Anatomic Alterations of the Lungs

On gross examination, the lungs of an infant with RDS are dark red and liver-like. Under the microscope the lungs appear solid because of countless areas of alveolar collapse. The pulmonary capillaries are congested, and the lymphatic vessels are distended. Extensive interstitial and intraalveolar edema and hemorrhage are evident.

In what appears to be an effort to offset alveolar collapse, the respiratory bronchioles, alveolar ducts, and some alveoli dilate. As the disease intensifies, the alveolar walls become lined with a dense, rippled hyaline membrane identical to the hyaline membrane that develops in acute respiratory distress syndrome (ARDS) of the adult patient (see Chapter 27). The membrane contains fibrin and cellular debris.

During the later stages of the disease, leukocytes are present, and the hyaline membrane is often fragmented and partially ingested by macrophages. Type II cells begin to proliferate, and secretions begin to accumulate in the tracheobronchial tree. The anatomic alterations in RDS produce a restrictive type of lung disorder (see Figure 34-1).

As a consequence of the anatomic alterations associated with RDS, babies with this disorder often develop hypoxia-induced pulmonary arterial vasoconstriction and vasospasm, causing a state of transient pulmonary hypertension. This results in blood shunting from right to left through the ductus arteriosus and foramen ovale. Occasionally, intrapulmonary shunting may also occur. As a consequence, the blood flow is diverted away from the lungs (pulmonary hypoperfusion), which worsens the hypoxemia. It should be noted that if this condition does not resolve within 24 hours or so, shunting will begin to flow from left to right through the patent ductus arteriosus. This condition can lead to excessive lung fluid, pulmonary hyperperfusion, and pulmonary edema.

The major pathologic or structural changes associated with RDS are as follows:

Etiology and Epidemiology

Although the exact cause of RDS is controversial, the most popular theory suggests that the early stages of RDS develop as a result of (1) a pulmonary surfactant abnormality or deficiency, and (2) pulmonary hypoperfusion evoked by hypoxia. The pulmonary hypoperfusion evoked by hypoxia is probably a secondary response to the surfactant abnormality. The probable sequence of steps in the development of RDS is as follows:

1. Because of the pulmonary surfactant abnormality, alveolar compliance decreases, resulting in alveolar collapse.

2. The pulmonary atelectasis causes the infant’s work of breathing to increase.

3. Alveolar ventilation decreases in response to the decreased lung compliance and infant fatigue, causing the alveolar oxygen tension (Pao₂) to decrease.

4. The decreased Pao₂ (alveolar hypoxia) stimulates a reflex pulmonary vasoconstriction.

5. Because of the pulmonary vasoconstriction, blood bypasses the infant’s lungs through fetal pathways—the patent ductus and the foramen ovale.

6. The lung hypoperfusion in turn causes lung ischemia and decreased lung metabolism.

7. Because of the decreased lung metabolism, the production of pulmonary surfactant is reduced even further, and a vicious cycle develops (Figure 34-2).

It is estimated that approximately 30,000 cases of RDS occur annually in the United States. RDS is the leading cause of death in preterm infants. About 50% of the neonates born at 26 to 28 weeks’ gestation develop RDS. About 25% of the babies born at 30 to 31 weeks’ gestation develop RDS. RDS occurs more often in male babies and is usually more severe than in female babies. The higher incidence and severity of RDS in male infants is explained by the increased circulating androgens in males—which, in turn, slows the maturation of the infant’s lung. The delayed lung maturation results in immature alveolar type II cells (granular pneumocytes) and a decreased pulmonary surfactant production.

RDS is also more commonly seen in infants of diabetic mothers (the high fetal insulin levels decrease lung surfactant and structural maturation), white preterm babies compared with black preterm infants, and infants delivered by cesarean. RDS is also associated with low birth weight (1000 to 1500 g), multiple births, prenatal asphyxia, prolonged labor, maternal bleeding, and second-born twins.

Diagnosis

There are three primary tests that can be performed to determine the lung maturity of the fetus: the lecithin/sphingomyelin ratio, the presence of phosphatidylglycerol (PG), and, more recently, the surfactant/albumin ratio.

The lecithin/sphingomyelin ratio (L : S ratio) is commonly used to test lung maturity. Lecithin, also called dipalmitoyl phosphatidylcholine, is the most abundant phospholipid found in surfactant. When the concentration of lecithin is two times greater than that of sphingomyelin—an L : S ratio of 2 : 1—the infant’s lung maturity is likely great enough that the lungs will produce adequate pulmonary surfactant at birth. Most infants with an L : S ratio less than 1 : 1 develop RDS. The L : S ratio is not reliable in pregnancies associated with diabetes and Rh isoimmunization.

PG is the second most abundant phospholipid found in surfactant. Because the PG level normally increases toward term, the presence of PG in the amniotic fluid indicates a low risk for RDS. When the amniotic fluid reveals an L : S ratio less than 2 : 1 and a lack of PG, the infant has more than an 80% risk for the development of RDS. However, when the amniotic fluid shows an L : S greater than 2 : 1 and when PG is present, the risk drops to almost zero.

The surfactant/albumin ratio (S : A ratio) is reported as milligrams of surfactant per gram of protein. An S : A ratio <35 indicates immature lungs. An S : A ratio of 35 to 55 indicates uncertain lung maturity. When the S : A ratio is >55, adequate lung maturity is present.

 OVERVIEW of the Cardiopulmonary Clinical Manifestations Associated with Respiratory Distress Syndrome

The following clinical manifestations result from the pathologic mechanisms caused (or activated) by Atelectasis (see Figure 9-8), Alveolar Consolidation (see Figure 9-9), and Increased Alveolar-Capillary Membrane Thickness (see Figure 9-10)—the major anatomic alterations of the lungs associated with respiratory distress syndrome (RDS) (see Figure 34-1).

CLINICAL DATA OBTAINED AT THE PATIENT’S BEDSIDE

The Physical Examination

Vital Signs

Increased Respiratory Rate (Tachypnea)

Normally, a newborn infant’s respiratory rate is about 40 to 60 breaths per minute. During the early stages of RDS, the respiratory rate is generally well over 60 breaths per minute. The respiratory pattern of the baby with RDS commonly is described as “hard, fast, and deep breathing.” Several pathophysiologic mechanisms operating simultaneously may lead to an increased ventilatory rate:

• Stimulation of peripheral chemoreceptors (hypoxemia)

• Decreased lung compliance–increased ventilatory rate relationship

• Stimulation of central chemoreceptors

Increased Heart Rate (Pulse) and Blood Pressure

Apnea (See Table 31-1)

Clinical Manifestations Associated with More Negative Intrapleural Pressures during Inspiration

• Intercostal retractions

• Substernal retraction and abdominal distention (seesaw movement)

• Cyanosis of the dependent portions of the thoracic and abdominal areas

• Flaring nostrils

Chest Assessment Findings

• Bronchial (or harsh) breath sounds

• Fine crackles

Expiratory grunting

Cyanosis

CLINICAL DATA OBTAINED FROM LABORATORY TESTS AND SPECIAL PROCEDURES

Pulmonary Function Test Findings (Extrapolated Data for Instructional Purposes) (Restrictive Lung Pathophysiology)

FORCED EXPIRATORY FLOW RATE FINDINGS

FVC	FEVT	FEV1/FVC ratio	FEF25%-75%
↓	N or ↓	N or ↑	N or ↓
FEF50%	FEF200-1200	PEFR	MVV
N or ↓	N or ↓	N or ↓	N or ↓

LUNG VOLUME AND CAPACITY FINDINGS

VT	IRV	ERV	RV
N or ↓	↓	↓	↓
VC	IC	FRC	TLC	RV/TLC ratio
↓	↓	↓	↓	N

Arterial Blood Gases

MILD TO MODERATE RESPIRATORY DISTRESS SYNDROME

Acute Alveolar Hyperventilation with Hypoxemia (Acute Respiratory Alkalosis)

pH	Paco2		Pao2
↑	↓	↓ (slightly)	↓

SEVERE RESPIRATORY DISTRESS SYNDROME

Acute Ventilatory Failure with Hypoxemia (Acute Respiratory Acidosis)

pH*	Paco2	*	Pao2
↓	↑	↑ (slightly)	↓

^*When tissue hypoxia is severe enough to produce lactic acid, the pH and values will be lower than expected for a particular Paco₂ level.

Oxygenation Indices*

	Do2†			O2ER
↑	↓	N	N	↑	↓

^†The Do₂ may be normal in patients who have compensated to the decreased oxygenation status with (1) an increased cardiac output, (2) an increased hemoglobin level, or (3) a combination of both. When the Do₂ is normal, the O₂ER is usually normal.

---

^*, Arterial-venous oxygen difference; DO₂, total oxygen delivery; O₂ER, oxygen extraction ratio; , pulmonary shunt fraction; , mixed venous oxygen saturation; , oxygen consumption.

RADIOLOGIC FINDINGS

Chest Radiograph

• Increased opacity (ground-glass appearance)

On chest x-ray film of infants with RDS, the air-filled tracheobronchial tree typically stands out against a dense opaque (or white) lung. This white density is often described as having a fine ground-glass appearance throughout the lung fields. Because of the pathologic processes, the density of the lungs is increased. Increased lung density resists x-ray penetration and is revealed on the x-ray film as increased opacity. Therefore the more severe the RDS, the whiter the x-ray image (Figure 34-3).

General Management of Respiratory Distress Syndrome

During the early stages of RDS, continuous positive airway pressure (CPAP) is the treatment of choice. Mechanical ventilation usually is avoided as long as possible. CPAP generally works well with these patients because it (1) increases the functional residual capacity, (2) decreases the work of breathing, and (3) works to increase the Pao₂ through alveolar recruitment while the infant is receiving a lower inspired concentration of oxygen. A Pao₂ of 40 to 70 mm Hg is normal for newborn infants. No effort should be made to get an infant’s Pao₂ within the normal adult range (80 to 100 mm Hg). Special attention should be given to the thermal environment of the infant with RDS because the infant’s oxygenation can be further compromised if the body temperature is above or below normal.

Finally, because of the decreased pulmonary surfactant associated with RDS, the administration of exogenous surfactant preparations such as beractant (Survanta), calfactant (Infasurf), and poractant alfa (Curosurf) is helpful. The term exogenous, used to describe these artificial surfactant agents, indicates that these preparations are from outside the patient’s body. Exogenous surfactant preparations originate from other humans, from animals, or from laboratory synthesis. These agents replace the missing pulmonary surfactant of the premature or immature lungs of the baby with RDS until the lungs are mature enough to provide adequate pulmonary surfactant. Figure 34-4 provides comparison chest radiographs of an infant without exogenous surfactant and the same infant 45 minutes after treatment.

A premature male infant was delivered after 30 weeks’ gestation. The mother was a 19-year-old, unmarried primigravida patient who claimed to be in good health during the entire pregnancy until 6 hours before admission. At that time, she noticed the onset of painless vaginal bleeding. She called her obstetrician, who told her he would meet her in the emergency department of the medical center.

On examination she was found to be a healthy young woman, approximately 30 weeks pregnant, in early labor, and bleeding slightly from the vagina. Her vital signs were stable and within normal limits. A diagnosis of premature separation of the placenta was made. Because bleeding was minimal and both mother and fetus seemed to be doing well, it was decided to deliver the baby vaginally. She was monitored very closely, and labor progressed satisfactorily for about 8 hours, at which time she delivered the infant under epidural anesthesia without any obstetric complications. The baby weighed 2100 g. The Apgar scores were 7 after 1 minute and 9 after 5 minutes. Physical examination findings were entirely normal for an infant of this size.

On admission to the newborn nursery 30 minutes after delivery, the infant was noted to have some moderate respiratory distress. His respiratory rate was 40/min. There was flaring of the nostrils. A chest x-ray film obtained at this time suggested the presence of left upper lobe atelectasis, but no other pulmonary abnormality was noted.

During the next 5 hours, the infant deteriorated rapidly and the respiratory distress became markedly accentuated. The baby was cyanotic, retracting, and using the accessory muscles of respiration. The respiratory rate was 64/min, and respirations were described as “grunting.” His heart rate was 165 bpm. Crackles were heard bilaterally. A chest x-ray film taken at this time revealed generalized haziness that one radiologist described as “ground glass.” Arterial blood gases on an Fio₂ of 0.30 via an oxygen hood were pH 7.25, Paco₂ 52, 21, and Pao₂ 35. The Sao₂ was 60%. At this time, the respiratory therapist working with the baby recorded the following assessment and plan.

Respiratory Assessment and Plan

The baby was intubated by the therapist and put on a ventilator. The initial ventilator settings were respiratory rate (RR) of 40, inspiratory time (Ti) 0.35, Fio₂ 0.40, positive inspiratory pressure (PIP) +25 cm H₂O, positive end-expiratory pressure (PEEP) +5 cm H₂O, and flow 8 L/min. Artificial surfactant (Exosurf) therapy was begun. Fluid and electrolyte balance was maintained within normal levels. On this management the baby was weaned from PEEP in 72 hours, and from artificial ventilation in 96 hours. Chest x-ray examination on the seventh day was unremarkable. The baby was discharged on the fifteenth day and has been healthy ever since.

Discussion

RDS is a fascinating disorder in which meticulous respiratory care of the infant is crucial. Most respiratory therapy students greatly look forward to and enjoy their NICU rotation. In these units the expertise of the respiratory care practitioner is crucial to the functioning of the unit because the majority of patients there have respiratory disorders. Indeed, many of the first reports of therapist-driven protocols came from this setting.

Many of the clinical manifestations seen in this case are associated with Atelectasis (see Figure 9-8) and Increased Alveolar-Capillary Membrane Thickness (see Figure 9-10). For example, the use of accessory muscles of inspiration was likely a compensatory mechanism activated to offset the increased stiffness of the lungs (decreased lung compliance) caused by the atelectasis and alveolar hyaline membrane. The atelectasis and alveolar hyaline membrane were objectively verified by the chest x-ray film. In addition, the severity level of the anatomic alterations and clinical manifestations seen in this case was very high. This was objectively confirmed by the arterial blood gas analysis that identified the acute ventilatory failure with severe hypoxemia.

Thus the aggressive implementation of mechanical ventilation and use of artificial surfactant were certainly justified. Neonatal intensive care units usually are staffed by an in-house neonatologist, who can guide the respiratory therapist through the intricacies of therapy. Artificial surfactant has markedly improved the outlook for these infants. However, the respiratory care practitioner should be on the alert for sudden changes in lung compliance that often occurs shortly after the administration of artificial surfactant. If the infant is on a pressure-cycled ventilator, this is especially important to avoid volutrauma.* As in adults with ARDS, in which the pathology is very similar, constant attention must be given to the possibility of nosocomial infection, fluid overload, and cardiovascular instability. In addition, lung protection strategies such as PEEP, permissive hypercapnia, and use of small ventilator tidal volumes are commonly used in RDS cases.