Respiratory Care in the Neonate

Marjorie J Arca, MD, Sarah K Walker, MD

Introduction

see also Respiratory Care

Content in this topic is referenced in SCORE Lung Physiology, Pathophysiology, Ventilators, and Pneumonia overview

Embryology

The primitive foregut is derived from endoderm. A tracheoesophageal ridge forms at four weeks gestation, separating the tracheal diverticulum from the esophagus. The trachea subdivides into lung buds. The lung buds are lined by endodermally derived epithelium that differentiate into epithelium that lines the airways and specialized alveolar epithelium. Some bronchial epithelial cells further differentiate into Type II alveolar surfactant producing cells. Mesodermal elements in the lung give rise to cartilage, blood vessels and smooth muscle. Nerves are derived from ectoderm. The bronchial tree is fully developed by sixteen weeks gestation. Lung development occurs between 28 and 32 weeks.

There are four stages of lung development:

  1. pseudoglandular stage (5 to 16 weeks) - characterized by branching of the terminal bronchioles
  2. canalicular stage (16 to 26 weeks) - the terminal bronchioles subdivide into two or more respiratory bronchioles that divide into three to six alveolar ducts.
  3. terminal sac stage (26-weeks to birth) - terminal sacs or primitive alveoli form and alveolar capillaries establish close contact with the alveoli
  4. alveolar stage (birth to childhood) - alveoli mature and divide further to reach adult numbers

Surfactant is a substance that is secreted by Type II pneumocytes which decreases surface tension in the lung. It consists of 85% phospholipid, 5% carbohydrate and 10% protein. The phospholipids consist primarily of phosphotidylcholine (lecithin) and sphingomyelin. Initially, sphingomyelin predominates as the primary phospholipid. At 32 weeks gestation, lecithin production increases while sphingomyelin production remains stable. An L:S ratio greater than or equal to 2:1 indicates lung maturity.

There are several strategies employed by the fetus to optimize oxygen delivery. These are also seen in newborns as they transition to normal adult circulation. Firstly, the fetal hematocrit is 55% - higher than the mother’s (approximately 35%). Therefore, the fetus and newborn have a higher capacity to bind to oxygen. Secondly, fetal hemoglobin (HgbF), the major hemoglobin present during gestation, has a higher affinity for oxygen compared to adult hemoglobin (HgbA). HgbA has two alpha units and two beta units; it is able to bind four molecules of oxygen. HgbF has two alpha units and two gamma units. 2,3 diphosphoglycerate (2,3 DPG) helps unload oxygen. In HgbA, 2,3 DPG binds to the beta subunits and facilitates the dissociation of oxygen from the HgbA molecule. In contrast, the gamma subunits in HgbF do not allow 2,3 DPG to bind easily and therefore HgF holds on to O2 more tightly than HgbA. On the oxygen dissociation curve, HgbF represents a leftward shift compared to the normal curve because of its lack of affinity to bind 2,3-DPG and therefore a lower p50 compared to normal HgbA. (see also Transfusion and Coagulation Therapy Embryology)

Anatomy

How do the anatomic changes of the developing thorax effect ventilation?

Infants are preferential nasal breathers. Nasal flaring can signify respiratory distress.

Accessory muscles such as the scalene muscles are not well developed in neonates and therefore, ineffective in augmenting respiratory efficacy.

The anterior posterior (AP) diameter of the thoracic cage is larger in neonates compared to older infants and children. The AP distance of the neonatal chest is nearly equal to the lateral distance. The neonatal chest wall is more compliant compared to older children and adults. In the paralyzed state, the compliance of the chest wall is quite high and often greater than 25 mL/cm H2O. The ribs of the newborn infant are made mostly of cartilage and are quite elastic. The ribs are positioned in a more horizontal state compared to adults. The shape of the infant thorax is triangular - unlike the dome shaped adult chest. Consequently, the lateral bucket handle action of the chest that usually occurs during inspiratory phase does not help significantly in increasing tidal volume in infants. The infant intercostal muscles serve more as stabilizers of the chest wall rather than expanders during inspiration.

The neonatal diaphragm is flatter in shape and located higher in the torso compared to adults. This configuration leads to a bellows type action of the infant diaphragm compared to piston like mechanism in adults. Further, the contact area of the diaphragm around the chest is small, limiting its ability to expand the thoracic circumference. These limitations makes increasing tidal volume difficult in infants. Therefore, they use faster breathing as the primary mechanism of increasing minute ventilation.

In general, muscles can be classified into two types: type I fibers are "slow twitch fibers" that generate peak tension slowly but are more fatigue resistant and type II fibers are "fast twitch" that generate peak tension quickly but fatigue more rapidly. Type II fibers are subclassified at IIa (fast twitch oxidative) and IIb (fast twitch glycolytic) according to their staining uptake of NADH tetrazolium reductase. Type IIb fibers fatigue very rapidly. The diaphragm of a preterm baby has ten percent type I fibers which increases to 25% at term and 55% at childhood. This means that preterm babies have more fatigue prone fibers in their muscles of respiration compared to infants and older children.

The heart occupies a larger proportion of the chest cavity in infants compared to older children. The abdomen is also relatively large and pushes against the diaphragm. These anatomic and physiologic factors contribute to a low respiratory reserve in babies [1].

Prenatal Concerns

Prenatal Care

A course of antenatal steroids administered to women at risk for preterm delivery has been shown to decrease the incidence and severity of respiratory distress syndrome in infants [2]. Treatment typically consists of two doses of 12 mg of betamethasone given intramuscularly 24 hours apart or four doses of 6 mg of dexamethasone given intramuscularly twelve hours apart. The optimal benefit begins 24 hours after initiation of therapy and lasts seven days. The most recent review showed no clear advantage of one regimen over the other but the patients treated with dexamethasone may have less intraventricular hemorrhage and shorter stay in the intensive care unit. Current recommendations for the use antenatal steroids include pregnant women between 24 and 34 weeks gestation at risk of preterm delivery, those who are being treated with tocolytics and fetuses with an immature lung profile. It should be noted that antenatal steroid use has also been shown to decrease the incidence of intraventricular hemorrhage in preterm infants. Contraindications to steroid use include chorioamnionitis and other severe maternal infections.

Recently, the American College of Obstetricians and Gynecologists issued a practice advisory that administration of antenatal betamethasone may be of benefit for pregnancies at high risk of late preterm birth between 34 0/7 and 36 6/7 weeks of gestation [3]. The Antenatal Late Preterm Steroids Trial [4] showed that the primary outcome impacted by administration of antenatal corticosteroids in this gestational age was the decreased need for respiratory support, as well as decreases in severe respiratory complications, transient tachypnea of the newborn (TTN), bronchopulmonary dysplasia (BPD), a composite of respiratory distress syndrome, TTN and apnea, the use of postnatal surfactant and the need for immediate postnatal resuscitation. There was also a decrease in the proportion with prolonged neonatal intensive care unit (NICU) stays. Hypoglycemia is more common in infants of mothers treated with betamethasone and therefore glucose should be carefully monitored in these infants.

Medical Treatment

What are the indications for mechanical ventilation in an infant?

The indications for mechanical ventilation in infants include prolonged or repeated episodes of apnea, tachypnea, hypopnea, and/or irregular respiratory patterns. Respiratory distress can result from neurologic depression related to seizures, intraventricular hemorrhage, sepsis, or medications such as opioids or sedatives. A pO2 less than 50 mm Hg, a pCO2 greater than 55 mmHg and a pH less than 7.25 are laboratory values that signify respiratory compromise and the need for ventilator support.

How is the airway controlled in infants?

Neonates and infants are intubated with uncuffed endotracheal tubes to decrease the risk of subglottic stenosis. Infant ventilators have low compliance tubes, measuring 0.5 mL/cm H2O compared to a 3 mL/cm H2O pressure in adults. Infant circuits have narrow tubing and therefore higher resistance. However, since the flow rates used in infant ventilators are so low the high resistance typically does not matter. Infant circuits have in line water traps or heated wires because water in the narrow tubing is more of an obstruction problem than in the adult circuit.

How is mechanical ventilation different in infants?

A traditional pressure triggered ventilator typically would not allow the baby to trigger the demand valve because the pressure required to start a breath may be higher than a baby can generate. Because the endotracheal tubes are uncuffed, it is challenging for the patient to trigger the demand valve by reaching a preset negative pressure. When a breath is not triggered, the patient may rebreathe CO2 (i.e.autocycling). Most ventilators used in the neonatal intensive care unit are continuous flow devices that do not have a triggering mechanism. The patient’s spontaneous breathing occurs off of a continuous positive airway pressure flow of around 10 +/- 2 liters per minute and the machine delivers the breath based on time cycling [5].

Infants were traditionally placed on pressure control modes due to the inability to consistently and accurately deliver a guaranteed small tidal volume in patients with uncuffed tubes - especially in babies weighing less than ten kilograms. As a result, pressure limited (also called pressure controlled) ventilation has been the mainstay of mechanical ventilatory support in infants and young children. However, delivery of volume targeted breaths in neonates (three to six mL/kg) has now been made possible by microprocessor technology [6]. There is no data to support either pressure or volume ventilation as being superior in infants but either modality is possible in contemporary neonatal intensive care units. Most current generation neonatal ventilators offer multiple modes and modalities with sophisticated interfaces. These ventilators enable the clinician to customize ventilation to the individual needs and the pathophysiology of the individual patient [7].

The initial ventilator settings in infants (weight of 2000 gm or less) with full support would typically consist of intermittent mandatory ventilation(IMV) with a respiratory rate of 60, 
FiO2 0.6, 
flow rate 6 to 8 Lpm, Itime 0.20 to 0.30 seconds, peak inspiratory pressure (
PIP) 20 to 25 cm H20, 
peak end expiratory pressure (PEEP) 5 cm H2O, thus yielding an I: E ratio of 1:3 or 1:4. Larger infants require a lower respiratory rate of 30 to 40 , Itime 0.40 seconds, 
flow rate 10 Lpm +/- 2, PIP 20 cm H2O, PEEP 
5 cm H2O and 
FiO2 less than 0.6 [5].

Prone positioning in infants has been shown to increase oxygenation slightly without effecting sustained clinical improvements [7].

How are infants weaned from the ventilator?

Similar to pediatric patients, there are no consensus criteria in mechanical ventilation weaning for extubation in infants. When weaning mechanical ventilation, an assessment of the patient’s overall ability to breathe independently and systematic reduction of ventilator settings go hand in hand. Often, weaning occurs according to institutional guidelines or the physician’s individual judgment. If the baby’s oxygen saturation and/or paO2 is stable, FiO2 is decreased until it is lower than 0.6 to prevent O2 toxicity. When the patient’sFiO2 requirement is less than 0.3 other parameters may also be weaned. As lung compliance improves, the PaCO2 improves with the same PIP (or TV). PIP is then dropped by 1 to 2 points. When the PIP is about 16 to 18 cm H2O, the back up respiratory rate is decreased by one to two breaths per minute. Maintaining the O2 saturation above 92% is a reasonable goal. Once the PIP is 18 or less, the rate is less than 20 and the FiO2 is 0.3 or less, the patient can be weaned to continuous positive airway pressure (CPAP). If the PaCO2 and the PaO2 are reasonable, the infant can be extubated and placed on CPAP by nasal cannula or high flow nasal cannula depending on what the patient requires [8].

What is the role of surfactant replacement therapy?
Respiratory distress syndrome (RDS) in a newborn is clinically manifest by impaired gas exchange in a premature infant. Typical radiographic findings of the lungs include a ground glass appearance, air bronchograms and reduced lung volume.

neonatal respiratory distress syndrome
Descriptive text is not available for this image
Chest radiograph of a newborn with neonatal respiratory distress syndrome. Salient features include low lung volumes, air bronchograms and ground glass or salt and pepper appearance of the lung fields.

Surfactant is a substance secreted by type II pneumocytes. Surfactant lines the alveoli surface and decreases surface tension thereby decreasing the work of breathing and preventing atelectasis. Surfactant contains phospholipids and four types of proteins: hydrophilic (SP-A and SP-D) and hydrophobic (SP-B and SP-C) proteins. Phosphatidylcholine comprises 80% of mature surfactant, half of which is dipalmitoylphosphatidylcholine (DPPC). The production of endogenenous surfactant increases between 30 and 32 weeks of gestational age.

Premature infants less than 32 weeks gestational age have immature lungs with inadequate surfactant production. Many studies have been performed on the efficacy of surfactant replacement in babies with RDS. The following are the current recommendations for surfactant replacement [9][10][11].

  1. Infants with RDS should receive exogenous surfactant therapy (grade A recommendation). Babies with RDS treated with surfactant have shorter hospital stays and lower costs of treatment compared to infants receiving no surfactant.
  2. Infants with meconium aspiration syndrome who require mechanical ventilation and an FiO2 greater 0.5 should receive exogenous surfactant therapy (grade A).
  3. Infants who are at a significant risk for RDS should receive prophylactic natural surfactant therapy as soon as they are stable and within a few minutes after intubation (grade A).
  4. Exogenous surfactant therapy should be considered in newborn infants with pneumonia and an oxygenation index greater than 15 (grade C).
  5. Intubated newborn infants with pulmonary hemorrhage which causes clinical deterioration should receive exogenous surfactant therapy as one aspect of clinical care (grade C).
  6. When possible, natural surfactants should be used instead of artificial surfactants since they seem to have greater efficacy (grade A).
  7. If there is a persistent or recurrent oxygen requirement (FiO2 greater than 0.3) and ventilatory requirements are present within the first 72 hours of life, repeated doses of surfactant should be considered. However, administering more than three doses has not been shown to have a benefit (grade A).
  8. Retreatment doses may be given as early as two hours after the initial dose or, more commonly, four to six hours after the initial dose of 120 mg phospholipids/kg body weight (grade A).
  9. If an infant requires transport it is recommended that exogenous surfactant therapy be administered before transport (grade C).

The typical administration of surfactant is intratracheal through an indwelling endotracheal tube. However, administration of surfactant through an intratracheal catheter in patients on CPAP has been described.

For a discussion of permissive hypercapnia and inhaled nitric oxide see Respiratory Care Medical Treatment

There is no role for the routine use of diuretics to treat RDS [12].

Complications

What is pulmonary interstitial emphysema?
Pulmonary interstitial emphysema (PIE) occurs when the alveoli and terminal bronchioles rupture releasing air into the perivascular and peribronchial tissues of the lung. Two factors are the sine qua non for the development of PIE.

  • decreased lung compliance such as seen in respiratory distress syndrome (RDS), meconium aspiration syndrome, amniotic fluid aspiration, infection and prematurity
  • high intra-alveolar pressures with positive pressure ventilation

The air leak observed in PIE can be: centrifugal (characterized by the development of subpleural bubbles and pneumothorax), centripetal (where air pockets migrate centrally and rupture causing pneumothorax, pnemomediastium or pneumopericardium) and/or systemic air embolism (rarely found and almost always fatal where the air disseminates through lymphatic channels and or alveolovascularfistulae into the heart chambers and arterial and/or venous vessels). In more mature infants, the air pockets are seen under the visceral and mediastinal pleural surfaces, while in premature babies the pockets are more likely to be on the lung surface along the costal margins. In either case, the abnormal air pockets may compress adjacent structures such as functional lung and blood vessels [13].

On chest radiographs, PIE manifests as hypoattenuating, serpentiform, tubular, and sometimes cystic changes that do not fit the air bronchogram pattern. On computerized tomography the lung parenchyma has a pattern described as lines and dots intermingled with large gaseous inclusions which represent peribronchovascular bundles compressed by the air filled interstitium. Although the findings are typically present bilaterally, unilateral PIE has been described. Furthermore, PIE can be focal or diffuse [14].

The treatment for PIE is mainly supportive and varies with the presentation of the disease as well as the patient status. For mechanically ventilated infants, decreasing the airway pressure is mandatory and high frequency oscillatory ventilation or high frequency jet ventilation is often used to achieve this goal. Changing from pressure control to volume control ventilation would likely not achieve the goal of decreasing alveolar pressure in patients with poor lung compliance. If the disease is unilateral, placing the diseased lung down compresses the affected lung and improves the ventilation of the better lung. If there is continued and clinically significant air leak involving one lung, selective bronchial intubation of the contralateral lung may help seal the leak [15]. Pneumomediastinum is treated expectantly, but pneumopericardium and pneumothorax may require decompression when they cause physiologic compromise.

The mortality associated with PIE ranges from 24 to 68%. In infants with birth weights less than 1600 g and RDS, the mortality approaches 80%. Importantly, survivors have a high likelihood of developing chronic lung disease of the newborn.

What is acquired subglottic stenosis?

Historically, acquired subglottic stenosis was found in up to 24% of infants who required prolonged endotracheal intubation. More recent data show a two percent incidence in subglottic stenosis after prolonged intubation [16]. Factors implicated in the development of subglottic stenosis include the size of the endotracheal tube relative to the child’s larynx, the duration of intubation, the motion of the tube and repeated intubations. Additional factors that affect wound healing include systemic illness, malnutrition, gastroesophageal reflux and tracheitis.

Perspectives and Commentary

To submit comments about this topic please contact the editors at think@apsapedsurg.org.

Additional Resources

APSA Handbook of Pediatric Surgical Critical Care

Discussion Questions and Cases

To submit interesting cases which display thoughtful patient management please contact the editors at think@apsapedsurg.org.

References

  1. Neonatal Respiratory Disorders, Second Edition. Anne Greenough and Anthony D. Milner, Editors. Copyright 2003 by Taylor and Francis Group LLC
  2. Roberts D, Dalziel S. Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst Rev. 2006.  [PMID:16856047]
  3. Practice Advisory: Antenatal Corticosteroid Administration in the Late Preterm Period. www.acog.org. Accessed May 1, 2016

    Rating: LOE Review

  4. Gyamfi-Bannerman C, Thom EA, Blackwell SC, et al. Antenatal Betamethasone for Women at Risk for Late Preterm Delivery. N Engl J Med. 2016;374(14):1311-20.  [PMID:26842679]
  5. Donn SM. Neonatal ventilators: how do they differ? J Perinatol. 2009;29 Suppl 2:S73-8.  [PMID:19399015]
  6. Arca MJ, Uhing M, Wakeham M. Current concepts in acute respiratory support for neonates and children. Semin Pediatr Surg. 2015;24(1):2-7.  [PMID:25639802]
  7. Balaguer A, Escribano J, Roqué i Figuls M, et al. Infant position in neonates receiving mechanical ventilation. Cochrane Database Syst Rev. 2013;3:CD003668.  [PMID:23543520]
  8. Bancalari E, Claure N. Strategies to accelerate weaning from respiratory support. Early Hum Dev. 2013;89 Suppl 1:S4-6.  [PMID:23809348]
  9. El Shahed AI, Dargaville PA, Ohlsson A, et al. Surfactant for meconium aspiration syndrome in term and late preterm infants. Cochrane Database Syst Rev. 2014;12:CD002054.  [PMID:25504256]
  10. Sweet DG, Halliday HL, Speer CP. Surfactant therapy for neonatal respiratory distress syndrome in 2013. J Matern Fetal Neonatal Med. 2013;26 Suppl 2:27-9.  [PMID:24059549]
  11. Walsh BK, Daigle B, DiBlasi RM, et al. AARC Clinical Practice Guideline. Surfactant replacement therapy: 2013. Respir Care. 2013;58(2):367-75.  [PMID:23359726]
  12. Stewart A, Brion LP, Soll R. Diuretics for respiratory distress syndrome in preterm infants. Cochrane Database Syst Rev. 2011.  [PMID:22161366]
  13. Verma RP, Chandra S, Niwas R, et al. Risk factors and clinical outcomes of pulmonary interstitial emphysema in extremely low birth weight infants. J Perinatol. 2006;26(3):197-200.  [PMID:16493434]
  14. Agrons GA, Courtney SE, Stocker JT, et al. From the archives of the AFIP: Lung disease in premature neonates: radiologic-pathologic correlation. Radiographics. 2005;25(4):1047-73.  [PMID:16009823]
  15. Joseph LJ, Bromiker R, Toker O, et al. Unilateral lung intubation for pulmonary air leak syndrome in neonates: a case series and a review of the literature. Am J Perinatol. 2011;28(2):151-6.  [PMID:20703979]
  16. Walner DL, Loewen MS, Kimura RE. Neonatal subglottic stenosis--incidence and trends. Laryngoscope. 2001;111(1):48-51.  [PMID:11192899]
  17. Brownfoot FC, Gagliardi DI, Bain E, et al. Different corticosteroids and regimens for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst Rev. 2013;8:CD006764.  [PMID:23990333]
Last updated: November 2, 2020