Accidental Alkyl Nitrite (Poppers) Ingestion in a 37‐Year‐Old Patient: A Case Report

ABSTRACT

This case demonstrates severe methemoglobinemia in a male patient following accidental ingestion of alkyl nitrites (“Poppers”). Prompt recognition and treatment with methylene blue ensured rapid recovery. Clinicians must consider this condition in patients with unexplained cyanosis and discordant oxygen saturation. Public awareness to prevent such incidents is important due to the easy accessibility of the drug.

1. Introduction

The collective term “poppers” stands for liquid preparations that contain substances from the group of alkyl nitrites. Alkyl nitrites are volatile substances that cause brief euphoria and have a vasodilatory effect. They are used recreationally by nasal inhalation. Ingestion of alkyl nitrites is rare and potentially dangerous [1]. It can be either accidental or deliberate (suicide attempt). From a chemical perspective, alkyl nitrites oxidize hemoglobin from its ferrous (Fe²⁺) state to its ferric (Fe³⁺) state, commonly known as methemoglobin. In this state, hemoglobin cannot transport oxygen, leading to peripheral and central cyanosis, and eventually cardio‐respiratory failure or death if untreated. The antidote for methemoglobinemia is methylene blue, which reduces Fe³⁺ back to Fe²⁺ [2].

This case describes a patient who accidentally ingested a bottle containing, according to the label, 15 mL of concentrated propyl nitrites, leading to significant methemoglobinemia. Rapid administration of methylene blue allowed full recovery, and the patient was discharged the following day. This report emphasizes the importance of quick treatment to improve outcomes in such rare intoxications from a widely accessible drug.

2. Case History and Examination

A 37‐year‐old man with no significant medical history was admitted to the emergency department after accidentally ingesting 13 mL of propyl nitrites during a concert, mistaking it for a small bottle of strong alcohol. His companions immediately called an ambulance before any symptoms developed. In the ambulance, caregivers observed 70% oxygen saturation on 10 L/min of oxygen and a blood pressure of 88/50 mmHg, which improved to 100/60 mmHg after the bolus administration of 500 mL saline solution.

The paramedic who treated the patient had reported that he recently read about popper intoxication and knew that the patient needed to be transported quickly for antidote therapy. The situation was reported by telephone to the emergency department, where the methylene blue was prepared before the patient arrived.

Upon arrival at the emergency department, the patient reported dizziness and headaches. He denied using any other illicit substances and had no significant psychiatric or medical history. He was a non‐smoker and physically active, without regular medications. The patient had brought the bottle with him and confirmed having ingested the contents (Figure 1). We were able to calculate the remains and deduced that he had ingested roughly 13 mL of concentrated propyl nitrites in total.

FIGURE 1.

Image of the product ingested by the patient (with permission of the author of the photo).

On admission, the patient presented with central and peripheral cyanosis, manifesting as a grayish complexion and blue lips. Despite being on 15 L/min of oxygen, his oxygen saturation remained at 75%, with a respiratory rate of 10 breaths/min and no signs of respiratory distress. Lung auscultation was unremarkable. Tachycardia was noted at 110 bpm, and blood pressure was 156/66 mmHg. He was alert and oriented, with a Glasgow Coma Scale score of 15/15 and a body temperature of 35.8°C.

3. Differential Diagnosis, Investigation, and Treatment

Methemoglobinemia is highly probable in the setting of cyanosis that is refractory to supplemental oxygen and the presence of an oxygen saturation gap, especially in the setting of exposure to a known oxidative agent. Besides hemoglobinopathies, central cyanosis can be caused by hypoxemia due to neurogenic hypoventilation or pulmonary pathologies, hypothermia, as well as cardiovascular diseases like heart failure or conditions leading to right‐to‐left shunting. In our patient, these differential diagnoses could rapidly be excluded, considering his medical history and clinical examination that showed no signs of pulmonary, cardiovascular, or neurologic disease.

The prehospital notification allowed the emergency team to prepare methylene blue at a dose of 1 mg/kg (80 mg diluted in 250 mL of 5% glucose solution). The antidote was administered promptly after a quick history taking and clinical examination, without waiting for the arterial blood gas results—about 5 min after the patient's arrival and 40 min post‐ingestion of the substance. An arterial catheter was then placed for hemodynamic monitoring and repeated blood gas measurements.

Laboratory results showed normal transaminases and creatinine, electrolytes, and complete blood count. The first arterial blood gas, taken 50 min post‐ingestion and 15 min after the beginning of methylene blue infusion, revealed a methemoglobin level of 30.3%, with a pH of 7.35, PaO₂ at 30.5 kPa, PaCO₂ at 5.4 kPa, HCO₃ at 21 mmol/L, base excess of −3.3 mmol/L, SaO₂ at 99%, lactate at 2.3 mmol/L, and glucose at 6.7 mmol/L (Table 1). Pre‐treatment methemoglobin level is unknown in this case, due to the rapid antidote administration. Urine toxicology was negative for other illicit substances. ECG showed no abnormalities.

TABLE 1.

Sequential monitoring of arterial blood gas analysis.

Parameter	Reference values	Unit	23:16	23:49	01:20	03:16	20:19 (last)
pH	7.37–7.45	—	7.35	7.38	7.38	7.38	7.40
PaO2	11.2–13.8	kPa	30.5	45.2	28.0	43.3	12.7
PaCO2	4.7–6.1	kPa	5.4	3.9	4.3	4.8	5.0
Bicarbonate	22–28	mmol/L	21	17	19	21	23
Base Excess	−2 to 3	mmol/L	−3.3	−7.2	−5.6	−3.4	−1.2
O2 Saturation	97–100	%	99	99	99	99	97
FiO2		%	100	100	36	50	21
PaO2/FiO2	> 60	kPa	30.5	45.2	77.8	86.6	60.6
Hemoglobin	140–180	g/L	145	120	127	131	147
Hematocrit	0.42–0.52	L/L	0.45	0.37	0.39	0.40	0.45
Oxyhemoglobin	94–98	%	69	87	93	97	96
Methemoglobin	< 1.2%	%	30.3	12.3	5.6	2.2	0.9
Carboxyhemoglobin	0.5–1.5	%	0.0	0.0	0.0	0.2	0.8
Lactate	0.8–1.8	mmol/L	2.3	1.4	1.7	1.9	1.8
Glucose	3.9–6.1	mmol/L	6.7	4.6	5.8	5.9	7.9
Anion gap	8–16	mmol/L	—	5.1	1.4	4.8	4.3

Note: Bold values were pathological/abnormal values.

Following advice from the Swiss Toxicology Center in Zurich, arterial blood gases were repeated every 30 min and methylene blue was to be administered if the patient's methemoglobin remained above 30%. The second blood gas, taken after admission to the intensive care unit at 30 min after the first, showed a reduction in methemoglobin to 12.3%. The patient showed no more clinical signs of tissue hypoxia at this point; thus, further methylene blue administration was not indicated.

4. Conclusion and Results

The patient was transferred to the intensive care unit after initial treatment, with symptoms resolving and oxygen saturation and methemoglobinemia normalizing within less than a day. He was discharged 24 h later.

This case highlights the importance of rapid recognition and appropriate treatment of methemoglobinemia induced by accidental alkyl nitrite ingestion. Though ingestion is rare, clinicians must consider this possibility in patients with unexplained cyanosis and discordant oxygen saturation. Methylene blue administration, along with supportive care, remains the treatment of choice, usually leading to rapid recovery. Raising public awareness of the dangers of easily accessible substances like alkyl nitrites is of high importance.

Indeed, the success of this care also comes from the speed of action of the patient's friends, who directly called the ambulance without waiting for the first symptoms to appear because they were aware of the dangers of ingesting alkyl nitrites. The call from the paramedics on the way also allowed us to contact the toxicologic information center beforehand and prepare the antidote before the patient arrived. As we know that preparing products to be injected can take some time, these minutes saved were precious for the successful outcome of this patient.

5. Discussion

The collective term “poppers” stands for liquid preparations that contain substances from the group of alkyl nitrites (amyl, butyl, isobutyl, propyl, and others). They are sold commercially in small bottles (10–15 mL) as a volatile liquid for inhalation. Although the bottles are labeled with the chemical ingredients, studies have shown that the declared contents and purity often differed from laboratory analysis [3, 4]. Alkyl nitrites act as vasodilators and oxidants with a very short half‐life of 14 min, making their effect very rapid [1]. Since the 1970s, alkyl nitrites have mainly been used in the male homosexual community for sexual arousal and improved sexual performance, particularly by inducing muscle relaxation. In a 2019 Irish study, the incidence of use among Irish gay men was as high as 33% [5]. However, the usage of alkyl nitrites has extended to adolescents and young adults due to easy commercial access and their short‐lasting euphoric and hallucinogenic effects [6]. A 2017 French study found that 8.7% of the population aged 18–64 had used the substance [7]. In 2010, inhalants ranked fourth among recreational drugs used by 15‐year‐olds in Switzerland, after alcohol, tobacco, and cannabis [8]. The prevalence of Poppers use in Switzerland in 2016 was 0.2% [9].

In our country, alkyl nitrites, although banned from the market under Article 5, Paragraph 1 of the Chemical Legislation (LChim, art. 5, al. 1), occupy a regulatory gray area. They are not classified as narcotics because they are considered non‐addictive, nor as medications due to their lack of therapeutic purpose. This situation allows for their possession and private use, even though their purchase, sale, and distribution for inhalation purposes are strictly prohibited [10].

This regulatory duality makes alkyl nitrites easily accessible through informal channels or online purchases, exacerbating the risks associated with accidental or abusive consumption. In the absence of clear sanctions for personal use and targeted awareness campaigns, the public may underestimate the potential dangers of these substances.

To address this gap, it is crucial to develop public awareness initiatives emphasizing the toxic effects of alkyl nitrites, particularly their capacity to induce severe methemoglobinemia, as demonstrated in this clinical case. Educational efforts could include school‐based information sessions, social media campaigns, and collaborations with public health organizations to reduce informal accessibility and promote a better understanding of the risks involved [11].

In Switzerland, it is customary for ambulances to inform the emergency department about arriving patients by telephone, no matter how serious the illness or injury. In other countries, emergency departments are only alerted when patients' conditions are serious or deteriorating. Studies have shown a significant improvement in patient care for certain time‐sensitive pathologies, such as stroke, STEMI, or polytrauma, when they are reported by emergency services in a timely manner to prepare resources and personnel [12]. Intoxications should also be seen as potentially rapidly progressing conditions. In our case, the pre‐alert led to an extremely rapid administration of the antidot upon arrival. We can conclude from this that a standardized pre‐alert by the ambulance in the event of poisoning could benefit these patients, as is already the case with trauma, infarction, or stroke patients.

Sodium nitrite intoxications have been known since the beginning of the 20th century. Until the 1980s, these were mainly environmental and accidental events related to meat preparation and industry. The most common cause of currently reported nitrite intoxications is suicide, accounting for > 60% of poisonings since 2015. Since the 1990s, accidental intoxications with alkyl nitrites have been reported, mainly through ingestion, but also through excessive inhalation. These account for less than 10% of nitrite intoxications since 2015, so they remain a rare entity [13].

Alkyl nitrites oxidize ferrous (Fe²⁺) iron to ferric (Fe³⁺) iron, converting hemoglobin into methemoglobin. Methemoglobin cannot effectively bind and transport oxygen, leading to functional anemia. The affinity of the remaining hemoglobin for oxygen is increased, worsening tissue hypoxia. The typical clinical presentation of significant methemoglobinemia includes cyanosis with normal or slightly lowered oxygen saturation, depending on the device used for pulse oximetry. Blood gases can reveal chocolate‐colored blood, further indicating methemoglobinemia. The clinical presentation varies based on methemoglobin levels (Table 2) [13, 14, 15].

TABLE 2.

Clinical presentation based on the level of methemoglobinemia.

Methemoglobin level	Clinical presentation
< 1%	No physiological consequence
1%–10%	Mild cyanosis, often asymptomatic
10%–20%	Obvious cyanosis, fatigue, slight dyspnea
20%–30%	Moderate symptoms including headaches, dizziness, marked cyanosis
30%–50%	Severe symptoms such as confusion, tachycardia, arrhythmia, generalized cyanosis
50%–70%	Life‐threatening emergency with convulsions, coma, imminent risk of death
> 70%	Generally fatal without immediate intervention

In physiological conditions, about 1% of methemoglobin is present in the blood and is constantly reduced by enzymatic mechanisms, primarily by NADH‐dependent methemoglobin reductase. Significant methemoglobinemia is mostly acquired by the use or abuse of certain drugs or environmental substance exposure. Other than nitrites and nitrates, some drugs known to potentially cause methemoglobinemia include Dapsone, Primaquine, and Benzocaine. Congenital methemoglobinemia is very rare, with only a few cases documented worldwide [2, 15].

Methylene blue is considered an antidote to methemoglobinemia, as it acts as a substrate of the NADPH‐MetHb reductase system (Figure 2). The usual dosage of methylene blue is 1–2 mg/kg; methemoglobin levels usually drop after 30 min of administration. Higher doses cause discoloration of urine and skin; cumulative doses should not exceed 7 mg/kg, as they can lead to paradoxical methemoglobinemia. In cases where methylene blue treatment is ineffective, or in patients with G6PD deficiency, which increases the risk of hemolysis, an exchange transfusion may be considered [2, 15].

FIGURE 2.

Reduction of methemoglobin (MetHb), main and secondary metabolic pathways.

After initial treatment, patients should be closely monitored. The half‐life and pharmacokinetics of the toxin or medication causing methemoglobinemia need to be known to evaluate continued production of methemoglobin. Control blood gas analysis is indicated to ensure effective treatment and evaluate further therapeutic interventions; either arterial or venous blood may be used. Indication for repeated methylene blue therapy and supplemental oxygen administration also depends on the clinical signs of remaining tissue hypoxia and the presence of comorbidities causing concomitant hypoxemia. Patients can be discharged without further intervention once methemoglobinemia is reversed and the causing agent is considered eliminated [15].

Author Contributions

Laurie‐Anne De Pauw: conceptualization, visualization, writing – original draft. Youcef Guechi: validation, writing – review and editing. Jessica Schwaller: supervision, validation, visualization, writing – review and editing.

Ethics Statement

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013).

Consent

The patient provided oral and written informed consent for this case report.

Conflicts of Interest

The authors declare no conflicts of interest.

Data Availability Statement

Data sharing not applicable—no new data generated.