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Methemoglobinemia (congenital or acquired) occurs when red blood cells (RBCs) contain methemoglobin at levels higher than 1%. Methemoglobin results from the presence of iron in the ferric form instead of the usual ferrous form. This results in a decreased availability of oxygen to the tissues. Symptoms are proportional to the methemoglobin level and include skin color changes and blood color changes at levels up to 15% (see the image below). As levels rise above 15%, neurologic and cardiac symptoms arise as a consequence of hypoxia. Levels higher than 70% are usually fatal.

See Clues on the Skin: Acute Poisonings, a Critical Images slideshow, to help diagnose patients based on their dermatologic presentations.

Key elements of the history include the following:

Symptoms are proportional to the fraction of methemoglobin. A normal methemoglobin fraction is about 1% (range, 0-3%). Symptoms associated with higher levels of methemoglobin are as follows:

Physical findings may include the following:

See Presentation for more detail.

Laboratory studies that may be ordered include the following:

Oxygen-carrying capacity of the blood may be determined with the help of the following:

Other studies that may be considered are as follows:

See Workup for more detail.

Early clinical recognition of methemoglobinemia is paramount. Treatment is determined by the symptoms:

Initial care includes the following:

After acute exposure to an oxidizing agent, it is advisable to treat patients with methemoglobin levels of 20% or higher (or lower levels, such as 10%, if there are significant comorbidities especially in the presence of end-organ dysfunction.

Treatment modalities include the following:

Methylene blue – The primary emergency treatment for documented symptomatic methemoglobinemia (contraindicated in G6PD deficiency and ineffective with hemoglobin M)

Exchange transfusion – Can be considered for patients who do not respond to methylene blue or G6PD-deficient individuals who are severely symptomatic

Hyperbaric oxygen treatment – Another option when methylene blue therapy is ineffective or contraindicated

IV hydration and bicarbonate (for metabolic acidosis)

Other medications – These include ascorbic acid, riboflavin, cimetidine, and N-acetylcysteine

Dietary measures – Avoidance of precipitants in food or drink

See Treatment and Medication for more detail.

Methemoglobin contains iron in the ferric state (Fe3+) rather than the reduced ferrous form (Fe2+) found in hemoglobin. This structural change causes an alteration in the blood’s ability to bind oxygen. Methemoglobin is a naturally occurring oxidized metabolite of hemoglobin, and physiologic levels (< 1%) are normal. Problems arise as methemoglobin levels increase. Methemoglobin does not bind oxygen, thus effectively leading to a functional anemia. [1, 2, 3, 4]

In addition, methemoglobin causes a leftward shift of the oxygen-hemoglobin dissociation curve, resulting in decreased release of oxygen to the tissues. The presence of anemia and cyanosis despite oxygen treatment results from both of these effects. [4, 5] (See Pathophysiology and Etiology.)

Methemoglobinemia occurs when red blood cells (RBCs) contain methemoglobin at levels higher than 1%. This may be from congenital causes, increased synthesis, or decreased clearance. Increased levels may also result from exposure to toxins that acutely affect redox reactions, increasing methemoglobin levels.

Clinically, methemoglobinemia has a variable course (see Presentation). Because of the nonspecificity of the clinical findings, mild cases may go undiagnosed. Fatigue, flulike symptoms, and headaches may be the only manifestations in the initial phase. Symptoms are proportional to the methemoglobin level and include skin color changes (cyanosis with blue or grayish pigmentation) and blood color changes (brown or chocolate color). As levels of methemoglobin rise above 15%, neurologic and cardiac symptoms arise as a consequence of hypoxia. Levels higher than 70% are usually fatal. [4]

Tests to rule out hemolysis and to test for organ failure and general end-organ dysfunction should be performed. Urine pregnancy tests should be performed in females of childbearing age. Tests to evaluate a hereditary cause for methemoglobinemia should be ordered when appropriate. (See Workup.)

The most important aspects of the management of methemoglobinemia are recognition of the condition and prompt initiation of treatment, when indicated. For mild asymptomatic cases, treatment is purely for cosmetic or psychological reasons. When methemoglobinemia is severe or symptomatic, specific therapy may be indicated. Initial care includes supplemental oxygen and removal of the offending oxidizing substance. Various agents can reduce the methemoglobin levels to within the reference range or at least to acceptable levels. (See Treatment.)

RBCs contain hemoglobin, which has a quaternary structure. Each hemoglobin molecule is composed of 4 polypeptide chains. Each of these chains is associated with a heme group, which contains iron in the reduced or ferrous form (Fe2+). In this form, iron can combine with oxygen by sharing an electron, thus forming oxyhemoglobin. When oxyhemoglobin releases oxygen to the tissues, the iron molecule is restored to its original ferrous state.

Hemoglobin can accept and transport oxygen only when the iron atom is in its ferrous form. When hemoglobin loses an electron and becomes oxidized, the iron atom is converted to the ferric state (Fe3+), resulting in the formation of methemoglobin. Methemoglobin lacks the electron that is needed to form a bond with oxygen and thus is incapable of oxygen transport.

Under normal conditions, methemoglobin levels remain below 1%; however, under conditions that cause oxidative stress, levels will rise. The low level of methemoglobin is maintained through 2 important mechanisms. The first is the hexose-monophosphate shunt pathway within the erythrocyte. Through this pathway, oxidizing agents are reduced by glutathione.

The second and more important mechanism involves two enzyme systems, diaphorase I and diaphorase II, and requires nicotinamide adenine dinucleotide (NADH) and nicotinamide adenine dinucleotide phosphate (NADPH), respectively, to reduce methemoglobin to its original ferrous state.

NADH-dependent methemoglobin reduction (diaphorase I pathway) is the major enzymatic system involved. [6] Cytochrome b5 reductase plays a major role in this process by transferring electrons from NADH to methemoglobin, an action that results in the reduction of methemoglobin to hemoglobin. This enzyme system is responsible for the removal of 95-99% of the methemoglobin that is produced under normal circumstances.

NADPH-dependent methemoglobin reduction (diaphorase II pathway) usually plays only a minor role in the removal of methemoglobin. This enzyme system utilizes glutathione production and glucose-6-phosphate dehydrogenase (G6PD) to reduce methemoglobin to hemoglobin. It assumes a larger and more important role in methemoglobin regulation in patients with cytochrome b5 reductase deficiencies.

The NADPH-dependent methemoglobin reduction pathway can be accelerated by exogenous cofactors such as methylene blue to as much as five times its normal level of activity. [3, 7, 6, 8] In the absence of further accumulation of methemoglobin, these methemoglobin reduction pathways can clear methemoglobin at a rate of approximately 15% per hour.

Acquired methemoglobinemia is considerably more common than congenital forms.

At least two forms of congenital cytochrome b5 reductase deficiency exist. Both are inherited in an autosomal recessive pattern. In type Ib5R deficiency, the more common form, cytochrome b5 reductase is absent only in RBCs. Homozygotes appear cyanotic but usually are otherwise asymptomatic. Methemoglobin levels typically range from 10% to 35%. Life expectancy is not adversely influenced, and pregnancies are not complicated. Heterozygotes may develop acute, symptomatic methemoglobinemia after exposure to certain drugs or toxins.

The type IIb5R form is substantially less common, accounting for only 10-15% of cases of congenital cytochrome b5 reductase deficiency. In this condition, cytochrome b5 reductase is deficient in all cells, not just RBCs. It is associated with several other medical problems, including mental retardation, microcephaly, and other neurologic complications. Life expectancy is severely compromised, and patients usually die at a very young age. The exact mechanism of the neurologic complications is not known.

Methemoglobinemia may also involve the presence of abnormal hemoglobins (hemoglobin M [Hb M]). In most of these hemoglobins, tyrosine replaces the histidine residue, which binds heme to globin. This replacement displaces the heme moiety and permits oxidation of the iron to the ferric state. Consequently, Hb M is more resistant to reduction by the methemoglobin reduction enzymes (see above). This results in a functionally impaired hemoglobin with a decreased affinity for oxygen.

The inheritance pattern for Hb M variants is autosomal dominant, whereas that for methemoglobinemia due to cytochrome b5 reductase deficiency is autosomal recessive. Patients with Hb M appear cyanotic but are otherwise generally asymptomatic. There are three phenotypic varieties of Hb M, corresponding to the globulin gene affected (alpha, beta, or gamma) as follows [6, 9, 10] :

Alpha-chain variants cause neonatal cyanosis that is persistent

Beta-chain variants do not cause cyanosis until several months after birth, when the level of fetal hemoglobin has decreased

Gamma-chain variants cause transient neonatal cyanosis that resolves once the level of fetal hemoglobin decreases

Another hemoglobin variant, hemoglobin E (Hb E), is associated with methemoglobinemia as well. In a study from the National Thalassemia Center in Sri Lanka, 45 patients who had a diagnosis of Hb E beta-thalassemia were found to have significantly higher median methemoglobin levels that normal control subjects and patients with other hemoglobinopathies (2.7% vs 0.3%.) Furthermore, methemoglobin levels were significantly elevated in patients who had undergone a previous splenectomy. [11]

Acquired methemoglobinemia is much more common than the congenital form and involves excessive production of methemoglobin. Often, it is associated with the use of or exposure to oxidant drugs, chemicals, or toxins, including dapsone, [12] local anesthetic agents, [13] and nitroglycerin. This increased production overwhelms the normal physiologic regulatory and excretory mechanisms. These oxidant agents can cause an increase in methemoglobin levels either by ingestion or by absorption through the skin. A study involving two tertiary care teaching hospitals indicated that methemoglobinemia was present in a significant proportion of all hospitalized patients, and the frequency may be much more than anticipated or expected. [14]

The presence of methemoglobin may also be a marker and predictor of sepsis, resulting from release of excessive amounts of nitrous oxide (NO). [15]

Organs with high oxygen demands (eg, the central nervous system [CNS] and the cardiovascular system) usually are the first systems to manifest toxicity. Oxygenated blood is bright red, deoxygenated blood is dark red, and blood containing methemoglobin is dark reddish brown (see the image below). This dark hue is responsible for clinical cyanosis.

Clinical evidence of cyanosis depends on the level of methemoglobin. Skin discoloration can occur in patients who are not anemic when as little as 1.5 g/dL (about 10%) of hemoglobin is in the form of methemoglobin. By comparison, a deoxyhemoglobin level of 5 g/dL is required to produce clinical cyanosis. When methemoglobin levels are relatively low, cyanosis may be observed without cardiopulmonary symptoms.

In methemoglobinemia, cyanosis is usually the first presenting symptom. In other conditions associated with cyanosis resulting from hypoxemia, it is a much later finding.

In patients with severe anemia, a higher percentage of methemoglobin is required for cyanosis to be obvious. These patients are more likely to exhibit signs of hypoxemia and have less cyanosis than is seen in patients who do not have anemia.

Hereditary methemoglobinemias may be divided into two categories, as follows [16] :

Several variants of hemoglobin M have been described, including Hb Ms, Hb MIwate, Hb MBoston, Hb MHyde Park, and Hb MSaskatoon. These are usually autosomal dominant in nature. Alpha-chain substitutions cause cyanosis at birth, whereas the effects of beta-chain substitutions become clinically apparent in infants at 4-6 months of age.

There are four types of hereditary methemoglobinemias that are secondary to deficiency of NADH cytochrome b5 reductase, which is encoded by the CYB5R3 gene. All of them are autosomal recessive disorders. Heterozygotes have 50% enzyme activity and no cyanosis; homozygotes who have elevated methemoglobin levels above 1.5% have clinical cyanosis. The four types are as follows:

Deficiency of NADPH-flavin reductase can also cause methemoglobinemia.

Acquired methemoglobinemia is usually due to the ingestion of drugs or toxic substances. Exposure to such substances in amounts that exceed the enzymatic reduction capacity of RBCs precipitates symptoms. [14] Acquired methemoglobinemia is more frequent in premature infants and infants younger than 4 months, and the following factors may have a role in the higher incidence in this age group:

Organic and inorganic nitrites and nitrates are common causes of methemoglobinemia. Many of these substances can also be absorbed through the skin, and many prescription cardiac medications contain these compounds. Treatment of preterm infants with inhaled nitric oxide may lead to methemoglobinemia; susceptibility to methemoglobinemia in these infants may be increased by carriage of a single-nucleotide polymorphism in the CYB5R3 gene. [18]

Dietary intake may occur in infants or adults who ingest well water that has been contaminated with nitrites caused by water runoff from fertilized fields. [19] Prepackaged foods may contain significant levels of nitrites. [20, 21]

Medarov et al reported methemoglobinemia associated with dialysis sessions using a portable dialysis unit in five critically ill hospitalized patients. The episodes were traced to inadequate clearance of the disinfectant chloramine from the tap water used for the dialysis. [22]

Chlorates are another group of oxidizing agents that can cause methemoglobinemia. These substances are found in matches, explosives, and fungicides.

Topical and injected local anesthetics (eg, benzocaine, [14, 23] lidocaine, [24] prilocaine, phenazopyridine, [25, 26] cerium nitrate, and silver sulfadiazine [27] ) have also caused methemoglobinemia. Predisposing factors for the development of this toxicity include the presence of a mucosal injury with resultant increased absorption or a previously undiagnosed methemoglobin reductase enzyme deficiency. This toxicity can also be idiosyncratic.

In a 10-year retrospective case-control study of 33 methemoglobinemia cases in patients undergoing a total of 94,694 procedures in which topical anesthetics were used, including bronchoscopy, nasogastric tube placement, esophagogastroduodenoscopy, transesophageal echocardiography, and endoscopic retrograde cholangiopancreatography, Chowdhary and colleagues found a low overall prevalence of methemoglobinemia (0.035%). However, risk was increased in hospitalized patients and those who received benzocaine-based anesthetics. [28]

Dapsone, a drug used to prevent and treat Pneumocystis jirovecii pneumonia (PCP) and to treat leprosy and other skin diseases (including a topical preparation used for acne [29] ), has also been associated with methemoglobinemia. This drug should be used with great caution in patients with known G6PD deficiency, methemoglobin reductase deficiency, or Hb M. [14, 30]

Rasburicase treatment for tumor lysis syndrome in patients with low catalase activity (inherited or acquired) may result in methemoglobinemia secondary to the formation of hydrogen peroxide. [31, 32, 33] Some authors have suggested that catalase activity be measured before rasburicase therapy is initiated in this setting.

RBCs in patients with liver cirrhosis undergo severe oxidative stress, especially in the setting of bleeding complications. [34] The level of methemoglobin is significantly higher in the RBCs of these patients than in those of nonbleeding patients.

Idiopathic methemoglobinemia can occur in association with systemic acidosis. This typically occurs in infants younger than 6 months and is usually caused by dehydration and diarrhea. Idiopathic methemoglobinemia is exacerbated by the lower levels of methemoglobin reductase enzyme found in infants (50% of adult levels).

Inadequately cooked vegetables (eg, spinach, beets, carrots) contaminated with bacteria have been associated with methemoglobinemia. Infants and patients on gastric acid−reduction therapy are particularly vulnerable to methemoglobinemia because gastric acid production may not be sufficient to maintain low levels of nitrate-reducing bacteria in the intestine.) Fava bean ingestion in patients with G6PD deficiency is another potential dietary cause of methemoglobinemia. [35]

Other substances that can cause methemoglobinemia include the following:

Hereditary methemoglobinemia is rare. The most common cause of congenital methemoglobinemia is cytochrome b5 reductase deficiency (type Ib5R). This enzymatic deficiency is endemic in certain Native American tribes (Navajo and Athabaskan Alaskans).

Most cases of methemoglobinemia are acquired and result from exposure to certain drugs or toxins. One of the more common causes of acquired methemoglobinemia is exposure to topical benzocaine during medical procedures. An estimated 0.115% of patients undergoing transesophageal echocardiography (TEE) develop methemoglobinemia. [13, 51, 52]

A large retrospective cohort study found a high incidence of methemoglobinemia (up to 19.8%) in 167 pediatric patients receiving dapsone for PCP prophylaxis. [53] The median methemoglobin level was 9% (range, 3.5-22.4%). The risk of developing methemoglobinemia was increased in those patients receiving a higher dose of dapsone (≥20% above the target dosage of 2 mg/kg/day).

A retrospective study from 2 large teaching hospitals in the United States identified 138 cases of acquired methemoglobinemia over a period of 28 months. [14]

Methemoglobinemia occurs rarely throughout the world. Cytochrome b5 reductase deficiency (type Ib5R) is also endemic in the Yakutsk people of Siberia.

Children, especially those younger than 4 months, are particularly susceptible to methemoglobinemia. The primary erythrocyte protective mechanism against oxidative stress is the NADH system. In infants, this system has not fully matured, and the NADH methemoglobin reductase activity and concentrations are low. Children between the ages of 6 and 10 years may have higher baseline levels of methemoglobinemia than adults do. [54]

Free iron deposition in the brains of sudden fetal and infant death victims has been identified as a possible catabolic product of maternal methemoglobinemia and may be a marker of maternal nicotine exposure. [55]

The inheritance pattern of the congenital enzyme deficiency form of the disease is autosomal recessive. Hb M is inherited in an autosomal dominant pattern. There is no association between sex and the frequency of congenital methemoglobinemia. However, because G6PD deficiency is X-linked, there is a higher risk of acquired methemoglobinemia in males with G6PD deficiency when they are subjected to oxidative stress. Otherwise, no difference exists between males and females with respect to the incidence of acquired methemoglobinemia.

The congenital form of methemoglobinemia due to cytochrome b5 reductase deficiency (type Ib5R) is endemic in certain ethnic groups. These groups include the Navajo, Athabaskan Alaskans, and the Yakutsk people in Siberia. Because G6PD deficiency is a risk factor for acquired methemoglobinemia, populations in which such deficiency is endemic, including populations of Mediterranean and African descent, are at higher risk for acquired methemoglobinemia.

The prognosis of mild cases of methemoglobinemia is very favorable. In severe cases, the prognosis is determined by the degree of anoxic end-organ damage. Complications of methemoglobinemia may include myocardial infarction, seizure, coma, and death. As methemoglobin levels increase, patients demonstrate evidence of cellular hypoxia. Death occurs when methemoglobin fractions approach 70%. Complications, including death, can occur at lower levels in patients with significant comorbidities.

The clinical course of hereditary forms of methemoglobinemia is generally benign. Patients are usually asymptomatic, except for the presence of chronic cyanosis. However, individuals with type IIb5 cytochrome reductase deficiency have a markedly shortened life expectancy, primarily because of multiple neurologic complications.

Acquired methemoglobinemia is usually mild but may be severe and rarely fatal, depending on the cause. Mild-to-moderate transient methemoglobinemia may be present but may escape clinical detection; a high index of suspicion must be maintained. [56]

Patients with acquired methemoglobinemia due to toxin exposure can be severely ill when diagnosed. In some cases, acquired toxic methemoglobinemia can be life-threatening, particularly when the exposure is intentional or the condition is not recognized. One fatality and 3 near-fatalities were reported in a study of 138 patients. [14] However, acquired toxic methemoglobinemia usually responds to treatment when it is recognized and properly treated.

Patients with inherited methemoglobinemia should be counseled regarding the avoidance of toxins, chemicals, and certain drugs (eg, dapsone). Genetic counseling is important. Treatment of type II cases does not prevent or reverse CNS progression.

Patients with both congenital and acquired methemoglobinemia should receive instructions regarding avoidance of precipitating factors.

Patients who develop methemoglobinemia from the oxidant stress of pharmaceutical agents should be warned about other potent oxidant compounds. Patients who develop methemoglobinemia secondary to environmental exposure require a meticulous workup to prevent reexposure to the offending agent. All workplace or household members should be evaluated.

Patients receiving therapy for chronic methemoglobinemia should receive adequate information regarding the risks and benefits expected with treatment.

For patient education resources, see Anemia.

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Chaurasia S, Ramappa M, Bhargava A. Corneal epitheliopathy in congenital methemoglobinemia. Cornea. 2014 Apr. 33(4):422-4. [Medline].

Yusim Y, Livingstone D, Sidi A. Blue dyes, blue people: the systemic effects of blue dyes when administered via different routes. J Clin Anesth. 2007 Jun. 19(4):315-21. [Medline].

Masavkar SS, Mauskar A, Patwardhan G, Bhat V, Manglani MV. Acquired Methemoglobinemia – A Sporadic Holi Disaster. Indian Pediatr. 2017 Jun 15. 54 (6):473-475. [Medline].

Kohli-Kumar M, Zwerdling T, Rucknagel DL. Hemoglobin F-Cincinnati, alpha 2G gamma 2 41(C7) Phe–>Ser in a newborn with cyanosis. Am J Hematol. 1995 May. 49(1):43-7. [Medline].

Faust AC, Guy E, Baby N, Ortegon A. Local Anesthetic-Induced Methemoglobinemia During Pregnancy: A Case Report and Evaluation of Treatment Options. J Emerg Med. 2018 May. 54 (5):681-684. [Medline].

US Food and Drug Administration. FDA Drug Safety Communication: Serious CNS reactions possible when methylene blue is given to patients taking certain psychiatric medications. Available at Accessed: December 23, 2015.

Martinez A, Sanchez-Valverde F, Gil F, Clerigué N, Aznal E, Etayo V, et al. 78 Cases Of Methemoglobinemia Induced By Vegetable Intake In Infants In North Spain. A Case-Control Study. J Pediatr Gastroenterol Nutr. 2013 Jan 1. [Medline].

Bergamaschi MM, Alcantara GK, Valério DA, Queiroz RH. Curcumin could prevent methemoglobinemia induced by dapsone in rats. Food Chem Toxicol. 2011 Jul. 49(7):1638-41. [Medline].

Mary Denshaw-Burke, MD, FACP Clinical Assistant Professor of Medicine, Jefferson Medical College of Thomas Jefferson University; Clinical Assistant Professor, Affiliated Clinical Faculty of the Lankenau Institute for Medical Research; Program Director of Hematology/Oncology Fellowship, Education Coordinator for Oncology, Lankenau Medical Center

Mary Denshaw-Burke, MD, FACP is a member of the following medical societies: American College of Physicians

Disclosure: Nothing to disclose.

Elizabeth DelGiacco, DO Chief Fellow, Department of Hematology/Oncology, Main Line Health, Lankenau Medical Center

Elizabeth DelGiacco, DO is a member of the following medical societies: American Society of Hematology, American Society of Clinical Oncology

Disclosure: Nothing to disclose.

Amy Lawser Curran, MD Fellow, Department of Hematology/Oncology, Lankenau Hospital

Amy Lawser Curran, MD is a member of the following medical societies: Alpha Omega Alpha, Sigma Xi

Disclosure: Nothing to disclose.

Deric C Savior, MD Fellow, Department of Hematology/Oncology, Lankenau Hospital

Disclosure: Nothing to disclose.

Mudra Kumar, MD, MRCP, FAAP Professor of Pediatrics, Course Director, Course 6 MSII, Preclerkship Director, Clinical Integration, Department of Pediatrics, University of South Florida Morsani College of Medicine

Mudra Kumar, MD, MRCP, FAAP is a member of the following medical societies: American Academy of Pediatrics, American Society of Hematology, American Society of Pediatric Hematology/Oncology

Disclosure: Nothing to disclose.

Emmanuel C Besa, MD Professor Emeritus, Department of Medicine, Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University

Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American Society of Clinical Oncology, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, New York Academy of Sciences

Disclosure: Nothing to disclose.

Steven K Bergstrom, MD Department of Pediatrics, Division of Hematology-Oncology, Kaiser Permanente Medical Center of Oakland

Steven K Bergstrom, MD is a member of the following medical societies: Alpha Omega Alpha, American Society of Clinical Oncology, American Society of Hematology, American Society of Pediatric Hematology/Oncology, Children’s Oncology Group, and International Society for Experimental Hematology

Disclosure: Nothing to disclose.

Matthew Bouchard, MD Consulting Staff, Department of Emergency Medicine, Altoona Regional Health System

Disclosure: Nothing to disclose.

Michael J Burns, MD Instructor, Department of Emergency Medicine, Harvard University Medical School, Beth Israel Deaconess Medical Center

Michael J Burns, MD is a member of the following medical societies: American Academy of Clinical Toxicology, American College of Emergency Physicians, American College of Medical Toxicology, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Marcel E Conrad, MD Distinguished Professor of Medicine (Retired), University of South Alabama College of Medicine

Marcel E Conrad, MD is a member of the following medical societies: Alpha Omega Alpha, American Association for the Advancement of Science, American Association of Blood Banks, American Chemical Society, American College of Physicians, American Physiological Society, American Society for Clinical Investigation, American Society of Hematology, Association of American Physicians, Association of Military Surgeons of the US, International Society of Hematology, Society for Experimental Biology and Medicine, and Southwest Oncology Group

Disclosure: Nothing to disclose.

Max J Coppes, MD, PhD, MBA Senior Vice President, Center for Cancer and Blood Disorders, Children’s National Medical Center; Professor of Medicine, Oncology, and Pediatrics, Georgetown University School of Medicine; Clinical Professor of Pediatrics, George Washington University School of Medicine and Health Sciences

Max J Coppes, MD, PhD, MBA is a member of the following medical societies: American Association for Cancer Research, American Society of Pediatric Hematology/Oncology, and Society for Pediatric Research

Disclosure: Nothing to disclose.

Kathy L Ferguson, DO Attending Physician, Department of Emergency Medicine, New York Hospital of Queens

Kathy L Ferguson, DO is a member of the following medical societies: American College of Emergency Physicians and American College of Medical Toxicology

Disclosure: Nothing to disclose.

Lance W Kreplick, MD, FAAEM, MMM Medical Director of Hyperbaric Medicine, Fawcett Wound Management and Hyperbaric Medicine; Consulting Staff in Occupational Health and Rehabilitation, Company Care Occupational Health Services; President and Chief Executive Officer, QED Medical Solutions, LLC

Lance W Kreplick, MD, FAAEM, MMM, is a member of the following medical societies: American Academy of Emergency Medicine and American College of Physician Executives

Disclosure: Nothing to disclose.

David C Lee, MD Research Director, Department of Emergency Medicine, Associate Professor, North Shore University Hospital and New York University Medical School

David C Lee, MD is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, American College of Medical Toxicology, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Sharada A Sarnaik, MBBS Professor of Pediatrics, Wayne State University School of Medicine; Director, Sickle Cell Center, Attending Hematologist/Oncologist, Children’s Hospital of Michigan

Sharada A Sarnaik, MBBS is a member of the following medical societies: American Association of Blood Banks, American Association of University Professors, American Society of Hematology, American Society of Pediatric Hematology/Oncology, New York Academy of Sciences, and Society for Pediatric Research

Disclosure: Nothing to disclose.

Paul Schick, MD Emeritus Professor, Department of Internal Medicine, Jefferson Medical College of Thomas Jefferson University; Research Professor, Department of Internal Medicine, Drexel University College of Medicine; Adjunct Professor of Medicine, Lankenau Hospital

Paul Schick, MD is a member of the following medical societies: American College of Physicians and American Society of Hematology

Disclosure: Nothing to disclose.

John Schoffstall, MD Associate Professor, Department of Emergency Medicine, Medical College of Pennsylvania

John Schoffstall, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Emergency Medicine, American College of Emergency Physicians, American Medical Association, Pennsylvania Medical Society, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Asim Tarabar, MD Assistant Professor, Director, Medical Toxicology, Department of Emergency Medicine, Yale University School of Medicine; Consulting Staff, Department of Emergency Medicine, Yale-New Haven Hospital

Disclosure: Nothing to disclose.

John T VanDeVoort, PharmD Regional Director of Pharmacy, Sacred Heart and St Joseph’s Hospitals

John T VanDeVoort, PharmD is a member of the following medical societies: American Society of Health-System Pharmacists

Disclosure: Nothing to disclose.

Michael J Verive, MD Medical Director, Pediatric Intensive Care, Department of Pediatrics, St Mary’s Hospital for Women and Children

Michael J Verive, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Chest Physicians, Pediatric Sedation, and Society of Critical Care Medicine

Disclosure: Nothing to disclose.

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.


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