A 3-year-old child is noted by her mother to have developed a funny grayish-blue skin tone over the past day. The child passes brown urine. The child is taken to the emergency department. Vital signs show T 37.1 C, P 100/min, RR 31/min, and BP 90/60 mm Hg. The physican assistant auscultates clear lungs, and the heart rate is regular with no murmurs. There are no remarkable findings except for the odd steel gray skin colour. A pulse oximetry measurement reveals an oxygen saturation of 75%. Laboratory studies show Hgb 13.1 g/dL, Hct 39.5%, MCV 93 fL, platelet count 199,950/microliter, and WBC count 6620/microliter. Her serum glucose is 75 mg/dL and creatinine 0.4 mg/dL. Adminisitration of 5L of oxygen by face mask does not improve the child's skin colour. An arterial blood gas shows pH, 7.43, pO₂ 285 mm Hg, pCO₂ 32 mm Hg, and oxygen saturation 99%. The technician doing the radial arterial puncture notes an odd brown colour to the blood in the syringe.

Questions:

8.1 What is suggested by these findings?

The relatively sudden onset of cyanosis that does not change with administration of oxygen suggests a toxic exposure affecting hemoglobin. The clear lungs on auscultation suggest that no anatomic shunt (increased dead air space) is present. However, the pulse oximetry and the pO₂ do not correlate. A methemoglobin level, was obtained and was 27% (normal, 0.4-1.5). Her carboxyhemoglobin is not elevated.

The administration of methylene blue intravenously results in resolution of cyanosis over the next 15 minutes, and the pulse oximetry reading improves to 95%.

8.2 Explain the biochemistry behind this phenomenon.

Methemoglobinemia results from oxidation of ferrous to ferric iron in the heme of hemoglobin. Oxygen cannot bind to the ferric form. Oxidants in the blood can cause conversion of hemoglobin to methemoglobin. NADH is required to power the reductase enzyme to convert ferric iron back to the ferrous form. However, infants and young children have less NADH in their RBCs and are more susceptible to oxidants. Methemoglobinemia may present with a gray to blue skin coloration and brown urine.

This oxidant effect is similar to G6PD deficiency, in which oxidants damage the RBC, but in a general way, because though NADH is present, NADPH is not generated from lack of G6PD, and NADPH powers glutathione reductase.

8.3 What caused this problem?

An ingestion of a drug or a substance such as napthylamine (in moth balls) can cause methemoglobinemia. Oxidant drugs, such as antimalarials, antibiotics such as sulfa or nitrofurantoins, or antipyretics such as acetaminophen (Tylenol) can have this effect. Nitrites or nitrates (for angina) may also cause it.

Long ago, a lecture from a certain medical school was distinctive because the lecturer, when discussing parenting in a behavioral medicine class, remarked that he had never allowed his children to use red, orange, or yellow crayons because the kids might eat them and develop methemoglobinemia. The first year class didn't know what that was, but instead pondered the potential effects of the odd-coloured drawings on child development. One student in the class then researched the subject to discover that a child would have to ingest at least 100 to 150 crayons to achieve significant methemoglobinemia. The lecturer should have been more concerned about bottles of pills in the home, not crayons.

8.4 Explain the use of pulse oximetry

Pulse oximetry is a non-invasive way of continuously monitoring oxygen saturation. The pulse oximeter measures absorbtion by hemoglobin of two wavelengths of light pulsed in a continuous fashion through the skin of the fingertip into capillaries. There is a differential absorbtion of these wavelengths by oxygenated and unoxygenated hemoglobin, so a calculation of the oxygen saturation of the hemoglobin, SaO₂, can be made.

However, since saturation of Hgb changes little above a PaO₂ of 60 mm Hg, the pulse oximeter is not exquisitely sensitive to variations in PaO₂ above 60 mm Hg.

The standard two wavelength oximeter cannot distinguish abnormal hemoglobins such as methemoglobin or carboxyhemoglobin. Thus, a patient with carbon monoxide poisoning or methemoglobinemia would not be detected by this method.

The oximeter gives no indication of the PaCO₂.

The high PO₂ after administration of oxygen reflects the high PAO₂ of the alveoli on 100% FIO₂. However, since much of the hemoglobin has been altered, the actual oxygen carrying capacity is reduced.