Cyanosis and the Clinical Assessment of Hypoxemia
Cyanosis is a bluish or purplish tinge to the skin and mucous membranes.
Cyanosis of nail beds.
Cyanotic lips in a woman with hypoxia.
Before the era of rapid blood gas analysis, clinicians often assessed hypoxemia on clinical grounds alone, primarily by looking for cyanosis in the perioral area and fingers.1 Clinical assessment of hypoxemia is now known to be notoriously unreliable for the following reasons:
- A host of factors, from natural skin pigment to room lighting, can affect detection of cyanosis. As with many other physical examination findings, significant interobserver variation occurs in detecting cyanosis.2 Physicians may diagnose cyanosis as an indicator of hypoxemia when the patient has normal oxygen saturation; alternatively, physicians may miss cyanosis when it should be present (the patient has very low oxygen saturation with normal hemoglobin).3
- Approximately 5 g/dL of unoxygenated hemoglobin in the capillaries generates the dark blue color appreciated clinically as cyanosis. For this reason, patients who are anemic may be hypoxemic without showing any cyanosis.
- Ancillary signs and symptoms of hypoxemia (eg, tachycardia, tachypnea, mental status changes) are nonspecific and of no value in reliably detecting hypoxemia. For example, patients may be dyspneic at rest for reasons other than hypoxemia (ie, they have normal PaO2 and SaO2). Conversely, many patients who are chronically hypoxemic (low PaO2 and/or low SaO2) are perfectly lucid and without any obvious physical signs of their low oxygen state (at least while at rest).
Generation of Cyanosis
The requirement of 5 g/dL of reduced (ie, deoxygenated) hemoglobin in the capillaries translates into a reduced hemoglobin content of 3.4 g/dL in arterial blood.4 For this reason, patients with normal hemoglobin manifest cyanosis at higher SaO2 values than patients with anemia. Refer to Media File 3 below and consider the following examples:
- A patient whose hemoglobin content is 15 g/dL (hematocrit approximately 45%) would not generate 5 g/dL of reduced (ie, deoxygenated) hemoglobin in the capillaries until his/her SaO2 level reached about 85% (PaO2 50 mm Hg).
- When hemoglobin content is 9 g/dL (hematocrit approximately 27%), the threshold SaO2 level for manifesting cyanosis is lowered to about 73% (PaO2 38 mm Hg). At this level of hypoxemia, the patient would certainly have other manifestations of hypoxemia (eg, respiratory symptoms, mental status changes) apart from cyanosis.
- With a hemoglobin content of less than 9 g/dL, the patient would likely succumb from hypoxemia before cyanosis became evident.
Oxygen and hemoglobin values at which central cyanosis occurs: The threshold for central cyanosis is a capillary reduced hemoglobin content of 5 g/dL, which can occur at varying values of the 2 parameters that are measured most commonly, arterial oxygen saturation (SaO2) and arterial hemoglobin content. The vertical axis shows values for venous, capillary, and arterial reduced hemoglobin (RHB, g/dL blood), and the horizontal axis shows a percent saturation of hemoglobin in arterial blood (SaO2) along with corresponding PaO2 (mm Hg). Each diagonal line represents a different hemoglobin content (g/dL). For example, central cyanosis can manifest when SaO2 is 85% in a patient with a hemoglobin of 15 g/dL. From Martin L, Khalil H: How much reduced hemoglobin is necessary to generate central cyanosis? Chest 1990 Jan;97(1):182-5.
If hypoxemia is suspected for any reason, some measurement of the oxygen level is necessary (eg, arterial blood gas determination, pulse oximetry). No reliable alternative is available to measurement of PaO2 or SaO2 when diagnosing hypoxemia or assessing the need for supplemental oxygen therapy.5 At the same time, one should not rely on the absence of cyanosis as reassurance that hypoxemia is not present.
Most often, cyanosis is detected in the lips and fingers.
Cyanosis of nail beds.
Cyanotic lips in a woman with hypoxia.
A case report of Eisenmenger syndrome (interrupted aortic arch with ventricular septal defect) in a 31-year-old pregnant woman discusses the rare condition of differential cyanosis.6 In this situation, cyanosis is evident in both the fingers and the toes, but SaO2 level (measured by pulse oximetry) is much lower in the toes.
Other Causes of Cyanosis
Other causes of cyanosis include the following:
- Methemoglobin
- Normal hemoglobin unbound to oxygen is called reduced hemoglobin and is symbolized HbFe+2. Methemoglobin (metHb), the oxidized form of hemoglobin, is HbFe+3. Normally, as much as 2% of hemoglobin is in the form of metHb. Because metHb is unable to bind with oxygen, arterial oxygen saturation is reduced by the same amount that metHb is increased.
- MetHb imparts an intense bluish tinge to the skin; therefore, the cyanosis that comes with methemoglobinemia is not related to reduced hemoglobin but to oxidized hemoglobin.7,8 Methemoglobinemia usually occurs as a drug reaction, especially to nitrite or nitrate-containing compounds (eg, nitroglycerin) and to some topical anesthetics. Dahshan and Donovan report a case of severe methemoglobinemia from topical benzocaine in a toddler.9 Dapsone, a drug used in HIV and non-HIV conditions, can also cause methemoglobinemia.
- Although excess metHb reduces the measured SaO2, PaO2 is not affected; this is because metHb does not affect transfer of oxygen from the atmosphere to the lungs. A low PaO2 in a patient with excess metHb suggests a concomitant pulmonary problem. MetHb can be measured in a co-oximeter, a companion to the blood gas machine available in most hospital blood gas laboratories. The co-oximeter also measures carboxyhemoglobin, hemoglobin content, and SaO2. Note that standard pulse oximeters, which measure SaO2 using 2 wavelengths of light, do not measure metHb (or carboxyhemoglobin). However, a new generation of pulse oximeters that uses 8 wavelengths of light does have the ability to measure carboxyhemoglobin and metHb (Barker 2006).of light does have the ability to measure COHb and metHb.10
- Sulfhemoglobin
- Sulfhemoglobinemia is a rare condition caused by sulfur binding with hemoglobin so that oxygen cannot be bound.
- Unlike metHb, the iron moiety remains in the reduced state (HbFe+2).
- Sulfhemoglobin is similar to metHb in causing low SaO2 but not affecting PaO2 and in imparting an intense bluish color to the skin.
- Peripheral cyanosis
- Peripheral cyanosis is a dusky or bluish tinge to the fingers and toes and may occur with or without central cyanosis (ie, with or without hypoxemia).
- When unaccompanied by hypoxemia, as determined by blood gas analysis, peripheral cyanosis is caused by peripheral vasoconstriction.
- Pseudocyanosis
- Pseudocyanosis is a bluish tinge to the skin and/or mucous membranes that is not associated with either hypoxemia or peripheral vasoconstriction. Most causes are related to metals (eg, silver nitrate, silver iodide, silver, lead) or drugs (eg, phenothiazines, amiodarone, chloroquine hydrochloride). One report describes blue-gray discoloration in a man who for years ingested colloidal silver for a urinary tract infection11 ; his oxygen levels were normal.
- One report describes a girl with intensely blue skin from food coloring.12 Consider pseudocyanosis when the patient has no cardiopulmonary symptoms and the skin does not blanch under pressure. To be sure of the diagnosis, obtain a pulse oximetry or arterial blood gas measurement.
Multimedia
 | Media file 1: Cyanosis of nail beds. |
 | Media file 2: Cyanotic lips in a woman with hypoxia. |
 | Media file 3: Oxygen and hemoglobin values at which central cyanosis occurs: The threshold for central cyanosis is a capillary reduced hemoglobin content of 5 g/dL, which can occur at varying values of the 2 parameters that are measured most commonly, arterial oxygen saturation (SaO2) and arterial hemoglobin content. The vertical axis shows values for venous, capillary, and arterial reduced hemoglobin (RHB, g/dL blood), and the horizontal axis shows a percent saturation of hemoglobin in arterial blood (SaO2) along with corresponding PaO2 (mm Hg). Each diagonal line represents a different hemoglobin content (g/dL). For example, central cyanosis can manifest when SaO2 is 85% in a patient with a hemoglobin of 15 g/dL. From Martin L, Khalil H: How much reduced hemoglobin is necessary to generate central cyanosis? Chest 1990 Jan;97(1):182-5. |
Keywords
cyanosis, blue skin, oxygen deficit, blood gas analysis, blood gases, hypoxemia, methemoglobin, sulfhemoglobin, peripheral cyanosis, pseudocyanosis, pseudo-cyanosis, low oxygen saturation with normal hemoglobin, oxidized hemoglobin, dapsone, peripheral vasoconstriction, differential cyanosis
More on Cyanosis |
| References |
References
Lundsgaard C, Van Slyke DD. Cyanosis. Medicine. 1923;2:1-76.
Carpenter KD. A comprehensive review of cyanosis. Crit Care Nurse. Aug 1993;13(4):66-72. [Medline].
Comroe JH, Botelho S. The unreliability of cyanosis in the recognition of arterial anoxemia. Am J Med Sci. 1947;214:1-5.
Martin L, Khalil H. How much reduced hemoglobin is necessary to generate central cyanosis?. Chest. Jan 1990;97(1):182-5. [Medline].
Martin L. All You Really Need to Know to Interpret Arterial Blood Gases. 2nd ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 1999.
Chou WR, Kuo PH, Shih JC, Yang PC. A 31-year-old pregnant woman with progressive exertional dyspnea and differential cyanosis. Chest. Aug 2004;126(2):638-41. [Medline].
Bradberry SM. Occupational methaemoglobinaemia. Mechanisms of production, features, diagnosis and management including the use of methylene blue. Toxicol Rev. 2003;22(1):13-27. [Medline].
Umbreit J. Methemoglobin--it's not just blue: a concise review. Am J Hematol. Feb 2007;82(2):134-44. [Medline].
Dahshan A, Donovan GK. Severe methemoglobinemia complicating topical benzocaine use during endoscopy in a toddler: a case report and review of the literature. Pediatrics. Apr 2006;117(4):e806-9. [Medline].
Barker SJ, Curry J, Redford D, Morgan S. Measurement of carboxyhemoglobin and methemoglobin by pulse oximetry: a human volunteer study. Anesthesiology. Nov 2006;105(5):892-7. [Medline].
Baernstein A, Smith KM, Elmore JG. Singing the blues: is it really cyanosis?. Respir Care. Aug 2008;53(8):1081-4. [Medline].
Zillich AJ, Kuhn RJ, Petersen TJ. Skin discoloration with blue food coloring. Ann Pharmacother. Jul-Aug 2000;34(7-8):868-70. [Medline].
Further Reading
Keywords
cyanosis, blue skin, oxygen deficit, blood gas analysis, blood gases, hypoxemia, methemoglobin, sulfhemoglobin, peripheral cyanosis, pseudocyanosis, pseudo-cyanosis, low oxygen saturation with normal hemoglobin, oxidized hemoglobin, dapsone, peripheral vasoconstriction, differential cyanosis
