Assisted Ventilation of the Neonate and Its Complications

Physiology of CPAP

When used to treat respiratory distress syndrome (RDS), CPAP prevents collapse of the alveoli at end-expiration, maintaining some degree of alveolar inflation. It thus decreases the work of breathing in accordance with LaPlace's law, in which the pressure required to overcome the collapsing forces generated by surface tension is reduced, because the radius of curvature is greater when the alveolus is partially inflated. In this way, CPAP helps to maintain functional residual capacity and to facilitate gas exchange. In addition, CPAP helps to maintain upper airway stability by stenting the airway and decreasing obstruction. It may also augment stretch receptors and decrease diaphragmatic fatigue and thus be useful in treating apnea of prematurity.

Nasal Continuous Positive Airway Pressure

Continuous positive airway pressure is a form of continuous distending pressure (CDP), which is defined as the maintenance of increased transpulmonary pressure during the expiratory phase of respiration. When positive pressure is applied to the airways of spontaneously breathing infants, it is called continuous positive airway pressure (CPAP), whereas distending pressure applied to a mechanically ventilated infant is called positive end expiratory pressure (PEEP). Thus, both CPAP and PEEP are types of CDP (although not technically a form of ventilation) that provide low-pressure distension of the lungs and prevent the collapse of alveoli at the end of expiration. Continuous distending pressure helps to maintain functional residual capacity (FRC) and thus facilitates gas exchange throughout the respiratory cycle. In addition, CPAP supports the breathing of premature infants in a number of other ways, including abolition of upper airway occlusion and decreasing upper airway resistance, enhancement of diaphragmatic tone and activity, improvement in lung compliance and decrease in lower airway resistance, increase in tidal volume delivery by improving pulmonary compliance, conservation of surfactant at the alveolar surface, and reduction in alveolar edema.

CPAP may be administered invasively through an indwelling endotracheal tube, or it may be provided noninvasively using a variety of different nasal interfaces. This is referred to as nasal CPAP (NCPAP). Single nasal prongs are usually cut from endotracheal tubes and passed 1-2 cm into one nostril with about 3 cm residing externally. Resistance along the length of the cannula adds to the loss of pressure from the other nostril. Nasal masks are now used in the belief that they reduce trauma to the nostrils. However, it is often difficult to produce a good seal without undue pressure, which may still cause injury in the region between the nasal septum and the philtrum. Short binasal prongs are available in several designs; all have two short tubes that provide the least resistance of any other nasal interface. They may be more effective at maintaining extubation and preventing reintubation than single nasal prongs as shown in a recent meta-analysis of controlled studies.

Sustained Inflation at Neonatal Resuscitation

Sustained inflation (SI) uses pressures of 20-30 cm H ₂ O for 5-15 seconds during resuscitation to recruit lung airspaces immediately after delivery and to establish functional residual capacity. Thus far, studies have failed to demonstrate a benefit of presumed lung recruitment (and a decrease in the rates of death or BPD). More randomized controlled studies are underway to evaluate the efficacy and safety of SI.

CPAP Immediately After Birth

In a meta-analysis of randomized controlled trials comparing CPAP started in the immediate postnatal period in very low birth infants at risk for RDS, to support with mechanical ventilation (including 3123 babies), Subramaniam et al. found CPAP to decrease the need for mechanical ventilation and surfactant treatment and to reduce the incidence of BPD at 36 weeks and the incidence of death or BPD.

High-Flow Nasal Cannula (HFNC)

Flow of gas in excess of 1 L/min, and up to 8 L/min, through a small nasal cannula might provide some degree of CPAP. The physiologic benefits of HFNC are attributed to washout of the nasopharyngeal dead space, possible reduction of the inspiratory resistance, and provision of a degree of CPAP. However, a major problem is that the CPAP level is usually not measurable in clinical practice and has been shown to be highly variable depending on the leak at the nose and/or mouth. The cannula tips should not be more than 50% of the internal diameter of the nares to allow optimal washout of the dead space. This leak around the nasal cannula affects the measured CPAP in an in vitro study. In another study of preterm infants, a flow of 2 liters/minute generated 9.8 cm H ₂ O pressure (measured by an esophageal balloon) when a nasal cannula of certain diameter was used (0.3-cm outer diameter), emphasizing the potential risk of inappropriate size selection of the nasal cannula. Utilization of this technique has increased in many units as a result of the simpler patient interface compared to CPAP, and because the use of HFNC appears to be associated with less nasal trauma. HFNC in preterm infants has been used as a primary mode of support shortly after birth, postextubation, and for apnea. In general, HFNC was no worse than CPAP in a meta-analysis of controlled trials. However, there is a paucity of evidence in the extremely preterm infant. In a large randomized, controlled, noninferiority trial, published subsequently, early (after birth) use of HFNC for primary support for RDS in infants older than 27 weeks was associated with more frequent treatment failures compared to CPAP. Additional studies are needed to demonstrate safety and efficacy for HFNC under various clinical conditions.

CPAP and Surfactant Administration

Intubation with surfactant administration, followed by extubation (INSURE), is a way for surfactant administration to premature infants supported with CPAP. Dani et al. described variation in the threshold for surfactant treatment in multiple studies using this technique of surfactant administration, with the lower threshold seemingly better. Less invasive surfactant administration (LISA) describes administering surfactant to spontaneously breathing premature infants without traditional endotracheal intubation. LISA is used with the hope of decreasing exposure to mechanical ventilation and subsequently to decrease the risk for lung injury. A meta-analysis of six randomized studies, enrolling 895 infants, demonstrated that LISA was associated with a lower need for mechanical ventilation and a reduction in the composite outcome of death or BPD.

Practical Problems of NCPAP

Despite its widespread use, a number of problems still persist. Nasal prongs rarely fit tightly into the nares, thus resulting in gas leak and inability to maintain a baseline pressure. The set CPAP level is rarely maintained in the pharynx. The best way to reduce nasal leak is to ensure that the prongs are of sufficient size to snugly fit the nostrils without making them blanch. A chin strap can be used to reduce leaks around the mouth, but it is not simple to use in practice.

Complications of CPAP

Nasal trauma is a common problem with NCPAP especially in very premature infants. Proposed interventions include alternating binasal prongs with a nasal mask and using a nasal barrier dressing. Excessive CPAP may contribute to lung overinflation and increase the risk for air leaks. CPAP can increase intrathoracic pressure and decrease venous return and cardiac output. If set too high, CPAP may result in carbon dioxide retention and impaired gas exchange. Gastric distension is a commonly encountered problem and can be at least partially alleviated by placement of an orogastric tube.

Postextubation CPAP

Ferguson et al., in a meta-analysis of studies that evaluated rates of successful extubation, found that continuous positive pressure reduces extubation failure compared to head-box oxygen, NIPPV was superior to CPAP, and that HFNC had similar efficacy to CPAP. Lemyre's meta-analysis did not find enough evidence to demonstrate superiority of synchronized over nonsynchronized NIPPV after extubation, although a postextubation benefit was consistently observed in studies using synchronized NIPPV.

Discontinuing CPAP

There are several methods of discontinuing NCPAP, including transition to HFNC. A gradual decrease in CPAP before discontinuing it was associated with success in the initial trial off NCPAP in two randomized controlled studies of very low birth weight infants.

Long-Term Outcomes

The use of CPAP immediately after birth and selective surfactant treatment has generally replaced the practice of prophylactic or early surfactant replacement in preterm infants. This change in practice was influenced by the evidence from multiple randomized trials that used CPAP for initial stabilization and demonstrated a decreased risk of death or BPD compared to prophylactic surfactant therapy. That change in practice also included using the INSURE strategy in surfactant administration in an attempt to decrease exposure to mechanical ventilation. There has been an increase in the use of noninvasive forms of pulmonary support over time in an attempt to decrease exposure to mechanical ventilation and to decrease the risk for lung injury and potentially decrease the risk of death or BPD. The temporal increase in the use of noninvasive ventilation was demonstrated in longitudinal studies using single-center and regional datasets. Vliegenthart et al., in a single center in the Netherlands, reported a decrease in the rate of intubation and a decrease in the duration of mechanical ventilation over two epochs spanning 2004-2011, but there was no significant decrease in BPD. However, the investigators reported a significant decrease in the rate of death or neurodevelopmental impairment at 24 months.

A regional Australian evaluation that compared pulmonary support and outcomes in three periods, 1991-1992, 1997, and 2005, demonstrated a longitudinal increase in duration of noninvasive pulmonary support without a significant change in duration of endotracheal mechanical ventilation and no significant decrease in duration of oxygen therapy or in the rate of oxygen dependence at 36 weeks. In addition, survivors of that population born in the most recent time period had lower expiratory volumes, suggesting more airflow obstruction at their 8-year evaluation. Although these longitudinal evaluations have many limitations, they are not showing the hoped-for pulmonary benefits of the increased use of noninvasive pulmonary support. It seems that more work needs to be done to identify better noninvasive pulmonary support practices and the ideal patient population.

Oxygenation

The two major factors that are responsible for oxygenating the blood are the fraction of inspired oxygen and the pressure to which the lung is exposed ( Box 65.4 ). The role of inspired oxygen can be understood from the alveolar gas equation (see Chapter 63 ). Oxygenation is also proportional to mean airway pressure (mean Paw), which is the average pressure applied to the lungs during the respiratory cycle and is represented by the area under the curve for the pressure versus time waveform. Inflation of the lung recruits more airspaces and exposes more of the pulmonary surface area to alveolar gas. Thus, those factors that increase mean airway pressure will, up to a certain point, improve oxygenation ( Fig. 65.1 ).

The most direct impact comes from positive end expiratory pressure (PEEP), because it is applied throughout the respiratory cycle. PEEP is the baseline pressure, the lowest level to which airway pressure falls. It is used to take advantage of LaPlace's law by maintaining some degree of alveolar inflation during expiration, thus reducing the pressure necessary to further inflate the alveolus during inspiration. There is a 1 : 1 relationship between PEEP and mean Paw; for every 1-cm H ₂ O increase in PEEP, there is a 1-cm H ₂ O increase in mean Paw. Excessive PEEP is potentially harmful. It may overdistend the alveoli, increasing the risk of air leaks; it may impede venous return and cardiac output; and it may decrease the amplitude, leading to carbon dioxide retention (see Complications of CPAP ).

Peak inspiratory pressure (PIP) will also increase the mean Paw, but this will be proportional to the inspiratory time (T _I ) or duration of positive pressure. PIP is the driving pressure and also establishes the upper limit of the amplitude. Excessive PIP poses many of the same risks as excessive PEEP, including hyperinflation (overdistension) of the lung, leading to excessive stretch of the alveolar units (baro- or volutrauma); high intrathoracic pressure with decreased venous return and cardiac output; and air leaks. Additionally, if PIP and/or PEEP is/are inadequate, there may be alveolar atelectasis and resultant damage to the lung from cyclic opening and closing of lung units, a process referred to as atelectrauma.

Mean Paw is also affected by T _I and the duration of positive pressure. As T _I increases, the mean Paw will also increase if all other parameters are held constant. Similarly, on machines wherein the inspiratory:expiratory (I:E) ratio is adjusted, mean Paw will increase as the inspiratory phase is lengthened or the expiratory phase is shortened. If the T _I is too long, however, there is an increased risk of gas trapping, inadvertent PEEP, and air leak. If it is too short, there may be inadequate lung expansion, air hunger, and patient-ventilator asynchrony, leading to inefficient gas exchange.

Changes in the ventilator rate will have a slight effect on mean Paw. At faster rates, the mean Paw will rise, because there are more breaths delivered per minute and the cumulative area under the curve per unit of time increases. Rapid rates may result in incomplete emptying of the lung, with gas trapping, inadvertent PEEP, and lung hyperinflation.

Finally, circuit gas flow will also impact mean Paw. If the T _I is held constant, more volume (and hence higher pressure) will be delivered as flow is increased. If the flow is set too high, turbulence, incomplete emptying of the lung, inadvertent PEEP, and hyperinflation may occur. If the flow is set too low, air hunger and asynchrony will result. The injurious effects of improper airway flow have been referred to as rheotrauma .

Ventilation

Ventilation refers to carbon dioxide removal. Its two primary determinants are tidal volume and frequency ( Box 65.5 ). Tidal volume is determined by the amplitude of the mechanical breath, or the difference between the peak (PIP) and baseline (PEEP) pressures. During conventional ventilation, carbon dioxide removal is the product of tidal volume and frequency. Clinically, this is usually expressed as the minute volume, or mL/kg/min, of exhaled gas. It is also important to consider the contribution of spontaneous breathing to minute ventilation (which is not always measured) and that pulmonary blood flow is also a key element in carbon dioxide removal, as well as oxygenation. During high-frequency ventilation, carbon dioxide removal is the product of frequency and the square of the tidal volume. Thus, small changes in amplitude may have a profound effect on arterial carbon dioxide tension (see later).

Control of ventilation during patient-triggered ventilation requires an understanding of the physiology of gas exchange. Most newborns will have intact chemoreceptors and will seek to maintain normocapnia. This is accomplished by adjustments in minute ventilation. Thus, if the amplitude is set too low, the baby will compensate by increasing the spontaneous (and hence, triggered) breathing rate. Conversely, if the amplitude is set too high, the infant's hypercapnic drive will be abolished, and the baby will “ride” the ventilator rate.

Carbon dioxide tension is affected by minute ventilation, which in turn is the product of tidal volume and frequency during conventional mechanical (tidal) ventilation (CMV). Of these two parameters, adjustment in tidal volume (by adjusting the amplitude) has a more predictable effect on minute ventilation.

Time Constant

Use of mechanical ventilators requires an understanding of the respiratory time constant. The respiratory time constant refers to the time required to allow pressure and volume equilibration of the lung. Mathematically, the time constant is the product of compliance and resistance. When the lung is stiff (low compliance) and has limited expansibility, such as occurs during RDS, it takes less time to fill and empty than it does at higher compliance. This pattern is clinically illustrated by observing the spontaneous breathing pattern of an infant with RDS not requiring assisted ventilation. Early on, when compliance is poor, the baby will breathe rapidly and take shallow breaths. As the disease process remits, compliance improves, and the baby breathes more slowly and takes deeper breaths.

If expiratory time is set at one time constant, approximately 63% of the change in pressure or volume will occur; if it is lengthened to three time constants, changeover will increase to 95%; and at a five time constant-length, it will approach 99%. Thus, setting the expiratory time at less than 3-5 times the length of the time constant will increase the risk of gas trapping and potentially inadvertent PEEP and alveolar rupture.

Control Variables (Ventilatory Modalities)

At any one time, the ventilator can control only a single variable—time, pressure, or volume. However, the same ventilatory device can operate using different control variables at different times. Ventilatory modalities can target either pressure or volume as the primary variable. Because volume is the integral of flow, volume- and flow-controlled ventilation are actually the same. When pressure is controlled, volume will fluctuate according to the compliance of the lungs, and conversely, when volume is controlled, pressure will fluctuate as a function of compliance.