Uncomplicated Respiratory Distress Syndrome Research Articles

Management Practices During Perinatal Respiratory Transition of Very Premature Infants.

The present review considers some controversial management practices during extremely premature perinatal transition. We focus on perinatal prevention and treatment of respiratory distress syndrome (RDS) in immature infants. New concerns regarding antenatal corticosteroid management have been raised. Many fetuses are only exposed to potential adverse effects of the drug. Hence, the formulation and the dosage may need to be modified. Another challenge is to increase the fraction of the high-risk fetuses that benefit from the drug and to minimize the harmful effects of the drug. On the other hand, boosting anti-inflammatory and anti-microbial properties of surfactant requires further attention. Techniques of prophylactic surfactant administration to extremely immature infants at birth may be further refined. Also, new findings suggest that prophylactic treatment of patent ductus arteriosus (PDA) of a high-risk population rather than later selective closure of PDA may be preferred. The TREOCAPA trial (Prophylactic treatment of the ductus arteriosus in preterm infants by acetaminophen) evaluates, whether early intravenous paracetamol decreases the serious cardiorespiratory consequences following extremely premature birth. Lastly, is inhaled nitric oxide (iNO) used in excess? According to current evidence, iNO treatment of uncomplicated RDS is not indicated. Considerably less than 10% of all very premature infants are affected by early persistence of pulmonary hypertension (PPHN). According to observational studies, effective ventilation combined with early iNO treatment are effective in management of this previously fatal disease. PPHN is associated with prolonged rupture of fetal membranes and birth asphyxia. The lipopolysaccharide (LPS)-induced immunotolerance and hypoxia-reperfusion-induced oxidant stress may inactivate NO-synthetases in pulmonary arterioles and terminal airways. Prospective trials on iNO in the management of PPHN are indicated. Other pulmonary vasodilators may be considered as comparison drugs or adjunctive drugs. The multidisciplinary challenge is to understand the regulation of pregnancy duration and the factors participating the onset of extremely premature preterm deliveries and respiratory adaptation. Basic research aims to identify deficiencies in maternal and fetal tissues that predispose to very preterm births and deteriorate the respiratory adaptation of immature infants. Better understanding on causes and prevention of extremely preterm births would eventually provide effective antenatal and neonatal management practices required for the intact survival.

Endothelin-1 Signaling Promotes Fibrosis In Vitro in a Bronchopulmonary Dysplasia Model by Activating the Extrinsic Coagulation Cascade

Neonatal respiratory distress syndrome can progress to bronchopulmonary dysplasia (BPD), a serious pulmonary fibrotic disorder. Given the involvement of the extrinsic coagulation cascade in animal models of lung fibrosis, we examined its role in BPD. We observed a higher number of neutrophils expressing tissue factor (TF) in bronchoalveolar lavage fluid (BALF) from infants with BPD than from those with uncomplicated respiratory distress syndrome together with a parallel decrease in TF and connective tissue growth factor (CTGF) in BALF supernatants during the disease course. The involvement of coagulation in the fibrotic process associated with BPD was further evaluated by treating primary human colonic myofibroblasts with BALF supernatants from infants with BPD. These human colonic myofibroblasts demonstrated an enhanced C5a- and thrombin-dependent migration. Moreover, they expressed TF in an endothelin-1-dependent manner, with subsequent activation of the extrinsic coagulation cascade and CTGF production mediated by protease-activator receptor-1 signaling. These data provide a novel mechanism for the development of BPD and indicate that endothelin-1 signaling contributes to fibrosis by upregulating a TF/thrombin amplification loop responsible for CTGF production, and offer novel and specific therapeutic targets for pulmonary fibrotic disease.

Volume-targeted Ventilation

After completing this article, readers should be able to: 1. Understand the importance of controlling tidal volume and avoiding hyperventilation/excessive tidal volume. 2. Recognize the importance of optimizing lung inflation and avoiding atelectasis. 3. Delineate the limitations of traditional volume-controlled ventilation in newborns. 4. Describe the various modes of volume-targeted ventilation and their advantages and disadvantages. 5. Describe the key steps in the clinical application of volume guarantee ventilation. Mechanical ventilation has improved to the point where few infants die because of acute respiratory failure. Mortality now is predominantly from other complications of extreme prematurity, such as infection, necrotizing enterocolitis, and intracranial hemorrhage. Consequently, focus has shifted from merely reducing mortality to reducing the incidence of chronic lung disease, which has increased in recent years with improved survival of extremely preterm infants. Although high-frequency ventilation has shown promise, results of clinical trials have been inconsistent, and continued concerns about the hazards of inadvertent hyperventilation have limited its acceptance as first-line therapy in infants who have uncomplicated respiratory distress syndrome (RDS). At the same time, technologically advanced synchronized ventilation has become widely available. The most exciting development in neonatal respiratory support, however, is the advent of volume-targeted modalities of conventional ventilation that, for the first time, allow effective control of delivered tidal volume for neonatal ventilation. Pressure-limited, time-cycled, continuous flow ventilation has been the standard of care in neonatal ventilation for more than 30 years. One of the advantages cited for the preference for pressure-limited over volume-controlled ventilation has been the ability to control the inspiratory pressure directly. Preoccupation with high inspiratory pressure as the chief culprit in lung injury and air leak has been a constant theme in neonatal respiratory support until recently, despite accumulating evidence over more than a decade that volume, rather than pressure, is the critical determinant of ventilator-induced lung injury. Dreyfuss …

FUNCTIONAL RESIDUAL CAPACITY AND STATIC COMPLIANCE DURING THE FIRST YEAR IN PRETERM INFANTS TREATED WITH SURFACTANT

Individual lung development during the first year of life was studied in surfactant treated preterm infants with respiratory distress syndrome (RDS) and healthy controls, as well as in a group who subsequently developed chronic lung disease of the newborn (CLDN). Lung development was assessed from functional residual capacity (FRC) and compliance of the respiratory system (Crs). Twenty-one infants with RDS after preterm birth received surfactant treatment. Six of them developed CLDN. Eighteen preterm infants without RDS served as a control group. Lung function measurements were performed at term age and 4, 8, and 12 months afterwards. FRC was obtained by means of the closed-system helium dilution technique whereas static Crs was obtained by means of the weighted spirometer technique. At term age, FRC was lower in the CLDN group compared with uncomplicated RDS and controls (p < 0.05). No significant differences between groups were found in the development of FRC during the first year of life (p = 0.4). No differences were found in Crs during the first year of life in surfactant treated infants who recovered from uncomplicated RDS and the control group. However, lower values were found in the CLDN group (p < 0.05). We conclude that surfactant treated infants without CLDN have similar lung development during the first year of life as control preterm infants.

Chronic Inflammation of the Airways is Associated with Prolonged Fibrin Turover in Infants Developing Chronic Lung Disease † 1497

Intraalveolar fibrin deposition is a prominent histologic feature of neonatal respiratory distress syndrome (RDS). We hypothesized that in infants in whom RDS progresses into CLD, chronic inflammation of the airway would derarrange alveolar-capillary integrity and lead to prolonged fibrin deposition in the alveolar spaces. To test this hypothesis, we determined concentrations of inflammatory cells (neutrophils,N, and macrophages, M,) and products of fibrin turnover (D-dimers) in the bronchoalveolar lavage (BAL) fluid of infants who initially had RDS and developed CLD than infants who had uncomplicated RDS. Methods: twenty-three preterm infants who required mechanical ventilation because of RDS underwent BAL on day 1 of life and thereafter every other day during endotracheal intubation. The samples collected on dexamethasone admninistration were not included. After cell counts were made, BAL fluids were centrifuged and D-dimers measured (ELISA).Results: Fourteen patients (EG: 27wks±2, BW:805g±187) developed CLD (02≥28 days) and 9 did not (EG:28wks±2, BW: 899g±166). Median values ± SD of N and D-dimers are shown below. M counts did not statistically differ between the two groups of infants.*p<0.05 Table

Evaluation of two endotracheal suction regimes in babies ventilated for respiratory distress syndrome

All low birthweight babies ventilated for the respiratory distress syndrome during a period of fourteen months were randomised to receive endotracheal suction 12-hourly or 6-hourly. There were no significant differences in respiratory outcome between the groups. These observations suggest that it is safe to aspirate endotracheal tubes infrequently during the first few days in uncomplicated respiratory distress syndrome.

The timing of spontaneous closure of the ductus arteriosus in infants with respiratory distress syndrome

Previous studies evaluating the incidence of patent ductus arteriosus have not made a distinction between physiologic ductal patency and abnormally persistent ductus arteriosus. However, it has recently been shown that healthy premature infants without respiratory distress syndrome (RDS) undergo spontaneous closure of the ductus arteriosus in the first 4 days of life at times comparable to full-term infants. Thus, ductal patency within this time frame would appear to be physiologic. Although sick premature infants are well recognized to be at risk for ductal shunting, the purpose of this investigation was to evaluate systematically the actual impact that RDS has on duration of ductal shunting by assessing the timing of spontaneous functional closure. The presence of ductal shunting was evaluated using echocardiographic color flow Doppler techniques. Thirty-six premature infants (30 to 37 weeks gestational age) were evaluated. By the fourth day of life, only 4 of 36 (11.1%) of the infants continued to have evidence of ductal patency. The remainder of the infants underwent spontaneous functional closure of the ductus arteriosus at times comparable to healthy infants without RDS. For most infants ≥30 weeks gestation, uncomplicated RDS does not alter the usual timing of functional ductal closure.

Tracheal lavage and plasma fibronectin: Relationship to respiratory distress syndrome and development of bronchopulmonary dysplasia

Plasma for fibronectin determinations was obtained from 39 neonates with uncomplicated respiratory distress syndrome (RDS) and from 15 infants with RDS who developed bronchopulmonary dysplasia (BPD). Tracheal lavage fibronectin and albumin concentrations were measured in 15 infants with RDS and 15 with BPD. Control plasma fibronectin values were obtained from 20 healthy preterm infants on days 1, 2, 3, 14, and 30 of life. Control tracheal lavage fibronectin and albumin concentrations were measured in 17 neonates of various gestational ages who required tracheal intubation for nonpulmonary indications. Mean plasma fibronectin concentrations from patients with RDS was 121 +/- 11 micrograms/ml on days 1, 2, and 3, versus control level of 163 +/- 12 micrograms/ml (P less than 0.01). Mean tracheal lavage fibronectin/albumin ratio was 3.8 +/- 0.6 ng per microgram of albumin on days 1 to 5 for infants with RDS, versus control level of 5.6 +/- 3.6 (P = NS). Tracheal lavage fibronectin/albumin ratio from patients with BPD was elevated at 16.3 +/- 5.0 ng fibronectin per microgram of albumin on days 14 to 21, and 23.6 +/- 7.4 on day 30 (P less than 0.05 versus control and and versus RDS days 1 to 10). Low plasma fibronectin concentrations early in RDS may contribute to the development of pulmonary capillary leak. High tracheal lavage fibronectin levels may foster the development of pulmonary fibrosis in patients with BPD.

Serum levels of C-reactive protein in neonatal respiratory distress syndrome.

Serum levels of C-reactive protein (CRP) were measured within 96 hours of birth in 55 neonates with respiratory distress syndrome (RDS), 19 neonates with no significant medical illness other than an unstable cardiovascular state, and 13 neonates with a variety of pulmonary and extra-pulmonary problems either alone or in combination with RDS. The median serum CRP level in patients with RDS (2 micrograms/ml) was neither elevated nor different from CRP levels in infants with unstable cardiovascular systems (median CRP level, 2 micrograms/ml); however, neonates with other problems including pneumonia, aspiration, and extrapulmonary sepsis had significantly elevated serum CRP values (median 24 micrograms/ml). CRP levels are not elevated in neonatal RDS. Measurement of this acute phase reactant provides a rapid and reliable means of helping to distinguish infants with uncomplicated RDS from those with other serious pulmonary and extrapulmonary disease.

Streptococcal Pneumonia in Neonatal Respiratory Distress

To the Editor.— We refer to the article by Miller et al (243:1176, 1980) concerning neonatal respiratory distress. We would like to add a note regarding the importance of streptococcal pneumonia. As greater strides have been made in the prevention and treatment of both respiratory distress syndrome (RDS) and meconium aspiration syndrome, we and others have found that streptococcal pneumonia persists and thus is becoming the most notable killer among the various causes of respiratory distress in the newborn. 1,2 It is treatable with penicillin early in its course but tragically is not often treated until too late, because the chest roentgenogram is interpreted as uncomplicated RDS. 1,3,4 We believe it is crucial that the roentgenographic appearance of neonatal streptococcal pneumonia is often indistinguishable from uncomplicated RDS, (ie, diffuse granular appearance with or without air bronchograms) and that trying to make the distinction can result in a lethal delay in

RESPIRATORY DISTRESS SYNDROME IN 32-WEEK GESTATION PREMATURES: NEUROBEHAVIORAL PROFILE

To investigate the effects of respiratory distress syndrome (RDS) on the neurobehavioral function of premature infants, 26 infants of ≤32 weeks gestation were evaluated by a modification of the Brazelton Neonatal Scale within the first four days of life. 17 were infants with uncomplicated prematurity (PBLCs). 9 had RDS, uncomplicated by depression at birth, sepsis, seizures, hyperbilirubinemia, or intracranial hemorrhage. When examined, 3 were on respirators and 3 had nasal prongs in place. Infants with RDS showed decreased ability to adapt to repeated stimuli and to attend to and orient toward light, sound, face, and voice, compared to PBLCs. Infants with RDS were also less alert. A higher level of irritability and a higher peak of arousal were noted in infants with RDS. The two groups did not differ in level of activity or in response to a cloth on the face. Grasp reflexes were diminished in infants with RDS, but Moro and deep tendon reflexes were not. Resting muscle tone was similar in the two groups. Since in our study tone, reflexes, and activity were not affected by even severe uncomplicated RDS, the development of hypotonia, hyporeflexia, or hypoactivlty in an infant with RDS therefore points toward a complication such as sepsis or intracranial hemorrhage. However, our results suggest that cortical functions such as adaptation, orientation, and alertness are impaired in infants with RDS.

A THERAPEUTIC APPROACH IN 100 CASES OF THE RESPIRATORY DISTRESS SYNDROME OF THE NEWBORN INFANT

A method of treatment in 100 cases of the idiopathic respiratory distress syndrome of severe degree is described. This includes the rapid correction of metabolic acidosis with 8.4% solution of sodium bicarbonate (1 ml = 1 mEq). The sodium bicarbonate is given by periodic intravenous injections by the umbilical vein, and the dosage is controlled by frequent estimations in the blood of the pH, pCO2, plasma standard bicarbonate and base excess by means of the Astrup micro-apparatus. The total daily fluid intake by the same route is brought up to 60 ml/kg with 20% fructose solution. In view of the serious prognostic significance of severe or persisting respiratory acidosis, which cannot be relieved by sodium bicarbonate, a trial of Tris-(hydroxymethyl)-aminomethane (THAM) was made in 26 cases. In each of these very severely affected infants the pCO2 was above 70 mm Hg. The results failed to show sufficient advantage to justify the increased risks with THAM. The mortality figures in the trial series have been compared with those recorded in the same hospital in cases of comparable severity which were treated by standard methods in 1960 and 1961. The over-all mortality rates in 1960, 1961, and the trial series, including patients who also had intraventricular hemorrhage or other major complications, were 66, 64, and 46% respectively. The mortality rates in cases of the uncomplicated respiratory distress syndrome in 1960, 1961, and the trial series were 49, 44.7, and 11.5% respectively. It is considered that the improvement in the mortality figures with this type of supportive therapy is sufficiently striking to encourage its trial use in other centers.