Vol. 16 •Issue 9 • Page 47
The intricacies of managing lung disease in newborns
DURING fetal life, the placenta is the site of gas exchange, and the lungs are filled with fluid and have limited blood flow. Successful transition from fetal to neonatal life is dependent upon a significant increase in pulmonary blood flow, clearance of lung liquid, and establishment of an air-fluid interface with surfactant in the lung.
Abnormal events related to any of the above factors can give rise to neonatal lung disease. Lung disease is a common indication for admission and mechanical ventilation in the neonatal intensive care unit and is caused by various conditions. (See Table.)
Great strides have been made in our understanding of neonatal lung disease and its management. Optimal evidence-based respiratory management should target long-term respiratory and neurological well-being and avoid toxicity associated with ventilation and oxygen exposure.
Interpretation of blood gas in newborns
The basic principles of blood gas interpretation in the newborn are similar to adults. The umbilical cord provides a convenient, non-traumatic, and painless site for arterial and central venous access in newborns. (See Figure 1.)
Capillary samples obtained by a warmed heel stick often are used in newborn infants. Warming the skin increases blood flow through the capillary bed, so values for capillary pH and pCO2 usually correlate closely with values from arterial specimens. However, capillary pO2 measurements don’t correlate well with arterial values. Blood gases obtained from arterial stick or heel stick can be influenced by crying and agitation, resulting in hyperventilation and decreased pCO2.
The saturation of hemoglobin in blood gas reports often is influenced by the presence of fetal hemoglobin (HbF). Term newborn babies have approximately 70 percent HbF (higher in preterm). Fetal Hb is bound more avidly to oxygen and has higher oxygen saturations for a given PaO2 compared to adult Hb. The content of HbF in newborn babies also can vary markedly with transfusion (from adult donors) of packed red blood cells.
In hypoxic babies with minimal or no respiratory distress, all that may be required to keep the baby’s PaO2 higher than 60 mm Hg is administration of warmed humidified supplementary oxygen via hood. Many babies with transient tachypnea or mild meconium aspiration syndrome and some preterm babies > 30 weeks gestation with minimal lung disease can be managed with oxygen hood alone. It isn’t recommended to use nasal cannula for oxygen delivery in the first 24 hours because it’s less clear what effective oxygen concentration is required while the baby’s respiratory status is evolving.
For convalescing babies, including babies requiring prolonged oxygen therapy for bronchopulmonary dysplasia, administration of oxygen by nasal cannula allows the baby to be picked up and cuddled or fed. It’s more difficult to assess the effective oxygen concentration or pressure delivered, especially if using high-flow (> 2L/min) nasal cannula. A useful Web site for calculating effective oxygen concentration on nasal cannula is http://www.pub.emmes.com/study/rop/stop-js.html.
Continuous positive airway pressure
CPAP is defined as the application of positive airway pressure throughout the respiratory cycle. Neonatal lungs have a tendency to collapse and not maintain functional residual capacity (FRC) at the end of expiration. Early CPAP from the delivery room for premature infants with respiratory distress syndrome can provide lung stability, while avoiding the trauma of positive pressure ventilation. The major effects of CPAP are to increase FRC, stabilize the chest wall, and improve ventilation-perfusion (V/Q) matching.
CPAP may be delivered using an underwater seal; vigorous bubbling results in chest vibrations that may contribute to gas exchange (similar to oscillatory ventilation). Short binasal prongs are more effective than single nasal or nasopharyngeal prongs.
The infant’s work of breathing is reduced in more recent CPAP systems by providing variable pressures during the respiratory cycle. These systems use fluidic flip technology and the Coanda effect to redirect gas flow to the expiratory limb (away from the infant) during exhalation to decrease the work of breathing. Variable-flow nasal CPAP systems are associated with better lung recruitment compared to continuous flow CPAP. Nasal CPAP levels of 4 to 6 cm H2O may be used initially.
If adequate response isn’t obtained and there’s no evidence of hyperinflation, higher levels may be considered. Excessive CPAP may result in overdistension, CO2 retention, and pneumothorax. Prolonged application of nasal prongs occasionally is associated with nasal septal injury. Weaning from CPAP can be accomplished by reducing pressure or by “sprinting” off CPAP to nasal cannula for progressive durations.
Assisted ventilation that provides positive pressure with phasic increases without an endotracheal tube is referred to as noninvasive ventilation. These devices appear to be more effective than conventional CPAP in preventing extubation failure and reducing apnea frequency. Rates ranging from 10 to 20/min and inspiratory times from 0.4 to 1 second have been used in various studies.
Intubation in neonates is performed with 2.5 to 4.0 size uncuffed endotracheal tubes (ETT). The size of the ETT is determined by the patient’s gestational age or birth weight (e.g., < 28 weeks/ < 1,000 g usually have a 2.5 ETT). Adding 6 to the weight in kg is a general guide for ETT insertion length at the level of the lip in cm (e.g., 6 + 2 = 8 cm from the lip if the birth weight is 2,000 g). The position should be confirmed with a capnograph and a chest X-ray.
Intermittent positive pressure ventilation
Time-cycled pressure-limited ventilation (TCPLV) results in relatively square-wave inspiratory pressure pattern. (See Figure 2.) This is the most commonly used mode in the NICU. The peak inspiratory pressure (PIP) is set to provide an adequate, but not excessive, chest wall expansion (usually a delivered tidal volume of approximately 4-6 mL/kg).
Positive end-expiratory pressure (PEEP) always should be used in neonatal ventilation as it maintains FRC and stabilizes surfactant during expiration. Excessive PEEP combined with a short expiratory time results in gas trapping. Low PEEP is adequate in preterm babies with respiratory insufficiency related to prematurity or apnea without lung disease. High PEEP is required in severe RDS even after surfactant, pulmonary edema, or pulmonary hemorrhage and also in more severe BPD.
Mean airway pressure (MAP) and inspired oxygen concentration determine oxygenation. MAP is increased by prolonging the inspiratory time, increasing PEEP or PIP. Increasing PEEP is the most effective way of increasing MAP, lung volumes, and oxygenation. Ventilator rate and tidal volume determine minute ventilation and CO2 levels.
A/C, SIMV, PSV
Inspiratory activity is detected by changes in abdominal position (Graseby capsule), airflow, airway pressure, or impedence. The patient’s inspiratory activity either triggers or synchronizes with a ventilator breath. Synchronized intermittent mandatory ventilation (SIMV) uses this synchronization for all ventilator breaths at the set rate.
Assist control (A/C) gives full ventilator breaths with all breaths triggered by the baby. Frequently, additional spontaneous triggered breaths are partially supported to decrease the work of breathing associated with ETT resistance.
The use of A/C and SIMV reduce the duration of ventilation but have no impact on the incidence of BPD, intracranial hemorrhage, or air-leak syndromes. Weaning that involves reducing PIP during A/C is more effective and shorter than reducing SIMV rate below 20/min.
The patient’s inspiratory effort triggers a flow-cycled breath. Pressure support ventilation (PSV) is helpful in overcoming the work of breathing imposed by the narrow-lumen, high-resistance ETT in neonates.
Hybrid ventilation modes
In neonates with varying compliance (such as preterm infants with RDS receiving surfactant), TCPLV can result in varying tidal volumes, producing in fluctuations in PaCO2. Wide fluctuations in PaCO2 are associated with intraventricular hemorrhage (IVH) in preterm babies. PIP is maintained for the complete duration of inspiration, and these features can be an advantage in patients with poor lung compliance (e.g., RDS). Opening pressure is reached quickly because of the rapid initial flow followed by deceleration in TCPLV. (See Figure 2.)
Volume-controlled ventilation (VCV) delivers a predetermined tidal volume and is associated with less hypotension and shorter duration of ventilation in some trials. The main problem is that not all of the tidal volume is delivered to the baby because of compression of gas in the ventilator circuit and the baby’s respiratory system and leak around the uncuffed ETT. VCV is associated with a constant flow rate during inspiration. (See Figure 2). It takes longer to achieve PIP.
Moreover, high flow rates lead to more rapid filling of the lungs, set tidal volumes are achieved faster, which leads to an inverse relationship between flow and inspiratory time in VCV. Hence, PIP isn’t maintained for the complete duration of inspiration.
Hybrid modes attempt to combine the best features of TCPLV and VCV. Hybrid modes such as volume guarantee and pressure-regulated volume control (PRVC) combine the flow characteristics of pressure ventilation while providing optimal tidal volume. Generally, a targeted tidal volume is assured within a predetermined range of PIP.
High frequency ventilation
This is a form of mechanical ventilation that uses small tidal volumes and extremely rapid ventilator rates. It allows for pulmonary gas exchange with less stretch injury and volutrauma than conventional ventilation. In babies with PPHN, the use of high frequency ventilation with inhaled nitric oxide (NO) is effective in improving oxygenation. Two modes of high frequency ventilation are used in the NICU.
During high frequency jet ventilation (HFJV), a high pressure source delivers gas in short bursts through a small-bore cannula pointing toward the lung and located in the ETT. The bursts of gas entrain additional gas from surrounding areas. Expiration is passive. PEEP is increased to optimize lung volume, and a low background rate (provided by a conventional ventilator) is employed to open up alveoli during inspiration.
HFJV is used as a rescue mode in patients not responding to conventional ventilators and also is effective in air leak syndromes, pulmonary interstitial emphysema, and broncho-pleural fistula. Effective humidification must be used to avoid tracheal damage during HFJV.
With high frequency oscillatory ventilation (HFOV), gas movement is accomplished primarily by the mixing of gas in the upper airway with gas in the alveoli by a “back-and-forth” movement of a piston. Oxygenation is determined by the MAP (set directly on the ventilator). Ventilation is influenced by frequency and amplitude. Unlike other modes of mechanical ventilation, expiration is active in HFOV.
The relationship between frequency and CO2 removal is complex. At low frequency, pressure amplitude is transmitted more efficiently to the alveolus resulting in higher alveolar amplitude. At high frequency, pressure amplitude is attenuated resulting in low alveolar amplitude and less removal of CO2.
Generally, higher frequencies (such as 15 Hz) are recommended for very small premature infants, while lower frequencies (e.g., 10 Hz) are used for large term infants. During HFOV, increase in amplitude is more effective in decreasing pCO2 than decreasing frequency.
Adjuvant therapy to mechanical ventilation
Surfactant is a surface-active complex mixture of phospholipids and specific proteins that are synthesized and secreted into the alveolar space by the alveolar type II cells of the lung. Surfactant production is regulated developmentally and can be stimulated by administration of antenatal steroids (betamethasone or dexamethasone). Preterm infants are born with a relative or total lack of surfactant resulting in RDS.
Animal-derived natural surfactants such as Infasurf (calfactant), Survanta (beractant), and Curosurf (poractant) have phospholipids with small quantities of surfactant proteins (SP) B and C. They’re administered via the ETT and are effective in reducing the morbidity and mortality of premature newborn babies.
Surfactant also is effective in term neonates with surfactant inactivation secondary to meconium aspiration or pneumonia. A new synthetic surfactant (Surfaxin) with an incorporated synthetic peptide modeled after SP-B also has been studied in neonates.
Inhaled NO is effective in term infants with hypoxemic respiratory failure and PPHN. It’s a potent and selective dilator of the pulmonary vasculature. Inhaled NO is effective in reducing the need for ECMO in infants with PPHN. Recently there has been increasing interest in the use of inhaled NO in preterm neonates. In extremely low birth weight infants (< 1,000 g), the use of inhaled NO doesn't improve outcome in severe hypoxemic respiratory failure.
Prophylactic prolonged use of inhaled NO starting between day seven to 14 in preterm infants still intubated appears to significantly reduce the incidence of BPD. Early use of low-dose NO appears to reduce neurological morbidity in some preterm infants. Currently, pending long-term follow-up data, inhaled NO isn’t recommended in preterm neonates outside the realm of clinical trials.
Exposure to 100 percent oxygen is toxic to tissues because it forms free radicals. Tracheitis, pulmonary edema, surfactant dysfunction, and absorption atelectasis (from nitrogen washout) are common in adults exposed to 100 percent oxygen.
Term neonates generally are more resistant to toxicity related to very high levels of oxygen than adults. However, although < 60 percent oxygen rarely does harm in adults, the effect of lower concentrations of oxygen on the neonatal lung isn't clear. For premature infants, even room air oxygen levels are significantly higher than what would have been present in utero. Oxidant stress is an important consideration. There are currently multiple clinical trials ongoing to examine the appropriate target for oxygen saturation both during neonatal resuscitation and the postnatal period, particularly for premature infants.
Application of excessive levels of oxygen in premature neonates, especially < 32 weeks of gestation, is associated with a vasoproliferative retinal disorder called retinopathy of prematurity. Utmost caution should be exercised in maintaining target saturations in these infants. Extremely premature infants can develop the condition when inspired oxygen and blood oxygen tensions are controlled carefully and even when in room air.
A developing lung with immature anti-oxidant defenses is susceptible to oxygen toxicity, inflammation, and barotrauma from the ventilator. BPD generally is defined by the presence of clinical and radiological evidence of chronic lung disease associated with an oxygen requirement at 36 weeks of postconceptional age. Increased airway resistance and bronchial hyperreactivity can be demonstrated in BPD. Infants with established BPD generally require larger tidal volume breaths and a slower rate to enhance the distribution of gas due to heterogeneity of alveolar units. Pharmacological adjuvants such as diuretics, bronchodilators, and in some severe cases, corticosteroids, may be necessary.
Important advances have made respiratory technology more user- and patient-friendly. These advances need to be translated into improved neonatal outcomes.
1.Donn SM, Wiswell TE. Clinics in perinatology: surfactant and mechanical ventilation. WB Saunders Company. Philadelphia, March 2007.
2.Rennie J. Roberton’s textbook of neonatology: pulmonary disease of the newborn. Churchill Livingstone, June 2005.
3.Goldsmith JP, Karotkin EH. Assisted ventilation of the neonate. WB Saunders Company. Philadelphia, August 2003.
4.Donn SM. Neonatal and pediatric pulmonary graphics — principles and clinical applications. Futura Publishing Company Inc. Armonk, NY, 1998.
5.Donn SM, Sinha SK. Manual of neonatal respiratory care. Mosby Elsevier, Philadelphia, 2006.
Satyan Lakshminrusimha, MD, is an assistant professor of pediatrics (neonatology) at University at Buffalo and Women and Children’s Hospital of Buffalo, N.Y. His research interests include persistent pulmonary hypertension of the newborn and effect of ventilation on pulmonary transition at birth. Marc Leaderstorf, RRT-NPS, is the critical care and transport coordinator, respiratory care, at the same facility. He focuses on new modalities of neonatal ventilation, ECMO, and open lung strategies in the neonatal and pediatric patients. Rita Ryan, MD, is the chief of the division of neonatology, associate professor of pediatrics (neonatology), pathology and anatomical sciences, and gynecology-obstetrics also at the same facility. She also is the director of the Center for Developmental Biology of the Lung at Buffalo. Her interests include growth factors in the lung, hyperoxia, and surfactant.