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Respiratory distress syndrome
Introduction
Respiratory distress syndrome (RDS) is a developmental lung disease of preterm infants primarily caused by inadequate production of surfactant. Infants with RDS have difficulty maintaining adequate functional residual capacity (FRC), leading to alveolar atelectasis, hypoventilation, and ventilation-perfusion mismatch. Affected infants present shortly after birth with worsening tachypnea, nasal flaring, grunting, retractions, hypercapnia, and hypoxemia. Extensive research in the management of RDS has led to major improvements in the care of preterm infants and increased survival. In this chapter, we summarize the most current evidence-based management of RDS.
Case 1
A 31-year old gravida 2 para 1 mother presents to the local community hospital at 32 weeks’ gestation due to leaking vaginal fluid since earlier that day and increasing regular, painful uterine contractions. She has a history of previous preterm delivery at 28 weeks’ gestation. She is concerned about the risk of RDS in this infant, as she remembers her previous preterm daughter was ventilated for several days after she was born.
Exercise 1
Questions
- 1.
Which of the following prenatal interventions will have the MOST beneficial effect in reducing the severity of RDS in this case?
- A.
Delivery is advised as the infant is moderately preterm and risk of RDS is negligible.
- B.
Antenatal steroids should be administered to accelerate fetal lung maturity and improve infant outcomes.
- C.
Tocolysis to delay preterm delivery would not be effective and thus should not be offered given her previous history of preterm delivery.
- A.
- 2.
Which of the following statements is TRUE regarding tocolysis to delay preterm delivery?
- A.
Short-term tocolysis is beneficial to allow for administration of antenatal steroids and transfer to tertiary facility.
- B.
Maintenance therapy with tocolytics is effective for preventing preterm birth and improving neonatal outcomes.
- C.
The tocolytic agent of choice to delay preterm delivery is a calcium channel blocker.
- A.
Answers
- 1.
B. Antenatal steroids should be administered to accelerate fetal lung maturity and improve infant outcomes.
- 2.
A. Short-term tocolysis is beneficial to allow for administration of antenatal steroids and transfer to tertiary facility.
Effective prenatal care for decreasing RDS
Prevention of preterm delivery
The most effective way of decreasing the risk and severity of RDS is to prevent preterm delivery. Unfortunately, effective interventions for preventing preterm birth remain limited. Factors that increase risk for preterm delivery include previous history of preterm labor, multiple gestation, and short cervix. Mothers identified as high risk for preterm labor should be closely monitored during pregnancy, and interventions to prevent preterm delivery (such as progesterone administration or cerclage placement) should be considered when appropriate. Elective cesarean delivery without labor for late preterm infants (34-36 weeks’ gestation) should also be avoided, as the risk for RDS remains increased in this population compared with term infants.
Antenatal steroids for pharmacologic acceleration of fetal lung maturity
For mothers who go into preterm labor or are at imminent risk for preterm delivery, antenatal corticosteroids should be given immediately. Antenatal corticosteroids promote accelerated maturity of the fetal lung and remain one of the most important interventions to decrease RDS and improve outcomes. The most recent Cochrane metaanalysis of antenatal steroids for fetal acceleration of lung maturity showed that antenatal steroids significantly reduce the incidence of RDS (RR 0.66, 95% CI 0.56-0.77) and overall neonatal mortality in preterm infants (RR 0.69, 95% CI 0.59-0.81). Long-standing recommendations from the American College of Obstetricians and Gynecologists call for routine administration of antenatal steroids to women between 24 to 34 weeks of gestation who are at risk of preterm delivery. Antenatal corticosteroids should also be considered for pregnant women as early as 23 weeks of gestation and to those between 34 and 36 weeks’ gestation in light of recent evidence showing benefits to steroid-exposed infants born within this gestational age range.
Transfer to tertiary facility
Not all delivery centers have adequate equipment and skilled personnel to take care of preterm infants. Mothers at risk for imminent preterm delivery should thus be transferred to tertiary care facilities whenever possible. Transfer of a pregnant mother is preferable to neonatal transport, as studies have consistently shown better survival and long-term outcomes for infants born in referral centers.
Tocolytic therapy
Tocolytic therapy to delay preterm delivery has not been shown to improve neonatal outcomes. Nevertheless, short-term use is recommended to allow completion of antenatal corticosteroids and transfer of the mother to a tertiary facility. Common tocolytic agents include calcium channel blockers, nonsteroidal antiinflammatory drugs, beta-adrenergic receptor agonists, and magnesium sulfate. Although efficacy is generally similar, potential side effects on mother and infant can differ widely. Tocolytic therapy should thus be individualized based on each patient’s unique circumstances.
Case 2
A 22-year-old pregnant woman was rushed to the emergency room due to rupture of membranes and onset of labor at 26 weeks’ gestation. She received a dose of betamethasone, started on magnesium sulfate for tocolysis, and transferred to the regional perinatal center for further management. Upon admission to labor and delivery, her cervix was noted to be 3 cm dilated. Magnesium sulfate was continued, and she was able to receive a second dose of betamethasone. However, she continued to have uterine contractions with progressive cervical dilation. The NICU team was called, and preparations were made for imminent vaginal delivery.
Exercise 2
Questions
- 1.
Immediately following delivery, the infant was noted to have weak cry and spontaneous movement. Based on the 2015 American Heart Association guidelines on neonatal resuscitation, which of the following umbilical cord management should be performed?
- A.
Delayed cord clamping
- B.
Cord milking or stripping
- C.
Immediate cord clamping
- A.
- 2.
The infant was brought to the radiant warmer, where a quick assessment revealed the infant is not breathing and has a heart rate of 80 beats per minute. Which of the following interventions is most appropriate?
- A.
Bag-mask ventilation with initial Fi o 2 of 30%
- B.
Bag-mask ventilation with initial Fi o 2 of 60%
- C.
Continuous positive airway pressure (CPAP) with initial Fi o 2 of 30%
- D.
CPAP with initial Fi o 2 of 60%
- A.
Answer
- 1.
A. Delayed cord clamping
- 2.
A. Bag-mask ventilation with initial Fi o 2 of 30%
Delivery room stabilization
Optimal delivery room resuscitation is important in decreasing neonatal morbidity, including RDS. The most recent guidelines on Neonatal Resuscitation 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care.
Delayed cord clamping
Delayed clamping of the umbilical cord for 30 to 60 seconds following delivery allows for blood flow from the placenta to the infant to continue, resulting in an increase in blood volume and blood pressure. A metaanalysis of randomized controlled trials (18 studies, 2834 infants) of early versus delayed cord clamping in preterm infants showed that delayed cord clamping decreased hospital mortality (RR 0.70, 95% CI 0.51-0.95) and reduced the need for blood transfusions by 10%. Current guidelines regard delayed cord clamping as reasonable for preterm infants who are breathing or crying immediately after birth. Cord milking or stripping of the unclamped umbilical cord several times to push blood toward the infant has been suggested as an alternative to delayed cord clamping, especially in cases when the preterm infant is clearly depressed and immediate resuscitation is desired. However, routine cord milking is currently not recommended, as further studies are needed to establish its effectiveness and safety—particularly in the resuscitation of depressed preterm infants.
Thermoregulation
Thermoregulation in the delivery room is important, as both hypothermia and hyperthermia are associated with increased neonatal morbidity and mortality. Preterm infants are especially vulnerable and require advanced preparation. Before a delivery, the room temperature is ideally set at 26° to 28° C (79°–82° F) and the radiant warmer turned on to maximum power. Warm blankets and a hat should also be available. For preterm infants less than 32 weeks’ gestation, additional strategies are recommended to prevent hypothermia. Placing the preterm infant immediately in a plastic bag without drying decreases evaporative heat loss while still allowing in heat from the radiant warmer. Warm humidified resuscitation gas and additional exothermic mattress may also be used. The overall goal is to maintain body temperature between 36.5° C and 37.5° C.
Ventilation
The most important step in stabilization at birth is establishment of effective ventilation. Preterm infants are especially at risk and frequently need support to establish adequate ventilation because of their immature airways and surfactant deficiency. A quick assessment of the infant’s need for respiratory support includes evaluation of the heart rate and respiratory effort. If the heart rate is less than 100 beats per minute or if the infant is apneic or gasping, positive pressure ventilation via bag-mask or T-piece is needed. Placement of electrocardiographic leads may be considered for more rapid and accurate measurement of heart rate, as clinical assessment by auscultation or palpation can be challenging especially in preterm infants. Care should be exercised with the inflation pressures because excessive tidal volume is associated with lung injury. Inadequate pressure can lead to ineffective ventilation and is also harmful. Sustained lung inflation—a technique whereby relatively high peak inspiratory pressure is administered for more than 5 seconds—has been evaluated as an alternative to intermittent positive pressure breaths for establishment of adequate FRC, but there remains insufficient evidence for its effectiveness and safety.
Oxygenation
Optimal management of oxygenation is also important, as both inadequate and excessive oxygenation are potentially harmful to newborn infants. Resuscitation with 100% oxygen may increase mortality compared with room air resuscitation in term and late preterm babies. Though few studies have been performed in preterm infants, there is some evidence to suggest that low oxygen strategy for resuscitation of preterm infants may be more beneficial compared with resuscitation with 100% oxygen. Current guidelines recommend starting resuscitation of preterm infants < 35 weeks of gestation with low oxygen (21%–30%) and titrating supplemental oxygen using a blender to target the normal gradual increase in oxygen saturations following birth (80%–85% at 5 minutes, 85%–95% at 10 minutes).
Case 3
A preterm male infant at 25 weeks’ gestation was delivered vaginally and was noted to be crying and breathing immediately after birth. After 30 seconds of delayed cord clamping, he was received by the resuscitation team in a warm blanket and immediately placed under a radiant warmer and inside a plastic bag without drying. A quick assessment revealed poor respiratory effort and HR less than 100 despite gentle stimulation. Positive pressure ventilation was initiated via bag-mask device with appropriate pressures and 30% oxygen, and a pulse oximeter was placed on his right hand to allow targeted administration of oxygen. At 3 minutes, he had spontaneous breathing with a HR greater than 100 beats per minute.
Exercise 3
Question
Which of the following is the most appropriate next step in the management of this infant?
- A.
Continue positive pressure ventilation via bag-mask device
- B.
Intubate and administer surfactant
- C.
Provide continuous positive airway pressure (CPAP)
Answer
-
Provide continuous positive airway pressure (CPAP)
Prophylactic intubation with surfactant administration versus prophylactic CPAP initiated at delivery
On the basis of trials showing benefits of early surfactant administration over later treatment, the practice of routinely intubating preterm infants in the delivery room to administer surfactant became widespread. This practice, however, exposes preterm infants who may not have needed mechanical ventilation to unnecessary ventilator-associated lung injury. Recent trials have evaluated an alternative strategy of prophylactic CPAP initiated at delivery, with later intubation and surfactant administration reserved for infants who failed CPAP. This less invasive strategy, evaluated in three large randomized controlled trials (RCTs) including 2364 preterm infants born at less than 30 weeks’ gestation, was shown to decrease rate of intubation in the delivery room and decrease overall duration of mechanical ventilation. A metaanalysis of these trials demonstrated a small but significant treatment effect of decreasing death or bronchopulmonary dysplasia (BPD) at 36 weeks (RR 0.89, 95% CI 0.81–0.97) with prophylactic CPAP. Based on this evidence, prophylactic CPAP started at delivery for spontaneously breathing extremely preterm infants with RDS is recommended as an alternative and potentially better practice than prophylactic intubation.
Case 4
A preterm infant born at 27 weeks’ gestation with birth weight of 900 g is admitted to the NICU on nasal CPAP. Over the past hour, his work of breathing has increased significantly. His oxygen requirement to maintain oxygen saturations at goal range increased from 25% to 55%, and his most recent arterial blood gas shows pH of 7.32, P co 2 of 52 mm Hg, P o 2 of 50 mm Hg, and HCO 3 of 22 mEq/L. He had two brief, self-resolving apneic spells in the past hour.
Exercise 4
Questions
- 1.
For which of the following indications would you consider intubating this infant and administering surfactant?
- A.
Increasing work of breathing
- B.
Oxygen need of 55%
- C.
P co 2 of 52 mm Hg
- D.
Brief, self-resolving apneic spells
- E.
None of the above
- A.
- 2.
Which of the following statement is true regarding surfactant at this time?
- A.
Synthetic surfactant is superior to natural surfactant
- B.
A single dose of surfactant is as effective as multiple doses of surfactant
- C.
Earlier surfactant therapy is superior to late surfactant therapy
- A.
Answers
- 1.
B. Oxygen need of 55%
- 2.
C. Earlier surfactant therapy is superior to late surfactant therapy
Indications for intubation and surfactant administration
Although early CPAP at birth is a safe and effective form of respiratory support for preterm infants with RDS, CPAP does not completely eliminate the need for intubation, surfactant administration, or mechanical ventilation. Data from RCTs that assessed early CPAP versus routine intubation at birth demonstrated that 45% to 51% of infants randomized to early CPAP eventually needed to be intubated and given surfactant. Criteria used to determine CPAP failure differed slightly among the different RCTs and included (1) Fi o 2 greater than 40% to 60% to meet target oxygen saturations, (2) Pa co 2 greater than 60 mm Hg to 65 mm Hg, (3) apnea requiring intervention, and (4) hemodynamic instability. Interestingly, increased work of breathing based on subjective assessment was not a criterion for CPAP failure in any of the studies.
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