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Neonatal respiratory failure remains a primary cause of admission to neonatal intensive care units (NICUs) worldwide. Premature birth, affecting an estimated 15 million neonates annually globally, is strongly correlated with pulmonary immaturity and an elevated risk of respiratory complications (1). In such cases, respiratory support is frequently indispensable for reducing morbidity and improving survival outcomes.

Common causes of neonatal respiratory insufficiency include respiratory distress syndrome (RDS), transient tachypnea of the newborn (TTN), pneumonia, and apnea of prematurity. Without timely intervention, these conditions can lead to rapid clinical deterioration and significant long-term sequelae, such as bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH), or mortality.

The physiological immaturity of the neonatal lung significantly contributes to the high incidence of respiratory complications in preterm and term neonates with perinatal distress. In premature infants, incomplete alveolarization and insufficient surfactant production often lead to alveolar collapse.

These factors, coupled with a compliant chest wall, underdeveloped respiratory musculature, and increased oxygen demands, create a scenario where neonates are prone to atelectasis, hypoventilation, and respiratory failure (2). Consequently, mechanical or non-invasive ventilatory support is frequently initiated shortly after birth to stabilize gas exchange and reduce the work of breathing.

Over the past few decades, the field of neonatal respiratory support has evolved dramatically. Mechanical ventilation, once the cornerstone of neonatal respiratory care, has increasingly been supplanted by lung-protective strategies designed to minimize the risks of ventilator-induced lung injury (VILI).

Innovations such as volume-targeted ventilation (VTV), high-frequency oscillatory ventilation (HFOV), and neurally adjusted ventilatory assist (NAVA) have significantly improved synchronization and pressure control. Parallel advances in monitoring technology, including electrical impedance tomography (EIT) and artificial intelligence (AI)-based ventilator analytics, now offer real-time, individualized feedback for optimized care (3).

This review aims to provide a comprehensive overview of current strategies and innovations in neonatal respiratory support. It covers the physiological basis for respiratory assistance in neonates, details conventional and emerging ventilatory approaches, and explores the implications of novel technologies.

Additionally, it discusses the persistent challenges encountered in low-resource settings and outlines future directions for research and clinical practice. Through this review, we seek to inform clinicians, researchers, and policymakers about the current state and future potential of neonatal respiratory care worldwide.

Physiology and Pathophysiology in Neonatal Respiratory

The transition from intrauterine to extrauterine life presents substantial respiratory challenges for neonates, particularly those born prematurely. In utero, gas exchange occurs via the placenta, with the fetal lungs remaining fluid-filled and relatively inactive.

At birth, this abruptly changes, necessitating rapid clearance of lung fluid, the onset of spontaneous breathing, and functional pulmonary circulation. The success of this transition is highly dependent on lung maturity, surfactant availability, and coordinated cardiorespiratory function.

Lung development progresses through several distinct stages: embryonic, pseudoglandular, canalicular, saccular, and alveolar. Alveolarization—the formation of functional gas-exchange units—begins around 36 weeks of gestation and continues postnatally.

In preterm infants, especially those born before 32 weeks, alveolar and capillary networks are insufficiently developed to support efficient gas exchange (2). This underdevelopment contributes to poor lung compliance, increased airway resistance, and ineffective ventilation.

One of the most critical deficits in preterm lung function is the lack of surfactant, a lipoprotein complex that reduces surface tension and prevents alveolar collapse. Surfactant deficiency leads to decreased lung compliance, atelectasis, and impaired oxygenation—the hallmark features of Respiratory Distress Syndrome (RDS).

Additionally, the neonatal chest wall is highly compliant, offering little resistance to inward recoil, and the diaphragm is relatively underpowered, further limiting ventilation efficiency.

Several pathophysiological conditions arise from these anatomical and functional limitations. Transient Tachypnea of the Newborn (TTN) is common in term and near-term infants and is caused by delayed absorption of fetal lung fluid.

In contrast, apnea of prematurity results from the immaturity of brainstem respiratory centers, leading to episodic cessation of breathing. While the underlying mechanisms differ for these conditions, both may necessitate some form of respiratory assistance, whether invasive or non-invasive.

In addition to pulmonary immaturity, hemodynamic and systemic challenges—such as persistent pulmonary hypertension of the newborn (PPHN), patent ductus arteriosus (PDA), or sepsis—can compound respiratory compromise. Hypoxemia and acidosis further increase pulmonary vascular resistance, worsening oxygenation and potentially causing right-to-left shunting.

Collectively, these factors explain why many neonates, especially those born prematurely or with perinatal complications, require respiratory support. Understanding the unique physiology and vulnerabilities of the neonatal lung is essential for selecting the appropriate support strategy and optimizing outcomes.

Invasive Ventilatory Support

Invasive mechanical ventilation (IMV) is a critical intervention for neonates with life-threatening respiratory failure, often due to surfactant deficiency, structural lung immaturity, or systemic complications such as sepsis or persistent pulmonary hypertension.

While IMV can be life-saving, it is associated with significant risks, necessitating careful selection of ventilatory modes, parameters, and weaning strategies to optimize outcomes and reduce harm (4, 5).

Invasive Ventilation Modes and Strategies

Several ventilatory modes are used in neonatal intensive care units (NICUs), each tailored to specific clinical needs:

• Assist-Control Ventilation (A/C): Delivers preset breaths, which can be initiated by the neonate or the ventilator. While maintaining adequate minute ventilation, this mode carries an increased risk of asynchrony and volutrauma (lung injury caused by excessive tidal volumes).
• Synchronized Intermittent Mandatory Ventilation (SIMV): Synchronizes mandatory breaths with spontaneous respiratory efforts, improving patient comfort and reducing the risk of hyperventilation.
• Volume-Targeted Ventilation (VTV): Automatically adjusts pressure to deliver consistent tidal volumes. Studies indicate that VTV reduces the incidence of bronchopulmonary dysplasia (BPD), hypocarbia, and intraventricular hemorrhage compared to pressure-limited modes (6, 7).
• High-Frequency Oscillatory Ventilation (HFOV): Utilizes rapid oscillations at small tidal volumes, thereby maintaining lung recruitment while minimizing barotrauma. Newer strategies now emphasize volume targeting during HFOV, leading to better control of CO₂ and improved outcomes (7, 8).

Lung-Protective Strategies

Modern neonatal ventilation prioritizes lung protection by minimizing injury from overdistension and repetitive collapse-reopening:

• Permissive Hypercapnia: This strategy tolerates moderate hypercapnia to reduce ventilation pressures and associated lung injury.
• Open Lung Strategy: This approach incorporates lung recruitment maneuvers and optimal PEEP (Positive End-Expiratory Pressure) titration to prevent atelectasis and minimize dynamic strain (9).
• Volume Guarantee Modes: Integrated into many modern ventilators, these modes ensure the delivery of targeted volumes during each breath, regardless of compliance changes.

Innovations such as artificial intelligence (AI)-guided pressure titration and real-time electrical impedance tomography (EIT) are increasingly integrated to personalize lung protection strategies (2, 3).

Risks and Adverse Outcomes

Invasive mechanical ventilation (IMV) is associated with several short- and long-term complications, including:

• Ventilator-Induced Lung Injury (VILI): This encompasses barotrauma, volutrauma, atelectrauma, and biotrauma, all of which are primary contributors to bronchopulmonary dysplasia (BPD).
• Ventilator-Associated Pneumonia (VAP): A significant nosocomial infection risk that can prolong NICU stay and worsen outcomes.
• Laryngeal and Airway Injury: Prolonged intubation can lead to subglottic stenosis and tracheomalacia, particularly in very low birth weight (VLBW) infants.
• Chronic Lung Disease: Up to 50% of preterm infants requiring prolonged IMV develop BPD, with lasting implications for pulmonary and neurodevelopment (10).

Extubation and Weaning in Neonates

The transition from invasive mechanical ventilation (IMV) to spontaneous breathing is a critical juncture in neonatal respiratory care. Premature or failed extubation can lead to increased morbidity, prolonged hospital stays, and a higher risk of complications such as ventilator-associated pneumonia (VAP), airway trauma, and bronchopulmonary dysplasia (BPD) (11). Therefore, the timing and strategy for weaning and extubation must be both evidence-based and individualized.

Physiological Readiness for Extubation

Successful extubation depends on the maturity and coordination of respiratory control, adequate gas exchange, and respiratory muscle endurance. Clinicians assess multiple physiological parameters before attempting extubation, including:

• Adequate Spontaneous Respiratory Drive: Demonstrated by consistent respiratory effort with an acceptable respiratory rate.
• Stable Gas Exchange: Pre-extubation arterial blood gases should show a pH > 7.25, PaCO₂ < 60 mmHg (for most neonates), and SpO₂ in the target range on an FiO₂ < 0.4.
• Minimal Ventilator Support: Indicated by peak inspiratory pressure (PIP) < 20 cmH₂O, PEEP ≤ 5 cmH₂O, and mean airway pressure (MAP) within safe limits.
• Hemodynamic Stability: Absence of significant cardiovascular instability, apnea, or bradycardia episodes.

Premature infants are especially vulnerable to extubation failure due to underdeveloped respiratory musculature, immature central respiratory control, and a highly compliant chest wall (12).

Clinical Predictors and Tools

While there is no universally accepted extubation readiness index, several approaches have shown promise:

• Spontaneous Breathing Trials (SBTs): Typically lasting 3–5 minutes, SBTs assess the neonate’s ability to breathe spontaneously with minimal pressure support. Success in SBTs correlates strongly with extubation success in older infants but has mixed predictive value in preterm infants (13).
• Extubation Readiness Scores (ERS): Composite tools incorporating variables like gestational age, respiratory pattern, minute ventilation, and neurological status are under investigation to standardize assessments (3).
• Diaphragmatic Ultrasound and EIT: Novel non-invasive imaging modalities such as diaphragmatic excursion measurement and electrical impedance tomography (EIT) can aid in assessing respiratory effort and lung aeration prior to extubation (2).

Weaning Strategies

Weaning protocols can be gradual or abrupt, depending on the patient’s underlying condition, lung maturity, and ventilator settings. Common strategies include:

• Stepwise Reduction: This involves progressively decreasing ventilator support parameters (e.g., Peak Inspiratory Pressure [PIP], respiratory rate, FiO₂) while continuously monitoring for signs of distress or desaturation.
• Mode Transitioning: This strategy involves transitioning from synchronized intermittent mandatory ventilation (SIMV) or assist-control (A/C) to pressure support ventilation (PSV) or continuous positive airway pressure (CPAP) before extubation.
• Volume Guarantee Titration: Ensuring the delivery of a minimum tidal volume, even during low spontaneous effort, helps prevent underventilation before extubation.

Extubation Failure and Its Implications

Extubation failure—defined as the need for reintubation within 48–72 hours—occurs in up to 30–40% of extremely preterm infants. Risk factors include:

• Birth weight < 1000g
• Gestational age < 28 weeks
• History of sepsis or intraventricular hemorrhage (IVH)
• High FiO₂ (> 0.5) at the time of extubation
• Poor weight gain or neuromuscular tone

The consequences of failed extubation are significant: repeated intubation increases the risk of vocal cord injury, subglottic stenosis, and worsens lung inflammation, potentially exacerbating bronchopulmonary dysplasia (BPD) (9, 11).

To mitigate this risk, post-extubation support strategies include the early use of non-invasive ventilation (e.g., nasal continuous positive airway pressure [nCPAP], bilevel positive airway pressure [BiPAP], high-flow nasal cannula [HFNC]) and pharmacologic agents like caffeine citrate, which has been shown to reduce apnea and improve extubation outcomes in preterm infants (10).

Non-Invasive Ventilation Strategies in Neonatal Respiratory

Non-invasive ventilation (NIV) plays a pivotal role in neonatal respiratory support, particularly in preterm infants, by providing respiratory assistance while avoiding the risks associated with endotracheal intubation. The primary goal of NIV is to maintain adequate gas exchange, reduce the work of breathing, and prevent lung injury associated with invasive ventilation. Over the past two decades, this field has evolved significantly, offering a range of NIV modalities with improved patient outcomes.

Modes of Non-Invasive Ventilation

Nasal Continuous Positive Airway Pressure (nCPAP) is the most widely used non-invasive technique in neonatal units. It operates by maintaining a constant distending pressure in the airways, thereby preventing alveolar collapse, improving functional residual capacity, and decreasing the work of breathing.

NCPAP is particularly effective in the early management of Respiratory Distress Syndrome (RDS) and has been shown to reduce the need for mechanical ventilation and the risk of bronchopulmonary dysplasia (14).

Nasal Intermittent Positive Pressure Ventilation (NIPPV) and its variant, Bilevel Positive Airway Pressure (BiPAP), deliver intermittent pressure boosts over a CPAP baseline. NIPPV improves minute ventilation, augments tidal volumes, and is especially effective during weaning or post-extubation. Studies indicate that NIPPV reduces extubation failure compared to nCPAP, although its superiority in primary respiratory support is less conclusive (15, 16).

Heated Humidified High-Flow Nasal Cannula (HHHFNC) delivers warmed, humidified air-oxygen blends at flow rates sufficient to wash out nasopharyngeal dead space and provide a low level of positive pressure. Its simplicity, comfort, and ease of use have led to its widespread adoption. However, HHHFNC may provide insufficient support in infants with moderate to severe RDS, particularly those younger than 28 weeks of gestation (17).

Non-invasive Neurally Adjusted Ventilatory Assist (NAVA) utilizes diaphragmatic electromyographic signals to trigger ventilator assistance, offering highly synchronized support. While promising, this modality is currently limited to specialized centers and remains under evaluation in large-scale clinical trials (18).

Interfaces and Delivery Systems

The effectiveness of non-invasive ventilation (NIV) is profoundly influenced by the interface used. Poorly fitted or inappropriate interfaces can lead to pressure leak, ineffective ventilation, or skin injury. A range of nasal interfaces is available, each with unique advantages and trade-offs:

There is no definitive consensus on the most effective interface; however, rotating between nasal prongs and masks is widely recommended to prevent skin breakdown (19, 20).

Failure Criteria and Escalation Indicators

Recognizing non-invasive ventilation (NIV) failure early is essential to avoid delays in mechanical ventilation, which are associated with higher morbidity. Failure criteria include:

• Arterial pH < 7.25 with PaCO₂ > 65 mmHg
• Sustained FiO₂ > 0.4 to maintain SpO₂ targets
• Recurrent apnea (>6 episodes/hour) or severe bradycardia
• Respiratory muscle fatigue and signs of distress
• Hemodynamic instability

Adjuncts such as rescue surfactant therapy—administered via the INSURE (Intubation, Surfactant, Extubation) or LISA (Less Invasive Surfactant Administration) methods—can help reduce the likelihood of NIV failure and progression to mechanical ventilation (17, 21).

Clinical Outcomes and Ongoing Controversies

Non-invasive ventilation (NIV) has been instrumental in reducing rates of intubation, bronchopulmonary dysplasia (BPD), and ventilator-associated complications. However, several debates remain unresolved:

• NIPPV vs. CPAP: While evidence supports NIPPV as superior for reducing extubation failure, its effectiveness in avoiding initial intubation is not uniformly conclusive (15).
• HFNC as Primary Support: Although user-friendly and well-tolerated, high-flow nasal cannula (HFNC) may be suboptimal for more severe cases of respiratory distress syndrome (RDS) in preterm infants (14, 16).
• Nasal Trauma: Nasal skin breakdown remains a significant complication, particularly with prolonged nCPAP use. Preventive measures include hydrocolloid barriers, alternating interfaces, and vigilant skin checks (19).
• Protocol Variability: A lack of standardized protocols for the initiation, escalation, and weaning of NIV persists across institutions, highlighting the need for consensus guidelines and further research (22).

References

1.      Greenough, A., Alberti, P., & Ade-Ajayi, N. (2025). Respiratory support strategies for surgical neonates: A review. Children, 12(6), Article e1009. https://pmc.ncbi.nlm.nih.gov/articles/PMC11941308/

2.      Ako, A. A., Ismaiel, A., & Rastogi, S. (2025). Electrical impedance tomography in neonates: A review. Pediatric Research. https://www.nature.com/articles/s41390-025-03929-x

3.      Hsu, J. F., Lin, Y. C., Lin, C. Y., Chu, S. M., & Cheng, H. J. (2025). Deep learning models for early and accurate diagnosis of ventilator-associated pneumonia in mechanically ventilated neonates. Computers in Biology and Medicine, 162, Article 107511. https://www.sciencedirect.com/science/article/pii/S0010482525002938

4.      Chakkarapani, A. A., Adappa, R., Ali, S. K. M., & Gupta, S. (2020). Current concepts in assisted mechanical ventilation in the neonate: Part 2. International Journal of Pediatrics and Adolescent Medicine, 7(4), 179–186. https://doi.org/10.1016/j.ijpam.2020.07.006

5.      Schulzke SM, Stoecklin B. Update on ventilatory management of extremely preterm infants. Pediatr Anesth. 2022;32(5):432-40.  https://doi.org/10.1111/pan.14369

6.      Keszler, M. (2017). Volume-targeted ventilation: One size does not fit all. Seminars in Fetal and Neonatal Medicine, 22(6), 369–375. https://doi.org/10.1016/j.siny.2017.08.002

7.      Tingay, D. G., Dahm, S. I., & Sett, A. (2025). Are we ready for volume targeting during high-frequency oscillatory ventilation in neonates? Pediatric Research. https://www.nature.com/articles/s41390-025-04015-y

8.      Hodgson, C. L., Tuxen, D. V., & Adritsos, D. (2020). Application of new ARDS guidelines at the bedside. Critical Care, 24(1), 1307-16. https://pmc.ncbi.nlm.nih.gov/articles/PMC6591785/

9.      Van Kaam, A. H., & Rimensberger, P. C. (2007). Lung-protective ventilation strategies in neonatology: What do we know and what do we need to know? Critical Care Medicine, 35(3), 925–931. https://journals.lww.com/ccmjournal/Abstract/2007/03000/Lung_protective_ventilation_strategies_in.35.aspx

10.   Shi, Y., & De Luca, D. (2019). Noninvasive respiratory support strategies after extubation in preterm neonates. BMC Pediatrics, 19, Article 1625. https://doi.org/10.1186/s12887-019-1625-1

11.   Ozer, E. A. (2020). Lung-protective ventilation in neonatal intensive care unit. Journal of Clinical Neonatology, 9(3), 105–113. https://10.4103/jcn.JCN_96_19

12.   Egbuta, C., & Easley, R. B. (2022). Update on ventilation management in the Pediatric Intensive Care Unit. Pediatric Anesthesia, 32(6), 698–708. https://doi.org/10.1111/pan.14374

13.   Colaizy, T. T., Elgin, T. G., Berger, J. N., & Thomas, B. A. (2022). Ventilator management in extremely preterm infants. NeoReviews, 23(10), e661–e671. https://doi.org/10.1542/neo.23-10-e661

14.   Shi, Y., Muniraman, H., & Biniwale, M. (2020). A review on non-invasive respiratory support for management of respiratory distress in extremely preterm infants. Frontiers in Pediatrics, 8, Article 270. https://doi.org/10.3389/fped.2020.00270

15.   Yuan, G., Liu, H., Wu, Z., & Chen, X. (2021). Comparison of the efficacy and safety of three non-invasive ventilation methods in the initial treatment of premature infants with respiratory distress syndrome. International Journal of Clinical and Experimental Medicine, 14(2), 375–383. https://e-century.us/files/ijcem/14/2/ijcem0116814.pdf

16.   More, K., Ramaswamy, V. V., & Roehr, C. C. (2020). Efficacy of noninvasive respiratory support modes for primary respiratory support in preterm neonates with respiratory distress syndrome: systematic review and meta-analysis. Pediatric Pulmonology, 55(6), 1325–1335. https://doi.org/10.1002/ppul.25011

17.   Dassios, T., Kaltsogianni, O., & Greenough, A. (2023). Neonatal respiratory support strategies—short and long-term respiratory outcomes. Frontiers in Pediatrics, 11, Article 1212074. https://doi.org/10.3389/fped.2023.1212074

18.   Karnati, S., & Sammour, I. (2020). Non-invasive respiratory support of the premature neonate: from physics to bench to practice. Frontiers in Pediatrics, 8, Article 214. https://doi.org/10.3389/fped.2020.00214

19.   Boel, L., Hixson, T., Brown, L., Sage, J., & Kotecha, S. (2022). Non-invasive respiratory support in preterm infants. Paediatric Respiratory Reviews, 44, 1–10. https://doi.org/10.1016/j.prrv.2022.01.004

20.   Ramaswamy, V. V., Devi, R., & Kumar, G. (2023). Non-invasive ventilation in neonates: a review of current literature. Frontiers in Pediatrics, 11, Article 1248836. https://doi.org/10.3389/fped.2023.1248836

21.   Permall, D. L., Pasha, A. B., & Chen, X. (2019). Current insights in non-invasive ventilation for the treatment of neonatal respiratory disease. Italian Journal of Pediatrics, 45, 70. https://doi.org/10.1186/s13052-019-0707-x

22. Hussain, W. A., & Marks, J. D. (2019). Approaches to noninvasive respiratory support in preterm infants: from CPAP to NAVA. NeoReviews, 20(4), e213–e225. 

Mechanical ventilation plays a critical role in addressing the pathophysiological mechanisms underlying acute respiratory failure (ARF). By correcting gas exchange abnormalities, reducing respiratory muscle workload, and preventing complications, it provides essential support for patients in critical conditions (1,5,7,8). Below, specific mechanisms of mechanical ventilation are linked to the pathophysiological issues they target to enhance clarity and coherence.

Correction of Hypoxemia

One of the primary goals of mechanical ventilation in ARF is to address hypoxemia caused by mechanisms such as ventilation-perfusion (V/Q) mismatch, shunting, or diffusion impairment.

• Mechanism: Mechanical ventilation increases the fraction of inspired oxygen (FiO₂), ensuring higher oxygen availability in the alveoli, which is crucial for patients with reduced oxygenation due to pneumonia, ARDS, or pulmonary embolism.
• PEEP (Positive End-Expiratory Pressure): PEEP prevents alveolar collapse during exhalation by maintaining positive pressure in the lungs, thereby improving functional residual capacity (FRC). This is particularly effective in conditions involving alveolar instability, such as ARDS or atelectasis.
• Link to Pathophysiology: In cases of shunting, where blood bypasses ventilated alveoli, PEEP recruits collapsed alveoli and redistributes ventilation, reducing hypoxemia.

Removal of Hypercapnia

Hypercapnia in ARF arises from hypoventilation or increased dead space, as seen in conditions like COPD exacerbations or severe obesity hypoventilation syndrome.

• Mechanism: Mechanical ventilation increases minute ventilation by optimizing tidal volume (VT) and respiratory rate. By enhancing the removal of carbon dioxide, it normalizes arterial pH and relieves respiratory acidosis.
• Pressure-Control Ventilation (PCV): PCV is particularly beneficial in hypercapnic ARF as it delivers preset pressure during inspiration, ensuring adequate ventilation while minimizing airway pressures.
• Link to Pathophysiology: In hypoventilation-related hypercapnia, increasing ventilatory support reduces carbon dioxide retention, reversing acidemia and preventing hemodynamic instability.

Reduction of Work of Breathing

ARF often places a high workload on respiratory muscles, leading to fatigue and eventual failure, especially in conditions like COPD exacerbations or severe asthma.

• Mechanism: Mechanical ventilation reduces the effort required to breathe by delivering positive pressure during inspiration. Modes like pressure support ventilation (PSV) and assist-control ventilation (ACV) enable respiratory muscle rest while maintaining adequate ventilation.
• Link to Pathophysiology: By decreasing the work of breathing, mechanical ventilation prevents respiratory muscle exhaustion, a key contributor to hypercapnic ARF.

Alveolar Recruitment and Stabilization

Alveolar recruitment strategies are critical for restoring effective gas exchange in conditions like ARDS, where alveolar collapse and severe V/Q mismatch are common.

• Mechanism: PEEP and lung-protective ventilation strategies, such as low tidal volumes, recruit and stabilize alveoli, increasing the surface area available for gas exchange.
• Link to Pathophysiology: In ARDS, where alveolar collapse exacerbates shunting, PEEP opens collapsed alveoli, improving oxygenation and reducing the severity of hypoxemia.

Prevention of Secondary Complications

Mechanical ventilation provides controlled respiratory support that reduces the risk of secondary complications such as aspiration, ventilator-associated pneumonia (VAP), or multi-organ failure.

• Mechanism: Secure airway management with invasive mechanical ventilation protects against aspiration, while precise ventilator settings minimize barotrauma and ventilator-induced lung injury (VILI).
• Link to Pathophysiology: By addressing hypoxemia and hypercapnia, mechanical ventilation prevents systemic complications like hypoxia-induced multi-organ failure and maintains hemodynamic stability.

Mechanical ventilation compensates for the physiological disruptions seen in ARF by targeting specific mechanisms like V/Q mismatch, diffusion impairment, and increased work of breathing. Each intervention, whether optimizing oxygenation, reducing carbon dioxide levels, or stabilizing alveolar function, is tailored to the patient’s underlying pathology.

This ensures effective management of ARF while minimizing complications, emphasizing the indispensable role of mechanical ventilation in critical care settings (1-8,10).

Types of Mechanical Ventilation

Mechanical ventilation is classified into invasive and non-invasive methods, each with specific applications based on the patient’s condition and therapeutic needs (9-11). Both types play a vital role in the management of acute respiratory failure (ARF), with the choice determined by the severity of respiratory dysfunction and the clinical response to treatment (10).

Non-Invasive Ventilation (NIV)

Non-invasive ventilation delivers respiratory support through a mask or nasal interface, avoiding the need for intubation. It is particularly effective in patients with mild to moderate ARF who are conscious and able to protect their airway.

• Mechanism: NIV enhances oxygenation and ventilation using positive airway pressure, which prevents alveolar collapse and reduces the work of breathing.
• Common Modes:
  • Continuous Positive Airway Pressure (CPAP): Maintains constant positive airway pressure throughout the respiratory cycle, improving oxygenation in conditions such as cardiogenic pulmonary edema.
  • Bilevel Positive Airway Pressure (BiPAP): Alternates between inspiratory positive airway pressure (IPAP) and expiratory positive airway pressure (EPAP), facilitating both oxygenation and ventilation, particularly in hypercapnic ARF seen in COPD exacerbations.
• Clinical Application: NIV is widely used in exacerbations of chronic conditions like COPD, mild ARDS, and heart failure, where it can stabilize gas exchange and reduce the need for intubation.

Invasive Mechanical Ventilation (IMV)

In cases where non-invasive ventilation fails to stabilize ARF or is contraindicated, invasive mechanical ventilation provides controlled respiratory support through an endotracheal or tracheostomy tube.

• Mechanism: IMV directly accesses the airway, ensuring precise delivery of oxygen, removal of carbon dioxide, and reduction of respiratory muscle workload. It also facilitates better protection against aspiration in patients with altered mental status or significant secretions.
• Common Modes:
  • Assist-Control Ventilation (ACV): Delivers a preset tidal volume or pressure with every breath, whether initiated by the patient or the ventilator. ACV provides full respiratory support, ideal for patients with severe ARF and minimal respiratory effort.
  • Synchronized Intermittent Mandatory Ventilation (SIMV): Combines mandatory ventilator-delivered breaths with the patient’s spontaneous breaths. It is frequently used during weaning to encourage respiratory muscle activity.
  • Pressure Support Ventilation (PSV): Supports spontaneous breathing by delivering a set inspiratory pressure. It is commonly employed during recovery or as a step-down mode in the weaning process.
• Clinical Application: IMV is indicated in severe ARF with refractory hypoxemia, hypercapnia unresponsive to NIV, or conditions like ARDS, where invasive strategies like lung-protective ventilation and high PEEP are essential.

Non-invasive ventilation often serves as the first-line treatment in ARF. However, in some cases, such as persistent hypoxemia, rising carbon dioxide levels, or respiratory distress that worsens despite NIV, transitioning to invasive mechanical ventilation becomes necessary to ensure adequate respiratory support and prevent further deterioration (9–11). The specific criteria and clinical scenarios guiding this transition will be examined in a subsequent section.

By tailoring the type of mechanical ventilation to the patient’s condition and response, clinicians can optimize outcomes while minimizing complications.

Modes of Mechanical Ventilation for ARF Treatment

The choice of mechanical ventilation mode in acute respiratory failure (ARF) is determined by the underlying pathology, severity of respiratory compromise, and patient-specific factors (11,12). Optimizing the mode of ventilation is essential to ensure adequate gas exchange while minimizing complications (12). Below, the most commonly used modes are outlined, with an emphasis on their applications and clinical significance.

Assist-Control Ventilation (ACV)

ACV provides full respiratory support by delivering a preset tidal volume (VT) or pressure with each breath, regardless of whether the breath is initiated by the patient or the ventilator.

• Application: This mode is typically used in severe ARF, particularly in conditions such as ARDS or pneumonia, where patients may have minimal or absent spontaneous respiratory effort.
• Advantages: Guarantees consistent ventilation and simplifies management in critically ill patients.

Synchronized Intermittent Mandatory Ventilation (SIMV)

SIMV delivers a set number of mandatory breaths, synchronized with the patient’s spontaneous respiratory efforts, allowing for unassisted breaths in between.

• Application: Often employed as an intermediate step in patients transitioning from full ventilatory support to spontaneous breathing, such as during the weaning process.
• Advantages: Promotes respiratory muscle activity while providing a safety net of mandatory ventilator breaths.

Pressure Support Ventilation (PSV)

PSV augments spontaneous breathing by providing a preset level of inspiratory pressure, reducing the effort required for inspiration.

• Application: Commonly used in patients with preserved respiratory drive, such as those recovering from ARF or during non-invasive ventilation (NIV).
• Advantages: Improves patient comfort, reduces work of breathing, and facilitates weaning from invasive ventilation.

Volume-Controlled and Pressure-Controlled Ventilation (VCV/PCV)

• Volume-Controlled Ventilation (VCV) delivers a preset tidal volume, with airway pressure varying depending on lung compliance and resistance.
  
  Application: Used in patients requiring precise control of minute ventilation, such as those with hypercapnia.

• Pressure-Controlled Ventilation (PCV) delivers a preset pressure during inspiration, with tidal volume varying based on lung compliance.
  
  Application: Beneficial in patients with reduced lung compliance, such as in ARDS, to limit peak airway pressures and reduce the risk of barotrauma.

High-Frequency Oscillatory Ventilation (HFOV)

HFOV delivers very small tidal volumes at high frequencies, maintaining continuous positive airway pressure.

• Application: A rescue strategy for refractory hypoxemia in ARDS when conventional ventilation fails.
• Advantages: Minimizes ventilator-induced lung injury (VILI) by preventing alveolar overdistension.

Clinical Significance

The selection of the appropriate mode of mechanical ventilation in ARF is crucial for optimizing outcomes and minimizing complications. For instance, lung-protective ventilation strategies, such as low tidal volume ventilation in ARDS, reduce the risk of ventilator-induced lung injury (11).
Modes like SIMV and PSV play key roles in facilitating weaning and restoring spontaneous respiratory function (11). By tailoring ventilation modes to the individual needs of patients, clinicians can address the specific pathophysiological challenges of ARF while improving survival and recovery rates (11-15).

Advanced Modes of Mechanical Ventilation: ASV, SAV, and NAVA

With the evolution of mechanical ventilation, advanced modes like Adaptive Support Ventilation (ASV), SmartCare/Automated Ventilation (SAV), and Neurally Adjusted Ventilatory Assist (NAVA) have emerged as pivotal tools in modern respiratory care. These modes leverage intelligent algorithms and neural control mechanisms to enhance patient outcomes, improve synchronization, and simplify clinical workflows. Below is a comprehensive discussion of each mode and its clinical significance (23-25).

Adaptive Support Ventilation (ASV)

• What is ASV?
  ASV is an intelligent mode of mechanical ventilation that automatically adjusts ventilatory support based on the patient’s respiratory mechanics and effort. It uses algorithms to calculate the ideal tidal volume and respiratory rate based on the patient’s predicted body weight, lung compliance, and airway resistance (22-25).
• How ASV Works:
  • ASV continuously monitors the patient’s spontaneous breathing.
  • It dynamically adjusts the inspiratory pressure and ventilatory rate to meet the patient’s metabolic demand while preventing over-distension or atelectasis.
  • This mode ensures minimal work of breathing while maintaining target minute ventilation.
• Benefits of ASV:
  • Automatically reduces support as the patient’s respiratory effort improves, facilitating a smooth transition from controlled to spontaneous breathing.
  • Decreases the risk of hyperventilation, barotrauma, and ventilator-induced lung injury (VILI) (23,24).
  • Improves patient-ventilator synchrony, reducing discomfort and sedation requirements (24).
• Evidence and Clinical Applications:
  • Studies have shown ASV to be effective in both acute and chronic respiratory failure. For example, research published in Critical Care (Arnal et al., 2008) demonstrated that ASV reduced ventilation duration compared to traditional modes in post-operative ICU patients (26).
  • It is widely used in settings requiring dynamic adaptation, such as weaning and managing variable lung mechanics in conditions like ARDS or COPD exacerbations (27).

SmartCare/Automated Ventilation (SAV)

• What is SAV?
  SmartCare/Automated Ventilation is a closed-loop ventilation system designed primarily to automate the weaning process. It uses an artificial intelligence algorithm to assess and adjust ventilatory support based on real-time patient parameters (25,28-31).
• How SAV Works:
  • SAV continuously monitors the patient’s respiratory rate, tidal volume, and end-tidal carbon dioxide (EtCO₂).
  • Based on these parameters, it adjusts pressure support levels to ensure adequate ventilation and oxygenation.
  • When the algorithm determines that the patient can sustain spontaneous breathing, it suggests readiness for extubation.
• Benefits of SAV:
  • Speeds up the weaning process by reducing the need for manual adjustments (22-31).
  • Prevents premature or delayed extubation by following evidence-based criteria.
  • Reduces the workload for ICU staff and standardizes the weaning process.
• Evidence and Clinical Applications:
  • Clinical trials, such as those published in Intensive Care Medicine (Lellouche et al., 2006), have shown that SmartCare reduces the duration of mechanical ventilation and ICU stay while improving extubation success rates (31).
  • SAV is especially useful in ICUs with high patient volumes or variability in care protocols (24-31).

Neurally Adjusted Ventilatory Assist (NAVA)

• What is NAVA
  Neurally Adjusted Ventilatory Assist (NAVA) is an advanced mode of mechanical ventilation that directly uses the patient’s neural respiratory drive to control ventilatory support. Unlike traditional modes that rely on airway pressure or flow triggers, NAVA is driven by electrical activity in the diaphragm (Edi), offering highly personalized and precise ventilation (25-34).

• How NAVA Works?
  
  Edi Catheter:
  A specialized nasogastric catheter detects electrical signals from the diaphragm during the patient’s spontaneous breathing efforts.
  
  Signal Processing:
  These signals (Edi) are analyzed in real-time to determine the timing, duration, and intensity of inspiratory effort.
  
  Ventilator Response:
  The ventilator delivers pressure support proportional to the patient’s effort, ensuring optimal synchronization and avoiding over-assistance or under-assistance.
  
• Advantages of NAVA
  
  Improved Patient-Ventilator Synchrony:
  NAVA directly responds to the patient’s neural respiratory signals, eliminating delays and mismatches that occur with pressure or flow triggering.
  Reduces asynchrony-related complications, such as ineffective efforts, double triggering, and patient discomfort.
  
  Reduction in Sedation Needs:
  By providing natural, synchronized support, NAVA minimizes the discomfort associated with mechanical ventilation, reducing the need for sedatives.
  
  Enhanced Respiratory Muscle Protection:
  Unlike traditional modes that can over-assist, leading to respiratory muscle atrophy, NAVA ensures the diaphragm remains active, maintaining muscle strength and endurance.
  
  Personalized Ventilation:
  Adapts dynamically to the patient’s changing respiratory demands, particularly in conditions like ARDS, COPD, or neuromuscular disorders.

• Clinical Applications of NAVA
  
  ARDS and Acute Respiratory Failure (ARF):
  NAVA provides lung-protective ventilation by avoiding overdistension and barotrauma while maintaining synchrony (38).
  
  Neonatal and Pediatric Ventilation:
  Especially useful in premature infants and pediatric patients, where synchrony challenges are common with traditional modes (36-37,39-43).
  
  Weaning:
  Facilitates a gradual reduction in ventilatory support by responding to the patient’s natural efforts (44-45).
  
  NAVA represents a significant advancement in mechanical ventilation, focusing on precision and patient-centric care by using the diaphragm’s electrical activity to guide support. Its ability to enhance patient-ventilator synchrony, reduce sedation needs, and protect respiratory muscles makes it an invaluable mode in both adult and pediatric populations. When combined with other modes like ASV and SAV, NAVA provides a versatile and comprehensive approach to managing acute respiratory failure.

When to Transition from Non-Invasive Mechanical Ventilation (NIMV) to Invasive Mechanical Ventilation (IMV) in ARF

Non-invasive mechanical ventilation (NIMV) is often the first-line treatment for acute respiratory failure (ARF) in specific conditions like COPD exacerbations or mild-to-moderate hypoxemia. However, in some cases, NIMV may fail to provide adequate support, requiring a transition to invasive mechanical ventilation (IMV) to prevent further deterioration. Here are the key indicators and clinical scenarios to consider transitioning:

1. Worsening Gas Exchange Despite NIMV

• Signs:
  • Persistent or worsening hypoxemia (PaO₂ < 60 mmHg on FiO₂ ≥ 0.6).
  • Rising PaCO₂ (> 50 mmHg) with associated respiratory acidosis (pH < 7.25).
• Reason: Indicates that NIMV is insufficient to meet oxygenation or ventilation demands.

2. Severe Respiratory Distress

• Signs:
  • Increased respiratory rate (> 35 breaths/min).
  • Use of accessory muscles, paradoxical breathing, or nasal flaring.
  • Inability to speak in full sentences due to dyspnea.
• Reason: Suggests that the patient’s work of breathing has exceeded the support provided by NIMV, risking respiratory muscle fatigue and collapse.

3. Altered Mental Status

• Signs:
  • Confusion, agitation, or inability to cooperate with NIMV.
  • Progression to somnolence or coma (indicating hypercapnia or hypoxemia affecting cerebral function).
• Reason: Neurological impairment reduces the ability to maintain spontaneous breathing or adhere to NIMV.

4. Hemodynamic Instability

• Signs:
  • Hypotension (systolic blood pressure < 90 mmHg) unresponsive to fluid resuscitation.
  • Shock or signs of reduced cardiac output.
• Reason: Indicates systemic compromise that requires better oxygenation and ventilation control via IMV.

5. Risk of Aspiration or Airway Protection Issues

• Signs:
  • Inability to clear secretions or significant mucus plugging.
  • Frequent vomiting or risk of aspiration (e.g., altered consciousness).
• Reason: IMV is necessary to secure the airway with an endotracheal tube to prevent aspiration-related complications.

6. Failure to Tolerate NIMV

• Signs:
  • Poor mask seal due to facial anatomy or agitation.
  • Skin breakdown or discomfort causing discontinuation of therapy.
• Reason: Intolerance to NIMV can reduce adherence, rendering it ineffective.

7. No Clinical Improvement Within 1–2 Hours of NIMV

• Signs:
  • Lack of improvement in respiratory rate, gas exchange, or oxygenation after 1–2 hours of optimal NIMV.
• Reason: Delaying the switch to IMV increases the risk of respiratory arrest and worsens outcomes.

The decision to switch from NIMV to IMV in ARF should be guided by clinical judgment, monitoring of gas exchange, respiratory mechanics, and overall patient stability. Early recognition of NIMV failure and timely intubation improve outcomes and prevent complications associated with delayed intervention (12-14, 16-21).

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