Acquired Methemoglobinemia Following Nitrobenzene Poisoning: An Unusual Case Report

Abstract

Methemoglobinemia is a rare but potentially life-threatening condition characterized by the oxidation of hemoglobin iron from ferrous (Fe²⁺) to ferric (Fe³⁺) state, impairing its oxygen-carrying capacity. Acquired forms can be triggered by exposure to oxidizing agents, such as nitrobenzene. We present the case of a 32-year-old female who developed symptomatic methemoglobinemia following oral ingestion of a commercial stimulant product containing nitrobenzene. She presented with peripheral cyanosis, breathlessness, and hypoxia unresponsive to oxygen therapy. A diagnosis of methemoglobinemia was confirmed, and prompt administration of intravenous methylene blue led to rapid clinical improvement. This case emphasizes the importance of early recognition of acquired methemoglobinemia in the context of toxic exposure, especially when conventional respiratory or cardiac pathology is excluded. Methylene blue remains the first-line antidote, offering effective and timely reversal of symptoms.

Introduction

Methemoglobinemia is a hematologic disorder characterized by elevated levels of methemoglobin (MetHb), an oxidized form of hemoglobin incapable of binding and transporting oxygen. Normally, MetHb accounts for less than 1% of total hemoglobin, maintained by enzymatic reduction systems such as NADH-dependent cytochrome b5 reductase.^1,2 However, exposure to certain oxidizing agents can overwhelm this system, resulting in symptomatic methemoglobinemia. While congenital forms exist, most cases encountered clinically are acquired, commonly due to exposure to chemicals such as nitrites, aniline dyes, and nitrobenzene. Rapid identification and treatment are crucial, as MetHb levels above 30% can be life-threatening. This report describes a rare case of nitrobenzene-induced methemoglobinemia from a commercially available flower stimulant.^1,2 The flower stimulant ingested by the patient is commonly marketed in agricultural and decorative horticulture sectors to enhance floral longevity and appearance. Chemical analysis revealed that it contained approximately 59% nitrobenzene, a potent oxidizing agent, and 31% unidentified organic solvents. These products are often sold without adequate safety labeling or regulatory oversight, posing significant public health risks when ingested accidentally or intentionally. The widespread availability of such compounds underscores the need for increased awareness and regulation of consumer chemical agents.

Case Presentation

A 32-year-old previously healthy female presented to the emergency department with acute onset of breathlessness, generalized weakness, and bluish discoloration of the lips and extremities approximately 4 hours after ingesting a commercially available flowering stimulant supplement. The product was later analyzed and found to contain 59% nitrobenzene and 31% unidentified organic compounds, raising suspicion for oxidative toxicity. She denied any prior history of cardiopulmonary disease, recent infections, or medication use.

On examination, the patient was alert, oriented, and hemodynamically stable with a respiratory rate of 24 breaths per minute, pulse rate of 100 beats per minute, blood pressure of 110/70 mmHg, and oxygen saturation (SpO₂) of 82% on room air, which minimally improved to 83% with high-flow oxygen at 8 L/min via face mask (Figure 1). Central and peripheral cyanosis was evident, particularly involving the perioral region and fingertips. Cardiovascular and respiratory examinations were otherwise unremarkable, with normal heart sounds and clear vesicular breath sounds bilaterally, ruling out primary cardiac or pulmonary causes.

Figure 1.

Oxygen saturation (SpO₂) trend from admission through discharge, demonstrating clinical improvement following methylene blue administration.

Initial investigations, including electrocardiogram (ECG), echocardiography, chest radiography, and routine blood counts, were within normal limits. However, arterial blood gas (ABG) analysis revealed a pH of 7.50, pCO₂ of 15 mmHg, bicarbonate (HCO₃⁻) of 12 mmol/L, and a methemoglobin (MetHb) level of 35%, markedly elevated above the normal reference of less than 1-2%. Despite the cyanosis, the partial pressure of oxygen (PaO₂) on ABG was normal (95 mmHg), consistent with methemoglobinemia, which impairs oxygen delivery without affecting dissolved oxygen content. Given the clinical presentation, refractory hypoxia despite oxygen therapy, and exposure history, a diagnosis of acquired methemoglobinemia secondary to nitrobenzene ingestion was made. The patient was promptly treated with intravenous methylene blue at a dose of 1 mg/kg body weight administered slowly over 5 minutes. Within 20 minutes of administration, her cyanosis visibly improved, and oxygen saturation increased to 92% on pulse oximetry. Post-treatment, she passed green-colored urine, a benign and expected side effect of methylene blue metabolism.

The patient was subsequently monitored in a high-dependency unit for 24 hours, with serial SpO₂ measurements and ABG analyses (performed at 2-hour intervals) post methylene blue administration, confirming a steady decline in methemoglobin levels and normalization of acid-base status. She was discharged 48 hours post-admission in stable condition, with MetHb levels returning to normal (<2%), and advised to avoid further exposure to unknown chemical agents. At a 2-week follow-up, she remained asymptomatic, with no residual cyanosis or cardiopulmonary compromise. Arterial blood gas (ABG) analyses.

Discussion

Methemoglobinemia, an uncommon but potentially fatal condition, occurs when heme iron is oxidized from the ferrous (Fe²⁺) to the ferric (Fe³⁺) state, impairing its oxygen-carrying capacity and resulting in functional anemia. In the setting of nitrobenzene poisoning, this oxidative stress overwhelms endogenous reductive systems, leading to an accumulation of methemoglobin (MetHb) levels exceeding the normal physiological threshold of 1% to 2%.^1,2 Nitrobenzene, an aromatic nitro compound widely used in the chemical industry, has been increasingly reported as a cause of methemoglobinemia in non-occupational exposures, such as through ingestion of unregulated herbal products. ² Following absorption through mucosal surfaces, nitrobenzene is metabolized in the liver, where its oxidative metabolites promote hemoglobin oxidation, causing clinical manifestations of hypoxia despite adequate oxygen tension (PaO₂) on arterial blood gas (ABG) analysis.^3,4

In our patient, classical features such as cyanosis refractory to oxygen therapy, discrepancy between low SpO₂ and normal PaO₂, and elevated MetHb levels (35%) were diagnostic hallmarks. The gold-standard treatment for acquired methemoglobinemia is methylene blue, a synthetic dye that serves as an electron donor, reducing ferric iron back to its functional ferrous state via the NADPH-methemoglobin reductase pathway.^4,5 Standard dosing (1-2 mg/kg IV) is effective, with a rapid clinical response typically seen within 30 to 60 minutes. Our patient demonstrated marked improvement within 20 minutes, corroborating literature on the efficacy and safety of methylene blue in emergency settings. ⁶ However, caution must be exercised in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency, where methylene blue can exacerbate hemolysis. ⁷

Alternative or adjunctive therapies such as ascorbic acid (vitamin C) have been suggested in milder cases or when methylene blue is contraindicated, although their onset of action is slower. ⁸ Advanced interventions like exchange transfusion or hyperbaric oxygen therapy may be warranted in severe, refractory cases exceeding 50% MetHb levels or in the presence of comorbidities. ⁹ Importantly, this case highlights the emerging risk posed by unregulated herbal and commercial stimulant products containing industrial chemicals like nitrobenzene, emphasizing the need for public health policies and regulatory oversight. Physicians should maintain a high index of suspicion for methemoglobinemia in cyanotic patients with no apparent cardiopulmonary pathology, particularly when hypoxia is unresponsive to supplemental oxygen. Importantly, this case emphasizes the emerging threat posed by the unregulated availability of chemical agents, including floral stimulants containing industrial solvents like nitrobenzene. Such products, often marketed with vague or misleading labels, may be easily misused, intentionally or inadvertently, resulting in toxicologic emergencies. This necessitates not only clinical vigilance but also public health initiatives aimed at regulation, consumer education, and product surveillance.

This case report is limited by the lack of confirmatory toxicological quantification of all components in the ingested product, which may influence clinical effects. Additionally, G6PD deficiency testing was not performed before methylene blue administration, posing potential safety concerns. The short follow-up period and inability to fully exclude other environmental or occupational exposures further restrict the assessment of long-term outcomes and confounding factors.

Conclusion

Acquired methemoglobinemia is a unusual and critical condition, often overlooked in emergency settings due to its nonspecific presentation. Our case highlights the diagnostic challenges and therapeutic importance of recognizing nitrobenzene-induced methemoglobinemia, especially from non-traditional sources like herbal supplements. The discrepancy between SpO₂ and PaO₂, combined with clinical cyanosis, serves as a crucial diagnostic clue. Methylene blue remains the cornerstone of treatment, providing rapid and effective reversal of hypoxia. This case reinforces the need for clinician awareness, appropriate diagnostic evaluation, and timely management in toxicologic emergencies. Furthermore, it calls for greater regulatory control of consumer products to prevent inadvertent exposure to hazardous industrial chemicals like nitrobenzene.