Thursday, August 6, 2015

A “Blue Hue” Following Endoscopy -DrSudeepKC

A “Blue Hue” Following Endoscopy


A 39-year-old previously healthy female presents to the emergency department as a transfer
from an outpatient endoscopy clinic. She had been in her usual state of health until 45 minutes into her esophagogastroduodenoscopy when she was noted to have a  gradual decrease in her oxygen saturations and dyspnea. 

On arrival, her vital signs were as follows: pulse 125 beats per minute, blood pressure 96/43 mmHg, respiration 36 breaths per minute, and temperature 37.3° C. Her examination is unremarkable except for the skin findings pictured here (the patient’s hand is on the right, and the nurse’s hand on the left). Her lungs are clear, and her pulses are strong.

Question: Which of the following is the appropriate antidote for this toxicity?

A. Prussian blue
B. Physostigmine
C. Deferoxamine
D. Methylene blue
E. Naloxone


Answer: D
Diagnosis: Methemoglobinemia
Discussion: Methemoglobinemia occurs when the iron atom within the hemoglobin molecule is oxidized from the ferrous (Fe 2 + ) to the ferric (Fe 3 + ) form. This results in an impaired oxygen and carbon dioxide - carrying capacity  that can lead to a functional anemia and tissue hypoxia. It most commonly occurs as the result of exposure to oxidizing compounds or their metabolites (such as in this case, where the patient received benzocaine during endoscopy), but can also result from genetic, dietary, or idiopathic causes. Methemoglobin (MHb) renders the blood a chocolate color, which is pathognomonic at the bedside. Nonanemic healthy patients can tolerate MHb levels up to 15% without symptoms. Levels between 20% and 30% may result in anxiety, tachycardia, changes in
mental status, and headache. MHb levels  above 50% may cause coma, seizures, dysrhythmias, and death. However, reports of patients with levels greater than 70% have been reported with minimal symptoms. 

The most important mechanism for prevention of methemoglobinemia in humans is the nicotinamide
adenine dinucleotide (NADH) dependent methemoglobin reductase system (Figure 67.1 ). This enzyme is responsible for the removal of the majority of MHb that is produced in normal circumstances. The other enzyme, nicotinamide adenine dinucleotide phosphate (NADPH)
methemoglobin reductase, is a minor pathway for the removal of MHb under normal conditions. However, when high concentrations of MHb are present, the NADH enzyme pathway becomes saturated and the NADPH enzyme system becomes dominant. Cyanosis occurs in patients when as little as 1.5 g/dL hemoglobin is in the MHb form, whereas 5 g/dL deoxyhemoglobin is required to produce cyanosis. Pulse oximetry is misleading when MHb is present. 


Pulse oximetry only measures the relative absorbance of two wavelengths of light, thereby only differentiating oxyhemoglobin from deoxyhemoglobin. At high levels of MHb, the pulse oximeter reads a saturation of approximately 85%, which corresponds to equal absorbance of both wavelengths. The partial pressure of oxygen on the arterial blood gas refl ects plasma oxygen content and does not correspond to the oxygen - carrying capacity of hemoglobin. Therefore,in patients with MHb, their partial pressure of oxygen remains within the normal reference range. Co-oximetry should be requested to measure the MHb level. Cooximetry can measure the relative absorbance of four different wavelengths of light and can thereby differentiate MHb from carboxyhemoglobin, oxyhemoglobin, and deoxyhemoglobin.
Once the diagnosis has been made, treatment is supportive for patients with minimal signs or symptoms. For symptomatic patients, methylene blue is the treatment of choice. Methylene blue is an oxidizing agent that is reduced to leukomethylene blue via the NADPH methemoglobin reductase enzyme. Leukomethylene blue then reduces methemoglobin to hemoglobin through conversion
of iron from the ferric (Fe3+) to the ferrous (Fe2+) state. 

Methylene blue is dosed at 1–2 mg/kg of a 1% solution, infused intravenously over 3–5 minutes. If there is no improvement in symptoms, this dose can be repeated at 30-minute intervals up to a maximum dose of 7 mg/kg. Methylene blue, when infused, can cause burning at the site of injection. The intravenous line should be flushed promptly after injection. Rapid administration or higher doses of methylene blue can result in thoracic pain, dyspnea, hypertension, and diaphoresis. 


Doses above 15 mg/kg can cause direct damage to the erythrocyte and hemolysis with Heinz bodies. Dosing should be monitored  carefully in patients with renal failure, as the kidneys excrete both methylene blue and  eukomethylene blue. 

Methylene blue may also result in a false lowering of the pulse oximetry saturation readings.

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