Rebound paediatric methemoglobinemia from nitroethane ingestion: a case report

Introduction

Background

Methemoglobinemia (MetHb) is a rare but potentially life-threatening hematologic condition in which hemoglobin’s iron is oxidized to the ferric state, impairing oxygen delivery (1). Acquired MetHb in children often results from exposure to oxidant chemicals or drugs. One unusual cause is nitroethane, an organic solvent found in certain paint removers, hardeners, and nail polish removers.

Rationale and knowledge gap

Upon ingestion, nitroethane is metabolized to nitrite, a potent oxidizer that converts hemoglobin to methemoglobin (2). Even small volumes of nitroethane can cause severe toxicity in children; for example, as little as 10 mL of a 98% nitroethane solution has been reported to produce methemoglobin levels above 30%, leading to significant hypoxia and clinical cyanosis (3).

Objective

To describe a paediatric case of severe nitroethane-induced MetHb with rebound after initial antidote therapy, and to highlight the need for prolonged observation and preventive education. We present this case in accordance with the CARE reporting checklist (available at https://acr.amegroups.com/article/view/10.21037/acr-2025-315/rc) (4).

Case presentation

A previously healthy 6-year-old boy presented to the emergency department (ED) of a tertiary government hospital (Hospital Sungai Buloh) the morning after ingesting approximately one mouthful of paint chemical hardener (AkzoNobel), stored in a reused drinking water bottle. Immediately after ingestion, he experienced oral pain, ear discomfort and a burning sensation in the mouth and abdomen, which resolved spontaneously. The next morning, however, he developed abdominal pain, four episodes of vomiting (including one blood-stained), one episode of watery diarrhea and bluish discoloration of his lips and fingers.

On ED arrival, the child was alert and able to speak in full sentences. He exhibited cyanosis of the lips and extremities. Vital signs were as follows: heart rate 128 beats per minute (bpm), blood pressure 83/61 mmHg, respiratory rate 25 breaths per minute, and oxygen saturation (SpO₂) between 88% and 93% on room air. Venous blood gas (VBG) analysis showed a methemoglobin (MetHb) level greater than 30%, with pH 7.34, bicarbonate (HCO₃) 20.5 mmol/L, and lactate 4.3 mmol/L (Table 1). His glucose-6-phosphate dehydrogenase (G6PD) status was confirmed to be normal based on prior medical records. Notably, there was no observation of chocolate-brown discoloration of blood during sampling, a classic but sometimes absent clue in MetHb.

Initial management included high-flow nasal oxygen therapy [Airvo 30 L/min, fraction of inspired oxygen (FiO₂) 0.4] and intravenous fluid resuscitation. Intravenous methylene blue was administered at a dose of 1 mg/kg over five minutes under cardiac monitoring. One hour later, a repeat VBG demonstrated improvement: MetHb decreased to 9%, with pH 7.33, HCO₃ 24.0 mmol/L, and lactate 1.6 mmol/L.

The child was admitted to the intensive care unit (ICU) for close observation. During his ICU stay, his MetHb levels rose again to 16.6% with a concurrent drop in oxygen saturation. A second dose of intravenous methylene blue was administered, resulting in a reduction of MetHb to 4.1% and normalization of SpO₂. He remained stable without hemolysis.

He was managed in the ICU for 2 days before being transferred to the general pediatric ward for prolonged monitoring. He remained in the pediatric ward for an additional 6 days for monitoring of possible hemolysis as a late complication and awaiting input from the Department of Social Welfare, who planned a home visit to ensure a safe home environment and prevent future accidental exposures. The patient was discharged well on day 8.

Ethical considerations

All procedures performed in this case were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patient’s legal guardian for the publication of this case report. A copy of the written consent is available for review by the editorial office of this journal.

Discussion

Key findings

Toxicity of nitroethane ingestion: nitroethane is a nitroalkane solvent known to induce MetHb through its metabolic conversion to nitrites (2). In pediatric poisonings, nitroethane-containing products have caused serious, life-threatening MetHb even with minimal ingestion. The case presented here aligns with published reports: a volume of only a few milliliters can result in MetHb levels well above the usual symptomatic threshold of ~20%. Methemoglobin levels above ~30% typically produce pronounced cyanosis and can lead to lethargy, respiratory distress, and risk of seizures; levels >50% are considered critical and >70% can be lethal (3). Our patient’s MetHb >30% represented a severe intoxication.

Strengths and limitations (diagnostic pitfalls)

The diagnosis of MetHb can be challenging. A critical clinical clue is cyanosis that does not resolve with high-flow oxygen. In our patient, the persistent peripheral cyanosis and low oxygen saturation reading did not improve even after supplemental oxygen. This scenario is characteristic: central cyanosis with no apparent respiratory distress, a low pulse oximeter saturation that remains around ~85% despite 100% oxygen, and a normal arterial oxygen partial pressure (PaO₂) on blood gas analysis (the so-called saturation gap) are hallmark signs (5). Pulse oximetry is unreliable in this condition (1).

Additionally, the blood may appear a characteristic chocolate-brown color (5). In our case, this classic clue was absent. Diagnostic confusion may arise from the history. In this incident, the agent was stored in a reused drinking water bottle, increasing misidentification risk. Previous reports have described paediatric MetHb following ingestion of various cosmetic or solvent products, including nail polish remover and nail glue remover, highlighting that different commercial preparations may contain oxidizing ingredients capable of inducing toxicity (2,6). It is therefore essential for clinicians to confirm the specific product and its ingredients, as acetone-based nail polish remover and nitroethane-containing artificial nail glue remover have distinct toxicologic profiles. Co-oximetry (which directly measures fractional methemoglobin) is the diagnostic gold standard (7).

Comparison with similar research

A notable feature in this case was the rebound MetHb observed about 8 hours after the initial treatment. This phenomenon is well documented with nitroethane and other lipid-soluble or slowly metabolized oxidant agents (3,7). Pharmacokinetic analyses of pediatric nitroethane poisonings have estimated an effective half-life of at least ~8 hours for nitroethane’s oxidant activity (3). For instance, Osterhoudt et al. (8) reported a pediatric case with an initial MetHb of 48% that rebounded to 53% approximately 16 hours after methylene blue therapy (3). Recent literature continues to highlight the burden of MetHb in the pediatric population. A 2024 multicenter evaluation reported ongoing presentations of acquired MetHb in children, emphasizing the need for early recognition and prompt treatment (9). Rebound MetHb has also been increasingly described in recent reports, particularly following toxin-induced cases or delayed elimination of oxidizing agents (10). These findings support our patient’s clinical course.

Explanations of findings

The mechanism behind rebound MetHb likely involves continued biotransformation of the toxin (nitroethane) to nitrite after the initial antidotal effect has waned (7). Additionally, the half-life of methylene blue in blood is relatively short, so methemoglobin levels can rise again once the initial dose is cleared.

Implications and actions needed

Because of this risk, patients with nitroethane exposures require extended observation and serial methemoglobin level monitoring. Literature on nitroethane poisoning recommends close monitoring for at least 24 hours (3). Our case validates this recommendation. ICU admission is prudent for severe cases. Low dose repeat administration of methylene blue is effective in treating rebounds (7).

Preventive strategies: this case underscores the critical importance of poisoning prevention measures. Caregivers should enforce safe storage practices by keeping all hazardous chemicals in their original, clearly labeled containers, secured out of reach of children and never in food or drink containers (11). The use of child-resistant packaging has been one of the most effective interventions (12). However, “child-resistant” does not mean “child-proof” (13).

Public education and community awareness are vital (12). Multifaceted prevention programs, including educational interventions paired with safety devices, improve safe storage behaviors (14). Community-wide initiatives also raise awareness (15). Finally, caregivers should be ready to respond by immediately contacting a poison control center (16). Poison control centers provide rapid, expert guidance and can often prevent harm (12). It is recommended that families keep the Poison Help line number easily accessible (16).

Conclusions

This case demonstrates that a small volume of paint chemical hardener (AkzoNobel) can precipitate severe paediatric MetHb. The key diagnostic clues were persistent cyanosis with low pulse oximetry readings despite supplemental oxygen and confirmation of markedly elevated methemoglobin on venous co-oximetry (>30%). Early administration of methylene blue led to rapid clinical and biochemical improvement; however, a clinically significant rebound (MetHb 16.6%) occurred approximately 8 hours later, necessitating a second dose.

The patient’s stable course highlights the importance of serial methemoglobin measurements and prolonged observation (at least 24 hours) for nitroethane exposures, even when initial response is favourable. This case adds to the limited paediatric nitroethane literature and reinforces the need for prolonged observation to detect rebound MetHb. Beyond bedside management, this case underscores preventable factors, notably decanting chemicals into drink bottles. Safe storage in original containers, child-resistant packaging, and caregiver education are practical community-level measures that can reduce similar incidents.

Acknowledgments

The authors would like to appreciate and acknowledge the Ministry of Health Malaysia for allowing the publication of this case report.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://acr.amegroups.com/article/view/10.21037/acr-2025-315/rc

Peer Review File: Available at https://acr.amegroups.com/article/view/10.21037/acr-2025-315/prf

Funding: None.

Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://acr.amegroups.com/article/view/10.21037/acr-2025-315/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this case were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patient’s legal guardian for publication of this case report. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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