This case report highlights an occurrence of methemoglobinemia caused by the ingestion of liquid amyl nitrite, a substance often misused as a recreational drug. The patient in this case presented with cyanosis and elevated methemoglobin levels. Prompt administration of methylene blue successfully reversed the methemoglobinemia by reducing methemoglobin back to hemoglobin. This case emphasizes the importance of rapid diagnosis and treatment in nitrite-induced methemoglobinemia, demonstrating methylene blue as a highly effective antidote. It also highlights the risks associated with amyl nitrite misuse and the crucial role of healthcare providers in managing this potentially life-threatening condition.

For over 150 years, nitrates have been a cornerstone in the treatment of cardiovascular disease. Nitroglycerin - synthesized by Italian chemist Ascanio Sobrero in 1847 - was initially used in explosives, as the main component of dynamite, by Alfred Nobel. The Scottish physician Lauder Brunton first used amyl nitrite for angina in 1867, and in 1879 the English physician William Murrell described the benefits of nitroglycerin for angina pectoris. Organic nitrates, including nitroglycerin, act as nitric oxide donors, sharing the mechanism of NO release, which induces vasodilation. This paper reviews the fascinating history of nitroglycerin and nitroderivatives, the related discovery of nitric oxide as a cardiovascular signaling molecule, and the 1998 Nobel Prize awarded for this discovery. The paper also succinctly explores current and future roles of nitric oxide donors in cardiovascular treatment.

Stabilized isoamyl nitrite (SIAN) is a novel small molecule, therapeutic candidate for the treatment of cyanide poisoning. SIAN improves survival and has a demonstrated pharmacodynamic (PD) effect in cyanide challenged nonhuman primates. Here, we report results of phase 1, first-in-human study evaluating the safety, tolerability, pharmacokinetic (PK), and PD of SIAN nasal spray in healthy human subjects (NCT05194358). SIAN was intranasally administered in ascending doses at 2 sites in Texas and Tennessee in the United States. A total of 47 subjects were enrolled across 7 dose cohorts evaluating single doses from 20 to 300 μL. Following the dosing of sentinels in each cohort, safety, PK, and PD data were interpreted by a Safety Monitoring Committee to permit dosing of additional subjects in the cohort or escalation to the next dose level. Isoamyl alcohol peak plasma concentrations were reached within 2 minutes and were highest after a 250 μL dose (125 μL/nostril). This trend was also observed for PD parameters, including a metHB peak at 2 minutes with associated increase in heart rate and systolic and diastolic blood pressure. SIAN was generally well tolerated, no serious or severe drug-related effects were observed, and there were no clinically significant changes in vitals or laboratory parameters. We conclude that SIAN, a potential new treatment for cyanide poisoning, was safe, well tolerated, and showed a relationship between PK and PD parameters at the doses tested. SIGNIFICANCE STATEMENT: This is the first-in-human clinical study to evaluate intranasal stabilized isoamyl nitrite, which was shown to be safe, well tolerated, and to elicit a measurable pharmacokinetic and pharmacodynamic response in healthy human subjects at the doses tested. This study paves the way for investigating stabilized isoamyl nitrite further as a potential emergency treatment for cyanide poisoning.

Drug-induced hearing loss (DIHL) is highly prevalent, but a comprehensive picture of ototoxicity associated with drugs are still lacking. In order to comprehensively summarize the hearing safety information of current drugs, we used the real-world data from 2004 to 2023 in the FDA Adverse Event Reporting System (FAERS) database to integrate the reported ototoxicity information of drugs and applied disproportionality analysis to evaluate the hearing impairment risk induced by drugs. A total of 108,435 adverse event (AE) reports of hearing impairment were extracted from the FAERS database, involving 1300 reported culprit-drugs. On the whole, acetylsalicylic acid was the most frequently reported potential ototoxic drug, followed by levothyroxine sodium, adalimumab, omeprazole, and ergocalciferol. Immunosuppressants was the most frequently reported drug class, followed by analgesics, psychoanaleptics, agents acting on the renin-angiotensin system, and antineoplastic agents. In risk signal detection, 432 of 1300 drugs exhibited potential ototoxic risk, in which tafenoquine showed the strongest statistical correlation with hearing impairment, followed by teprotumumab, amyl nitrite, potassium iodide, and paromomycin. Among main drug classes, antibacterials for systemic use was the drug class contained the maximum number of drugs with positive ototoxic risk signals, followed by psychoanaleptics, agents acting on the renin-angiotensin system, antineoplastic agents, and analgesics. In conclusion, our study summarized a comprehensive drug list containing 1300 reported potential ototoxic drugs in the FAERS database and profiled their ototoxicity risk characteristic from the aspect of reporting frequency and risk signal strength, which can provide reference for clinical medical staff to strengthen monitoring and management of DIHL.

A 23-year-old female presented to the Emergency Department (ED) with altered mental status and acute respiratory failure with hypoxia after ingesting poppers (alkyl nitrite) at a music festival. She received initial treatment at the event medical tent but deteriorated during transport. Upon arrival at the ED, she required intubation and received methylene blue treatment for suspected methemoglobinemia. Labs confirmed methemoglobinemia, and her blood appeared chocolate brown. Despite requiring vasopressors, her condition improved after methylene blue administration. Following treatment, her oxygen saturation and blood gas improved. She was discharged within 24 hours. Poppers are often recreationally inhaled at social events. We present a case where drinking poppers led to a near-fatal methemoglobinemia. The presentation was recognized and treated with methylene blue. It is important for the healthcare team to consider alkyl nitrites when a patient presents with cyanosis and hypoxia not improving above 85%. Administration of methylene blue can reverse methemoglobinemia and prevent fatalities.

Acute cyanide toxicity is very rare but it is almost always associated with fatal outcomes. Here we describe the case of a 43-year-old healthy male who worked in a jewelry factory and presented with acute cyanide toxicity. He was successfully managed with all the supportive measures and an appropriate antidote kit containing amyl nitrite, sodium nitrite, and sodium thiosulfate. We also describe the relevant importance of knowing the history of easy access to cyanide as a part of the patient's profession, the critical nature of the patient at presentation, as well as the efforts needed to procure the antidote.

Inhaled amyl nitrites, once used to alleviate chest pain, are more commonly now being used for their euphoric effects. The recreational use of inhaled nitrites can lead to methemoglobinemia, a life-threatening condition that hinders the utilization of oxygen in the body. In 2021, 2.2 million people aged 12 or older used inhalants in the past year. Methemoglobinemia has favorable outcomes with treatment. We present the case of a 43-year-old man, with a medical history of type 2 diabetes mellitus and hypertension presenting with bluish discoloration of the fingers that progressed to his tongue and lips. He disclosed using a recreational inhalant called "Rush" before coming in. Vital signs showed low oxygen saturation on room air, and further investigation revealed elevated methemoglobin levels on the venous blood gas. Methylene blue was used for treatment, with complete resolution of the patient's symptoms and the only side effect of green urine. The patient was later discharged home in a stable condition. History taking is a crucial part of managing methemoglobinemia, as presentation to the clinical setting could vary. Our case presents the milder version of the disease with quick complete recovery after appropriate treatment. It demonstrates inhalant abuse in a less common age group. The case also demonstrates a common side effect of methylene blue that is often forgotten.

Sexualized substance use or "chemsex" may contribute to the HIV epidemic among men who have sex with men (MSM) in Thailand. Specific patterns of chemsex use may be associated with different HIV/STI transmission risks. We examined typologies and correlates of sexualized substance use among a sample of high-risk MSM (n = 532) who had attended a private sex party or circuit party in the past three years using latent class analysis. Multinomial regression was used to adjust for variables associated with the 3-class latent class model. We identified a 3-class model as the best fitting model, which included: (1) "negligible sexualized substance users" (36.7%), who had never engaged in chemsex in the past six months; (2) "sexualized substance users" (13.9%), who had a high level of sexualized alcohol use and a wide range of other substances before or during sex in the past six months; and (3) "exclusive chemsex users" (49.4%), who predominantly used crystal methamphetamine, amyl nitrite, and erectile dysfunctional drugs before or during sex in the past six months. Compared to negligible sexualized substance users, exclusive chemsex users were more likely to be HIV-positive, more likely to have six or more sexual partners in the past six months, less likely to have condom use at last anal intercourse, and more likely to have provided sex work. Relative to negligible sexualized substance users, sexualized substance users reported more frequent online sex-seeking behaviors. These subgroups of Thai MSM have unique substance use patterns and HIV-related risk profiles, underscoring the importance of targeted HIV prevention strategies.

We present a case of a man in his late 40s presenting with generalised tonic-clonic seizures and profound methaemoglobinaemia shortly after inadvertent ingestion of amyl nitrite. Arterial blood gas analysis demonstrated methaemoglobin levels exceeding the upper detection threshold of our analyser, accompanied with profound cyanosis despite apparent oxygen saturations of 94%. Prompt administration of intravenous methylene blue led to a rapid and complete recovery. This case highlights the importance of swift recognition and treatment of methaemoglobinaemia particularly when the precipitating factor may be unknown at the time of presentation. This case also demonstrates the potential limitations of bedside blood gas analysers in diagnosis.

Methemoglobinemia is a potentially life-threatening condition caused by the formation of methemoglobin, a form of hemoglobin that cannot bind oxygen. While there are some rare congenital causes of methemoglobinemia, most cases are acquired from the effects of specific drugs or environmental exposures. In this retrospective study, we analyzed a large data set of whole blood samples analyzed for methemoglobin at an academic medical center in Midwestern United States that provides both pediatric and adult services. For a 14 year timeframe (May 2009- June 2023), we performed detailed chart analysis of all patients with a methemoglobin concentration of 3.1 % or higher. For an earlier 13 year timeframe (January 1996-April 2009), we performed chart review for all patients with a methemoglobin concentration of 10.0 % or higher. For the 2009-2023 data, dapsone was the most frequent cause of methemoglobinemia (methemoglobin 3.1 % or higher) in both pediatric (73.3 %, 115 clinical encounters, 105 unique patients) and adult (65.3 %, 195 clinical encounters, 190 unique patients) populations. Inhaled nitric oxide as medical therapy was the next most frequent cause in both pediatric (18.1 %) and adult (13.2 %) populations. Causes associated with two or more unique episodes with methemoglobin concentrations of 10.0 % and higher included the following: dapsone (n = 40 episodes), benzocaine (n = 10), recreational use of amyl or isobutyl nitrite (n = 3), suicide attempt with sodium nitrite (n = 3 with 1 fatality; all 3 cases within last 3 years), food contaminated with nitrates (n = 2), and sepsis (n = 2). A total of 18 patients received treatment with methylene blue including 5 cases associated with benzocaine and all of the cases associated with amyl nitrite, isobutyl nitrite, sodium nitrite, and contaminated food. Only 3 patients with dapsone-associated methemoglobinemia received methylene blue, reflecting primary management by dose reduction or discontinuation of drug. Overall, our data reinforce previous studies showing dapsone, inhaled nitric oxide, and nitrites as common agents causing methemoglobinemia in a patient population seen at a medical center. Our data also are consistent with recent epidemiology trends showing increase in suicide attempts using sodium nitrite.