Cyanosis

CHAPTER 9
Cyanosis
KEY TEACHING POINTS

•C yanosis results from increased amounts of bluish-colored hemoglobin in the
superficial vessels of the skin. The usual cause is increased deoxyhemoglobin;
rare causes are increased methemoglobin or other abnormal hemoglobins.
• The blue color of cyanosis requires a minimum absolute amount of abnormal
hemoglobin (i.e., >2.38 g/dL arterial deoxyhemoglobin). This explains why
polycythemic patients develop cyanosis more easily than anemic patients.
• Cyanosis is either central or peripheral, a distinction made at the bedside. This
distinction, in turn, implies specific etiologies.
• In patients with chronic liver disease, the finding of cyanosis increases the
probability of hepatopulmonary syndrome.
• Pseudocyanosis, unlike cyanosis, does not blanch with pressure, a finding indi-
cating the color is not from abnormally colored blood but instead from abnor-
mal pigments in the skin (e.g., silver, amiodarone).
I. DEFINITIONS
Cyanosis is an abnormal bluish discoloration of the skin and mucous membranes,
caused by blue-colored blood circulating in the superficial capillaries and venules.
The blue color usually represents excessive amounts of deoxygenated hemoglobin,
although in some patients, it results from increased amounts of methemoglobin or
sulfhemoglobin. Cyanosis may be central or peripheral. In central cyanosis, the blood
leaving the heart is colored blue; in peripheral cyanosis, the blood leaving the heart
is red but becomes blue by the time it reaches the fingers and toes. Pseudocyanosis,
in contrast, refers to a permanent bluish discoloration caused by deposition of blue
pigments in the skin.
Cyanosis was first described in 1761 by Morgagni, who attributed it to pulmonic
stenosis.1 In 1869, Claude Bernard described the qualitative difference in blood
gases between blue venous blood and red arterial blood. The first person to quantify
how much deoxygenated hemoglobin was necessary to produce the blue color was
Lundsgaard in 1919.1
II. PATHOGENESIS
A. THE BLUE COLOR
Blood becomes blue when an absolute amount of blue pigment (usually deoxy-
hemoglobin) accumulates, probably because only then is the blue color deep
enough to be seen through the opaque epidermis.1-4 Once this minimal amount of
69
70 PART 3 GENERAL APPEARANCE OF THE PATIENT
deoxyhemoglobin accumulates and cyanosis appears, the amount of additional red

blood (or oxyhemoglobin) matters little to the overall skin color.
The color of the skin depends on the color of blood flowing through the der-
mal capillaries and subpapillary venous plexus, not the arteries and veins that
lie too deep to contribute to skin color.1,5 There has been much confusion over
the absolute concentration of deoxyhemoglobin required for cyanosis, primarily
because some investigators have mistakenly equated arterial levels of deoxyhe-
moglobin, which are easy to measure, with capillary levels, which impart the
blue color but must be higher than the measured arterial levels. In patients with
central cyanosis, the average amount of arterial deoxyhemoglobin is 3.48 ± 0.55
g/dL (or 5.35 g/dL in the capillaries and small venules). The minimal amount of
arterial deoxyhemoglobin causing cyanosis is 2.38 g/dL (or 4.25 g/dL in the capil-
laries and small venules).4*
Because cyanosis depends on the absolute quantity of deoxyhemoglobin, not
the relative amount, the appearance of cyanosis also depends on the patient’s total
hemoglobin concentration (i.e., 5 g/dL of capillary deoxyhemoglobin represents
a higher percent of oxygen desaturation for an anemic patient, who has less total
hemoglobin, than it does for a polycythemic patient). Table 9.1 displays this rela-
tionship: polycythemic patients (hemoglobin = 20 g/dL) may appear cyanotic with
only mild hypoxemia (i.e., oxygen saturation [SaO2] = 88% or pO2 = 56 mm Hg),
yet anemic patients (hemoglobin = 8 g/dL) do not develop the finding until hypox-
emia is severe (i.e., SaO2 = 70% or pO2 = 36 mm Hg).†
TABLE 9.1 Cyanosis and Hemoglobin Concentration

CYANOSIS APPEARS AT*
Hemoglobin Concentration Oxygen Saturation (%) Arterial pO2 (mm Hg)
(g/dL) Below Below
6 60 31
8 70 36
10 76 40
12 80 45
14 83 47
16 85 50
18 87 54
20 88 56
*These figures assume that central cyanosis begins to appear when 2.38 g/dL deoxygenated
hemoglobin accumulates in arterial blood (see the text for calculations). The corresponding pO2
was obtained from standard hemoglobin dissociation curves for oxygen.
* Capillary deoxyhemoglobin is 1.87 g/dL more than arterial levels, based on three assump-
tions: (1) the difference in oxygen content between the arteries and veins is 5 mL of oxygen/
dL blood; (2) the amount of deoxyhemoglobin in the capillaries is midway between that of the
arteries and vein; and (3) 1.34 mL of oxygen binds to 1 g of saturated hemoglobin. Therefore
5/(2 × 1.34) = 1.87.
† These figures are calculated as follows: for the polycythemic patient (hemoglobin = 20 g/
dL), 2.38 g/dL of arterial deoxyhemoglobin indicates that there is 20 − 2.38, or 17.62, g/dL of
arterial oxyhemoglobin. Oxygen saturation, therefore, is (17.62)/(20) = 0.88, or 88%. For the
anemic patient, the calculation is (8 − 2.38)/8 = 0.7, or 70% saturation.
CHAPTER 9 Cyanosis 71
B. PERIPHERAL CYANOSIS
In peripheral cyanosis, blood leaving the heart is red, but because of increased
extraction of oxygen by peripheral tissues, enough deoxyhemoglobin accumulates
to render it blue in the subepidermal blood vessels of the feet and hands. The clini-
cian can easily demonstrate peripheral cyanosis by wrapping a rubber band around
a finger and watching the distal digit turn blue as oxygen continues to be extracted
from the stagnant blood.
III. THE FINDING

Cyanosis is best appreciated in areas where the overlying epidermis is thin and sub-
epidermal vessels are abundant, such as the lips, nose, cheeks, ears, hands, feet, and
the mucous membranes of the oral cavity.1,6 Cyanosis is detected more easily with
fluorescent lighting than with incandescent lighting or daylight.4
A. CENTRAL CYANOSIS
Patients with central cyanosis have blue discoloration of the lips, tongue, and sub-
lingual tissues, as well as the hands and feet. The correlation between severity of
oxygen desaturation and depth of cyanotic color is best appreciated when examin-
ing the patient’s lips and buccal mucosa.7,8 Some patients with longstanding central
cyanosis have associated clubbing (see Chapter 28).
When central cyanosis is suspected but administration of oxygen fails to diminish
the blue color, the clinician should consider methemoglobinemia or sulfhemoglo-
binemia. The color of patients with methemoglobinemia often has a characteristic
brownish hue (chocolate cyanosis).9
Because cyanosis depends on blue blood being present in the underlying blood
vessels, maneuvers that express blood out of the vessels (e.g., pressure on the skin)
make the blue color temporarily disappear.
Peripheral cyanosis causes blue hands and feet, although the mucous mem-
branes of the mouth are pink. Warming the skin on patient’s limbs often dimin-
ishes peripheral cyanosis because blood flow to the involved area improves,
whereas the color of central cyanosis is unchanged or deepens after warming
of the skin.
C. PSEUDOCYANOSIS
In patients with pseudocyanosis, the mucous membranes of the mouth are pink, and
pressure on the skin fails to blanch the abnormal color.6
D. CYANOSIS AND OXIMETRY

Cyanosis affects co-oximetry (i.e., blood gas analysis in the laboratory) differ-
ently than it affects pulse oximetry (i.e., equipment used at the bedside; see
Chapter 20). Because co-oximetry can distinguish deoxyhemoglobin from other
abnormal hemoglobin, it indicates hypoxemia only in patients with central cya-
nosis (i.e., it samples arterial blood and therefore indicates normal oxygen levels
in peripheral cyanosis). Pulse oximetry, in contrast, detects the color of the pul-
satile waveform in the digit. Although it also indicates hypoxemia in patients
with central cyanosis, pulse oximetry may falsely indicate arterial hypoxemia in
patients with peripheral cyanosis or with abnormal hemoglobin (see Chapter
20). Both co-oximetry and pulse oximetry indicate normal oxygen levels in
pseudocyanosis.
72 PART 3 GENERAL APPEARANCE OF THE PATIENT
IV. CLINICAL SIGNIFICANCE

A. CENTRAL CYANOSIS
Any disorder causing hypoxemia may generate sufficient deoxyhemoglobin in the
blood leaving the heart to produce central cyanosis. Typical etiologies are pulmonary
edema, pneumonia, and intracardiac right-to-left shunts. The finding of central cya-
nosis increases greatly the probability of hypoxemia (likelihood ratio [LR] = 7.4; see
EBM Box 9.1). Hypoxemia is defined as arterial deoxyhemoglobin level ≥2.38 g/dL,
corresponding to SaO2 ≤80% and pO2 ≤45 mm Hg in patients with normal amounts
of hemoglobin (see Table 9.1). The absence of central cyanosis greatly decreases the
likelihood of such severe hypoxemia (LR = 0.2; see EBM Box 9.1).
In patients with chronic liver disease, the finding of cyanosis increases the prob-
ability of hepatopulmonary syndrome (LR = 3.6; see Chapter 8).
In clinical practice, common causes of peripheral cyanosis are low cardiac output,
arterial disease or obstruction (e.g., Raynaud disease), and venous disease.
C. PSEUDOCYANOSIS
Pseudocyanosis may occur after exposure to metals (argyria from topical silver com-
pounds; chrysiasis of gold therapy) or drugs (amiodarone, minocycline, chloroquine,
or phenothiazines).10,11
The references for this chapter can be found on www.expertconsult.com.
EBM BOX 9.1

Central Cyanosis, Detecting Arterial Deoxyhemoglobin
≥2.38 g/dL*
Likelihood Ratio† if
Finding Is
Finding Sensitivity Specificity
(Reference) (%) (%) Present Absent
Central cyanosis2,4 79-95 72-95 7.4 0.2
*Corresponding to O2 saturation of 80% and pO2 of 45 mm Hg if hemoglobin concentration is

12 g/dL (see Table 9.1).
†Likelihood ratio (LR) if finding present = positive LR; LR if finding absent = negative LR.
Click here to access calculator
CYANOSIS
Probability
Decrease Increase
– 45% –30% –15% +15% +30% +45%
LRs 0.1 0.2 0.5 1 2 5 10 LRs
Absence of cyanosis, arguing Presence of cyanosis, detecting

against arterial deoxyhemoglobin arterial deoxyhemoglobin
>2.38 g/dL >2.38 g/dL

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CHAPTER 9

KEY TEACHING POINTS

deoxyhemoglobin accumulates and cyanosis appears, the amount of additional red

TABLE 9.1 Cyanosis and Hemoglobin Concentration

III. THE FINDING

D. CYANOSIS AND OXIMETRY

IV. CLINICAL SIGNIFICANCE

The references for this chapter can be found on www.expertconsult.com.

EBM BOX 9.1

*Corresponding to O2 saturation of 80% and pO2 of 45 mm Hg if hemoglobin concentration is

Click here to access calculator

Absence of cyanosis, arguing Presence of cyanosis, detecting

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