How Much Reduced Hemoglobin Is Necessary to Generate Central Cyanosis: DISCUSSION

17 Mar

Central cyanosis (blueness of skin, lips, mucous membranes), as opposed to peripheral cyanosis, is always a manifestation of hypoxemia. Except for the relatively uncommon causes of methemoglobinemia, sulfhemoglobinemia, and some hemoglobinopathies, central cyanosis is always accompanied by a low arterial Po2. As a result of hypoxemia an excess amount of hemoglobin is not saturated with oxygen; in cur­rently accepted terminology this unsaturated hemo­globin is said to be reduced. It is the quantity of reduced hemoglobin (RHB) per deciliter of capillary blood, not the relative lack of oxygenated hemoglobin, that accounts for the bluish color of cyanosis.

In their monograph Lundsgaard and Van Slyke noted that:

since it is impossible to know what condition prevails [in the capillaries], we have, in relating cyanotic color to the content of reduced hemoglobin in the capillary blood, assumed . . . the average unsaturation of capillary blood is midway between that of the arterial and venous bloods respectively . . . and:
The effect of. . . modifying factors is to cause the mean capillary concentration of reduced hemoglobin at which cyanosis becomes perceptible to vary from 4 to 6 grams of reduced hemoglobin per 100 c.c. of blood, and perhaps sometimes even more widely, although it appears usually to lie near 5. Since, to our knowledge, no other investigators independently arrived at 5 g/dl RHB as the value necessary for central cyanosis, it is safe to assume that this widely quoted number originated with the 1923 Lundsgaard and Van Slyke article.

We began this review after reading a study that compared its arterial RHB with Lundsgaard and Van Slykes higher capillary RHB value yet failed to acknowledge the different locations of the two RHB values. After reviewing that papers references, plus additional articles and textbooks, we discovered other instances of such miscomparison, including assertions that the Lundsgaard and Van Slyke value of 5 g/dl value is too high, incorrect, or “false. levitra professional

The “false” label is an unreferenced assertion based on apparent ignorance of the Lundsgaard and Van Slyke paper. The author justifies his claim by stating that an Sa02 “of 87%-2.6 g of reduced Hb is readily detectable.” Calculations show that 2.6 g/dl of RHB in arterial blood represents a capillary RHB of about 4.4 g/dl (Fig 1). Had the author appreciated this fact it seems highly unlikely he would have labeled the 5 g/dl value “false.”

Flenley, the author of the “incorrect” label, states:

The commonly quoted figure of 5 g/dl of reduced haemoglobin for the detection of arterial cyanosis is incorrect, as with a normal haemoglobin concentration this would mean that central cyanosis can only be detected when the arterial Po2 is below 35 mm Hg—by which time the patient may well be nearly dead from hypoxaemia!

Assuming a hemoglobin content of 15 g/dl, this statement would be true only if the 5 g/dl RHB is in arterial blood. Figure 1 shows that a capillary RHB of 5 g/dl is reached when Sa02 is between 78 percent (hemoglobin content [HC] 15 g/dl; Pk02, 44 mm Hg) and 73 percent (HC, 12 g/dl; Pa02, 39 mm Hg). A threshold Pa02 of 35 mm Hg for detecting cyanosis occurs only when the HC is about 10 g/dl (ie, anemia).

Two recent original articles also manifest the error made by Flenley. Barnett et al found, in 20 patients with central cyanosis, a mean arterial deoxyhemoglobin concentration of 3.48 g/dl. . . [this concentration] rather than 5 g/dl, as suggested by others, is necessary before central cyanosis can be detected. However, note that the Barnett et al arterial RHB represents a capillary RHB of about 5.3 g/dl (Fig 1). Barnett et al found an arterial RHB “threshold value” for detecting cyanosis of 2.38 g/dl; this value represents a capillary RHB of about 4.3 g/dl.
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FIGURE 1. Values for capillary

FIGURE 1. Values for capillary and arterial reduced hemoglobin (RHB, g/dl blood) are shown on the vertical axis and percent saturation of hemoglobin in arterial blood (SaOJ on the horizontal axis, with corresponding Pa02 (mm Hg). Each diagonal line repre¬sents a different hemoglobin content (g/dl). Based on the study by Lundsgaard and Van Slyke,2 patients with capillary RHB around 5 g/dl (horizontal line) should manifest cyanosis. Calculations used to draw the graph are based on the following assumptions: Cardiac output =5 L/min; PSaC02 = 40 mm Hg; arterial pH =7.40; carboxyhemoglobin, methemoglobin = 0; oxygen uptake = 250 О/ min; С (A-v) 02 =5 ml O/dl blood.

Goss et al state:
The important new finding in our study was that central cyanosis can be detected reliably at deoxyhaemoglobin concentrations of 1.5 g/dl or more, thus confirming Flenleys conclusions No other original article has reported such a low arterial RHB threshold for cyanosis, yet even this arterial RHB value represents a capillary RHB content of about 3.30 g/dl (Fig 1).

Our review of original articles (Table 1) shows a wide range of Sa02 values at which cyanosis was detectable. Such variability in detection is explained by the numerous factors involved, including hemoglo­bin content, skin color and perfusion, lighting, and interobserver variation. Nonetheless, all other fac­tors being equal, the greater the hemoglobin content the more readily will cyanosis appear as SaOz falls; conversely, the lower the hemoglobin content the more Sa02 has to fall before cyanosis becomes manifest (Fig 1).
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It is best to view the value 5 g/dl RHB in the capillaries the way Lundsgaard and Van Slyke in­tended—as the quantity, plus or minus 1 g/dl, at which cyanosis should be detectable in the majority of patients. Our review of the literature does not support the contention that this value is too high, “false,” or “incorrect.” At this level of capillary RHB, cyanosis should be detectable when Sa02 is between 73 percent (hemoglobin, 12 g/dl) and 78 percent (hemoglobin, 15 g/dl, Fig 1). In some patients cyanosis may be detect­able at higher levels of oxygenation.