Cyanosis in the Newborn Infant

Theodore R. Thompson MD

Definitions

PaO2	Partial Pressure of Oxygen = Driving force for O2 molecules to move from plasma to tissues
O2 content	O2 bound to hemoglobin plus O2 dissolved in plasma
O2 capacity	Maximal quantity of O2 molecules that can be bound to hemoglobin
O2 saturation	Percentage of hemoglobin concentration combined with oxygen (1 gm with 1.34 ml oxygen)
Hypoxemia	Low O2 content of blood
Hypoxia	Low rate of O2 utilization by mitochondria in relationship to requirement
FIO2	Fractional inspired oxygen
Cyanosis	3 gm of reduced hemoglobin per 100 ml of arterial blood

Types of Cyanosis

Peripheral
vs
Central

Pink
Mucous membranes, tongue, lips, trunk
Blue

Cool
Extremities
Warm--> cool

Decreased
Perfusion
Normal to decreased

Normal
PaO2
Low

Usually benign
(R/O sepsis, shock, CHD)
Outcome
Urgent management
(pulmonary, CHD, sepsis, shock)

Types of Cyanosis
Peripheral	vs	Central
Pink	Mucous membranes, tongue, lips, trunk	Blue
Cool	Extremities	Warm--> cool
Decreased	Perfusion	Normal to decreased
Normal	PaO2	Low
Usually benign (R/O sepsis, shock, CHD*)	Outcome	Urgent management (pulmonary, CHD*, sepsis, shock)

Differential:

Pink right hand, head/blue feet-pulmonary hypertension, preductal coarctation with PDA
Pink feet, blue hands-transposition with coarctation

*CHD = congenital heart disease

Factors Affecting Detection of Cyanosis

Hemoglobin concentration

20 gm%: cyanosis at 85% saturation
9 gm%: cyanosis at 67% saturation

Proportion of fetal hemoglobin

Adult: cyanosis at PaO2 42-53 mmHg
Fetal: cyanosis at PaO2 32-42 mmHg

Crying
Site

Peripheral: hands, feet, circumoral area (early)
Central: lips, mucous membranes

Etiology of Respiratory Distress: Cardiac vs Pulmonary Causes

Cardiac Pulmonary

Maternal alcohol; lithium (?)
Maternal diabetes (TGV, VSD, L-sided obstruction)
Maternal phenylketonuria
Chromosomal disorder

Down syndrome
Trisomy 13, 18
Turner's syndrome

Multiple anomalies

VACTERL
Goldenhar's

Situs inversus - complex CHD
Midline liver, splenia - complex CHD
Tachypnea, tachycardia, cardiomegaly hepatomegaly, murmur
Weak pulses, poor perfusion, shock
Poor feeding, diaphoresis

Maternal aspirin, indomethacin, Naproxen (PPHN)
Maternal diabetes (RDS, wet lung)
Polyhydramnios, oligohydramnios
Meconium-stained amniotic fluid
Perinatal distress (PPHN)
Maternal anticonvulsants (hemorrhage)
Maternal group B streptococcus
Prolonged rupture of membranes (>18 hours)
Prematurity
Tachypnea, grunting, retractions, apnea
Poor perfusion, shock (pneumonia-sepsis)

Etiology of Respiratory Distress: Cardiac vs Pulmonary Causes
Cardiac	Pulmonary
Maternal alcohol; lithium (?) Maternal diabetes (TGV, VSD, L-sided obstruction) Maternal phenylketonuria Chromosomal disorder Down syndrome Trisomy 13, 18 Turner's syndrome Multiple anomalies VACTERL Goldenhar's Situs inversus - complex CHD Midline liver, splenia - complex CHD Tachypnea, tachycardia, cardiomegaly hepatomegaly, murmur Weak pulses, poor perfusion, shock Poor feeding, diaphoresis	Maternal aspirin, indomethacin, Naproxen (PPHN) Maternal diabetes (RDS, wet lung) Polyhydramnios, oligohydramnios Meconium-stained amniotic fluid Perinatal distress (PPHN) Maternal anticonvulsants (hemorrhage) Maternal group B streptococcus Prolonged rupture of membranes (>18 hours) Prematurity Tachypnea, grunting, retractions, apnea Poor perfusion, shock (pneumonia-sepsis)

Cyanosis-Etiology, Clinical Assessment

Etiology
Breathing Pattern
Responsive PaO2/SaO2
to FIO2 = 1.0
PaCO2

Pulmonary Distress: tachypnea, grunting, retractions
Usually
increased

Pulmonary hypertension Distress: tachypnea, grunting retractions
± (alkalosis - yes)
N or increased

Cardiac (R->L, admixture) Tachypnea; slow and deep respiratory effort
No
N or decreased

CNS Apnea, irregular
Yes
increased

Metabolic Apnea or tachypnea
Yes
N or increased

Hematologic Normal --> tachypnea
PaO2-yes; SaO2-No
cyanosis persists
N or decreased

Cyanosis-Etiology, Clinical Assessment
Etiology	Breathing Pattern	Responsive PaO2/SaO2 to FIO2 = 1.0	PaCO2
Pulmonary	Distress: tachypnea, grunting, retractions	Usually	increased
Pulmonary hypertension	Distress: tachypnea, grunting retractions	± (alkalosis - yes)	N or increased
Cardiac (R->L, admixture)	Tachypnea; slow and deep respiratory effort	No	N or decreased
CNS	Apnea, irregular	Yes	increased
Metabolic	Apnea or tachypnea	Yes	N or increased
Hematologic	Normal --> tachypnea	PaO2-yes; SaO2-No cyanosis persists	N or decreased

Cyanosis in the Newborn Infant

Low PaO2, SaO2

Cardiac Pulmonary or Other

increased cyanosis CRYING decreased cyanosis

tachypnea, slow, deep RESPIRATORY DISTRESS retractions, grunting, tachypnea, apnea

normal or decreased PaCO2 increased

minimal response FIO2 responsive (usually)

murmur, weai pulses CARDIAC EXAM normal

can be abnormal EKG normal

abnormal ECHO normal , pulmonary hypertension

heart abnormal or normal size situs inversus (complex)
reduced pulmonary blood flow CHEST X-RAY lung disease

**Cyanosis in the Newborn Infant**
Low PaO2, SaO2
Cardiac		Pulmonary or Other
increased cyanosis	CRYING	decreased cyanosis
tachypnea, slow, deep	RESPIRATORY DISTRESS	retractions, grunting, tachypnea, apnea
normal or decreased	PaCO2	increased
minimal response	FIO2	responsive (usually)
murmur, weai pulses	CARDIAC EXAM	normal
can be abnormal	EKG	normal
abnormal	ECHO	normal , pulmonary hypertension
heart abnormal or normal size situs inversus (complex) reduced pulmonary blood flow	CHEST X-RAY	lung disease

Cyanosis and Congenital Heart Disease

Heart Normal or Enlarged

Pulmonary Blood Flow Increased Pulmonary Blood Flow Decreased

TGV Tetralogy of Fallot

Truncus Pulmonary atresia (stenosis)

Doubl-outlet right ventricle Ebstein anomaly

Hypoplastic left heart syndrome Complex

Complex

**Cyanosis and Congenital Heart Disease**
Heart Normal or Enlarged
Pulmonary Blood Flow Increased		Pulmonary Blood Flow Decreased
TGV		Tetralogy of Fallot
Truncus	Pulmonary atresia (stenosis)
Doubl-outlet right ventricle	Ebstein anomaly
Hypoplastic left heart syndrome	Complex
Complex

Cycle of Events Often Present in the Sick Newborn Infant

Cardiopulmonary Interactions in PPHN

PVR = pulmonary vascular resistance; SVR = systemic vascular resistance; PDA = patent ductus arteriosus; FO = foramen ovale; RV = right ventricular; LV = left ventricular

Diagnostic Evaluation of the Newborn Infant with Cyanosis

History, physical examination
Serum glucose, calcium; central hematocrit; WBC with differential; platelet count
Arterial blood gases

100% oxygen - PaO2 above 70-100 mmHg (excludes most congenital heart defects)
Right radial, descending aorta (DA) - simultaneous PaO2

Right radial exceeds DA PaO2 by 10-20 mmHg in persistent pulmonary hypertension

Pulse oximetry: Preductal (right finger) oxygen saturation (SaO2) exceeds postductal (toe) SaO2 by >5%
Hyperventilation - usually PaO2 increases with lung disease

Oxygen Concentration [%]
Ventilator Status
PaCO2 Goal
PaO2:
PPH
PaO2:
Lung Disease
PaO2:
R --> L Cardiac

21% - room air
spontaneous
40
40
40
40

100% - hyperoxia
spontaneous or MV
40
40
>100
40

100% - Pre and Post-ductal shunt
spontaneous or MV
40
>10 - 15
<5
<5

100% - hyperoxia, hyperventilation
MV
20 - 25
>100
>150
40

Chest x-ray
Electrocardiogram
Echocardiogram - very important
PGE1 infusion and possibly cardiac catheterization if congenital heart disease cannot be excluded
Pulmonary vasodilator as nitric oxide inhalation if congenital heart disease excluded; monitor for toxicity

Assessment of Oxygenation

Arterial blood gases/SaO2

PaO2: 50-90 mmHg (torr)
SaO2: >90-96% (>95%-pulmonary hypertension)

Site

Arterial (umbilical, peripheral) - PaO2
Pulse oximetry - SaO2
Vein, capillary (NOT useful)

Management of the Newborn Infant with Cyanosis

Control of diabetes mellitus
Avoid aspirin near delivery

Low-dose aspirin probably not a problem

Indomethacin-preterm labor inhibitor

Monitor ductus arteriosus patency

Prevent perinatal stress
Immediate resuscitation, stabilization
Correct metabolic, hematologic abnormalities
Correct hypotension

Colloid
Inotropic agents

Dopamine (2-20 µg/kg/min)
Dobutamine (10-25 µg/kg/min)

Maintain SaO2 >95%, PaO2 above 70 mmHg (pulmonary hypertension)

FIO2 often 1.0
Hyperventilation to pH >7.50
NaHCO3 to pH

Surfactant administration (pulmonary disorder)
Suggested initial ventilatory settings - conventional

FIO2 = 1.0
Rate = 40-75
P-max = 25-50 cm H2O
PEEP = 5-7 cm H2O
Inspiratory time = 0.3-0.4

High-frequency ventilation (oscillatory) - suggested initial settings (pulmonary disorder)

Hertz = 10-14
Amplitude = 45-50
FIO2 = 1.0
MAP = 20-34

Analgesia, sedation - Fentanyl (3-10 µg/kg/hour); neuromuscular blocking agent
Pulmonary vasodilator - nitric oxide inhalation (10-20 ppm)
Prostaglandin E1 - 0.05-0.1 µg/kg/min (if cyanotic congenital heart disease is suspected)
ECMO if failure to respond to 100% oxygen, alkalosis and nitric oxide
Oxygenation Index (MAP x FIO2 x 100)/postductal PaO2 >=40-45
Slowly wean oxygen, ventilatory support

Formulas Useful for Ill Newborn Infants

Suggested endotracheal (ET) sizes and depth of insertion for newborn infants

Birth Weight/Gestational Age	Internal Diameter (mm)	Distance from Tip of Tube to Number on ET Tube Seen at Lower Lip
<1000 / 26-27 1000 / 27-28 2000 / 32-34 3000 / 37-40 4000 / above 39	2.5 2.5-3.0 3.0-3.5 3.5-4.0 4.0	6-7 cm 7 cm 8 cm 9 cm 10 cm

Most useful ET tube:

3.0 mm internal diameter, 13 cm length
3.5 mm internal diameter, 13 cm in length for full-term infants

Modified from Tochen ML. J Pediatr 95:1050, 1979

Umbilical artery catheter (UAC)

Length of insertion from abdominal wall

T6-T9 placement: 0.33 x crown-heel length or
3 x weight (kg) + 9 cm

Do NOT leave tip at T10-L3
Often place tip at L3-L4
End-holed (3.5, 5.0 French)
0.5 U heparin per ml of normal saline (1 ml/hr)

Umbilical vein catheter (UVC)

Length of insertion from abdominal wall

Right atrial placement: 0.5 x UAC tip placement (T6-T9) plus 1 cm position
Low-lying: Insert tip until blood return (3-5 cm)-temporary measure

End-holed (3.5-5.0 French)
250 U heparin/liter

Dopamine, Dobutamine, Isoproterenol, Nitroprusside infusion

(mg/100 ml = µg/kg/min x weight in kg x 6)/ml/hr

Example: Dopamine, 2.5 µg/kg/min in a 3 kg infant in an IV at 0.5 ml/hr = (2.5 x 3 x 7)/0.5 = 90 mg/100 ml

Dopamine: 5 µg/kg/min = 60 mg x (weight in kg) in 100 ml at 0.5 ml/hr
Dobutamine: 10 µg/kg/min = 120 mg x (weight in kg) in 100 ml at 0.5 ml/hr

Note: To minimize fluid input, order amounts to provide 5 µg/kg/min at 0.5 ml/hr for dopamine, 10 µg/kg/min at 0.5 ml/hr for dobutamine if infusion amounts are likely to increase

Nitroprusside: 1.25 µg/kg/min = 15 mg x (weight in kg) in 100 ml at 0.5 ml/hr
Isoproterenol: 0.2 µg/kg/min = 2.4 mg x (weight in kg) in 100 ml at 0.5 ml/hr
Prostaglandin E1: 0.05 µg/kg/min = 0.6 mg x (weight in kg) in 100 ml at 0.5 ml/hr

Not compatible with heparin, dopamine, dobutamine
Infuse with D10W
Respiratory depression (intubation)
Arrythmias, hypotension, flushing

Drug	Usual Dosage (µg/kg/min)	Dosage (µg/kg/min)	Rate	Amount (mg) x weight in kg to add to 100 ml of IV fluid
Dopamine	2.5-10	10	1 ml/hr	60 mg
Dobutamine	10-20	10	1 ml/hr	60 mg
Nitroprusside	0.5-8	1	1 ml/hr	6 mg
Isoproterenol	0.05-0.5	0.1	1 ml/hr	0.6 mg
Prostaglandin E1	0.05-0.1	0.1	1 ml/hr	0.6 mg

Partial exchange transfusion for hyperviscosity (hematocrit above 65%)

ml for exchange = blood volume (80-90 ml/kg) x (observed-desired [52-55%] hematocrit)/observed hematocrit

Use 5% albumin or plasmanate, not fresh frozen plasma

Transfusion

Packed red blood cells (PRBC)

ml PRBC = weight in kg x (desired-observed hematocrit) x 3

Whole blood

ml blood = weight in kg x (desired-observed hematocrit) x 6

Parenteral nutrition (not for MVI)

Units/ 100 ml = (100 x Units/kg)/ml/kg/day

Example: 3 g/kg/day of protein at 120 ml/kg/day
Grams/100 = (100 x 3)120 = 2.5 gm/100 ml

Phosphorus: 100 mg = 1 mM - 2 mEq
Calcium and phosphorus can be mixed to a maximal sum of 45 mEq
Dextrose provides 3.5 cal/gm

References

DiMaio AM, Singh J. The infant with cyanosis in the emergency room. Pediatr Clin North Am 39:987, 1992.
Duc G. Assessment of hypoxia in the newborn: Suggestions for a practical approach. Pediatrics 48:469, 1971.
Dudell G, Cornish JD, Bartlett RH. What constitutes adequate oxygenation: Pediatrics 85:39, 1990.
Kinsella JP, Abman SH. Recent developments in the pathophysiology and treatment of persistent pulmonary hypertension of the newborn. J Pediatr 126:853, 1995.
Kitterman JA. Cyanosis in the newborn infant. Ped Rev 4:13, 1982.
Kopelman AE, Mathew OP. Common respiratory disorders of the newborn. Ped Rev 16:209, 1995.
Lees MH. Cyanosis of the newborn infant: Recognition and clinical evaluation. J Peds 77:484, 1970.
Lees MH, King DH. Cyanosis in the newborn. Ped Rev 9:36, 1987.
Spitzer AR, Davis J, Clarke WT, Bernbaum J, Fox WW. Pulmonary hypertension and persistent fetal circulation in the newborn. Clin Perinatol 15:389, 1988.
Talner NS, Lister G. The pathophysiology of disorders of oxygen transport in the infant. Current Problems in Pediatrics, Volume XI:6, 1981.
Walsh-Sukys MC. Persistent pulmonary hypertension of the newborn: The black box revisited. Clin Perinatol 20:127, 1993.
Yabek SM. Neonatal cyanosis: Reappraisal of response to 100% oxygen breathing. Am J Dis Child 138:880, 1984.

Oxygen Concentration [%]	Ventilator Status	PaCO2 Goal	PaO2: PPH	PaO2: Lung Disease	PaO2: R --> L Cardiac
21% - room air	spontaneous	40	40	40	40
100% - hyperoxia	spontaneous or MV	40	40	>100	40
100% - Pre and Post-ductal shunt	spontaneous or MV	40	>10 - 15	<5	<5
100% - hyperoxia, hyperventilation	MV	20 - 25	>100	>150	40

Theodore R. Thompson MD

Definitions

Types of Cyanosis Peripheral vs Central Pink Mucous membranes, tongue, lips, trunk Blue Cool Extremities Warm--> cool Decreased Perfusion Normal to decreased Normal PaO2 Low Usually benign (R/O sepsis, shock, CHD*) Outcome Urgent management (pulmonary, CHD*, sepsis, shock)

Types of Cyanosis