Doctor123.org

Methemoglobinemia, Emergency Medicine

Basics

Description

- Antiparasitic drugs (high potential for MetHb formation): - Dapsone - Primaquine - Chloroquine

- Local anesthetics (high potential for MetHb formation): - Benzocaine - Lidocaine - Prilocaine

- Antibiotics: - Nitrofurantoin - Sulfones - Sulfonamides

- ABG for: - Methemoglobin level - Carboxyhemoglobin level - PaO2 and PaCO2

- Hypoxia: - CHF - COPD - Pulmonary embolism

- ABCs: - Cardiac monitor - Isotonic crystalloids as needed for hypotension

- Expect transient worsening of saturations on pulse oximetry after methylene blue is administered: - Interferes with pulse oximetry measurement and no specific intervention required

  • Iron molecule in hemoglobin is oxidized from ferrous (Fe2+) to ferric (Fe3+) state resulting in a form of hemoglobin that cannot transport oxygen.
  • Oxygen-carrying capacity of blood is reduced and cyanosis is generally present with significant levels.
  • Normal methemoglobin levels are ≤1%; symptoms usually occur with levels >20%.
  • More serious with coexisting anemia
  • Methemoglobin:Decreases total oxygen-carrying capacity (functional anemia)Shifts hemoglobin oxygen-dissociation curve to the left, impairing O2 release to tissuesMaintained at physiologic level (1 " “2%) by nicotinamide adenine dinucleotide (NADH)-methemoglobin (cytochrome B5) reductase in red blood cells (RBCs)
  • Congenital methemoglobinemia:NADH-methemoglobin (cytochrome B5) reductase deficiency (homozygous or heterozygous)Heterozygous hemoglobin M and other abnormal hemoglobins
  • Acquired methemoglobinemia results from oxidant stress on RBCs:Some methemoglobin-inducing agents are direct oxidants (e.g., nitrites)Many substances produce oxidant injury via N-hydroxylamine metabolites.Methemoglobinemia may be delayed relative to initial substance exposure.
  • Many methemoglobin-inducing agents also cause Heinz body hemolytic anemia (HA):Caused by oxidant injury of RBC proteinsGlucose-6-phosphate dehydrogenase (G6PD) " “deficient patients have higher risk.Patients with methemoglobinemia should be worked up for HA.
  • Methemoglobinemia may serve as marker for genetic abnormalities:Heterozygous NADH-methemoglobin (cytochrome B5) reductase deficiency

Etiology

  • Cyanide (CN) antidote kit:Induces methemoglobinemia via amyl and sodium nitriteCN will preferentially complex with methemoglobin, which can then be chelated by sodium thiosulfate.
  • Nitrates/nitrites:Nitrites (NO2)Nitrates (NO3) (e.g., nitroglycerine, via metabolic conversion to nitrites)Nitric oxide (NO)
  • Dyes:Aniline dyesMethylene blue (excessive)
  • Antiparasitic drugs (high potential for MetHb formation):DapsonePrimaquineChloroquine
  • Local anesthetics (high potential for MetHb formation):BenzocaineLidocainePrilocaine
  • Analgesics:Phenazopyridine (Pyridium)Phenacetin
  • Antibiotics:NitrofurantoinSulfonesSulfonamides
  • Others:MetoclopramideNaphthalene (mothballs)Paraquat (herbicide)Arsine gas (AsH3)Chlorates (ClO4)Phenols (e.g., dinitrophenol, hydroquinone)

Diagnosis

Signs and Symptoms

  • Central cyanosis, refractory to oxygen administration:Cyanosis evident at methemoglobin (MetHb) of 10 " “15% of total hemoglobin in nonanemic patient (or 1.5 g of MetHb/dL blood)
  • Dyspnea/tachypnea
  • Chest pain/dysrhythmias
  • Syncope
  • Altered mental status with levels >50%

History

  • Exposure to methemoglobin-inducing agent
  • All substances ingested and time(s) of ingestion
  • G6PD deficiency
  • Medical conditions vulnerable to impaired oxygen delivery (e.g., coronary artery disease)

Physical Exam

  • Cyanosis
  • Emphasis on mental status and cardiovascular findings
  • Icterus or dark-colored urine with accompanying HA

Essential Workup

  • Pulse oximetry is inaccurate in methemoglobinemia:MetHb interferes with pulse oximetry measurement of hemoglobin oxygen saturation.Saturation decreases to ¢ ˆ ¼85% with increasingly more severe methemoglobinemia.Pulse oximetry cannot be used to guide management.
  • ABG for:Methemoglobin levelCarboxyhemoglobin levelPaO2 and PaCO2
  • ECG

Diagnosis Tests & Interpretation

Lab

  • Blood classically described as chocolate colored
  • CBC with manual differential count and smear analysis for evidence of HA

Imaging

CXR to rule out other pulmonary pathology ‚

Differential Diagnosis

  • Hypoxia:CHFCOPDPulmonary embolism
  • Irritant gas exposure
  • Blue discoloration:HypoxiaSulfhemoglobinemiaCN poisoningHydrogen sulfide poisoningExcess methylene blue administrationTellurium toxicitySkin contact/staining with blue dye

Treatment

Pre-Hospital

  • Bring to hospital all substances patient may have ingested.
  • Question witnesses and observe scene for household products and other potential coingestants:Document and relay findings to emergency medical staff.
  • Commercial or industrial sites:Obtain relevant material safety data sheets (MSDSs) if available to identify commercial or chemical products.Avoid dermal exposures.

Initial Stabilization/Therapy

  • ABCs:Cardiac monitorIsotonic crystalloids as needed for hypotension
  • Naloxone, thiamine, and dextrose (D50W) as indicated for altered mental status
  • Supplemental oxygen

Ed Treatment/Procedures

  • Decontamination:If owing to acute ingestion/overdose within previous 1 " “2 hr, and protective airway reflexes are intact, administer 50 " “100 g of activated charcoal PO.
  • Remove source of oxidant stress.
  • Methylene blue:Indications:Asymptomatic with levels >30%Symptomatic patients with levels >10 " “20%, especially if comorbid diseases are presentExpect transient worsening of saturations on pulse oximetry after methylene blue is administered:Interferes with pulse oximetry measurement and no specific intervention requiredUse with caution in patients with glucose-6 pyruvate decarboxylase deficiency:
  • If no improvement with methylene blue, consider that source of oxidant stress is not eliminated, or that sulfhemoglobinemia is present:Sulfhemoglobin is sulfur molecule bound to hemoglobin. Presents similar to methemoglobin, but is self-limited and not responsive to methylene blue.
  • RBC transfusion:May be necessary to increase blood oxygen-carrying capacityConsider in the presence of HA.
  • Exchange transfusion:Especially with neonates/infants
  • Hyperbaric oxygen therapy:Increases oxygen delivery to tissues by allowing more oxygen to be dissolved in the blood, independent of hemoglobin.Use in life-threatening methemoglobinemia if immediately available.
  • Children may develop significant methemoglobinemia from apparently minor ingestions.
  • Symptoms delayed several hours after ingestion, so prolonged observation necessary
  • Neonates are also at higher risk of methemoglobinemia (owing to decreased stores of NADH methemoglobin reductase).

Medication

  • Dextrose 50%: 25 g (50 mL) (peds: 0.5 " “1 g/kg of dextrose) IV for hypoglycemia
  • Methylene blue: 0.1 " “0.2 mL/kg 1% solution IV over 5 min (adults and peds)May repeat if no improvement in 1 hrDoses of 0.3 to 1 mg/kg IV have been effective in neonates. Has been used IO over 3 " “5 min.
  • Naloxone: 0.4 " “2 mg (peds: 0.1 mg/kg) IV, may repeat up to 10 mg for suspected opioid intoxication
  • Thiamine: 100 mg (peds: 1 mg/kg) IM or IV

Follow-Up

Disposition

Admission Criteria

  • Severely symptomatic patients
  • Patients requiring multiple doses of methylene blue
  • Dapsone may cause prolonged recurrent methemoglobinemia

Discharge Criteria

Methemoglobin levels <20% and falling with no symptoms or comorbid disease ‚

Issues for Referral

Toxicology consult for significant exposures ‚

Followup Recommendations

Occupational medicine referral for work-related exposures ‚

Pearls and Pitfalls

  • Pulse oximetry is inaccurate in methemoglobinemia.
  • Obtain an ABG.
  • Administer methylene blue for significant levels/symptoms.

A special thanks to Dr. Gerald Maloney who contributed to the previous edition. ‚

Additional Reading

  • Barclay ‚ JA, Ziemba ‚ SE, Ibrahim ‚ RB. Dapsone-induced methemoglobinemia: A primer for clinicians. Ann Pharmacother. 2011;45:1103 " “1115.
  • Bradberry ‚ SM, Aw ‚ TC, Williams ‚ NR, et al. Occupational methaemoglobinaemia. Occup Environ Med. 2001;58:611 " “615.
  • Guay ‚ J. Methemoglobinemia related to local anesthetics: A summary of 242 episodes. Anesth Analg. 2009;108:837 " “845.
  • Price ‚ D. Methemoglobin inducers. In: Flomenbaum ‚ NE, Goldfrank ‚ LR, Hoffman ‚ RS, et al., eds. Goldfranks Toxicologic Emergencies. 9th ed. New York, NY: McGraw-Hill; 2011.
  • Wright ‚ RO, Lewander ‚ WJ, Woolf ‚ AD. Methemoglobinemia: Etiology, pharmacology, and clinical management. Ann Emerg Med. 1999;34:646 " “656.

Codes

ICD9

289.7 Methemoglobinemia ‚

ICD10

  • D74.0 Congenital methemoglobinemia
  • D74.8 Other methemoglobinemias
  • D74.9 Methemoglobinemia, unspecified
  • D74 Methemoglobinemia

SNOMED

  • 38959009 Methemoglobinemia (disorder)
  • 267550008 Congenital methemoglobinemia (disorder)
  • 295315008 Acquired methemoglobinemia