RESPIRATORY DISTRESS SYNDROME CARE

Medical Care:
• Prenatal prevention and prediction of RDS: Obstetricians with experience in fetal medicine should care for mothers whose infants are at an increased risk for developing RDS, preferably at a tertiary perinatal center. Strategies to prevent premature birth (eg, bed rest, tocolytics, appropriate antibiotics) and the prudent use of antenatal steroids to mature fetal lungs may decrease the incidence and severity of RDS. Fetal lung maturity can be predicted by estimating the lecithin-to-sphingomyelin ratio and the presence of phosphatidylglycerol in the amniotic fluid obtained via amniocentesis.

• Delivery and resuscitation: A neonatologist experienced in the resuscitation and care of premature infants should attend deliveries of fetuses when younger than 28 weeks' gestation. They are at a high risk of maladaptation, which further inhibits surfactant production.

• Surfactant replacement therapy: The mortality rate of RDS has decreased 50% during the last decade with the advent of surfactant therapy.
o Infants diagnosed with RDS who require assisted ventilation with more than 0.40 fraction of inspiratory oxygen (FIO2) should receive intratracheal surfactant as soon as possible, preferably within 2 hours after birth.
o Because surfactant is protective of delicate lungs, several investigators have recommended prophylactic use following resuscitation in extremely premature infants (<27 weeks' gestation). However, prophylactic surfactant is expensive and unnecessary in most instances because 40-60% of premature infants do not have surfactant deficiency and, thus, are intubated with its inherent risks.
o Premature infants with surfactant deficiency and RDS have an alveolar pool size of approximately 5 mg/kg. Full-term animal models have pool sizes with a range of 50-100 mg/kg. The recommended dose of the clinically available surfactant preparations has a range of 50-200 mg/kg, which is an approximation of the surfactant pool of term newborn lungs. Rapid bolus administration of surfactant after adequate lung recruitment using 2-4 cm positive end-expiratory pressure (PEEP) and adequate positive pressure may lead to its more homogenous distribution. Most infants require 2 doses; however, as many as 4 doses at 6- to 12-hour intervals have been used in several clinical trials. If the infant improves rapidly after only 1 dose, the infant most likely does not have RDS. Conversely, in infants who respond poorly or are nonresponders to surfactant, exclude PDA, pneumonia, and complications of ventilation (air leak), especially prior to using third and subsequent doses.
o Clinical trials with protein-containing natural surfactants result in fewer complications and a more rapid improvement in the infant's respiratory status. The currently marketed natural surfactants have varying amounts of phospholipids (mostly desaturated phosphatidylcholine) and apoprotein B and C but not apoprotein A. Apoprotein A may be important for host defense. In 2 recent reviews, Notter and Kresch et al summarized data from extensive biophysical studies, in vitro and whole animal biochemical studies, molecular and physiologic studies, and several large international clinical trials.

• Oxygen and continuous positive airway pressure: In 1971, continuous positive airway pressure (CPAP) was introduced as the primary therapeutic modality when Gregory et al demonstrated a marked reduction in RDS mortality. Oxygen was the primary therapeutic modality prior to the introduction of CPAP.
o Oxygen via hood still is used for treating infants with mild RDS.
o CPAP keeps the alveoli open at the end of expiration, thereby decreasing the right-to-left pulmonary shunt.
o CPAP may be administered via the endotracheal tube, nasal prongs, or nasopharyngeal tubes (in larger infants).
o CPAP is an adjunct therapy following surfactant administration, if prolonged assisted ventilation is not required.
o CPAP may be used following extubation in individuals with RDS to prevent atelectasis and/or prevent apnea in premature infants.
o The goal of therapy for patients with RDS is to maintain a pH of 7.25-7.4, an arterial oxygen (PaO2) of 50-70 mm Hg, and a carbon dioxide pressure (PCO2) of 40-65 mm Hg, depending on the infant's clinical status.

• Kirby and deLemos introduced assisted ventilation 2 decades ago. Assisted ventilation further decreased RDS-related mortality; however, earlier ventilators were associated with complications, such as air leaks, BPD (secondary to barotrauma or volutrauma), airway damage, and intraventricular hemorrhage. Advances in microprocessor-based technology, transducers, and real-time monitoring have enabled patient-driven ventilator control and synchronization of mechanical ventilation with patient effort. The novelty of the newer ventilation techniques has generated several controversies that remain to be resolved. Among these controversies are signal detection and transduction, optimal volume delivery (ventilation modes), and weaning from mechanical ventilation.

• Consider ventilation as a necessary physiologic support while the infant recovers from RDS. Several investigators have suggested that permissive hypercapnia with arterial carbon dioxide (PaCO2) with a range of 45-55 mm Hg (with adequate lung volume), may facilitate weaning during recovery from RDS.

To minimize the complications of conventional intermittent mandatory ventilation, newer ventilation techniques have been introduced, including the following:
o Synchronous intermittent mandatory ventilation is a technique wherein some of the patient's respirations are synchronized with breaths delivered by the ventilator. In a recent randomized controlled trial, the incidence of BPD (defined as oxygen requirement at corrected gestational age of 36 wk) was reduced significantly when compared with standard intermittent mandatory ventilation (47% vs 72%; p <0.05).
o Assist-control ventilation has also been suggested to improve outcome.
o Some physicians use pressure-support ventilation to wean the infants who have developed chronic lung changes.
o High-frequency ventilation (HFV) is a technique wherein small tidal volumes (less than anatomic dead space) are usually delivered at rapid frequencies. HFV was originally designed to treat patients with air leak. Numerous studies in animal models of RDS demonstrate that HFV promotes more uniform lung inflation, improves lung mechanics and gas exchange, and reduces exudative alveolar edema, air leak, and lung inflammation. Although animal studies are unequivocal, human data are less clear. Some clinical trials demonstrate that HFV can reduce the occurrence of chronic lung disease, whereas other studies have demonstrated no effect. Adequate clinical trials controlling for techniques of resuscitation, surfactant therapy, and comparing HFV with synchronous intermittent mandatory ventilation are awaited. HFV techniques have a learning curve, and the optimal ventilator strategy varies with the stage of RDS.

These ventilators include the following:
o High-frequency oscillatory ventilation (10-15 Hz): Because expiration occurs actively, monitor patients for hypocarbia in order to prevent periventricular leukomalacia. Controlled trials of the use of high-frequency oscillatory ventilation (HFOV) in reducing BPD in infants with RDS have been controversial. Perhaps the unfavorable outcome of HFOV in some of these studies can be attributed to (1) having very low incidence of BPD with antenatal steroid use and, therefore, inadequate sample size to detect a difference, (2) not using an optimal lung volume strategy in patients treated with HFOV, (3) definition and differences in chorioamnionitis, or (4) differences in resuscitation techniques at birth.

o High-frequency jet ventilation: Its frequency range is 4-11 Hz (usually 7 Hz), but it has to be used in tandem with a conventional ventilator to provide PEEP and sigh breaths. It has been demonstrated to decrease air leaks. Because the solenoid valves open intermittently to provide jet breaths, high-frequency jet ventilation may be preferred by some neonatologists to treat infants with air leaks.

o High-frequency flow interrupter: Its frequency range is 6-15 Hz, with the advantages of a built-in conventional ventilator and an ability to provide sigh breaths. Its use is also associated with a decrease in the incidence of air leaks in infants with RDS.

• Supportive therapy includes the following:
o Temperature regulation: Hypothermia increases oxygen consumption, thereby further compromising infants with RDS who are born prematurely. Therefore, prevent hypothermia in infants with RDS during delivery, resuscitation, and transport. Care for these infants in a neutral thermal environment with the use of a double-walled incubator or radiant warmer.

o Fluids, metabolism, and nutrition: In infants with RDS, initially administer 5% or 10% dextrose intravenously at 60-80 mL/kg/d. Closely monitor blood glucose (Dextrostix), electrolytes, calcium, phosphorous, renal function, and hydration (determined by body weight and urine output) to prevent any imbalance. Add calcium at birth to the initial intravenous fluid. Start electrolytes as soon as the infant voids and as indicated by electrolytes. Gradually increase the intake of fluid to 120-140 mL/kg/d. Extremely premature infants occasionally may require fluid intake of as much as 200-300 mL/kg or more because of insensible water loss occurring from their large body surfaces. Once the infant is stable, add intravenous nutrition with amino acids and lipid. After the respiratory status is stable, initiate a small volume of gastric feeds (preferably breast milk) via a tube to initially stimulate gut development and, thereafter, provide nutrition as intravenous nutritional support is being decreased.

o Circulation and anemia: Assess the baby's circulatory status by monitoring heart rate, peripheral perfusion, and blood pressure. Administer blood or volume expanders, and use vasopressors to support circulation. Monitor blood withdrawn for laboratory tests closely in tiny infants and replace the blood by packed cell transfusion when it has reached 10% of the infant's estimated blood volume or if the hematocrit level is less than 40-45%.

o Antibiotic administration: Start antibiotics in all infants who present with respiratory distress at birth after obtaining blood cultures; discontinue antibiotics after 3-5 days if blood cultures are negative. Exceptions to the use of antibiotics include a recent negative maternal cervical culture for GBBS or an infant delivered by a mother with intact amniotic membranes, no clinical or laboratory findings suggestive of chorioamnionitis, and adequate antenatal care.

o Support of parents and family: Often parents undergo much emotional and/or financial stress with the birth of a critically ill premature infant with RDS and the associated complications. The parents may feel guilty, be unable to relate to the infant in the intensive care setting, and be anxious about the prognosis for the infant. In addition, the infant may provide inadequate cues to arouse mothering. These factors interact to prevent maternal-infant bonding. Hence, provide adequate support for these parents and other family members to prevent or minimize these problems. Staff members (preferably a physician and a nurse) should keep the parents well informed by frequently talking to them, especially during the acute stage of RDS. Encourage parents and assist them in frequently visiting their child. Explain the equipment and procedures to the parents, and encourage them to touch, feed, and care for their infant as soon as possible. Prior to discharge from the hospital, the infant is immunized ,and follow-up care is arranged with a multidisciplinary team and coordinated by a pediatrician experienced in the care of problems of premature infants.

The goals of pharmacotherapy are to reduce morbidity and prevent complications.
Drug Category: Lung surfactants -- Exogenous surfactant can be helpful in treatment of airspace disease (eg, RDS). Following inhaled administration, surface tension is reduced and alveoli are stabilized, thus decreasing the work of breathing and increasing lung compliance.