Respiratory Disorders and Ventilation

Disorders of respiration and ventilation are extremely common in neonatal medicine. In infants born prematurely, lung development is incomplete and then arrested postdelivery, setting them up for difficulties oxygenating and ventilating after birth. Infants can be supported with noninvasive oximetry monitoring, supplemental oxygen, and positive pressure ventilation (PPV) by continuous positive airway pressure (CPAP) or other modes of assisted mechanical ventilation. Term infants and post-term infants may also have respiratory difficulties related to infection, underlying disorders, or delayed transition from fetal to neonatal life. Transition of the respiratory system from in utero (with gas exchange via the placenta) to ex utero (with gas exchange via alveoli) is often responsible for signs of tachypnea, increased work of breathing, and oxygen requirement.

Meconium Aspiration Syndrome (MAS)

MAS is a result of aspiration of meconium and causes severe oxygenation failure. Risk factors for MAS include fetal distress, hypoxia, and post-term birth. The presence of meconium-stained amniotic fluid indicates some degree of fetal distress during the late stages of pregnancy or labor. Infants aspirate meconium both in utero and during birth through meconium-stained amniotic fluid. Meconium causes inactivation of surfactant in the lungs, as well as a chemical pneumonitis.

Treatment: Neonatal Resuscitation Program (NRP) guidelines no longer recommend routine suctioning of the trachea in infants born through meconium-stained amniotic fluid. Evidence now suggests that the aspiration event occurs before delivery. Infants with MAS often present with significant respiratory distress including tachypnea, nasal flaring, grunting, retractions, and poor oxygenation, requiring assisted mechanical ventilation. Exogenous surfactant can be administered to reduce associated morbidities (including pneumothorax) that result from surfactant inactivation.

A chest radiograph often shows hyperinflation and patchy infiltrates throughout the lungs. (Radiograph courtesy of Tanzeema Hossain, MD)

Transient Tachypnea of the Newborn (TTN)

TTN typically occurs in term or early term infants and is more common in infants born via cesarean section or any birth without labor. Infants with TTN have tachypnea (infant respiratory rate >60), increased work of breathing, and poor oxygenation, due to delayed clearance of pulmonary fluid prior to delivery.

Treatment: Management is typically supportive, although infants may require supplemental oxygen and occasionally PPV.

A chest radiograph will often show retained fetal fluid with the classic finding of fluid in the right lung fissure. (Radiograph courtesy of Tanzeema Hossain, MD)

Persistent Pulmonary Hypertension of the Newborn (PPHN)

The fetal-to-neonatal transition requires several changes for neonates to breathe and provide their own oxygenation rather than rely on the placenta. The pulmonary vascular resistance must drop to shunt blood into the pulmonary vasculature for oxygenation. This occurs relatively quickly with the first few cries and breaths following birth.

However, in infants with PPHN, pulmonary vascular resistance remains elevated for a prolonged period and continues to shunt deoxygenated blood to the systemic circulation (right-to-left shunting through the patent foramen ovale). PPHN is diagnosed by observing cyanosis, auscultating a tricuspid regurgitation murmur, and demonstrating a differential in oxygen saturations >10% between the preductal (right arm) and a postductal (left arm, left leg, right leg) extremity. An echocardiogram is usually obtained to estimate the degree of pulmonary hypertension as measured by the tricuspid regurgitation jet and septal wall flattening.

Treatment: The management of PPHN requires supportive treatment until the pulmonary vascular resistance falls and blood can shift from right-to-left shunting to left-to-right and result in adequate oxygenation. Target preductal oxygen saturations are kept in the low- to mid-90s at a minimum. Oxygen is a potent pulmonary vasculature vasodilator and improves blood flow to the pulmonary bed. If 100% oxygen alone does not improve saturations, inhaled nitric oxide can be used as an adjunct to increase the amounts of circulating cyclic guanosine monophosphate (cGMP) to relax the pulmonary vasculature and ameliorate hypoxemia. Vasopressors are also often utilized to increase systemic vascular resistance and encourage blood flow to enter pulmonary circulation.

Respiratory Distress Syndrome (RDS)

RDS occurs primarily in premature infants with decreased lung compliance due to surfactant deficiency. Pulmonary surfactant is a complex mixture of lipids and surfactant-specific proteins produced by alveolar type II pneumocytes that increase lung compliance by decreasing surface tension, allowing adequate gas exchange across the alveoli. Depending on the gestational age at birth, an infant’s lungs may not be completely developed and may be unable to produce adequate amounts of surfactant. Infants with RDS clinically present with tachypnea, increased work of breathing (retractions, nasal flaring head bobbing), and inability to adequately oxygenate or ventilate. In addition to prematurity, maternal diabetes is a risk factor and males are affected more often than females.

Chest radiograph findings are typically described as a diffusely hazy, ground-glass appearance with air bronchograms. (Radiograph courtesy of Tanzeema Hossain, MD)

Treatment: Use of surfactant therapy is a major advance in the treatment of the premature neonate with RDS. Since the use of artificial surfactant began in the late 1980s and early 1990s, mortality and the severity of morbidity in the immediate postnatal period have decreased. However, the incidence of bronchopulmonary dysplasia (see BPD below), a long-term complication of prematurity, remains unchanged.

Four main types of exogenous surfactants are available with varying modes of delivery, including invasive and noninvasive methods. Either in the delivery room or once the infant is admitted to the NICU, a dose of surfactant may be administered by one of the following methods:

• endotracheal tube administration: the most common method; surfactant is delivered during mechanical ventilation

• INSURE (intubate, surfactant, and extubate): used when the infant may not require sustained mechanical ventilation

• LISA (less invasive surfactant administration): a small endotracheal tube is placed in the trachea while the infant continues to receive PPV and is removed immediately after delivery of the surfactant

• MIST (minimally invasive surfactant therapy): a feeding tube is placed into the trachea and surfactant is delivered while the infant is breathing spontaneously

• SALSA (surfactant administration through laryngeal or supraglottic airway): a supraglottic airway is placed and surfactant is delivered via a catheter with PPV to distribute surfactant

Apnea of Prematurity

Apnea is strictly defined as cessation of breathing for >20 seconds with an associated bradycardia or hypoxia event. Apnea of prematurity primarily affects infants <32 weeks’ gestational age. Three types of apnea of prematurity are central, obstructive, and mixed apnea. In the preterm infant, apnea is most often a centrally mediated process. Obstructive processes are caused by airway obstruction from mucus or the tongue. Mixed apnea of prematurity is a combination of both airway obstruction and central apnea.

The differential diagnosis of an infant presenting with apnea includes infection, metabolic abnormalities, an intracranial process (including bleeding or seizures), and medication adverse effects (including medications administered to the mother prior to delivery such as magnesium, general anesthesia, and opiates).

Treatment: In a large randomized placebo-controlled trial that examined the efficacy of caffeine therapy for apnea of prematurity, caffeine significantly improved survival without neurodevelopmental disability in preterm infants by decreasing the risk of bronchopulmonary dysplasia (BPD). Therefore, first-line treatment for centrally mediated apnea is medical treatment with caffeine, administered as an initial loading dose, followed by a daily maintenance dose. If apnea is persistent, respiratory support with PPV or intubation and mechanical ventilation may be indicated.

Bronchopulmonary Dysplasia (BPD)

Prematurity and the long-term effects of volutrauma and barotrauma due to ventilatory support in premature infants increases the risk for developing bronchopulmonary dysplasia (BPD), previously referred to as chronic lung disease of prematurity. Typically, BPD is defined as continued need for oxygen support after 36 weeks corrected gestational age. The incidence of BPD increases with decreasing gestational age and mostly occurs in infants born at <28 weeks and weighing <1000 grams.

Treatment: To reduce the risk of BPD, respiratory management goals aim to minimize volutrauma and barotrauma by administering surfactant (see surfactant therapy) and transitioning to CPAP and other methods of noninvasive ventilation to reduce intubation time. For more information on bronchopulmonary dysplasia, see the Pediatric Pulmonology rotation guide.

Ventilation

Neonatology utilizes several forms of ventilatory support (including noninvasive and invasive support). Invasive support includes both conventional mechanical ventilation and high-frequency methods (oscillator and jet ventilation). The goal of mechanical ventilation is to oxygenate (exchange oxygen across the alveolar membrane) and ventilate (exchange of CO₂) the infant while minimizing volutrauma (high volumes causing damage to the lungs), barotrauma (high pressures causing damage to the lungs), and oxygen toxicity, which can increase the risk for retinopathy of prematurity and chronic lung disease. Permissive hypercapnia is utilized in the neonate to limit volutrauma and barotrauma. Neonatologists allow a slightly higher target CO₂ of ≥55 and a slightly lower pH value of ≥7.25 than considered normal on blood gases in preterm infants. In term infants without evidence of lung disease, normal target CO₂ (35-45) and pH values (7.35-7.45) should be used.

Noninvasive Ventilation

Noninvasive support includes:

• nasal cannula

• continuous positive airway pressure (CPAP)

• noninvasive intermittent positive-pressure ventilation (NIPPV)

NAVA

Neurally adjusted ventilator assist (NAVA) is a mode of synchronous ventilation that uses a special nasogastric catheter to guide the amount and timing of support provided by the electrical activity of the patient’s diaphragm. This mode can be used noninvasively as well (NIV-NAVA).

Conventional Ventilation

Conventional ventilation includes two main methods of ventilation:

• volume-targeted: PEEP and volume are set to obtain a peak inspiratory pressure (PIP); often utilized after surfactant administration when compliance drastically increases, and pressures need to be weaned quickly to avoid pneumothoraxpressure-targeted: PEEP and PIP are set to obtain a tidal volume; often utilized in the initial moments after intubation when the lungs are less compliant and require higher pressure to obtain a resulting volume

High-Frequency Ventilation

High-frequency ventilation, either with the oscillator or the jet ventilator, is used when an infant has difficulty with oxygenation, ventilation, or both on the conventional ventilator.

• jet ventilator: specifically indicated for poor ventilation or pulmonary air leak; utilizes passive expiration; a specific indication includes pulmonary air leak (pneumothorax or pulmonary interstitial emphysema); may be indicated when an increased mean airway pressure is required (meconium aspiration or PPHN)

• oscillator: has the added benefit of separating oxygenation and ventilation to achieve gentler ventilation and utilizes active expiration; mean airway pressure can be set for oxygenation and the amplitude (delta P) is set for ventilation; the frequency is typically set at a standard number for gestational age

Ventilator Settings

This plot of pressure versus time describes the different aspects of ventilation. The blue bar at the bottom of the graph represents the constant distending pressure of the ventilator PEEP. When a breath is given, the pressure increases to represent a tidal volume or the volume of the breath given. The inspiratory time is the time that the lung is distended by the PIP.

Target Oxygen Saturations

Several multicenter trials (BOOST and SUPPORT) have investigated the optimal oxygen saturation for a preterm neonate. As a result, oxygen saturations of the most-premature infants are kept in the 91%-95% saturation range to prevent retinopathy of prematurity and reduce mortality.

Complications of Ventilation

Pneumothorax is defined as air entry into the pleural space with collapse of lung tissue. This may be spontaneous in term infants or caused by high inspiratory pressures or the use of PPV in lungs with little compliance. A pneumothorax is diagnosed by decreased breath sounds on the affected side, chest wall asymmetry, and hyperexpansion on the affected side. In addition, the chest wall will transilluminate on the affected side. A tension pneumothorax can lead to mediastinal shift and tracheal deviation away from the affected side. Treatment of the pneumothorax includes needle decompression and chest tube placement (see video).

(Photo courtesy of Tanzeema Hossain, MD)

Radiographic findings show hyperlucency on the affected side with separation of the parietal and visceral pleura. (Radiograph courtesy of Tanzeema Hossain, MD)

Pulmonary interstitial emphysema (PIE) is another complication of lung disease and mechanical ventilation. It is defined as air leak into the interstitial spaces, either diffusely or focally, and is diagnosed on chest film as linear lucency that radiates from the hilum, or cyst-like blebs. The treatment of PIE is gentle ventilation and supportive care as the interstitial air is reabsorbed over time.