methemoglobinemia has reduced O2 saturation with normal PaO2
- related: Step 3, Medicine, General Medicine, ICU intensive care unit
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Methemoglobinemia
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Methemoglobin is a form of hemoglobin in which 1 of the 4 iron molecules is oxidized to the ferric (Fe3+) rather than the normal ferrous (Fe2+) state. The ferric state has a decreased affinity for oxygen, but the remaining 3 ferrous heme sites have an increased oxygen affinity, which leads to decreased oxygen delivery to peripheral tissues.
Methemoglobinemia is most commonly acquired after excessive exposure to an oxidizing agent. Many commonly used drugs are oxidants that may cause methemoglobinemia in susceptible patients. These include chloroquine, dapsone, trimethoprim, sulfonamides, local anesthetics (benzocaine, lidocaine), and nitrates (nitroglycerin, nitroprusside, nitric oxide).
Metoclopramide is used commonly to increase gastric motility. It is an oxidizing agent, converting ferrous iron (Fe++) in hemoglobin to the ferric form (Fe+++), creating MetHb. When given in excessive doses or to patients with deficiency in enzyme systems that convert methemoglobin to hemoglobin, toxic levels of MetHb may develop. MetHb has a much higher affinity for oxygen than oxyhemoglobin, and its presence reduces the oxygen content of arterial blood. The presence of MetHb also shifts the oxyhemoglobin curve to the left. Thus, both decreased oxygen content of arterial blood and increased affinity of oxygen for hemoglobin lead to reduced tissue oxygenation and the symptoms associated with methemoglobinemia.
Patients typically have cyanosis and dark chocolate-colored blood. Standard pulse oximetry readings are low (85%) due to the absorption spectrum of methemoglobin and do not represent the true oxygen saturation.
The clue to the diagnosis is the reduced oxygen saturation with normal Pao2, and the diagnosis can be confirmed with cooximetry, measuring oxyhemoglobin, deoxyhemoglobin, carboxyhemoglobin, and methemoglobin (MetHb) as a percentage of total hemoglobin. Pulse oximetry is inaccurate in the diagnosis of methemoglobinemia, as the peak absorbance of that molecule is at 631 nm, while pulse oximetry estimates oxygen saturations at wavelengths of 660 nm and 940 nm. Pulse oximeters may initially read falsely high oxyhemoglobin levels, but when MetHb levels reach around 30%, the oximeter tends to read the oxygen saturation at a consistent value of around 85%, as in this patient. Patients usually develop cyanosis at MetHb levels of around 15%, symptoms at around 30%, and mental status changes at around 50%. MetHb levels exceeding 70% are usually fatal.
Due to the poor oxygen affinity of methemoglobin, the administration of supplemental oxygen does not improve cyanosis, blood color, or pulse oximetry readings. Because arterial blood gas testing analyzes unbound arterial oxygen (as opposed to hemoglobin-bound oxygen), the PaO2 is normal and overestimates the degree of true oxygen saturation. With severe cases of methemoglobinemia, the decreased oxygen delivery can result in altered mental status, seizures, and death.
Confirmation of the diagnosis requires a co-oximeter, which is a device that can accurately measure the presence of methemoglobin. The offending agent(s) should be discontinued in all patients with suspected methemoglobinemia, while symptomatic patients and those with a methemoglobin level > 20% require prompt administration of methylene blue (a reducing agent). Those in shock may also require blood transfusion or an exchange transfusion.
Treatment is usually indicated for methemoglobin levels >30%. Methylene blue is a cofactor of nicotinamide adenine dinucleotide phosphate (NADP)-MetHb-reductase and increases the capacity of the enzyme to reduce ferric iron levels. The usual dose is 1 to 2 mg/kg over 5 min; methylene blue may increase MetHb levels in doses >15 mg/kg and in patients with glucose-6-diphosphate deficiency.1
Treatment: Methylene blue acts as an electron acceptor for NADPH and is reduced to leucomethylene blue, which in turn reduces methemoglobin back to hemoglobin.2
Fomepizole is an inhibitor of alcohol dehydrogenase used in the treatment of methanol and ethylene glycol toxicity by reducing generation of toxic metabolites. Sodium nitrite and sodium thiosulfate are used as antidotes to cyanide poisoning through increasing methemoglobin levels to facilitate transport of cyanide as cyanomethemoglobin from mitochondrial cytochromes to hepatocytes. Heparin would be given to a patient with postoperative pulmonary embolism, but oxygen desaturation by pulse oximetry with a normal Pao2 would not occur in that condition.