General Principles And Pathophysiology

Respiratory distress syndrome (RDS) is characterized by generalized atelectasis due to a deficiency of pulmonary surfactant.
The primary goal of respiratory support is to establish and maintain functional residual capacity (FRC).
The lungs in RDS possess low compliance. This results in a short time constant.
Ventilation strategies must provide adequate positive end-expiratory pressure (PEEP) to keep alveoli open.
A short inspiratory time (Ti) is sufficient for gas exchange due to the short time constant.
Care must be taken to avoid volutrauma, barotrauma, and oxytrauma, which contribute to bronchopulmonary dysplasia (BPD).

Delivery Room Stabilization

Non-invasive respiratory support is the preferred initial approach for preterm infants with respiratory distress.
Early continuous positive airway pressure (CPAP) should be initiated in the delivery room.
A T-piece resuscitator is the preferred device for delivery room stabilization.
The T-piece device provides consistent peak inspiratory pressure (PIP) and PEEP.
Self-inflating bags should be avoided as they cannot reliably deliver PEEP without an attached valve.
Resuscitation should begin with a blended oxygen concentration of 21-30% for preterm infants.
Oxygen delivery must be titrated against preductal pulse oximetry to achieve target saturations of 80% at 5 minutes and 85-95% by 10 minutes of life.

Non-invasive modes reduce lung injury and are associated with a lower incidence of BPD.
Endotracheal intubation should be avoided whenever possible.

CPAP is the standard primary respiratory support for mild to moderate RDS.
It splints the airway, prevents alveolar collapse, and conserves endogenous surfactant.
Therapy is initiated at a pressure of 5-6 cm H2O.
Pressure can be titrated up to a maximum of 8 cm H2O based on the work of breathing and oxygen requirement.
Proper fixation of short, snugly fitting binasal prongs or nasal masks is crucial to prevent pressure leaks and nasal injury.

NIPPV provides continuous distending pressure along with intermittent peak pressure breaths.
It is more effective than CPAP as a primary mode in reducing the need for invasive ventilation.
NIPPV is highly recommended for post-extubation support to prevent extubation failure.

HFNC delivers heated, humidified, blended oxygen at high flow rates.
It provides unpredictable positive distending pressure.
HFNC has a higher failure rate when used as primary support for RDS.
It is generally reserved for weaning from CPAP or for post-extubation support in stable neonates.

Invasive ventilation is required when non-invasive support fails or when the infant develops recurrent apnea.
CPAP failure is typically defined by a fractional inspired oxygen (FiO2) requirement >0.4 to 0.6 despite optimal CPAP pressure (7-8 cm H2O).
Respiratory acidosis with pH <7.25 and pCO2 >60 mmHg is a strong indication for mechanical ventilation.
Immediate intubation may be necessary for extreme preterm neonates requiring early surfactant administration for severe RDS.

Ventilation Mode	Description	Clinical Utility In RDS
Volume-Targeted Ventilation (VTV)	The ventilator automatically adjusts PIP to deliver a preset tidal volume.	Strongly preferred. Reduces BPD, hypocarbia, and pneumothorax. Prevents volutrauma during compliance changes.
Assist Control (A/C)	All spontaneous efforts trigger a fully supported ventilator breath.	Preferred mode in the acute phase of RDS. Improves patient-ventilator synchrony.
Synchronized Intermittent Mandatory Ventilation (SIMV)	Delivers a set number of synchronized breaths. Spontaneous breaths in between are unsupported.	Less preferred during acute phase. Used primarily during weaning in combination with pressure support.

Settings must be tailored to achieve adequate gas exchange while minimizing lung overdistension.
The lungs in RDS are stiff and require specific parameter adjustments.

Parameter	Recommended Initial Setting	Rationale
Tidal Volume (VT)	4-6 ml/kg	Avoids volutrauma. Excess volume is more injurious than excess pressure.
Peak Inspiratory Pressure (PIP)	14-20 cm H2O	Adjust to achieve gentle chest rise if using pressure-controlled ventilation.
Positive End-Expiratory Pressure (PEEP)	5-6 cm H2O	Maintains FRC and prevents alveolar collapse at the end of expiration.
Inspiratory Time (Ti)	0.25-0.35 seconds	RDS lungs have short time constants. Longer Ti is unnecessary and impedes venous return.
Ventilator Rate	40-60 breaths per minute	Matches the physiological respiratory rate of the neonate to ensure adequate minute ventilation.

HFV utilizes supraphysiological respiratory rates (300-1500 breaths per minute) with very small tidal volumes.
It is primarily used as a rescue mode for severe RDS with refractory hypoxemia or when pulmonary air leaks (pneumothorax, interstitial emphysema) complicate conventional ventilation.
Some units employ HFV as a primary lung-protective mode for extremely low birth weight infants.
The strategy relies on optimizing mean airway pressure (MAP) to recruit atelectatic alveoli while minimizing tidal volume excursions.

Exogenous surfactant rapidly improves lung compliance and oxygenation.
Surfactant should ideally be given within the first two hours of life if criteria are met.
The InSurE (Intubate-Surfactant-Extubate) technique limits the duration of positive pressure ventilation by rapidly extubating the infant back to CPAP.
Less Invasive Surfactant Administration (LISA) or Minimally Invasive Surfactant Therapy (MIST) involves instilling surfactant via a thin catheter while the infant remains on CPAP, avoiding endotracheal intubation entirely.
Following surfactant therapy, lung compliance improves dramatically. Ventilator pressures must be rapidly downregulated to avoid volutrauma and air leaks.

Continuous pulse oximetry is mandatory. The target oxygen saturation (SpO2) is strictly maintained between 90% and 95%.
Hyperoxia must be avoided to prevent retinopathy of prematurity and oxidative lung injury.
Permissive hypercapnia is generally practiced. The target arterial carbon dioxide (pCO2) is 45-55 mmHg, provided the pH remains >7.25.
Hypocarbia (pCO2 <35 mmHg) is strictly avoided as it causes cerebral vasoconstriction and increases the risk of periventricular leukomalacia.

Weaning should commence as soon as lung compliance improves.
Fractional inspired oxygen (FiO2) is weaned first to maintain SpO2 targets.
PIP is gradually decreased in pressure-controlled modes. In volume-targeted modes, PIP automatically decreases.
Extubation is considered when the mean airway pressure is <8 cm H2O and FiO2 requirement is <0.30.
Early caffeine citrate therapy should be initiated. It stimulates the respiratory center, significantly reducing apnea of prematurity and post-extubation failure.
Infants are typically extubated to nasal CPAP or NIPPV to maintain airway splinting and prevent alveolar collapse.