Pediatric emergency medicine trisk 125

FIGURE 20.1 Approach to abrupt onset of severe crying in infancy. DTaP, diphtheria–
pertussis–tetanus (vaccine).

ACKNOWLEDGMENTS
The authors gratefully acknowledge the contributions of Barbara B. Pawel, MD
and Fred M. Henretic, MD to the content of this chapter.
Suggested Readings and Key References
Barr RG. Changing our understanding of infant colic. Arch Pediatr Adolesc Med
2002;156:1172–1174.
Barr RG. Crying as a trigger for abusive head trauma: a key to prevention.
Pediatr Radiol 2014;44(Suppl 4):S559–S564.
Biagioli E, Tarasco V, Lingua C, et al. Pain-relieving agents for infantile colic.
Cochrane Database Syst Rev 2016;9:CD009999.
Brazelton TB. Crying in infancy. Pediatrics 1962;29:579–588.
Brotherton H, Philip RK. Anomalous left coronary artery from pulmonary artery
(ALCAPA) in infants: a 5-year review in a defined birth cohort. Eur J Pediatr
2008;167:43–46.


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colic. Cochrane Database Syst Rev 2012;12:CD004796.
Evanoo G. Infant crying: a clinical conundrum. J Pediatr Health Care
2007;21:333–338.
Fireman L, Serwint J. Colic. Pediatr Rev 2006;27:357–358; discussion 357–358.
Garrison MM, Christakis DA. A systematic review of treatments for infant colic.
Pediatrics 2000;106:184–190.
Gordon M, Biagioli E, Sorrenti M, et al. Dietary modifications for infantile colic.
Cochrane Database Syst Rev 2018;10:CD011029.
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life-threatening events. Clin Pediatr 1991;30:281–285.
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1159.
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with vaccines in the united states: recommendations of the advisory committee
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CHAPTER 21 ■ CYANOSIS
DAVID A. LOWE

INTRODUCTION
Cyanosis, a bluish-purple discoloration of the tissues, is a disturbing condition
commonly confronted by the pediatric emergency physician. It is most easily
appreciated in the lips, nail beds, earlobes, mucous membranes, and locations
where the skin is thin and may be enhanced or obscured by lighting conditions
and skin pigmentation.

PATHOPHYSIOLOGY
The factors that ultimately determine the occurrence of cyanosis are the total

amount of hemoglobin (Hb) in the blood, the degree of Hb oxygenation,
qualitative changes in the Hb molecule, and finally, the state of the circulation.
Oxygenated Hb is bright red and deoxygenated Hb is purple. Cyanosis is
evident when the total amount of deoxygenated Hb in the blood exceeds 5 g/dL or
when oxygen saturation approaches 85%. When the total amount of Hb is
decreased, as in anemia, the patient may not appear cyanotic even in the presence
of significant amounts of deoxygenated Hb. Conversely, polycythemic patients
may appear ruddy because of the increased red cell mass, and the relative increase
in deoxygenated Hb can add a blue hue to the skin.
The degree of Hb oxygenation is determined by several factors, including the
concentration of inspired oxygen (FiO2 ), the ability of oxygen (O2 ) to diffuse
across the alveolar wall into the red cell, and the state of the Hb molecule itself. If
either the FiO2 or the alveolar ventilation falls, so does the alveolar PO2 , with an
associated fall in arterial PO2 (PaO2 ), ultimately resulting in an increased level of
deoxygenated Hb and cyanosis. The ability of O2 to diffuse across the alveolar
wall into the red cell, or blood–gas barrier, is greatly affected by the
circumstances of the barrier itself. According to Fick’s law, any condition that
diminishes alveolar surface area and/or increases its thickness will decrease gas
diffusion and hence PaO2 . Changes in the Hb molecule itself can affect the
amount of oxygen it can carry. Under normal circumstances, oxygen binds
reversibly to the iron molecule of the Hb subunit, changing its conformation from
a purple deoxygenated form to a bright red oxygenated Hb. Consequently, factors
that affect O2 binding to Hb will affect the color of the blood. For example, when
heme iron is oxidized from its normal ferrous to a ferric state, the result is the


formation of methemoglobin. Hemoglobin in this state is brownish purple in
color, is incapable of binding O2 , and results in cyanosis if the level exceeds 10%
to 15% of total Hb. Another important altered state of hemoglobin that affects O2
binding occurs with exposure to carbon monoxide and results in the formation of

carboxyhemoglobin. This abnormal form of Hb has a cherry red color, despite the
fact that little O2 is bound to the Hb molecule.
The state of the circulation plays an important role in the development and
degree of cyanosis. The first circulatory state that can result in cyanosis is
shunting, during which deoxygenated blood from the venous side of the
circulation enters the systemic side, without traveling through the ventilated
alveolar capillary bed. Shunts may be intrapulmonary or intracardiac. Some
degree of intrapulmonary shunting occurs physiologically. In the upright lung the
apex is ventilated more than the base, and the base is perfused more than the
apex. In addition, 5% of blood entering the lungs bypasses the pulmonary
capillaries through bronchial, pleural, and Thebesian veins. This results in a
ventilation/perfusion (V/Q) mismatch. In healthy subjects, the contribution of
V/Q inequality to lowering of PaO2 is not clinically relevant; however, cyanosis
can develop in patients with diseased lungs where the degree of shunting
increases with a consequently larger V/Q mismatch. Intracardiac shunting occurs
when venous blood directly enters the systemic circulation through an abnormal
communication within the heart or at the level of the ductus arteriosus, bypassing
the lungs. If the shunt is large, the reduction in PaO2 can be severe, leading to
marked cyanosis. The second circulatory change that can result in cyanosis is a
poor perfusion state which may be either systemic or localized. Oxygen is
normally unloaded to the tissues as blood travels through a capillary, with the
relative concentration of deoxygenated Hb increasing from the arterial side of the
capillary bed to the venous side. Poor perfusion states and cold temperature cause
sluggish movement of blood across the capillary bed and favor the unloading of
oxygen, increasing the amount of deoxygenated Hb in the tissue capillaries with
resulting cyanosis.

DIFFERENTIAL DIAGNOSIS
The most common causes of cyanosis are respiratory and cardiac diseases but
many other conditions can also cause a patient to appear blue ( Tables 21.1 and

21.2 ). Consideration of the pathophysiologic framework outlined previously
allows an orderly approach to the differential diagnosis of cyanosis. Lifethreatening causes of cyanosis are summarized in Table 21.3 .