- Open Access
Advances in respiratory support for high risk newborn infants
Maternal Health, Neonatology and Perinatology volume 1, Article number: 13 (2015)
A significant proportion of premature infants present with respiratory failure early in life and require supplemental oxygen and some form of mechanical respiratory support.
Many technical advances in the devices for neonatal respiratory support have occurred in recent years and new management strategies have been developed and evaluated in this population. This article describes some of these novel methods and discusses their application and possible advantages and limitations.
Newer methods of respiratory support have led to marked improvement in outcome of premature infants with respiratory failure. Some of these strategies are very promising but further investigation to evaluate their short term efficacy and impact on long term respiratory and other relevant outcomes is needed before wider use.
Different modes of respiratory support and oxygen supplementation are commonly used in premature infants in respiratory failure. The strategies of respiratory support and the devices utilized for this purpose have evolved considerably. Since the earlier studies describing the use of intermittent positive pressure ventilation, the advantages of continuous distending pressure in the form of nasal CPAP, the use of the T piece to provide a continuous flow of gas from which the patient can breathe spontaneously and the application of positive end-expiratory pressure [1-10] have constituted the basis of the modern neonatal respiratory support. These, combined with the introduction of therapies such as antenatal steroids and exogenous surfactant, have produced improvements in survival of high risk premature infants in respiratory failure.
The respiratory outcome of these high risk infants has also improved considerably compared to the severe lung injury induced by high positive pressure and elevated inspired oxygen observed during the early years of respiratory support in premature infants [11-13]. These improvements resulted from a better understanding of the damage associated with the aggressive use of mechanical ventilation and high inspired oxygen levels to maintain normal arterial blood gases and achieve control of the infant’s ventilation [14-16]. Current strategies of neonatal respiratory support aim to produce adequate gas exchange while minimizing the risk of lung injury and by facilitating weaning with ventilator strategies that primarily assist the infant’s spontaneous respiratory effort. More recent advances seek to adjust the different forms of respiratory support to the infant’s changing needs and further facilitate their spontaneous breathing and minimize the risk of lung injury. These include advances in monitoring technology and automation of specific parameters of the respiratory support.
Synchronized mechanical ventilation
The use of the T piece and the circulating bias flow in neonatal mechanical ventilators to maintain PEEP and provide cycles where the pressure increases to the set peak inspiratory pressure (PIP) level at fixed intervals became known as time-cycled pressure-limited (TCPL) ventilation. The intermittent tidal inflation during TCPL is also known as intermittent mandatory ventilation (IMV).
During IMV the clinician sets the PIP and cycling frequency depending on the level of ventilatory support required by the infant. The cycling frequency is gradually reduced as the infant contribution to minute ventilation increases. During this process there is continuous interaction between the infant’s spontaneous breathing and the ventilator positive pressure cycles. At times, ventilator cycles can interfere with the infant’s breathing when they occur late in the infant’s spontaneous inspiration or during exhalation.
The use of various sensors in neonatal ventilators to detect the infant’s spontaneous inspiration can achieve synchronized delivery of the positive pressure cycles with the onset of the infant’s inspiration. This resulted in the development of various modalities of support including synchronized IMV (SIMV), assist/control (A/C) and pressure support ventilation (PSV) [17-22]. The tracing in Figure 1 shows representative recordings from a premature infant undergoing SIMV.
Clinical studies have shown that the addition of the pressure generated by the infant’s respiratory pump and that produced by the ventilator during synchronized ventilation result in a more consistent tidal volume and improved ventilation compared to IMV, leading to a more stable and effective gas exchange [23-29]. Clinical trials have consistently shown faster weaning and shorter duration of mechanical ventilation with synchronized modes compared to IMV which is more evident among the more premature infants [30-35]. These studies underline the importance of preserving the infant’s spontaneous breathing and provide only the necessary level of support to assist ventilation better than controlling the infant’s ventilation and gas exchange.
In spite of the reduction in duration of mechanical ventilation the effects on respiratory outcome, namely bronchopulmonary dysplasia (BPD), have not been consistent. These however appear to be more striking in those studies enrolling more immature infants at higher risk of BPD . As described, the reduction in BPD by synchronized ventilation is greatest in those studies where the study population had a higher rate of BPD.
Studies have not shown clear advantages of one synchronized modality versus others except for a slightly faster weaning with A/C [37,38]. The similarity of the effect is likely due to the fact that these modalities provide comparable levels of support during the initial phase of acute respiratory distress where higher rates used in SIMV provide similar support as A/C or PSV. One study showed the additional use of PSV to SIMV can facilitate the weaning compared to SIMV alone. Lower peak pressure levels with PSV boosted the spontaneous breaths reducing the reliance on larger SIMV breaths . Figure 2 shows a representative recording from an infant receiving SIMV combined with pressure support.
Synchronized modalities of neonatal ventilation can be rendered ineffective if the breath sensing parameters are not set properly to detect the infant’s spontaneous inspiration. When this occurs the infant receives only mandatory breaths and can experience the consequent asynchrony. The most important concern with synchronized modalities is the risk of autocycling when artefacts or a too sensitive threshold for synchrony can result in the ventilator providing a cycle that is not necessarily triggered by a spontaneous inspiration. This is a greater concern in modes such as A/C and PSV when there is a risk of hypocapnia or gas trapping because of autocycling at very high ventilator rates .
Monitoring during mechanical ventilation
For many years the adequacy of ventilation was limited to monitoring of blood gases, radiographic evaluation, visual assessment of chest expansion and monitoring of breathing frequency by transthoracic impedance. The introduction of flow sensors for synchronization also provided the clinician with the ability to monitor the adequacy of tidal and minute volume. This led to a more objective evaluation of the tidal inflation and to a better titration of PIP which may be associated with reduced lung injury [41-43].
Non-invasive respiratory support
In recent years non-invasive respiratory support by nasal continuous positive airway pressure (NCPAP) and nasal intermittent positive pressure ventilation (NIPPV) have being increasingly used in the premature infant instead of mechanical ventilation. The effects of the application of a continuous distending pressure with NCPAP include stabilization of lung volume and airway patency leading to improved oxygenation and reduced apnea. NIPPV may enhance the effects of NCPAP by increasing ventilation and mean airway pressure, by washing out of CO2 from the upper airway and by a possible enhancement of the respiratory drive.
Clinical studies in preterm infants after extubation to NIPPV showed increased ventilation and reduced PaCO2 and breathing effort [44,45]. In more stable infants NIPPV did not increase ventilation or improve gas exchange but it reduced breathing effort compared to NCPAP [46-48]. This suggests a greater benefit of NIPPV over NCPAP in infants with some degree of ventilatory failure or those struggling to maintain adequate ventilation. Although NIPPV has not been consistently shown to be more effective than N-CPAP in reducing apnea, its efficacy appears to increase when synchronized to the infant’s spontaneous breathing [44,49-52].
Randomized controlled trials in premature infants with RDS have shown that NIPPV can reduce the need for mechanical ventilation compared to NCPAP [53-58]. The efficacy of synchronized NIPPV in reducing extubation failure compared to NCPAP has been shown consistently in randomized trials [59-63]. Although NIPPV is more effective than NCPAP in reducing the need for mechanical ventilation, studies have not demonstrated a significant impact of NIPPV compared to NCPAP on pulmonary outcome [53-64]. These clinical trials did not show increased risk of side effects such as serious gastrointestinal gas distension or pulmonary air leaks.
Although the use of both NCPAP and NIPPV has become very common, there is considerable need to further develop and test newer technologies to improve patient interfaces, synchronization of the ventilator with the patient and to improve transmission of the positive pressure to the infant’s airways.
Automation of respiratory support
The peak pressure during each ventilator cycle set by the clinician provides a constant level of ventilatory support. However, the ventilatory needs of the premature infant in respiratory failure can vary considerably within short periods of time. These fluctuations in respiratory mechanics and spontaneous breathing effort can lead to significant variations in ventilation. Because the support level provided by ventilatory modes such as SIMV, IMV, A/C or PSV provide constant peak pressure and/or mandatory rate, the set levels generally exceed those required by premature infants in order to maintain adequate ventilation at all times, even at times when the infant’s needs may be less. In order to adjust the ventilatory support to the infant’s needs, methods for automatic adjustment of the peak pressure and frequency have been incorporated to neonatal ventilators.
Volume targeted ventilation
During volume targeted ventilation, the peak pressure is automatically adjusted to maintain the tidal volume at the level set by the clinician. In this manner, when respiratory mechanics improve or the infant’s respiratory pump produces a larger tidal volume the ventilator reduces the peak pressure provided in each cycle and vice-versa. The adjustments in ventilator pressure are expected to provide better ventilation stability. Figure 3 shows a representative recording from a premature infant receiving volume guarantee ventilation.
During volume targeted ventilation the ventilator can only control the peak positive pressure applied on each cycle but cannot determine the negative pressure produced by the infant’s respiratory pump. The targeted volume in this modality is essentially a minimum tidal volume level but does not prevent the spontaneous inspiratory effort from generating breaths that exceed the target level.
Clinical studies have shown improved stability and reduced exposure to excessive or insufficient tidal volumes and an effective automatic reduction in PIP [65-67]. Clinical trials have demonstrated volume targeted ventilation modes can facilitate weaning from mechanical ventilation compared to conventional manual titration of peak pressure [68-72]. The combined data from these studies shows a significant reduction in the rate of the composite outcome BPD or death .
Although volume targeted ventilation appears to be safe there are important aspects to be considered in regards to its efficacy. Different ventilators utilize various methods to achieve volume targeted ventilation. Some of the ventilators make the automatic adjustments in pressure based on the volume delivered by the ventilator to the breathing circuit while others take the tidal volume measured with proximal flow sensors or from an estimate of the tidal volume from measurements obtained by flow sensors built in the ventilator. Ventilators also vary on whether the adjustments in pressure are made based on the tidal volume measured during the inspiratory phase or exhaled volume or in the timing of the pressure adjustment, i.e. instantaneously as the volume is delivered or from one cycle to the next.
Although there is sufficient evidence to recommend avoidance of extreme high or low tidal volumes, there is insufficient information in regards to the optimal tidal volume to be used in infants of different gestational ages, indications for mechanical ventilation and during the different phases of respiratory failure. Data are also lacking on the most adequate tidal volume target when volume targeted ventilation is provided at different mandatory rates with SIMV or when it is used to assist every spontaneous inspiration in A/C or PSV.
Targeted minute ventilation
The ventilatory support provided during conventional ventilation at a frequency set by the clinician provides a relatively constant minimum level of minute ventilation. This level of support may be adequate for most of the time but at times it can be insufficient and/or excessive to meet the infant’s needs. This is because the contribution of the infant’s spontaneous breathing effort to the total minute ventilation varies considerably depending on the consistency of the respiratory pump, stability of respiratory mechanics and the infant’s respiratory drive.
Targeted minute ventilation consist of automatic adjustments of the cycling frequency of the ventilator to maintain the minute ventilation at a level set by the clinician or alternatively to keep the total respiratory rate at a preset level. Because the ventilator can only control its own cycling frequency and not the infant’s, these modalities only target a minimum level of minute ventilation or respiratory rate.
In short term clinical studies in preterm infants these automatic modalities have been shown to be effective in reducing the ventilator frequency without affecting gas exchange [74,75]. Modalities such as PSV can be used to assist every spontaneous inspiration and in the event of apnea the ventilator provides mandatory cycles at a frequency and PIP set by the clinician. The effects of PSV as a stand- alone mode and the impact of the back-up ventilation provided during apnea have not been evaluated in preterm infants. Other methods include automatic adjustments to the cycling frequency not only when ventilation declines but also in response to decreases in arterial oxygen saturation .
Although these modalities are promising alternatives to tailor the respiratory support to the changing needs of the infant, to date there have not been randomized trials evaluating their efficacy in improving respiratory outcome in this population.
Newer experimental developments include simultaneous adjustments of both the cycling frequency and the peak pressure of the ventilator. The combined approach was more effective than conventional pressure ventilation or the individual automatic adjustment of pressure or frequency in maintaining oxygenation in an animal model of induced episodic hypoxemia .
Proportional assist ventilation and neurally adjusted ventilatory assist
In proportional assist ventilation (PAV) the ventilator assists the infant’s respiratory pump to overcome elastic or resistive loads due to the underlying lung disease. For this, the ventilator pressure is automatically adjusted in proportion to the measured tidal volume, flow or both. The proportionality factor set by the clinician determines the degree of unloading or compensation for the disease induced respiratory loads. When PAV is used the infant essentially perceives his respiratory mechanics have improved because of the simultaneous provision of positive pressure as the infant generates each inspiratory effort.
In clinical studies PAV has been shown to be effective in reducing the inspiratory effort and providing ventilation with lower ventilator pressures compared to conventional modes in premature infants recovering from respiratory failure or with evolving chronic lung disease [78,79].
Neurally adjusted ventilatory assist (NAVA) is a modality where the ventilator pressure is automatically adjusted in proportion to the measured electrical activity of the diaphragm. NAVA is intended to enhance the infant’s ability to generate VT and/or reduce the diaphragm’s activity. Figure 4 shows a representative recording from a premature infant undergoing NAVA.
In short term studies NAVA has been shown to maintain similar or better ventilation and gas exchange with lower pressures and better synchrony compared to conventional ventilation in preterm infants, but without a significant reduction in diaphragmatic activity [80-83].
PAV and NAVA are promising alternatives but their long term effects need to be explored to determine their impact on weaning from mechanical ventilation and on pulmonary outcomes in high risk preterm infants.
Automatic control of inspired oxygen
Most preterm infants in respiratory failure or with chronic lung disease require supplemental oxygen but because of their prematurity they are at risk of damage to their eyes and other organs if the arterial oxygen levels are excessive or insufficient [84,85]. Although arterial oxygen saturation levels are continuously monitored by pulse oximetry (SpO2) these infants spend considerable periods of time outside the intended prescribed range [86,87]. While fluctuations below the targeted range of oxygenation are usually episodic and due to the infant’s respiratory instability, high SpO2 levels in oxygen dependent infants are generally induced by excessive fraction of inspired oxygen (FiO2) [88-90].
Systems for automatic control of FiO2 have been developed with the goal of improving the maintenance of SpO2 within a target range and consequently reduce exposure to hyperoxemia and supplemental oxygen as well as to attenuate episodes of hypoxemia. Figure 5 shows representative recordings of SpO2 and FiO2 from a premature infant undergoing automatic control of FiO2.
In short term clinical studies these systems have been shown to be more effective than manual adjustments by the routine staff and by a fully dedicated nurse at bedside in keeping SpO2 within the target range [91-104]. In these studies the reduction in hyperoxemia and oxygen exposure was also significant particularly in premature infants with frequent fluctuations in oxygenation. In these infants the clinical staff often tolerates SpO2 levels well above the intended range to prevent or attenuate the episodes of hypoxemia.
Although the systems of automatic control of FiO2 have shown promising results, their impact on longer term ophthalmologic, respiratory and neurologic outcome still remains to be determined in large scale clinical trials.
These automated systems are intended to replace the repetitive task of manual titration of FiO2 and in this way enhance the efficacy of the clinical staff. The clinical studies mentioned above have shown a striking reduction in the number of manual FiO2 adjustments by the clinical staff during automatic FiO2 control. While this is a positive finding, these systems are not a substitute for continuous clinical observation of the patient and should not reduce attentiveness of the caregiver. The ability to integrate monitoring of SpO2 and the need for FiO2 into smarter alarms and warnings can mitigate potential situations when automatic adjustments could mask a respiratory deterioration and may also enhance the care since FiO2 levels are not commonly monitored at present time.
These automatic systems aim to maintain a range of SpO2 set by the clinician. However, at this time there is no consensus on the most appropriate target range of SpO2 for premature infants due to the conflicting and competitive clinical outcomes of different target ranges. In some trials lower oxygenation target ranges appear to reduce severe retinopathy of prematurity and BPD but also appear to reduce survival of the extremely premature infant [105-107]. It is also important to note that target ranges of SpO2 in observational and interventional randomized clinical trials were not closely matched by the actual SpO2 levels. Therefore caution is recommended when setting the target range in an automatic system as this would maintain such range more closely than the routine care. This may uncover effects of different target ranges that were not previously observed simply because the maintenance of SpO2 within such range was not adequate.
In summary, advances in the devices and new strategies to provide invasive and non-invasive respiratory support have achieved considerable improvements in the management of the critically ill premature infant. Further investigation to evaluate their short and long term efficacy and impact on respiratory and other relevant clinical outcomes is needed.
Continuous positive airway pressure
Positive end-expiratory pressure
Peak inspiratory pressure
Intermittent mandatory ventilation
Synchronized intermittent mandatory ventilation
Pressure support ventilation
Nasal continuous positive airway pressure
Nasal intermittent positive pressure ventilation
Respiratory distress syndrome
Proportional assist ventilation
Neurally adjusted ventilatory assist
- SpO2 :
Arterial oxygen saturation pulse oximetry
- FiO2 :
Fraction of inspired oxygen
Bloxsom A. Resuscitation of the newborn infant. Use of the positive pressure oxygen-air lock. J Pediatr. 1950;37:311–9.
Donald I. Augmented respiration: An emergency positive-pressure patient-cycled respirator. Lancet. 1954;1:895–9.
Benson F, Celander O. Respirator treatment of pulmonary insufficiency in the newborn. Acta Paediatr. 1959;48:49–50.
Heese H, Wittman W, Malan A. The management of the respiratory distress of the newborn with positive pressure respiration. S Afr Med Jour. 1963;37:123.
Delivoria-Papadopooulos M, Swyier P. Assisted ventilation in terminal hyaline membrane disease. Arch Dis Child. 1964;39:481–4.
Llewellyn MA, Tilak KS, Swyer PR. A controlled trial of assisted ventilation using an oro-nasal mask. Arch Dis Child. 1970;45:453–9.
Gregory GA, Kitterman JA, Phibbs RH, Tooley WH, Hamilton WK. Treatment of the idiopathic respiratory-distress syndrome with continuous positive airway pressure. N Engl J Med. 1971;284:1333–40.
Kirby R, Robison E, Schulz J, DeLemos RA. Continuous-flow ventilation as an alternative to assisted or controlled ventilation in infants. Anesth Analg. 1972;51:871–5.
Kattwinkel J, Fleming D, Cha CC, Fanaroff AA, Klaus MH. A device for administration of continuous positive airway pressure by the nasal route. Pediatrics. 1973;52:131–4.
DeLemos RA, McLaughlin GW, Robison EJ, Schulz J, Kirby RR. Continuous positive airway pressure as an adjunct to mechanical ventilation in the newborn with respiratory distress syndrome. Anesth Analg. 1973;52:328–32.
Northway Jr WH, Rosen RC, Porter DY. Pulmonary disease following respirator therapy of hyaline membrane disease: bronchopulmonary dysplasia. N Engl J Med. 1967;276:357–68.
Bancalari E, Abdenour GE, Feller R, Gannon J. Bronchopulmonary dysplasia: clinical presentation. J Pediatr. 1979;95:819–23.
Shennan AT, Dunn MS, Ohlsson A, Lennox K, Hoskins EM. Abnormal pulmonary outcomes in premature infants: prediction from oxygen requirement in the neonatal period. Pediatrics. 1988;82:527–32.
Taghizadeh A, Reynolds EO. Pathogenesis of bronchopulmonary dysplasia following hyaline membrane disease. Am J Pathol. 1976;82:241–64.
Dreyfuss D, Basset G, Soler P, Saumon G. Intermittent positive-pressure hyperventilation with high inflation pressures produces pulmonary microvascular injury in rats. Am Rev Respir Dis. 1985;132:880–4.
Dreyfuss D, Soler P, Basset G, Saumon G. High inflation pressure pulmonary edema. Respective effects of high airway pressure, high tidal volume, and positive end-expiratory pressure. Am Rev Respir Dis. 1988;137:1159–64.
Mehta A, Wright BM, Callan K, Stacey TE. Patient-triggered ventilation in the newborn. Lancet. 1986;2:17–9.
Greenough A, Greenall F. Patient triggered ventilation in premature neonates. Arch Dis Child. 1988;63:77–8.
Hird MF, Greenough A. Patient triggered ventilation using a flow triggered system. Arch Dis Child. 1991;66:1140–2.
Servant GM, Nicks JJ, Donn SM, Bandy KP, Lathrop C, Dechert RE. Feasibility of applying flow-synchronized ventilation to very low birthweight infants. Respir Care. 1992;37:249–53.
Bernstein G, Cleary JP, Heldt GP, Rosas JF, Schellenberg LD, Mannino FL. Response time and reliability of three neonatal patient-triggered ventilators. Am Rev Respir Dis. 1993;148:358–64.
Hummler HD, Gerhardt T, Gonzalez A, Bolivar J, Claure N, Everett R, et al. Patient-triggered ventilation in neonates: comparison of a flow-and an impedance-triggered system. Am J Respir Crit Care Med. 1996;154:1049–54.
Brochard L, Rua F, Lorina H, Lemaire F, Harf A. Inspiratory pressure support compensates for the additional work of breathing caused by the endotracheal tube. Anesthesiology. 1991;75:739–45.
Amitay M, Etches PC, Finer NN, Maidens JM. Synchronous mechanical ventilation of the neonate with respiratory disease. Crit Care Med. 1993;21:118–24.
Bernstein G, Heldt GP, Mannino FL. Increased and more consistent tidal volumes during synchronized intermittent mandatory ventilation in newborn infants. Am J Respir Crit Care Med. 1994;150(5 Pt 1):1444–8.
Cleary JP, Bernstein G, Mannino FL, Heldt GP. Improved oxygenation during synchronized intermittent mandatory ventilation in neonates with respiratory distress syndrome: a randomized, crossover study. J Pediatr. 1995;126:407–11.
Jarreau PH, Moriette G, Mussat P, Mariette C, Mohanna A, Harf A, et al. Patient-triggered ventilation decreases the work of breathing in neonates. Am J Respir Crit Care Med. 1996;153:1176–81.
Hummler H, Gerhardt T, Gonzalez A, Claure N, Everett R, Bancalari E. Influence of different methods of synchronized mechanical ventilation on ventilation, gas exchange, patient effort, and blood pressure fluctuations in premature neonates. Pediatr Pulmonol. 1996;22:305–13.
Lorino H, Moriette G, Mariette C, Lorino AM, Harf A, Jarreau PH. Inspiratory work of breathing in ventilated preterm infants. Pediatr Pulmonol. 1996;21:323–7.
Chan V, Greenough A. Randomised controlled trial of weaning by patient triggered ventilation or conventional ventilation. Eur J Pediatr. 1993;152:51–4.
Donn SM, Nicks JJ, Becker MA. Flow-synchronized ventilation of preterm infants with respiratory distress syndrome. J Perinatol. 1994;14:90–4.
Bernstein G, Mannino FL, Heldt GP, Callahan JD, Bull DH, Sola A, et al. Randomized multicenter trial comparing synchronized and conventional intermittent mandatory ventilation in neonates. J Pediatr. 1996;128:453–63.
Chen J-Y, Ling U-P, Chen J-H. Comparison of synchronized and conventional intermittent mandatory ventilation in neonates. Acta Paediatr Japonica. 1997;39:578–83.
Baumer JH. International randomised controlled trial of patient triggered ventilation in neonatal respiratory distress syndrome. Arch Disease Child. 2000;82:F5–10.
Beresford MW, Shaw NJ, Manning D. Randomised controlled trial of patient triggered and conventional fast rate ventilation in neonatal respiratory distress syndrome. Arch Dis Child. 2000;82:F14–8.
Claure N, Bancalari E. New modalities of mechanical ventilation in the preterm newborn: Evidence of benefit. Arch Dis Child Fetal Neonatal Ed. 2007;92:F508–12.
Chan V, Greenough A. Comparison of weaning by patient triggered ventilation or synchronous mandatory intermittent ventilation. Acta Paediatr. 1994;83:335–7.
Dimitriou G, Greenough A, Giffin FJ, Chan V. Synchronous intermittent mandatory ventilation modes versus patient triggered ventilation during weaning. Arch Dis Child. 1995;72:F188–90.
Reyes ZC, Claure N, Tauscher MK, D'Ugard C, Vanbuskirk S, Bancalari E. Randomized, controlled trial comparing synchronized intermittent mandatory ventilation and synchronized intermittent mandatory ventilation plus pressure support in preterm infants. Pediatrics. 2006;118:1409–17.
Bernstein G, Knodel E, Heldt GP. Airway leak size in neonates and autocycling of three flow-triggered ventilators. Crit Care Med. 1995;23:1739–44.
Fisher JB, Mammel MC, Coleman JM, Bing DR, Boros SJ. Identifying lung overdistention during mechanical ventilation by using volume-pressure loops. Pediatr Pulmonol. 1988;5:10.
Rosen WC, Mammal MC, Fisher JB, Bing DR, Holloman KK, et al. The effects of bedside pulmonary mechanics testing during infant mechanical ventilation. Pediatr Pulmonol. 1993;16:147–52.
Stenson BJ, Glover RM, Wilkie RA, Laing IA, Tarnow-Mordi WO. Randomized controlled trial of respiratory system compliance measurements in mechanically ventilated neonates. Arch Dis Child Fetal Neonatal Ed. 1998;78:F15–9.
Bisceglia M, Belcastro A, Poerio V, Raimondi F, Mesuraca L, Crugliano C, et al. A comparison of nasal intermittent versus continuous positive pressure delivery for the treatment of moderate respiratory syndrome in preterm infants. Minerva Pediatr. 2007;59:91–5.
Moretti C, Gizzi C, Papoff P, Lampariello S, Capoferri M, Calcagnini G, et al. Comparing the effects of nasal synchronized intermittent positive pressure ventilation (nSIPPV) and nasal continuous positive airway pressure (N-CPAP) after extubation in very low birth weight infants. Early Hum Dev. 1999;56:167–77.
Aghai ZH, Saslow JG, Nakhla T, Milcarek B, Hart J, Lawrysh-Plunkett R, et al. Synchronized nasal intermittent positive pressure ventilation (SNIPPV) decreases work of breathing (WOB) in premature infants with respiratory distress syndrome (RDS) compared to nasal continuous positive airway pressure (N-CPAP). Pediatr Pulmonol. 2006;41:875–81.
Ali N, Claure N, Alegria X, D’Ugard C, Organero R, Bancalari E. Effects of non-invasive pressure support ventilation (NI-PSV) on ventilation and respiratory effort in very low birth weight infants. Pediatr Pulmonol. 2007;42:704–10.
Chang HY, Claure N, D'ugard C, Torres J, Nwajei P, Bancalari E. Effects of synchronization during nasal ventilation in clinically stable preterm infants. Pediatr Res. 2011;69:84–9.
Ryan CA, Finer NN, Peters KL. Nasal intermittent positive-pressure ventilation offers no advantages over nasal continuous positive airway pressure in apnea of prematurity. Am J Dis Child. 1989;143:1196–8.
Lin CH, Wang ST, Lin YJ, Yeh TF. Efficacy of nasal intermittent positive pressure ventilation in treating apnea of prematurity. Pediatr Pulmonol. 1998;26:349–53.
Pantalitschka T, Sievers J, Urschitz MS, Herberts T, Reher C, Poets CF. Randomised crossover trial of four nasal respiratory support systems for apnoea of prematurity in very low birth weight infants. Arch Dis Child Fetal Neonatal Ed. 2009;94:F245–8.
Gizzi C, Montecchia F, Panetta V, Castellano C, Mariani C, Campelli M, et al. Is synchronised NIPPV more effective than NIPPV and NCPAP in treating apnoea of prematurity (AOP)? A randomised cross-over trial. Arch Dis Child Fetal Neonatal Ed. 2014 Oct 15. pii: fetalneonatal-2013-305892. doi:10.1136/archdischild-2013-305892. [Epub ahead of print]
Kugelman A, Feferkorn I, Riskin A, Chistyakov I, Kaufman B, Bader D. Nasal intermittent mandatory ventilation versus nasal continuous positive airway pressure for respiratory distress syndrome: A randomized, controlled prospective study. J Pediatr. 2007;150:521–6.
Sai Sunil Kishore M, Dutta S, Kumar P. Early nasal intermittent positive pressure ventilation versus continuous positive airway pressure for respiratory distress syndrome. Acta Paediatr. 2009;98:1412–5.
Lista G, Castoldi F, Fontana P, Daniele I, Cavigioli F, Rossi S, et al. Nasal continuous positive airway pressure (CPAP) versus bi-level nasal CPAP in preterm babies with respiratory distress syndrome: a randomised control trial. Arch Dis Child Fetal Neonatal Ed. 2010;95:F85–9.
Meneses J, Bhandari V, Guilherme Alves J, Herrmann D. Noninvasive ventilation for respiratory distress syndrome: a randomized controlled trial. Pediatrics. 2011;127:300–7.
Ramanathan R, Sekar KC, Rasmussen M, Bhatia J, Soll RF. Nasal intermittent positive pressure ventilation after surfactant treatment for respiratory distress syndrome in preterm infants <30 weeks' gestation: a randomized, controlled trial. J Perinatol. 2012;32:336–43.
Bhandari V, Gavino RG, Nedrelow JH, Pallela P, Salvador A, Ehrenkranz RA, et al. A randomized controlled trial of synchronized nasal intermittent positive pressure ventilation in RDS. J Perinatol. 2007;27:697–703.
Friedlich P, Lecart C, Posen R, Ramicone E, Chan L, Ramanathan R. A randomized trial of nasopharyngeal-synchronized intermittent mandatory ventilation versus nasopharyngeal continuous positive airway pressure in very low birth weight infants after extubation. J Perinatol. 1999;19:413–8.
Barrington KJ, Bull D, Finer NN. Randomized trial of nasal synchronized intermittent mandatory ventilation compared with continuous positive airway pressure after extubation of very low birth weight infants. Pediatrics. 2001;107:638–41.
Khalaf MN, Brodsky N, Hurley J, Bhandari V. A prospective randomized, controlled trial comparing synchronized nasal intermittent positive pressure ventilation versus nasal continuous positive airway pressure as modes of extubation. Pediatrics. 2001;108:13–7.
Moretti C, Giannini L, Fassi C, Gizzi C, Papoff P, Colarizi P. Nasal flow-synchronized intermittent positive pressure ventilation to facilitate weaning in very low-birthweight infants: unmasked randomized controlled trial. Pediatr Int. 2008;50:85–91.
O'Brien K, Campbell C, Brown L, Wenger L, Shah V. Infant flow biphasic nasal continuous positive airway pressure (BP- NCPAP) vs. infant flow NCPAP for the facilitation of extubation in infants' ≤ 1,250 grams: a randomized controlled trial. BMC Pediatr. 2012;12:43.
Kirpalani H, Millar D, Lemyre B, Yoder BA, Chiu A, Roberts RS, et al. A trial comparing noninvasive ventilation strategies in preterm infants. N Engl J Med. 2013;369(7):611–20.
Cheema IU, Ahluwalia JS. Feasibility of tidal volume-guided ventilation in newborn infants: a randomized, crossover trial using the volume guarantee modality. Pediatrics. 2001;107:1323–8.
Herrera CM, Gerhardt T, Claure N, Everett R, Musante G, Thomas C, et al. Effects of volume-guaranteed synchronized intermittent mandatory ventilation in preterm infants recovering from respiratory failure. Pediatrics. 2002;110:529–33.
Keszler M, Abubakar K. Volume guarantee: stability of tidal volume and incidence of hypocarbia. Pediatr Pulmonol. 2004;38:240–5.
Sinha SK, Donn SM, Gavey J, et al. Randomised trial of volume controlled versus time cycled, pressure limited ventilation in preterm infants with respiratory distress syndrome. Arch Dis Child Fetal Neonatal Ed. 1997;77:F202–5.
Singh J, Sinha SK, Clarke P, Byrne S, Donn SM. Mechanical ventilation of very low birth weight infants: Is volume or pressure a better target variable? J Pediatr. 2006;149:308–13.
Piotrowski A, Sobala W, Kawczynski P. Patient-initiated, pressure-regulated, volume-controlled ventilation compared with intermittent mandatory ventilation in neonates: a prospective, randomised study. Intensive Care Med. 1997;23:975–81.
D'Angio CT, Chess PR, Kovacs SJ, Sinkin RA, Phelps DL, Kendig JW, et al. Pressure-regulated volume control ventilation vs synchronized intermittent mandatory ventilation for very low-birth-weight infants: a randomized controlled trial. Arch Pediatr Adolesc Med. 2005;159:868–75.
Lista G, Colnaghi M, Castoldi F, Condò V, Reali R, Compagnoni G, et al. Impact of targeted-volume ventilation on lung inflammatory response in preterm infants with respiratory distress syndrome (RDS). Pediatr Pulmonol. 2004;37:510–4.
Wheeler KI, Klingenberg C, Morley CJ, Davis PG. Volume-targeted versus pressure-limited ventilation for preterm infants: a systematic review and meta-analysis. Neonatology. 2011;100:219–27.
Claure N, Gerhardt T, Hummler H, Everett R, Bancalari E. Computer controlled minute ventilation in preterm infants undergoing mechanical ventilation. J Pediatr. 1997;131:910–3.
Guthrie SO, Lynn C, Lafleur BJ, Donn SM, Walsh WF. A crossover analysis of mandatory minute ventilation compared to synchronized intermittent mandatory ventilation in neonates. J Perinatol. 2005;25:643–6.
Herber-Jonat S, Rieger-Fackeldey E, Hummler H, Schulze A. Adaptive mechanical backup ventilation for preterm infants on respiratory assist modes – a pilot study. Int Care Med. 2006;32:302–8.
Claure N, Suguihara C, Peng J, Hehre D, D'Ugard C, Bancalari E. Targeted minute ventilation and tidal volume in an animal model of acute changes in lung mechanics and episodes of hypoxemia. Neonatology. 2009;95:132–40.
Schulze A, Rieger-Fackeldey E, Gerhardt T, Claure N, Everett R, Bancalari E. Randomized crossover comparison of proportional assist ventilation and patient triggered ventilation in extremely low birth weight infants with evolving chronic lung disease. Neonatology. 2007;92:1–7.
Schulze A, Gerhardt T, Musante G, Schaller P, Claure N, Everett R, et al. Proportional assist ventilation in low birth weight infants with acute respiratory disease: A comparison to assist/control and conventional mechanical ventilation. J Pediatr. 1999;135:339–44.
Beck J, Reilly M, Grasselli G, Mirabella L, Slutsky AS, Dunn MS, et al. Patient-ventilator interaction during neurally adjusted ventilatory assist in low birth weight infants. Pediatr Res. 2009;65:663–8.
Longhini F, Ferrero F, De Luca D, Cosi G, Alemani M, Colombo D, et al. Neurally Adjusted Ventilatory Assist in Preterm Neonates with Acute Respiratory Failure. Neonatology. 2014;107:60–7.
Stein H, Alosh H, Ethington P, White DB. Prospective crossover comparison between NAVA and pressure control ventilation in premature neonates less than 1500 grams. J Perinatol. 2013;33(6):452–6.
Lee J, Kim HS, Sohn JA, Lee JA, Choi CW, Kim EK, et al. Randomized crossover study of neurally adjusted ventilatory assist in preterm infants. J Pediatr. 2012;161(5):808–13.
Flynn JT, Bancalari E, Snyder ES, Goldberg RN, Feuer W, Cassady J, et al. A cohort study of transcutaneous oxygen tension and the incidence and severity of retinopathy of prematurity. N Engl J Med. 1992;326(16):1050–4.
Collins MP, Lorenz JM, Jetton JR, Paneth N. Hypocapnia and other ventilation-related risk factors for cerebral palsy in low birth weight infants. Pediatr Res. 2001;50(6):712–9.
Hagadorn JI, Furey AM, Nghiem TH, Schmid CH, Phelps DL, Pillers DA, et al. AVIOx Study Group. Achieved versus intended pulse oximeter saturation in infants born less than 28 weeks' gestation: the AVIOx study. Pediatrics. 2006;118:1574–82.
Laptook AR, Salhab W, Allen J, Saha S, Walsh M. Pulse oximetry in very low birth weight infants: can oxygen saturation be maintained in the desired range? J Perinatol. 2006;26:337–41.
Sink DW, Hope SA, Hagadorn JI. Nurse:patient ratio and achievement of oxygen saturation goals in premature infants. Arch Dis Child Fetal Neonatal Ed. 2011;96:F93–8.
Ford SP, Leick-Rude MK, Meinert KA, Anderson B, Sheehan MB, Haney BM, et al. Overcoming barriers to oxygen saturation targeting. Pediatrics. 2006;118:S177–86.
van Zanten HA, Tan RN, Thio M, de Man-van Ginkel JM, van Zwet EW, Lopriore E, et al. The risk for hyperoxaemia after apnoea, bradycardia and hypoxaemia in preterm infants. Arch Dis Child Fetal Neonatal Ed. 2014;99:F269–73.
Beddis JR, Collins P, Levy NM, Godfrey S, Silverman M. New Technique for servo-control of arterial oxygen tension in preterm infants. Arch Dis Child. 1979;54:278–80.
Dugdale RE, Cameron RG, Lealman GT. Closed-loop control of the partial pressure of arterial oxygen in neonates. Clin Physics Physiol Meas. 1988;9:291–305.
Bhutani VK, Taube JC, Antunes MJ, Delivoria-Papadopoulos M. Adaptive control of the inspired oxygen delivery to the neonate. Pediatr Pulmonol. 1992;14:110–7.
Morozoff PE, Evans RW. Closed-loop control of SaO2 in the neonate. Biomed Instrum & Technol. 1992;26:117–23.
Sun Y, Kohane IS, Stark AR. Computer-assisted adjustment of inspired oxygen concentration improves control of oxygen saturation in newborn infants requiring mechanical ventilation. J Pediatr. 1997;131:754–6.
Morozoff EP, Smyth JA. Evaluation of three automatic oxygen therapy control algorithms on ventilated low birth weight neonates. Conf Proc IEEE Eng Med Biol Soc. 2009;2009:3079–82.
Claure N, Gerhardt T, Everett R, Musante G, Herrera C, Bancalari E. Closed-loop controlled inspired oxygen concentration for mechanically ventilated very low birth weight infants with frequent episodes of hypoxemia. Pediatrics. 2001;107:1120–4.
Urschitz MS, Horn W, Seyfang A, Hallenberger A, Herberts T, Miksch S, et al. Automatic control of the inspired oxygen fraction in preterm infants: a randomized crossover trial. Am J Respir Crit Care Med. 2004;170:1095–100.
Claure N, D'Ugard C, Bancalari E. Automated adjustment of inspired oxygen in preterm infants with frequent fluctuations in oxygenation: a pilot clinical trial. J Pediatr. 2009;155:640–5.
Claure N, Bancalari E, D'Ugard C, Nelin L, Stein M, Ramanathan R, et al. Multicenter Crossover Study of Automated Adjustment of Inspired Oxygen in Mechanically Ventilated Preterm Infants. Pediatrics. 2011;127:e76–83.
Wilinska M, Bachman T, Swietlinski J, Kostro M, Twardoch-Drozd M. Automated FiO2-SpO2 control system in neonates requiring respiratory support: a comparison of a standard to a narrow SpO2 control range. BMC Pediatr. 2014;14:130.
Hallenberger A, Poets CF, Horn W, Seyfang A, Urschitz MS, CLAC Study Group. Closed-loop automatic oxygen control (CLAC) in preterm infants: a randomized controlled trial. Pediatrics. 2014;133:e379–85.
Lal MK, Tin W, Sinha SK. Crossover study of automated control of inspired oxygen in ventilated newborn infants. Pediatric Academic Societies 2014. E-PAS 4680.7.
van Kaam A, Hummler H, Wilinska M, Swietlinski J, Lal M, te Pas A, et al. Automated versus manual FiO2 control at different saturation targets in preterm infants. Eur Soc Pediatric Res, 2014.
SUPPORT Study Group of the Eunice Kennedy Shriver NICHD Neonatal Research Network, Carlo WA, Finer NN, Walsh MC, Rich W, Gantz MG, et al. Target ranges of oxygen saturation in extremely preterm infants. N Engl J Med. 2010;362:1959–69.
Stenson B, Brocklehurst P, Tarnow-Mordi W. U.K. BOOST II trial; Australian BOOST II trial; New Zealand BOOST II trial. Increased 36-week survival with high oxygen saturation target in extremely preterm infants. N Engl J Med. 2011;364:1680–2.
Schmidt B, Whyte RK, Asztalos EV, Moddemann D, Poets C, Rabi Y, et al. Canadian Oxygen Trial (COT) Group. Effects of targeting higher vs lower arterial oxygen saturations on death or disability in extremely preterm infants: a randomized clinical trial. JAMA. 2013;309:2111–20.
We are grateful for the continuing support of the University of Miami Project NewBorn.
The system for closed loop inspired oxygen discussed in some of the publications cited here was developed and patented by Drs. Claure and Bancalari, who are Faculty of the University of Miami. The University of Miami, the assignee for this patent, has a licensing agreement with CareFusion. CareFusion provided research support for the studies with this system.
Drs. EB and NC reviewed the cited literature and drafted the review manuscript. Both authors read and approved the final manuscript.
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Bancalari, E., Claure, N. Advances in respiratory support for high risk newborn infants. matern health, neonatol and perinatol 1, 13 (2015) doi:10.1186/s40748-015-0014-5
- Mechanical ventilation
- Supplemental oxygen
- Premature infant