A Cobalt Schiff-Base Complex as a Putative Therapeutic for Azide Poisoning.

There is presently no antidote available to treat azide poisoning. Here, the Schiff-base compound Co(II)-2,12-dimethyl-3,7,11,17-tetraazabicyclo-[11.3.1]heptadeca-1(17)2,11,13,15-pentaenyl dibromide (Co(II)N4[11.3.1]) is investigated to determine if it has the capability to antagonize azide toxicity through a decorporation mechanism. The stopped-flow kinetics of azide binding to Co(II)N4[11.3.1] in the absence of oxygen exhibited three experimentally observable phases: I (fast); II (intermediate); and III (slow). The intermediate phase II accounted for ∼70% of the overall absorbance changes, representing the major process observed, with second-order rate constants of 29 (±4) M-1 s-1 at 25 °C and 70 (±10) M-1 s-1 at 37 °C. The data demonstrated pH independence of the reaction around neutrality, suggesting the unprotonated azide anion to be the attacking species. The binding of azide to Co(II)N4[11.3.1] appears to have a complicated mechanism leading to less than ideal antidotal capability; nonetheless, this cobalt complex does protect against azide intoxication. Administration of Co(II)N4[11.3.1] at 5 min post sodium azide injection (ip) to mice resulted in a substantial decrease of righting-recovery times, 12 (±4) min, compared to controls, 40 (±8) min. In addition, only two out of seven mice "knocked down" when the antidote was administered compared to the controls given toxicant only (100% knockdown).

Clinical and analytical problems of sodium azide poisonings as exemplified by a case of fatal suicidal poisoning.

AIM OF THE STUDY: To present clinical and analytical aspects associated with sodium azide poisoning. The problems were verified on the basis of a case of sodium azide poisoning which was unique due to its circumstances and the development of an analytical method applied for medico-legal practice. MATERIAL AND METHODS: The object of the study was a toxicological analysis of biological specimens collected from a woman who ingested two doses of sodium azide purchased over the Internet, in a suicide attempt. After the ingestion of the first dose, the clinical management in the form of symptomatic treatment indicated a possibility of recovery. However, the ingestion of a second dose of the xenobiotic, already in the hospital, caused death. Toxicological findings were obtained with the dedicated technique of gas chromatography-mass spectrometry (GC-EI-MS-MS) after extraction combined with derivatization using pentafluorobenzyl bromide (PFBBr). RESULTS: Post-mortem toxicological studies demonstrated sodium azide in the blood (0.18 mg/l) and urine (6.50 mg/l) samples collected from the woman. CONCLUSIONS: Cases of sodium azide poisoning are rare and difficult to treat, but a review of the literature over a longer interval of time shows that they continue to occur. Therefore, case studies of sodium azide poisoning, together with descriptions of research methodology, can be useful both in clinical terms and in the preparation of toxicological expert opinions for medico-legal purposes.

Multiple poisonings with sodium azide at a local restaurant.

BACKGROUND: Sodium azide is a chemical with a mechanism similar to cyanide. There is concern that it could be used as a chemical warfare agent. OBJECTIVES: We report a cluster of poisonings that occurred at a public restaurant and the subsequent investigation that identified iced tea contaminated with sodium azide (NaN3) and hydrazoic acid, as the foodborne vehicle and agents, respectively. CASE REPORT: Five patients became ill within minutes of drinking iced tea at a restaurant. They all presented to the same Emergency Department with similar symptoms, and improved with fluids, antiemetics, and supportive care. A joint investigation by the Dallas County Department of Health and Human Services, the Texas State Health Department, the Dallas County Southwestern Institute of Forensic Sciences, and the medical toxicologists at the University of Texas Southwestern School of Medicine identified iced tea, contaminated with sodium azide (NaN3) and hydrazoic acid, as the foodborne vehicle and agents, respectively. CONCLUSION: The recurrence, and seriousness, of these events suggests a need for continued education of emergency providers. Emergency physicians should consider exposures to toxic chemicals in their differential when a cluster of patients presents with similar symptoms over a short period of time.

Sodium azide poisoning at a restaurant - Dallas County, Texas, 2010.

In April 2010, Dallas County Health and Human Services (DCHHS) staff members investigated reports of acute-onset dizziness among patrons in a local restaurant. Symptoms, which included fainting resulting from low blood pressure, occurred within minutes of consuming food from the restaurant and were consistent with chemical poisoning. Toxicologic and epidemiologic investigations were begun to determine the cause of the poisonings and identify potentially exposed persons. This report summarizes the results of those investigations, including a case-control study that identified iced tea as the likely contaminated food or drink (odds ratio [OR] = 65; 95% confidence interval [CI] = 2.4-3,292). Approximately 5 months after the incident, extensive laboratory testing identified sodium azide (NaN3) and hydrazoic acid (formed when sodium azide contacts water) as the toxic agents in the iced tea. All five ill restaurant patrons recovered from their symptoms. For rapid-onset foodborne illnesses, chemical poisons should be considered as a potential cause, regardless of negative initial toxicologic screening tests. Although unusual chemicals can be challenging to detect, a multidisciplinary approach involving public health officials and forensic and medical toxicologists can lead to appropriate testing. In the absence of an identified agent, epidemiologic tools are valuable for active case-finding and confirming suspected contaminated food vehicles.

[Suicidal intoxication with sodium azide--a case report]. / Smiertelne samobójcze zatrucie azydkiem sodu--opis przypadku.

Sodium azide (NaN3) is an inorganic matrix compound with a very high toxicity. Mechanism of action is not clarified, and it is assumed to interfere with the processes of oxidative phosphorylation. The acute intoxications with sodium azide are extremely rare. We described a case of 19-year-old man who was found dead. In the course of prosecution the empty container, with label "NaN3, 20 g", was found near the body. There were traces of white powder detected in the container. Azide ions were determined by derivatization, i.e. they were transformed to pentafluorobenzaldehyde azide compound. Analysis of the final extract after derivatization was performed by gas chromatography coupled with mass spectrometry GC/MS. The largest concentration of azide ions were determined in the stomach content and vitreous humour, and much less one in whole blood, urine and kidney fluid.

[Sodium azide poisoning--a rare reason of hospitalization in toxicological units--case report]. / Zatrucie azydkiem sodu--rzadka przyczyna hospitalizacji w osrodkach toksykologicznych--opis przypadku.

Sodium azide poisonings are a rare reason for hospitalization in toxicological units. They are observed as rarely as once within a number of years per hospital. Consequently, an algorithm for the optimum procedure of treating such intoxications does not exist and, as a result, there is a need to describe every single clinical case. A female, aged 55, was directed to the toxicological unit from a county hospital after swallowing four tablets of sodium azide, 150 mg each, in the form of preservative for fresh milk samples. Two hours after the incident a gastric lavage was performed and the tableting blend was retrieved. In the clinical examination higher concentration of lactic acid, ALAT and TSH were observed. In the ECG record unspecific aberrations in the ST segment were noticed. Due to the patient's general good condition and the fact that the tableting blend had been retrieved from the gastric rinse, further use of the antidote indicated in the therapy of cyanide intoxications was abandoned. Symptomatic treatment was used along with the patient's eight-day observation. In the described case the early decontamination prevented the development of acute poisoning.

Sodium azide poisoning: a narrative review.

CONTEXT: Sodium azide is a highly toxic chemical. Its production has increased dramatically over the last 30 years due to its widespread use in vehicular airbags, and it is available for purchase online. Thus, accidental exposure to azide or use as a homicidal or suicidal agent could be on the rise, and secondary exposure to medical personnel can occur. No antidote exists for azide poisoning. We conducted a systematic review of azide poisoning to assess recent poisoning reports, exposure scenarios, clinical presentations, and treatment strategies. METHODS: We searched both medical and newspaper databases to review the literature between 01/01/2000 and 12/31/2020, pairing the controlled vocabulary and keyword terms "sodium azide" or "hydrazoic acid" with terms relating to exposures and outcomes, such as "ingestion," "inhalation," "exposure," "poisoning," and "death." We included all peer-reviewed papers and news articles describing human azide poisoning cases from English and non-English publications that could be identified using English keywords. Data abstracted included the number, age, and gender of cases, mode of exposure, exposure setting, azide dose and route of exposure, symptoms, outcome, and treatment modalities. RESULTS: We identified 663 peer-reviewed papers and 303 newspaper articles. After removing duplicated and non-qualifying sources, 54 publications were reviewed describing 156 cases, yielding an average of 7.8 reported azide poisoning cases per year. This rate is three times higher than in a previous review covering the period of 1927 to 1999. Poisoning occurred most commonly in laboratory workers, during secondary exposure of medical personnel, or from a ripped airbag. Hypotension occurred commonly, in some cases requiring vasopressors and one patient received an intra-aortic ballon pump. Gastric lavage and/or activated charcoal were used for oral azide ingestion, and sodium nitrite, sodium thiosulfate, and/or hydroxocobalamin were used in severely poisoned patients. CONCLUSIONS: Recent increases in azide poisoning reports may stem from greater commercial use and availability. Treatment of systemic poisoning may require aggressive hemodynamic support due to profound hypotension. Based on mechanistic considerations, hydroxocobalamin is a rational choice for treating azide poisoning.

[Sodium azide--clinical course of the poisoning and treatment]. / Azydek sodu--przebieg kliniczny zatrucia i leczenie.

Sodium azide poisonings occur very rarely. The mechanism of sodium azide toxic effect has not yet been fully explained. Despite the lack of an explicit procedure for the cases of sodium azide poisonings, in vitro tests and rare case reports suggest that treatment with antidotes for cyanide poisoning victims can be effective. This study describes two cases of suicidal sodium azide ingestion. Case 1. 30-year-old male ingested ca. 180 mg of sodium azide. On admission to hospital, within 4 hours from poisoning, the man complained of dizziness and anxiety. Physical examination revealed horizontal nystagmus, flapping tremor, HR 135/min. In laboratory tests, higher blood concentration of lactates (3 mmol/l) was detected, as well as lower potassium concentration (3.4 mmol/L) and increased transaminase activity (ALT 74 U/l, AST 90 U/l). Electrocardiographic tests showed a negative T wave in limb lead III. Other results were within normal. As the patient ingested a toxic dose of sodium azide, he was treated according to the therapy prescription for cyanide poisoning (amyl nitrite inhalation followed by intravenous administration of sodium nitrite and sodium thiosulphate). ECG record of the last day of hospitalization (7th day of treatment) showed negative T waves in lead III, V4-V6. He was discharged from hospital in good condition. Case 2.23-year-old male ingested 10 g of sodium azide 1.5 hours prior to admission to hospital. At the beginning, the patient's condition was good, but it changed to critical state within the first hours of hospitalization. He developed a deep coma, respiratory and circulatory insufficiency, metabolic acidosis, cardiac dysrrhythmias and anuria. Cardiac activity monitoring showed alternating tachycardia (140 beats per minute) and bradycardia (48 beats per minute), numerous additional supraventricular and ventricular extrasystoles and sinus dysrrhythmia. Cardiac arrest (asystolia) occurred twice, the second incident with fatal outcome. The patient received supportive therapy, he was also treated according to the therapy prescription for cyanide poisoning. Circulatory disturbances observed in both cases have been described in literature as symptoms of sodium azide poisoning. However, available literature data are scarce and lack systematization, most of them coming from several decades ago. The lack of patient's consent for detailed examination of circulatory system and liver made it impossible to gather further knowledge on the subject. The efficacy of treatment with antidotes for cyanide poisoning has not been unequivocally determined for this kind of intoxication.

Sodium azide ingestion and secondary contamination risk in healthcare workers.

This study reports the follow-up of healthcare staff directly involved in managing a fatal sodium azide ingestion. Clinical staff directly involved with the case were contacted by telephone or in person. Data collected were age, sex, time in contact with the patient, time off work following the incident and whether or not this was because of physical complications of exposure. Ten individuals had close contact with the case. Of these, five were men, median age was 39 years (range 22-52); four described being in close contact for greater than 60 min, three for 15-60 min and three for 5-15 min. Absence from work occurred in two cases for 1 day and several weeks, neither attributed to the physical effects of exposure. Our data do not support close contact with a sodium azide ingestion case as posing a high risk of significant postexposure complications in emergency service workers.

Suicidal Fatality from Azide Ingestion.

A 35-year-old man ingested an unknown amount of sodium azide and died within 2 h. The postmortem interval was 3 days. No alcohol or drugs were found in the blood and urine. Azide was derivatized in the peripheral blood, urine, and vitreous fluid with propionic anhydride. A portion of the headspace was injected onto a gas chromatograph with a nitrogen-phosphorus detector. Azide was quantitated in the peripheral blood (1.1 µg/mL), urine (7.5 µg/mL), and vitreous (43 µg/mL). The vitreous appears to be a better fluid for azide screening because of slower degradation.

[Sodium azide: a review of biological effects and case reports].

This report reviews the biological effects and case reports of suicidal or accidental ingestion of, and occupational exposure to sodium azide. Ingested doses of sodium azide were estimated for the 6 survival and 4 fatal cases studied. The lowest dose among survival cases was 5-10 mg. The patient reported headache, sweating, and faintness within approximately 5 minutes of ingestion. Four victims ingested 20 to 40 mg and recovered within 2 hours. However, a man who took 80 mg reported chest pain for 6 months after ingestion. The smallest doses among fatal cases were 0.7-0.8 g for women and 1.2-2 g for men. All victims suffered from hypotension, tachycardia, hyperventilation, diaphoresis, vomiting, nausea, and diarrhea. There is no antidote for sodium azide. Detoxicants for cyanide such as sodium nitrite or thiosulfate were tried, but were unfortunately, ineffective. Sodium nitrite may worsen the hypotension caused by sodium azide, and is not recommended. Occupational exposure to sodium azide is thought to be common, however, fatal exposure is rare. NIOSH "Recommended Exposure Limits" for sodium azide is 0.3 mg/m3.

[A case of fatal acute sodium azide poisoning].

A case of fatal sodium azide poisoning induced by suicidal ingestion was reported. When the patient arrived, her vital signs such as consciousness and blood pressure, were normal. But 25 hours after ingestion, she died from metabolic acidosis, ARDS (acute respiratory distress syndrome) and acute cardiac failure. We detected the azide ion in patient's serum using GCMS method and measured the blood concentration of sodium azide using the GC/NPD method. The half-life period of sodium azide in blood was calculated as about 2.5 hours.

[Neurotoxicity in sodium azide poisoning].

The effects of sodium azide administration on the central cholinergic functions were investigated utilizing mice to evaluate the neurotoxicity in the acute poisoning. Seven oral doses of the toxicant, ranging in dosage from 12.3 to 59.3 mg/kg, based upon a multiple of 1.3 x 27 mg/kg (an empirical LD50 for mice) or 27 mg/kg divided by 1.3 to calculate the lower three doses, were administered to facilitate the acute signs and to observe behavior. The behavior included locomotor activity, rectal temperature and rotarod performance which are convenient for the evaluation of central cholinergic involvement even if it may be partial, since no behavioral methods to study totally the cholinergic system have been known. Measurements of the activities of acetylcholinesterase (AChE) and choline acetyltransferase (ChAT), enzymes that hydrolyze and synthesize acetylcholine (ACh) and high-affinity choline uptake (HACU), a rate-limiting step in the synthesis of ACh, were determined in the presence of various concentrations of sodium azide in vitro. Adult (12-15 weeks) female ICR strain mice were utilized in this study. Mice were orally given sodium azide in doses from 27 to 59.3 mg/kg and appeared sedated within 5 min. Next we observed hyperpnea and dyspnea, which were followed by seizure and death for mouse groups which received more than 35.1 mg/kg. Oral administration of the sodium azide solution produced an increase in locomotor activity for the 12.3 mg/kg group and a decrease for the higher doses (ranging from 16.0 to 27.0 mg/kg). The sodium azide administration suppressed rectal temperature dose-dependently as well as rotarod performance at high doses (20.8 and 27.0 mg/kg). Such behavioral changes elicited by sodium azide administration suggest an involvement of the central cholinergic system. Sodium azide also caused a measured decrease in the activity of AChE, but an increase in the activities of ChAT and HACU, dose-dependently, in vitro. From the results obtained from the behavioral and the in vitro experiments, we concluded that acute sodium azide poisoning significantly affects the central cholinergic system.

Suicidal sodium azide intoxication: An analytical challenge based on a rare case.

INTRODUCTION: Intentional absorption of sodium azide is exceptional but remains extremely life-threatening because death rapidly occurs when significant doses are absorbed, either due to the direct effect of sodium azide or an indirect effect due to nitric oxide, cyanide ions or hydrazoic acid production from sodium azide. CASE REPORT: The body of a laboratory assistant, was discovered by his colleagues in the laboratory, seated on a chair located near a digital computer displaying information about sodium azide. Moreover, a half empty 99% sodium azide flask was found near the corpse. The laboratory staff confirmed that the young man was still alive 5h prior to discovery. RESULTS: Postmortem examination did not show any cutaneous signs of injury due to a defensive struggle. Bilateral ungual cyanosis was observed as well as a major cerebral edema and visceral congestion on autopsy. The elevated sodium azide concentration found in the gastric sample and the amount of gastric content allowed to conclude that sodium azide intake was more than 6g which was above the lethal dose, i.e. approximately 1g. Surprisingly, no sodium azide was found either in blood and serum, or in hepatic and renal tissue samplings. However, major concentrations were observed in the gastric contents, bile and urinary samples, as well as in cardiac and cerebral tissues samples. No other toxic element was found. Therefore, the post-mortem findings, the autopsy and the analytical results suggested that the laboratory assistant died after an intentional sodium azide ingestion. CONCLUSION: Sodium azide poisoning by ingestion has to date remained extremely rare and our case highlights the extreme lability of sodium azide as it was absent in the blood, in spite of significant concentrations in stomach content and some tissues. Therefore, the necessity of multiple tissues samples during autopsy should be underlined.