Online purchase of sodium nitrite for use as a suicide agent with resulting methaemoglobinemia

We would like to raise awareness amongst healthcare professionals of a potential emerging public health concern of using sodium nitrite to commit suicide in Asia. We present a recent case of a patient who attempted suicide by ingesting sodium nitrite that was purchased online in Singapore. The patient is a 30-year-old Chinese male with underlying generalised anxiety disorder and delusional disorder. He was recently discharged from inpatient psychiatric care following a 2-month stay for suicidal ideations on a background of mixed depressive and anxiety symptoms. Following his discharge, on 20 September 2023 at around 11:30 AM, he alleged to have conducted his own research and subsequently purchased 25 g of powdered sodium nitrite online which he subsequently consumed in its entirety without vomiting to commit suicide. Given that he weighed 70 kg, this worked out to be an ingested dose (g)/body weight (kg) of approximately 0.35 g/kg. Following ingestion, he approached his family for assistance in seeking medical attention. When the paramedics arrived on site, he was noted to have low oxygen saturation on pulse oximetry (SpO2 80% without supplemental oxygen, 88% despite the use of a non-rebreather mask with an oxygen flow rate of 15 L/min on scene by the paramedics) but was otherwise alert. On reaching the emergency department (ED) at approximately 12:30 PM, which was approximately 1 h after ingestion, he was noted to be cyanosed. However, he denied any symptoms including dyspnoea, chest pain, nausea and vomiting. There was also no family history of cytochrome B5 reductase deficiency, and he was also not on any other medications that could potentially cause methaemoglobinaemia. Physical examination was otherwise unremarkable with an unyielding cardiac, respiratory and abdominal examination. His initial vital signs in ED were as follows: Glasgow Coma Scale 15, blood pressure 108/57 mmHg, heart rate 121 beats per minute, and respiratory rate was 23 breaths/min with a low oxygen saturation reading on pulse oximetry (SpO2 of 86%–89% on a non-rebreather mask with an oxygen flow rate of 15 L/min). On venipuncture, he was noted to have chocolate-coloured blood. An arterial blood gas performed highlighted a discrepancy between his SpO2 and partial pressure of oxygen in the blood (SaO2) of 58 kPA. Given his clinical presentation, the methaemoglobin (MetHb) level was sent and his initial reading was 68.7%. We were unable to measure serum sodium nitrite concentrations due to the limitations of our laboratory. There was no suggestion of any end-organ damage from his investigations—cardiac enzymes, kidney panel, liver function test and lactate were all normal. Serum toxicology screen also picked up low concentrations of metoclopramide at 0.04 μg/mL, suggesting that there could be a concomitant additive in the agent that the patient purchased as metoclopramide was not administered to the patient in the hospital. Otherwise, the rest of his metabolic screen was otherwise unremarkable. As our patient was not glucose-6-phosphate dehydrogenase (G6PD) deficient and weighed 70 kg, following discussion with our toxicologist, 100 mg of methylene blue was administered intravenously (approximately 1.5 mg/kg) as an antidote. He was subsequently transferred to medical high dependency (MHD) for further monitoring. Serial MetHb levels, performed at a 2-h interval, were noted to be downtrending (68.7% > 37.3% > 7.0% > 0.3%). He was subsequently transferred to the general ward after 1 day of stay in MHD and eventually discharged after 2 more days in the ward. Sodium nitrite overdose can result in vasodilatory shock with resulting hypotension. Nitrite reduction to nitric oxide has been postulated1 to be the mechanism of action responsible for the vasodilatory effect. Henceforth, it is prudent to keep a close monitoring on the patient's vitals and institute the necessary supportive measuress such as fluid resuscitation and inotropic support as necessary. Sodium nitrite is also a strong oxidising agent that impairs oxygen transport and delivery with the formation of MetHb. It results in death from severe hypoxia.2 The lethal dose of sodium nitrite has been reported to be a range of between 0.7 and 6 g.3 Sodium nitrite toxicity results in the oxidation of ferrous iron (Fe2+) of haemoglobin to MetHb containing ferric iron (Fe3+).2 Hence, it is often diagnosed through symptoms and signs of methaemoglobinemia. Methaemoglobinemia results in a shift of the oxygen-dissociation curve to the left, resulting in an increase in the affinity of oxygen binding to ferrous iron, thus reducing oxygen delivery to tissues. Clinical manifestations include cyanosis, arrythmias, fatigue, weakness, seizures, coma and death in large consumption.4 'Refractory hypoxemia' is classically described in patients with methaemoglobinemia, whereby there is persistently depressed SpO2 despite supplemental oxygen and no other clear causes. Other diagnostic clues include 'saturation gap' whereby there is a discrepancy between a patient's SpO2 and SaO2, as well as the presence of chocolate-coloured blood. Diagnosis is confirmed following the measurement of MetHb levels via blood gas co-oximetry, which measures light absorption at four wavelengths as opposed to standard pulse oximeters (two wavelengths). MetHb is usually expressed as a percentage concentration of MetHb over the concentration of total haemoglobin. Levels >70% are often fatal. Treatment of methaemoglobinemia involves the cessation of the offending agent with the consideration of utilising methylene blue (tetramethylthionine chloride) as an antidote.5 It works by oxidising NADPH, hence forming leucomethylene blue which in turn reduces MetHb to haemoglobin. Methylene blue is indicated in symptomatic methaemoglobinemia and in patients whose MetHb level is above 30%.5 The drug dose is 1–2 mg/kg intravenously over 5 min and can be repeated in 30–60 min if symptoms persist or if levels remain above the treatment threshold.5 Some side effects of methylene blue include green or blue urine, precipitation of serotonin syndrome in patients on serotonergic agents, nausea or vomiting. It also may not be as effective in patients with G6PD deficiency. Other therapeutic options in the setting of refractory methaemoglobinaemia include ascorbic acid, hyperbaric oxygen and exchange transfusion.5 There have been no published cases of suicide attempt following online purchase and subsequent ingestion of sodium nitrite in Singapore previously. Death from sodium nitrite ingestion was previously uncommon and typically accidental. However, in the past 4 years, online purchases and subsequent ingestion of sodium nitrite have emerged as new methods for suicide overseas.6, 7 There are even shadow markets and online forums detailing how to purchase and step-by-step instructions on how to use sodium nitrite for suicidal purposes.7 Worryingly in our patient's case, he too cited that sodium nitrite is readily available for purchase, and information pertaining to its use in suicide was easily accessible. More alarmingly, the fact that metoclopramide was discovered in toxicology testing could possibly suggest that other additives may be added in combination with sodium nitrite in the formulation of these agents used for suicidal purposes, hence making them deadlier. It is therefore prudent to be cognisant of this potential trend and to be vigilant in the prompt identification and treatment of these patients to reduce mortality. Justin Jin Hao Jang: Conceptualisation; data curation; formal analysis; supervision; writing – original draft; writing – review writing – review & editing. This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. The author(s) declare(s) that there is no conflict of interest. National University Hospital (NUH) does not require ethical approval for reporting individual cases because anonymised information of the patient is used with no patient identifying information. Written informed consent was obtained from the patient for their anonymised information to be published in this article. Data sharing is not applicable to this article as no datasets were generated or analysed during the current study.