Baylor University Medical Center Proceedings April 2014, Volume 27, Number 2 | Page 60

Table 2. Laboratory workup done at admission
Blood test

Results

White blood cells (K/μL)

13.8

Hemoglobin (g/dL)

14.9

Hematocrit (%)

40.9

Platelets (per μl)

48

Sodium (mEq/L)

138

Potassium (mEq/L)

4.4

Chloride (mEq/L)

98

Bicarbonate (mEq/L)

13

Blood urea nitrogen (mg/dL)

14

Creatinine (mg/dL)

1.4

Anion gap (mEq/L)

27

Glucose (mg/dL)

32

vasopressors, but she remained unresponsive and had severely
impaired neurologic function. An electroencephalogram confirmed anoxic brain injury, and the patient died.
DISCUSSION
Red blood cells are under constant oxidative stress by being
exposed to drugs and oxygen, as well as byproducts of intracellular metabolism. In a normal physiologic state, there is roughly
1% methemoglobin in the RBCs. This amount is kept in check
by reducing enzymes within the erythrocytes (2, 3).
The human body has three main mechanisms for reducing methemoglobin. The nicotinamide adenine dinucleotide
(NADH) pathway, catalyzed by cytochrome b5 reductase, is the
most important. It is responsible for reduction of up to 95% of the
methemoglobin (4). This mechanism efficiently reduces the ferric
atom in methemoglobin by transferring an additional electron
from NADH to methemoglobin. Another reductive mechanism
utilizes G6P dehydrogenase and its capability to produce nicotine
adenine dinucleotide phosphate (NADPH), which can lead to
the reduction of methemoglobin (3, 4) (Figure 1). A third minor
and nonenzymatic pathway that works to reduce methemoglobin
involves reduced glutathione, ascorbic acid, and cysteine.
Methemoglobin becomes clinically relevant when the oxidative burden overwhelms the cellular capability for reduction.

Patients usually become symptomatic when the level of methemoglobin exceeds 15%. Symptoms tend to positively correlate
with the methemoglobin level.
Causes of methemoglobinemia can be divided into inherited
defects of the oxidizing enzymes and acquired forms. The most
common inherited forms are autosomal recessive conditions.
Patients have decreased levels of NADH-cytochrome-b5 reductase. There is no reason to suspect that our patient had any
genetic susceptibility to develop this condition.
A myriad of oxidizing compounds have been identified that
can quickly overwhelm the reducing capabilities of the RBC.
The list includes industrial dyes, nitrates, chlorates, herbicides,
antibiotics such as dapsone and sulfonamides, as well as local
anesthetics, notably benzocaine and prilocaine (2).
The diagnosis of methemoglobinemia is based on clinical
symptoms and requires a high index of suspicion in patients
with a known exposure. Patients will present with cyanosis out
of proportion to the respiratory status, in the presence of normal
arterial oxygen content (partial pressure of oxygen > 60 mm
Hg) (2). No symptomatic improvement is seen with oxygen
administration. The arterial blood draw is chocolate brown due
to the oxidized hemoglobin. ABG will reveal an oxygen saturation gap (2). Methemoglobinemia should be suspected when
the oxygen saturation from the ABG is higher than the oxygen
saturation reported by pulse oximetry. A saturation gap of over
5% strongly suggests methemoglobinemia (5). The differential
diagnosis of a saturation gap includes carbon monoxide poisoning as well as sulfhemoglobinemia (2).
A pulse oximeter emits monochromatic light at wavelengths
of 660 (red) and 940 (infrared) nm. As light travels through the
tissues, the pulsation of the arteries converts this light into an
alternating pattern. This alternating light reaches a photodetector
and is amplified. When light travels through a nonpulsatile tissue
such as a vein, it is not changed to alternating and therefore not
amplified by the photodetector. This allows pulse oximeters to
detect only the hemoglobin in arteries (Figure 2).
Different hemoglobin species absorb light differently at
both wavelengths, and the ratio of red to infrared absorption
is calculated. When the two major hemoglobin molecules are
oxygenated hemoglobin (oxyhemoglobin) and nonoxygenated
hemoglobin (reduced hemoglobin), the ratio of absorbance
at these two wavelengths can be converted to oxygen satura tion. Methemoglobin absorbs light equally at these two wavelengths and therefore always has a ratio of absorption of 1, which

Figure 1. The mechanism of methemoglobin reduction including the methylene blue rescue pathway.
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Baylor University Medical Center Proceedings

Volume 27, Number 2