Al-Quds University

Dentistry college

Pediatric dentistry

Methemoglobinemia

Hala Abu Haltm 21410414

Introduction
Methemoglobin is the oxidized form of hemoglobin in which the iron in the heme
component is oxidized from ferrous (+ 2) to ferric (+ 3) state. This renders the
hemoglobin molecule incapable of effectively transporting and releasing oxygen to
the tissues. Normally, there is about 1% of total hemoglobin in methemoglobin form.
A small amount of methemoglobin exists in red cells as a result of normal oxidative
functions.So Methemoglobinemia is a condition caused by elevated levels
of methemoglobin in the blood

Congenital methemoglobinemia occurs due to deficiency of enzymese Nicotinamide

Adenine Dinucleotide (NADH) b5 reductase. Acquired methemoglobinemia is more
common and occurs as a result of oxidising agents such as nitrate, phenytoin,
benzocaine, prilocaine, nitric oxide due to overwhelming of capacity of reducing
enzymes.

pathophysiology
Elevated levels of methemoglobin in the blood are caused when the mechanisms that
defend against oxidative stress within the red blood cell are overwhelmed and the
oxygen carrying ferrous ion (Fe2+) of the heme group of the hemoglobin molecule is
oxidized to the ferric state (Fe3+). This converts hemoglobin to methemoglobin,
resulting in a reduced ability to release oxygen to tissues and thereby hypoxia. This
can give the blood a bluish or chocolate-brown color.

Spontaneously formed methemoglobin is normally reduced (regenerating normal

hemoglobin) by protective enzyme systems for example NADH methemoglobin
reductase (cytochrome-b5 reductase) (major pathway), NADPH methemoglobin
reductase (minor pathway) and to a lesser extent the ascorbic acid and glutathione
enzyme systems.

Signs and symptoms

Symptoms are proportional to the fraction of methemoglobin. A normal
methemoglobin fraction is about 1% (range, 0-3%). Symptoms associated with higher
levels of methemoglobin are as follows:

 3-15% - Slight discoloration (eg, pale, gray, blue) of the skin

 15-20% - Cyanosis, though patients may be relatively asymptomatic
 25-50% - Headache, dyspnea, lightheadedness (even syncope), weakness,
confusion, palpitations, chest pain
  50-70% - Abnormal cardiac rhythms; change mental status, delirium, seizures,
coma; profound acidosis
 >70% - Usually, death

Physical findings may include the following:

 Discoloration of the skin and blood (the most striking physical finding)
 Cyanosis – This occurs in the presence of 1.5 g/dL of methemoglobin (as
compared with 5 g/dL of deoxygenated hemoglobin)
 Seizures
 Coma
 Dysrhythmia (eg, bradyarrhythmia or ventricular dysrhythmia)
 Acidosis
 Cardiac or neurologic ischemia
 Pallor of the skin or conjunctiva (suggestive of anemia and possible hemolysis)
 Skeletal abnormalities and mental retardation

Acquired methemoglobinemia
Acquired methemoglobinemia results from exposure to noxious substances that cause
the rate of methemoglobin formation to exceed its rate of reduction. This cause is
particularly relevant when clinicians are treating pediatric and elderly patients.5 In
clinical practice, the most common medications associated with methemoglobinemia
are linked to an alanine ring that is found in many over-the-counter medications and
in all anesthetics .
Although nearly all topical anesthetic preparations have been associated with
methemoglobinemia, benzocaine is the most common and is the largest component of
Cetacaine topical anesthetic (benzocaine/butamben/tetracaine hydrochloride) (Cetylite
Industries, Pennsauken, NJ) formulations.

Treatment
Methemoglobinemia can be treated with supplemental oxygen and methylene
blue 1% solution (10 mg/ml) 1 to 2 mg/kg administered intravenously slowly over
five minutes. Although the response is usually rapid, the dose may be repeated in one
hour if the level of methemoglobin is still high one hour after the initial infusion.
Methylene Blue inhibits monoamine oxidase and serotonin toxicity can occur if taken
with an SSRI (selective serotonin reuptake inhibitor) medicine.

Genetically induced chronic low-level methemoglobinemia may be treated with oral

methylene blue daily. Also, vitamin C can occasionally reduce cyanosis associated
with chronic methemoglobinemia but has no role in treatment of acute acquired
methemoglobinemia. Diaphorase normally contributes only a small percentage of the
red blood cell's reducing capacity, but can be pharmacologically activated by
exogenous cofactors (such as methylene blue) to 5 times its normal level of activity.