Acalypha indica induced acute oxidative haemolysis and methaemoglobinaemia: two case reports.

BACKGROUND: Herbal products and traditional remedies are commonly used by individuals worldwide for the management of common ailments, even though most are not without risks. Acalypha indica is a popular medicinal plant consumed in some Asian countries. CASE PRESENTATION: This case report presents a 40-year-old previously unevaluated Sri Lankan female and her 8-year-old son who presented with severe glucose-6-phosphate dehydrogenase (G6PD) deficiency related acute intravascular oxidative haemolysis and methaemoglobinaemia precipitated by Acalypha indica consumption, successfully managed with supportive care and blood transfusion. CONCLUSIONS: This case highlights the potential hemolytic and methaemoglobinaemic effects of ingesting oxidant herbal products and the importance of considering such exposures in patients presenting with hemolysis and multiorgan involvement, particularly in communities where herbal product intake is popular. Healthcare providers should be aware of the risks associated with traditional remedies and maintain a high index of suspicion to ensure prompt recognition and appropriate management.

Indoxacarb poisoning causing methemoglobinemia treated with parenteral vitamin C: a case report.

INTRODUCTION: This case study reports on a suicide attempt involving indoxacarb and vitamin C. Indoxacarb is a neurotoxic insecticide used in agriculture and as a flea controller in pets. Cotton, vegetables, and fruits are treated with indoxacarb, an insecticide that can be applied both indoors and outdoors. It causes skin allergies, methemoglobinemia, and hemolytic anemia. It is also attributed to allergic reactions through ingestion, inhalation, physical contact, and translaminar action. This case report highlights use of vitamin C in methemoglobinemia caused by indoxacarb poisoning. Indoxacarb poisoning has the potential to be extremely serious and even lethal. In this instance, the patient initially had no symptoms after ingesting a substance containing indoxacarb in an attempt at suicide. However, further tests revealed methemoglobinemia and low oxygen levels. CASE PRESENTATION: A 28-year-old south-east Asian female patient ingested an insecticide containing 5.25% novaluron, 4.5% indoxacarb, and 25% thiamethoxam, and reported that she noticed muddy brown urine but presented with no active signs or symptoms of poisoning. Upon examination, the patient was fully conscious, alert, and hemodynamically stable, but had an oxygen saturation of 84%. Gastric lavage was performed, and blood investigations revealed a muddy-brown-colored blood sample and methemoglobin levels of 12%. The patient was treated with high-dose vitamin C and showed significant improvement, with a drop in methemoglobin levels to 1.2% and an increase in oxygen saturation to 97%. DISCUSSION: Indoxacarb poisoning can cause severe methemoglobinemia. Vitamin C may be a useful treatment option for methemoglobinemia caused by indoxacarb, particularly in cases in which traditional treatment with methylene blue is contraindicated or not tolerated. Hence high doses of ascorbic acid, that is, vitamin C, were administered to the patient, which lowered their methemoglobin levels and improved oxygen levels without much safety concerns. CONCLUSION: This example emphasizes the significance of early indoxacarb poisoning detection and treatment as well as the possible advantages of utilizing ascorbic acid in the management of methemoglobinemia, and highlights the use of vitamin C in the treatment of methemoglobinemia caused by indoxacarb poisoning. Therefore, it is important for healthcare professionals to be aware of the potential for indoxacarb to cause methemoglobinemia and to consider vitamin C as a treatment option.

Detection of methaemoglobinaemia in a COVID-19 patient on dapsone.

Methaemoglobinaemia occurs when iron in haemoglobin is oxidised into a form that cannot transport oxygen. At low levels, it is asymptomatic, though at rising levels symptoms arise from impaired oxygenation, and it can ultimately be fatal. While uncommon, it is important to consider in hypoxaemic COVID-19 patients, especially if they are not clinically improving on standard treatments and workup for other causes does not explain the ongoing hypoxaemia. It is often diagnosed through a mismatch in peripheral and arterial oxygen, with the former typically less than the latter. We present the case of a COVID-19 patient who was found to have methaemoglobinaemia due to dapsone use for Pneumocystic jirovecii pneumonia (PJP) prophylaxis while on chemotherapy. Dapsone was stopped and supplemental high-flow nasal cannula was provided, and methaemoglobin levels improved over a 5-day period. She was discharged to follow-up with her haematologist in the clinic.

Methemoglobinemia in Hemodialysis Patients due to Acute Chlorine Intoxication: A Case Series Calling Attention on an Old Problem.

INTRODUCTION: Hemodialysis uses municipal water that must be strictly purified and sterilized to be used for that procedure. Large amounts of decontaminants are often used, such as chlorine, and if these compounds are not subsequently removed they can be transferred to the blood of patients causing complications including methemoglobinemia. METHODS: In this case series study, dialysis patients in one unit were evaluated. We reviewed clinical characteristics and laboratory findings obtained on the day when the water supply was disinfected with chlorine, with the aim to quantify methemoglobin concentrations. Our objective was to characterize the clinical presentation and management of patients who presented with methemoglobinemia on a specific index day. We also reviewed reported cases in the literature regarding this underreported complication. RESULTS: Eight patients who presented with chlorine intoxication were evaluated. The methemoglobin concentrations were between 1.3% and 7.9% (reference value 0-1%). We believe this to be caused by water containing 0.78 mg/L of total chlorine. Seven patients presented with cyanosis, 4 with dizziness, 6 with dark brown blood, 4 with dyspnea, and 4 with headache and hemolytic anemia. Subjects were treated with supplemental oxygen, methylene blue, intravenous vitamin C, blood transfusions, and increased doses of erythropoietin. No patient died, and all continued with their usual hemodialysis sessions. CONCLUSION: Acute chlorine intoxication transferred by the water used during hemodialysis sessions can present with methemoglobinemia accompanied by cyanosis, oxygen desaturation, and hemolytic anemia. Chlorine levels should be carefully monitored in the water used for hemodialysis treatment.

Asymptomatic benzocaine spray-induced methaemoglobinaemia in preoperative sedation for oesophagogastroduodenoscopy.

Methaemoglobinaemia is defined as elevated methaemoglobin in the blood which is characterised by conversion of some of the reduced ferrous iron elements [Fe2+] to the oxidised ferric [Fe3+] form which does not have capacity to bind and transport oxygen resulting in functional anaemia. Causes can be genetic mutations or acquired by medications such as dapsone, nitrates or benzocaine. Benzocaine is currently being used as a topical anaesthetic agent before certain procedures. We report a case of benzocaine spray-induced methaemoglobinaemia in a patient who underwent oesophagogastroduodenoscopy for evaluation of upper gastrointestinal bleeding.

Methaemoglobinaemia in pregnancy with chronic kidney disease an uncommon case: A case report.

The development of methaemoglobinaemia due to prilocaine, which is used for local anaesthesia, is a rare, life-threatening, but well-known side effect. The development of this side-effect in a pregnant patient with chronic kidney disease can lead to foetal distress. The case presented here is of a 21-year old pregnant female with chronic kidney disease who required haemodialysis in the 22nd week of pregnancy due to the progression to end-stage kidney disease. During haemodialysis, a right jugular tunneled double-lumen catheter was inserted using prilocaine as the local anaesthetic. Prilocaine-induced methaemoglobinaemia was diagnosed. In the 24-hour follow-up, the methaemoglobin level decreased to normal with oxygen supply of 10-15 L/min, 2 units of erythrocyte suspension and accompanying haemodialysis.

Acalypha indica -induced transient glucose-6-phosphate dehydrogenase deficiency with acute haemolysis.

Acalypha indica is a tropical herb found in Asia. The entire plant, especially the leaves, is used in herbal medicine for several therapeutic purposes. Acute intravascular haemolysis and methaemoglobinaemia have been reported in patients who consume this herb. We present a case of a previously healthy middle-aged man who ingested boiled leaves of A. indica The patient developed clinical symptoms and signs of intravascular haemolysis 7 days after ingestion. Peripheral blood smear showed typical findings of glucose-6-phosphate dehydrogenase (G6PD) deficiency with acute haemolysis. The G6PD activity was low during active haemolysis. The G6PD level, however, returned to normal after 4 months of follow-up. The patient was further tested for common G6PD gene mutations in Southeast Asia and was negative. Ingestion of A. indica may induce transient G6PD deficiency, which in this patient led to acute haemolysis and methaemoglobinaemia.

Acute hemolysis and methemoglobinemia secondary to fava beans ingestion in a patient with G6PD deficiency: A case report of a rare co-occurrence.

RATIONALE: Favism is a well-known cause of acute hemolytic anemia. Rarely, methemoglobinemia can also happen because of fava bean ingestion in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Few cases with this co-occurrence have been reported in the literature. PATIENT CONCERNS: We report a case of a 47-year-old patient who presented with jaundice that started 2 days after eating fava beans. DIAGNOSES: Laboratory investigations revealed anemia with evidence of hemolysis (high reticulocytes count, high indirect bilirubin, bite cells in peripheral smear). Blood gases showed high methemoglobin level. Reduced level of G6PD enzyme confirmed the diagnosis of G6PD deficiency. INTERVENTION: The patient was kept on supplemental oxygen. He was counselled to avoid food and drugs that can cause acute hemolysis. OUTCOMES: Oxygen saturation improved gradually. The patient was discharged without any complications after 2 days. LESSONS: Patients with G6PD deficiency can develop both acute hemolytic anemia and methemoglobinemia secondary to fava beans ingestion. These patients should not receive methylene blue to avoid worsening hemolysis.

Effect of organo-selenium anticancer drugs on nitrite induced methemoglobinemia: A spectroscopic study.

Selenium containing drugs like selenomethionine, selenocystine, selenourea and methylseleninic acid are reported to exhibit potential anticancer effect. However, these anticancer drugs may exert adverse effects when used over a prolonged period. Little is known about the interaction of these selenium containing drugs with the vital erythroid protein hemoglobin. In this work a comparative study of the interaction of organo-selenium drugs with hemoglobin and heme moiety has been performed using different spectroscopic techniques to find out their role on drug induced methemoglobinemia. We found that though these selenium containing drugs have similar binding affinity towards hemoglobin, they have differential interactions with the heme group. Isothermal calorimetric titration study showed that selenourea has the lowest binding affinity (Kd 19.28 µM) towards HbA as compared to other drugs, selenomethionine, selenocystine and methylseleninic acid (Kd 7.69 µM, 4.88 µM and 10.5 µM at 37 °C respectively). This result is also supported by the molecular docking study. Methylseleninic acid was found to have detrimental effects on nitrite induced methemoglobinemia, a hematological disorder caused due to excessive conversion of Fe2+ to Fe3+ in hemoglobin. Hence the results of the study would help to develop a better insight on the mechanism of action and anticipate the toxicity of these drugs which require further optimization before their actual use in the treatment of cancer.

Siblings with pediatric sodium chlorite toxicity causing methemoglobinemia, renal failure and hemolytic anemia.

INTRODUCTION: Over the past decade, Miracle Mineral Solution (sodium chlorite) has been promoted as a cure-all for many conditions. CASE REPORT: A 9-year-old boy presented with his brother after they accidentally ingested a small amount of undiluted 22.4% sodium chlorite. Symptoms included nausea, vomiting, diarrhea, and dyspnea. Oxygen saturation remained 71% despite supplemental oxygen (15L/min). The patient was noted to have dark chocolate-appearing blood, minimal urine output, diffuse pallor and cyanosis. He developed methemoglobinemia, renal failure requiring renal replacement therapy and hemolysis requiring blood transfusion. DISCUSSION: These are the 7th and 8th reported cases of sodium chlorite toxicity by ingestion and the second and third in children. Takeaway for Physicians: Miracle Mineral Solution is a commonly purchased potentially lethal compound that can cause methemoglobinemia with respiratory failure, hemolytic anemia requiring transfusion and renal failure requiring dialysis.

High dose vitamin C induced methemoglobinemia and hemolytic anemia in glucose-6-phosphate dehydrogenase deficiency.

Investigational use of intravenous vitamin C has been on the rise, but its side effects may be underreported. A 75-year-old woman presented with acute onset of jaundice, dark urine and shortness of breath after receiving 30 g of vitamin C infusion as an unconventional therapy for her hemifacial spasm. Diagnosis of methemoglobinemia and hemolytic anemia was made clinically and confirmed on laboratory tests. She recovered with supportive treatment and packed cell transfusion. Her previously unrecognised underlying condition of glucose-6-phosphate dehydrogenase (G6PD) deficiency was confirmed months after the initial presentation. This is the first reported case of methemoglobinemia and hemolytic anemia induced by high dose vitamin C in a female patient with G6PD deficiency. The dosage of vitamin C administered was also relatively low compared with previous adult reports. When administered at physiological dose, vitamin C can be used as an alternative to methylene blue in treatment of methemoglobinemia in patients with G6PD deficiency. However at supraphysiological dose vitamin C can paradoxically lead to hemolytic anemia in the same group of patients. Physicians should be alert of these potential complications of high dose vitamin C.

The effects of dietary nitrate on plasma glucose and insulin sensitivity in sheep.

Nitrate (NO3 ¯ ) is an effective non-protein nitrogen source for gut microbes and reduces enteric methane (CH4 ) production in ruminants. Nitrate is reduced to ammonia by rumen bacteria with nitrite (NO2 ¯ ) produced as an intermediate. The absorption of NO2 ¯ can cause methaemoglobinaemia in ruminants. Metabolism of NO3 ¯ and NO2 ¯ in blood and animal tissues forms nitric oxide (NO) which has profound physiological effects in ruminants and has been shown to increase glucose uptake and insulin secretion in rodents and humans. We hypothesized that absorption of small quantities of NO2 ¯ resulting from a low-risk dose of dietary NO3 ¯ will increase insulin sensitivity (SI ) and glucose uptake in sheep. We evaluated the effect of feeding sheep with a diet supplemented with 18 g NO3 ¯ /kg DM or urea (Ur) isonitrogenously to NO3 ¯ , on insulin and glucose dynamics. A glucose tolerance test using an intravenous bolus of 1 ml/kg LW of 24% (w/v) glucose was conducted in twenty sheep, with 10 sheep receiving 1.8% supplementary NO3 ¯ and 10 receiving supplementary urea isonitrogenously to NO3 ¯ . The MINMOD model used plasma glucose and insulin concentrations to estimate basal plasma insulin (Ib ) and basal glucose concentration (Gb ), insulin sensitivity (SI ), glucose effectiveness (SG ), acute insulin response (AIRg) and disposition index (DI). Nitrate supplementation had no effect on Ib (p > .05). The decrease in blood glucose occurred at the same rate in both dietary treatments (SG ; p = .60), and there was no effect of NO3 ¯ on either Gb , SI , AIRg or DI. This experiment found that the insulin dynamics assessed using the MINMOD model were not affected by NO3 ¯ administered to fasted sheep at a low dose of 1.8% NO3 ¯ in the diet.

Methemoglobinemia in an Infant After Sclerotherapy With High-Dose Doxycycline.

Methemoglobinemia occurs when the heme moiety of hemoglobin (Hb) is oxidized from the ferrous to ferric state, leading to impairments in oxygen transport and delivery. Methemoglobinemia is rare in pediatric patients but has been described in the setting of congenital abnormalities in the Hb structure, inherited enzyme deficiencies, oxidative Hb injury in response to illness, and oxidative Hb injury due to toxicants. We present a 1-week-old infant born with a cervical lymphangioma who developed persistent desaturations that were unresponsive to oxygen after sclerotherapy with doxycycline. Arterial blood gas revealed a high Pao2 despite low saturations being found on pulse oximetry and a methemoglobin level that was found to be elevated. Further sclerotherapy was discontinued, the saturations eventually normalized, and the methemoglobin level decreased. This is a novel report of sclerotherapy with doxycycline associated with the development of methemoglobinemia.

[1,4-diaminobenzene and diphenylamine-induced severe methemoglobinaemia treated by hyperbaric oxygen therapy - Case report]. / Zastosowanie tlenoterapii hiperbarycznej w ciezkiej methemoglobinemii wywolanej zatruciem 1,4-diaminobenzenem i difenyloamina ­ opis przypadku.

Methemoglobin is an oxidized form of hemoglobin that is not capable of carrying oxygen. Exposure to exogenous oxidizing agents can cause severe methemoglobinemia and subsequent hypoxia. This article presents the rare case of a 23-year old patient with methemoglobinemia of 54.2% of total hemoglobin, induced by workplace exposure to 1,4-diaminobenzene and diphenylamine. Following the hyperbaric oxygen therapy the patient was discharged in good general condition and referred to a district hospital for observation. Med Pr 2018;69(3):345-350.

Local Anesthetic-Induced Methemoglobinemia During Pregnancy: A Case Report and Evaluation of Treatment Options.

BACKGROUND: Methemoglobinemia is a well-recognized adverse drug reaction related to the use of certain local anesthetic agents. The mainstay of treatment for methemoglobinemia is i.v. methylene blue, along with provision of supplemental oxygen; however, methylene blue is listed as a category X teratogen. This poses an issue should methemoglobinemia develop during pregnancy. CASE REPORT: A 35-year-old, 20-week and 5-day gravid female was transferred from an outpatient oral surgeon's office for hypoxia. She was undergoing extraction of 28 teeth and was administered an unknown, but "large" quantity of prilocaine during the procedure. Given this exposure, the concern was for methemoglobinemia. This was confirmed with co-oximetry, which showed 34.7% methemoglobin. The initial treatment plan was methylene blue; however, this drug is a category X teratogen. Thus, an interdisciplinary team deliberated and decided on treatment with high-dose ascorbic acid and transfusion of a single unit of packed red blood cells. The patient was managed with noninvasive ventilation strategies and a total of 8 g ascorbic acid. She was discharged on hospital day 3 with no obstetric issues noted. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Intravenous ascorbic acid appears to be a potential alternative to methylene blue in this patient population. The data surrounding teratogenicity of methylene blue are mostly related to intra-amniotic or intra-uterine administration. In life-threatening cases of methemoglobinemia during pregnancy, the benefits of i.v. methylene blue may outweigh the risks.

What are pharmacists recommending for infant teething treatment?

OBJECTIVES: In 2011, the Food and Drug Administration issued a warning to avoid the use of any benzocaine-containing products for infant teething treatment owing to a risk of methemoglobinemia. Several benzocaine-containing products targeted for infant teething are currently available over the counter. Pharmacists are commonly asked for medical advice in the community, and there is no current literature evaluating what pharmacists are recommending for infant teething. The objectives of this study were to evaluate what pharmacists are currently recommending for infant teething treatment and assess what percentage would inappropriately recommend a benzocaine-containing product. METHODS: From March to June 2016, a 16-item in-person paper-and-pen questionnaire was administered to 200 pharmacists in the San Francisco Bay area at 115 outpatient over-the-counter pharmacies. Questions included demographic information, work and educational background, infant teething recommendations, and preferred educational resources. RESULTS: The overall response rate was 94.3%. One-half (50.5%) of the pharmacists' approaches to infant teething treatment was to recommend a nondrug option first and then, if needed, an over-the-counter medication. A majority (63.0%) of the pharmacists surveyed would inappropriately select a benzocaine-containing product. CONCLUSION: Despite warnings, the majority of pharmacists would still inappropriately recommend a benzocaine-containing product for treatment of infant teething. Further education is warranted to ensure that all pharmacists, health care providers, and consumers are aware of the potential harm of benzocaine use in infants.

Methemoglobinemia in a Case of Paint Thinner Intoxication, Treated Successfully with Vitamin C.

BACKGROUND: Methemoglobin (MetHb) is an oxidized form of hemoglobin. It is a poor transporter of oxygen and is unable to deliver oxygen to the tissue. Globally, drug & toxin induced methemoglobinemia is more common as compared with the congenital form. Methemoglobinemia caused by paint thinner intoxication is rare. Methylene blue is well established as the first-line therapy for severe methemoglobinemia. CASE REPORT: A 25-year old man was brought to the Emergency Department after accidental consumption of paint thinner. On clinical examination, he had cyanosis and there were discrepancies in his pulse oximetry and arterial blood gas (ABG) analysis results. With this clue and supporting laboratory investigations, the diagnosis of toxin-induced methemoglobinemia was made. Due to the unavailability of methylene blue, alternative treatment with high-dose vitamin C was attempted, to which the patient responded. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: The role of vitamin C in the treatment of methemoglobinemia has not been well established, with only a few published case reports. This patient had severe methemoglobinemia, with MetHb of 46.4%, which responded dramatically to vitamin C therapy, with no side effects. This case shows that high-dose vitamin C is safe and has the potential to be an effective alternative for the treatment of severe methemoglobinemia. In the presence of cyanosis, mismatch of pulse-oximetry and ABG-analysis are the key for the physician to suspect methemoglobinemia.

Transient Methemoglobinemia in three Neonates due to Maternal Pudendal Anesthesia.

Methemoglobin (MetHb) is a form of hemoglobin which contains iron in ferric state. The delivery of oxygen to tissues is impaired and cellular hypoxia develops with an increase in MetHb levels. Methemoglobinemia is a rare but potentially lethal complication of local anesthetics. In this clinical brief, three cases of transient neonatal methemoglobinemia, caused by maternal pudendal anesthesia with prilocaine, are reported.

Metahemoglobinemia relacionada con ingesta de puré de acelgas / Methemoglobinemia due to ingestion of chard puree

La metahemoglobinemia es un síndrome clínico dado por la presencia de una forma aberrante de hemoglobina, ocasionada por diversos agentes oxidantes. Se describe un caso clínico de metahemoglobinemia severa asociada a la ingesta de puré de acelgas con alto contenido en nitratos y nitritos. Paciente de un año, con antecedentes de comunicación interauricular (CIA), que presentó un cambio en coloración de la piel 7 h antes, en forma progresiva, acompañado de vómitos. Ingresó al Departamento de Emergencia con cianosis generalizada que no mejoró con oxigenoterapia, taquicardia y tendencia a hipotensión arterial. En cuidados intensivos se realizó ecocardiograma que evidenció CIA sin repercusión hemodinámica. Metahemoglobinemia 37%. Se realizó dosis de azul de metileno al 1% por vía intravenosa, con franca mejoría clínica a la hora de la administración del antídoto y descenso de niveles de metahemoglobina. Alta médica a las 36 horas del ingreso. Existía una relación cronológica entre la exposición a nitratos por ingesta de un puré de acelgas y la aparición del cuadro. Los niveles de nitratos hallados en dicho alimento fueron muy elevados considerando estándares internacionales, lo que sumado a una inadecuada conservación del alimento cocido los días previos, permitió confirmar el planteo etiológico realizado. Resulta importante sospechar esta entidad patológica poco frecuente frente a cianosis que no mejora con oxígeno, y prevenir cuadros similares al descrito mediante una adecuada manipulación y conservación de las verduras con alto contenido en nitratos.

Methemoglobinemia is a clinical syndrome due to the presence of an aberrant form of hemoglobin, caused by various oxidizing agents. The study reports a case of severe methemoglobinemia associated with the ingestion of chard puree with high levels of nitrates and nitrites. A 1-year-old patient with a history of atrial septal defect (ASD), who progressively showed change of skin color 7 hours earlier, accompanied by vomiting. She was admitted to the Emergency Department with generalized cyanosis not improving with oxygen therapy, tachycardia and tendency to hypotension. In the intensive care unit, an echocardiogram showed ASD without hemodynamic complications. Methemoglobinemia 37%. A 1% methylene blue dose was administered intravenously, with clinical improvement one hour after antidote administration and decrease in methemoglobin levels. Medical discharge at 36 hours of admission. There was a chronological relationship between nitrates exposure by ingestion of chard puree and the clinical onset of methemoglobinemia. The toxic cause was confirmed after high nitrates levels were found in this vegetable considering international standards, and an inadequate preservation of the cooked chard on previous days. It is important to suspect this rare pathological entity when cyanosis fails to improve with oxygen, and to prevent poisonings similar to those described by an adequate manipulation and preservation of vegetables with high nitrate levels.