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[Methemoglobinemia induced by repeated abuse of lidocaine viscous gel].

Lidocaine use may lead to methemoglobinemia. Lidocaine is clinically widely used as an anaesthesic drug, however its toxic effect is rare. We report a high methemoglobinemia level of 31.1% following repeated Xylocaine gel oral applications. New metabolic pathways of lidocaine have been reported leading to dimethylphenylhydroxylamine in humans. This metabolism is very similar to the aniline derivative ones, and may explain lidocaine methemoglobinemia effect.

Adult↗

Methemoglobinemia following unintentional ingestion of sodium nitrite--New York, 2002.

Methemoglobinemia is an unusual and potentially fatal condition in which hemoglobin is oxidized to methemoglobin and loses its ability to bind and transport oxygen. The most common cause of methemoglobinemia is the ingestion or inhalation of oxidizing agents such as nitrates or nitrites (e.g., sodium nitrite, which is used commonly as a preservative in curing meats and fish). This report summarizes the investigation of an incident of methemoglobinemia in five members of a household in New York who became ill after eating a meal seasoned with a white crystalline substance from a plastic bag labeled "Refined Iodized Table Salt" (Figure). The findings underscore the need for proper storage of hazardous materials to avoid unintentional ingestion and the importance of collaboration by multiple agencies to address a potential public health emergency.

Adult↗

Suspected methemoglobinemia following awake intubation: one possible effect of benzocaine topical anesthesia--a case report.

Methemoglobinemia is a potential negative side effect associated with the use of benzocaine for topical anesthesia. A healthy patient admitted for an outpatient orthopedic procedure developed the clinical symptomatology of methemoglobinemia after topicalization of the airway with benzocaine. The patient subsequently responded to appropriate treatment and was fit for discharge the same day. Methemoglobinemia should be suspected in cases where decreased pulse oximeter readings develop in patients who have received benzocaine preoperatively. Appropriate steps should be taken to support the airway and oxygenation and monitor the patient while medication is administered to reduce methemoglobin to hemoglobin.

Adult↗

Congenital methemoglobinemia due to NADH-methemoglobin reductase deficiency in three Indian families.

Congenital methemoglobinemia is a relatively rare clinical disorder characterized by life-long cyanosis, caused by either an inherited mutant hemoglobin (Hb-M) or deficiency of physiologically active NADH-dependent methemoglobin reductase (NADH-MR). NADH-MR deficiency leads to two different types of recessive congenital methemoglobinemia. In type I, cyanosis is the only major symptom and NADH-MR deficiency is restricted only to the red blood cells. In type II, cyanosis is associated with severe mental retardation and neurological impairment. The objective of this study is to establish the cause of cyanosis in our cases of congenital methaemoglobinemia. Erythrocyte NADH-MR activity was assayed spectrophotometrically. Spectral analysis of the hemolysate treated with potassium ferricyanide was recorded between 400-700 nm and Hb electrophoresis on starch gel at pH 7.0 was done to rule out the presence of Hb-M. NADH-MR deficiency was detected in 3 families. There was a history of consanguinity in one of these cases. The three propositi presented with breathlessness, fever and peripheral cyanosis. There was no history of cardiac illness or exposure to drugs and chemicals. There were no signs and symptoms of mental retardation. The presence of Hb-M was ruled out. Hb-A2, Hb-F, G6PD activity and reduced glutathione levels were normal. NADH-MR activity in all the cases ranged from 4.1 to 9.2 IU/g Hb (normal range 7.0-24.0 IU/g Hb). We describe NADH-MR deficiency in three unrelated cases (age 4 months to 6 years) where the activity of the enzyme was 30-40% of normal. These three cases of congenital methemoglobinemia are due to type-I NADH-MR deficiency without mental retardation.

Child↗

Prolonged hemolysis and methemoglobinemia following organic copper fungicide ingestion.

Acute ingestion of copper sulfate has been reported to cause gastrointestinal injury, hemolysis, methemoglobinemia, hepatorenal failure, shock; or even death. The toxicity of organocopper compounds, however, remains largely unknown. A 40-y-old man attempted suicide by ingesting some 50 ml of Sesamine fungicide. He immediately developed headache, vomiting and abdominal pain, followed by progressive dyspnea, cyanosis, dark urine and diarrhea. Severe methemoglobinemia and hemolysis were documented, and treatment with ascorbic acid and hydration was commenced. He was referred to our service 3 d later for methylene blue treatment. Despite the above treatment, his symptomatology persisted and it was not until 5 d post-ingestion that the implicated fungicide was identified as copper-8-hydroxyquinolate. BAL therapy and plasma exchange were instituted, which decreased his plasma hemoglobin from 1,300 mg/dL to 29.1 mg/dL, and lowered his methemoglobin level from 20.9% to 1.1%. His serum and urine copper concentration dropped from 238 microg/dL to 96 microg/dL and from 112 microg/dL to 16 microg/dL, respectively. He was discharged uneventfully 18 d post-ingestion. Pre-existing glucose-6-phosphate dehydrogenase (G6PD) deficiency as well as copper-induced inhibition of G6PD activity was documented during hospitalization. Organocopper compounds may cause prolonged hemolysis and methemoglobinemia through oxidative stress, especially among patients with G6PD deficiency. Antidotal therapy with methylene blue is not likely to be effective in this setting: treatment with intensive supportive measures and other therapeutic options, such as plasma exchange, should be sought.

Adult↗

[Congenital methemoglobinemia: a rare case of cyanosis in the newborn].

We report the case of a newborn presenting a cyanosis after the birth with a good general state. Congenital methemoglobinemia is a rare disease which is characterized by a brutal appearance, in early infancy, of a bluish skin color not regressing with oxygen inspiration, and by a good general state. It is due to the recessive autosomal NADH-cytochrome b5 reductase (EC. 1.6.2.2) deficiency. This enzyme normally allows the reduction of the physiologically formed methemoglobinemia. Two forms of congenital methemoglobinemia have to be distinguished: the benign form (type I) and the severe form (type II).

Cyanosis↗

Benzocaine-induced methemoglobinemia during transesophageal echocardiography.

Acquired or toxic methemoglobinemia is an uncommon complication of topically administered anesthetic agents in patients of all ages-but particularly in pediatric and elderly patients. This report describes a case of acquired methemoglobinemia that occurred after benzocaine spray was applied orally to a 69-year-old white woman weighing 175 lb who was undergoing transesophageal echocardiography. Patient care was successfully managed. Fundamental concepts regarding methemoglobinemia are also reviewed to heighten physician awareness of this potentially life-threatening complication associated with the application of common topical anesthetic agents.

Aged↗

Serine-proline replacement at residue 127 of NADH-cytochrome b5 reductase causes hereditary methemoglobinemia, generalized type.

Hereditary methemoglobinemia is an autosomal recessive disorder characterized by NADH-cytochrome b5 reductase (b5R) deficiency. In an attempt to clarify the molecular mechanisms involved in the enzyme deficiency, we isolated the b5R gene from a patient homozygous for hereditary methemoglobinemia, generalized type, and compared its nucleotide sequence with that of the normal NADH-cytochrome b5R gene. Only one difference was observed; a thymidine at the first position of codon 127 (TCT) was altered to a cytidine in the b5R gene of the patient, resulting in replacement of serine with proline. Dot blot hybridization of the amplified DNA samples with allele-specific oligonucleotide probes showed that the proband and her brothers were homozygous for this mutation and that their father was heterozygous. Although the activity of b5R in lymphoblastoid cells from homozygotes was reduced to 10% of the normal level, RNA blot and protein blot analyses of the lymphoblastoid cells showed that synthesis of b5R messenger RNA and the b5R polypeptide were normal. Serine at residue 127 is presumed to be in an alpha-helix structure that is part of a nucleotide-binding domain. These observations suggest that replacement of Pro-127 causes a significant conformation change in the nucleotide-binding domain that affects electron transport from NADH to cytochrome b5. Functional enzyme deficiency results in a generalized type of hereditary methemoglobinemia.

Adult↗

[Molecular analysis of the structure of the mutant NADH-cytochrome b5 reductase gene causing methemoglobinemia].

Hereditary methemoglobinemia is a genetic disorder, transmitted as an autosomal recessive trait, characterized by NADH-cytochrome b5 reductase (b5R) deficiency. It is classified three types, erythrocyte, generalized, and blood cell types, in terms of tissues in which the enzyme is deficient. In attempt to analyse molecular mechanisms involved in the enzyme deficiency, we isolated b5R genes from the patient of hereditary methemoglobinemia, generalized type. 1. Sequence comparison of both b5R genes indicated that a thymidine at first position of codon 127 was altered to a cytidine, resulting in replacement of serine with proline. 2. Dot blot hybridization of the PCR-amplified DNA with allele-specific oligonucleotide probes showed that the patient was homozygous for this mutation. 3. Secondary structure prediction by the Chou-Fasman method showed that Ser-127 is presumed to be in an alpha-helix structure of a nucleotide-binding domain. 4. These observations showed that extension of the alpha-helix structure caused by replacement of Pro-127 affects the electron transport and the result is a generalized type of hereditary methemoglobinemia.

Amino Acid Sequence↗

Methemoglobinemia resulting from smoke inhalation.

Methemoglobinemia following fire exposure is largely unrecognized. Fire related morbidity and mortality are customarily attributed to thermal injury, associated trauma, and carbon monoxide poisoning. More recently, cyanide poisoning has been described from the inhalation of hydrogen cyanide liberated from of burning plastics (1). Symptoms of tissue hypoxia and cyanosis resulting from methemoglobinemia may be difficult to diagnose in the presence of thermal injury, cyanide and/or carbon monoxide poisoning. Relatively low levels of methemoglobin could complicate concomitant carbon monoxide poisoning by additive or synergistic effects on oxygen binding and delivery. We report 3 cases of significant methemoglobinemia (levels of 19, 12, and 12%) in survivors of a dwelling fire and review the literature with regard to this phenomenon.

Aged↗

[Cyanosis in children caused by inherited methemoglobinemia due to deficiency of NADH-dependent methemoglobin reductase in erythrocytes].

Two cases of the congenital methemoglobinemia in children due to the deficiency of NADH-dependent methemoglobin reductase in erythrocytes. These children were referred to the Cardiological Ward at the Child Health Centre with suspected cyanotic heart defect. Cardiological examinations excluded heart defect but an increased blood methemoglobin level and decreased activity of NADH-dependent methemoglobin reductase were found, that caused methemoglobinemia. Methylene blue and vitamin C diminished cyanosis. These cases advocate inclusion of methemoglobinemia into differential diagnosis of cyanotic disorders especially if there is no evident pathology in cardio-vascular system.

Adolescent↗

Methemoglobinemia following metoclopramide therapy in an infant.

An infant with persistent vomiting was found to have methemoglobinemia. Review of his history revealed that he had been treated with metoclopramide. No other etiology of the methemoglobinemia was identified. It is concluded that the use of metoclopramide in a sick neonate can cause transient methemoglobinemia. Similar cases reported in the foreign literature are reviewed.

Humans↗

Enzymopenic hereditary methemoglobinemia: a clinical/biochemical classification.

Recessively inherited NADH-cytochrome B5 reductase deficiency, when present in the homozygous or doubly heterozygous form, is manifested by two different clinical presentations, depending on the nature and cellular distribution of the mutant enzyme. The observations supporting a clinical and biochemical classification of enzymopenic hereditary methemoglobinemia are summarized. Type I, with deficiency demonstrable only in the erythrocytes, presents as uncomplicated, benign methemoglobinemia. Type II, generalized cytochrome B5 deficiency demonstrable in all of the tissues that have been examined, is accompanied by severe, lethal, progressive neurological disability, in addition to methemoglobinemia. Type III deficiency is limited to hematopoietic cells and resembles Type I clinically. Type IV, also clinically like Type I, is associated with deficiency of the cofactor, cytochrome B5. Except for Type IV, the different types appear to be the result of mutations in paired alleles of a gene on chromosome 22 that affect the catalytic activity or stability of the cytochrome B5 reductase.

Cytochrome Reductases↗

Methemoglobinemia resulting from absorption of nitrates.

Three cases of toxic methemoglobinemia resulted from absorption of nitrate salts through burned skin areas. In addition to the unusual route of intoxication, this report emphasizes the occupational hazard of methemoglobinemia in workers exposed to nitrogen salts and the importance of rapid diagnosis and treatment. The diagnosis of methemoglobinemia should be suspected in any case of cyanosis refractory to oxygen therapy. Appropriate treatment should include oxygen, methylene blue, and exchange transfusion in clinically severe cases.

Accidents, Occupational↗

[Carrot soup as the cause of methemoglobinemia in an infant. Case report].

The AA. report a typical case of methemoglobinemia from carrot soup ingestion in an infant. In the discussion they point out: first, clinical findings for diagnosis of methemoglobinemia; second, criteria for an etiological diagnosis; third, they analyse the pathogenesis of methemoglobinemia resulting from carrot soup in infants. At last the AA. briefly indicate how to prevent and treat this complication.

Food Preservation↗

Boilerbaisse: an outbreak of methemoglobinemia in New Jersey in 1992.

BACKGROUND: On October 20, 1992, > 40 children from one elementary school visited the school nurse due to the acute onset of blue lips and hands, vomiting, and headache during and after the school lunch periods. Forty-nine children were seen by physicians that day and 14 were hospitalized. Laboratory analysis revealed methemoglobinemia in many of the children. All recovered in 36 hours. OBJECTIVE: A case-control study was supplemented by environmental and laboratory investigations to determine the outbreak source. METHODS: Cases were selected based on the laboratory diagnosis of methemoglobinemia (methemoglobin level > 2%). Children whose methemoglobin levels were missing or < 2% were excluded from analysis. Controls were obtained by selecting every third name from a school roster. The parents of 29 students who met the case definition and 52 controls were interviewed. RESULTS: All 29 cases and 33% (17/52) of the controls ate soup during the school lunch (odds ratio undefined, lower 95% confidence limit 16.1). Two pots of soup were prepared from ready-to-serve cans, which were diluted with water and enriched with a commercially prepared flavor enhancer. The school's boiler, dormant during the previous 5 months, was restarted on the morning of the outbreak. The boiler also served as a tankless hot water heater. Laboratory analysis of the soup identified abnormally high quantities of nitrite (459 ppm) and sodium metaborate, major components of the boiler water treatment solution. Undiluted soup from the same lot had 2.0 ppm nitrites; the flavor enhancer had 2.2 ppm nitrites. Nitrites were present in the hot potable water system (4 to 10 ppm) and absent in the cold potable water system. CONCLUSIONS: This outbreak of methemoglobinemia due to nitrite poisoning was traced to soup contaminated by nitrites in a boiler additive. Nitrites are ubiquitous and potentially hazardous inorganic ions. Extreme caution should be used when the possibility for toxic human exposure to nitrites exists.

Case-Control Studies↗

[Congenital and acquired methemoglobinemia and its therapy].

The hemoglobin (Hb) function is to bear oxygen. Hb is under the exposition of high oxygen concentration in the lung capillaries and it is very slowly oxidated to methemoglobin (MetHb) which is not able to bear oxygen. Enzymatic equipment of erythrocyte protects Fe2+ in HEM in front of the oxidation to Fe3+. It is created 3% of MetHb daily. This action is considered to be autooxidation and it is simultaneously reduced by creation of "complex formation" of MetHb and cytochrome b5. The physiological level of MetHb is 0-2% in the peripheral blood. The MetHb level is enhanced by hereditary impairment of the erythrocyte enzyme apparatus or by changed Hb structure. The patients have enhanced MetHb level in peripheral blood in the range of 1-30%. The only symptom which is created is peripheral cyanosis with neither subjective nor objective difficulties. The patients do not require any treatment. They are very sensitive on receipt of oxidative agents. Occurrence of acquired methemoglobinemia is more frequent in clinical praxis. Administration of oxidative agents is the reason of the disease. The most frequent oxidative agents are sulfones, local anesthetics, enhanced contents of nitrates in vegetables from unsuitable manure soil. The acquired methemoglobinemia causes minimal clinical problems depending on the doses of administered drug and abates after its discontinuation quickly. Only occasionally it causes clinically expressive symptoms. The level above 10% of MetHb causes peripheral cyanosis. The level of MetHb higher than 35% causes general symptoms which are results of the tissue hypoxia. The level about 70% of MetHb is associated with coma and may have fatal outcome. When the level of MetHb is not very high it abates after discontinuation of the administration of causative drug. In the case of high level of MetHb the drug of choice is administration of hyperbaric oxygen, methylene blue, ascorbic acid intravenously or riboflavin in high doses. In the case of deficit of glucoso-6-phosphate-dehydrogenase the administration of methylene blue is contraindicated, because of worsen of the methemoglobinemia.

Humans↗

Methemoglobinemia caused by benzocaine topical spray.

Acute methemoglobinemia is a medical emergency that can rapidly become fatal. A substantial number of drugs, including topical preparations, can precipitate this condition. I report a rare example of severe, acute methemoglobinemia caused by oropharyngeal anesthesia with topical benzocaine spray for orogastric intubation. The pathophysiology, diagnosis, and treatment of methemoglobinemia are reviewed briefly.

Acute Disease↗