Methemoglobinaemia Following Insecticide Poisoning-A Case Series

Received: 07-Jan-2022, Manuscript No. ijmrhs-22-52804; Editor assigned: 22-Jan-2022, Pre QC No. ijmrhs-22-52804 (PQ); Reviewed: 04-Feb-2022, QC No. ijmrhs-22-52804 (Q); Revised: 18-Feb-2022, Manuscript No. ijmrhs-22-52804 (R); Published: 28-Feb-2022

Introduction

Methemoglobinemia is an impaired state of oxygen delivery to tissues, seen when ferrous iron of haem is oxidized to ferric iron. Ingestion of nitrobenzene (rarely Indoxacarb) containing pesticides either accidentally or with a suicidal intent leads to methemoglobinemia.

Exposure to nitrobenzene-containing compounds can occur via ingestion, inhalation, and absorption through the skin which can result in methemoglobinemia [1-5]. Methemoglobinemia is a condition where red blood cells contain methemoglobin at levels higher than 1%. It has a clinical spectrum ranging from mild, underdiagnosed cases to fatal cases [6].

Methemoglobinemia has remarkably normal arterial oxygen saturation with significant cyanosis which presents a diagnostic dilemma. The non-availability of co-oximetry, which is the most accurate tool to detect and measure dyshemoglobinemia, is a problem faced by most peripheral hospitals in India. In our study, we have tried to prognosticate the outcome of these patients based on the time from exposure, history and clinical presentation, pulse oximetry findings, laboratory investigations like Arterial blood gas analysis, and liver function tests, throughout their hospital stay.

Here we present a series of five cases of Methemoglobinemia who presented to us over 2 years (2013-2015). Written informed consent has been taken from the patient’s relatives by institutional protocol.

Case Presentation

Case 1

A 30 years old female patient with a history of nitrobenzene compound consumption 5.5 hours prior, came in an unconscious state with signs of central cyanosis. Vitals were unstable with a saturation of 83% on room air. She was intubated and a stomach wash was given. Arterial Blood Gas (ABG) (Table 1) was consistent with methemoglobinemia. Her laboratory reports (Table 2) showed neutrophil leucocytosis. Methylene blue 2 mg/kg and ascorbic acid (500 mg) TID were started and continued on day 2 since the saturation remaining 80% (70% FiO2). Ionotropes started on day 3. GCS dropped to 3/15 and she succumbed on day 4.

Case 2

A 22 years old male presented in an unconscious state and central cyanosis with a history of unknown agricultural compound consumption 4 hours prior. Vitals were unstable with a saturation of 85% (face mask 5 lt/min). He was intubated. ABG analysis (Table 1) was consistent with methemoglobinemia. Laboratory report (Table 2) showed neutrophilic leucocytosis and deranged LFT and RFT. Blood drawn for analysis was chocolate brown. Intravenous methylene blue 2 mg/kg and ascorbic acid 500 mg started TID. Though GCS and SO2 improved on day 2, he needed ionotropic support and GCS dropped by day 4, and he succumbed on the same day.

Case 3

A 30 yrs old male patient with a history of nitrobenzene compound consumption 4 hours prior brought with mechanical ventilation through a 6ET tube had peripheral and central cyanosis. Vitals were unstable, saturation was 89% (100 FiO2). ABG analysis (Table 1) was consistent with methemoglobinemia. Laboratory reports (Table 2) showed neutrophil leucocytosis and deranged LFT (day 4). Inj. Methylene blue 2 mg/kg and ascorbic acid 500 mg intravenous thrice daily started. Though saturation picked up to 89% (50% FiO2), he deteriorated further with a drop-in GCS and saturation of 82% (FiO2-90%) by day 4. He succumbed on day 5.

Case 4

A 28 years old male patient with a history of Bloom flower insecticide consumption 4.5 hours prior, came unconscious, with deranged vitals central and peripheral cyanosis, and a saturation of 80% (room air). He was intubated. ABG analysis (Table 1) was consistent with methemoglobinemia. Laboratory reports (Table 2) showed neutrophil leucocytosis. Methylene blue 2 mg/kg and ascorbic acid 500 mg thrice daily started. He was weaned off the ventilator with improvement in GCS and saturation (92% on 40% FiO2). He was discharged on day 6.

Case 5

A 27 years old male patient was brought with altered sensorium, central cyanosis, icterus, unstable vitals and a saturation of 84% (room air) with a history of Indoxacarb pesticide agent consumption 5 hrs prior. The blood drawn was chocolate-coloured. ABG (Table 1) and clinical signs were consistent with methemoglobinemia. Methylene blue 2 mg/kg and ascorbic acid 500 mg intravenous with high flow oxygen (face mask) started. He was discharged on day 6 since cyanosis resolved and the saturation improved (95% room air).

Discussion

Methemoglobinaemia is caused by exposure to an oxidizing chemical or drug, leading to the removal of an electron from ferrous haemoglobin (Fe2+) to create ferric haemoglobin (Fe3+) at a rate that surpasses the endogenous reducing mechanisms. This methemoglobin is unable to transport oxygen to the tissues [1]. This results in a left shift of the oxygen-haemoglobin dissociation curve and subsequent tissue hypoxia [5]. The mechanisms that maintain the methemoglobin levels less than 1% are the endogenous HMP shunt, and the diaphorase I and II enzyme pathways [1]. Excessive oxidative stresses produce MeHb at a very high rate, leading to a rise above 1% [1,2]. The estimated lethal dose ranges from 2 g to 6 g in adults [3,6].

Nitrobenzene, an oxidizing nitrite compound leads to the rapid development of methemoglobinemia after acute ingestion [2,7-11]. Methemoglobinemia occurs due to the intermediates (nitroso benzene and phenylhydroxylamine) formed during the metabolism of nitrobenzene to aniline [7]. All cases presented to us were of ingestion of nitrobenzene products except case 5 of Indoxacarb poisoning. Our patients had features of pallor, cyanosis, and decreased consciousness. Four patients required intubation and ventilator support. The time of presentation ranged from 4 hours-5.5 hours after consumption and had no bearing on the outcome. In case 4, the nature of the compound was unknown, symptoms at presentation, graded desaturation with normal SO2 led us to the diagnosis of methemoglobinemia and treatment accordingly. Indoxacarb, an oxadiazine pesticide is used for the control of cotton ball worm and native budworm in cotton and soya beans. The indoxacarb metabolizes to aniline and aromatic compounds producing methemoglobin [12].

The symptomatology depends on the percentage of methemoglobin in the blood (Table 3) [5]. Diagnosis is made by eliciting a history of chemical ingestion, the characteristic smell of bitter almonds, persisting cyanosis on oxygen therapy, low arterial oxygen saturation, with normal ABG (calculated) oxygen saturation. This is because the arterial blood gas analysis measures any haemoglobin as normal and results in overestimation compared to calculated saturation. This is a “saturation gap” [11]. A gap of more than 5% indicates the presence of carboxyhemoglobin, sulfhemoglobin, or methemoglobin [11]. Dark brown blood that fails to turn bright red on shaking, suggests methemoglobinemia [1-5]. Once suspected, measurement of methemoglobin levels must be done using co-oximetry or spectrophotometry [1,5]. However, in our setup, laboratory measurement of methemoglobin levels was not possible, hence, clinical judgment was relied upon.

Neutrophilic leukocytosis was a finding in all our patients as has been noted from previously reported cases. [10]. Liver dysfunction was noted in three cases. Severe derangement with high bilirubin levels and deranged enzyme levels culminated in the death of two of the patients suggesting patients probably setting into MODS. Treatment includes supportive measures like gastric lavage, high flow oxygen, correction of electrolyte and acid-base abnormalities [1,5,8]. Inject methylene blue, a thiazine dye that accelerates the NADPH-dependent methemoglobin reductase system diaphorase II by five times reducing its half-life from 15 hours-20 hours to 40 minutes-90 minutes [11]. It is given at a dose of (1-2) mg/kg as a 1% solution over 5 minutes [1,5]. It is indicated if MeHb levels are >30%, or the patient has comorbidities that worsen hypoxia [5,9]. All our patients had symptoms of severe methemoglobinemia and were started on methylene blue and ascorbic acid. Ascorbic acid acts as an antioxidant and increases levels of NADH and NADPH [10]. All patients received blood transfusions based on clinical diagnosis. Exchange transfusion can be used as the second line of treatment [1,3,9].

Conclusion

A series of rare but fatal cases of methemoglobinemia following self-poisoning with nitrobenzene or indoxacarb (Case 5) containing pesticides is reported. Due to the non-availability of co-oximetry in our institution, we focused on the prognostication of the patient's outcome based on the time from consumption, history and clinical presentation, pulse oximetry, series of ABG analysis, and lab investigations. Though time from consumption did not have any bearing on the outcome, deranged LFT and clinical findings could be used to guide management and prognostication. Since the number of cases studied is small, further research needs to be done to prove the findings of our case series.

Declarations

Conflict of Interest

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Declarations

Conflict of Interest

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Refrence

1. Saxena, Hema, and Anand Prakash Saxena. "Acute methaemoglobinaemia due to ingestion of nitrobenzene (paint solvent)." Indian Journal of Anaesthesia, Vol. 54, No. 2, 2010, pp. 160-62.
   Google Scholar          Crossref
2. Agrawal, Avinash, et al. "Acute cardiogenic pulmonary oedema with multiorgan dysfunction-Still to learn more about nitrobenzene poisoning." Case Reports, Vol. 2011, 2011.
   Google Scholar          Crossref
3. George, Tarun, et al. "Severe methemoglobinemia due to insecticide poisoning." Indian Journal of Critical Care Medicine: Peer-reviewed, Official Publication of Indian Society of Critical Care Medicine, Vol. 18, No. 2, 2014, pp. 113-14.
   Google Scholar          Crossref
4. Lee, Chang Hwan, et al. "Two cases of methemoglobinemia induced by the exposure to nitrobenzene and aniline." Annals of Occupational and Environmental Medicine, Vol. 25, No. 1, 2013, pp. 1-7.
   Google Scholar          Crossref
5. do Nascimento, Tatiana Souza et al. "Methemoglobinemia: From diagnosis to treatment." Brazilian Journal of Anesthesiology, Vol. 58, No. 6, 2008, pp. 651-64.
   Google Scholar          Crossref
6. Harris, John C., et al. "Methemoglobinemia resulting from absorption of nitrates." JAMA, Vol. 242, No. 26, 1979, pp. 2869-71.
   Google Scholar          Crossref
7. National Research Council, and Safe Drinking Water Committee. "Toxicity of selected organic contaminants in drinking water." Drinking Water and Health: Volume 4, National Academies Press (US), 1982.
   Google Scholar          Crossref
8. Perera, Mark, et al. "Acute methaemoglobinaemia after massive nitrobenzene ingestion." Case Reports, Vol. 2009, 2009, p. bcr0720080515.
   Google Scholar          Crossref
9. Palange, PB, et al. "A fatal case of nitrobenzene poisoning with severe methemoglobinemia and ARDS due to drowning." International Journal of Biomedical Research, Vol. 5, No. 12, 2014, pp. 783-84.
   Google Scholar          Crossref
10. Singh, Ranju, Stalin Vinayagam, and Homay Vajifdar. "Methemoglobinemia as a result of accidental lacquer thinner poisoning." Indian Journal of Critical Care Medicine: Peer-reviewed, Official Publication of Indian Society of Critical Care Medicine, Vol. 16, No. 1, 2012, pp. 44-47.
    Google Scholar          Crossref
11. Messmer, Anna Sarah, Christian Hans Nickel, and Dirk Bareiss. "P-chloroaniline poisoning causing methemoglobinemia: A case report and review of the literature." Case Reports in Emergency Medicine, Vol. 2015, 2015.
    Google Scholar          Crossref
12. Solecki, Roland. "Toxicology of miscellaneous insecticides." Pesticide Toxicology and International Regulation, 2004, p. 159.
    Google Scholar          Crossref