Epidemiology
- G6PD Deficiency (see Glucose-6-Phosphate Dehydrogenase Deficiency, [[Glucose-6-Phosphate Dehydrogenase Deficiency]]): risk factor for acquired methemoglobinemia
- Endemic in populations of Mediterranean and African descent
Etiology
Hereditary/Congenital Methemoglobinemia
Hemoglobin M Disease
- General Comments: usually autosomal dominant
- Hb Ms
- Hb MIwate
- Hb MBoston
- Hb MHyde Park
- Hb MSaskatoon
Hemoglobin E Disease
- Hb E beta-thalassemia patients have been demonstrated to have increased methemoglobin levels
NADH Cytochrome b5 Reductase (cyb5R) Deficiency
- General Comments
- Autosomal recessive
- Mechanism: decreased enzymatic reduction of methemoglobin back to normal hemoglobin
- Type I Cytochrome b5 Reductase (cyb5R) Deficiency: most common type (represents 85-90% of cases)
- Endemic in specific Native American tribes (Navajo, Athabaskan Alaskans) and Yakutsk people of Siberia
- Cytochrome b5 reductase (cyb5R) deficiency is limited to red blood cells
- Type II Cytochrome b5 Reductase (cyb5R) Deficiency: represents 10-15% of cases
- Cytochrome b5 reductase (cyb5R) deficiency in multiple tissues (including red blood cells, liver, fibroblasts, and brain)
- Clinical features
- Severe central nervous symptoms (encephalopathy, microcephaly, hypertonia, athetosis, opisthotonos, strabismus, mental retardation, growth retardation)
- Cyanosis: evident at an early age
- Type III Cytochrome b5 Reductase (cyb5R) Deficiency
- Cytochrome b5 reductase (cyb5R) deficiency in red blood cells, white bood cells, platelets
- Clinical features: cyanosis is the only symptom
- Type IV Cytochrome b5 Reductase (cyb5R) Deficiency
- Cytochrome b5 reductase (cyb5R) deficiency is limited to red blood cells
- Clinical features: cyanosis is the only symptom
NADPH-Flavin Reductase Deficiency
- May also cause methemoglobinemia
Cytochrome b5 Deficiency
Anesthetics
- General Comments: while skin/mucosal breaches may increase absorption of the anesthetic agents, methemoglobinemia may occur due to either a previously-undiagnosed methemoglobin reductase enzyme deficiency or idiosyncratic toxicity
- Benzocaine (see Benzocaine, [[Benzocaine]])
- Epidemiology: common etiology
- Incidence of methemoglobinemia when using benzocaine during trans-esophageal echocardiogram (TEE) has been reported to be 1:1000 cases
- In TEE-associated cases, active infection and anemia appear to increase the risk of methemoglobinemia
- Physiology: unclear mechanism, as prior/subsequent benzocaine exposure may not elicit methemoglobinemia in affected patients
- Clinical: severe methemoglobinemia may occur
- Bupivicaine (see Bupivicaine, [[Bupivicaine]])
- Epidemiology: common etiology
- Cetacaine
- Epidemiology: common etiology
- Lidocaine (see Lidocaine, [[Lidocaine]])
- Epidemiology: common etiology
- Prilocaine
- Epidemiology: common etiology
Nitrites and Nitrates (see Nitrites and Nitrates, [[Nitrites and Nitrates]])
- Amyl Nitrite
- Cerium Nitrate
- Farryl Nitrite
- Ingestion of High Nitrite/Nitrate Foods: beets, spinach, carrots, borage, chard
- Ingestion of Nitrite-Contaminated Well Water: cases have been reported where well water has been contaminated by nitrite runoff from fertilized farm fields
- Ingestion of Nitrites in Packaged Foods
- Inhaled Nitric Oxide (iNO) (see Nitric Oxide, [[Nitric Oxide]]): however, in clinical trials of iNO in ARDS, clinically significant methemoglobinemia was not observed
- Isobutyl Nitrite (Inhaled “Rush”, “Poppers”) (see Isobutyl Nitrite, [[Isobutyl Nitrite]])
- Isosorbide Dinitrate (see Isosorbide, [[Isosorbide]])
- Methyl Nitrite
- Nitroglycerin (see Nitroglycerin, [[Nitroglycerin]])
- Nitroprusside (Nipride) (see Nitroprusside, [[Nitroprusside]])
- Silver Nitrate (see Silver Nitrate, [[Silver Nitrate]])
- Sodium Nitrite (see Sodium Nitrite, [[Sodium Nitrite]])
Anti-Malarials
Anti-Neoplastic Agents
- 3-Aminopyridine-2-Carboxaldehyde Thiosemicarbazone (Triapine): ribonucleotide reductase inhibitor
- Cyclophosphamide (Cytoxan) (see Cyclophosphamide, [[Cyclophosphamide]])
- Flutamide (Eulexin) (see Flutamide, [[Flutamide]])
- Ifosfamide (Ifex) (see Ifosfamide, [[Ifosfamide]]): due to interaction between 4-thiofosfamide metabolite and glutathione -> resulting in oxidative stress
Other Drugs/Toxins
- 2,4-Dinitrophenol: weight loss agent
- Acetaminophen (Tylenol) (see Acetaminophen, [[Acetaminophen]])
- Acetanilid (see Acetanilid, [[Acetanilid]])
- Ammonium Carbonate: smelling salts
- Benzene Derivatives
- Aniline/Aniline Dyes/Aniline Derivatives (Aminophenol, Phenylhydroxylamine)
- Naphthalene
- Nitrobenzene: precursor to aniline
- Resorcinol
- Bromates: municipal water contaminants
- Chrlorates: oxidizers which are found in matches, explosives, and fungicides
- Clofazimine (see Clofazimine, [[Clofazimine]])
- Cocaine (see Cocaine, [[Cocaine]])
- Copper Sulfate
- Curcumin: the main curcuminoid in turmeric has been demonstrated to cause methemoglobinemia in rats treated with dapsone
- Dapsone (see Dapsone, [[Dapsone]])
- Epidemiology: common etiology
- Significant methemoglobinemia may be seen with Dapsone use to treat dermatitis herpetiformis or pneumocystis jirovecii
- Risk is probably dose-related
- Induction of Dapsone Tolerance: cimetidine (see Cimetidine, [[Cimetidine]]) may be used to chronically enhance Dapsone tolerance, as it is a selective inhibitor of N-hydroxylation and chronically lowers methemoglobin levels by >25%
- Ingestion of Fava Beans in a Patient with G6PD Deficiency (see Favism, [[Favism]])
- Herbicides/Pesticides
- Aluminum Phosphide
- Indoxacarb
- Paraquat (Dipyridylium) (see Paraquat, [[Paraquat]])
- Indigo Carmine: intravenous dye used during urologic surgery (it is rapidly filtered by the kidneys and turns the urine blue)
- Menadione (“Vitamin K3”): nutritional supplement (it is an analog of 1,4-naphthoquinone)
- Methylene Blue (see Methylene Blue, [[Methylene Blue]])
- At high doses, methylene blue functions as an oxidant: it can cause acute hemolysis in patients with G6PD deficiency -> further decreasing oxygen delivery
- At high doses, methylene blue can also paradoxically cause methemoglobinemia
- Metoclopramide (Reglan) (see Metoclopramide, [[Metoclopramide]])
- Naphthalene (see Naphthalene, [[Naphthalene]]): moth balls
- Naphthoquinone: plants with compounds derived from naphthoquinone are used in China and South America for their medicinal properties
- Nitroethane: nail polish remover
- Nitrofurans: anti-microbials
- Furazolidone
- Furylfuramide
- Nifuratel
- Nifuroxazide
- Nifurquinazol
- Nifurtimox
- Nifurtoinol
- Nifurzide
- Nitrofurantoin (Macrodantin) (see Nitrofurantoin, [[Nitrofurantoin]])
- Nitrofurazone
- Ranbezolid
- P-Aminosalicylic Acid
- Phenacetin (see Phenacetin, [[Phenacetin]])
- Phenazopyridine (Pyridium) (see Phenazopyridine, [[Phenazopyridine]])
- Phenylamine: psychoactive stimulant used as a recreational drug
- Rasburicase (Elitek) (see Rasburicase, [[Rasburicase]])
- Patients with low inherited or acquired catalase activity may be at risk for methemoglobinemia after rasburicase administration: due to the formation of hydrogen peroxide
- Some authors recommend the measurement of catalase activity before administering rasburicase
- Smoke Inhalation (see Smoke Inhalation, [[Smoke Inhalation]]): due to inhalational exposure to oxidants
- Sodium Chlorite (see Sodium Chlorite, [[Sodium Chlorite]])
- Sulfonamides (see Sulfonamides, [[Sulfonamides]])
- Toxic Mushrooms (see Toxic Mushrooms, [[Toxic Mushrooms]]): for gyromitrin-containing mushrooms
- Zopiclone (Imovane, Zimovane) (see Zopiclone, [[Zopiclone]])
Miscellaneous Other Conditions
- Cirrhosis (see End-Stage Liver Disease, [[End-Stage Liver Disease]]): red blood cells in cirrhotic patients undergo severe oxidative stress, especially in the setting of bleeding complications: levels of methemoglobin are significantly higher in the red blood cells of bleeding cirrhotics than in non-bleeding cirrhotics [MEDLINE]
- Post-Splenectomy: increased methemoglobin levels have been observed in patients following splenectomy
- Sepsis (see Sepsis, [[Sepsis]]): methemoglobin levels may increase in sepsis [MEDLINE]
- May be related to synthesis of nitric oxide that occurs in sepsis: nitric oxide is converted to methemoglobin and nitrate
Physiology
Normal Methemoglobin Physiology
- Auto-Oxidation of Hemoglobin to Methemoglobin: in normal individuals, hemoglobin is auto-oxidized to methemoglobin at the rate of 0.5-3% per day
- Methemoglobin levels of <1-3% are considered normal
- Potential Chemical Mechanisms to Reduce Methemoglobin Back to Hemoglobin
- NADH-Dependent Reaction Catalyzed by Cytochrome b5 Reductase (b5R): this is the only physiologically important mechanism under normal conditions (accounting for clearance of 95-99% of the methemoglobin that is produced under normal circumstances)
- Generation of NADPH by Glucose-6-Phosphate Dehydrogenase (G6PD) in the Hexose Monophosphate Shunt within the Red Blood Cell: this mechanism is not natively physiologically active, as it requires an extrinsically-administered electron acceptor (such as methylene blue and riboflavin)
- This mechanism becomes important in the treatment of methemoglobinemia: methylene blue accelerates the NADPH-dependent methemoglobin reduction pathway
- Note: G6PD deficiency is a risk factor for acquired methemoglobinemia
Pathophysiology in Patient with Methemoglobinemia
- Oxidation of Iron in Hemoglobin from the Ferrous (Fe2+) to the Ferric (Fe3+) State: results in a “functional anemia” and consequent decreased oxygen delivery to tissues
- Ferric Hemes of Methemoglobin are Unable to Bind Oxygen
- Left-Shifting of Hemoglobin Dissociation Curve: due to increased oxygen affinity by the remaining ferrous hemes in the hemoglobin tetramer
- Left shifting results in impaired oxygen unloading at the tissues
Predisposition of Premature Neonates and Infants to Methemoglobinemia
- Factors Increasing Risk of Methemoglobinemia in Premature Neonates/Infants <4 mo of Age
- Propensity of fetal hemoglobin to more easily oxidize than adult hemoglobin
- Low levels of NADH reductase at birth: NADH reducase levels increase to adult levels by 4 mo of age
- Higher gastric pH with increased basterial conversion of dietary nitrates to nitrites
- Association of methemoglobinemia with gastroenteritis illnesses in infants: this may be related to increased stool loss of bicarbonate
Diagnosis
Pulse Oximetry
- Decreased SpO2
- When Methemoglobin is <30%: pulse oximetry will overestimate the percentage of oxyhemoglobin in presence of methemoglobin by an amount roughly equal to 50% of the amount of methemoglobin present
- In presence of 20% methemoglobin and a SpO2 of 90%: percentage of oxyhemoglobin will be 80%
- When Methemoglobin is >30%: pulse oximetry will plateau at about 85%
- Note that severity of the cyanosis does not correspond to the pulse oximetry reading
- Principle of Pulse Oximetry: pulse oximeter only measures the relative absorbance of 2 light wavelengths (660 nm and 940 nm) to differentiate oxyhemoglobin from deoxyhemoglobin
- Methemoglobin increases absorption of both light wavelengths (although moreso at 940 nm): therefore, it optically interferes with the pulse oximetry
- Newer Generation Multi-Wavelength Pulse Oximeters: while these are being developed, their accuracy is still being investigated
Arterial Blood Gas (ABG)
- Appearance of Blood in ABG Syringe: chocolate or brown-blue color
- pO2: normal
- Note that the pO2 reflects the plasma oxygen content and does not reflect the oxygen-carrying capacity of hemoglobin
- Co-Oximetry SaO2: normal
- “Saturation Gap” (occurs in methemoglobinemia): difference between SpO2 measured from pulse oximetry and the SaO2 calculated from co-oximetry
- Co-Oximetry
- Principle: co-oximeter is a simplified spectrophotometer that can measure the relative absorbance of 4 different wavelengths of light
- It quantifies the percentages of methemoglobin (absorbs at 631 nm), carboxyhemoglobin, oxyhemoglobin, and deoxyhemoglobin
- Newer co-oximeters can also measure sulfhemoglobin, which may be confused with methemoglobin on older devices
- Normal Range of Methemoglobin: <1-3%
- Relationship of Percentage of Methemoglobin to Clinical Symptoms: clinical symptoms are correlated with the precentage of methemoglobin
- False-Positive Results
- May occur in presence of sulhemoglobinemia
- May occur in the presence of methylene blue
- May occur in the presence of lipemia
- Inaccuracy: may occur with the use of blood substitutes
Evelyn-Malloy Assay of Methemoglobin
- Technique
- Addition of cyanide, which binds to positively charged methemoglobin -> eliminates the peak at 630-635 nm
- Subsequent addition of ferricyanide -> converts entire specimen to cyanomethemoglobin, which allows measurement of total hemoglobin concentration
- Specificity: more specific than co-oximetry for detection of methemoglobin
- Clinical Utility: this assay is a good confirmatory test and is especially useful after methylene blue administration
Potassium Cyanide Test
- Distinguishes between methemoglobin and sulfhemoglobin
- Methemoglobin reacts with cyanide to form cyanomethemoglobin: bright red color change
- Sulfhemoglobin does not react with cyanide: lack of bright red color change
Drop Test
- Technique: place 1-2 drops of blood onto white filter paper -> in the presence of significant methemoglobinemia, blood will remain dark (ie: will not oxygenate as normal blood would)
- May accelerate process by gently blowing 100% onto the blood drop on the filter paper
Aeration of Tube of Blood with 100% Oxygen
- Technique: bubble 100% oxygen through blood -> in the presence of significant methemoglobinemia, blood will remain dark (ie: will not oxygenate as normal blood would)
Hemoglobin Electrophoresis
- May be used to identify hemoglobin M
Clinical Manifestations
Congenital Methemoglobinemia
Type I Cytochrome b5 Reductase Deficiency-Related Methemoglobinemia
- General Comments: functional deficiency of cytochrome b5 reductase is limited to red blood cells
- Methemoglobin Level: usually 10-35%
- Asymptomatic Cyanosis (see Cyanosis, [[Cyanosis]]): usually the only clinical manifestation and is often present from birth
- Cyanosis is clinically apparent when methemoglobin levels exceed 8-12% (at a normal hemoglobin concentration): equivalent to >1.5 g/dL
- Polycythemia (see Polycythemia, [[Polycythemia]]): rarely observed
Type II Cytochrome b5 Reductase Deficiency-Related Methemoglobinemia
- General Comments: cytochrome b5 reductase is deficient in all cells
- Cyanosis (see Cyanosis, [[Cyanosis]]): often present from birth
- Developmental Abnormalities
- Mental Retardation
- Death Within First Year of Life
Acquired Methemoglobinemia
General Comments
- Relationship of Clinical Symptoms to Methemoglobin Level
- Methemoglobin <1-3%: normal
- Methemoglobin Level 3-15%: slight cyanosis (pale, gray-blue)
- Methemoglobin Level 15-20%: cyanosis (although patients may be relatively asymptomatic)
- Methemoglobin Level 25-50%: headache, dyspnea, dizziness, syncope, weakness, confusion/delirium, palpitations, chest pain
- Methemoglobin Level 50-70%: arrhythmia, delirium, seizures, coma, metabolic acidosis
- Methemoglobin Level >70%: usually fatal
- Influence of Heterozygous State for Cytochrome b5R Deficiency: although patients heterozygous for cytochrome b5R deficiency may develop methemoglobinemia more readily than normals, most acquired methemoglobinemia cases occur in patients who are not heterozygous for cytochrome b5R deficiency
- Influence of Anemia: the clinical symptoms of methemoglobinemia are exacerbated in the presence of anemia
Cardiovascular Manifestations
Neurologic Manifestations
Pulmonary Manifestations
- Appearance of Chocolate-Brown Blood in the Bronchoscopic Field of View: may be observed in cases that occur during bronchoscopy (or during other videoscopic procedures)
- Cyanosis (see Cyanosis, [[Cyanosis]])
- Bluish-brown coloration of skin and mucous membranes
- Cyanosis is clinically apparent when methemoglobin levels exceed 8-12% (at a normal hemoglobin concentration): equivalent to >1.5 g/dL
- Note: in contrast, a deoxyhemoglobin level of 5 g/dL is required to produce clinical cyanosis
- In patients with severe anemia, a higher percentage of methemoglobin is required for cyanosis to be clinically apparent
- These patients are more likely to exhibit signs of hypoxemia and have less degrees of cyanosis, as compared to non-anemic patients
- The clinical symptoms of methemoglobinemia are exacerbated in the presence of anemia
- Lack of Response of Cyanosis to Supplemental Oxygen (in Absence of Cardiopulmonary Disease): hallmark of methemoglobinemia
- While cyanosis in most pulmonary diseases will respond to supplemental oxygen, cyanosis in cardiac disease with a right-to-left intra-cardiac shunt usually do not respond to oxygen administration
- Dyspnea/Respiratory Distress (see Dyspnea, [[Dyspnea]])
Renal Manifestations
Treatment
Treatment of Congenital Methemoglobinemia
- Ascorbic Acid (Vitamin C) (see Vitamin C, [[Vitamin C]]): may cosmetically decrease cyanosis
- Riboflavin (Vitamin B2) (see Vitamin B2, [[Vitamin B2]]): may cosmetically decrease cyanosis
- Methylene Blue (see Methylene Blue, [[Methylene Blue]]): may cosmetically decrease cyanosis
Treatment of Hemoglobin M Disease-Associated Methemoglobinemia
Treatment of Acquired Methemoglobinemia
Withdraw or Avoid the Drug or Offending Agent
- Recommended
- Dietary avoidance of orally ingested precipitant agents
- Removal of clothing that may contain the agent
- Withdrawal/avoidance alone may be adequate in an asymptomatic patient with methemoglobin <20%
Supplemental Oxygen
Dextrose-Containing Intravenous (IV) Fluid
- The NADPH-dependent methemoglobin reductase enzyme system requires glucose for the clearance of methemoglobin
Correction of Metabolic Acidosis
- Bicarbonate therapy may be necessary (especially in cases in infants)
Methylene Blue (see Methylene Blue, [[Methylene Blue]])
- Pharmacology: reduces methemoglobin (by serving as an artificial electron transporter) via a NADPH-dependent pathway
- Results in rapid clinical improvement
- Indications: methylene blue is considered the preferred treatment for patients with the appropriate indications
- Hypoxic Symptoms
- Methemoglobin >20-30%: these levels are considered life-threatening
- Methemoglobin 10% In Setting of Significant Co-Morbid Disease or End-Organ Dysfunction (Cardiac Ischemia, etc): treatment of this group should be considered
- Contraindications
- Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency (see Glucose-6-Phosphate Dehydrogenase Deficiency, [[Glucose-6-Phosphate Dehydrogenase Deficiency]]): methylene blue is ineffective in this group (since it requires NADPH generated by G6PD) and these patients are at high risk for hemolysis after administration
- G6PD Deficiency is found in African-Americans, Mediterranean Descent, Southeast Asians
- Use of Other Serotonergic Agents (see Serotonin Syndrome, [[Serotonin Syndrome]]): since methylene blue functions as a reversible monoamine oxidase (MAO) inhibitor (see Monoamine Oxidase Inhibitors, [[Monoamine Oxidase Inhibitors]]), it may preceipitate the serotonin syndrome
- Hemoglobin M Disease
- NADPH Methemoglobin Reductase (Diaphorase II) Deficiency
- Sulfhemoglobinemia
- Administration: 1-2 mL/kg (of 1% solution) IV over 5 min
- Latency: resolution typically occurs within 1 hr (often within 20 min)
- Re-Treatment: treatment can be repeated in 1 hr if methemoglobin level remains elevated
- Serial Monitoring of Methemoglobin Level (by Evans-Malloy Method)
- Co-oximetry cannot be used to follow serial methemoglobin levels after methylene blue dosing, since methylene blue is erroneously “read” as methemoglobin
- Serial monitoring of methemoglobin levels is recommended, due to prolonged absorption of the offending drug from topical sites/GI tract
- Some cases may manifest significant rebound methemoglobinemia up to 18 hrs later
- Dapsone undergoes enterohepatic recirculation: re-treatment may be necessary
- Adverse Effects/Cautions
- Blue Discoloration of Skin After Administration: methylene blue can impart a blue discoloration to the skin after administration -> note that this does not imply treatment failure
- Excessive Dosing: cumulative doses >7 mg/kg can cause hemolysis, dyspnea, and chest pain
- Interference with Pulse Oximetry: since methylene blue interferes with subsequent pulse oximetry, must not rely on improving SpO2 as a marker for successful treatment
- Serotonin Syndrome (see Serotonin Syndrome, [[Serotonin Syndrome]])
Ascorbic Acid (Vitamin C) (see Vitamin C, [[Vitamin C]])
- Indication
- Administration: moderate dose 300-1000 mg/day in divided doses
- Avoid high dose as this may cause oxidant hemolysis in G6PD deficient patients
Hyperbaric Oxygen (see Hyperbaric Oxygen, [[Hyperbaric Oxygen]])
- Technique: permits tissue oxygenation to occur through oxygen dissolved in plasma, rather than through hemoglobin-bound oxygen
- Indications
- Methemoglobinemia with Either Resistance to Methylene Blue or Contraindications to Its Use
- G6PD Deficiency
- Methemoglobinemia Associated with Aniline Derivatives: may be resistant
PRBC Transfusion/Exchange Transfusion (see Packed Red Blood Cells, [[Packed Red Blood Cells]])
- Indications
- Methemoglobinemia with Either Resistance to Methylene Blue or Contraindications to Its Use
- G6PD Deficiency
- Methemoglobinemia Associated with Aniline Derivatives: may be resistant
Other Agents
- Cimetidine (Tagamet) (see Cimetidine, [[Cimetidine]]): may be used in the setting of dapsone to increase tolerance to this agent
- N-Acetylcysteine (see N-Acetylcysteine, [[N-Acetylcysteine]]): although has been effective in some studies, not currently approved for the treatment of methemoglobinemia
- Riboflavin (Vitamin B2) (see Vitamin B2, [[Vitamin B2]])
References
- Failure of methylene blue treatment in toxic methemoglobinemia. Association with glucose-6-phosphate dehydrogenase deficiency. Ann Intern Med 1971;75:83-6
- Toxic methemoglobinemia after topical anesthesia for transesophageal echocardiography. J Am Soc Echocardiogr. Nov-Dec 1996;9(6):874-6
- Acute effects of inhaled nitric oxide in adult respiratory distress syndrome. Eur Respir J 1998; 12:1164-1171
- Effects of inhaled nitric oxide in patients with acute respiratory distress syndrome: results of a randomized phase II trial. Crit Care Med 1998; 26:15-23
- Elevated methemoglobin in patients with sepsis. Acta Anaesthesiol Scand. Jul 1998;42(6):713-6 [MEDLINE]
- Innovations in mechanical ventilation. Current Opin Crit Care 1999; 5:43-51
- Inhalation of nitric oxide in acute lung injury: results of a European multicentre study. Intensive Care Med 1999; 25:911-919
- Inhaled nitric oxide in ARDS: modulator of lung injury? Intensive Care Med 1999; 25:1024-1026
- Metoclopramide-induced methemoglobinemia in a patient with co-existing deficiency of glucose-6-phosphate dehydrogenase and NADH-cytochrome b5 reductase: failure of methylene blue treatment Haematologica 2001;86:659
- Toxicol Review 2003: 22: 13-27
- J Am Soc Echocardiograpy 2003: 16: 170-175
- Recognition and management of methemoglobinemia and hemolysis in a G6PD-deficient patient on experimental anticancer drug Triapine. Am J Hematol 2006;81:210-1 [MEDLINE]
- Methemoglobinemia and transesophageal echo. Proc West Pharmacol Soc. 2007;50:134-5
- Level of oxidative stress in the red blood cells of patients with liver cirrhosis. Indian J Med Res. Sep 2007;126(3):204-10 [MEDLINE]
- Infection and the Risk of Topical Anesthetic Induced Clinically Significant Methemoglobinemia after Transesophageal Echocardiography. Echocardiography. Aug 31 2009
- Coma, metabolic acidosis, and methemoglobinemia in a patient with acetaminophen toxicity. J Popul Ther Clin Pharmacol. 2013;20(3):e207-11. Epub 2013 Sep 6 [MEDLINE]