Introduction
The care of premature infants with respiratory failure has advanced considerably over the past decades, but a substantial proportion of very premature infants survive with some degree of respiratory, visual, and neurodevelopmental impairment. This reality highlights the need for further improvements in the methods and monitoring of respiratory support in this population. There is a wide variety of “standard” modes of respiratory support discussed in other chapters of this book. New strategies and techniques to provide mechanical ventilation and supplemental oxygen to the premature infant have become available as a result of advances in the hardware, software, and sensing technologies that enable a more dynamic control of ventilator functions. The technology is still evolving, and these techniques have not yet come into widespread use for regulatory reasons or because of a paucity of definitive evidence of their benefits. This chapter describes these modalities of respiratory support and discusses the rationale and the evidence for the advantages and possible limitations.
Closed-Loop Control of Inspired Oxygen
Most premature infants require supplemental oxygen to maintain adequate arterial oxygen levels. However, it is well documented that in routine clinical care, manual adjustment of the fraction of inspired oxygen (FiO 2 ) commonly fails to keep arterial oxygen saturation (SpO 2 ) within the prescribed target range. It has been reported that premature infants spend nearly a third of the time with SpO 2 levels above the target range owing to excessive FiO 2 . The resulting hyperoxemia increases the risk of damage to the eye, brain and other organs, whereas excessive exposure to inspired oxygen increases the risk of oxidant damage to the lungs. The same report showed that premature infants spend nearly a fifth of the time with SpO 2 below the target range. This is because hypoxemia episodes are frequently observed in premature infants owing to their respiratory instability. These episodes increase in frequency with postnatal age, especially in infants with chronic lung disease. Most of these episodes are spontaneous, but some are related to care procedures. The response of the clinical staff can influence the duration and severity of these episodes. However, staff availability to perform this task during standard care is often limited. FiO 2 is increased during the episodes, but the resolution of hypoxemia is not always followed by a prompt return of FiO 2 to baseline, resulting in subsequent hyperoxemia. The occurrence of hypoxemia episodes is in part related to the basal level of SpO 2 . Higher SpO 2 levels are often tolerated in infants with frequent hypoxemia episodes in an attempt to prevent their occurrence, but this practice can lead to hyperoxemia. On the other hand, the use of lower SpO 2 target ranges to avoid hyperoxemia can lead to an increased frequency of episodes of hypoxemia.
The impact of staff availability on the maintenance of SpO 2 within target was documented by a decline in the proportion of time with SpO 2 within range as the nurse-to-infant ratio decreased, and this was mainly due to an increased time in hyperoxemia.
Because consistent maintenance of SpO 2 within the prescribed target range is seldom achieved in premature infants receiving supplemental oxygen, exposure to hyperoxemia and hypoxemia is common. Systems for automatic closed-loop control of FiO 2 incorporated into neonatal ventilators have been proposed as a tool to assist caregivers in the maintenance of SpO 2 within the prescribed target range and reduce the exposure to extremes of high and low SpO 2 levels. These systems continuously adjust FiO 2 , aiming at keeping SpO 2 within the target range set by the clinician. Figure 21-1 shows representative recordings of SpO 2 and FiO 2 from a premature infant with frequent episodes of hypoxemia during manual and automated FiO 2 control.
Short-term feasibility and efficacy studies have shown that closed-loop FiO 2 control systems are more effective in keeping SpO 2 within the target range than manual control during routine care and equal to or better than a fully dedicated nurse. The relative efficacy of automated systems compared to conventional manual adjustment obtained in these clinical studies is shown in Table 21-1 . Closed-loop FiO 2 control also produced a consistent reduction in the proportion of time with SpO 2 above the target range compared to manual control.
| SpO 2 Target Range | % TIME WITHIN TARGET RANGE | ||
|---|---|---|---|
| Manual FiO 2 Control | Closed-Loop FiO 2 Control | ||
| Bhutani, 1992 | 94%-96% | 54 | 81 |
| Morozoff, 1993 | 90%-95% | 39 | 50 |
| Claure, 2001 | 88%-96% | 66 | 75 |
| Urschitz, 2004 | 87%-96% | 82 | 91 |
| Claure, 2009 | 88%-95% | 42 | 58 |
| Morozoff, 2009 | 90%-96% | 57 | 73 |
| Claure, 2011 | 87%-93% ∗ | 39 | 47 |
| Waitz, 2014 | 88%-96% | 69 | 76 |
| Hallenberger, 2014 | Four centers (90%-95%, 80%-92%, 83%-93%, 85%-94%) | 61 | 72 |
| Zapata, 2014 | 85%-93% | 34 | 58 |
| Lal, 2015 | 90%-95% | 60 | 69 |
| Van Kaam, 2015 | 89%-93% ∗ | 54 | 62 |
| 91%-95% | 58 | 62 | |
∗ Includes periods with SpO 2 > target range while FiO 2 = 0.21.
The proportion of time with SpO 2 below target was not consistently reduced by closed loop compared to manual FiO 2 control. Studies in infants with frequent hypoxemia episodes showed a greater number of mild episodes with SpO 2 slightly below the target range but a consistent reduction in the severe and prolonged episodes of hypoxemia during closed-loop FiO 2 control. This finding illustrates the fact that closed-loop FiO 2 control systems do not prevent hypoxemia episodes but can attenuate their duration and severity.
In these studies, the number of manual changes in FiO 2 was minimal during automatic FiO 2 control. This suggests potential savings in staff workload and the possibility of shifting the staff effort to other areas of clinical care.
SpO 2 alarms are among the most common events in the neonatal intensive care unit. Although not evaluated yet during extended use, systems for automatic FiO 2 control may have an impact on SpO 2 alarm fatigue in the staff. On the other hand, reduced staff attentiveness is a potential unintended consequence of automated FiO 2 control systems. An automatic increase in FiO 2 during hypoxemia can mask a respiratory deterioration that would otherwise manifest as a persistently lower SpO 2 . Hence, it is essential that monitoring of the ventilatory status by the clinical staff remains as usual when these systems are in use and that closed-loop FiO 2 control systems alert the clinician when there is a persistent need for a higher FiO 2 .
Neonatal centers have adopted specific target ranges of SpO 2 for premature infants. However, significant discrepancies can exist between the target and the actual range of SpO 2 during routine care. Caution is recommended when setting the range of SpO 2 to be targeted by automatic systems because there may be important clinical implications that become evident when SpO 2 is kept more consistently within such range. This is particularly important because the optimal range of SpO 2 for this population has not been clearly established.
In summary, short-term clinical studies showed that closed-loop FiO 2 control can improve SpO 2 targeting and reduce exposure to hyperoxemia, supplemental oxygen, and episodes of severe hypoxemia. Whether extended clinical use of this technology can have an impact on long-term visual, respiratory, and neurodevelopmental outcomes in premature infants is still to be determined.
Ventilation Techniques
Proportional Assist Ventilation
The underlying lung disease can significantly affect the mechanical properties of the premature infant’s respiratory system. Restrictive conditions such as respiratory distress syndrome (RDS) result in a decrease in lung compliance that imposes an elastic load on the infant’s respiratory pump, whereas obstructive conditions (increased airway resistance) impose resistive loads. In most cases these higher loads lead to an increased breathing effort to sustain ventilation, resulting in increased work of breathing and increased oxygen consumption and caloric expenditure, as well as distress. When the infant fatigues or the effort is insufficient, the patient develops hypoventilation and respiratory failure.
Proportional assist ventilation (PAV) is a modality in which the pressure generated by the ventilator is increased in proportion to the volume, flow, or both, generated by the infant’s inspiratory effort. The gain or proportionality factors by which the positive pressure increases in relation to the measured tidal volume (V T ) or flow are the elastic gain (volume proportional, in units of pressure per milliliter of measured volume) or resistive gain (flow proportional, in units of pressure per unit of measured flow). The simultaneous increase in ventilator pressure with the infant’s spontaneous inspiration augments the patient’s own effort and thus can achieve a normal transpulmonary pressure and maintain a normal V T with less spontaneous inspiratory effort. Generating the same or larger V T with less inspiratory effort is perceived by the infant as a reduction in the mechanical loads, decreases the work of breathing, and reduces oxygen consumption. The proportional increase in ventilator pressure to the infant’s spontaneous effort is illustrated in Figure 21-2 .
Studies in infants recovering from RDS showed that PAV produced similar ventilation with lower ventilator and transpulmonary pressures compared to pressure-controlled modalities such as assist/control and intermittent mandatory ventilation. The elastic and resistive gains are set to produce the unloading necessary to compensate for the disease-induced respiratory loads. These gains must be individualized to the infant’s lung compliance and airway resistance. An elastic gain that exceeds what is needed to compensate for the decrease in lung compliance can result in a runaway increase in pressure. A resistive gain that exceeds what is needed to overcome the increased airway resistance can induce rapid oscillations in pressure. It should be recognized that the underlying assumption of PAV is that the patient’s respiratory drive is appropriate and the device is simply overcoming disease-induced mechanical loads. When applied to premature infants with immature respiratory control, there is a potential for this positive feedback system to generate excessive pressures and volumes when an infant is disturbed and briefly generates a large spontaneous inspiratory effort, whereas inadequate support may be provided during periods of hypopnea that are common in preterm infants. Because the system by necessity responds to inspiratory flow and volume, the commonly encountered large leak around the endotracheal tube (ETT) would be interpreted as a large inspiration and given correspondingly a high level of inflation pressure, potentially leading to dangerously large V T . To minimize the risk of overinflation, the peak pressure and V T limits must be set appropriately by the clinician.
A clear understanding of the theory behind unloading by PAV is essential because the management of ventilatory support with PAV differs considerably from that of conventional ventilation. Clinicians must understand how to choose the setting of elastic or resistive gains and the possible effects these may have on the infant. When compliance changes, the gain must be adjusted accordingly to maintain the same degree of unloading. This is particularly important as compliance improves, to avoid excessive unloading that could result in large V T and increase the potential risk for prolonged ventilator dependence due to poor respiratory muscle fitness. Because PAV amplifies only the spontaneous breathing effort, a backup rate of mandatory inflations is required in infants with apnea to prevent hypoventilation.
In summary, published data indicate that PAV is effective in the short term in maintaining comparable ventilation with lower peak ventilator pressure compared to conventional modalities. However, the safety and effectiveness of this approach for long-term support have not been fully established. Further studies are needed to determine if longer term use of this strategy can be advantageous in reducing the need for ventilatory support and improving respiratory outcome. The complexity of this modality and limited availability appear to have limited its penetration into clinical practice. As of this writing, this mode of support is unique to the Stephanie ventilator (F. Stephan GmbH Medizintechnik, Gackenbach, Germany), which is not available in the United States.
Neurally Adjusted Ventilatory Assist
Neurally adjusted ventilatory assist (NAVA) is a novel modality in which the ventilator pressure is adjusted in proportion to the electrical activity of the diaphragm measured by esophageal electrodes mounted on a modified feeding tube. The ventilator pressure during NAVA is directly proportional to the diaphragmatic activity with a proportionality factor or gain set by the clinician (in units of pressure per microvolt of electrical activity), known as the “NAVA level.” When the ventilator pressure is increased simultaneously with and proportionally to the rise in the diaphragm’s electrical activity, NAVA can enhance the diaphragm’s ability to generate a larger V T or maintain a similar V T with less inspiratory effort on the part of the infant. The increase in the ventilator pressure in proportion to the magnitude of the diaphragmatic activity is illustrated in Figure 21-3 .
