Methemoglobinemia
Background
- Methemoglobin refers to ferric form of hemoglobin (Fe3+) that is unable to bind O2
- Suspect in any patient with cyanosis not responsive to supplemental O2
- Consider in pediatric patient (<6 months) with diarrhe and low oxygen saturation
Causes
- Rarely congenital, NADH reductase deficiency - unable to reduce ferric to ferrous iron (Fe3+ → Fe2+)
- Exposure to oxidizing agent[1][2]
- Benzocaine and other local anesthetics
- Cyanokit, nitrites, nitrates, well water (nitrates)
- Antimalarials
- Quinolones
- Dapsone (used to treat leprosy, PCP pneumonia, toxoplasmosis, dermatitis herpetiformis, brown recluse bite)
- Aniline dyes
- Phenazopyridine[3]
Clinical Features
MetHb level (%) | Signs & Symptoms^ |
<3 | None |
3-15 | Blue/slate-gray skin |
15-30 | Cyanosis, chocolate-brown blood |
30-50 | Breathlessness, headache, dizziness, syncope |
50-70 | Tachypnea, myocardial ischemia, lactic acidosis, arrythmia, seizure, CNS depression, coma |
>70 | Death |
^Patients with anemia or preexisting cardiopulmonary disease will show symptoms sooner
- Ask about family or personal history of G6PD deficiency as methylene blue contraindicated[4]
Differential Diagnosis
- Consider rare entity of sulfhemoglobinemia
- Sulfonamides, sulfasalazine, phenazopyridine
- Occupational exposure
- Conventional co-oximerty misidentifies sulfhemoglobin as methemoglobin so diagnosis is suspected when patient does not respond to methylene blue
- Typically requires no treatment other than removal of offending agent
- Blue-green discoloration of blood
Acute dyspnea
Emergent
- Pulmonary
- Airway obstruction
- Anaphylaxis
- Angioedema
- Aspiration
- Asthma
- Cor pulmonale
- Inhalation exposure
- Noncardiogenic pulmonary edema
- Pneumonia
- Pneumocystis Pneumonia (PCP)
- Pulmonary embolism
- Pulmonary hypertension
- Tension pneumothorax
- Idiopathic pulmonary fibrosis acute exacerbation
- Cystic fibrosis exacerbation
- Cardiac
- Other Associated with Normal/↑ Respiratory Effort
- Other Associated with ↓ Respiratory Effort
Non-Emergent
- ALS
- Ascites
- Uncorrected ASD
- Congenital heart disease
- COPD exacerbation
- Fever
- Hyperventilation
- Interstitial lung disease
- Neoplasm
- Obesity
- Panic attack
- Pleural effusion
- Polymyositis
- Porphyria
- Pregnancy
- Rib fracture
- Spontaneous pneumothorax
- Thyroid Disease
- URI
Evaluation
- Diagnosis requires high index of suspicion; lack of improvement in oxygen saturation with high-flow oxygen plus discrepancy in oxygen saturation >5% between measurements by ABG vs pulse oximetry ("saturation gap") should raise suspicion. Diagnosis is then confirmed by measuring level of methemoglobin in blood
- Co-oximetry
- Measures relative levels of oxyhemoglobin, carboxyhemoglobin, methemoglobin, reduced hemoglobin
- Usually performed on arterial blood sample, but fingertip CO-oximeter devices are available
- Normal PaO2
- SpO2 will initially be falsely elevated
- Once MetHb >30% → SpO2 will fall to 80-85%
- Mid-80s SpO2 due to light absorption of both oxyHb and deoxyHb
- "Chocolate brown" color of blood
Management
- High-Flow Oxygen
- All patients warrant supplemental oxygen. Symptoms may improve with a non-rebreather but the pulse oximeter reading will remain unchanged and patients may remain cyanotic. This is a diagnostic clue.
- Methylene blue
- Treat if symptomatic OR asymptomatic with MetHb >25%
- 1-2mg/kg Methylene blue IV over 5min; repeat dose if no effect
- Improvement seen within 20min
- Contraindicated in G6PD deficiency
- May induce acute hemolytic anemia
- Instead use moderate dose of ascorbic acid (vitamin C), 300 to 1000 mg/day orally in divided doses
- Other treatment modalities[5]
- Exchange transfusion for symptomatic methemoglobinemia in patient with G6PD deficiency
- Hyperbaric O2 when methylene blue ineffective or contraindicated
- IV hydration and bicarbonate for metabolic acidosis
Disposition
- Will vary depending on response to the antidote and persistence of symptoms. Discuss with toxicologist/poison control
See Also
External Links
References
- ↑ Fernandez-Frackelton M, Bocock J: Cyanosis, in Marx JA, Hockberger RS, Walls RM, et al (eds): Rosen’s Emergency Medicine: Concepts and Clinical Practice, ed 7. St. Louis, Mosby, Inc., 2010, (Ch) 29:p 211-216.
- ↑ Mody, A., Silverman, B.: Problems in the Early Neonatal Period, In Fleisher and Ludwig's Textbook of Pediatric Emergency Medicine, Lippincott, WIlliams and Wilkins 2010, Page 995.
- ↑ Jeffery WH, Zelicoff AP, Hardy WR. Acquired methemoglobinemia and hemolytic anemia after usual doses of phenazopyridine. Drug Intell Clin Pharm. 1982 Feb;16(2):157-9.
- ↑ Denshaw-Burke et al. Methemoglobinemia: Practice Essentials. Jan 4, 2016. http://emedicine.medscape.com/article/204178-overview
- ↑ Denshaw-Burke et al. Methemoglobinemia: Practice Essentials. Jan 4, 2016. http://emedicine.medscape.com/article/204178-overview