Evidence suggests that the addition of VTV to PLV significantly reduces BPD, intraventricular hemorrhage (IVH), air leaks, duration of ventilation, and composite outcomes of death and BPD [11]. Despite the strong evidence, the application of VTV in neonatal units is far from universal. This is probably due to the use of so-called universal ventilators, which may lack the accuracy required for the delivery of tiny VT required for extremely low birth weight (ELBW) infants, along with the reluctance of clinicians to move away from the comfort zone of using the traditional mode (PLV) [7, 8]. Older and universal ventilators often measure VT at the proximal end, thereby grossly underestimating VT. With current dedicated neonatal ventilators, it is possible to measure VT at the patient end of the circuit, thereby making it more accurate. In VTV, the pressure changes according to the compliance of the lung to ensure the set VT delivery to the airway. This means that with improved lung compliance, PIP is automatically reduced, resulting in real-time weaning. This feature makes it attractive for weaning, including the period immediately after surfactant administration. VTV has variable nomenclature according to ventilator manufacturers; therefore, users should be conversant with the ventilator used in their units. The commonly used terms for VTV are VG and pressure-regulated volume control (PRVC). These modes are essentially the same in principle, with slight variability in the way VT for the next breath is calculated. In VG, the user chooses a target VT based on the lung condition and the pressure limit. The ventilator then compares the exhaled VT of the previous inflation and adjusts the PIP to achieve the set VT. An important practical consideration is that the user must attempt to reduce peri-endotracheal tube leaks. Although recent ventilators compensate for leaks, in practice, leaks of more than 30–40% make VT measurements inaccurate and can be subject to excessive VT delivery at inspiration. This can also lead to wide variability in breath-to-breath pressure, making it difficult to provide smooth gas flow delivery.

Because the main driving factor is VT, the choice of an appropriate VT is critical for the successful use of VTV. Set VT is affected by the infant’s size, postnatal age, and underlying lung disease. A general guide for selecting an appropriate VT is provided elsewhere [7, 8]. Box 1 provides a general guide for VTV. Once the initial settings are deployed, it is essential to carefully monitor the infant and titrate them accordingly.

Ventilation is a blend of art and science. Unfortunately, titration of mechanical ventilation in neonates is still more of an art than science itself. Therefore, titration of ventilation requires an experienced clinician who can make an informed judgment based on meticulous bedside clinical assessment (rate, retraction, chest rise, oxygen saturation measured by a pulse oximeter or SpO2, etc.) coupled with real-time pulmonary graphics and transcutaneous CO2 or blood gas monitoring. Modern ventilators provide a large amount of data on delivered volumes, volume leaks, and compliance/resistance of the system, which can help in the real-time titration of ventilation. In this section, we briefly discuss pulmonary graphics.

Pulmonary graphics refer to the visual representation of the interplay of respiratory mechanics (pressure, flow, volume, and time), displayed in the form of waveforms (scalars) and loops [12,13,14]. These graphs provide real-time information about airflow, pressure, and volume changes in the lungs, allowing clinicians to assess lung function and optimize mechanical ventilation settings.

In neonates, common types of pulmonary graphics include pressure–volume (P–V) loops, flow–volume (F-V) loops, and time-based scalars (time against pressure, flow, and volume). Of these P–V loops, F-V loops and flow-time scalars are commonly used in clinical practice. We have provided a typical P–V loop, F-V loop, and flow-time scalar (Fig. 1A–C). The graphics can help in the early identification of air trapping (Fig. 1D-F) and hence guide clinicians in adjusting positive end-expiratory pressure (PEEP) and flow rate without waiting for chest radiographs. Similarly, peri-endotracheal tube leaks could be easily identified (Fig. 1G-I) and corrected in real-time. These graphics can help assess the response in real-time (for example, applying cricoid pressure in case of a peri-endotracheal tube leak will be reflected immediately on pulmonary graphics). Pulmonary graphics can also help optimize the PIP and hence avoid overdistension (Fig. 1J). They can also provide evidence of high airway resistance (Fig. 1K). Last but not least, they can provide guidance on the need for suction in the presence of airway secretions (Fig. 1L). Because the changes are reflected in real-time, they can be used to provide guidance for weaning (particularly in pressure-controlled ventilation). Although clinicians use pulmonary graphics, there are no clinical trials to determine whether their use actually results in better outcomes [14]. In the authors’ experience, they help clinicians make “informed decisions” in the titration of mechanical ventilation. Nevertheless, there is a need for RCTs to provide definitive scientific evidence for their utility to impact clinical outcomes.

HFV delivers a very small VT (less than the anatomical dead space) to the lungs at extremely rapid rates (up to 900 per minute). Since volutrauma is the major factor for VILI, this mode aims to reduce VILI with less VT, while maintaining constant alveolar distending pressure and improving gas exchange. The three main ventilator modalities used to provide HFV are HF oscillatory ventilation (HFOV), HF jet ventilation (HFJV), and HF flow interruption (HFFI). The first two are commonly used in neonates and are discussed here.

HFOV is generated using a specialized ventilator that produces rapid, small-amplitude oscillations (up to 900 per minute) using a piston or diaphragm within the ventilator to rapidly shift air in and out of the lungs. A constant distending pressure or CDP (known as mean airway pressure or MAP) is set, which helps in alveolar recruitment and oxygenation. Amplitude and frequency are mainly responsible for ventilation, which is independent of oxygenation. VT is very low (1–3 mL/kg), and the mechanism of VT delivery is very different from that of conventional ventilators. There are many postulated mechanisms for the physiological basis of its function, including alveolar pendelluft, cardiogenic mixing, Taylor dispersion, and molecular diffusion [15, 16]. In clinical trials, HFOV has been used as a primary as well as rescue modality [17, 18]. When used as the primary elective mode in preterm infants, it has been shown to have a slight benefit in composite outcomes (death or BPD) and retinopathy of prematurity; however, the evidence is very uncertain [17]. Owing to this uncertainty over its benefits, the need for specialized equipment to deliver HFOV, and advancements in CMV technology and strategies, its use as the first-line mode in neonates is very limited. It is commonly used as a rescue mode in clinical practice in situations of actual air leaks or when air leaks are highly likely, for example, in hypoplastic lungs or the requirement of very high PIP in extremely premature infants. However, data to support or refute its superiority (or inferiority) over conventional ventilation are limited [18, 19].

The HFJV uses short rapid (240–660 per minute) pulses of pressurized gases that are released as a jet, either directly into the endotracheal tube or into the Y-piece of the circuit. In contrast to HFOV, exhalation is passive, and to minimize the risk of gas trapping, lower operating frequencies are often applied. The settings of the conventional ventilator (PIP, PEEP, Ti, and respiratory rate or frequency or f), which is used in tandem with HJV, contribute to a MAP comparable to that of CMV. The inspiratory times are very short (0.02 to 0.03 s) with prolonged expiratory times, making this ventilator very effective in the management of air leaks. This mode is gaining popularity in extremely premature neonates (22–26 weeks), although there is limited data on its efficacy and safety [4, 15, 19].

As mentioned earlier, invasive ventilation is a major reason for VILI; therefore, ventilation strategies are directed toward gentle ventilation for as minimal duration as possible. Once an infant is intubated, a clear and written plan for extubation is required. Infants should be assessed regularly for extubation readiness. Unfortunately, there is no ready-made “one size fits all” model or single tool for assessing readiness for successful extubation. Lower gestation, sepsis, pre-extubation acidosis, pre-extubation high fraction of inspired O2 (FiO2), and higher respiratory distress severity scores were associated with an increased risk of extubation failure [20]. Many trials have used the spontaneous breathing trial (SBT) test to predict extubation success. A recent systematic review suggested that SBT in preterm infants can accurately predict extubation success, but not extubation failure. Therefore, there is a lack of evidence supporting its use as an independent predictor of extubation failure in premature infants [21]. Instead of relying on a single parameter, we suggest using a checklist to assess extubation readiness (Box 2). In general, the condition for which the infant was intubated should have been resolved, and the infant should be on minimal settings (PIP 12–15 cm H2O, PEEP 5–6 cm H2O, FiO2 < 0.30) and should have good spontaneous efforts. Infants < 32 weeks should preferably be extubated to nasal intermittent positive pressure ventilation (NIPPV) to improve extubation success. Postextubation care is a critical determinant of extubation success; therefore, appropriate airway management, positioning, physiotherapy, good nursing care, humidification, nasal care along with appropriate NIV support are crucial.

Currently, the focus in neonatology has shifted from survival to “intact survival.” Preterm infants on invasive mechanical ventilation are at an increased risk of sepsis, ventilator-associated pneumonia, air leaks, BPD, and adverse neurodevelopmental outcomes [22]. Therefore, strategies to prevent such complications should be developed and implemented from birth. In general, invasive mechanical ventilation should be avoided as much as possible. If needed, gentle lung ventilation for as minimum as possible duration is recommended. Apart from gentle ventilation, gentle resuscitation, appropriate antibiotic use, early caffeine use, early surfactant administration (if needed) through less-invasive surfactant administration (LISA), Vitamin A supplementation, exclusive human milk feeding with increased energy uptake, avoiding excessive positive fluid balance, and maintaining oxygen saturation between 90 and 95% are evidence-based strategies for BPD prevention. A detailed description of evidence-based recommendations as per the various stages of BPD is beyond the scope of this article and is provided elsewhere [22,23,24].