Respiratory Distress and Chronic Lung Disease
An early complication of extreme prematurity is respiratory distress syndrome (RDS)
caused by surfactant deficiency. Clinical signs include tachypnea
(>60 breaths/min), cyanosis, chest retractions, nasal flaring, and
grunting. Untreated RDS results in increasing difficulty in breathing
and increasing oxygen requirement over the first 24-72 hours of life.
Chest radiography reveals a uniform reticulogranular pattern with air
bronchograms.
As a result of surfactant deficiency, the alveoli collapse, causing a worsening of atelectasis, edema, and decreased total lung capacity. Surfactants decrease the surface tension of the smaller airways so that the alveoli or the terminal air sacs do not collapse, which results in less need for supplemental oxygen and ventilatory support.
The incidence of RDS is inversely proportional to gestational age, with an incidence of 60% at 29 weeks' gestation. RDS affects about 40,000 infants in the United States annually (most infants with extremely low birth weight [ELBW] are affected). Common complications include air leak syndromes, chronic lung disease or bronchopulmonary dysplasia (BPD), and retinopathy of prematurity (ROP).
Synthetic surfactants currently on the market lack the proteins found in animal-derived surfactants and may not be as effective as the latter. Newer synthetic surfactants with a synthetic surfactant protein analog are being tested.
The incidence of RDS in preterm infants has been significantly reduced with the use of antenatal steroids to promote lung maturity; an additive effect was seen with the use of both antenatal steroids and early surfactant treatment. The use of antenatal steroids also has been linked to a reduction in the incidence of clinically significant patent ductus arteriosus (PDA) and severe intraventricular hemorrhage (IVH); however, concerns have surfaced regarding neurodevelopmental sequelae of repeated antenatal courses of steroids.
In the last decade, surfactants have been widely used to treat RDS, and it was suggested that surfactants should be routinely administered as prophylaxis in infants younger than 30 weeks' gestation. However, this results in unnecessary treatment in some infants. A shift in practice is occurring, and fewer infants are immediately intubated after birth, making prophylactic treatment with surfactant impossible.
If used as prophylactic treatment, surfactants should be administered as soon after birth as possible. When administered as rescue treatment, a reasonable approach is to treat most infants as soon as clinical signs of RDS appear or if the respiratory picture does not improve after the initial resuscitation.
A retrospective analysis studied the first 48 hours in 225 infants of 23-28 weeks' gestational age and noted that 140 of these infants could be stabilized with nasal CPAP in the delivery room, 68 with a favorable outcome and 72 with a failed outcome within 48 hours. History or initial blood gas results were poor predictors of subsequent nasal CPAP failure. A threshold fraction of inspired oxygen (FiO2) of greater than or equal to 0.35-0.45 compared with greater than or equal to 0.6 for intubation may shorten the time to surfactant delivery, without a relevant increase in intubation rate.
A study by Geary et al was promising for a reported decrease in incidence of chronic lung disease using this approach (along with lowered oxygen saturation limits and aggressive early nutrition).
BPD is a staged disease that was originally described by Northway et al in 1967 as the clinical sequelae of prolonged ventilation associated with radiographic and pathologic findings; it is the result of abnormal reparative processes in response to injury and inflammation.
The NICHD Neonatal Network reported that the incidence of BPD at 36 weeks in all infants who weighed 501-1500g increased from 19% in 1990 to 23% in 1996.This figure remained steady at 22% in 2000. Sixty percent of very low birth weight infants requiring prolonged mechanical ventilation were oxygen dependent at age 28 days, and 30% remained oxygen dependent at 36 weeks' postmenstrual age. For infants with extremely low birth weights, the overall incidence of BPD was 40%, with as many as 77% of infants requiring mechanical ventilation developing the disease. No further decrease in the incidence of BPD has been observed since 1996.
Inhaled nitric oxide (iNO) has been used in attempts to either rescue extremely ill preterm infants or to help prevent BPD. As a rescue, this treatment is linked to an increase in severe IVH. Unfortunately, iNO is also relatively ineffective in preventing BPD. However, it may decrease serious brain injury and improve rates of survival without BPD in mildly ill preterm infants when consistently used. Further studies are currently underway.
A study by Wilkinson et al reported changes in brainstem auditory evoked responses (BAER) in infants with BPD.Their results suggested that these infants had "poor myelination and synaptic function of their brainstem, resulting in impaired functional integrity." Their peripheral neural function did not appear to be affected by their lung disease. Additional studies of brainstem function in infants with BPD are needed to further define what neurologic abnormality, if any, is present.
As a result of surfactant deficiency, the alveoli collapse, causing a worsening of atelectasis, edema, and decreased total lung capacity. Surfactants decrease the surface tension of the smaller airways so that the alveoli or the terminal air sacs do not collapse, which results in less need for supplemental oxygen and ventilatory support.
The incidence of RDS is inversely proportional to gestational age, with an incidence of 60% at 29 weeks' gestation. RDS affects about 40,000 infants in the United States annually (most infants with extremely low birth weight [ELBW] are affected). Common complications include air leak syndromes, chronic lung disease or bronchopulmonary dysplasia (BPD), and retinopathy of prematurity (ROP).
Surfactant agents and antenatal steroids
Surfactant agents may be administered as prophylaxis or as rescue intervention after RDS. Prophylactic use in infants younger than 28 weeks' gestation has been shown to decrease short-term ventilatory needs; neither strategy has resulted in a decreased incidence of chronic lung disease (BPD).Synthetic surfactants currently on the market lack the proteins found in animal-derived surfactants and may not be as effective as the latter. Newer synthetic surfactants with a synthetic surfactant protein analog are being tested.
The incidence of RDS in preterm infants has been significantly reduced with the use of antenatal steroids to promote lung maturity; an additive effect was seen with the use of both antenatal steroids and early surfactant treatment. The use of antenatal steroids also has been linked to a reduction in the incidence of clinically significant patent ductus arteriosus (PDA) and severe intraventricular hemorrhage (IVH); however, concerns have surfaced regarding neurodevelopmental sequelae of repeated antenatal courses of steroids.
In the last decade, surfactants have been widely used to treat RDS, and it was suggested that surfactants should be routinely administered as prophylaxis in infants younger than 30 weeks' gestation. However, this results in unnecessary treatment in some infants. A shift in practice is occurring, and fewer infants are immediately intubated after birth, making prophylactic treatment with surfactant impossible.
If used as prophylactic treatment, surfactants should be administered as soon after birth as possible. When administered as rescue treatment, a reasonable approach is to treat most infants as soon as clinical signs of RDS appear or if the respiratory picture does not improve after the initial resuscitation.
Continuous positive airway pressure
Infants who are not immediately intubated are usually maintained with nasal continuous positive airway pressure (CPAP), which has been shown to improve endogenous surfactant production. These infants are intubated and given surfactant only if they fail the initial trial of CPAP, as evidenced by increasing PaCO2, increasing respiratory distress, or persistently high oxygen requirement.A retrospective analysis studied the first 48 hours in 225 infants of 23-28 weeks' gestational age and noted that 140 of these infants could be stabilized with nasal CPAP in the delivery room, 68 with a favorable outcome and 72 with a failed outcome within 48 hours. History or initial blood gas results were poor predictors of subsequent nasal CPAP failure. A threshold fraction of inspired oxygen (FiO2) of greater than or equal to 0.35-0.45 compared with greater than or equal to 0.6 for intubation may shorten the time to surfactant delivery, without a relevant increase in intubation rate.
A study by Geary et al was promising for a reported decrease in incidence of chronic lung disease using this approach (along with lowered oxygen saturation limits and aggressive early nutrition).
Chronic lung disease
A major morbidity of premature birth is chronic lung disease (BPD), which is defined as a need for supplemental oxygen or ventilatory support at 36 weeks' postmenstrual age. This definition has, to a relative extent, replaced the former definition of oxygen dependence beyond age 28 days.BPD is a staged disease that was originally described by Northway et al in 1967 as the clinical sequelae of prolonged ventilation associated with radiographic and pathologic findings; it is the result of abnormal reparative processes in response to injury and inflammation.
The NICHD Neonatal Network reported that the incidence of BPD at 36 weeks in all infants who weighed 501-1500g increased from 19% in 1990 to 23% in 1996.This figure remained steady at 22% in 2000. Sixty percent of very low birth weight infants requiring prolonged mechanical ventilation were oxygen dependent at age 28 days, and 30% remained oxygen dependent at 36 weeks' postmenstrual age. For infants with extremely low birth weights, the overall incidence of BPD was 40%, with as many as 77% of infants requiring mechanical ventilation developing the disease. No further decrease in the incidence of BPD has been observed since 1996.
Inhaled nitric oxide (iNO) has been used in attempts to either rescue extremely ill preterm infants or to help prevent BPD. As a rescue, this treatment is linked to an increase in severe IVH. Unfortunately, iNO is also relatively ineffective in preventing BPD. However, it may decrease serious brain injury and improve rates of survival without BPD in mildly ill preterm infants when consistently used. Further studies are currently underway.
A study by Wilkinson et al reported changes in brainstem auditory evoked responses (BAER) in infants with BPD.Their results suggested that these infants had "poor myelination and synaptic function of their brainstem, resulting in impaired functional integrity." Their peripheral neural function did not appear to be affected by their lung disease. Additional studies of brainstem function in infants with BPD are needed to further define what neurologic abnormality, if any, is present.
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