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 Dobson D, Lucassen PL, Miller JJ, et al Manipulative therapies for infantile 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 Hardoin RA, Henslee JA, Christenson CP, et al Colic medication and apparent life-threatening events Clin Pediatr 1991;30:281–285 Herman M, Le A The crying infant Emerg Med Clin North Am 2007;25:1137– 1159 Liang JL, Tiwari T, Moro P, et al Prevention of pertussis, tetanus, and diphtheria with vaccines in the united states: recommendations of the advisory committee on immunization practices (ACIP) MMWR Recomm Rep 2018;67(2):1–44 Ong TG, Gordon M, Banks SS, et al Probiotics to prevent infantile colic Cochrane Database Syst Rev 2019;3:CD012473 Reijneveld SA, Brugman E, Hirasing RA Excessive infant crying: the impact of varying definitions Pediatrics 2001;108:893–897 Savino F Focus on infantile colic Acta Paediatr 2007;96:1259–1264 Sondergaard C, Henriksen TB, Obel C, et al Smoking during pregnancy and infantile colic Pediatrics 2001;108:342–346 St James-Roberts I Persistent infant crying Arch Dis Child 1991;31(3):653–655 Sung V, D’Amico F, Cabana MD, et al Lactobacillus reuteri to treat infant colic: a meta-analysis Pediatrics 2018;141(1):e20171811 Wessel MA Paroxysmal fussing in infancy, sometimes called “colic.” Pediatrics 1975;14:421–435 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 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 ... definitions Pediatrics 2001;108:893–897 Savino F Focus on infantile colic Acta Paediatr 2007;96 :1259 –1264 Sondergaard C, Henriksen TB, Obel C, et al Smoking during pregnancy and infantile colic Pediatrics... reuteri to treat infant colic: a meta-analysis Pediatrics 2018;141(1):e20171811 Wessel MA Paroxysmal fussing in infancy, sometimes called “colic.” Pediatrics 1975;14:421–435 CHAPTER 21 ■ CYANOSIS... 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