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Premature infants present with frequent episodes of spontaneous intermittent hypoxemia. These episodes are more prevalent in infants who require prolonged mechanical ventilation.
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A common mechanism triggering intermittent hypoxemia is contractions of the abdominal muscles that splint the respiratory system, resulting in decreased lung volume, impaired lung mechanics, and hypoventilation.
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Episodes of intermittent hypoxemia are often followed by hyperoxemia induced by excessive oxygen supplementation used to prevent or correct the episodes.
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Because of the frequency and severity of intermittent hypoxemia, it can have detrimental effects on long-term outcome.
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The mechanisms and consequences of intermittent hypoxemia need to be further investigated to identify effective therapeutic and preventive strategies.
As a consequence of their respiratory instability, premature infants experience frequent fluctuations in oxygenation and intermittent hypoxemia (IH) episodes. These episodes can be induced, but most are spontaneous and their severity and duration can be influenced by staff responsiveness. Premature infants who show fluctuations in arterial oxygen saturation as measured by pulse oximetry (Sp o 2 ) require frequent adjustment to the fraction of inspired oxygen (F io 2 ). However, maintenance of Sp o 2 within the prescribed range is not always achieved, and infants can spend considerable time with Sp o 2 below or above this range.
This chapter describes the mechanisms leading to fluctuations in oxygenation, discusses the management strategies used to prevent or attenuate these fluctuations, and provides an overview of the possible long-term consequences of oxygenation instability in the premature infant.
Mechanisms of Oxygenation Instability in Ventilated Infants
Most preterm infants receiving mechanical ventilation present with respiratory instability that make them susceptible to IH. These episodes of IH can complicate the respiratory management and prolong the need for respiratory support and oxygen supplementation, both of which may be associated with long-term sequelae. The mechanisms leading to IH, their clinical management, and possible consequences are discussed in the following sections.
Episodic hypoxemia in neonates has been traditionally attributed to hypoventilation owing to central or obstructive apnea, but these mechanisms mainly apply to spontaneously breathing infants. Most extremely premature infants present with an increasing frequency of IH after the first weeks after birth while they still require mechanical ventilation and supplemental oxygen. The occurrence of spontaneous IH in mechanically ventilated infants is often perplexing because they occur despite continued cycling of the ventilator and patency of the airway. These episodes of hypoxemia are characterized by a rapid decline in Sp o 2 that become more frequent with advancing postnatal age.
One of the most common mechanisms leading to spontaneous IH in mechanically ventilated preterm infants are forced exhalations secondary to contractions of the abdominal musculature that impinge on the respiratory system and impair respiratory mechanics. The resultant decrease in lung volume and hypoventilation cause hypoxemia that becomes more severe and persistent with successive abdominal contractions. This is illustrated in Fig. 14.1 .
Electromyographic measurements show that these forced exhalations are caused by contractions of the abdominal muscles that produce a marked increase in abdominal and intrathoracic pressure, some in excess of 25 cm H 2 O. As shown in Fig. 14.2 , repeated contractions of the abdominal muscles can prolong the episodes and increase their severity. It is important to note that in ventilated infants, the endotracheal tube bypasses the glottis and eliminates the protective upper airway’s function to preserve lung volume during the rise in intrathoracic pressure.
The factors that elicit these forced exhalations leading to loss in lung volume and hypoventilation with hypoxemia have not been clearly defined. However, behavioral disturbances appear to trigger IH. Increased body activity, agitation, squirming, and tachycardia are frequently present moments before the onset of the episodes. Intermittent hypoxia is observed more frequently during awake or indeterminate sleep states than during quiet or active sleep. These observations are important because indeterminate sleep is the most common sleep state in preterm infants. The prone position has also been associated with fewer and shorter IH episodes compared with the supine position.
The combination of increased activity leading to ventilation changes and poor lung function owing to the underlying lung disease may aggravate the frequency and severity of IH. In addition, the low functional residual capacity and decreased lung compliance characteristic of these infants, combined with bypassing of the glottis by the endotracheal tube, may increase the likelihood of reaching closing volume in some areas of the lung with even small decreases in lung volume.
The decline in Sp o 2 during these episodes of hypoxemia is more abrupt than what is expected from a decline in ventilation alone and often persists after ventilation has been reestablished. This observation suggests that the initial loss in lung volume and hypoventilation may produce ventilation-perfusion inequalities and some degree of intrapulmonary shunting, thereby causing a rapid decline in Sp o 2 . The onset of hypoxemia can also provoke an increase in pulmonary vascular resistance and induce right-to-left shunting through extrapulmonary channels. These circulatory changes can explain why episodes of IH are observed more frequently in infants with chronic lung disease and increased pulmonary vascular reactivity. In many of these infants, normoxemia is restored only after the fraction of inspired oxygen (F io 2 ) is increased, which may restore oxygenation not only by increasing the alveolar-capillary oxygen gradient but also by attenuating the hypoxia-induced pulmonary vasoconstriction.
Oxygenation Instability in Spontaneously Breathing Infants After Mechanical Ventilation
Episodes of hypoxemia are frequently observed in premature infants after extubation while the infants are receiving noninvasive respiratory support or breathing spontaneously. IH during this period have been mainly attributed to central or mixed apnea. However, a study showed that most IH in spontaneously breathing preterm infants after a prolonged course of ventilation may also be caused by episodes of forced exhalation, which induce a decline in lung volume and hypoventilation similar to the IH observed in intubated infants ( Fig. 14.3 ). In this study almost all infants were receiving caffeine. Hence, it is possible that use of stimulants after extubation may have decreased the proportion of IH caused by central apnea during the postextubation period. It is also possible that preterm infants after prolonged mechanical ventilation may be more susceptible to lung volume instability because the prolonged presence of the endotracheal tube may impair the upper airway’s ability to preserve lung volume. The extent to which this contributes to extubation failure remains to be determined. (Oxygenation instability in spontaneously breathing infants resulting from central and obstructive apnea is discussed in Chapter 13 .)
Management of Oxygenation Instability
Ventilatory Strategies
To reduce the frequency, severity, or duration of IH, clinicians often resort to higher levels of mechanical respiratory support. However, this may be of limited efficacy and can lead to unwanted consequences. A high positive end-expiratory pressure (PEEP) may increase lung volume and increase basal oxygenation levels, but this maneuver may be only partially effective in preventing IH caused by active exhalations. This is because the rise in intrathoracic pressure during forceful contraction of the abdominal muscles exceeds the level of positive end-expiratory pressure considerably. Higher peak inspiratory pressure (PIP) or ventilator frequency can be effective in attenuating IH, but this strategy provides excessive support during periods when the infant is not presenting with episodic hypoxemia. Improving infant-ventilator interaction by using synchronized ventilation has been shown to reduce IH in preterm infants.
Volume-targeted ventilation (VTV) automatically adjusts the ventilator PIP to maintain a set tidal volume ( V T ). The efficacy of VTV in attenuating the decrease in V T and minute ventilation that precedes each episode of hypoxemia was evaluated in preterm infants with frequent IH. In these studies, VTV attenuated the decrease in ventilation and the severity and duration of the episodes of IH compared with conventional pressure-controlled (PC) ventilation but failed to prevent them. However, this required setting a target V T that was larger than the V T delivered during PC ventilation, possibly exposing the infants to excessive V T and PIP during periods when ventilation was stable. In a recent study matching the target V T during VTV to that during PC ventilation, VTV reduced the duration of episodes of IH and the F io 2 provided by the caregivers in response to these episodes. The limited effectiveness of VTV is likely because infants continue to increase intrathoracic pressure and reduce their lung volume despite the continuous cycling of the ventilator. Fig. 14.4 shows VTV adjustments in PIP during an episode of hypoxemia.
Automatic increases in ventilator frequency when minute ventilation or Sp o 2 declines are effective in reducing the duration but not the frequency of IH. The parallel increase in ventilator frequency and PIP, to maintain minute ventilation and V T , respectively, was more effective in reducing the duration and severity of IH in an animal model. This approach has not been evaluated in infants.
Supplemental Oxygen
The goal of oxygen supplementation in preterm infants is to maintain adequate oxygenation while minimizing hyperoxemia and oxygen exposure. However, this is complicated by fluctuations in oxygenation. F io 2 is adjusted to maintain Sp o 2 within a target range and avoid exposure to high and low Sp o 2 , but this is only partially achieved during routine care. Data from 14 centers showed that in preterm infants receiving supplemental oxygen the Sp o 2 was within the target range only 48% of the time. These data showed preterm infants spend 16% of the time below the target range (0%–47% between centers). This is mainly due to IH episodes that are predominantly spontaneous but with a duration and severity that can be influenced by staff responsiveness. In these infants Sp o 2 was above the target for 36% of the time (5%–90% between centers); which is almost always induced by provision of an F io 2 that exceeds that required to maintain Sp o 2 within target. This is frequently done in an attempt to avert IH, whereas in other cases the staff increases F io 2 in response to a hypoxemia alarm but often F io 2 is not promptly returned to baseline after the episode resolves. As shown in Fig. 14.5 , high basal levels of Sp o 2 can attenuate the frequency or severity of IH, but this increases the exposure to high F io 2 and hyperoxemia.
