic production, agricultural products (plant-growth regulators, herbicides, fungicides, insecticides), and polymers.[8] It is also used as an oxygen scavenger to prevent corrosion in boiler water and water-heating systems. Naturally occurring hydrazines are rare and can be found as mycotoxins in the Gyromitra and Agaricus species of mushrooms. The Gyromitra mushrooms contain the toxin gyromitrin (n-methyl-N-formyl hydrazone) and undergo hydrolysis to the principal toxic compound monomethylhydrazine (MMH), which is responsible for seizures in severe poisoning. Small amounts of hydrazine have been reported in tobacco; however, there have been no documented toxicities from human exposures.[9]

Epidemiological studies of the consequences of exposure to hydrazine can be divided into acute and chronic exposures. Acute Exposure Acute exposures have been documented since 1965 and were primarily associated with military occupational exposures to hydrazine. Frierson et al. described 2 cases where young men were exposed to vapors of hydrazine mixed with unsymmetrical dimethyl hydrazine (UDMH). Both were treated with pyridoxine with rapid improvement of their symptoms.[10] Reid et al. described a young sailor who accidentally ingested liquid hydrazine while working in the ship’s engine room.[11] Sotaniemi et al. 1971 described a fatal accidental exposure to a machine worker with chronic repeated exposures for six months.[12] Kirklin et al. described a case of a man exposed to a hydrazine industrial explosion and went into a coma that responded to pyridoxine.[13] Harati and Niakin describe a case of a young man who accidentally ingested a mouthful of liquid hydrazine.[14] Dhennin et al. described a chemical technician exposed to a UDMH industrial explosion.[15] Kao et al. 2007 described a case of a fighter jet technician who experienced hepatic injury after exposure to a hydrazine fuel leak.[16] Binyamin et al 2018 described a case of an aircraft technician who developed elevated creatine phosphokinase (CPK) levels after exposure to hydrazine vapor. Dermal exposures are mostly linked to occupational injuries through the gold-plating industry, chicken feed additives, herbicides, or steam power plants.[17][18][19] Chronic Exposure Chronic exposures have been further studied in epidemiological studies for various reasons, but mainly to determine the carcinogenicity of hydrazine. Unfortunately, many epidemiological studies on hydrazine were confounded by concomitant exposure to other chemicals, making direct correlations difficult.[20][21][22][23] Wald et al. studied 427 men exposed to varying levels of hydrazine, among other chemicals, in a hydrazine manufacturing plant.[24] He concluded that the overall number of deaths in the hydrazine-exposed group was lower than expected, and mortality rates from lung and all types of cancer were similar to expected values.[24] Roe et al. had previously examined 423 of these same individuals in 1978. They also determined that occupational exposures to hydrazine were not significantly associated with a greatly increased cancer incidence.[25]

Wald et al. studied 427 men exposed to varying levels of hydrazine, among other chemicals, in a hydrazine manufacturing plant.[24] He concluded that the overall number of deaths in the hydrazine-exposed group was lower than expected, and mortality rates from lung and all types of cancer were similar to expected values.[24] Roe et al. had previously examined 423 of these same individuals in 1978. They also determined that occupational exposures to hydrazine were not significantly associated with a greatly increased cancer incidence.[25] Contassot et al. described 130 men exposed to hydrazine at various levels over six months. They showed a statistically significant higher incidence of cancer in the high-exposure group (>1 ppm), which was reduced when skin cancers were excluded.[26] Morris et al. followed up with 95% of the workers initially evaluated by Wald et al. (1984) and Roe et al. (1978) 10 years after their initial evaluation. They determined that there was also no all-cause mortality increase from occupational exposure to hydrazine.[27] Ritz et al. 2006 performed an epidemiological study of 6107 aerospace workers exposed to varying amounts of hydrazine for at least 2 years and showed an increased risk of lung cancer mortality, increased incidence of colon and rectal cancers, and a possible dose-response association with pancreatic cancer. This study also had patients who developed leukemias, lymphomas, and kidney cancers; however, the numbers of exposed individuals were too small to show significance.[22] Common criticisms of this study are that there were many other chemicals the workers may have been exposed to.[20] Zhao et al. 2005 examined the same group and found a higher incidence of lung cancers and melanoma with a possible higher incidence of esophageal cancer, stomach cancer, non-Hodgkin lymphoma, and leukemias; however, they concluded that it was most likely attributed to mineral oil exposure. In addition, they found a higher incidence of kidney cancers, which they attributed to trichloroethylene exposure.[28] Krishnadasan et al. 2007 also evaluated the same cohort of aerospace workers and found a higher incidence of prostate cancer; however, they attributed it to trichloroethylene exposure.[23]

Zhao et al. 2005 examined the same group and found a higher incidence of lung cancers and melanoma with a possible higher incidence of esophageal cancer, stomach cancer, non-Hodgkin lymphoma, and leukemias; however, they concluded that it was most likely attributed to mineral oil exposure. In addition, they found a higher incidence of kidney cancers, which they attributed to trichloroethylene exposure.[28] Krishnadasan et al. 2007 also evaluated the same cohort of aerospace workers and found a higher incidence of prostate cancer; however, they attributed it to trichloroethylene exposure.[23] The World Health Organization (WHO) in 1987 described populations with potentially high occupational exposures as workers at facilities producing hydrazine itself and/or its salts and derivatives, propulsion testing facilities, rocket launching sites, and locations where aircraft using hydrazine as an emergency fuel are assembled or refueled.[26] The Agency for Toxic Substances and Disease Registry (ATSDR) in 1997 stated that human exposures to hydrazine and 1,1-dimethylhydrazine occur mainly in the workplace or the vicinity of aerospace or industrial facilities or hazardous waste sites.

Hydrazine's pathophysiology depends on the route of exposure and the system it affects. Inhalation exposure causes direct pulmonary injury due to the caustic nature of hydrazine and may also lead to an increased incidence of lung cancer.[22] In animal studies, hydrazine inhalational injuries have been shown to cause pulmonary edema and localized bronchial mucosal damage.[29] Importantly, there have been reports of inhalation injury causing systemic effects such as neurotoxicity and hepatotoxicity.[30] The pathophysiology of dermatological injury of hydrazine toxicity is mostly derived from animal studies and a few human case reports. Hydrazine can cause contact dermatitis or caustic injury.[31][17][18] This is due to hydrazine's strong alkali properties and can cause liquefactive necrosis similar to other alkali-caustic burns.[29][32] There are 2 cases of people developing systemic symptoms from dermal exposure, including neurotoxicity and hepatotoxicity; however, these were exposures to industrial explosions, so there was likely a combination of dermal and inhalational exposures.[13][15] Ingested oral exposure to hydrazines has the potential to cause systemic symptoms, mostly secondary to taking medications that have hydrazine as a metabolite. Asymptomatic patients taking isoniazid (INH) at therapeutic doses (300 mg/day) for two weeks showed elevated levels of hydrazine in their blood and plasma.[26][33] There have also been acute oral exposures to hydrazine through ingestion of hydrazine-containing fuel, which produced systemic symptoms including neurotoxicity, specifically seizures, loss of consciousness, altered mental status, agitation, nystagmus, and peripheral neuropathy.[11][14] Hydrazine's neurotoxicity occurs from disrupting the equilibrium between gamma-aminobutyric acid (GABA) and glutamate (the human body's primary inhibitory and excitatory neurotransmitters, respectively). Through various mechanisms, hydrazine-containing compounds inhibit pyridoxine (vitamin B6) and its downstream metabolite, pyridoxal 5' phosphate (P5P), the essential cofactor for glutamic acid decarboxylase and GABA synthesis, resulting in reduced GABA levels and subsequent clinical effects of seizures. Hydrazine metabolites are found in INH and gyromitrin mycotoxin (from the gyromitra mushroom species).

Hydrazine's neurotoxicity occurs from disrupting the equilibrium between gamma-aminobutyric acid (GABA) and glutamate (the human body's primary inhibitory and excitatory neurotransmitters, respectively). Through various mechanisms, hydrazine-containing compounds inhibit pyridoxine (vitamin B6) and its downstream metabolite, pyridoxal 5' phosphate (P5P), the essential cofactor for glutamic acid decarboxylase and GABA synthesis, resulting in reduced GABA levels and subsequent clinical effects of seizures. Hydrazine metabolites are found in INH and gyromitrin mycotoxin (from the gyromitra mushroom species). Isoniazid toxicity stems from several mechanisms of its downstream metabolites. INH hydrazine, 1,1-dimethylhydrazine, and hydrazones directly inhibit the enzyme pyridoxine phosphokinase by complexing its essential cofactor, pyridoxine.[26] Thus, pyridoxine cannot convert to P5P, the catalysis for the enzyme glutamic acid decarboxylase, in effect inhibiting the conversion of glutamate to GABA. INH hydrazines also directly bind with pyridoxal phosphate to form a hydrazone complex that is renally excreted. Through these mechanisms, hydrazine and its derivatives cause a functional pyridoxine deficiency, resulting in the depletion of GABA and an excess of glutamate, leading to refractory seizures.[26] Additionally, in animal studies, hydrazine has been shown to affect the urea cycle by increasing the activity of argininosuccinase and inhibiting ornithine-ketoacid transaminase, leading to hyperammonemia which can contribute to its neurotoxicity.[34][29] Secondary to these mechanisms, hydrazine-induced neurotoxicity can present as any of the following: twitching, hyperreflexia, clonic movements, restlessness, violent behavior, altered mental status, ataxia, paresthesias, lethargy, seizures, and coma.[32] Similarly, hydrazine's hepatotoxicity is mainly known from isoniazid toxicity. Hydrazines metabolized from isoniazid by direct hydrolyzation or metabolism by N-acetyltransferase type 2 to acetylhydrazine are oxidized by CYPE1 to reactive metabolites that induce oxidative stress and alter lipid metabolism, causing hepatotoxicity.[35] This leads to focal hepatic necrosis, cell degeneration, and fatty liver.[32] Gyromitrin compounds from the Gyromitra species of mushrooms are metabolized to monomethylhydrazine and inhibit the conversion of glutamate to GABA by similar mechanisms.[35]

Similarly, hydrazine's hepatotoxicity is mainly known from isoniazid toxicity. Hydrazines metabolized from isoniazid by direct hydrolyzation or metabolism by N-acetyltransferase type 2 to acetylhydrazine are oxidized by CYPE1 to reactive metabolites that induce oxidative stress and alter lipid metabolism, causing hepatotoxicity.[35] This leads to focal hepatic necrosis, cell degeneration, and fatty liver.[32] Gyromitrin compounds from the Gyromitra species of mushrooms are metabolized to monomethylhydrazine and inhibit the conversion of glutamate to GABA by similar mechanisms.[35] Hydrazine's hemotoxicity is known through in vitro studies with human red blood cells. This showed the development of hemolytic anemia, methemoglobinemia, and Heinz body formation.[29] It is hypothesized that hydrazine and its derivatives cause denaturing of hemoglobin, which destroys red blood cells.[29]

To recognize hydrazine toxicity, it is essential to be familiar with occupational and environmental risk factors known to be commonly exposed to hydrazine and its derivatives. The occupations most commonly exposed to hydrazine are facilities producing or storing rocket fuels, such as propulsion testing facilities, rocket launching sites, aerospace facilities, hazardous waste sites, and military installations.[26] A medical history of concurrent tuberculosis may include isoniazid (INH), which metabolizes into hydrazine. Mushroom foragers may be exposed to the false morel, Gyromitra, which contains the mycotoxin gyromitrin that metabolizes into monomethylhydrazine (MMH). Hydrazine toxicity can occur through inhalation and oral and dermal exposures. Exposures may be categorized as acute (<14 days), intermediate (15 to 364 days), and chronic (>365 days).[26] Chronic exposure to hydrazine can lead to similar symptoms in the acute setting but also includes additional carcinogenic risk.[22][25][24] Hydrazine has been associated with various cancers, including lung, lymphopoietic, liver, colorectal, and skin cancers.[26] Dermal exposure has been mostly linked to occupational injuries through the gold-plating industry, chicken feed additives, herbicides, or steam power plants. [17][18][19] Skin irritation and caustic liquefactive necrosis may occur within 1 hour. Hydrazine sulfate has been reported to cause contact dermatitis, suggesting it is a sensitizing agent.[29][42][43][18][17] Chronic dermal exposure by a factory worker in a steam power station has also been linked to the development of multiple basal cell carcinomas in a case report.[19] Acute inhalational hydrazine exposure has been associated with pulmonary edema and pleural effusions.[29] Exposed individuals to hydrazine and 1,1-dimethylhydrazine vapors exhibited symptoms of dyspnea, sore throat, burning sensation of the face and nasal mucosa, and chest tightness.[29] This may progress to delayed pulmonary edema with pleural effusions and death. Hydrazine has also been associated with an ammonia-like odor.[32] Respiratory arrest in toxic inhalational exposures may be more attributed to hydrazine's neurotoxic and convulsive effects.

Acute inhalational hydrazine exposure has been associated with pulmonary edema and pleural effusions.[29] Exposed individuals to hydrazine and 1,1-dimethylhydrazine vapors exhibited symptoms of dyspnea, sore throat, burning sensation of the face and nasal mucosa, and chest tightness.[29] This may progress to delayed pulmonary edema with pleural effusions and death. Hydrazine has also been associated with an ammonia-like odor.[32] Respiratory arrest in toxic inhalational exposures may be more attributed to hydrazine's neurotoxic and convulsive effects. Neurotoxicity from acute exposures to hydrazine, monomethylhydrazine (MMH), and 1,1-dimethylhydrazine (UDMH) may range from central nervous system (CNS) depression to seizures.[11] Hydrazine has been found to induce seizures at high doses but CNS depression at low doses. The CNS depression described in human exposures has been reported to last up to 3 days. In contrast, the alkyl derivatives of hydrazine, MMH, and UDMH induce primarily neuroexcitatory effects and tonic-clonic seizures, with MMH being more potent than UDMH. Other neuroexcitatory effects include twitching, hyperreflexia, and clonus.[29] Hydrazine and its derivatives may cause hemolytic anemia and methemoglobinemia. MMH has been described as having the most severe hemotoxic effects.[29] Hydrazine exposure has been shown to cause an elevation in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) within 5 hours and lasting up to 1 week, with resolution after 4 to 5 weeks.[4] Focal hepatic necrosis and fatty liver degeneration have been described in chronic exposures.[44][45] In humans, there has been a case of an inhalation injury of a machinist exposed to hydrazine hydrate once a week for 6 months, which proved fatal; the patient presented with hepatorenal failure and died secondary to complications from pneumonia.[12] An aircraft technician also had an acute inhalation exposure (<10 minutes) that caused transient hepatotoxicity.[16]

Hydrazine exposure has been shown to cause an elevation in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) within 5 hours and lasting up to 1 week, with resolution after 4 to 5 weeks.[4] Focal hepatic necrosis and fatty liver degeneration have been described in chronic exposures.[44][45] In humans, there has been a case of an inhalation injury of a machinist exposed to hydrazine hydrate once a week for 6 months, which proved fatal; the patient presented with hepatorenal failure and died secondary to complications from pneumonia.[12] An aircraft technician also had an acute inhalation exposure (<10 minutes) that caused transient hepatotoxicity.[16] Chronic exposure to hydrazine can lead to similar symptoms in the acute setting but also includes additional carcinogenic risk.[22][25][24] A study of chronic inhalation exposure to hydrazine in aerospace workers also showed an increased risk of lung cancer mortality.[22] Prior studies with intermediate-to-chronic inhalation injury in a hydrazine-manufacturing plant did not show a statistically significant increase in lung cancer mortality due to the small sample sizes.[24][21] Hydrazine has been associated with various cancers, including lung, lymphopoietic, liver, colorectal, and skin cancers.[26]

Oral ingestions of hydrazine may cause caustic injury and liquefactive necrosis due to its alkali properties.[14][11] If the patient exhibits any 2 of these 3 symptoms—drooling, stridor, or vomiting—the patient should be evaluated by endoscopy to assess the extent of the esophageal and gastric injury.[46] Airway protection may be needed if there is extensive edema and caustic injury to the oropharynx and the inability to tolerate secretions. The patient's mental status may range from CNS depression to CNS excitation, and seizures refractory to standard treatment with benzodiazepines, barbituates, and propofol may occur. Fingerstick blood glucose level should be obtained as hydrazine is associated with hypoglycemia.[47] The pulmonary exam and chest radiography may show signs of pleural effusion to pulmonary edema. Blood gas oximetry may show methemoglobinemia. A complete blood count may show hemolytic anemia, and a blood smear may show Heinz bodies.[29] The basic metabolic panel may show rhabdomyolysis and liver function testing may range from transient transaminitis to fulminant hepatic failure.[45] Prolonged hepatic injury has been seen to last up to 1 week and resolves in patients surviving the initial exposure after 4 or 5 weeks.[16] Chronic exposures to hydrazine in the occupational setting should also be evaluated for certain cancers, as hydrazine is carcinogenic. Cancers of the colon, skin, nasal epithelium, lung, and liver have all been described but may be confounded due to exposures to other toxins in these studies.[48][22] Hydrazine exposure has also been associated with basal cell carcinoma.[19]

Treatment of hydrazine exposures involves decontamination, supportive care, and administration of pyridoxine for neurological sequelae, especially seizures. Patients should be removed from the site of exposure to a minimum of 75 feet away. Full decontamination, including removing all clothing and copious irrigation of exposed skin and/or eyes with water for a minimum of 15 minutes.[29] First responders and emergency medical services at the site of hydrazine exposure should wear Level A personal protective equipment against vapors, skin, and eyes. Caustic burns to the skin should be treated similarly to soft tissue injuries and may require special management at a burn center.[13] Inhalational exposures to hydrazine are managed by supportive care, including supplemental oxygen and close airway observation. Delayed pulmonary edema may occur, and observation for 24 to 48 hours may be required. Oral ingestions of hydrazines may cause caustic injury to the upper airway and gastrointestinal tract; thus, activated charcoal is not recommended in this situation. Since hydrazines are rapidly absorbed when ingested, activated charcoal administered after arrival to the emergency department may be futile. Early activated charcoal decontamination is recommended for acute isoniazid and gyromitra ingestions.[35] Hydrazine neurotoxicity, ranging from coma and seizures, has been treated successfully with pyridoxine.[13][49] In INH-induced seizures, adults are given 1 g of IV pyridoxine for each gram of INH ingested, with a maximum dose of 5 g. If the amount ingested is unknown, 5 g of IV pyridoxine may be given empirically. Pediatric dosing is 70 mg/kg of IV pyridoxine with a maximum of 5 g.[35][50] For the actively seizing patient, pyridoxine may be given 0.5 g/min until the cessation of seizure or the maximum dose is reached. After seizure control, the remainder of the dose may be infused over 4 to 6 hours to maintain pyridoxine concentrations while INH is eliminated.[50] Repeat dosing is indicated if the patient has CNS depression or non-convulsive status epileptics. For hydrazine, MMH, and UDMH poisonings, using the same dosage as INH poisoning is reasonable. The dosing of pyridoxine for hydrazine toxicity has varied from 200 mg intravenous with 400 mg intramuscular to 10 grams intravenously.[13][51] Benzodiazepines and barbituates should also be used to stop seizure activity rapidly.

For the actively seizing patient, pyridoxine may be given 0.5 g/min until the cessation of seizure or the maximum dose is reached. After seizure control, the remainder of the dose may be infused over 4 to 6 hours to maintain pyridoxine concentrations while INH is eliminated.[50] Repeat dosing is indicated if the patient has CNS depression or non-convulsive status epileptics. For hydrazine, MMH, and UDMH poisonings, using the same dosage as INH poisoning is reasonable. The dosing of pyridoxine for hydrazine toxicity has varied from 200 mg intravenous with 400 mg intramuscular to 10 grams intravenously.[13][51] Benzodiazepines and barbituates should also be used to stop seizure activity rapidly. Methemoglobinemia should be treated with standard treatment with methylene blue.

Pulmonary Irritants Phosgene Chlorine Ammonia Ethylene oxide Chloramine Hepatotoxicity Amantia mushrooms Alkali Caustic Burns Sodium hydroxide Potassium hydroxide Sodium hypochlorite Ammonia Seizures Status epilepticus of unknown origin Severe hyponatremia Substance-induced Sedative-hypnotic withdrawal Hypoxic syncope Anti-NMDA receptor encephalitis CNS Depression/Coma Sedative-hypnotic intoxication Opioid intoxication Hepatic encephalopathy Hypoglycemia Cerebrovascular accident

The prognosis for hydrazine toxicity depends on the dose and route of exposure. There have only been 2 reported cases of death from direct hydrazine toxicity.[45][12] Most exposure cases show rapid improvement in neurologic symptoms and eventual improvement of hepatic injury.[29] There have been cases of persistent neuropathy and hepatic injury.[15] This excludes the prognosis of isoniazid or other medications with hydrazine metabolites.

Pulmonary toxicity: Mucosal irritation, pleural effusion, delayed pulmonary edema Neurotoxicity: CNS depression, coma, clonus, refractory seizures Cutaneous toxicity: Dermatitis and liquefactive necrosis Hepatoxicity: Fulminant hepatic failure[29] Nephrotoxicity: Rhabdomyolysis[45] Hemotoxicity: Methemoglobinemia and hemolytic anemia Possible long-term sequelae are secondary to the potential carcinogenic nature of hydrazine exposure. These include lung, lymphopoietic, skin, colorectal, and liver cancers.[22][48][19]

Please consider consulting your poison control center for advice on managing hydrazine toxicity. Depending on the patient’s status, consider consulting an intensivist, general surgery, or burn specialist, a gastroenterologist, and a nephrologist.

To avoid hydrazine toxicity, those potentially exposed to it through manufacturing or the military should be aware of the recommended exposure guidelines. The National Institute of Occupational Health and Safety (NIOSH) has set out certain Acute Exposure Guideline Levels for Hazardous Substances. The guideline level for the airborne concentration for which the general population is expected to experience discomfort or irritation for hydrazine is 0.1 ppm. The guideline level for the airborne concentration for which the general population is expected to experience long-lasting effects is 1.6 ppm in 8 hours. The guideline level for the airborne concentration for which the general population is expected to experience life-threatening health effects or death is 4.4 ppm in 8 hours. Overall, the NIOSH exposure limit is 0.03 ppm with a 2-hour ceiling. The odor threshold for hydrazine’s ammonia-like odor is 3 to 4 ppm. There are also guidelines from the Occupational Safety and Health Administration, American Conference of Governmental Industrial Hygienists, and Short-Term Public Emergency Guidance Level. Those exposed to hydrazine should also be educated about the possible symptoms that acute exposure may cause.[26]

Hydrazine exposure is commonly seen in occupations involving the handling, production, and use of rocket fuel. Patients treated for tuberculosis and presenting with refractory seizures strongly suggest isoniazid overdose. Decontamination and good supportive care will manage most cases of hydrazine exposures. Respiratory arrest and death are primarily secondary to the neurological sequelae of coma and refractory seizures and are treated with IV pyridoxine in addition to benzodiazepines and barbiturates. Admissions observing for delayed pulmonary edema is reasonable as it may occur up to 24 to 48 hours after inhalational exposure.

For the best outcomes for patients with hydrazine toxicity, interprofessional team coordination and management are essential. First responders should be aware of the potential danger of hydrazine if exposed, and appropriate decontamination and personal protective equipment should be performed. Upon arrival at the emergency department, clinicians should fully decontaminate the patient if not already performed, and consult their local poison control center to discuss management with a medical toxicologist. Nursing and lab technologists should aid in obtaining laboratory workup that aids in diagnosis and prognosis. Interprofessional care coordination with open communication is crucial to successful outcomes in hydrazine toxicity cases. [Level 5]