Background: In India, poisoning is one of the common modalities for attempting suicide especially farmers. There is varied presentation among these patients. One such uncommon presentation is Methemoglobinemia. Methemoglobinemia is a rare but potentially life-threatening condition characterized by the oxidation of hemoglobin to methemoglobin (MetHb), rendering it incapable of effectively transporting oxygen, resulting in tissue hypoxia. This condition can be congenital or acquired, often due to exposure to certain chemicals, drugs, or toxins. Acquired methemoglobinemia is frequently seen in cases of poisoning, as highlighted in this case series of three patients admitted to a tertiary care hospital in central India following suicidal ingestion of toxic substances Material and Methods: This study was conducted in a tertiary care teaching hospital of central India where patients of Toxin induced Methemoglobinemia were recruited. It was an observational study of 6 months duration. Informed consent was obtained and duly signed by the patient or next of kin. History, Physical examination, Routine investigations, ABG, Co-Oximetry studies were done. Patients were managed as per established protocol with no additional out of protocol investigation or treatment was done pertaining to this study. Patient's confidentiality was maintained throughout this study. Results: This case series involved three patients who developed toxic methemoglobinemia following ingestion of different toxic substances. - Effectiveness of Methylene Blue: In cases with moderate to severe methemoglobinemia (MetHb 33.5% to 41.4%), methylene blue proved effective in reducing MetHb levels and improving clinical outcomes. The initial treatment significantly improved MetHb levels and patient symptoms, with favorable outcomes observed in two of the three cases. - Severe Outcomes: The third case, with an exceptionally high MetHb level of 74%, demonstrated the limits of methylene blue treatment. Despite multiple doses, the patient’s condition deteriorated, indicating that extremely high MetHb levels and delayed treatment can lead to poor outcomes.Complications and Mortality: The case with the highest MetHb level resulted in mortality, underscoring the critical importance of early diagnosis and intervention. The other two cases, despite initial severe symptoms, responded well to timely methylene blue treatment and supportive care. Conclusion: This case series illustrates the clinical variability and challenges in managing toxin-induced methemoglobinemia. The condition should be suspected in cases of poisoning, particularly when there is a mismatch between oxygen saturation and arterial blood gas measurements. Early intervention with methylene blue, guided by co-oximetry, is essential for improving outcomes. Severe cases, especially those with MetHb levels exceeding 70%, carry a poor prognosis despite aggressive treatment, highlighting the need for early recognition, monitoring, and advanced supportive care
Methemoglobinemia is a rare hematological condition in which normal Hemoglobin (Hb) gets oxidized to Methemoglobinemia (MetHb) rendering it incapable to deliver oxygen to tissues. Methemoglobinemia is characterized by high levels of MetHb in the blood. It occurs when the iron moiety of hemoglobin is oxidized from the ferrous (Fe2+) to ferric state (Fe3+), forming MetHb. This change renders MetHb incapable of oxygen transport and shifts the oxygen dissociation curve leftward. This hence increases the risk of tissue hypoxia [1,2]. The normal steady state MetHb levels are <1%. Methemoglobinemia is diagnosed if the methemoglobin level is >5 percent [1,2]. It has two forms- congenital and acquired. Congenital forms of methemoglobinemia are due to autosomal recessive defects in the enzyme cytochrome b5 reductase (CYB5R) or due to autosomal dominant mutations in the genes that code for globin proteins collectively known as hemoglobin M.Acquired methemoglobinemia, which is much more common, is the result of exposure to substances that cause oxidation of the hemoglobin either directly or indirectly. This exposure results in the production of methemoglobin that exceeds the body’s capacity to convert the iron within the hemoglobin back to its ferrous state. [2]In adults, it can be acquired on being exposed to certain chemical substances like aniline dyes, herbicides, nitrates etc or due to consumption of drugs [1][3].The usual presentation may vary widely from being clinically asymptomatic to mild clinical features like headache, dizziness, dyspnea, cyanosis and in some cases can lead to arrythmias, seizures, coma & even death [2][4]. Over the years it has also been found to be associated with ingestion of poisonous substances [2]. These varied presentations with sometimes inadequate history in cases of poisoning makes it difficult for the physician to diagnose this condition, especially in Indian subcontinent
This case series study was conducted in a tertiary care teaching hospital of central India. This study was conducted in Medical ICU where patients with alleged history of ingestion of toxic substances with accidental/suicidal intent were recruited.
This study was initiated after obtaining clearance from Institute Ethics Committee.
It was an observational study of 6 months duration conducted among confirmed cases of Toxin induced Methemoglobinemia, with data gathered and analyzed. Data regarding occupational history, comorbidities, past history were collected and analyzed.
Patients were thoroughly assessed by history, clinical examination, routine investigations. ABG & Co-oximetry studies were done. All cases were treated with IV Methylene Blue as per treatment protocol of the disease. Patients were completely managed as per established protocol. No additional treatment planned or given pertaining to this study.
All participants were recruited after detailed explanation of study objectives, methods, potential advantage or risk to the participants in their native language. Confidentiality of the participant was maintained throughout the study. Informed consent was obtained duly signed by the patient/ next of kin.
Microsoft Excel was used to enter the information, tabulate and analyze the data gathered from study participants.
We treated 3 cases of Methemoglobinemia associated with self-harm ingestion of poisonous substance in our tertiary care teaching hospital of central India. The clinical presentation and relevant investigations are summarized in Tables 1-2
Case1: 32 years old male with no comorbidities and psychiatric illness presented with alleged consumption of about 20 ml insecticide named “KILLER” containing Deltamethrin-1.8% EC which is a Pyrethroid with suicidal intent. He was admitted in hospital after 8hours of consumption. His admission vitals were HR=92bpm, BP=124/80mmHg, spO2=92%Room Air, RBS=104mg/dl. Systemic examination revealed no abnormality, chest being clear bilaterally. The patient was given supportive treatment but the condition of patient deteriorated and he developed uneasiness and shortness of breath with spO2 dropping to around 92% Room Air. Bedside test for methemoglobinemia (Figure 1) revealed darker blood of patient as compared to healthy person’s blood as control.6 ABG with co-oximetry was done immediately which reflected MetHb% as 33.5%. After ensuring patient’s G6PD(Glucose 6 Phosphate Dehydrogenase) enzyme levels to be normal, he was given IV Methylene blue at dose of 2mg/kg over 5 mins. Repeat co-oximetry after 1 hour showed reduction MetHb% to 9.4% with improvement of symptoms. Subsequently the condition of patient improved with resolution of dyspnea, headache. MetHb% normalized on day 3 of hospitalization with no further complications during the hospital stay.
Figure 1: Bedside test for Methemoglobinemia: Red arrow showing dark chocolate brown colored blood of patient as compared to red colored blood of control (Black arrow)
Case 2: 27 years old married female with suicidal intent allegedly consumed 30 ml of Paint thinner containing Turpentine oil. She presented to casualty after 2 hours of ingestion and treatment was provided as per protocol. On admission, her vitals were stable and systemic examination showed no abnormality. On day 2 of hospitalization, she experienced dyspnea and was tachypneic with respiratory rate of 28/min with use of accessory muscles of respiration. She had no obvious features of cyanosis and on respiratory examination- Bilateral vesicular breathing with adequate air entry & no added sounds. spO2 showed 78% RA with only mild improvement after oxygenation, suggestive of refractory hypoxia. CBC showed raised leucocyte count, LFT, RFT, serum electrolytes were within normal limit. ABG showed mild respiratory alkalosis with co-oximetry study suggestive of Methemoglobinemia with MetHb% -41.4%. After ruling out G6PD deficiency, the patient was given IV Methylene Blue 2mg/kg over 5 mins. Repeat co-oximetry at 1 hour showed falling trend of MetHb% to 28% but her symptoms persisted and was tachypneic with spO2 level around 85%. Therefore, second dose of IV Methylene blue was administered. Her condition gradually improved with improvement in dyspnea and spO2 improving to around 94% on room air. Repeat co-oximetry study showed MetHB as 6.4%. She had no evidence of hemolysis and was further monitored closely clinically, biochemically and with subsequent ABG and co-oximetry studies for detecting any rebound increase of MetHb. The patient improved very well with normal respiratory rate and complete resolution of dyspnea and SpO2 improved to 97%RA by day 5 of hospitalization. The patient was further monitored and subsequently discharged on day 8 with follow up.
Case 3:
47 years old male, farmer by occupation with comorbidities of Hypertension on treatment with good compliance for last 6 years presented to casualty of our tertiary care hospital after 10 hours with alleged consumption of insecticide containing “Indoxacarb” with suicidal intent. He had no previous psychiatric illness or neurological deficit. On presentation he was unconscious with poor GCS score of 5. He had pulse of 134 bpm, RR-24/min BP-114/76mmHg spO2-71% RA RBS-184mg/dl and had cyanosis. He was immediately intubated & put on ventilatory support. His blood was also dark brown in color which raised the suspicion of Toxin induced methemoglobinemia. ABG showed Metabolic acidosis with respiratory compensation and co-oximetry showed MetHb as 74%. The patient was started on supportive treatment and G6PD deficiency was ruled out. We administered IV Methylene blue 2mg/kg over 5 minutes. Co-oximetry showed reduction in MetHb levels to 52%. The condition of patient didn’t improve and CBC showed leucocytosis with mildly raised AST/ALT levels. He received total 3 doses of IV Methylene blue and MetHb% dropped to 24% on day2 of hospitalization. The patient remained unconscious and continued on ventilatory support and condition further deteriorated despite maximal appropriate adjustments of ventilator. He experienced 2 episodes of seizures followed by cardiac arrest and finally succumbed to his illness on day 6 of hospitalization.
Table 1: Table showing clinical presentation, examination and outcome of methemoglobinemia patients
RA-Room Air, MetHb %- Methemoglobinemia percentage in Co-Oximetry studies
Table 2: Table showing relevant investigations and treatment administered to Methemoglobinemia patients
pO2- partial pressure of Oxygen, pCO2- partial pressure of Carbon Dioxide, Methb%- Methemoglobinemia percentage
In a developing nation like India, there have been increased rates of suicidal attempt due to multifactorial causes including but not limited to stress, depression, debt to farmers etc. Ingestion of insecticides, pesticides, fertilizers and other substances remain one of the common modality for suicide pertaining to its easy availability [3]. These can cause various known and uncommon adverse effects to health of the person. One such uncommon presentation which we have discussed in this case series is Toxin Induced Methemoglobinemia. Methemoglobin (MetHb) may arise from a variety of etiologies including genetic, dietary, idiopathic, and toxicologic sources. Toxin-induced Methemoglobinemia may be further complicated by the drug’s effect on other organ systems such as the liver or lungs [5,6].
Methemoglobinemia is a condition where levels of methemoglobin in the blood exceed levels of 5% [7,8]. Toxin-induced methemoglobinemia is also called toxic methemoglobinemia. It is a hematologic disorder attributed to exposure to toxic oxidizing agents and is commonly seen in cases of poisoning
Due to toxin related oxidative stress, ferrous ions undergo oxidation leading to decreased oxygen delivery and shift of O2-Hb dissociation curve to left thus causing tissue hypoxia [6]. The clinical spectrum of this condition varies from mild symptoms like nausea, vomiting to headache, cyanosis, acidosis altered mental status to arrythmias, seizures coma, acidosis and even death.2 The typical pattern seen is cyanosis, low hemoglobin oxygen saturation on pulse oximetry, normal partial pressure of oxygen in arterial blood (PaO2) on ABG and dark colored blood. It can be diagnosed by Co-oximetry studies which reflects the percentage of Methemoglobinemia. MetHb levels of up to 20% are usually well tolerated by otherwise healthy individuals. MetHb levels of >70% are usually fatal [7-9].
In this case series we presented three cases of toxic methemoglobinemia associated with ingestion of Deltamethrin (pyrethroid), Turpentine oil, Indoxacarb (Oxadiazine pesticide) [10,11]. It is an uncommon complication associated with these poisonous substances and there have been very few case reports globally [12,13]. We have described the varied presentation of the patient in different scenarios which had two favorable outcome and patients were subsequentially discharged, but one patient succumbed to this complication despite adequate resuscitative measures.
The mainstay of the treatment of acquired methemoglobinemia is identification and withdrawal of the offending agent. The treatment depends on MetHb% levels and clinical status of patient [14]. Conservative management can be considered in asymptomatic patients with low MetHb levels and may attempt antidotes like Methylene blue, Ascorbic acid for managing symptomatic and severe cases. The essential thing to be kept in mind before administering IV Methylene Blue is to rule out Glucose-6 Phosphate Dehydrogenase(G6PD) deficiency as this may lead to severe hemolysis thus worsening prognosis of the patient. Few case reports have also shown the role of exchange transfusion and hyperbaric oxygen therapy [15].
tions for BP measurement protocols in clinical settings.
This case series highlights the importance of early recognition and management of methemoglobinemia, particularly in cases involving toxic ingestions, as prompt treatment can significantly improve patient outcomes. The clinical presentation of methemoglobinemia can vary widely, ranging from mild symptoms such as dizziness and dyspnea to severe complications like seizures, arrhythmias, coma, and even death, as seen in the fatal case in this series.
High Clinical Suspicion: In cases of poisoning, especially with a history of ingestion of pesticides, insecticides, or other oxidizing agents, physicians should have a high index of suspicion for methemoglobinemia. Cyanosis unresponsive to oxygen therapy, refractory hypoxia, and dark-colored blood are important clinical clues. Diagnostic Confirmation: Pulse oximetry may provide misleading readings, and arterial blood gases (ABG) alone may not reflect the true oxygen-carrying capacity of the blood. Co-oximetry remains the most useful and readily available modality for diagnosing methemoglobinemia by directly measuring MetHb levels, as highlighted in all three cases. Treatment with Methylene Blue: Methylene blue is the first-line treatment in symptomatic or severe cases of methemoglobinemia. In two of the cases, prompt administration of methylene blue resulted in significant improvement and a favorable prognosis. However, the severity of methemoglobinemia and the patient’s overall clinical condition are critical determinants of the outcome. The third patient, despite treatment, had a fatal outcome likely due to the high initial MetHb level (74%) and late presentation.
Role of Supportive Care: In addition to methylene blue, supportive care, including oxygen supplementation and, in severe cases, mechanical ventilation, is essential for managing hypoxia. Exchange transfusion and hyperbaric oxygen therapy have also been suggested as potential treatments in refractory cases, although these were not used in this series. Mortality Risk: The mortality rate increases with higher levels of MetHb, as demonstrated in the case with a fatal outcome, where the initial MetHb level exceeded 70%. Early intervention before MetHb levels reach critical thresholds (>50%) is key to reducing mortality. Precautionary Considerations: Before administering methylene blue, it is crucial to rule out glucose-6-phosphate dehydrogenase (G6PD) deficiency, as methylene blue can cause hemolysis in these patients. Fortunately, none of the patients in this series had G6PD deficiency, and methylene blue was administered safely.
In conclusion, methemoglobinemia should be suspected in cases of poisoning, particularly in regions like the Indian subcontinent, where toxic substances like pesticides and insecticides are frequently ingested. Early recognition, rapid confirmation with co-oximetry, and timely administration of methylene blue are critical to improving survival rates. This case series emphasizes the varied clinical presentation and outcomes of methemoglobinemia and underscores the importance of vigilance in diagnosing and managing this rare but serious condition.
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