Infant respiratory distress syndrome
Infant respiratory distress syndrome, also known as surfactant deficiency disorder , and previously called hyaline membrane disease, is a syndrome in premature infants caused by developmental insufficiency of pulmonary surfactant production and structural immaturity in the lungs. It can also be a consequence of neonatal infection and can result from a genetic problem with the production of surfactant-associated proteins.
IRDS affects about 1% of newborns and is the leading cause of morbidity and mortality in preterm infants. Data have shown the choice of elective caesarean sections to strikingly increase the incidence of respiratory distress in term infants; dating back to 1995, the UK first documented 2,000 annual caesarean section births requiring neonatal admission for respiratory distress. The incidence decreases with advancing gestational age, from about 50% in babies born at 26–28 weeks to about 25% at 30–31 weeks. The syndrome is more frequent in males, Caucasians, infants of diabetic mothers and the second-born of premature twins.
IRDS is distinct from pulmonary hypoplasia, another leading cause of neonatal death that involves respiratory distress.
The European Consensus Guidelines on the Management of Respiratory Distress Syndrome highlight new possibilities for early detection, and therefore treatment of IRDS. The guidelines mention an easy to use rapid point-of-care predictive test that is now available and how lung ultrasound, with appropriate training, expertise and equipment, may offer an alternative way of diagnosing IRDS early.
Signs and symptoms
IRDS begins shortly after birth and is manifested by fast breathing, a fast heart rate, chest wall retractions, expiratory grunting, nasal flaring, and blue discoloration of the skin during breathing efforts.As the disease progresses, the baby may develop ventilatory failure and prolonged cessations of breathing. Whether treated or not, the clinical course for the acute disease lasts about two to three days. During the first day, the child worsens and requires more support. During the second day, the baby may be remarkably stable on adequate support and resolution is noted during the third day, heralded by a prompt diuresis. Despite huge advances in care, IRDS remains the most common single cause of death in the first month of life in the developed world. Complications include metabolic disorders, patent ductus arteriosus, low blood pressure, chronic lung changes and bleeding in the brain. The syndrome is frequently complicated by prematurity and its additional effect on other organ functions.
Histopathology
The characteristic histopathology seen in babies who die from RDS was the source of the name "hyaline membrane disease", first described in 1903 by Hochheim. Waxlike layers of hyaline membrane line the collapsed alveoli of the lung. In addition, the lungs show bleeding, overdistention of airways, and damage to the lining cells.Pathophysiology
The lungs of infants with respiratory distress syndrome are developmentally deficient in a material called surfactant, which helps prevent the collapse of the terminal air spaces throughout the normal cycle of inhalation and exhalation. This deficiency of surfactant is related to inhibition from the insulin that is produced in the newborn, especially those of diabetic mothers.Pulmonary surfactant is a complex system of lipids, proteins and glycoproteins that is produced in specialized lung cells called Type II cells or Type II pneumocytes. The surfactant is packaged by the cell in structures called lamellar bodies, and extruded into the air spaces. The lamellar bodies then unfold into a complex lining of the air space. This layer reduces the surface tension of the fluid that lines the alveolar air space. Surface tension is responsible for approximately 2/3 of the inward elastic recoil forces. In the same way that a bubble will contract to give the smallest surface area for a given volume, so the air/water interface means that the liquid surface will tend toward being as small as possible, thereby causing the air space to contract. By reducing surface tension, surfactant prevents the air spaces from completely collapsing on exhalation. In addition, the decreased surface tension allows reopening of the air space with a lower amount of force. Therefore, without adequate amounts of surfactant, the air spaces collapse and are very difficult to expand.
Microscopically, a pulmonary surfactant-deficient lung is characterized by collapsed air spaces alternating with hyperexpanded areas, vascular congestion, and, in time, hyaline membranes. Hyaline membranes are composed of fibrin, cellular debris, red blood cells, rare neutrophils and macrophages. They appear as an eosinophilic, amorphous material, lining or filling the air spaces and blocking gas exchange. As a result, blood passing through the lungs is unable to pick up oxygen and unload carbon dioxide. Blood oxygen levels fall and carbon dioxide rises, resulting in rising blood acid levels and hypoxia. Structural immaturity, as manifested by a decreased number of gas exchange units and thicker walls, also contributes to the disease process. Therapeutic oxygen and positive-pressure ventilation, while potentially life-saving, can damage the lung.
Diagnosis
The diagnosis is made by the clinical picture and the chest X-ray, which demonstrates decreased lung volumes, absence of the thymus, a small, discrete, uniform infiltrate that involves all lobes of the lung and air-bronchograms. In severe cases, this becomes exaggerated until the cardiac borders become indiscernible.Point-of-care lung maturity test
To improve clinical outcomes very early treatment with surfactant is necessary. However, only about half of infants with a gestational age below 30 weeks need surfactant treatment and prophylactic surfactant treatment increases the combined mortality and incidence of bronchopulmonary dysplasia contrary to selective rescue surfactant treatment. Therefore, there is a need for a rapid diagnostic test to guide early targeted surfactant treatment.Professor Henrik Verder has worked with lung-maturity diagnostics on gastric aspirates obtained at birth. With the introduction of surfactant treatment for IRDS, Verder developed additional lung maturity tests based on gastric aspirates ; for example, the microbubble stability test and lamellar body counts as well as a large randomised trial using lamellar body counts to guide surfactant treatment. However, a common problem with all these methods is dilution with foetal urine. Additionally, the methods are time‐consuming laboratory tests and are too slow to be used as a point‐of‐care test to guide surfactant treatment.
Verder, in collaboration with chemometric scientist Agnar Höskuldsson, developed a rapid point-of-care method for predicting IRDS by measuring the lecithin-sphingomyelin ratio in gastric aspirate. The new method, which is based on mid‐red Fourier Transform Infrared spectroscopy, was shown to measure the L/S ratio at birth with a high sensitivity. This rapid bedside test for surfactant components in gastric aspirate is also now available, and clinical trials of this new point-of-care test to determine surfactant need at birth are underway.
Lung ultrasound
Lung ultrasound, with appropriate expertise, equipment, and training, may offer an alternative way to diagnose the severity of IRDS. A semi-quantitative lung ultrasound score performed during bedside lung echography was first described by Brat et al. and found to correlate with the oxygenation status of infants with RDS. Since then, several studies have supported the use of lung ultrasound scores to earlier predict an initial dose of surfactant when compared to current oxygenation-guided recommendations.Treatment
Oxygen is given with a small amount of continuous positive airway pressure, and intravenous fluids are administered to stabilize the blood sugar, blood salts and blood pressure. CPAP application to preterm neonates with respiratory distress is associated with a reduction in respiratory failure, mechanical ventilation and mortality. However, CPAP is associated with an increased rate of pneumothorax compared to spontaneous breathing with or without supplemental oxygen. If the baby's condition worsens, an endotracheal tube is inserted into the trachea and intermittent breaths are given by a mechanical device. An exogenous preparation of pulmonary surfactant, either synthetic or extracted from animal lungs, is given through the breathing tube into the lungs. Surfactant medications can decrease the risk of death for very low-birth-weight infants who are hospitalized by 30%. Such small premature infants may remain ventilated for months. A study shows that an aerosol of a perfluorocarbon such as perfluoromethyldecalin can reduce inflammation in swine model of IRDS. Chronic lung disease, including bronchopulmonary dysplasia, is common in severe RDS. The etiology of BPD is problematic and may be the result of oxygen, overventilation or underventilation. The mortality rate for babies greater than 27 weeks of gestation is less than 20%.INSURE (Intubation Surfactant Extubation) and LISA (Less Invasive Surfactant Administration)
Henrik Verder invented the INSURE and LISA methods combined with nasal CPAP, effective approaches to managing preterm neonates with respiratory distress. In 1989 he used this pioneering method to successfully treat the first premature infant with severe RDS.The INSURE method has been shown, through meta-analysis, to successfully decrease the use of mechanical ventilation and lower the incidence of bronchopulmonary dysplasia. Since its conception in 1989, the INSURE method has been academically cited in more than 500 papers. The first randomised study involving the INSURE method was published in 1994 and a second randomised study in infants less than 30 weeks gestation was published by the group in 1999. Based on the INSURE method, Verder has since developed a rapid bedside test that predicts IRDS at birth.