Role of lung ultrasound score and optimal timing in predicting the need for surfactant administration in neonates with respiratory distress syndrome
Rolul scorului ecografic pulmonar şi planificarea optimă în vederea anticipării necesităţii de administrare a surfactantului în cazul nou-născuţilor cu sindrom de detresă respiratorie
Abstract
Respiratory distress syndrome is one of the most important causes of morbidity and mortality among premature newborns. The diagnosis of this condition is based on the imaging results obtained at cardiopulmonary radiography. Recently, lung ultrasound has gained a crucial role in the early diagnosis and evaluation of respiratory distress in newborns. It is a fast and safe technique, having the advantage that it does not radiate and it can be repeated dynamically both for establishing the diagnosis and for guiding neonatologists in order to establish the optimal moment of surfactant administration. The indication for surfactant administration is guided by parameters such as cardiothoracic radiography, the ratio of arterial/alveolar oxygen pressure (a/A), and the inspiratory fraction of oxygen (FiO2). Over the years, numerous studies, still ongoing, have attempted to demonstrate the usefulness of lung ultrasound for the management of respiratory distress syndrome and the prediction of surfactant administration according to the ultrasound score. This review article aims to describe the technique of lung ultrasound and the interpretation of the score obtained in order to determine the optimal moment of administration of exogenous surfactant, taking into account the current European recommendations that consider lung ultrasound a useful tool to determine the severity of the respiratory distress syndrome and guide the administration of surfactant.Keywords
respiratory distress syndromesurfactantlung ultrasoundcardiothoracic X-ray ultrasound scorepremature newbornneonatal intensive careRezumat
Sindromul de detresă respiratorie reprezintă una dintre cele mai importante cauze de morbiditate şi mortalitate în rândul nou-născuţior prematuri. Diagnosticul acestei afecţiuni se bazează pe rezultatele imagistice obţinute la radiografia cardiopulmonară. În ultima vreme, ecografia pulmonară a căpătat un rol crucial în diagnosticarea precoce şi evaluarea detresei respiratorii la nou-născuţi. Este o tehnică rapidă şi sigură, având avantajul că nu iradiază şi poate fi repetată în dinamică atât pentru stabilirea diagnosticului, cât şi pentru ghidarea medicilor neonatologi în vederea stabilirii momentului optim de administrare a surfactantului. Indicaţia administrării surfactantului este ghidată de parametri precum radiografia cardiotoracică, raportul dintre presiunea oxigenului arterial/alveolar (a/A) şi fracţia inspiratorie de oxigen (FiO2). De-a lungul anilor, prin numeroase studii, în continuă desfăşurare până în prezent, s-a încercat demonstrarea utilităţii ecografiei pulmonare pentru managementul sindromului de detresă respiratorie şi predicţia administrării surfactantului în conformitate cu scorul ecografic. Acest articol de revizuire îşi propune descrierea tehnicii ecografiei pulmonare şi interpretarea scorului obţinut în vederea stabilirii momentului optim de administrare a surfactantului exogen, ţinând cont de recomandările europene actuale, care consideră ecografia pulmonară un instrument util pentru a determina severitatea sindromului de detresă respiratorie şi a ghida administrarea de surfactant.Cuvinte Cheie
sindrom de detresă respiratoriesurfactantecografie pulmonarăscor ecograficradiografie cardiotoracicănou-născut prematurterapie intensivă neonatalăIntroduction
Respiratory distress syndrome (RDS) accounts for 30-40% of admissions to neonatal intensive care units (NICU), affecting 5.8% of live births and representing a significant cause of neonatal morbidity and mortality among premature infants(1,2). It often manifests within hours after birth, with incidence inversely proportional to gestational age(3).
As the most common pathology among premature newborns, respiratory distress syndrome affects approximately 24,000 newborns annually in the United States of America. Major risk factors include prematurity and low birth weight. Other risk factors comprise Caucasian race, male sex, maternal diabetes mellitus, perinatal hypoxia and ischemia, or lack of labor. The incidence of RDS increases with decreasing gestational age at birth(3).
The main demonstrated functions of surfactant include reducing surface tension at the air-liquid interface, thereby preventing alveolar collapse at the end of expiration, avoiding excessive alveolar distension during inspiration, improving alveolar capillary circulation, and exerting immunomodulatory activity through interaction and participation in pathogen elimination or prevention of their dissemination, as well as modulating immune responses(4).
The management is based on timely administration of exogenous surfactant along with the use of continuous positive airway pressure (CPAP). However, identifying the narrow window for surfactant administration remains a challenge, considering the benefits of early rescue surfactant therapy in reducing the risk of acute lung injury, neonatal mortality, and chronic lung diseases(4).
In newborns diagnosed with respiratory distress syndrome, the early administration of exogenous surfactant plays a crucial role in treatment. Among the short- and long-term effects of surfactant administration, there are reducing the incidence of pneumothorax, improving survival rates, avoiding invasive mechanical ventilation, minimizing the development of bronchopulmonary dysplasia, and reducing mortality(4).
The classic description of altered surfactant components in neonatal respiratory distress syndrome due to surfactant deficiency underscores the continued use of exogenous surfactant replacement therapy as a cornerstone in managing this condition, particularly in premature infants. Surfactant deficiency-related respiratory distress syndrome remains the primary cause of respiratory dysfunction in newborns. However, in recent years, other acute or chronic pulmonary pathologies have been described that also interfere with and lead to quantitative and qualitative deficiencies in surfactant composition(5).
Neonatal lung ultrasound has gained a crucial role in the early diagnosis of respiratory distress in newborns. It is a rapid and safe technique that offers the advantage of being repeatable several times a day in neonatal intensive care units, thus allowing dynamic monitoring of the evolution of newborns(6).
Surfactant (derived from the acronym SURFace ACTive AgeNT) is essential for ensuring survival. Its biochemical structure predominantly includes phospholipid substances, especially dipalmitoylphosphatidylcholine, mixed with four proteins: SP-A, SP-B, SP-C, and SP-D. These proteins play an essential role in maintaining surfactant quality and integrating immunological functions(6,7).
Scoring in lung ultrasound (LUS)
Ultrasound imaging of the lungs in newborns is preferably performed using a high-frequency linear probe, considering their small chest size and thinner chest walls, which allows for better image quality and visualization of the entire lung surface. Ultrasound can be conducted with the newborn lying in a dorsal, lateral, or supine position(8,9).
Each lung is divided into three zones: superior anterior, inferior anterior, and lateral. Each zone is scored individually on a scale from 0 to 3 points, with a total score ranging from 0 to 18 points(9).
Interpretation of lung ultrasound scoring 0-3:
0 = A-lines, maximum of 2 B-lines, and normal pleural line (indicating normal lung aeration).
1 = ≥3 non-confluent B-lines (indicating an interstitial syndrome).
2 = Confluent B-lines with or without subpleural consolidations <1 cm and thickened pleural line (indicating severe interstitial syndrome or “white lung” appearance).
3 = Extensive consolidations >1 cm(8,9).
The current European recommendations consider lung ultrasound a useful tool for assessing the severity of respiratory distress syndrome (RDS) and guiding surfactant administration. Oxygenation depends on both FiO2 and mean airway pressure. Therefore, consensus guidelines suggest administering surfactant to noninvasively ventilated newborns when the fraction of inspired oxygen (FiO2) is greater than 30% during continuous positive airway pressure (nCPAP) of at least 6 cmH2O(8,9).
Additionally, a study by Brat et al., from 2015, involving 65 preterm newborns with gestational ages below 34 weeks, established an objective assessment of surfactant administration based on lung ultrasound, with a cutoff score of 4(9).
The decision to administer surfactant varies across neonatal intensive care units and is guided by parameters such as chest radiography, the arterial/alveolar oxygen ratio (a/A), and FiO2 levels. Currently, exogenous surfactant administration is primarily guided by FiO2 values, which can be arbitrary and nonspecific(11).
A randomized, multicenter study involving 668 premature infants with gestational ages between 25 and 29 weeks, who initially breathed spontaneously at birth but required noninvasive nCPAP respiratory support with positive pressure of 6-8 cm H2O to maintain peripheral oxygen saturation (SpO2) between 90 and 95%, and mandatory inclusion criterion of lung imaging supporting the diagnosis of respiratory distress syndrome, concluded that lung ultrasound can predict with greater accuracy which premature newborns with respiratory distress syndrome assisted with nasal CPAP may benefit from the early administration of surfactant, using the pulmonary ultrasound scoring(12).
From a radiological standpoint, pathognomonic signs in respiratory distress syndrome include decreased lung transparency with diffuse atelectasis, classically described as a reticulogranular or ground glass appearance, accompanied by progressively reduced visibility of the cardiac silhouette and presence of air bronchograms(11).
There are studies confirming that lung ultrasound has both high specificity and sensitivity in diagnosing neonatal respiratory distress syndrome(11).
The main ultrasonographic features of this syndrome include pulmonary consolidations, the presence of air bronchograms, abnormalities of the pleural line, pleural effusions, and bilateral white lung appearance(12). Among these, pulmonary consolidation is considered the most important indicator of neonatal respiratory distress syndrome, useful for both diagnosis and severity staging(12).
Furthermore, lung ultrasound has demonstrated its utility in diagnosing complications associated with this syndrome, such as pulmonary hemorrhage, pneumothorax or atelectasis(11,12).
Another aspect is the correlation of clinical and laboratory data with lung ultrasound for a more precise diagnosis, especially when other conditions such as pneumonia, early sepsis or air leak syndrome coexist(13).
For establishing the diagnosis and initiating surfactant replacement therapy, lung ultrasound represents the imaging method with the most advantages, capable of visualizing the following at the patient’s bedside: the “white lung” appearance, presence of more than three consolidated B-lines, thickening of the pleural line, multiple subpleural consolidations suggestive of alveolar collapse. These ultrasound findings, described by Copetti et al. (2008), have a specificity and sensitivity of 100% for diagnosing respiratory distress syndrome(14).
In recent years, studies have contributed to the development of a lung ultrasound score for predicting surfactant administration(7,8), demonstrating its utility in the management of respiratory distress syndrome. In 2012, Raimondi et al. highlighted the role of lung ultrasound in respiratory distress in neonates and, subsequently, studies have been conducted to establish the role of lung ultrasound in guiding surfactant administration in premature newborns with respiratory distress syndrome. It has now become increasingly recognized as a primary modality for evaluating this pathology in newborns(15).
In the following years – specifically, in 2022 – an observational prospective study was conducted in a level III neonatal intensive care unit in India, involving 100 newborns with gestational ages below 34 weeks who presented with respiratory distress at birth. Lung ultrasound was performed after the initial stabilization of the newborns. The conclusions of this study were as follows: 58% were diagnosed with respiratory distress syndrome, and surfactant was administered to 40% of the newborns. According to the 2019 European Consensus Guidelines, the cutoff for the pulmonary ultrasound score was 7 for the first dose of surfactant therapy, with a sensitivity of 92.5% and specificity of 96.67%. For the second dose of surfactant administration, the cutoff was set at 10. Similar findings to the study described above were also reported by De Martino et al., who analyzed multiple cohorts of premature newborns with gestational ages ≤30 weeks(16).
Another cutoff value for the lung ultrasound score in surfactant therapy was set at 9, established by Raimondi et al. and reported in a recent multicenter study. This study included 240 premature newborns with gestational ages between 25 and 30 weeks, who were monitored using lung ultrasound at birth. Among them, 108 received at least one dose of surfactant. It was found that the pulmonary ultrasound score of 9 had a specificity of 83% and a sensitivity of 79% for predicting the need for surfactant therapy. Another finding of this study was that the score significantly decreased within the first 24 hours in newborns who received a surfactant dose(17).
Another study, conducted in 2021, supports the validity of lung ultrasound as a diagnostic tool for predicting exogenous surfactant therapy in newborns with gestational ages between 27 and 33 weeks. The analysis included 78 newborns with respiratory distress syndrome, out of which 62 received surfactant (79.48%). A lung ultrasound score ≥9 was deemed optimal, with a sensitivity of 70.97% and a specificity of 68.75% for predicting the need for surfactant therapy(18).
Discussion
Neonatal lung ultrasound plays a crucial role in early diagnosis of respiratory distress in newborns and is increasingly replacing chest X-ray in this regard(5). It is a rapid and safe technique that offers the advantage of being repeatable multiple times a day in neonatal intensive care units, allowing for dynamic monitoring of newborns’ progression(6).
Multiple studies confirm that lung ultrasound has high specificity and sensitivity in diagnosing neonatal respiratory distress syndrome and is valuable in establishing management strategies and prognostic assessment of the disease(11).
For establishing the diagnosis and initiating surfactant replacement therapy, lung ultrasound represents the imaging method with the most advantages, which can be objectively assessed at the patient’s bedside, with a specificity and sensitivity of 100% for diagnosing respiratory distress syndrome(14).
When other conditions coexist, such as pneumonia, early sepsis or air leak syndrome, it’s important to correlate clinical and laboratory data with lung ultrasound for a more precise diagnosis(13).
Conclusions
Over the years, lung ultrasound has gained ground over chest X-rays in diagnosing respiratory distress syndrome (RDS). Lung ultrasound has now become the most recognized method for guiding surfactant administration in newborns with RDS.
The lung ultrasound score (LUS) represents an objective tool for guiding the management of respiratory distress syndrome, and performing neonatal lung ultrasound is a common practice in neonatal intensive care units.
The main ultrasound characteristics of neonatal respiratory distress syndrome include pulmonary consolidations, presence of air bronchograms, abnormalities of the pleural line, pleural effusions, and bilateral white lung appearance. Among these, pulmonary consolidation is the most important indicator of neonatal RDS, useful both for establishing the diagnosis and assessing severity.
Ultimately, neonatal lung ultrasound is indispensable in the diagnosis, management and prognosis of neonatal respiratory distress syndrome, particularly among premature newborns.
Autori pentru corespondenţă: Alexandra-Elena Popa E-mail: alex_7691_andra@yahoo.com
CONFLICT OF INTEREST: none declared.
FINANCIAL SUPPORT: none declared.
This work is permanently accessible online free of charge and published under the CC-BY.
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