Acute exposure to hydrazine reported to four United States regional poison centers: reconsidering a paradigm.

INTRODUCTION: Exposures to hydrazines occur during aeronautic and space operations and pose a potential risk to personnel. Historically, extensive preparatory countermeasures have been taken due to concern for severe toxicity. This study seeks to better understand manifestations of acute occupational exposures to hydrazine to guide recommendations for management. MATERIALS AND METHODS: A retrospective database review of records from four United States regional poison centers was conducted of all human exposures to hydrazine, monomethylhydrazine, or 1,1-dimethylhydrazine over two decades. Following case abstraction, descriptive statistics were performed to characterize demographics, manifestations, treatments, and outcomes. RESULTS: One hundred and thirty-five cases were identified, and most were adult males exposed to inhaled hydrazine propellant vapors. Fifty-seven percent of patients were asymptomatic following exposure; otherwise, common symptoms were dyspnea, throat irritation, cough, ocular irritation, and headache. All patients were evacuated or received decontamination, with a few reports of symptomatic treatments, including oxygen supplementation and salbutamol (albuterol). Patients usually recovered quickly and were released after a brief healthcare facility evaluation or observed locally. No patients developed delayed symptoms. Symptoms of severe toxicity were not observed, and there were no deaths. DISCUSSION: Acute exposures to hydrazines during operations within the aerospace industry appear to be limited primarily to mucosal and mild pulmonary irritation without significant neurologic, hepatic, or hematologic toxicity. These findings are contrary to previously established expectations and may be related to low-level exposures or possibly due to current emergency countermeasures. CONCLUSIONS: Care in occupational hydrazine exposure will focus on evacuation, decontamination, and symptomatic management of chemical irritant properties of hydrazines. It is reasonable to manage mild cases outside of a healthcare facility. Continued endeavors in human space exploration and habitation will increase the risk of these exposures, making it imperative that clinicians be comfortable with the care and management of these patients.

Occupational Exposure to Hydrazine and Subsequent Risk of Lung Cancer: 50-Year Follow-Up.

PURPOSE: Hydrazine is carcinogenic in animals, but there is inadequate evidence to determine if it is carcinogenic in humans. This study aimed to evaluate the association between hydrazine exposure and the risk of lung cancer. METHODS: The cause specific mortality rates of a cohort of 427 men who were employed at an English factory that produced hydrazine between 1945 and 1971 were compared with national mortality rates. RESULTS: By the end of December 2012 205 deaths had occurred. For men in the highest exposure category with greater than two years exposure and after more than ten years since first exposure the relative risks compared with national rates were: 0.85 (95% CI: 0.18-2.48) for lung cancer, 0.61 (95% CI: 0.07-2.21) for cancers of the digestive system, and 0.44 (95% CI: 0.05-1.57) for other cancers. CONCLUSIONS: After 50 years of follow up, the results provide no evidence of an increased risk of death from lung cancer or death from any other cause.

Hydrazine--the space era agent.

Hydrazine is considered a dangerous toxic compound. It is flammable, easily ignitable and may explode upon contact with different materials, including clothing. As a volatile liquid, it affects mainly the upper respiratory tract, mucous membranes and skin. The characteristics and availability of this agent warrant our attention. Medical personnel should be familiar with its properties, major health effects and the treatment needed. The key principles in treating hydrazine victims include protection from further exposure and aggressive antidotal treatment with pyridoxine (vitamin B6), as well as supportive treatment as required. Finally, medical teams should also be equipped with the proper protection measures (appropriate suits, gloves and breathing apparatuses) in order to avoid secondary exposure of themselves and others.

Intoxicación aguda por hidrato de hidracina / No disponible

Se aporta un caso de exposición aguda, debido a un vertido accidental de unos 25 litros de hidrato de hidracina, que el trabajador estuvo recogiendo sin ningún tipo de equipo de protección individual. El trabajador presentó alteraciones bucales, cutáneas y dolores abdominales difusos. De las pruebas complementarias únicamente se detectó un aumento de la bilirrubina total con predominio de la indirecta. Se le separó de la exposición, se le administró un tratamiento sintomático y en un periodo de un mes se recuperó íntegramente. Se comenta los principales casos de intoxicación por hidracina descritos en la literatura médica y se enfatiza en las medidas preventivas que se deben tomar para evitar casos como éste

We report a case of poisoning by acute exposure to hydrazine hydrate in a worker clearing up an accidental spillage of about 25 litres of the product who had no type of individual protective equipment. The patient presented buccal and cutaneous involvement and diffuse abdominal pain. Complementary tests were unremarkable except for an increase in total bilirubin with a predominance of indirect bilirubin. The patient was removed from the occupational exposure, symptomatic treatment was administered and the patient recovered completely after one month. We review the main reported cases of hydrazine poisoning and emphasize the preventive measures that should be taken to avoid this type of poisoning

Pyridoxine in clinical toxicology: a review.

Pyridoxine (vitamin B6) is a co-factor in many enzymatic pathways involved in amino acid metabolism: the main biologically active form is pyridoxal 5-phosphate. Pyridoxine has been used as an antidote in acute intoxications, including isoniazid overdose, Gyromitra mushroom or false morrel (monomethylhydrazine) poisoning and hydrazine exposure. It is also recommended as a co-factor to improve the conversion of glyoxylic acid into glycine in ethylene glycol poisoning. Other indications are recommended by some sources (for example crimidine poisoning, zipeprol and theophylline-induced seizures, adjunct to d-penicillamine chelation), without significant supporting data. The value of pyridoxine or its congener metadoxine as an agent for hastening ethanol metabolism or improving vigilance in acute alcohol intoxication is controversial. This paper reviews the various indications of pyridoxine in clinical toxicology and the supporting literature. The potential adverse effects of excessive pyridoxine dosage will also be summarized.

Occupational exposure to hydrazines: treatment of acute central nervous system toxicity.

Exposure to hydrazine and hydrazines' alkylated derivatives is an important occupational health issue, which will increase in significance as space applications increase. Despite their widespread usage as rocket fuels in manned and unmanned space and missile systems, serious exposures to hydrazines are rare. While a significant number of experimental studies were performed in the late 1950s through the mid-1960s, conflicting information exists concerning the most appropriate treatment for these exposures. A cross-sectional study evaluating the most common rocket fuels such as hydrazine; 1,1-dimethylhydrazine (UDMH); mono-methylhydrazine (MMH); and Aerozine-50 against the most commonly suggested therapies, such as pyridoxine, traditional antiseizure therapies, and arginine is needed to clarify the treatment implications for human exposure. Treatments that have been useful for hyperammonemic states, such as those for the six inherited urea cycle defects, have significant potential for the improvement of hydrazine exposure treatment.

[The glutathione-dependent antioxidant system in rats during acute intoxication by hydrazine]. / Glutation-zavisimaia antioksidantnaia sistema u krys v usloviiakh ostrogo otravleniia proizvodnymi gidrazina.

Intensity of lipid peroxidation in the liver, kidney and brain tissues, and functioning of the glutathione system were studied in purebred rats after acute intoxication by 1.1-dimethyl hydrazine at the dose of 104.5 mg/kg of body mass (LD50) and phenyl hydrazine at the dose of 170 mg/kg of body mass (LD50). According to results of the investigation, the character and direction of changes in LPO and the antioxidant system due to intoxication by hydrazines are materially dependent on their structure and affected organs and tissues. For instance, intoxication by phenyl hydrazine markedly activates free-radical activation in all analyzed tissue with accumulation of malone dialdehyde against depletion of reduced glutathione in tissue and deactivation of enzymes involved in the antioxidant defense. Intoxication by dimethyl hydrazine was associated with moderate activation of free-radical oxidation in liver with a downward LPO trend in kidney and brain at the cost of exaggerated activity of enzymes in the glutathione system and maintenance of sufficient reserve of reduced glutathione. Hence, aryl hydrazine derivatives possess more distinct pro-oxidant properties.

Pyridoxine therapy in a patient with severe hydrazine sulfate toxicity.

OBJECTIVE: To report hydrazine sulfate as a cause of severe encephalopathy and to report its response to high-dose pyridoxine therapy. DESIGN: Case report. SETTING: An adult six-bed medical/surgical intensive care unit of a general hospital. PATIENT: One patient who developed severe encephalopathy after hydrazine sulfate. INTERVENTION: 5 g i.v. pyridoxine. MEASUREMENTS AND MAIN RESULTS: After 180 mg/day for 2 wks followed by 360 mg/day of hydrazine sulfate ingestion, our patient suffered severe encephalopathy. He received mechanical ventilation with attendant supportive measures and high-dose pyridoxine. The patient's encephalopathy resolved 24 hrs after receiving pyridoxine. CONCLUSION: Severe encephalopathy could result from hydrazine sulfate toxicity. High-dose pyridoxine is an effective treatment to reverse this encephalopathy.

[Progress in the protective medicine against [correction of aganist] rocket propellents].

To review the progress in the major assignment, the organization and implementation of protection against liquid rocket propellent. The safety detection methods of the rocket [correction of rocked] propellent in the launching field were also discussed. Three steps of the sanitation and protection of the liquid propellent, the toxicity and the toxicology of hydrazine on central nervous system, blood circulatory system, assimilation system, respiratory system, immune system, liver, kidney, eye, skin and its hereditary toxicology were described. In addition, the clinical types of poisoning, the current principle and the common ways of the prevention and treatment of hydrazine and nitrogen oxides poisoning were summarized.

Hydrazine production in children receiving isoniazid for the treatment of tuberculous meningitis.

OBJECTIVE: To study the generation of the hepatotoxin hydrazine in 32 malnourished children receiving isoniazid for the treatment of tuberculous meningitis. DESIGN AND SETTING: This observational study was undertaken in the pediatric ward of a teaching hospital admitting children with advanced forms of tuberculous meningitis for treatment and management of complications. METHODS: Thirty-two children (mean age 2.28 years) receiving isoniazid 20 mg/kg/d were studied. Plasma isoniazid, acetylisoniazid, and hydrazine concentrations were determined by an HPLC method. Fourteen children were studied at weekly intervals for the first month of treatment and again after six months of therapy; 18 additional children were studied on one or more occasions during the first month of treatment only. RESULTS: The area under the curve for hydrazine two to five hours after the isoniazid dose correlated with the isoniazid elimination rate and with acetylisoniazid generation. Hydrazine production increased significantly during the first month of treatment, but decreased to approximate initial values at six months. No correlation was found between any clinical or biochemical indicator of liver dysfunction and hydrazine production. CONCLUSIONS: Hydrazine is formed in significant concentrations during the metabolism of isoniazid in young children. However, additional factors such as preexisting liver damage (e.g., from viral hepatitis) may be necessary for it to reach its toxic potential.

Acute intoxication of a hydrazine-like gas by 19 workers in a garbage dump.

Nineteen workers (18 males, 1 female) of a garbage dump (mean age 39.9 years, range 19-58 years) were admitted to our hospital because of inhalation of a hydrazine-like gas of unknown origin. They complained of an ammoniacal odor with sweet taste followed by burning of the eyes, rawness in the throat and dyspnea, dizziness and nausea. Ten patients (group A) arrived about 2 h after they had experienced their first symptoms. The nine other patients (group B) were admitted about 70 h later. On the second day the white cell counts were significantly elevated compared to those of the days before and after (P < 0.02-0.005). The lung function showed in two patients a moderate obstruction. The PO2 was significantly reduced within 1 to 12 h after admission (P < 0.02-0.005) compared to the measurement before (P < 0.005) and after 25 (P < 0.02) and 50 (P < 0.01) h. A significantly reduced PCO2 was found after 25 h compared to the time of admission (P < 0.03). These investigations show that workers of a garbage dump had an alarming decrease of oxygen after inhalation of nitrogenous gases released by the trash.

Residual neurobehavioral impairment in a water technician exposed to hydrazine-containing mixtures.

Residual neurobehavioral impairment in concentration, comprehension, memory, task performance and mood status persisted in a water technician with respiratory and dermal exposures to hydrazine-containing mixtures prior to treatment with steroids for concurrent thrombocytopenia. The findings call attention to the possibility that residual neurobehavioral impairment may be an effect of exposure to hydrazine mixtures.

[Cerebral bioelectrical activity disorders in acute hydrazine poisoning]. / Zaburzenia czynnosci bioelektrycznej mózgu w ostrych zatruciach hydrazydem.

The authors report changes in the bioelectric activity of the brain in acute, severe, suicidal poisoning with hydrazide. The observed group comprised 10 patients, 9 were admitted in coma, 7 had convulsions. Normal EEG tracing was found in a case of combined poisoning with hydrazide and diazepam. Low-voltage tracings with a tendency for bioelectric inactivity development were observed in 2 cases with lethal outcome. In the remaining cases high-grade diffuse changes were present, in three of them seizure activity was present additionally. Full evolution of bioelectric changes was observed in 5 patients. The time of return of normal activity ranged from several days to several weeks. Very slow improvement with incomplete normalization was found in mixed intoxication (hydrazide, barbiturates) treated with haemodialysis. The authors think that in cases with persistence of EEG changes despite regression of acute signs of poisoning intensive treatment with vitamins B should be continued.