CASE SERIES |
https://doi.org/10.5005/jp-journals-11006-0156 |
Methemoglobinemia: The Common Presenter of Diverse Toxins with Varied Outcomes
1Department of General Medicine, Sri Venkateshwara Medical College, Tirupati, Andhra Pradesh, India
2,4Department of Oncology, SVICCAR, Tirupati, Andhra Pradesh, India
3,5Department of General Medicine, Sri Venkateswara Institute of Medical Sciences, Tirupati, Andhra Pradesh, India
Corresponding Author: Praveen Kumar Javvaji, Department of General Medicine, Sri Venkateshwara Medical College, Tirupati, Andhra Pradesh, India, Phone: +91 7207170794, e-mail: praveenmedico.in@gmail.com
Received: 29 September 2024; Accepted: 04 December 2024; Published on: 25 February 2025
ABSTRACT
Aim and background: To study the clinical presentation in two cases of poisoning presenting with methemoglobinemia. To review common causes of methemoglobinemia and study differences in their presentation and management. Methemoglobinemia is a common presenting feature among patients presenting to the hospital following deliberate ingestion of various poisons.
Case description: We report two patients who had consumed two different groups of toxins and presented with the common manifestation of methemoglobinemia. The first case involves indoxacarb ingestion, whereas the second case presents with consumption of organic fertilizer. Although presenting features and initial management were similar in both patients, the response to therapy, complications, and time to recovery were quite different.
Conclusion and clinical significance: In rural backgrounds, suicidal attempts with chemical compounds used for agriculture are common. These compounds are numerous, and it is difficult to have knowledge regarding all of their presentations. Methemoglobinemia is one such presentation, which can easily be missed without a high degree of clinical suspicion. A thorough knowledge of all the toxins capable of causing methemoglobinemia and their unique features is necessary for the appropriate management of these cases.
Keywords: Indoxacarb, Methemoglobinemia, Organic fertilizer poisoning, Saturation gap
How to cite this article: Javvaji PK, Adusumilli P, Prasanth P, et al. Methemoglobinemia: The Common Presenter of Diverse Toxins with Varied Outcomes. Indian J Crit Care Case Rep 2025;4(2):31–33.
Source of support: Nil
Conflict of interest: None
Patient consent statement: The author(s) have obtained written informed consent from the patients (for case 1 and 2) for publication of the case report details and related images.
INTRODUCTION
Methemoglobinemia is characterized by low oxygen-carrying capacity of hemoglobin and tissue hypoxia due to poor oxygen delivery. Each hemoglobin molecule has four iron species, usually all of them in a ferrous state. When one of them oxidizes to a ferric state, the resultant allosteric changes in the hemoglobin molecule lead to a shift of the oxygen dissociation curve to the left. This causes impaired oxygen release to the tissues, resulting in hypoxia.1
Physiologically, methemoglobin levels are maintained below 1% by two enzymatic pathways. One involves cytochrome-b5 reductase, which utilizes nicotinamide adenine dinucleotide (NAD) formed during glycolysis to reduce hemoglobin. The second one, known as the alternate pathway, involves nicotinamide adenine dinucleotide phosphate hydrogen methemoglobin (NADPH-MetHb) reductase, utilizing NADPH formed by the action of glucose-6-phosphate dehydrogenase (G6PD) in the hexose monophosphate shunt.1
Methemoglobinemia can be classified into hereditary or acquired. Acquired methemoglobinemia occurs mainly after exposure to an exogenous oxidizing agent like nitrates, chlorates, and aniline compounds. Some drugs are also known to cause methemoglobinemia, namely dapsone, benzocaine, and primaquine.2
Clinical presentation of methemoglobinemia depends on the level of MetHb. Cyanosis occurs when serum methemoglobin is above 1.5 gm/dL, which corresponds to 15% of total hemoglobin in a normal individual. When methemoglobin increases to 20% of total hemoglobin, one may experience headache, dizziness, and anxiety. Levels between 30 and 50% can manifest as fatigue, confusion, and shortness of breath. At levels of 50% or above, it produces arrhythmias, acidosis, seizures, and coma.2
Clinical suspicion of methemoglobinemia should arise in the presence of cyanosis and hypoxemia, which is not corrected by supplemental oxygen. The presence of a “saturation gap,” calculated by the difference between oxygen saturation by pulse oximeter and that derived by arterial blood gas analysis, and the finding of chocolate-colored blood confirm the diagnosis.2
Treatment of acquired methemoglobinemia involves finding the causative agent and withdrawing it promptly. In severe cases, methylene blue can be given intravenously at 1–2 mg/kg over 5 minutes. It accelerates the reduction of MetHb via the NADPH-MetHb reductase pathway and is the treatment of choice. Other therapeutic options include vitamin C, exchange transfusion, and hyperbaric oxygen therapy.1
Here, we are reporting two cases of poisoning with different agents but presenting with the common manifestation of methemoglobinemia.
CASE DESCRIPTION
Case 1
A 45-year-old farmer with no known comorbidities presented to the hospital following consumption of about 50 mL of the pesticide Indoxacarb, approximately 4 hours prior to arrival at our hospital. General physical examination revealed central cyanosis. His pulse rate was 108 beats/minutes, blood pressure 114/70 mm Hg, while pulse oximetry showed a saturation of 90% with 10 L of oxygen via facemask. The patient was drowsy, with a Glasgow Coma Scale (GCS) score of E2V1M5. Auscultation of the chest revealed bilateral diffuse wheeze and basal crepitations. Arterial blood gas analysis revealed a pH of 7.24, PaO2—142, pCO2—57, and bicarbonate—25. Arterial blood was chocolate brown in color (Fig. 1). Renal and liver function tests were normal. The patient was intubated in view of low GCS score and poor respiratory effort and was kept on mechanical ventilator support. Gastric lavage was done, and antibiotics were started in view of features of aspiration pneumonitis on chest X-ray. A diagnosis of acquired methemoglobinemia due to indoxacarb was made, and he was treated with intravenous methylene blue 1 mg/kg stat over 30 minutes and vitamin C 1.5 gm IV OD for 2 days. The patient recovered from hypoxia in a day and was extubated and kept on oxygen support on the 2nd day. On the 5th day, after complete recovery, the patient was discharged in stable condition.
Fig. 1: Arterial blood showing chocolate brown color
Case 2
A 38-year-old male with no known comorbidities was found lying unconscious in the fields and was brought to the hospital with alleged ingestion of about 150 mL of the organic fertilizer Hiss approximately 5 hours before. The patient had undergone gastric lavage at a local hospital on the day of ingestion of the compound. General physical examination revealed central cyanosis and a pulse of 106 beats/minute, blood pressure 110/78 mm Hg, and SpO2 of 80% with 10 L of oxygen via facemask. Lungs were clear on auscultation. The patient was drowsy, with a GCS score of E1V1M5. He was intubated given poor sensorium and was put on mechanical ventilator support. Arterial blood gas analysis showed pH 7.2, PaO2 464, pCO2 57, and bicarbonate 25. In view of the saturation gap between pulse oximetry and the PaO2 levels in the arterial blood gas (ABG), a diagnosis of methemoglobinemia was considered. The patient was treated with intravenous methylene blue and other supportive measures. Hypoxemia persisted despite therapy, requiring additional doses of methylene blue, which were administered for 5 days. Additionally, the patient developed jaundice from the third day with features of hemolytic anemia on peripheral smear. Hemoglobin was 7.1 gm/dL, and total bilirubin was 4.2 mg/dL, with direct bilirubin 1.1 and indirect 3.1 mg/dL, while liver enzymes were normal. He was given 2 pints of packed cells, and other supportive care was continued. He was extubated on the 5th day and put on oxygen support with 10 L of oxygen. After 2 weeks of therapy, his condition improved, and he was shifted from the intensive care unit to the general ward and was maintained on room air. His liver function tests were normal after 2 weeks of therapy. He was discharged in stable condition after 3 weeks of admission.
DISCUSSION
The above two cases highlight that a wide range of poisonous substances taken for self-harm can have manifestations in the form of methemoglobinemia, which may be easily misdiagnosed in the absence of a high degree of suspicion. The list of toxins that cause methemoglobinemia is long. A list of some of them is enumerated (Table 1).3,4
| A list of some chemicals known to cause methemoglobinemia3,4 | ||
|---|---|---|
| Acetanilide | Hydroxylamine | Phenazopyridine |
| Alloxan | Indoxacarb | Phenacetin |
| Aniline (dyes, ink) | Lidocaine | Phenylhydrazine |
| Antipyrine | Menadione | Phenytoin |
| Arsine | Metoclopramide | Paraquat/diquat |
| Benzene derivatives | Methylene blue | Phenol |
| Benzocaine | Naphthalene | Prilocaine |
| Chlorates | Nitroprusside | Primaquine |
| Chlorobenzene | Nitrites | Smoke inhalation |
| Chloroquine | Nitroalkanes | Sulfonamide antibiotics |
| Dapsone | Nitro chlorobenzene | Trinitrotoluene |
| Dinitrophenol | Nitrofuran | |
| Dinitro toluene | Nitroglycerine | |
Also, not all causes of methemoglobinemia have the same prognosis. While indoxacarb ingestion had a better prognosis and an early recovery, the same was not seen with organic fertilizer poisoning. The hemolytic anemia, which was more profound in organic fertilizer ingestion, was not apparent in the first case. Indoxacarb is a pesticide belonging to the oxadiazine group. The active intermediates derived from aromatic metabolites of indoxacarb cause methemoglobinemia. In the case of organic fertilizers, the ingredients included plant extracts (12%), surfactant (5%), emulsifier (10%), and filler (73%). The exact ingredient causing methemoglobinemia is not known. However, the possible cause could be biological extracts, which are usually rich in nitrogenous products.5,6
CONCLUSION
A wide range of chemicals, when ingested, can cause methemoglobinemia, which is a life-threatening emergency. A high index of suspicion is needed to diagnose such cases early. Since most of the time patients are comatose, the history may not be forthcoming. Compounds ingested may not have labels indicating their toxicity, and some products may not list the ingredients that are likely to cause methemoglobinemia. Hence, clinical findings of central cyanosis and the gap between measured oxygen levels in blood gas analysis and pulse oximetry should be a cornerstone in making the diagnosis, enabling us to start the treatment without much delay. A more elaborate study on all compounds causing methemoglobinemia and the clinical course in those patients will help in better management of such cases.
ORCID
Praveen Kumar Javvaji https://orcid.org/0000-0002-1563-8862
Poojitha Adusumilli https://orcid.org/0009-0008-7516-9202
Praveena Prasanth https://orcid.org/0009-0000-2664-0389
Mamatha Sree Kannuru Paparaju https://orcid.org/0009-0006-8490-3339
Bonny R Beeda https://orcid.org/0009-0006-2990-2624
REFERENCES
1. Ludlow JT, Wilkerson RG, Nappe TM. Methemoglobinemia. StatPearls Publishing; 2024.
2. Iolascon A, Bianchi P, Andolfo I, et al. Recommendations for diagnosis and treatment of methemoglobinemia. Am J Hematol 2021;96:1666–1678. DOI: 10.1002/ajh.26340
3. Wright RO, Lewander WJ, Woolf AD. Methemoglobinemia: etiology, pharmacology, and clinical management. Ann Emerg Med 1999;34:646–656. DOI: 10.1016/S0196-0644(99)70167-8
4. Mohammed AO, Saeed MM, Ahmad AS, et al. Indoxacarb poisoning presenting as methemoglobinemia: a case report. Int J Crit Illn Inj Sci 2024;14:59–61. DOI: 10.4103/ijciis.ijciis_37_23
5. George T, Shaikh AI, Thomas L, et al. Severe methemoglobinemia due to insecticide poisoning. Indian J Crit Care Med 2014;18:113. DOI: 10.4103/0972-5229.126087
6. Malkarnekar SB, Anjanappa R, Naveen L, et al. Acute methemoglobinemia with hemolytic anemia following bio-organic plant nutrient compound exposure: two case reports. Indian J Crit Care Med 2014;18:115: DOI: 10.4103/0972-5229.126089
________________________
© The Author(s). 2025 Open Access. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted use, distribution, and non-commercial reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.