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.     

Intraventricular haemorrhage in the preterm infant without hyaline membrane disease.

The clinicopathological associations of 33 singleton infants who died with intraventricular haemorrhage (IVH) without hyaline membrane disease (HMD) (''IVH only'') were compared with those of 39 infants who died with IVH+HMD over the same gestation range in order to determine what factors other than those related to HMD may contribute to the pathogenesis of IVH. The incidence of ''IVH only'' was inversely related to gestational age in the Hammersmith birth population, whereas the incidence of IVH+HMD rose to a peak at 28-29 weeks'' gestation. Infants with ''IVH only'' lived longer on average than those with IVH+HMD despite a lower birthweight and shorter gestation. Infants who died in the first 12 hours from ''IVH only'' had suffered severe birth asphyxia but in those who died later the main symptom was recurrent apnoea. Fewer infants with asphyxia but in those who died later the main symptom was.recurrent apnoea. Fewer infants with ''IVH only'' were given alkali therapy or were connected to the ventilator as compared to those with IVH+HMD, but there were no differences in alkali therapy in those who lived for 12 hours or more. In the ''IVH only'' group there was a high incidence of haemorrhage from other sites and of bacterial infections. It is suggested that, in the absence of HMD, extreme immaturity is the main factor determining the occurrence of IVH. Birth asphyxia, apnoeic attacks, haemorrhage, and infections may play subsidiary roles, possibly through development of metabolic acidosis.     

Antecedents of periventricular haemorrhage in infants weighing 1250 g or less at birth.

Fifty infants who weighed 1250 g or less at birth were studied with serial real time cerebral ultrasound to evaluate the temporal relation of various perinatal factors to the onset and progression of periventricular haemorrhage (PVH). The significant antecedents of PVH were severe bruising at birth, low birthweight, short gestation, ratio of arterial oxygen pressure (PaO2) to fractional inspired oxygen (FiO2), and haematocrit on admission, hyaline membrane disease, assisted ventilation, pneumothorax, administration of tubocurarine, hypercapnia, hypoxaemia, and hypotension. Case control studies, in which infants with PVH at 26 weeks'' and 28 weeks'' gestation were compared with matched infants without PVH, confirmed that the antecedents identified were independent of gestational influences. A multivariate discriminant analysis for the antecedents of PVH showed that hyaline membrane disease, hypercapnia, and short gestation correctly classified presence or absence of PVH in 78% of the study group. A similar analysis comparing infants with germinal layer haemorrhage or intraventricular haemorrhage with those who developed intracerebral extension of haemorrhage showed that three factors found on admission (hypothermia, a low PaO2:FiO2 ratio, and severe bruising) combined to classify correctly 90% of the haemorrhages. Our data suggest that prevention of perinatal trauma and asphyxia as well as respiratory illness, especially hyaline membrane disease, and stabilisation of blood gas tensions, blood pressure, and haematocrit within the physiological range, are likely to be the most effective ways of preventing PVH in extremely preterm infants.     

Surfactant replacement therapy in neonates less than 32 weeks gestation: Effect on neonatal intensive care resource utilization

Abstract  The effect of synthetic surfactant (Exosurf) replacement on complications from hyaline membrane disease (HMD) in infants <32 weeks gestation and their resource utilization within a neonatal intensive care unit was studied in 1991-92. A control group was selected from infants admitted to the same unit during the preceding 3 years when Exosurf was not available. The infants were controlled for gestation, weight and severity of HMD.
Infants given Exosurf had a significant reduction in the incidence of pulmonary interstitial emphysema (PIE), and a marginal decrease in the incidence of pneumothorax. They required fewer days on the ventilator and consumed less of the scarce financial resources. There was no difference in the mortality rate among the two groups. The changes seen were more evident among those infants between 30 and 31 weeks gestation, compared to those <28 weeks.     

预防性经鼻持续气道正压对28～32孕周早产儿透明膜病的影响

目的 探讨早期经鼻持续气道正压(nCPAP)对28～32孕周早产儿肺透明膜病(HMD)的预防作用.方法 54例胎龄28～32周,出生体重小于1 500 g的早产儿在生后30 min内无论有无缺氧均用nCPAP进行呼吸管理,观察HMD的发生率及外源性肺表面活性物质(PS)和机械通气的应用率.结果 观察组HMD的发生率为44%(24/54),明显低于对照组的69%(33/48),P＜0.05,差异有显著性意义,但Ⅲ～Ⅳ级HMD的发生率,两组相比差异无显著性意义,(P＞0.05);观察组30%(16/29)需应用PS,明显少于对照组的50%(24/48),差异有显著性意义P＜0.05;机械通气率及颅内出血的发病率两组相比差异均无显著性意义(P＞0.05).结论 早期nCPAP对28～32孕周早产儿发生HMD有一定的预防作用,能减少外源性PS的应用,但不减少对机械通气的需要.     

Surfactant quantity and composition during recovery from hyaline membrane disease

The appearance of phosphatidylglycerol in the tracheal wash of infants with hyaline membrane disease (HMD) has been reported to be associated with clinical signs of recovery. We analyzed lung tissue and bronchoalveolar lavage surfactant in an animal model of HMD to determine whether phosphatidylglycerol or some other component is necessary for recovery. The amount and composition of phospholipid (PL) was determined in the premature Macaca nemestrina monkey (140 days' gestation) during an acute stage of HMD, and in two stages of recovery. These changes were compared to observations made in healthy premature controls (140 days), gestational age-matched fetuses (140 days), and fetuses of 150 days' gestation (term = 168 days). The amount of PL and its surfactant composition in lung homogenates of the right lower lobe and in lavage of the excised left lung was determined. Compared to 140-day fetuses, the healthy controls had a several-fold increase in lavage PL and disaturated phosphatidylcholine (DSPC) during the first few days of life (p less than 0.05). Prior to recovery, animals with HMD had no such increase in lavage PL or DSPC and demonstrated poor deflation stability. Recovery was associated with increased tissue and lavage PL (p less than 0.05) and increased fractions of phosphatidylinositol and DSPC (p less than 0.05), but not phosphatidylglycerol. The tissue compositional changes observed during recovery reflected maturational changes observed in the fetal animals studied at 10 days' greater gestational age.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hyaline membrane disease,alkali, and intraventricular haemorrhage.

The relation between intraventricular haemorrhage (IVH) and hyaline membrane disease (HMD) was studied in singletons that came to necropsy at Hammersmith Hospital over the years 1966-73. The incidence of IVH in singleton live births was 3-22/1000 and of HMD 4-44/1000. Although the high figures were partily due to the large number of low birthweight infants born at this hospital, the incidence of IVH in babies weighing 1001-1500 g was three times as great as that reported in the 1658 British Perinatal Mortality Survey. Most IVH deaths were in babies with HMD, but the higher frequency of IVH was not associated with any prolongation of survival time of babies who died with HMD as compared with the 1958 survey. IVH was seen frequently at gestations of up to 36 weeks in babies with HMD but was rare above 30 weeks'' gestation in babies without HMD. This indicated that factors associated with HMD must cause most cases of IVH seen at gestations above 30 weeks. Comparison of clinical details in infants with HMD who died with or without IVH (at gestations of 30-37 weeks) showed no significant differences between the groups other than a high incidence of fits and greater use of alkali therapy in the babies with IVH. During the 12 hours when most alkali therapy was given, babies dying with IVD received a mean total alkali dosage of 10-21 mmol/kg and those dying without IVH 6-34 mmol/kg (P less than 0-001).There was no difference in severity of hypoxia or of metabolic acidosis between the 2 groups. Babies who died with HMD and germinal layer haemorrhage (GLH) without IVH had received significantly more alkali than those who died with HMD alone, whereas survivors of severe respiratory distress syndrome had received lower alkali doses than other groups. It is suggested that the greatly increased death rate from IVH in babies with HMD indicates some alteration of management of HMD (since 1958) as a causative factor. Liberal use of hypertonic alkali solutions is the common factor which distinguishes babies dying with GLH and IVH from other groups of babies with HMD. Although the causal nature of this association remains unproved, it seems justifiable to lrge caution in alkali usage.     

Intraventricular haemorrhage in the preterm infant without hyaline membrane disease

The clinicopathological associations of 33 singleton infants who died with intraventricular haemorrhage (IVH) without hyaline membrane disease (HMD) ('IVH only') were compared with those of 39 infants who died with IVH+HMD over the same gestation range in order to determine what factors other than those related to HMD may contribute to the pathogenesis of IVH. The incidence of 'IVH only' was inversely related to gestational age in the Hammersmith birth population, whereas the incidence of IVH+HMD rose to a peak at 28-29 weeks' gestation. Infants with 'IVH only' lived longer on average than those with IVH+HMD despite a lower birthweight and shorter gestation. Infants who died in the first 12 hours from 'IVH only' had suffered severe birth asphyxia but in those who died later the main symptom was recurrent apnoea. Fewer infants with asphyxia but in those who died later the main symptom was.recurrent apnoea. Fewer infants with 'IVH only' were given alkali therapy or were connected to the ventilator as compared to those with IVH+HMD, but there were no differences in alkali therapy in those who lived for 12 hours or more. In the 'IVH only' group there was a high incidence of haemorrhage from other sites and of bacterial infections. It is suggested that, in the absence of HMD, extreme immaturity is the main factor determining the occurrence of IVH. Birth asphyxia, apnoeic attacks, haemorrhage, and infections may play subsidiary roles, possibly through development of metabolic acidosis.     

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.     

Effect of fibrinogen degradation products and lung ground substance on surfactant function

Acute lung injury syndromes have many characteristics including protein-rich alveolar edema, hyaline membranes, and abnormal surface tension at the alveolar air-liquid interface. Increased surface tension can occur because of a relative surfactant deficiency and/or dysfunction. It has been previously demonstrated that surfactant dysfunction occurs when plasma protein inhibitors leak into the alveolar space during the induction of the lung injury and edema formation. The present study investigated whether inhibitors that would be generated during the stage of repair from lung injury could impair surfactant function. We determined whether fibrinogen degradation products (FDP) which would be released during lysis of the fibrin(ogen)-containing alveolar exudate and hyaline membranes, and components of the lungs' ground substance could inhibit the in vitro function of a lipid extract surfactant preparation. FDP were prepared by incubating human fibrinogen with plasmin or neutrophil elastase for 4 min to 60 h and were characterized by SDS-PAGE. Early (fragment X and Y) and late (fragment D and E) plasmin-derived FDP (MW greater than 40,000) inhibited surfactant function as assessed by a bubble surfactometer. The early elastase-derived FDP also inhibited surfactant, but the later and much smaller fragments (MW less than 15,000) did not affect surfactant function. Laminin also inhibited surfactant in a dose-dependent manner. Neither hyaluronic acid nor heparan sulfate affected surfactant performance in vitro. We conclude that plasmin-induced lysis of intraalveolar fibrinogen and hyaline membranes will result in prolonged generation (i.e. days) of surfactant inhibitors.(ABSTRACT TRUNCATED AT 250 WORDS)     

Transcutaneous Measurement of Oxygen Tension in Infants with Hyaline Membrane Disease

Barr, P. A. (1979). Aust. Paediatr. J. , 15, 3–6. Transcutaneous measurement of oxygen tension in infants with hyaline membrane disease . Transcutaneous oxygen tension (tcPO2) using the Roche electrode, was compared with arterial oxygen tension (PaO2) from an indwelling arterial catheter or cannula in thirty-two infants with hyaline membrane disease. tcPO2 monitoring was performed by neonatal intensive care nurses for as long as seven days. Although the correlation of tcPO2 with PaO2 was good (r 0.713, P <.001), the tcPO2 monitor frequently failed to detect hypoxaemia and hyperoxaemia. Seventy-eight per cent of recorded PaO2 values < 50 mmHg were associated with tcPO2 values ≥ 50 mmHg and 41% of PaO2 values > 90 mmHg were associated with tcPO2 values ≤ 90 mmHg. tcPO2 measurement was not an acceptable alternative to PaO2 measurement. The incidence of hyperoxaemia in seven tcPO2 monitored infants with severe hyaline membrane disease (HMD) (5%) was significantly less than in five unmonitored infants with equally severe HMD (32%) (X², P < .001). tcPO2 monitoring was useful as a PaO2 trend recorder.     

Surfactant Replacement Therapy in Preterm Neonates: A Comparison of Postmortem Pulmonary Histology in Treated and Untreated Infants

New histological lesions have been reported in the lungs of preterm neonates treated with surfactant for respiratory distress syndrome (RDS). Globular deposits of hyaline material in parenchymal air spaces, absence of hyaline membranes, and increased interstitial cellularity and edema without associated fibrosis have been described. Fifteen histological findings were assessed in the lung pathology of 76 infants with RDS from three study groups. Group I (24 infants) died in the presurfactant era (before 1982), group II (26 infants) died despite having surfactant treatment, and group III (26 infants) were either untreated controls or did not receive surfactant for other reasons. The three groups were comparable in respect of sex and survival time. All infants were 34 weeks of gestation or less. Infants with a significant congenital abnormality or pulmonary hypoplasia were excluded. The 76 cases were assessed independently and “blindly” by two pathologists. The histological findings assessed were alveolar collapse; epithelial necrosis, proliferation, and metaplasia; hyaline membranes; dilated lymphatics; pulmonary interstitial emphysema; interstitial edema, inflammation, and fibrosis; arteriolar muscular hyperplasia; interstitial and intra-alveolar hemorrhage; massive pulmonary hemorrhage; and pneumonia. No significant differences were found in any of the histological findings between the three groups. The hyaline membranes seen in the surfactant-treated infants were identical to those in the untreated lungs and were of the characteristic linear type. Interstitial fibrosis, inflammation, and edema were present in all three groups. It has also been suggested that surfactant therapy protects preterm infants from interstitial hemorrhage but predisposes them to intra-alveolar hemorrhage. No significant difference in the incidence of intra-alveolar and interstitial hemorrhage in the three groups was identified.     

Growth of Japanese Fetuses -Analysis from the Viewpoint of Population and Biological Growth Curves-

In 1984, Peter Dunn postulated that infants from 28 weeks ‘gestation till 18 weeks’ postnatal age who grow normally have almost identical potential growth velocities, regardless of racial and geographic differences. He suggested that the straight line growth curve in this period could be used as a perinatal growth chart for international reference. We composed biological growth curves for Japanese fetuses by eliminating data with risk factors for fetal growth, and compared them with the curves of Dunn. Our conclusions are as follows: 1) Japanese population fetal growth curves correspond with the curve of Dunn between 28 and 38 weeks' gestation. 2) Even in ideal conditions, flattening of fetal growth after 38 weeks' gestation always occurs. 3) In the early postnatal period, infants grow with the same straight line velocity as during fetal growth between 28–38 weeks' gestation. Infants from 28 weeks' gestation to 18 weeks' postnatal age have an almost identical growth potential in spite of some degree of growth constraint in utero after 38 weeks' gestation.     

Different patterns of pulmonary sequelae after hyaline membrane disease: heterogeneity of bronchopulmonary dysplasia? A clinicopathologic study.

In an autopsy study of 37 infants who suffered from hyaline membrane disease (HMD), two distinct patterns of pulmonary lesions could be defined. One pattern, characterized by marked interstitial fibrosis in the absence of airway abnormalities, was labelled 'interstitial-type' histology. A second type, labelled 'bronchiolar-type' histology, showed marked airway lesions and alveolar emphysema. Nine patients of each type were analysed. Nineteen other patients had a 'mixed-type' histology and were not further studied. Retrospectively, the clinical and radiological characteristics of both series were analysed. No differences in birth weight, gestational age and initial radiological HMD grade could be demonstrated. The pulmonary function of the bronchiolar-type patients however was significantly worse at the onset, and these infants needed more oxygen and ventilatory support during the first 10 days of life. They all died from respiratory failure whereas 4 patients from the interstitial group had non-pulmonary fatalities. In the bronchiolar group chest X-rays showed atelectasis and pulmonary interstitial emphysema in the early stages, and hyperinflation with bullae and irregular streaky densities in the later. Patients in the interstitial group had no or minor emphysema with more homogeneously spread densities over both lungs. We conclude that both types of evolution represent two extremes of the bronchopulmonary dysplasia spectrum.     

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.     

影响机械通气治疗肺透明膜病患儿疗效的因素分析

目的探讨机械通气治疗新生儿肺透明膜病(HMD)的预后及其影响因素。方法回顾2002年1月至2006年1月我院新生儿重症监护室经机械通气治疗的116例肺透明膜病病例,分析其疗效,对治愈组和死亡组的胎龄、体重、胸片分级、入院时肛温、血pH、有无使用肺表面活性物质(PS)、呼吸机参数、并发症等对比分析。结果机械通气治疗HMD的治愈率是86·2%,早期酸中毒、上机时高吸气峰压(PIP)及肺出血等严重并发症是死亡率增加的危险因素,而同时采用PS替代治疗可以明显提高治愈率。结论机械通气是治疗HMD的重要手段,同时采用PS治疗可以取得更好疗效,早期酸中毒及上机时高PIP提示疗效较差,积极防治并发症可改善疗效。     

肺表面活性物质治疗肺透明膜病Ⅱ级的疗效评价

目的 探讨肺表面活性物质(PS)在治疗新生儿肺透明膜病(HMD)Ⅱ级的疗效。方法 对60例经X线胸片检查为HMDⅡ级的患儿。30例6小时内应用肺表面活性物质;30例无应用肺表面活性物质,通过用药后20小时(或约生后24小时)X线胸片的诊断与上呼吸机时间、并发症的比较分析,评价肺表面活性物质治疗肺透明膜病的疗效。结果 两组病例在生后24小时的X线胸片,平均上呼吸机时间,住院天数、死亡率,有显著性差异,P<0.05。并发症方面,肺炎发生率显著性差异,P<0.05。结论 PS在治疗HMD中可以明显改善肺透明膜病的转归,减少并发症,降低死亡率。     

Effects of tracheal instillation of natural surfactant in premature lambs. I. Clinical and autopsy findings

Ten pairs of twin lambs 118--122 days of gestation were given either natural surfactant or diluent endotracheally before the first breath. By using the premature twin lamb model, we have been able to show that instillation of natural surfactant produced 100% survival for the duration of the study period (2 hr); stable blood gases on room air; lungs that became increasingly compliant while on the respirator; generally well aerated lungs at autopsy; good lung pressure-volume relationships; normal lung surface tension measurements; and histologic evidence of good alveolar expansion with large amounts of free intraluminal phospholipid, no epithelial damage, and no hyaline membranes. It is concluded that tracheal instillation of natural surfactant into the premature lamb protects the lungs from developing many features characteristic of the respiratory distress syndrome.     

Bedside prediction of neonatal pulmonary maturity by single step gastric aspirate shake test

Single step gastric aspirate shake test was carried out on 400 newborns (300 term and 100 preterm)to evaluate its reliability in the prediction of hyaline membrane disease (HMD). Eighty five percent of preterm neonates with a negative shake test developed HMD. This was statistically significant (p<0.001). Two preterm babies with a positive shake test and one with an intermediate result developed hyaline membrane disease. Amongst term neonates in 6 cases the test was false negative. The reasons for the test being negative in these sixcases have been discussed. None of the term infants with a positive or intermediate shake test developed hyaline membrane disease.     

�׼�������α���������������ض���������͸��Ĥ���ٴ��۲�

目的 比较首荆不同剂量的肺表面活性物质(PS)时新生儿肺透明膜病(HMD)治疗效果的影响.方法 随机将2006年6月至2007年6月广东省妇幼保健院48例Ⅲ、Ⅳ级HMD早产儿分为两组:首刺大剂量组(PS治疗剂量150～200 mg/kg)和首剂小刺量组(Ps治疗剂量50～100 mg/kg).比较两组患儿用药次数、用药总剂量,使用6 h后血气分析,PaO2/FiO2,呼吸机通气治疗时间以及监护室住院时间等.结果 两组治疗用药总剂量差异无统计学意义,首剂大剂量组的机械通气时间、氧疗时间、监护室住院时间显著低于首剂小剂量组,治疗后6 h两组的PaO2,PaO2/FiO2均显著升高,但升高程度两组间差异无统计学意义.结论 PS首剂治疗量达150～200 mg/kg时治疗重度HMD的效果优于首剂治疗量为50～100 mg/kg,值得在临床中推广.