This Initial Check will help you assess your current knowledge about nitrate/nitrite toxicity. To take the initial check, read the case below, and then answer the questions that follow.
A 2‑month‑old infant is vomiting and has diarrhea, tachypnea, and cyanosis.
A two-month-old female infant is brought to your clinic in a rural area for a routine well-baby checkup. According to the child’s chart, she was delivered two weeks early because of maternal toxemia. There was no neonatal distress; her birth weight was 7 pounds and 2 ounces.
Today, the mother states that she has noticed an intermittent bluish discoloration of the baby’s lips, tip of the nose, and ears. Physical examination of the infant is negative for cardiac murmurs and abnormalities on lung auscultation. You note a below‑average weight gain. Feedings consist of 4 ounces of diluted formula every two hours. The infant has occasional loose stools. You instruct the parents to increase caloric feedings, which should include vitamin and mineral supplements. You tell the parents to call you immediately if any further episodes of the bluish discoloration occur.
Approximately three weeks later, the baby’s frantic parents call your office; the infant is crying incessantly and has vomiting and profuse diarrhea.
When the baby is brought to your clinic a few minutes later, she is afebrile but has tachypnea, central cyanosis, and drowsiness. You note her vital signs as follows
blood pressure (BP) = 78/30 mm Hg (normal 50th percentile for her age is 80/46 mm Hg)
An ambulance is summoned and 100% oxygen is administered by face mask. No improvement in the cyanosis is noted on her arrival at the hospital emergency department.
The examining emergency physician now notes a grade II/VI systolic murmur and central cyanosis, which has not improved despite administration of 100% oxygen for nearly 1 hour. The infant shows no evidence of cardiac failure, atelectasis, pneumonitis, or pneumothorax. Treatment with methylene blue is started, which results in a dramatic resolution of the cyanosis. The infant is discharged on the second hospital day with no evidence of central nervous system hypoxic damage.
In an infant with no known cardiopulmonary disease, cyanosis that is unresponsive to oxygen therapy is most likely due to methemoglobinemia. Carboxyhemoglobinemia and sulfhemoglobinemia should also be considered.
The clinical and laboratory tests that should be interpreted in diagnosing methemoglobinemia are
blood color,
methemoglobin (MHg) levels and total hemoglobin, and
arterial blood gases.
When a drop of blood is placed on filter paper, the chocolate brown appearance of blood does not change with time because MHg does not change when it comes in contact with atmospheric oxygen. Deoxyhemoglobin appears dark red or violet initially, but it brightens after exposure to atmospheric oxygen. The level of MHg in the blood can be measured and should be interpreted in light of the total hemoglobin. Analysis of arterial blood gases will reveal normal or slightly low partial pressure of oxygen with falsely elevated oxygen saturation values. Pulse oximetry results will be inaccurate; they will show a constant oxygen saturation close to 85%. Co-oximetry may be used to directly measure oxygen saturation, rather than the “calculated” level on arterial blood gases.
The initial step in preventing a recurrence of the infant’s cyanosis and distress is to identify the cause of the cyanosis. The next step is to correct or eliminate the cause. If the infant is suffering from acquired methemoglobinemia, the agent must be identified and removed from the infant’s environment. In the case of infantile acquired methemoglobinemia, well water used to prepare formula should be tested for the presence of nitrates. Ingestion of nitrate‑containing water is a common cause of methemoglobinemia in infants, especially those living in rural areas.
The information for this answer comes from section Who Is At Risk?
Questions that may help define the cause of the cyanosis include
Where is the home located?
What activities have been occurring around the home?
What type of sewer system connects to the home?
What are family members’ occupations, avocations, and hobbies?
What is the source of the family’s drinking water and how is it supplied?
Information to gather from families with infants includes
the type of formula, feeding regimen, and source of dilution water;
the infant’s history of recent gastroenteritis; and
family history, including recent use of all medications by both infant and mother.
Causes of high nitrate concentrations in well water include runoff from the use of nitrogen‑containing agricultural fertilizers (including anhydrous ammonia) and seepage of organic nitrogen-containing material from animal wastes or septic sewer systems.
The well water should be tested for nitrate concentration and the presence of coliform bacteria. The family can contact the local health department to perform these tests. It is most important to identify the source of the methemoglobin-inducing agent and to preclude any further exposure. If nitrate-contaminated well water is the source, you should recommend using bottled water or an alternative water source other than the contaminated well to dilute formula.
The information for this answer comes from section Who Is At Risk?
Infants younger than 4 months of age are more susceptible to developing methemoglobinemia because the pH of their gut is normally higher than in older children and adults. The higher pH enhances the conversion of ingested nitrate to the more potent nitrite. The bacterial flora of a young infant’s gut is also different from that found in older children and adults and might be more likely to convert ingested nitrate to nitrite. Gastroenteritis can increase in vivo transformation of nitrate to nitrite and systemic absorption of nitrite from the large intestine.
A large proportion of hemoglobin in young infants is in the form of fetal hemoglobin. Fetal hemoglobin is more readily oxidized to methemoglobin (MHg) by nitrites than is adult hemoglobin. In addition, in infants, NADH-dependent methemoglobin reductase, the enzyme responsible for reduction of induced MHg back to normal hemoglobin, has only about half the activity it has in adults.
The information for this answer comes from section Who Is At Risk?
Laboratory tests useful for screening a patient with suspected methemoglobinemia include
examination of blood color with bedside “filter paper,”
arterial blood gases (ABGs) with co-oximetry,
MHg level,
complete blood counts (CBC) with peripheral blood smear,
