ascorbic-acid and Methemoglobinemia

There is an increased number of reports being published on rasburicase-induced methemoglobinemia recently. We aimed to identify and critically evaluate all the descriptive studies that described the rasburicase-induced methemoglobinemia, its treatment approach, and their outcomes.. PubMed, Scopus and grey literature databases were searched from inception to January 2022 using search terms "rasburicase" and "methemoglobinemia" without any language and date restriction. A bibliographic search was also done to find additional studies. Only descriptive studies on Rasburicase-induced methemoglobinemia were included for our review. Two contributors worked independently on study selection, data abstraction, and quality assessment, and any disagreements were resolved by consensus or discussion with a third reviewer.. A total of 24 reports including 27 patients (23 male, 3 female patients, and 1 study did not specify the gender of the patient) aged from 5 to 75 years were included in the review. Immediate withdrawal of the drug and administering methylene blue, ascorbic acid, blood transfusion, and supportive oxygen therapy are the cornerstone in the management of rasburicase-induced methemoglobinemia.. Rasburicase administration should be followed by careful monitoring of patients for any severe complication and treat it as early as possible appropriately. In a patient who presents with rasburicase-induced haemolysis or methemoglobinemia, it is often important to expect a diagnosis of G6PD deficiency unless otherwise confirmed and to avoid administering methylene blue, even though the patient is from a low-risk ethnicity for G6PDD.

Topics: Ascorbic Acid; Female; Glucosephosphate Dehydrogenase Deficiency; Hemolysis; Humans; Male; Methemoglobinemia; Methylene Blue

The objectives of this review are to describe the acquired and hereditary causes of methemoglobinemia, to recommend the most sensitive diagnostic tests, and to enable critical care clinicians to rapidly detect and treat methemoglobinemia. To meet these objectives, Internet search engines were queried with the keywords to select articles for review that included case reports, case series, observational, longitudinal, and surveillance studies. The most common causes of methemoglobinemia include oxidizing reactions to cocaine-derived anesthetics, such as benzocaine and lidocaine, to antibiotics, such as dapsone and other sulfonamides, and to gases, such as nitric oxide. Additionally, CO-oximetry is superior to standard pulse oximetry in detecting methemoglobinemia. Finally, effective treatments for methemoglobinemia include intravenous administration of methylene blue, ascorbic acid, and riboflavin. In this manuscript we will discuss methemoglobinemia, how it occurs, and how to treat it.

Topics: Administration, Intravenous; Adult; Aged; Aged, 80 and over; Anesthetics, Local; Ascorbic Acid; Critical Care; Early Diagnosis; Female; Humans; Male; Methemoglobinemia; Methylene Blue; Middle Aged

Topics: Ascorbic Acid; Cyanosis; Daucus carota; Diagnosis, Differential; Dyspnea; Emergency Treatment; Humans; Infant; Male; Methemoglobinemia; Nitrites; Severity of Illness Index; Shock, Septic; Tunisia

Topics: Ascorbic Acid; Cytochrome-B(5) Reductase; Erythrocytes; Glutathione; Hemoglobins; Humans; Intellectual Disability; Methemoglobin; Methemoglobinemia; Metmyoglobin; NAD; NADP; Oxidation-Reduction

Topics: Ascorbic Acid; Chlorates; Cytochrome-B(5) Reductase; Humans; Methemoglobin; Methemoglobinemia; Methylene Blue; Nitrites; ortho-Aminobenzoates; Oxidants, Photochemical; Pharmacogenetics; Phenacetin; Quinones; Stimulation, Chemical

This study investigated in vivo and in vitro kinetics of o-toluidine-induced methemoglobinemia and the influence of ascorbic acid on resulting methemoglobin concentrations. o-Toluidine is a metabolite of prilocaline and ascorbic acid is recommended for treatment of methemoglobinemia as an alternative to methylene blue.. We measured the formation of methemoglobin in vitro in a whole blood culture system of 8 healthy individuals 30, 60, and 360 min after the addition of different concentrations of o-toluidine (0.5, 5, 50 micrograms/ml) with and without addition of ascorbic acid (0.5 and 5 mg/ml). In a prospective randomized clinical study, a total of 72 patients of ASA risk I-III were investigated. The 3 groups of 24 patients received either an axillary, an infraclavicular vertical brachial plexus, or a combined femoral and ischiadic blockade. In each plexus anesthesia group, 12 patients were given 2,000 mg ascorbic acid intravenously before applying the local anesthetics. For surgery of the upper limb the patients received 40 ml 1% prilocaine and 10 ml 0.5% bupivacaine, for surgery of the lower limb they received 60 ml 1% prilocaine and 0.25 mg adrenaline. Blood samples for measurement of methemoglobin concentrations were taken before and 30, 60, 120, 180 and 360 min after the injection of the regional anesthetic. A p < 0.05 was considered to be significant.. There was a dose-dependent increase of methemoglobin due to addition of o-toluidine after 360 min in vitro. The application of 0.5 mg/ml ascorbic acid to the whole blood samples with 0.5 and 5 micrograms/ml o-toluidine resulted in a further increase of methemoglobin formation whereas there was no difference in the samples with 50 micrograms/ml. The higher concentration of 5 mg/ml ascorbic acid attenuated the methemoglobin formation only with 50 micrograms/ml o-toluidine. No effect was observed with lower concentrations of o-toluidine. In the in vivo study plexus anesthesia with prilocaine resulted in an increase of the methemoglobin concentration with a maximum after 120-180 min. The highest measured methemoglobin concentration found was 11.3%. The methemoglobin concentration already showed a decrease 360 min after the application of the regional anesthetic 2,000 mg ascorbic acid given intravenously before plexus anesthesia was not able to influence the resulting methemoglobin concentrations.. In vitro high concentrations of ascorbic acid are able to reduce the resulting methemoglobin concentration 360 min after addition of 50 micrograms/ml o-toluidine. The application of 2,000 mg ascorbic acid i.v. before plexus anesthesia with prilocaine does not reduce the concentration of methemoglobin.

Topics: Adult; Anesthetics, Local; Antioxidants; Ascorbic Acid; Dose-Response Relationship, Drug; Female; Humans; In Vitro Techniques; Male; Methemoglobinemia; Middle Aged; Nerve Block; Prilocaine; Prospective Studies; Toluidines

Topics: Ascorbic Acid; Humans; Methemoglobinemia; Ozone

The drugs containing nitrates like isosorbide dinitrate, isosorbide mononitrate and glyceryl trinitrate, etc., trigger the oxidation of hemoglobin which is manifested in the pathological disorder named methemoglobinemia. It was considered interesting to investigate the preventive roles of vitamin C towards the toxic effects of nitrate containing drugs used for the treatment of angina. The aim is to find whether these drugs need to be administered with special care to diabetic patients who are more prone to develop methemoglobinemia. Vitamin C (500 mg/day) was administered orally to reduce the methemoglobin (metHb) level in both the diabetic and nondiabetic patients consuming nitrate containing drugs regularly, keeping diabetic and nondiabetic patients not on nitrate drugs as control. Concentration of metHb and hemoglobin A (HbA) was estimated spectrophotometrically assuming the molar extinction coefficient values of metHb as 3.78 mM

Topics: Ascorbic Acid; Diabetes Mellitus; Humans; Methemoglobinemia; Nitrates

Methemoglobinemia is a common complication of dapsone poisoning. Its´ treatment usually relies on methylene blue infusion. The aim of this study was to report a case of an acute dapsone poisoning with methemoglobinemia treated only with ascorbic acid and activated charcoal. A 16-year-old female voluntary ingested 3 grams of dapsone in an attempt of suicide and presented with desaturation and tachypnea. Lab findings were compatible with methemoglobinemia. After two days of treatment with ascorbic acid and activated charcoal, we observed the disappearance of desaturation and tachypnea. Methemoglobinemia can be treated with ascorbic acid and activated charcoal in limited resource settings.

Topics: Adolescent; Ascorbic Acid; Charcoal; Dapsone; Female; Humans; Methemoglobinemia; Tachypnea

Methaemoglobinaemia occurs when there is >1% methaemoglobin in erythrocytes. In an infant, they can present either congenitally or in an acquired form. We present a rare case of methaemoglobinaemia presenting simultaneously in a mother and infant pair. The mother and infant were discharged well on Day-4 post-delivery with both mother and baby recording oxygen saturation levels of 100%. On Day-7, during a routine clinic visit, they were incidentally found to be centrally cyanosed. There were no other abnormalities. On investigation, the methaemoglobin levels were elevated in the infant (23.9%) and mother (14.3%). Treatment with ascorbic acid normalised mother's methaemoglobin levels; but baby's levels remained high until the administration of oral methylene blue. Both baby and mother remained well and pink at last follow-up at 2 years 8 months of age. This case illustrates difficulties in ascertaining the cause of methaemoglobinaemia. Postdelivery, the mother-neonate pair were pink, and their haemoglobin electrophoresis were normal, hence it was unlikely to be congenital methaemoglobinaemia. The team could not identify any triggering factors for acquired methaemoglobinaemia. There was also the uncertainty of the necessity to treat the baby. This is because treatment is not without harmful effects and despite the high methaemoglobin levels, the infant was otherwise well. Only a single published paper recommended that high methaemoglobin levels must be treated, and the recommendation was not supported by evidence. Lessons learnt from our case are that neonates with methaemoglobinaemia can be safely treated with oral methylene blue, but more research is needed on the benefitrisk profile of treatment.

Topics: Ascorbic Acid; Female; Hemoglobin M; Humans; Infant; Infant, Newborn; Male; Methemoglobinemia; Mothers

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.

Topics: Aged; Anemia, Hemolytic; Ascorbic Acid; Female; Glucosephosphate Dehydrogenase Deficiency; Hemifacial Spasm; Humans; Methemoglobinemia; Vitamins

Exposure to naphthalene, which is widely used in mothballs, does not usually produce adverse effects. However, naphthalene can be toxic, especially in individuals with underlying conditions such as glucose-6-phosphate-dehydrogenase (G6PD) deficiency.. A 3-year-old boy was brought to our Emergency Department after accidentally ingesting naphthalene mothballs 3 days prior to presentation. Laboratory investigations revealed that he had severe hemolytic anemia and mild methemoglobinemia (6%), which were treated with ascorbic acid and N-acetylcysteine. The patient tested positive for G6PD deficiency after stabilization and completion of his treatment. All provided treatments were administered empirically; test results were available only after the patient was discharged. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Naphthalene exposure is a common pediatric presentation with various complications that can occur in certain high-risk individuals, such as those with G6PD deficiency. Emergency physicians should be aware of this to anticipate and be able to treat worsening toxicity.

Topics: Ascorbic Acid; Child, Preschool; Glucosephosphate Dehydrogenase Deficiency; Humans; Male; Methemoglobinemia; Naphthalenes

Methemoglobinemia is a rare disorder of the blood in which there is an increase in methemoglobin, which occurs when hemoglobin is present in the oxidized form. Methemoglobin impairs hemoglobin's ability to transport oxygen, produces functional anemia, and leads to tissue hypoxia. We report the successful management of a case of refractory hypoxia due to acutely acquired methemoglobinemia in a patient undergoing treatment for coronavirus disease 2019 (COVID-19) pneumonia. The cause of methemoglobinemia in this patient remains unknown. Hypoxia and methemoglobinemia did not respond to methylene blue and required administration of packed red blood cell transfusions.

Topics: Acute Kidney Injury; Aged; Antibodies, Monoclonal, Humanized; Antioxidants; Ascorbic Acid; Betacoronavirus; Coronavirus Infections; Corynebacterium; Corynebacterium Infections; COVID-19; Cytokine Release Syndrome; Enzyme Inhibitors; Erythrocyte Transfusion; Hematinics; Humans; Hydroxocobalamin; Hydroxychloroquine; Hypoxia; Male; Methemoglobinemia; Methylene Blue; Pandemics; Pneumonia, Bacterial; Pneumonia, Viral; Renal Replacement Therapy; Respiratory Insufficiency; SARS-CoV-2; Shock, Septic

A 14-year-old boy of Asian origin presented with a history of bluish discolouration of the finger and toenail bed with associated mild fatiguability on exertion since early childhood. Clinical examination revealed bilaterally symmetric uniform central cyanosis with no associated clubbing. Cardiovascular and respiratory system examination was normal. Pulse oximetry revealed an oxygen saturation of 87% in all four limbs. Transthoracic and transoesophageal echocardiography showed no evidence of shunt lesions. In view of the past diagnosis of pulmonary arteriovenous fistulae made at 4 years of age, a repeat cardiac catheterisation study was done, which revealed no shunt at any level. Interestingly, arterial oxygen tension of the chocolate-brown blood was normal in all the samples, suggesting the possibility of methaemoglobinaemia. Co-oximetry revealed methaemoglobin levels of 36%, confirming the diagnosis. Secondary causes were ruled out. The family was counselled about the hereditary nature of the condition.

Topics: Adolescent; Antioxidants; Ascorbic Acid; Blood Gas Analysis; Cardiac Catheterization; Color; Cyanosis; Directive Counseling; Fatigue; Genetic Testing; Humans; Male; Methemoglobin; Methemoglobinemia; Nails, Malformed; Oximetry; Treatment Outcome

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.. 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.

Topics: Adult; Antioxidants; Ascorbic Acid; Blood Gas Analysis; Cyanosis; Humans; Male; Methemoglobinemia; Methylene Blue; Oxygen; Paint

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.. 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.

Topics: Adult; Anesthetics, Local; Antioxidants; Ascorbic Acid; Emergency Service, Hospital; Enzyme Inhibitors; Female; Fentanyl; Humans; Ketamine; Methemoglobinemia; Methylene Blue; Pregnancy

Methaemoglobin is a form of haemoglobin in which the ferrous (Fe

Topics: Acute Disease; Adult; Anemia, Hemolytic; Antioxidants; Ascorbic Acid; Blood Transfusion; Diagnosis, Differential; Glucosephosphate Dehydrogenase Deficiency; Humans; Male; Methemoglobinemia; Nepal; Severity of Illness Index

Topics: Administration, Topical; Anesthetics, Local; Ascorbic Acid; Benzocaine; Cyanosis; Diagnosis, Differential; Humans; Infant, Newborn; Male; Methemoglobinemia; Perineum

Topics: Ascorbic Acid; Humans; Male; Methemoglobinemia; Middle Aged; Nitric Oxide; Vitamins

Topics: Anesthetics, Local; Ascorbic Acid; Female; Humans; Methemoglobinemia; Methylene Blue; Prilocaine; Treatment Outcome; Young Adult

We report a case of a young man who allegedly consumed 100 mL of an indigenous pesticide which is used for the killing of rats in households in India. The constituents were azadirachtin oil (40%), tea oil (15%), pine oil (25%) and kerosene oil (20%). He presented to us with shortness of breath and altered sensorium and was found to have fMetHb (fraction of methaemoglobin) level of 80%, which has been postulated to have a fatal outcome. He responded to a low dose of methylene blue along with intravenous vitamin C and the level of fMetHb came down to 20% within 1 hour. His sensorium improved markedly with a decrease in fMetHb to non-toxic levels and he was discharged 5 days after admission. A literature review pertaining to these constituents individually or in combination causing methaemoglobinaemia is discussed in the context of this case.

Topics: Adult; Ascorbic Acid; Diagnosis, Differential; Emergency Treatment; Humans; Infusions, Intravenous; Kerosene; Male; Methemoglobinemia; Methylene Blue; Pesticides; Plant Oils; Suicide, Attempted

Topics: Abdominal Pain; Anemia; Antioxidants; Ascorbic Acid; Child, Preschool; Cough; Cytochrome-B(5) Reductase; Diagnosis, Differential; Emergency Service, Hospital; Glucosephosphate Dehydrogenase Deficiency; Headache; Humans; Hypoxia; Intensive Care Units; Jaundice; Male; Methemoglobinemia; Methylene Blue; Morocco; Oxygen Inhalation Therapy; United States; Vicia faba

A case of apparent rasburicase-induced methemoglobinemia and acute kidney injury treated with i.v. ascorbic acid because of suspected glucose-6-phosphate dehydrogenase (G6PD) deficiency is reported.. A 46-year-old African-American man with a recent diagnosis of multiple myeloma and renal insufficiency was admitted to the hospital with a cough, hemoptysis, and fatigue. His medical history included hypertrophic cardiomyopathy, ventricular tachycardia, attention deficit/hyperactivity disorder, and pleural effusion. No treatments for multiple myeloma were started before hospital admission. Levofloxacin 750 mg orally daily for possible pneumonia, lenalidomide 10 mg orally daily, and dexamethasone 20 mg orally weekly were administered. Plasmapheresis was also initiated. Laboratory test results revealed sustained hyperuricemia, which was believed to be due in part to tumor lysis, and a single dose of rasburicase 6 mg i.v. was administered. Subsequently, the patient experienced a decrease in oxygen saturation. Methemoglobinemia was suspected, and the patient's methemoglobin fraction was found to be 14.5%. The patient developed worsening shortness of breath and a drop in hemoglobin concentration, consistent with methemoglobinemia and hemolysis. Ascorbic acid 5 g i.v. every 6 hours was initiated for a total of six doses. Because the patient was assumed to have G6PD deficiency, which was later confirmed, methylene blue was avoided. Within 24 hours, the patient's oxygen saturation values and symptoms improved.. A patient with apparent rasburicase-induced methemoglobinemia and acute kidney injury was treated with i.v. ascorbic acid (5 g every six hours for six doses) because of the possibility, later proved, that he had G6PD deficiency. The methemoglobinemia resolved without worsening of renal function.

Topics: Acute Kidney Injury; Administration, Intravenous; Aged; Ascorbic Acid; Glucosephosphate Dehydrogenase Deficiency; Gout Suppressants; Humans; Male; Methemoglobinemia; Treatment Outcome; Urate Oxidase

In 2008, self-poisoning with the herbicide propanil had a case-fatality of around 11% in Sri Lanka. A simple quantitative methaemoglobinemia bedside test was developed so that treatment could be titrated according to the methaemoglobin level.. To determine whether the new method influenced patient management and changed the case fatality of propanil self-poisoning.. The bedside test (using an inexpensive validated colour chart) was introduced in three hospitals (Anuradhapura, Polonnaruwa and Galle) in Sri Lanka from 2008. Junior ward staff were given a brief training on how to use the chart for quantitative estimation of methaemoglobin in patients with propanil poisoning and utilize the results in the context of the national treatment guidelines for propanil poisoning. It was taught that the bedside test should be done repeatedly from admission until it showed consistently low values of methaemoglobin. Treatment with the antidote methylene blue was suggested for patients whose methaemoglobin was greater than 20%. Limited clinical data on poisoning have been prospectively collected from these hospitals from 2003. The case-fatality and management before and after the change were compared with data up to December 2014.. The case-fatality decreased from (38/401) 9.5% to (8/262) 3.1% [difference: -6.4%, 95% CI: -10 to -3]. Methylene blue use increased from under 10% of patients before to 55% of patients after the intervention. More patients received repeat doses and infusions, and few received ascorbic acid and exchange transfusion.. The simple bedside test for methaemoglobinemia was readily adopted into routine practice and led to large changes in management. A substantial reduction in mortality from propanil poisoning occurred after this intervention.

Topics: Adult; Antidotes; Ascorbic Acid; Dose-Response Relationship, Drug; Female; Herbicides; Hospitalization; Humans; Male; Methemoglobin; Methemoglobinemia; Methylene Blue; Middle Aged; Poisoning; Propanil; Retrospective Studies; Sri Lanka; Young Adult

A 15-year-old boy presented to emergency services with accidental naphthalene ball ingestion. Following consumption he developed methaemoglobinaemia, massive intravascular haemolysis and acute kidney injury. He had no history suggestive of congenital haemoglobin M disease. Development of severe methaemoglobinaemia and intravascular haemolysis is quite unusual after consumption of a single ball of naphthalene. The patient was managed with ascorbic acid and intravenous N-acetyl cysteine. He also required haemodialysis for acute kidney injury that developed secondary to pigment nephropathy.

Topics: Acute Kidney Injury; Adolescent; Antioxidants; Ascorbic Acid; Cysteine; Hemolysis; Humans; Male; Methemoglobinemia; Naphthalenes; Renal Dialysis

Methylene blue is the first-choice treatment of methemoglobinemia, but it is not readily available in most Korean emergency departments because of an import suspension. An 84-year-old woman with dapsone-induced massive methemoglobinemia visited our emergency department for unclear mentality and cyanosis. Because methylene blue was not available, we intravenously administrated vitamin C (VC) for symptomatic methemoglobinemia, although VC is not a universally accepted treatment. Vitamin C (10 g intravenously) administered 6 hourly successfully treated the dapsone-induced methemoglobinemia and did not adversely affect renal functions. Thus,we recommend that if methylene blue is unavailable, 6 hourly intravenous administrations of 10 g of VC should be considered for dapsone-induced methemoglobinemia.

Topics: Aged, 80 and over; Ascorbic Acid; Dapsone; Female; Humans; Methemoglobin; Methemoglobinemia; Vitamins

Topics: Ascorbic Acid; Humans; Methemoglobinemia; Vitamins

Topics: Ascorbic Acid; Dapsone; Female; Humans; Methemoglobinemia; Vitamins

Topics: Anemia, Hemolytic; Antioxidants; Ascorbic Acid; Cyclophosphamide; Glucosephosphate Dehydrogenase Deficiency; Hemolysis; Humans; Male; Methemoglobinemia; Middle Aged; Multiple Myeloma; Myeloablative Agonists; Treatment Outcome; Tumor Lysis Syndrome; Urate Oxidase

Topics: Antioxidants; Ascorbic Acid; Child; Color; Female; Hinduism; Holidays; Humans; India; Inpatients; Male; Methemoglobinemia; Methylene Blue; Treatment Outcome

Topics: Anesthetics, Local; Antioxidants; Ascorbic Acid; Circumcision, Male; Cyanosis; Humans; Infant; Male; Methemoglobinemia; Prilocaine

An acute poisoning with nitrobenzene presenting as methaemoglobinemia is an uncommon medical emergency. A young girl with nitrobenzene induced methaemoglobinaemia died despite use of mechanical ventilator, administration of oral methylene blue and parenteral ascorbic acid. Here author highlights the rare occurrence of such cases, methaemoglobin induced severe oxidative stress, unexplained splenomegaly and leucocytosis and the ineffectivity of oral methylene blue and other supportive measures in evading death due to nitrobenzene poisoning.

Topics: Adolescent; Antidotes; Ascorbic Acid; Fatal Outcome; Female; Humans; Methemoglobinemia; Methylene Blue; Nitrobenzenes; Suicide

During investigations of the phenotypic diversity of hemoglobin (Hb) E β thalassemia, a patient was encountered with persistently high levels of methemoglobin associated with a left-shift in the oxygen dissociation curve, profound ascorbate deficiency, and clinical features of scurvy; these abnormalities were corrected by treatment with vitamin C. Studies of erythropoietin production before and after treatment suggested that, as in an ascorbate-deficient murine model, the human hypoxia induction factor pathway is not totally dependent on ascorbate levels. A follow-up study of 45 patients with HbE β thalassemia showed that methemoglobin levels were significantly increased and that there was also a significant reduction in plasma ascorbate levels. Haptoglobin levels were significantly reduced, and the high frequency of the 2.2 haptoglobin genotype may place an additional pressure on ascorbate as a free-radical scavenger in this population. There was, in addition, a highly significant correlation between methemoglobin levels, splenectomy, and factors that modify the degree of globin-chain imbalance. Because methemoglobin levels are modified by several mechanisms and may play a role in both adaptation to anemia and vascular damage, there is a strong case for its further study in other forms of thalassemia and sickle-cell anemia, particularly when splenic function is defective.

Topics: Adult; Ascorbic Acid; Ascorbic Acid Deficiency; beta-Thalassemia; Family; Female; Hemoglobin E; Humans; Male; Methemoglobin; Methemoglobinemia; Young Adult

Naphthalene, a widely used industrial and household chemical, has rarely been an agent of poisoning worldwide. Severe haemolysis from naphthalene poisoning is rare and can be a challenge to clinicians. We report a 22-year-old female, who accidentally ingested naphthalene mixed coconut oil and got admitted with recurrent vomiting, headache and passage of dark urine. Severe intravascular haemolysis with hypotension and neutrophilic leukocytosis was detected. She was treated with red blood cell transfusions, intravenous saline infusion and ascorbic acid.

Topics: Administration, Oral; Anemia, Hemolytic; Ascorbic Acid; Coconut Oil; Erythrocyte Transfusion; Female; Glucose; Hemoglobinuria; Hemolysis; Humans; Hypotension; Infusions, Intravenous; Methemoglobinemia; Naphthalenes; Plant Oils; Poisoning; Severity of Illness Index; Treatment Outcome; Young Adult

Acute aluminum phosphide (AlP) poisoning is one of the most common causes of acute pesticide poisoning in Iran. Hydrogen phosphide or phosphine gas is produced following reaction of AlP with water even at ambient humidity. Methemoglobinemia is a rare finding following phosphine poisoning. In this paper, two cases of fatal AlP poisoning complicated by methemoglobinemia are reported.. Two patients presented following suicidal ingestion of AlP tablets. In the Emergency Department (ED), they received gastric lavage with sodium bicarbonate and potassium permanganate. Both of them received supportive care. In each case, hematuria and hemolysis were significant events. The patients also showed a decrease in O(2) saturation in spite of high FIO(2). Methemoglobin levels of 40% and 30% were detected by co-oximetry. Neither patient responded to treatment (ascorbic acid in one case, methylene blue in the other). Both patients died due to systemic effects of phosphine poisoning.. Hemolysis and methemoglobinemia may complicate the course of phosphine poisoning that seems resistant to methylene blue and ascorbic acid. Therefore, other treatments including hyperbaric oxygen therapy and exchange blood transfusion should be considered.

Topics: Adult; Aluminum Compounds; Antidotes; Ascorbic Acid; Calcium Gluconate; Fatal Outcome; Fluid Therapy; Humans; Magnesium Sulfate; Male; Methemoglobinemia; Methylene Blue; Middle Aged; Pesticides; Phosphines; Sodium Bicarbonate; Suicide, Attempted

Methemoglobinemia is characterized by varying degrees of cyanosis due to increased hemoglobin concentrations containing oxidized iron. Prilocaine is a widely used local anesthetic and can cause methemoglobinemia in infants even in therapeutic doses. We present two female infants (younger than 2 months) who developed severe cyanosis after transcatheter pulmonary balloon valvuloplasty and were diagnosed with toxic methemoglobinemia. Both infants were anesthetized with local prilocaine application before balloon valvuloplasty. Methemoglobin levels of the patients were measured as 49.6% and 37.7%, respectively. Both were successfully treated with intravenous methylene blue and ascorbic acid.

Topics: Anesthetics, Local; Ascorbic Acid; Catheterization; Cyanosis; Female; Humans; Infant; Methemoglobinemia; Methylene Blue; Prilocaine; Treatment Outcome

A 15-year-old girl presented after intentional ingestion of dapsone (7.2 g) and small quantities of azathioprine, methotrexate and prednisolone. The resulting methaemoglobinaemia and lactic acidosis persisted despite treatment with methylene blue, multiple-dose activated charcoal and ascorbic acid. Continuous veno-venous haemofiltration for 75 hours was used to treat the dapsone overdose. The patient's serum dapsone concentrations were measured during and after continuous veno-venous haemofiltration. The rate of elimination of dapsone was over three times higher during, compared to after, continuous veno-venous haemofiltration. Continuous renal replacement therapy successfully reduced toxic dapsone concentrations in this patient with a good outcome.

Topics: Acidosis, Lactic; Adolescent; Anti-Infective Agents; Antidotes; Antioxidants; Ascorbic Acid; Blood Gas Analysis; Charcoal; Dapsone; Drug Overdose; Female; Gastric Lavage; Hemofiltration; Humans; Methemoglobinemia; Renal Replacement Therapy; Respiration, Artificial

Topics: Ascorbic Acid; Azathioprine; Blood Gas Analysis; Dapsone; Female; Follow-Up Studies; Humans; Hypercapnia; Hypoxia; Methemoglobinemia; Methylene Blue; Middle Aged; Myositis; Oximetry; Polysomnography; Prednisone; Respiratory Function Tests; Respiratory Insufficiency; Risk Assessment; Severity of Illness Index; Treatment Outcome

An acute poisoning with nitrobenzene presenting as methaemoglobinemia is an uncommon medical emergency. A young girl with nitrobenzene induced methaemoglobinaemia died despite use of mechanical ventilator, administration of oral methylene blue and parenteral ascorbic acid. Here author highlights the rare occurrence of such cases, methaemoglobin induced severe oxidative stress, unexplained splenomegaly and leucocytosis and the ineffectivity of oral methylene blue and other supportive measures in evading death due to nitrobenzene poisoning.

Topics: Adolescent; Antidotes; Ascorbic Acid; Fatal Outcome; Female; Humans; Methemoglobinemia; Methylene Blue; Nitrobenzenes; Respiration, Artificial

Topics: Anesthetics, Local; Ascorbic Acid; Circumcision, Male; Cyanosis; Humans; Infant; Male; Methemoglobinemia; Postoperative Complications; Prilocaine; Reducing Agents

Type II methemoglobinemia is a somatic deficiency of cytochrome b5 reductase with severe global neurologic impairment. We report a novel mutation in exon 3 of the CYB5R3 gene on chromosome 22 consisting of homozygous 1-base pair (bp) deletion noted as c.215delG; p.Gly72AlafsX100. The patient had improvement of gross motor skills, chewing, and swallowing that may be due to the initiation of daily ascorbic acid therapy. We hypothesize that a possible response to ascorbic acid may be related to the effect of making additional ferrous iron available for its role as a cofactor in carnitine synthesis.

Topics: Adult; Ascorbic Acid; Child; Cytochrome-B(5) Reductase; Dyskinesias; Female; Honduras; Humans; Male; Methemoglobinemia; Mothers; Sequence Analysis, DNA; Sequence Deletion; Treatment Outcome; Vitamins

Ingestional naphthalene mothball poisoning leading to prolonged haemolysis and methaemoglobinaemia can present with diagnostic and therapeutic challenges. A 19-year-old woman ingested 12 mothballs, and presented two days later with haemolysis and methaemoglobinaemia. She was treated with red blood cell transfusions, intravenous methylene blue, N-acetylcysteine and ascorbic acid. Continuous venovenous haemofiltration was conducted for 45 hours. Haemolysis with anaemia and methaemoglobinaemia persisted even after five days post-ingestion. Clinical and biochemical parameters improved. We describe a case of ingestional naphthalene poisoning with a good outcome after treatment.

Topics: Acetylcysteine; Adult; Anemia, Hemolytic; Ascorbic Acid; Erythrocyte Transfusion; Female; Hemolysis; Humans; Methemoglobinemia; Methylene Blue; Naphthalenes; Poisoning; Suicide, Attempted; Time Factors; Treatment Outcome

The development of cyanosis at birth, the so-called blue baby syndrome, alerts paediatricians to the presence of congenital heart disease. In rare cases where the arterial blood gas analysis is normal the cyanosis is a consequence of methaemoglobinaemia. There are three distinct origins of methaemoglobinaemia; the presence of a haemoglobin variant, environmental toxicity and deficiency of cytochrome b5 reductase (cb(5)r). Two children born to two sets of first-degree related parents were cyanotic from birth. Differential diagnosis eliminated cardiac and pulmonary abnormalities. Measurement of methaemoglobin levels confirmed recessive congenital methaemoglobinaemia (RCM) and treatment with ascorbic acid was commenced. In the absence of neurological defects, type I disease was diagnosed. Sequence analysis of CYB5R3 revealed two different missense mutations (one which is novel, Ile85Ser) in the two families. Neither of the mutations was located in the FAD or the NADH binding sites of cb(5)r, thus supporting a diagnosis of type I disease.

Topics: Ascorbic Acid; Child; Consanguinity; Cytochrome-B(5) Reductase; Female; Genes, Recessive; Humans; Infant; Male; Methemoglobinemia; Mutation, Missense; Turkey

Local anesthesia with prilocaine has become a routine part of ambulatory circumcision procedures. Methemoglobinemia is a rare but potentially lethal complication of local anesthetics. We report the case of a 42-day-old boy who presented with cyanosis after receiving local anesthesia with prilocaine. Methemoglobin level revealed severe methemoglobinemia (methemoglobin=44.5%). His cyanosis promptly resolved after intravenous administration of ascorbic acid. Cases of local anesthetic-induced methemoglobinemia in urology are under recognized. Although the association between prilocaine use and methemoglobinemia has generally restricted prilocaine use in infants, it is still widely used in ambulatory procedures, especially during circumcision in the neonatal period. Prilocaine should not be used in infants less than 3 months of age because of the risk of methemoglobinemia and alternative local analgesics should be considered among this age group. We also discuss the use of ascorbic acid during treatment in light of the literature.

Topics: Anesthetics, Local; Antioxidants; Ascorbic Acid; Circumcision, Male; Humans; Infant; Injections, Intravenous; Male; Methemoglobinemia; Prilocaine

Topics: Adolescent; Ascorbic Acid; Clinical Trials as Topic; Cystine; Female; History, 20th Century; Homocystinuria; Humans; Male; Methemoglobinemia; Siblings; United Kingdom

Dapsone can alter the oxygen carrying capacity of haemoglobin. Some patients are more susceptible to these effects because of genetic factors, comorbidities or peri-operative factors such as anaemia. We present a 57-year-old lady who underwent elective coronary artery bypass grafting. Deterioration in neurological and respiratory condition prompted a review of her drug treatment. A combination of long-term dapsone therapy, co-existing cardiac and respiratory disease, postoperative anaemia and renal impairment contributed to her decompensation, despite a relatively low level of methaemoglobin. Successful management included stopping dapsone therapy, supportive care and administration of ascorbic acid.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Ascorbic Acid; Coronary Artery Bypass; Dapsone; Female; Humans; Hypoxia, Brain; Methemoglobinemia; Middle Aged; Postoperative Complications

Haemoglobin initiates free radical chemistry. In particular, the interactions of peroxides with the ferric (met) species of haemoglobin generate two strong oxidants: ferryl iron and a protein-bound free radical. We have studied the endogenous defences to this reactive chemistry in a rabbit model following 20% exchange transfusion with cell-free haemoglobin stabilized in tetrameric form [via cross-linking with bis-(3,5-dibromosalicyl)fumarate]. The transfusate contained 95% oxyhaemoglobin, 5% methaemoglobin and 25 microM free iron. EPR spectroscopy revealed that the free iron in the transfusate was rendered redox inactive by rapid binding to transferrin. Methaemoglobin was reduced to oxyhaemoglobin by a slower process (t(1/2) = 1 h). No globin-bound free radicals were detected in the plasma. These redox defences could be fully attributed to a novel multifunctional role of plasma ascorbate in removing key precursors of oxidative damage. Ascorbate is able to effectively reduce plasma methaemoglobin, ferryl haemoglobin and globin radicals. The ascorbyl free radicals formed are efficiently re-reduced by the erythrocyte membrane-bound reductase (which itself uses intra-erythrocyte ascorbate as an electron donor). As well as relating to the toxicity of haemoglobin-based oxygen carriers, these findings have implications for situations where haem proteins exist outside the protective cell environment, e.g. haemolytic anaemias, subarachnoid haemorrhage, rhabdomyolysis.

Topics: Animals; Ascorbic Acid; Blood Substitutes; Cell-Free System; Electron Spin Resonance Spectroscopy; Erythrocyte Membrane; Erythrocytes; Exchange Transfusion, Whole Blood; Free Radicals; Heme; Hemodilution; Hemoglobin A; Humans; Hydrogen Peroxide; Iron; Male; Methemoglobin; Methemoglobinemia; Oxidation-Reduction; Oxidative Stress; Oxyhemoglobins; Peroxides; Rabbits; Transferrin

A 22-year-old woman with an initial diagnosis of 'ruptured ectopic pregnancy' and 'hemorrhagic shock' was sent to the operation room for surgical treatment. The mucocutaneous color was deeply cyanosed and the pulse oximeter oxygen saturation (SpO2) was only 86% after tracheal intubation (100% O2). 'Chocolate-brown' blood was observed and methemoglobinemia was considered. Then the arterial blood gas (ABG) sample was obtained, an intravenous infusion of methylene blue and vitamin C followed. The patient recovered quickly, and later two other patients with similar symptoms were treated in the same way. The success was due to a correct diagnosis accompanied with prompt treatment and quick recognition of the etiology.

Topics: Adult; Antidotes; Antioxidants; Ascorbic Acid; Blood Gas Analysis; Diagnosis, Differential; Female; Food Preservatives; Humans; Meat; Methemoglobinemia; Methylene Blue; Nitrates; Oxygen; Pregnancy; Pregnancy, Ectopic; Rupture; Shock, Hemorrhagic; Sodium Nitrite

Methemoglobinemia, although rare, must be considered in surgical patients presenting with acute respiratory distress and cyanosis. We report two cases of methemoglobinemia in patients undergoing aortic reconstruction. The first patient developed methemoglobinemia while on a nitroglycerin infusion, and the second after receiving benzocaine spray before intubation. Both patients were treated with methylene blue and ascorbic acid, with resolution of their hypoxia and cyanosis. The pathophysiology, etiology, diagnosis, and treatment of methemoglobinemia are reviewed.

Topics: Aged; Antioxidants; Ascorbic Acid; Blood Vessel Prosthesis Implantation; Cyanosis; Enzyme Inhibitors; Female; Humans; Methemoglobinemia; Methylene Blue; Middle Aged; Postoperative Complications; Treatment Outcome

A baby centrally cyanosed from birth was investigated for a congenital cardiac defect. Echocardiography and angiography revealed patent foramen ovale without any other cardiac abnormality. Congenital methaemoglobinaemia was considered as the methaemoglobin level was 27%, suggesting either Hb M or a deficiency of the NADH-cytochrome b5 reductase (cytb5r) enzyme. Measurement of the cytb5r enzyme activity of this patient indicated a reduced level of 7.3 IU/g Hb (normal range 11.5-26.9 IU/g Hb). Sequencing the DIA 1 gene that encodes cytb5r revealed a novel C403T base change, predicting a proline to serine change at codon 144. This amino-acid change is not located in the enzyme's active site and does not cause loss of function. Instead it results in reduced stability of the enzyme and development of the less severe or Type I form of recessive congenital methaemoglobinaemia. The infant was started on daily ascorbic acid treatment. She has very mild cyanosis and normal growth and developmental parameters on follow-up at 10 months of age.

Topics: Amino Acid Substitution; Ascorbic Acid; Cytochrome-B(5) Reductase; Female; Humans; Infant; Methemoglobinemia; Mutation, Missense; Proline; Serine; Treatment Outcome; Turkey

Topics: Ascorbic Acid; Humans; Methemoglobinemia; Methylene Blue

Topics: Antioxidants; Ascorbic Acid; Emergency Service, Hospital; Emergency Treatment; Humans; Infusions, Intravenous; Methemoglobinemia

An 11-year-old, spayed female Dalmatian was presented with suspected acetaminophen toxicosis. The dog was severely depressed. Methemoglobinemia, facial edema, and hemoglobinuria responded to treatment with intravenous fluids, N-acetylcysteine, ascorbic acid, and sodium bicarbonate. There was no clinical evidence of hepatic damage typical of acetaminophen toxicity in the dog.

Topics: Acetaminophen; Acetylcysteine; Analgesics, Non-Narcotic; Animals; Ascorbic Acid; Dog Diseases; Dogs; Emergency Treatment; Female; Fluid Therapy; Free Radical Scavengers; Liver; Methemoglobinemia; Sodium Bicarbonate; Treatment Outcome

Topics: Ascorbic Acid; Cathartics; Constipation; Enzyme Inhibitors; Female; Humans; Infant; Methemoglobinemia; Methylene Blue

Topics: Adult; Ascorbic Acid; Cyanosis; Humans; Male; Methemoglobinemia; Oxygen

Methylene blue is used to check tubal patency during laparoscopy. A case of methemoglobinemia which was induced by methylene blue is presented. Methemoglobinemia is usually treated with methylene blue; however, in patients with glucose-6-phosphate dehydrogenase deficiency, methylene blue can induce methemoglobinemia.

Topics: Adult; Ascorbic Acid; Coloring Agents; Cyanosis; Fallopian Tube Patency Tests; Female; Glucosephosphate Dehydrogenase Deficiency; Humans; Infertility, Female; Injections, Intravenous; Laparoscopy; Methemoglobinemia; Methylene Blue

The objective of the present study was to investigate the treatment of nitric oxide (NO)-induced methemoglobinemia by ascorbate and its consequences on red blood cell (RBC) glutathione in vitro. RBC were obtained from five healthy volunteers. The following experiments were carried out: (1) After methemoglobin generation by NO, ascorbate was added (2) RBC were simultaneously exposed to NO and ascorbate (3) Methemoglobin was generated by NO, ascorbate was added and incubation with NO continued. (1) After discontinuation of NO, the mean half life for methemoglobin was reduced from 195 min (controls) to 60 min (10 mM ascorbate) in a dose-dependent manner. (2) Methemoglobin formation after 3 h of NO exposure was 2.7 +/- 0.3% in controls and 1.8 +/- 0.1% with 10 mM ascorbate (p < 0.01). (3) Further methemoglobin formation was inhibited only by 10 mM ascorbate (p < 0.001). NO incubation did not affect RBC glutathione (86.5 +/- 19.6 and 86.5 +/- 19.6 mg/l, respectively). Treatment with 10 mM ascorbate significantly decreased glutathione (p < 0.002). In vitro, NO-induced methemoglobin formation is significantly decreased only by a high (10 mM) ascorbate concentration. Glutathione, critical for ascorbate activity, is not influenced by NO.

Topics: Adult; Analysis of Variance; Ascorbic Acid; Dose-Response Relationship, Drug; Erythrocytes; Glutathione; Humans; In Vitro Techniques; Methemoglobin; Methemoglobinemia; Nitric Oxide; Oxidation-Reduction; Spectrophotometry; Time Factors

Topics: Accidents, Home; Ascorbic Acid; Central Nervous System; Child, Preschool; Dapsone; Humans; Male; Methemoglobinemia; Poisoning

Topics: Ascorbic Acid; Chloramines; Diagnosis, Differential; Dialysis Solutions; Humans; Methemoglobin; Methemoglobinemia; Nitrates; Prognosis; Renal Dialysis

Two horses with red maple (Acer rubrum) toxicity responded to treatment with high doses of vitamin C (ascorbic acid), in addition to blood transfusions, and intravenous fluid therapy. The clinical course included Heinz body anemia, marked methemoglobinemia, depression, and evidence of severe tissue anoxia. Clinical recovery was dramatic with stabilization achieved 36 hours following the initiation of ascorbic acid therapy.

Topics: Anemia; Animals; Ascorbic Acid; Heinz Bodies; Horse Diseases; Horses; Hypoxia; Male; Methemoglobinemia; Plant Poisoning; Trees

Sodium nitrite induced poisoning resulted into oxidation-reduction disorders with concomitant changes in the ratio of the oxidated and reduced forms towards accumulation of the oxidated equivalents. Antioxidants unithiol, tocopherol acetate, ascorbic acid, methylene blue, violuric acid influenced the oxidation-reduction balance in different ways. The protective action of violuric acid was comparable with that of methylene blue and exceeded the unithiol protective properties. Violuric acid, as compared with unithiol, ascorbic acid and tocopherol, was more effective in decreasing methemoglobin and nitrates contents in blood in methemoglobinemia cases. The violuric acid and methylene blue protective mechanisms are in all probability influenced by the antioxidant properties of these substances and their reductase activity.

Topics: Animals; Antioxidants; Ascorbic Acid; Disease Models, Animal; Drug Evaluation, Preclinical; Drug Therapy, Combination; Male; Methemoglobinemia; Rats; Unithiol; Vitamin E

The successful management of nitrobenzene poisoning in a 21-year-old patient is presented. We report our experience of ventilatory care with additional intravenous methylene blue and ascorbic acid therapy. Pulse oximeters available at present are not useful in patients treated with methylene blue and should be used cautiously in the presence of cyanosis of unknown aetiology.

Topics: Adult; Ascorbic Acid; Humans; Male; Methemoglobinemia; Methylene Blue; Nitrobenzenes; Oximetry; Poisoning

The blood of healthy men and patients with methemoglobinemia of different genesis was incubated with chromosmon, ascorbic acid, riboflavin and glutathione, the percentage of erythrocytes with thorn-shaped protuberances-echinocytes being subsequently determined in the blood smears. The absorbtion spectra at the range 400-650 nm were investigated both in the smooth erythrocytes and in echinocytes. A correlation was found between the percentage of echinocytes and the methemoglobin content in the blood. The methemoglobin amount in the echinocytes was determined to be higher than in the smooth erythrocytes. It is discovered that effects of chromosmon, glutathione and riboflavin on production of methemoglobin depend on the dose, individual peculiarities of erythrocytes and on the illness that caused methemoglobinemia. The calculation of echinocyte percentage may be used as an express-diagnostics of methemoglobinemia and for purposes of studying the effect of methemoglobin-producing substances and drugs.

Topics: Ascorbic Acid; Bronchitis; Chronic Disease; Dose-Response Relationship, Drug; Erythrocytes; Glutathione; Hemoglobins; Humans; Methemoglobin; Methemoglobinemia; Methylene Blue; Pulmonary Heart Disease; Riboflavin; Sepsis; Shock, Traumatic; Spectrophotometry

Seventeen infants under 2 months of age are described who presented with methaemoglobinaemia and acute diarrhoea during a period of 2 years. No infants beyond this age presented with such characteristics. In none of them was one of the known mechanisms of methaemoglobin formation found. All infants recovered with conventional therapy. Methaemoglobin associated with diarrhoea relapsed in three infants before they were 2 months old. Twenty-six similar cases have been reported in the literature. The mechanism of methaemoglobinaemia in these infants is unclear.

Topics: Acidosis; Ascorbic Acid; Diarrhea, Infantile; Female; Fluid Therapy; Humans; Infant; Infant, Newborn; Male; Methemoglobinemia; Methylene Blue

Topics: Acidosis; Ascorbic Acid; Child, Preschool; Cyanosis; Diagnosis, Differential; Fluid Therapy; Humans; Infant, Newborn; Male; Methemoglobinemia; Methylene Blue

Topics: Acute Disease; Administration, Topical; Ascorbic Acid; Benzocaine; Humans; Infant; Male; Methemoglobinemia; Methylene Blue; Nonprescription Drugs; Tooth Eruption

Methaemoglobin is haemoglobin in which the sixth coordination position of heme iron is in the ferric state, having lost an unpaired electron. In normal human blood the level of methaemoglobin is 1% or less. This stable level results from an equilibrium between the rate at which ferric heme is formed and the rate at which it is reduced back to the ferrous state. Congenital methaemoglobinaemia caused by a deficiency or absence of methaemoglobin reductase represents a disturbance of this equilibrium wherein the methaemoglobin formed at physiological rate is not efficiently reduced. A chronically elevated level of oxidized haemoglobin results. Methaemoglobin is incapable of binding oxygen. Instead of the bright red colour imparted by oxyhaemoglobin, blood containing more than 10% methaemoglobin is dark brown. A concentration exceeding 1.5 g/d1 gives rise to cyanosis. The majority of patients with congenital enzymopenic methaemoglobinaemia are asymptomatic despite the intense cyanosis. This is a very important differentiating point from the cyanosis of cardiopulmonary causes. Methaemoglobin reductase deficiency is uncommon. Most proven cases had been in persons of European descent with sporadic reports of non-Caucasoid patients. We report here a Chinese patient whom we believe is the first in South East Asia to have methaemoglobin reductase deficiency unequivocally documented.

Topics: Adult; Ascorbic Acid; China; Cytochrome-B(5) Reductase; Humans; Male; Methemoglobin; Methemoglobinemia; NADH, NADPH Oxidoreductases; Singapore

Topics: Ascorbic Acid; Child; Female; Food Additives; Humans; Male; Meat; Methemoglobinemia; Methylene Blue; Nitrites

Oxygen transport, the major function of hemoglobin, is dependent upon reduced heme iron. In the red cell, the heme iron is maintained in the reduced form by the methemoglobin reduction system. When the balance between oxidation and reduction of heme iron is perturbed due to the presence of excessive oxidants, decreased reducing capacity or the presence of abnormal hemoglobin, methemoglobinemia ensues. In most cases methemoglobinemia is transitory and of no major clinical consequence. Occasionally, however, it can be life threatening and must be rapidly diagnosed and treated. When methemoglobinemia is of hereditary nature, either due to deficiency of red cell NADH-methemoglobin reductase or due to the presence of M hemoglobin, it is a lifelong problem. Since most of these patients do not have major disabling symptoms, the treatment is aimed at correction of cyanosis.

Topics: Ascorbic Acid; Chemical Phenomena; Chemistry; Cytochrome Reductases; Cytochrome-B(5) Reductase; Heme; Hemoglobin M; Hemoglobins; Humans; Hydrogen-Ion Concentration; Methemoglobin; Methemoglobinemia; Methylene Blue; NADH, NADPH Oxidoreductases; Oxidation-Reduction

The formation of plasma nitrite and levels of methemoglobin (MH) were studied after oral treatment with NaNO3 in female SD rats. No effects were observed when NaNO3 was administered in aqueous solution. However, feeding of diets containing an added 5% NaNO3 daily during 1 h significantly increased plasma NO2- and MH. These effects were significantly inhibited by the addition of ascorbic acid or of tocopherol to the NaNO3-containing diet. The transplacental transfer of NO2- was demonstrated as well as fetal methemoglobinemia.

Topics: Animals; Ascorbic Acid; Diet; Female; Kinetics; Maternal-Fetal Exchange; Methemoglobinemia; Nitrates; Nitrites; Placenta; Pregnancy; Rats; Rats, Inbred Strains; Vitamin E

Interspecies differences were demonstrated with respect to the occurrence of sodium nitrite-induced methemoglobin (METHB) in the erythrocytes of rats, dorset sheep, and normal humans, with the rats displaying approximately 25-33% of the sensitivity of sheep and human erythrocytes. Ascorbic acid incubation along with the nitrite was able to significantly reduce METHB formation in a dose-dependent manner in both rats and humans but not in sheep.

Topics: Animals; Ascorbic Acid; Drug Interactions; Erythrocytes; Female; Glutathione; Humans; In Vitro Techniques; Male; Methemoglobinemia; Nitrites; Rats; Rats, Inbred Strains; Sheep; Species Specificity

Nitrate poisoning was induced in a cow by giving it 200 g potassium nitrate through a rumen fistula for three to four days in succession. The effect of treatment with methylene blue, ascorbic acid and menadione, administered intravenously in different dosages was assessed by measuring methaemoglobin as a percentage of total haemoglobin and comparing the results with those from the untreated cow. The results obtained indicate that ascorbic acid and menadione are unsuitable for treatment of methaemoglobinaemia in nitrate poisoned cattle, but treatment with methylene blue at 1 mg/kg body weight appears to be adequate.

Topics: Animals; Ascorbic Acid; Cattle; Cattle Diseases; Female; Hemostatics; Methemoglobinemia; Methylene Blue; Nitrates; Potassium Compounds; Vitamin K; Vitamin K 3

Topics: Ascorbic Acid; Copper; Erythrocytes; Glucosephosphate Dehydrogenase Deficiency; Glutathione; Humans; Methemoglobinemia; Oxidation-Reduction

Four diets, each containing different levels of ascorbic acid were fed to duplicate groups of steelhead trout (Salmo gairdneri) in two four-week periods. Tolerance to nitrites increased when the concentration of ascorbic acid was high. Flow-through bioassays in fingerlings showed that when the temperature increased the percent of methemoglobin in their blood also increased. The tolerance to nitrite toxicity was less in large fish than in those smaller fed the same concentration of ascorbic acid. Possibly ascorbic acid acts in the reduction of methemoglobin to hemoglobin, and also it has a protective effect against stress in the fish. A "safe" level of 200 mg/kg of ascorbic acid in practical diets was reached.

Topics: Animal Feed; Animals; Ascorbic Acid; Body Weight; Methemoglobin; Methemoglobinemia; Nitrites; Salmonidae; Temperature; Trout

The influences of methylene blue (MB), thionine, ascorbic acid (ASA), sodium thiosulfate (STS), N-(2-mercaptopropionyl)-glycine (MPG) and reduced glutathione (GSH) on methemoglobin-(MHb)-emia and sulf-hemoglobin (SHb)-emia induced by 4-chloroaniline (4-Cl-A) i.p. were studied. Preventive or therapeutic effect on MHb-emia and preventive effect on SHb-emia in mice: MHb formation was inhibited by MB i.p. whether it was administered simultaneously with or after 4-Cl-A, but SHb formation was increased. Similar effects were seen with thionine. Both compounds proved to have MHb and SHb forming activities. STS or MPG, if administered i.p. simultaneously with 4-Cl-A, inhibited formation of MHb, but exerted no effect on delayed SHb formation. However, if administered i.p. or i.v. 120 minutes after 4-Cl-A when the peak of MHb formation had passed, there was a preventive effect on delayed SHb formation. GSH inhibited MHb formation and prevented SHb formation only when it was administered i.v. 120 minutes after 4-Cl-A. ASA did not inhibit MHb formation when it was administered either i.p. or i.v., but showed a preventive effect on SHb formation, if administered 120 minutes after 4-Cl-A. Combined i.v. administration of the corresponding doses to the clinical ones of MB and ASA 120 minutes after 4-Cl-A showed a therapeutic effect on MHb-emia and a preventive effect on SHb-emia. However, at higher dose levels, MB masked the preventive effect of ASA on SHb-emia. Therapeutic effect on SHb-emia in mice and rats: None of MB, STS, GSH and ASA proved to have any therapeutic effects for established SHb-emia. On the basis of these results, significance of clinical usage of drugs in the treatment of chemically induced MHb-emia and SHb-emia is discussed.

Topics: Aniline Compounds; Animals; Ascorbic Acid; Ergothioneine; Glutathione; Male; Methemoglobinemia; Methylene Blue; Mice; Rats; Sulfhemoglobinemia; Thiosulfates; Tiopronin

Topics: Animals; Antidotes; Ascorbic Acid; Dexamethasone; Dogs; Dose-Response Relationship, Drug; Humans; Hyperbaric Oxygenation; Methemoglobinemia; Methylene Blue; Rabbits; Respiratory Therapy; Tissue Distribution; Tolonium Chloride

A study of the concentration of met- and sulfhemoglobine in patients on admission to the clinic and at the end of the preoperative management and treatment was carried out upon 35 surgical cases. The medicamentous therapy included the drugs favouring the restoration of methemoglobin (10.20% and 40% glucose solutions, ascorbic acid etc.). Therewith the concentration of non-active hemoglobine derivatives dropped at the end of the preoperative management and treatment.

Topics: Acute Disease; Ascorbic Acid; Cholecystitis; Female; Glucose; Humans; Male; Methemoglobinemia; Middle Aged; Sulfhemoglobinemia

Topics: Ascorbic Acid; Cystamine; Humans; Methemoglobin; Methemoglobinemia; Methylene Blue

Methemoglobinemia developed in three dogs after the owners' use of benzocaine-containing products for topical treatment of the dogs' pruritic skin conditions. The products were intended for use in man. In two of the dogs, clinical signs of shock were observed within a few hours after the application of a skin lotion containing 5% benzocaine. Methemoglobin was assayed in one case and found to be 51% of total hemoglobin. Both dogs recovered after whole blood transfusions were given. The third dog, which had been treated for several weeks with small amounts of an anesthetic aerosol containing 20% benzocaine, was anorectic and lethargic when examined. Methemoglobin content was 30%, and Heinz bodies were observed in 20% of the erythrocytes. The methemoglobin content and proportion of Heinz bodies decreased rapidly after use of the spray was discontinued. The two benzocaine-containing products incriminated in development of the methemoglobinemia did not induce measurable increases in methemoglobin content in clinically normal dogs, when applied to unbroken skin. Small increases in methemoglobin content were measured, however, when these products were given orally to clinically normal dogs. It was concluded that the skin lesions in the three clinically affected dogs enhanced absorption of the drug, resulting in methemoglobin formation.

Topics: Animals; Ascorbic Acid; Benzocaine; Dog Diseases; Dogs; Erythrocytes; Female; Male; Methemoglobinemia; Methylene Blue; Pruritus

Topics: Adolescent; Adult; Ascorbic Acid; Drug Evaluation; Humans; Infant; Male; Methemoglobinemia; Riboflavin

Chloramines, compounds made up of chlorine and ammonia, when present in tap water used for dialysis cause methemoglobinemia and hemolysis. Ascorbic acid addition has been reported to effectively neutralize chloramines in vitro and in patients dialyzed with the single batch dialysis delivery system. We extended these observations to patients dialyzed with the proportioning dialysis delivery system where exposure time of ascorbic acid to chloramines is shorter. This may be important since we found that the half time of the reaction between ascorbic acid and chloramines is 4 minutes. Red cell oxidant sensitivity in 15 patients was assessed by incubating red cells with ascorbate-cyanide and measuring methemoglobin which averaged 2.17 +/- 0.42 g/100 ml (SEM) before dialysis and 2.87 +/- 0.52 g/100 ml after dialysis (NS). Reduced glutathione (GSH) levels were also measured as an index of red cell oxidant damage. GSH decreased from a mean of 7.40 +/- 0.59 micromoles/g Hb before dialysis to 6.98 +/- 0.52 micronmoles/g Hb after dialysis (P less than 0.01). In 2 patients there was no change in 51Cr red cell survival when dialyzed on either the proportioning system or other chloramine free systems. We conclude that addition of ascorbic acid to neutralize chloramines in tap water is also effective when using the proportioning dialysis delivery system.

Topics: Adult; Aged; Ascorbic Acid; Chloramines; Erythrocyte Aging; Glutathione; Hemolysis; Humans; Kidney Failure, Chronic; Methemoglobin; Methemoglobinemia; Middle Aged; Renal Dialysis

Ascorbic acid and dehydroascorbic acid penetrate the human erythrocyte membrane. In vitro methemoglobin is reduced nonenzymatically by both substances in concentrations of 10(-2) M to 10(-3) M. Dehydroascorbic acid is reduced nonenzymatically to ascorbic acid by GSH, even with low GSH-content of erythrocytes. Under physiological conditions ascorbic acid induced methemoglobin reduction is far less important than reduction by the NADH dependent methemoglobin reductase system. In methemoglobinemic conditions caused by toxic effects or by congenital methemoglobin reductase deficiency treatment with ascorbic acid is possible. However, critically increased methemoglobin content of the blood higher than 30% makes therapy with methylene blue necessary.

Topics: Ascorbic Acid; Dehydroascorbic Acid; Erythrocytes; Glucose; Glutathione; Humans; In Vitro Techniques; Methemoglobin; Methemoglobinemia; Oxidation-Reduction

Topics: Ascorbic Acid; Blood Protein Electrophoresis; Cyanosis; Dihydrolipoamide Dehydrogenase; Erythrocytes; Genes, Recessive; Homozygote; Humans; Infant, Newborn; Male; Methemoglobinemia; Pedigree; Prognosis

Topics: Ascorbic Acid; Cyanosis; Dihydrolipoamide Dehydrogenase; Erythrocytes; Female; Heterozygote; Humans; Intestines; Kinetics; Metabolism, Inborn Errors; Methemoglobin; Methemoglobinemia; Middle Aged; NAD; Neomycin

Topics: Anesthesia, Inhalation; Ascorbic Acid; Blood Gas Analysis; Cyanosis; Female; Hemoglobins; Humans; Methemoglobin; Methemoglobinemia; Methylene Blue; Middle Aged; Nitrous Oxide; Spectrum Analysis; Thiopental; Tubocurarine

Topics: Ascorbic Acid; Dihydrolipoamide Dehydrogenase; Electrophoresis, Polyacrylamide Gel; Erythrocytes; Female; Hemoglobins; Humans; Infant; Methemoglobinemia; Methylene Blue; NAD; Oxidation-Reduction; Pedigree

Topics: Animal Nutritional Physiological Phenomena; Animals; Ascorbic Acid; Body Weight; Dose-Response Relationship, Drug; Fertilizers; Guinea Pigs; Hemoglobins; Male; Methemoglobin; Methemoglobinemia; Methionine; Nitrates; Nitrites; Plants; Vegetables

Topics: Administration, Topical; Ascorbic Acid; Digitalis; Eczema; Follow-Up Studies; Humans; Infant; Male; Methemoglobinemia; Oxygen Inhalation Therapy; Phenols; Phytotherapy; Plants, Medicinal; Plants, Toxic; Resorcinols; Solutions

Topics: Arteriosclerosis; Ascorbic Acid; Common Cold; Humans; Methemoglobinemia

Topics: Animals; Ascorbic Acid; Body Weight; Carbon Isotopes; Drug Stability; Guinea Pigs; Hydroxylamines; Male; Methemoglobinemia; Nitrites; Oxygen Consumption; Thiocyanates; Time Factors

Topics: Aniline Compounds; Ascorbic Acid; Child, Preschool; Diarrhea, Infantile; Erythrocytes; Glycolysis; Humans; Infant; Male; Methemoglobinemia; Methylene Blue; Oxidation-Reduction; Poisoning

Topics: Adult; Aldehyde-Lyases; Ascorbic Acid; Erythrocytes; Fructosephosphates; Glucose-6-Phosphate Isomerase; Glucosephosphate Dehydrogenase; Glutathione Reductase; Glyceraldehyde-3-Phosphate Dehydrogenases; Glycerophosphates; Hexokinase; Humans; Isomerases; L-Lactate Dehydrogenase; Male; Methemoglobin; Methemoglobinemia; Oxidoreductases; Phosphofructokinase-1; Phosphoglucomutase; Phosphogluconate Dehydrogenase; Phosphoglycerate Kinase; Phosphopyruvate Hydratase; Pyruvate Kinase; Transferases; Trioses

Topics: Acetanilides; Ascorbic Acid; Cyanosis; Drug Industry; Humans; Methemoglobinemia; Methylene Blue; Occupational Diseases; Poisoning

Topics: Ascorbic Acid; Dihydrolipoamide Dehydrogenase; Female; Heterozygote; Humans; Infant, Newborn; Infant, Newborn, Diseases; Metabolism, Inborn Errors; Methemoglobinemia; Methylene Blue; Pedigree

Topics: Adult; Anemia, Hemolytic; Ascorbic Acid; Female; Heinz Bodies; Humans; Methemoglobinemia

Topics: Ascorbic Acid; Child, Preschool; Cyanosis; Dapsone; Dyspnea; Female; Heart Rate; Hemoglobins; Humans; Hyperkinesis; Infant; Leukocyte Count; Male; Methemoglobinemia; Methylene Blue; Vomiting

Topics: Abortion, Spontaneous; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Blood Volume; Female; Fetal Death; Fetus; Guinea Pigs; Hemoglobinometry; Hysterectomy; Laparotomy; Methemoglobin; Methemoglobinemia; Methylene Blue; Nitrites; Pregnancy; Pregnancy Complications; Pregnancy, Animal

Topics: Animals; Ascorbic Acid; Female; Hemoglobins; Male; Methemoglobin; Methemoglobinemia; Nitrites; Poultry; Sex Factors

Topics: Adrenal Glands; Anemia; Animals; Ascorbic Acid; Chemical Industry; Environmental Exposure; Environmental Health; Maximum Allowable Concentration; Methemoglobinemia; Mice; Occupational Medicine; Phenols; Rabbits; Rats; Skin Absorption

Topics: Adult; Ascorbic Acid; Blood Protein Electrophoresis; Clinical Enzyme Tests; Hematocrit; Hemoglobinometry; Humans; Male; Metabolism, Inborn Errors; Methemoglobin; Methemoglobinemia; Oxidoreductases; Spectrophotometry; Thailand

Topics: Anesthesia, Obstetrical; Anesthesia, Spinal; Anesthetics, Local; Animals; Anura; Ascorbic Acid; Cats; Female; Fetus; Humans; Infant, Newborn; Maternal-Fetal Exchange; Methemoglobinemia; Methylene Blue; Pregnancy; Prilocaine; Umbilical Arteries; Umbilical Veins

Topics: Adult; Ascorbic Acid; Erythrocytes; Humans; Male; Methemoglobinemia; Methylene Blue; Oxidoreductases

Topics: Ascorbic Acid; Child; Child, Preschool; Female; Humans; Methemoglobin; Methemoglobinemia; Methylene Blue

Topics: Ascorbic Acid; Carbon Dioxide; D-Amino-Acid Oxidase; Erythrocytes; Glutathione; Glycolysis; Hexosephosphates; Humans; Hydrogen Peroxide; In Vitro Techniques; Methemoglobinemia

Topics: Ascorbic Acid; Benzocaine; Clinical Laboratory Techniques; Cyanosis; Drug Therapy; Humans; Infant; Laboratories; Methemoglobinemia; Methylene Blue; Suppositories; Toxicology

Topics: Ascorbic Acid; Diseases in Twins; Humans; Methemoglobinemia; Piperazine; Piperazines; Poisoning; Toxicology; Twins

Topics: Ascorbic Acid; Erythrocytes; Humans; In Vitro Techniques; Methemoglobinemia; Oxidation-Reduction

Topics: Adult; Aged; Ascorbic Acid; Central Nervous System Stimulants; Child, Preschool; Exchange Transfusion, Whole Blood; Humans; Infant; Methemoglobinemia; Methylene Blue; Middle Aged; Oxygen Inhalation Therapy

Topics: Animals; Ascorbic Acid; Blood Chemical Analysis; Brassica napus; Cooking; Fertilizers; Food Analysis; Guinea Pigs; Methemoglobin; Methemoglobinemia; Nitrates; Research; Toxicology; Vegetables

Topics: Ascorbic Acid; Blood Protein Electrophoresis; Child; Cyanosis; Genetics, Medical; Heart Diseases; Hemoglobins; Humans; Infant; Infant, Newborn; Methemoglobin; Methemoglobinemia; Methylene Blue; Oxidoreductases; Pathology; Spectrophotometry

Topics: Ascorbic Acid; Cyanosis; Diagnosis, Differential; Electrocardiography; Genetics, Medical; Humans; Methemoglobinemia

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Biomedical Research; Humans; Hungary; Infant; Infant, Newborn; Methemoglobinemia; Nitrates; Toxicology; Water Pollution; Water Supply; Water Wells

Topics: Adenosine Triphosphate; Anemia; Anemia, Hemolytic; Ascorbic Acid; Blood Chemical Analysis; Blood Glucose; Carbon Dioxide; Erythrocyte Count; Erythrocytes; Geriatrics; Glucosephosphate Dehydrogenase; Glutathione; Hemoglobinometry; Hemolysis; Kidney Diseases; Metabolism; Methemoglobinemia; Nucleosides; Pyelonephritis; Renal Insufficiency; Sulfamethizole; Sulfathiazoles; Sulfonamides; Toxicology; Urinary Catheterization

Topics: Ascorbic Acid; Dihydrolipoamide Dehydrogenase; Drug Therapy; Erythrocytes; Humans; Metabolism, Inborn Errors; Methemoglobin; Methemoglobinemia; Methylene Blue; NAD; Sulfites; Vitamin K; Vitamin K 3

Topics: Ascorbic Acid; Cytochrome-B(5) Reductase; Dihydrolipoamide Dehydrogenase; Drug Therapy; Genetics, Medical; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Metabolic Diseases; Methemoglobinemia; Methylene Blue; NAD; NADP

Topics: Ascorbic Acid; Cyanosis; Diagnosis, Differential; Dihydrolipoamide Dehydrogenase; Humans; Metabolic Diseases; Methemoglobinemia

Topics: Ascorbic Acid; Humans; Male; Methemoglobin; Methemoglobinemia; Methylene Blue; Vitamins

Topics: Ascorbic Acid; Humans; Methemoglobin; Methemoglobinemia; Nitrates; Vitamins

Topics: Ascorbic Acid; Copper; Humans; Methemoglobinemia

Topics: Ascorbic Acid; Methemoglobinemia; Nitrites; Vitamins

Topics: Ascorbic Acid; Child; Humans; Infant; Methemoglobinemia; Methylene Blue

Topics: Ascorbic Acid; Humans; Methemoglobinemia; Methylene Blue; Vitamins

Topics: Ascorbic Acid; Cyanosis; Erythrocytes; Humans; Methemoglobinemia; Methylene Blue; Vitamins

Topics: Ascorbic Acid; Hemoglobins; Humans; Methemoglobinemia

Topics: Ascorbic Acid; Hemoglobins; Humans; Methemoglobin; Methemoglobinemia