Radiological changes after therapeutic use of surfactant in infants with respiratory distress syndrome

The aims of this study were to determine the incidence of typical chest radiography findings – (1) uniform improvement, (2) asymmetrical improvement, (3) no improvement or (4) interstitial emphysema – after therapeutic use of surfactant and to analyse clinical course and outcome. Chest radiographs of 138 infants of very low birth weight treated with surfactant were analysed. Twenty-eight infants with a diagnosis other than typical respiratory distress syndrome (RDS), i. e., sepsis, congenital pneumonia and congenital malformation, were excluded. In 110 patients with clinical and radiological evidence of typical RDS (median gestational age 28 weeks, median birth weight 1070 g) adequate chest radiographs from before and within 72 h after surfactant treatment were available. The time of surfactant application ranged between 1 and 12 h after birth. The most common finding after surfactant treatment was uniform or asymmetrical improvement of pulmonary aeration (80 of 110 patients). Patients with uniform clearing had the best long-term outcome. Asymmetrical clearance was often localised on the right side or in central regions of the lung, and usually disappeared after retreatment with surfactant without clinical significance. In 11 patients no change in aeration was found and retreatment was absolutely ineffective. Development of pulmonary inter- stitial emphysema after surfactant treatment was a grave prognostic sign: 73 % of these infants died within the first 2 weeks of life compared with 10 % of those with uniform or asymmetrical improvement of ventilation. Received: 18 October 1995 Accepted: 14 February 1996     

Therapeutic use of surfactant in neonatal respiratory distress syndrome

As part of a multicenter surfactant rescue study, the chest X-rays of 239 preterm and term infants were analyzed. To study the influence of surfactant administration on radiographic appearance, 130 patients with a clinical and radiological diagnosis of typical respiratory distress syndrome were selected, in whom adequate chest x-rays before and within 48 h after treatment were available. Median gestational age was 30 weeks (range 25–38 weeks), median birth weight was 1335 g (range 625–3450). The time of surfactant application ranged between 90 min and 24 h after birth (median 6 h). The most common finding after surfactant administration was uniform (n=47) or disproportionate (n=46) improvement of pulmonary aeration, which showed a significant correlation to posttreatment reduction of oxygen requirement (p<0.001). Asymmetric clearance was more often localized on the right side and usually disappeared within two to five days. Only in 13 patients no change of ventilation was found. Development of interstitial emphysema (n=24, including three patients with pneumothorax) after surfactant treatment was an unfavourable prognostic sign. 54% of these patients (13 of 24) died within the first month of life, compared to 8% (7 of 93) in the group of patients with initial improvement of ventilation.Presented at the ESPR meeting in Stockholm 1991     

The lungs in immature infants: How important is surfactant therapy in preventing chronic lung problems?

Seventy-five premature infants weighing between 600 and 3200 g were studied over a period of 1 year. All of the infants received surfactant therapy for hyaline membrane disease immediately after birth and, thereafter, up to four doses every 6 h. The roentgenographic findings in all patients were documented at birth and at 2 days, 7–10 days, and 21–28 days of life. Larger babies responded to surfactant therapy better than did smaller infants. The smaller infants, even after initial clearing, were prone to develop pulmonary edema and the bubbly lungs of bronchopulmonary dysplasia. These data suggest that small infants, while initially responding to surfactant therapy with clearing of their lungs, are still at considerable risk of developing chronic lung disease in the form of pulmonary edema and bronchopulmonary dysplasia. An explanation is offered for why this occurs; at the same time it is suggested that, in view of our findings and those in the literature, the problems of pulmonary edema and bubbly lungs be more clearly separated.     

Right Diaphragmatic Hernia in the Newborn

Right diaphragmatic hernia in the newborn. It is uncommon for herniation of the liver through a right diaphragmatic defect to present in the neonatal period. Four infants are described who developed respiratory distress within four hours of birth and were thought to have a Group B beta haemolytic streptococcal infection. In all four the diaphragm seemed normal on the first X-rays. Progressive herniation of the liver, which occurred during the first week after birth, initially resulted in confusing clinical and radiological findings which were ascribed to worsening pneumonia and pleural effusion. The importance of serial X-rays of the chest and abdomen and the presence of loops of gas-containing bowel in the right upper quadrant of the abdomen, as indicators of right diaphragmatic herniation, are emphasized. Two diagnostic techniques are described: in two infants, a right pneumothorax after oxygen-induced pneumoperitoneum confirmed a communication between the peritoneal and right pleural cavities; in the other two infants, comparison of X-rays taken during spontaneous breathing and forced inspiration revealed in the latter substantial clearing of the right lung field and descent of the liver shadow.     

The effect of dexamethasone on respirator-dependent very-low-birth-weight infants is best predicted by chest X-ray

BACKGROUND: Chronic lung disease (CLD) in premature infants shows a variable clinical course with different radiological manifestations. OBJECTIVE: To evaluate the correlation between parameters of trans-membrane permeability [albumin/secretory component (SC)] and oxidative stress [malondialdehyde (MDA)/SC] in tracheal aspirate fluid (TAF) and radiological findings with the effect of a 5-day course of dexamethasone (0.5 mg/kg per day). MATERIALS AND METHODS: Fifty ventilator-dependent premature infants with birth weights < 1,500 g (gestational ages 23-31 weeks) and radiological signs of early chronic lung disease (CLD) were treated with dexamethasone at day of life 5-27 (median 10 days) because of respiratory deterioration. TAF was collected serially. Chest X-rays taken before and 8-10 days after dexamethasone were scored for changes of opacification, consolidation and hyperinflation/emphysema, and classified into three groups. RESULTS: Twenty-four infants had a positive response to dexamethasone, defined as a reduction of the ventilation index FiO2 x mean airway pressure > 40% at day 5, compared to pretreatment values. About 80% of the responders showed homogeneous lung opacification on chest X-ray, reflecting leaky lung syndrome. In contrast, seven of eight infants with predominantly emphysema on radiology were non-responders; 80% of infants with a mixed radiological picture characterized by predominance of consolidations alternating with regions of emphysema were also non-responders. Ratios of albumin/SC and MDA/SC in TAF decreased significantly within 3 days after the onset of dexamethasone. However, MDA/SC was persistently higher in non-responders compared to responders. Opaque lungs were largely improved by dexamethasone, in contrast to streaky or patchy consolidations and emphysema. In a logistic regression model, radiographic classification was the most important factor influencing the response to dexamethasone with a positive predictive value of 86%, followed by albumin/SC ratio. CONCLUSIONS: The optimum timing of dexamethasone treatment may be determined by the stage of developing CLD and radiological findings rather than by the age of the premature infant.     

Improved outcomes following the introduction of surfactant to an Australian neonatal unit

Objective : To study the impact of the introduction of artificial surfactant therapy for hyaline membrane disease (HMD) in an Australian neonatal intensive care unit.
Methodology : Infants <32 weeks gestation admitted between June 1991 and Dec 1993 who received treatment with artificial surfactant were compared with infants admitted during the preceding 30 months who would have been candidates for such treatment.
Results : For treated infants with gestations in the range 24-27 weeks, there was a significant reduction in neonatal death (adjusted odds ratio 0.28) and a significant increase in the incidence of chronic lung disease (CLD) (adjusted odds ratio 3.4). With gestations in the range 28-31 weeks, there was no significant change in neonatal death or CLD, but there was a significant reduction in incidence of pneumothorax (adjusted odds ratio 0.32).
Conclusions : A reduced incidence of pneumothorax and neonatal death following the introduction of artificial surfactant. therapy was readily demonstrable in the Australian setting.     

Pneumothorax revealing cystic adenomatoid malformation of the lung in a 13 year old child]

CASE REPORT: A 13 year old boy had a seven day history of chest pain and dyspnea. His right hemithorax was immobile with abolished breathing sounds. Initial chest X-ray revealed a right tension pneumothorax. A chest tube was inserted and the right lung re-expanded. However, despite two intrapleural injections of tetracyclin, the pneumothorax reappeared. Lung CT scan showed an intraparechymal cyst in the posterior part of the right upper lobe. Lobectomy was performed and histological study confirmed the diagnosis of type I cystic adenomatoid malformation of the lung. Two months after surgery, clinical and radiological examinations were normal. CONCLUSION: Spontaneous pneumothorax, as the initial manifestation of cystic adenomatoid malformation of the lung, is rare (three cases reported in children beyond the neonatal period, and two in adults). CT scan features correlate well with the pathologic features. Because of the risk of recurrent pulmonary infections and malignancy change, removal of the cystic lesions is advisable.     

Primary alveolar capillary dysplasia (acinar dysplasia) and surfactant protein B deficiency: a clinical, radiological and pathological study

Background: Full-term infants with severe and prolonged respiratory distress represent a diagnostic challenge. Plain radiographic findings may be nonspecific or similar to classic surfactant deficiency disease for infants with surfactant protein B deficiency and acinar dysplasia. Objectives: To describe the similar clinical-radiolgical patterns of two rare neonatal conditions. Materials and methods: Six newborn babies with severe respiratory distress at birth demonstrated clinical and radiographically prolonged and progressive diffuse pulmonary opacification. Results: All infants demonstrated hyperinflation of the lungs. The diffuse hazy opacification, which varied from mild (n=3) to moderate (n=3), progressed to severe diffuse opacification preceding death, which occurred at 12–36 days of life. Open lung biopsy confirmed the diagnosis of primary alveolar acinar dysplasia (AD) in four infants and surfactant protein B deficiency (SPBD) in two infants. Conclusions: In full-term babies with unexplained progressive respiratory distress from birth and progress of radiological changes, both AD and SPBD should be considered.     

Double-blind clinical trial of calf lung surfactant extract for the prevention of hyaline membrane disease in extremely premature infants

A prospective, double-blind, controlled trial was conducted to determine whether instillation of an exogenous surfactant into the lungs before the first breath could prevent hyaline membrane disease. The surfactant is calf lung lipid extracted from saline lung lavage. Entry was limited to infants who were 24 to 28 weeks' gestation, who were born at Children's Hospital of Buffalo, and whose mothers had not received betamethasone for more than 24 hours before birth. Treated infants received 3 mL (90 mg) of calf lung surfactant extract instilled into their trachea before the first breath; control infants received 3 mL of normal saline. A prospective scoring system and respiratory support variables were used to compare the groups. At 48 hours of age, only two of 14 calf lung surfactant extract-treated infants (14%) had hyaline membrane disease compared with seven of 13 control infants (54%) (P = .033). Inspired oxygen, mean airway pressure, ventilator rate and ventilator efficiency index were also lower in the treated group during the first 48 hours of life (P less than .01 to P less than .001). Calf lung surfactant extract instillation at birth appears to be an effective material and method of preventing hyaline membrane disease in extremely premature infants.     

鼻塞式呼吸机间歇指令通气联合肺表面活性物质治疗早产儿肺透明膜病的临床研究

目的 观察鼻塞式呼吸机间歇指令通气(NIMV)联合肺表面活性物质(PS)治疗早产儿肺透明膜病(NHMD)的临床疗效,并与常规机械通气及持续气道内正压通气(CPAP)的疗效进行比较.方法 NIMV组25例患肺透明膜病的早产儿经气管内滴入PS[100 mg/(kg·次)],然后拔管,予NIMV支持治疗,并与25例常规机械通气及24例CPAP的患儿进行比较,指标包括患儿的临床症状、体征、血气变化及并发症.结果 治疗后1 h,患儿症状体征明显好转;6、12及24 h,3组患儿的血气较治疗前显著改善,NIMV、常规机械通气及CPAP比较,差异无显著性(P＞0.05).但治疗过程中NIMV组的肺部感染及慢性肺疾病的发生率明显低于机械通气组[(8%vs 36%)、(20%vs 72%)],且NIMV组的反复呼吸暂停和二氧化碳潴留的发生率也明显低于常规CPAP组[(8%vs 36%)、(20%vs72%)].结论 应用NIMV治疗早产儿肺透明膜病既可减少或避免呼吸机相关性肺炎、慢性肺病等并发症,又可治疗早产儿常发生的反复呼吸暂停,避免二氧化碳潴留.     

Early and late surfactant treatments in baboon model of hyaline membrane disease

Because the issue of optimal time for artificial surfactant therapy for hyaline membrane disease has not been established, the effects of treatment with a reconstituted bovine surfactant (surfactant TA) were compared at two time periods in a hyaline membrane disease model in a premature baboon. The baboons were delivered by cesarean section at 75% of gestation (139.5 +/- 1.5 days, mean +/- SD). One group was treated with surfactant TA within ten minutes after birth (ultraearly), another group was treated at two hours of age (late) and a third (comparison group) did not receive the surfactant. Both treatment groups had significantly higher compliance and ratio of arterial to alveolar Po2 ratio and lower mean airway pressure and oxygen requirement (Fio2) than the comparison group. At autopsy, the largest residual volume and hysteresis in pulmonary pressure-volume curves were noted in the ultraearly group, intermediate values were found in the late group, and least values were found in the comparison group. These data indicate that early surfactant therapy for hyaline membrane disease results in greater improvement in lung mechanics than delaying treatment, even for two hours. Delivery room treatment with surfactant of infants at risk for hyaline membrane disease is perhaps better than therapy for established hyaline membrane disease.     

Neonatology in the 1990's: surfactant replacement therapy becomes a reality

It has been more than 35 years since the lung was discovered to be lined with a layer of surface-active material that is important in lung stability and mechanics of respiration. The absence of this "anti-atelectasis" factor was proposed by Avery and Mead in 1959 to be the cause of hyaline membrane disease of premature infants. An indepth historical review of pulmonary surfactant by Tierney was recently published. In the years since 1959, there has been an exhaustive amount of research aimed at elucidating the structure and function of pulmonary surfactant, the ultimate goal being a safe and effective exogenous surfactant for the treatment of the Respiratory Distress Syndrome (RDS). The days of surfactant research are far from over, but the era of surfactant replacement therapy is now upon us. The practitioner needs to be knowledgeable about surfactant and aware of his or her role in surfactant therapy for premature infants. The following is intended to clarify some of the important issue of surfactant replacement.     

Randomized controlled trial of exogenous surfactant for the treatment of hyaline membrane disease

We conducted a prospective, randomized, unblinded, controlled trial of exogenous bovine surfactant (surfactant TA) in premature infants requiring ventilator support for the treatment of severe hyaline membrane disease. Forty-one low birth weight infants with severe hyaline membrane disease were randomly assigned to saline or surfactant therapy and treated within eight hours of birth. Significant improvements in oxygenation (increased arterial/alveolar PO2) and respiratory support (decreased mean airway pressure) were seen in the group receiving surfactant within four hours after treatment. These improvements were maintained in the surfactant-treated infants, who also had fewer pneumothoraces and fewer number of days in environments of fractional inspiratory oxygen greater than 0.4 mm Hg. No problems were associated with administration of surfactant, and no acute side effects were detected. We conclude that exogenous surfactant, administered early in the course of severe hyaline membrane disease, is an effective therapy that can diminish the amount of respiratory support required during the first 48 hours of life.     

Hyaline Membrane Disease: II: Lung Lecithin

The lecithin content of lung, together with its surface tension properties, were determined in 34 stillbirths, and 61 neonatal deaths. Lecithin content ranged widely from 1·5 to 18·6% of dry lung tissue.In 24 cases the `palmitic-lecithin'' was also measured; it formed 44-79% of the total lecithins. Since the two were related linearly, changes in palmitic-lecithin could be adequately studied by measuring total lecithins.Lecithin content was negatively correlated with minimum surface tension of lung extract in both fresh stillbirths and neonatal deaths. Cases with hyaline membranes had lung lecithin in the lower range (< 8% dry tissue). Lung lecithin content may be a measure of surfactant reserve.After 29 weeks'' gestation, fresh stillbirths and neonatal deaths, other than those with hyaline membranes, had normal lung surfactant. The exception was a small group of infants having immature lungs lacking surfactant, and who survived less than 2½ hours; some of these, it is surmised, would have developed hyaline membranes had they survived longer. This was consistent with the fact that well-formed hyaline membranes were only found in infants that had survived for at least 3 hours.Surfactant deficiency probably develops only after birth (except in very immature infants), and as a consequence of an initial rapid consumption of surfactant to form a lining layer covering the alveolar surface, when a gas-liquid interface is created by aeration of lung. Surfactant deficiency, by promoting interstitial pulmonary oedema, is thought to be the immediate cause of hyaline membrane disease.A scheme for the pathogenesis of hyaline membrane disease is set out. It provides a possible mechanism for the different ways in which surfactant deficiency may arise in immature and mature infants.Cases where hyaline membranes occur with normal surfactant fall into three groups: (1) Cases with hyaline membrane disease that have survived several days, the lungs being in the stage of repair. (2) Cases with massive lung haemorrhage, with severe anaemia from haemolytic disease, or with heart failure; extravasation of oedema fluid or blood may be the common factor in this group. (3) Infants of diabetic mothers.     

Lung volume and pulmonary blood flow measurements following exogenous surfactant

Lung function in eight infants with clinical and radiological features of surfactant defiency treated with exogenous porcine surfactant was studied before and at 15 min, 2h and 6h after the intratracheal administration of porcine surfactant. We measured alveolar-arterial oxygen tension difference, dynamic lung compliance, lung volume and effective pulmonary blood flow in all infants. The alveolar-arterial oxygen tension difference fell from a mean (SD) 43.3 (14.5) kPa before treatment to 8.8 (8.8) kPa at 1 h and 12.2 (6.8) kPa 6h after treatment (P<0.001). There was no change in mean (SD) dynamic compliance (0.39 [0.10] ml/cmH₂O/kg pre dose; 0.36 [0.13] ml/cmH₂O/kg 6h post treatment). Accessible functional residual capacity and effective pulmonary blood flow were measured using an adaptation of the argon/freon rebreathing method and showed an increase in mean (SD) functional residual capacity from 7.5 (1.4) ml/kg predose to 10.8 (3.3) ml/kg within 15 min of treatment, 11.4 (3.4) ml/kg 2h later and 12.7 (3.1) ml/kg 6h after treatment (P=0.009). Mean (SD) effective pulmonary blood flow values did not differ significantly, changing from 78.2 (20.9) ml/kg per min predose to 88.7 (24.1) ml/kg per min 15 min post dose, 87.6 (21.7) ml/kg per min 2h post dose and 90.0 (22.7) ml/kg per min 6h post dose (P=0.711).Conclusion The improvement in oxygenation after surfactant treatment is associated with an increase in lung volume but is not related to an improvement in dynamic lung compliance or effective pulmonary blood flow. The change in lung volume is detectable within 15 min of administration of the surfactant.     

The significance of recurrent lung opacities in neonates on surfactant treatment for respiratory distress syndrome

Purpose. To determine the significance of recurrent opacities in chest radiographs of neonates on surfactant therapy for respiratory distress syndrome (RDS) after an initial period of improvement.¶Materials and methods. Serial pre- and post-surfactant chest radiographs on 94 preterm infants with RDS were analyzed and the pattern of chest radiographic response was classified as (a) clear, (b) recurrent opacities, and (c) no response. Their clinical characteristics were also recorded.¶Results. In 34 infants the RDS changes cleared within 3 days. 31 infants developed lung opacities within 10 days after an initial period of improvement. Twenty-nine infants failed to respond to the surfactant. The corresponding mean birth weights for the three groups were 1.74, 1.19, and 0.76 kg and the mean gestation ages 32.6, 27.7, and 25.4 weeks. The incidence of bronchopulmonary dysplasia (BPD) was highest among the slumping infants (72. % vs 50 % in no responders, P < 0.001)¶Conclusions. The pattern of chest radiographic response is primarily affected by gestation age and birth weight. Recurrent lung opacity after an initial positive response to surfactant therapy may be caused by such factors as edema from barotrauma and patent ductus arteriosus. Infants with intraventricular hemorrhage may demonstrate neurogenic edema. Other contributory factors include pneumonia and abnormal consumption of surfactant. Recurrent lung opacities after surfactant may be a predictor of chronic lung disease in the preterm infant.     

Treatment of severe meconium aspiration syndrome with porcine surfactant: a multicentre, randomized, controlled trial

Aim: A randomized, controlled clinical trial was performed in 19 Chinese neonatal intensive care units to evaluate the safety and efficacy of exogenous surfactant replacement therapy for severe meconium aspiration syndrome (MAS) in term and near‐term neonates. Methods: Sixty‐one term infants with severe MAS were randomly assigned to either a surfactant or a control group within 36 h after birth. The infants in the surfactant group (n=31) received an initial dose of porcine lung‐derived surfactant (Curosurf®) at 200 mg/kg, and repeated doses of 200, 100 and 100 mg/kg were given at 6–12 h intervals to a maximum of four doses if oxygenation index (OI) deteriorated by >2 from baseline. The primary outcomes were a reduction of OI to less than 10 and an increase of the pre‐treatment a/A PO₂ ratio of 100% over baseline 24 h after surfactant treatment. The secondary outcomes were duration of mechanical ventilation, incidence of complications and survival to discharge from hospital. Results: The general demographic characteristics of the study subjects were similar. There was a trend for surfactant‐treated infants to have an improvement in arterial oxygenation compared to the control group. In comparison with the control group at 24 h, the surfactant group had a lower mean OI (8.1 vs 10.9), more infants with a 100% increase of a/A PO₂ (83% vs 48%, p<0.01) over baseline, and a larger area under the curve for PaO₂/FiO₂ over baseline (3762±1877 vs 2715±1644 mmHg^.h, p<0.05). Repeated measures of these parameters were also in favour of the surfactant group during 24 h to 3 and 7 d compared to the baseline (p<0.05). No differences were found in mean duration of mechanical ventilation, incidence of major complications and number of survivors between the two groups. Conclusion: Surfactant replacement therapy improved oxygenation in the study subjects, suggesting that surfactant may have a role in the treatment of severe MAS in term and near‐term infants.     

Comparison of chest radiography and static respiratory compliance in the assessment of the severity of pulmonary diseases in newborns with respiratory distress

In 55 newborn infants with respiratory distress syndrome (RDS) we compared chest radiographs and static respiratory compliance to see which of the two methods would best characterize the severity of pulmonary disease. There was a significant correlation between radiological score and compliance (r_s=−0.5776,n=55,p<0.001). Healthy newborns, newborns with RDS who did not need artificial ventilation and those newborns who needed respirator treatment had significantly different values of radiological score and compliance. RDS may be differentiated into groups of diagnoses. Newborns with HMD could be separated from those with wet lung syndrome or aspiration pneumonia by analyzing the radiogram or measuring the compliance. When survivors are compared with those newborns who died, the static respiratory compliance alone could predict the final outcome.     

Diagnostic imaging of primitive neuroectodermal tumour of the chest wall (Askin tumour)

Objectives. To describe the radiological features of primitive neuroectodermal tumour (PNET) of the chest wall (Askin tumour) at diagnosis and to analyse the radiological changes occurring as a consequence of treatment and during follow-up. Materials and methods. Nine children with histologically proven PNET were studied. At diagnosis, all patients underwent chest X-ray (CXR), chest CT and bone scintigraphy; three patients also had MR and three had US. During treatment and follow-up, CT was performed in all patients. Results. CT demonstrated a solid heterogeneous chest wall mass in all children at diagnosis and six had a rib lesion. Small nodular densities in the extra-pleural fat were identified in three patients at diagnosis. US, performed in three patients, excluded tumour infiltration of the lung or diaphragm, which had been suspected on CT. On MR, the lesions showed high signal intensity in T1-weighted/proton-density images and intermediate/high signal intensity in T2-weighted images compared with muscle. Minimal chest wall involvement was demonstrated in one case by MRI. Extensive necrosis of tumour mass with pseudo-cystic appearance was documented in the five patients who underwent chemotherapy. Macroscopically complete resection was performed in five patients but there was early local recurrence after surgery in two, identified by CT in one and by MR in the other. Conclusions. PNET of the chest wall should be considered in a child with a chest wall mass. CT is valuable for evaluating tumour extension at diagnosis, the effects of chemotherapy and assessing tumour recurrence after surgery. However, CT can overestimate pleural, lung or diaphragmatic infiltration, which are better evaluated by US. MR was superior to CT in the evaluation of tumour extension in one of three patients and may be considered complementary to CT, particularly in very large chest wall tumours. Received: 23 May 1997 Accepted: 23 February 1998