A. Organogenesis is virtually complete after the 12th gestational week.

a. The lungs begin as a bud on the embryonic gut in the 4th week of gestation. Failure of separation of the lung bud from the gut later results in the formation of a tracheoesophageal fistula (TEF).

b. The diaphragm forms during the 4th through 10th week of gestation, dividing the abdominal and thoracic cavities.

1. If the diaphragm is not completely formed when the midgut reenters the abdomen from the umbilical pouch, the abdominal contents can enter the thorax.

2. The presence of abdominal contents within the thorax is associated with arrested lung growth.

3. The lungs from patients with congenital diaphragmatic hernia (CDH) have a decreased number of arterioles in the hypoplastic lung. In addition, the pulmonary arteries of both lungs are abnormally thick and reactive, resulting in increased pulmonary vascular resistance.

a. Lung development is generally insufficient for survival at less than the 23rd week of gestation, prior to the saccular stage of lung development when thinning of the pulmonary interstitium due to decreased collagen fiber deposition, increased cellular differentiation, and capillary development begins the capacity for gas exchange.

b. Secretion of surfactant, which reduces alveolar wall surface tension and promotes alveolar aeration, is often inadequate until the last month of gestation.

1. Birth before 32 weeks of gestation is associated with respiratory distress syndrome (RDS).

2. Because glucose metabolism affects lung surfactant maturation, infants of diabetic mothers are at increased risk of RDS when prematurely born at later stages of gestation.

3. Antenatal treatment with steroids is associated with a decrease in the incidence of RDS in prematurely born infants.

c. After birth, the onset of breathing is stimulated by hypoxemia, hypercarbia, tactile stimulation, and a decrease in plasma prostaglandin E₂. After aeration and distension of the lung, the pulmonary vascular resistance decreases, and pulmonary blood flow increases nearly 10-fold. Failure of the reduction of pulmonary vascular resistance after birth is associated with extrapulmonary shunting of blood and severe hypoxemia and is called persistent pulmonary hypertension of the newborn (PPHN).

b. The primitive cardiac tube consists of the sinoatrium, the ventricle, the bulbus cordis (primitive right ventricle), and the truncus (primitive main pulmonary artery). During the 2nd month of gestation, a heart with two parallel pumping systems develops out of this initially tubular system. During this process, various structures divide and migrate. Failure of structural maturation at this stage of development causes numerous cardiac malformations. For example:

1. Failure of division of the sinoatrium into the two atria results in a single atrium. Improper closure results in an atrial septal defect.

2. Failure of migration of the ventricular septum and atrioventricular valve between the primitive ventricle and the bulbus cordis results in a double-outlet left ventricle (single ventricle). Minor migrational defects result in ventriculoseptal defects.

3. Failure of division of the truncus into the pulmonary artery and the aorta results in truncus arteriosus.

c. The aortic arch system initially consists of six pairs of arches.

1. The sixth arches produce the pulmonary arteries. The ductus arteriosus develops from the distal portion of the right sixth arch. Although the left proximal sixth arch usually degenerates, it can persist and form an aberrant left ductus arteriosus.

2. Failure of regression of various portions of the aorta and arch system also can result in aberrant vessels and vascular rings. For example, failure of regression causes a double aortic arch. Regression of the left-sided but not the right-sided arches can result in a right-sided aortic arch.

a. Fetal circulation: After the 12th week, the circulatory system is in its final form. Oxygenated blood from the placenta passes through the umbilical vein and the ductus venosus and returns to the heart. Subsequently, 85% to 95% of fetal cardiac output bypasses the pulmonary circulation by flowing right to left through the foramen ovale and the ductus arteriosus into the aorta.

b. At birth, umbilical placental circulation ceases with the clamping of the umbilical cord, and blood flow through the ductus venosus ceases. However, the ductus venosus often remains patent for up to a week. Also, the interruption of umbilical blood flow at birth reduces right atrial pressure and causes functional closure of the foramen ovale. Moreover, pulmonary resistance decreases as the lungs are distended and ventilated at birth, while systemic resistance increases with removal of the high-capacitance placental circulation. Constriction of the ductus arteriosus occurs with increasing PaO₂. Cessation of ductus arteriosus blood flow often occurs within several hours to days in term infants but may be delayed in prematurely born or sick infants.

1. Extracellular fluid (ECF) and total body water decrease as the fetus grows, while intracellular fluid increases with gestational age. ECF is 90% of total body weight at 28 weeks, 80% at 36 weeks, and 75% at term.

2. After birth, a physiologic diuresis occurs, with the term infant losing 5% to 10% of ECF in the first few days of life. Premature infants may lose up to 15% of ECF.

3. Before 32 weeks of gestation, the neonatal kidney is immature and has a relatively low glomerular filtration rate and altered tubular function. This leads to difficulties in excreting water loads and diminished capacity to reabsorb sodium and water and thereby concentrate urine. In part, this is due to incomplete glomerular development, tubule insensitivity to vasopressin, loops of Henle that have not yet penetrated into the medulla, low osmolality in the medullary interstitium, and low serum urea levels. Renal tubular function increases with postnatal age, and the concentrating ability of the kidney reaches adult levels at 6 to 12 months postnatal age.

1. In collecting the neonatal patient’s medical history, it is important to include information about antenatal events. Fetal growth and development are affected by maternal disorders, including hypertension, diabetes, lupus, and drug, cigarette, and alcohol use. Poly- or oligohydramnios, abnormal α-fetoprotein, maternal infections, and premature labor are often associated with neonatal problems.

2. Perinatal history also includes gestational age, time of onset of labor and rupture of membranes, use of tocolytics and fetal monitors, signs of fetal distress, type of anesthesia used and mode of delivery (spontaneous, forceps or vacuum assisted, or cesarean), condition of the infant at delivery, and immediate resuscitation steps required (e.g., intubation for meconium, ventilatory assistance, surfactant administration, CPR, or medication administration). The Apgar score should be noted as it reflects the degree of intrapartum stress as well as the effectiveness of initial resuscitation (Table 30.1). Points are awarded for each of the five criteria, with the maximum score being 10. Although the Apgar score at 1 minute correlates with intrauterine conditions, the 5- and 10-minute Apgar scores correlate best with neonatal outcome. In addition, ensure that vitamin K and ocular antibiotic ointment were given after birth to prevent hemorrhagic disease of the newborn and ophthalmia neonatorum, respectively.

1. A complete, systematic evaluation is needed. No assumptions should be made about the development, location, or function of organ systems. An abnormality in one system may be associated with abnormalities in another.

2. Vital signs provide a useful physiologic screen of organ function. If a cardiac abnormality is suspected, a chest x-ray (CXR), electrocardiogram (ECG), and four extremity blood pressure measurements are required. Postductal oxygen saturation should be greater than 94%. In addition, an echocardiogram and pediatric cardiology consultation should be considered. Normal vital signs are summarized in Table 30.2.

3. Gestational age influences care, management, and survival potential of the neonate. An infant is considered preterm if the gestational age is less than 37 weeks, term if it is 37 to 41 weeks, and postterm if the gestational age is more than 42 weeks. Although the date of conception and ultrasound examination can be used to predict gestational age, a physical examination to determine gestational age should be performed. The Dubowitz-Ballard scoring system involves evaluation of physical characteristics of the skin, external genitalia, ears, breasts, and neuromuscular behavior to assess gestational age.

4. Weight determination. Similar to gestational age, birth weight is an important prognostic factor for premature infants. By convention, low birth weight (LBW) infants weigh less than 2,500 g, very low birth weight infants (VLBW) less than 1,500 g, and extremely low birth weight (ELBW) infants less than 1,000 g. Intrauterine growth restriction (IUGR) is defined as a rate of growth less than a fetus’ predetermined genetic potential. Small-for-gestational age (SGA) infants at birth are less than 10th percentile of the standard population-based weight. This may be the result of chromosomal defects, maternal hypertension, chronic placental insufficiency, maternal cigarette or drug use, or congenital infection. These infants have a high incidence of hypoglycemia, hypocalcemia, and polycythemia. Infants who are large for gestational age (LGA) are greater than 90th percentile of standard population-based weight and may have mothers with diabetes. In the immediate postnatal period, LGA newborns should be evaluated for hypoglycemia and polycythemia. Infants of diabetic mothers and LGA infants are at risk of complications from fetal macrosomia, including shoulder dystocia and brachial plexus injuries.

5. Respiratory. Signs of respiratory distress include tachypnea, grunting, nasal flaring, intercostal and subcostal retractions, rales, rhonchi, asymmetry of breath sounds, and apnea. Pulse oximetry is used to screen the levels of systemic oxygenation in neonates. Blood gas tensions should be measured in patients with suspected cardiopulmonary abnormalities.

6. Cardiovascular. Central cyanosis and capillary refill should be assessed. Distal pulses should be palpated, noting whether they are bounding.
A delay between brachial and femoral pulses is suggestive of coarctation of the aorta. Note the character and location of murmurs and splitting of the second heart sound. During the first 48 hours after birth, murmurs may appear as intracardiac pressure gradients change and disappear as the ductus arteriosus closes.

7. Abdominal exam. A scaphoid abdomen suggests diaphragmatic hernia. A normal umbilical cord has two arteries and one vein. In nearly 40% of cases, the existence of a single umbilical artery is associated with renal abnormalities. The size of the liver, spleen, and kidneys and the presence of hernias or abdominal masses should be determined by inspection and palpation. The location and patency of the anus should be assessed.

8. Neurologic. A thorough examination includes evaluation of motor activity, muscle strength and tone, and newborn reflexes (Moro, tonic neck, grasp, suck, and stepping reflexes). Full-term newborns should have an up-going Babinski reflex and brisk deep tendon reflexes.

9. Genitourinary. The gonads may be differentiated or ambiguous, and in males, the testes should be palpable. The location of the urethra should be determined, remembering that hypospadias precludes a circumcision. A male infant with hypospadias and bilateral cryptorchidism must be evaluated for congenital adrenal hyperplasia.

10. Musculoskeletal. Any deformities, unusual posturing, or asymmetric limb movement should be noted, and the hips should be examined for possible dislocation with congenital hip dysplasia, particularly in breech infants. A clavicle or humerus may be fractured during a difficult delivery.

11. Craniofacial. One should determine head circumference, the location and size of the fontanelles, the presence of a cephalohematoma or caput, and ensure the palate is intact. Observing nasal gas flow despite occluding each naris or passage of a nasogastric tube will rule out choanal atresia.

C. Laboratory Studies. Routine initial laboratory studies may include hematocrit and serum glucose. Additional studies should be guided by the individual problem. For example, blood type and Coombs determination may be indicated in infants at risk for hyperbilirubinemia such as those whose mothers who are blood type O. In addition, a CBC and blood culture should be checked and wide spectrum antibiotic therapy initiated if there is suspicion of neonatal sepsis or maternal chorioamnionitis.

1. The total fluid requirement varies with birth weight.

a. Less than 1.0 kg, use 100 mL/kg/d.

b. 1.0 to 1.5 kg, use 80 to 90 mL/kg/d.

c. 1.5 to 2.5 kg, use 80 mL/kg/d.

d. Greater than 2.5 kg, use 60 mL/kg/d.

2. Isosmolar solutions should be used.

a. Electrolyte supplementation is not required within the first day of life for maintenance fluids in full-term infants. For premature infants, check the electrolytes at 8 to 12 hours of life and consider adjusting the fluid infusion rate and/or adding electrolytes as indicated.

b. 10% Dextrose in water is typically used as the initial IV fluid in preterm and term infants. Blood glucose concentrations should be monitored closely in high-risk infants and the dextrose concentration of IV fluids should be adjusted as required to maintain serum glucose levels described below.

3. Additional fluids may be required for insensible water loss.

a. Fluid requirements increase with lower birth weight and gestational age, as well as with many neonatal interventions including phototherapy, radiant warmer use, and support of infant with respiratory distress.

b. Insensible losses from pathologic causes (e.g., omphalocele, gastroschisis, neural tube defect, bladder exstrophy) must similarly be taken into account and replaced. The electrolyte composition of the replacement fluid should match that of what is lost.

c. Infants who are mechanically ventilated absorb free water through their respiratory system.

4. Several signs will determine the adequacy of fluid infusions.

a. Urine output at least 1 mL/kg/h.

b. Only a 1% loss in body weight per day for the first 10 days of life.

c. Stable hemodynamics and good perfusion.

1. The usual electrolyte requirements after the first 12 to 24 hours of life are as follows:

a. Na⁺, 2 to 4 mEq/kg/d.

b. K⁺, 1 to 2 mEq/kg/d.

c. Ca⁺², 150 to 220 mEq/kg/d.

2. The frequency of laboratory tests for serum electrolyte levels will be determined by the rate of insensible loss.

F. Glucose. Supplemental glucose should be given after birth to keep blood glucose levels between 50 and 125 mg/dL.

1. In most infants, 10% D/W at maintenance fluid rates will provide adequate glucose. This infusion rate provides the 5 to 8 mg/kg/min of glucose that is required for basal metabolism.

2. Infants with hyperinsulinism, intrauterine growth restriction, or metabolic defects can require glucose infusion rates as high as 12 to 15 mg/kg/min.

3. In peripheral intravenous lines, up to 12.5% D/W may be infused. In central lines, 15% to 20% D/W may be infused.

4. Hypoglycemia (glucose <50 mg/dL) is treated with a bolus of glucose and increased glucose infusion rate.

a. Glucose at 200 mg/kg intravenously (IV) is given over a minute (e.g., 10% D/W at 2 mL/kg).

b. The glucose infusion rate is increased from the current level or started at 8 mg/kg/min IV.

c. Serial blood tests are necessary to determine the effectiveness of the increased glucose.

G. Nutrition. The gastrointestinal tract is functional after 28 weeks of gestation but is of limited capacity. Requirements vary with each neonate.

1. Calories. Requirements are 100 to 130 kcal/kg/d.

2. Protein. Requirements are 2 to 4 g/kg/d.

3. Fat. Initiate at 1 g/kg/d and increase gradually as tolerated up to 3 to 4 g/kg/d so that the fat provides 40% of the daily calories.

4. Vitamins A, B, D, E, C, and K should be provided.

5. Iron. Requirements are 2 to 4 mg/kg/d of elemental iron. The adequacy of iron supplementation can be assessed by measuring the hemoglobin or hematocrit and the reticulocyte count.

6. Minerals. Calcium, phosphate, magnesium, zinc, copper, manganese, selenium, and iron need to be replaced. Premature infants, in particular, have increased calcium and phosphate requirements in order to prevent metabolic bone disease of prematurity.

7. Enteral feedings. Feedings are usually initiated with breast milk or a formula contains the whey-to-casein ratio that is contained in breast milk. For infants that exhibit lactose intolerance, non- or low-lactose containing formulas are available. Infants less than 32 weeks of gestation often have poor suck and swallow reflexes and require gavage feedings. For premature infants or ill full-term neonates, small volume enteral feedings are generally initiated once the baby is stable. Subsequently, the volumes of the feedings are gradually increased every 12 to 24 hours as they are tolerated. Once the desired goal volume of enteral feedings is reached, the breast milk or formula is supplemented with additional calories, as needed, to attain the desired weight gain.

8. Parenteral feeding. If enteral feeding is impossible, parenteral nutrition should be started as soon as possible to promote positive nitrogen balance and growth. The metabolic status of the infant should be assessed frequently so that the parenteral formulation can be adjusted to meet the infant’s needs and to identify signs of toxicity from hyperalimentation. Usual studies include serum glucose, electrolytes, osmolality, liver function tests, blood urea nitrogen, creatinine, lipid levels, and platelet count.

H. Thermoregulation. It is critical to measure the newborn’s body temperature and use active measures to maintain it in a euthermic range. Babies exhibit thermal instability because of decreased epidermal and dermal thickness, minimal subcutaneous fat, immature nervous system, and increased surface area to body weight ratio with a relatively large head size. Moreover, premature newborns are particularly susceptible to hypothermia because they lack thermogenic brown fat cells. Measures to maintain the newborn’s body heat include using a warm incubator during transport to and from the nursery; keeping the ambient operating room temperature at 85°F (30°C); using warming blankets, radiant warmers, and a head cover; and prewarming intravenous fluids. Neonates with significant cold stress are particularly prone to hypoglycemia.

1. Conditions that require emergent surgery in neonates are often accompanied with medical problems. As a result, the care for these critically ill newborns requires careful coordination of medical, surgical, and nursing management. In some cases, surgical procedures might occur in the neonatal intensive care unit. In these instances, before the surgical procedure is initiated, it is important to identify and integrate the key resources and care measures provided by the NICU team into the anesthetic management of the surgical procedure.

2. Routine standard monitoring for neonates undergoing surgical procedures includes blood pressure monitoring and continuous electrocardiograph, temperature, pulse oximetry, and O₂ and CO₂ gas measurements. Specialized monitoring for surgical procedures detailed below may also include postductal pulse oximetry, chest piece stethoscopes, and continuous blood pressure monitoring and intermittent blood sampling through arterial and central lines. In infants with umbilical arterial and venous catheters, it is important to confirm the precise location of the tips of the lines and their suitability for fluid and drug infusions and blood sampling.

3. Nonrebreathing circuits are effective for ventilating and for delivering gaseous anesthetic agents to newborns and infants. The system must
have provisions for humidification of the inspired gases to decrease the insensible fluid losses and thereby help maintain the patient’s thermostability. If gaseous anesthetic agents are to be used in the NICU, it is important to scavenge the gases that are exiting the ventilator. In some cases, it is better to continue to use the specialized ventilators used in the NICU (e.g., high-frequency oscillator ventilator) rather than the anesthesia machine to support the patient during surgery. A warm operating room (85°F), underbody heaters, radiant warmers, head wraps, and prewarmed intravenous and surgical fluids are also critical in helping the infant maintain thermoregulation.

4. A warm neonatal transport isolette complete with monitors, adequate oxygen supply, and emergency airway and drugs is required for moving neonatal patients to and from the intensive care unit and OR.

1. Differential diagnosis. The following diseases present similarly as pulmonary parenchymal disease and should be considered when evaluating an infant with respiratory distress.

a. Airway obstruction. Choanal atresia, vocal cord palsy, laryngomalacia, tracheal malacia or stenosis, and compression of the trachea by external masses (e.g., cystic hygroma, hemangioma, and vascular ring).

b. Developmental anomalies. TEF, CDH, congenital lobar emphysema, pulmonary sequestration, bronchogenic cysts and congenital pulmonary airway malformations (CPAMs)/congenital cystic adenomatoid malformations (CCAMs).

c. Nonpulmonary. Cyanotic heart disease, PPHN, congestive heart failure, and metabolic disturbances.

2. Laboratory studies for an infant in respiratory distress should include an arterial blood gas, pre- and postductal oxygen saturation (determined by pulse oximetry), hemoglobin or hematocrit, 12-lead ECG, and CXR. If these results are abnormal, potential cardiac disease should be evaluated by assessing blood gas tensions while the neonate breathes 100% O₂ (hyperoxia test). As indicated, cardiology consultation and an echocardiogram will help evaluate potential congenital heart disease.

1. Central apnea is due to immaturity or depression of the respiratory center (e.g., narcotics). It is related to the degree of prematurity and is exacerbated by metabolic disturbances (e.g., hypoglycemia, hypocalcemia, hypothermia, hyperthermia, and sepsis). Before 34 weeks of gestational age, central apnea is often treated with methylxanthines such as caffeine citrate.

2. Obstructive apnea is caused by inconsistent maintenance of a patent airway. It can result from incomplete maturation and poor coordination of upper airway musculature. This form of apnea may respond to changes in head position, insertion of an oral or nasal airway, or placement of the infant in a prone position. Occasionally, administration of continuous positive airway pressure (CPAP) or a high-flow oxygen nasal cannula may be beneficial. These therapies especially may be effective in infants with a large tongue, such as with trisomy 21 or Beckwith-Wiedemann syndrome.

3. Mixed apnea represents a combination of both central and obstructive apnea.

1. Apnea may be associated with anesthesia in infants that are born prematurely. Although it has been observed following general anesthesia, apnea has been reported in infants treated with local anesthesia.

2. If it is not possible to delay surgery until the patient is more mature, it is prudent to use postoperative apnea monitoring in neonates who undergo anesthesia at less than 60 weeks postconceptual age.