[Relationship between serum estradiol levels in the early postnatal period and the occurrence of hyaline membrane disease and bronchopulmonary dysplasia in neonates].

OBJECTIVE: This study examined the changes of serum levels of estradiol during the early postnatal period in neonates in order to investigate the possible relationship between the serum estradiol levels and the occurrence of pulmonary hyaline membrane disease (HMD) and bronchopulmonary dysplasia (BPD). METHODS: Fifty-nine premature infants with the gestational age between 26 and 32 weeks and 61 full-term infants with the gestational ages between 37 and 42 weeks were enrolled. Serum levels of estradiol were measured on postnatal days 1, 3 and 7. RESULTS: Serum levels of estradiol decreased rapidly after birth in both premature and term infants and there were significant differences among different postnatal ages groups. However, there were no significant differences in the serum estradiol levels between the premature and term groups on postnatal days 1, 3 and 7. Serum estradiol levels measured in premature infants with HMD were not statistically different from those in premature infants without HMD on all time points. Serum estradiol levels in premature infants with BPD were higher than those in premature infants without BPD on postnatal day 3, but there were no noticeable differences on postnatal days 1 and 7. CONCLUSIONS: Serum estradiol levels decline rapidly within 7 days after birth in both premature and term infants. Serum estradiol levels in the early postnatal period are not associated with the occurrence of HMD and BPD, suggesting that serum estradiol in the early postnatal period can not be used as a marker for predicting the development of HMD and BPD.

[Treatment of hyaline membrane disease in the preterm newborn with exogenous lung surfactant: a controlled study]. / Estudio controlado del tratamiento de la enfermedad de membrana hialina del recién nacido pretérmino con surfactante pulmonar exógeno (porcino vs. bovino).

BACKGROUND: Hyaline membrane disease (HMD) due to lung surfactant deficiency in the preterm newborn is an important cause of neonatal morbidity and mortality. Exogenous lung surfactant has transformed HMD therapy in developed countries, but an equivalent benefit has not been accomplished in developing countries due to a variety of factors. Porcine surfactant developed in Cuba is an inexpensive alternative to other surfactants, and its use has not been studied in our settings. METHODS: A randomized, open, prospective and controlled trial was undertaken in 44 preterm newborns with HMD diagnosis. One group received bovine surfactant (BS) (Survanta) and the other Cuban porcine surfactant (PS) (Surfacen). The following clinical response variables were evaluated: oxygenation and ventilation indexes, days with supplementary oxygen, days with mechanical ventilation, incidence of complications, time of hospitalization, and mortality. RESULTS: 23 Patients received bovine surfactant and 21 the porcine type. The two groups were clinically similar, with patterns of oxygenation and ventilation response that were the same between groups, with a tendency to higher initial oxygenation increase in the PS group. The incidence of complications was similar between groups. 10 Patients (47.6%) died in the PS group, versus 12 (52.2%) in the BS group (p > 0.05). CONCLUSIONS: Porcine surfactant had similar clinical effects than bovine surfactant in the oxygenation and ventilation variables, with no significant differences in complications ormortality. Porcine surfactant is an effective and lower cost altenative to bovine surfactant in the treatment of HMD.

Estudio controlado del tratamiento de la enfermedad de membrana hialina del recién nacido pretérmino con surfactante pulmonar exógeno (porcino vs. bovino) / Treatment of hyaline membrane disease in the preterm newborn with exogenous lung surfanctant. A controlled study

Introducción: La enfermedad de membrana hialina (EMH) por deficiencia de surfactante pulmonar en el neonato prematuro es una causa importante de morbimortalidad. El surfactante pulmonar exógeno ha revolucionado el tratamiento de esta entidad en países desarrollados, aunque este beneficio ha sido menor en países en vías de desarrollo. El surfactante porcino de manufactura cubana es económico, y su uso comparado con otros surfactantes es desconocido. Material y métodos: Se llevó a cabo un estudio prospectivo, controlado, aleatorizado, abierto, en 44 recién nacidos prematuros con EMH. Un grupo recibió surfactante bovino (SB) (Survanta), y el otro surfactante porcino (SP) de fabricación cubana (Surfacen). Se evaluó la respuesta en variables de oxigenación y ventilación, días de oxígeno suplementario, ventilación mecánica, incidencia de complicaciones, tiempo de hospitalización y mortalidad. Resultados: 23 pacientes recibieron el surfactante bovino, y 21 el porcino. Los dos grupos fueron similares clínicamente y en sus patrones de respuesta de oxigenación y ventilación, con una tendencia a mayor incremento inicial en la oxigenación en el grupo tratado con SP. La incidencia de complicaciones fue similar en los dos grupos. Fallecieron 10 pacientes (47.6%) en el grupo SP, y 12 (52.2%) en el grupo SB (p>0.05). Conclusiones: El surfactante porcino tuvo efectos clínicos similares al bovino en las variables de oxigenación y ventilación estudiadas; no hubo diferencia significativa en complicaciones y mortalidad. El surfactante porcino es una alternativa efectiva y de menor costo que el surfactante bovino para el tratamiento de la EMH.

Background: Hyaline membrane disease (HMD) due to lung surfactant deficiency in the preterm newborn is an important cause of neonatal morbidity and mortality. Exogenous lung surfactant has transformed HMD therapy in developed countries, but an equivalent benefit has not been accomplished in developing countries due to a variety of factors. Porcine surfactant developed in Cuba is an inexpensive alternative to other surfactants, and its use has not been studied in our settings. Methods: A randomized, open, prospective and controlled trial was undertaken in 44 preterm newborns with HMD diagnosis. One group received bovine surfactant (BS) (Survanta) and the other Cuban porcine surfactant (PS) (Surfacen). The following clinical response variables were evaluated: oxygenation and ventilation indexes, days with supple mentary oxygen, days with mechanical ventilation, incidence of compli cations, time of hospitalization, and mortality. Results: 23 Patients received bovine surfactant and 21 the porcine type. The two groups were clinically similar, with patterns of oxygenation and ventilation response that were the same between groups, with a tendency to higher initial oxygenation increase in the PS group. The incidence of complications was similar between groups. Ten Patients (47.6%) died in the PS group, versus 12 (52.2%) in the BS group (p>0.05) Conclusions: Porcine surfactant had similar clinical effects than bovine surfactant in the oxygenation and ventilation variables, with no significant differences in complications or mortality. Porcine surfactant is an effective and lower cost alternative to bovine surfactant in the treatment of HMD.

Deposition of whole blood platelets on extracellular matrix under flow conditions in preterm infants.

BACKGROUND: A previous study showed greater adhesion by platelets of healthy full term infants to subendothelial extracellular matrix (ECM) under flow conditions compared with healthy adult platelets. AIM: To investigate the adhesion and aggregation of platelets from preterm infants on ECM under defined shear conditions. METHODS: In vitro platelet function was investigated in 106 preterm infants, 74 full term infants, and 26 healthy adults. Blood samples were obtained from all infants within 24 hours of birth, and weekly until discharge from preterm infants only. Citrated whole blood was placed in ECM precoated tissue culture plates and subjected to shear stress (1300 s-1) for two minutes using a rotating Teflon cone. Platelet adhesion (surface coverage) and aggregation (average size) to ECM were assayed using an image analyser. Assays for von Willebrand factor (vWF) antigen, ristocetin cofactor, and vWF collagen-binding activity were performed on samples from an additional 70 preterm infants, 23 healthy full term infants, and 24 healthy adults. Preterm infants with hyaline membrane disease (HMD) were analysed separately in both cohorts. RESULTS: Platelets from preterm infants displayed significantly less platelet adhesion than those from full term infants but similar aggregation and levels of vWF antigen, ristocetin cofactor, and collagen binding activity. Mean surface coverage was 22.0 (8.4)% for preterm infants with HMD, 28.7 (8.0)% for healthy preterm infants, and 35.7 (7.9)% for full term infants. Surface coverage in the preterm infants correlated with gestational age during the first 24 hours only, and did not reach full term levels during 10 weeks of follow up. CONCLUSION: Platelet adhesion to ECM is significantly poorer in preterm than in full term infants, and poorer in preterm infants with HMD than in healthy preterm infants. Intrinsic platelet properties rather than the concentration or activity of vWF may be responsible for this difference.

Pulmonary surfactant-associated protein A levels in cadaveric sera with reference to the cause of death.

Pulmonary surfactant-associated protein A (SP-A) is an exclusively lung specific protein, and is considered to leak into the blood stream in alveolar septal damage. In this study we examined the serum SP-A level in forensic autopsy materials using an enzyme immunoassay with monoclonal antibodies to assess the postmortem level in relation to the cause and mode of death. Although a gradual postmortem degradation should be taken into consideration, topological relationship of serum level seemed to be fairly stable (arterial> or =venous blood in most cases), indicating no evident influence of postmortem diffusion. Significant elevation of serum SP-A (76.7-250 ng/ml in left heart blood) was observed in hyaline membrane diseases from various causes independent of the postmortem intervals (<30 h). However, mean SP-A levels in postmortem heart blood were usually low in asphyxia including hanging, strangulation and choking (left, 25.5 ng/ml; right, 22.3 ng/ml), polytrauma (left, 13.1 ng/ml; right, 9.0 ng/ml) and stab wound to the neck (left, 34.1 ng/ml; right, 29.4 ng/ml). Prominent elevation was noted in a case of fatal strangulation with complication of idiopathic interstitial pneumonia, and also in some deaths due to drowning, burns in fires, blunt and gunshot chest injuries. These findings indicated that postmortem elevation of serum SP-A levels was associated with alveolar septal damage due to inflammation, mechanical and physical stresses, which caused leakage of SP-A into the bloodstream.

The effect of selenium supplementation on outcome in very low birth weight infants: a randomized controlled trial. The New Zealand Neonatal Study Group.

BACKGROUND: Low selenium (SE) status has been documented in preterm infants and has been suggested to be a risk factor for chronic lung disease. METHODS: A total of 534 infants with birth weight <1500 g were enrolled in 8 New Zealand centers in a double-blind placebo-controlled randomized trial of SE supplementation from week 1 of life until 36 weeks' postmenstrual age or discharge home. Supplemented infants received 7 microg/kg/d of SE when fed parenterally and 5 microg/kg/d when fed orally. Plasma SE and glutathione peroxidase concentrations were measured in mothers after delivery and in infants before randomization and at 28 days and 36 weeks' postmenstrual age. Primary outcome measures were oxygen dependency at 28 days and total days oxygen dependency. RESULTS: No significant differences were seen between the groups with respect to primary or secondary outcome measures, with the exception that fewer supplemented infants had an episode of sepsis after the first week of life (P <.038). Mean plasma SE concentrations were 0.33 micromol/L before randomization in both groups and at 28 days had risen in the supplemented group (0.56 micromol/L) but fallen in the control group (0.29 micromol/L) (P <.0001). There was no association between outcome measures and SE concentrations at 28 days or 36 weeks' postmenstrual age. However, lower maternal and infant prerandomization SE concentrations were associated with increased respiratory morbidity. CONCLUSIONS: Postnatal SE supplementation in very low birth weight infants did not improve neonatal outcome. Further investigation of SE supplementation of mothers from the second half of pregnancy is warranted.

Haemodynamic effects of altering arterial oxygen saturation in preterm infants with respiratory failure.

AIMS: To examine the haemodynamic effects of brief alteration in arterial oxygenation in preterm infants with respiratory failure. METHODS: Eighteen preterm infants with respiratory failure, aged 9-76 hours, underwent detailed Doppler echocardiographic assessment at 86%, 96%, and 100% SaO2, achieved by altering the FIO2. Sixteen were receiving intermittent positive pressure ventilation, median FIO2 0.45 (0.20-0.65), median mean airway pressure 12 cm H2O (0-20). SaO2 was stable for 15 minutes at each stage. Four parameters of pulmonary arterial pressure were measured: peak velocity of tricuspid regurgitation and peak velocity of left to right ductal flow, TPV:RVET ratio and PEP:RVET ratio, measured at the pulmonary valve, along with flow velocity integrals at the aortic and pulmonary valves, and systemic arterial pressure. Ductal size was graded into closed, small, moderate, large with imaging, pulsed and continuous wave Doppler. RESULTS: Between 86% and 96% SaO2, there were no consistent changes, but in three of the 12 with a patent ductus arteriosus (PDA) there was ductal constriction, with complete closure in one. Between 96% and 100% SaO2, peak ductal flow velocity rose significantly in four of eight with a PDA. Ductal constriction occurred in four infants; in three this was associated with a significant fall in aortic flow integral and a rise in aortic pressure (4-6 mm Hg). Overall, 11 infants went from 86% to 100% SaO2 and pulmonary arterial pressure fell significantly in seven. CONCLUSION: A brief rise in SaO2 within the range maintained by most neonatal units can cause significant ductal constriction. The fall in pulmonary arterial pressure with 100% SaO2 seen in most infants was associated with a fall in pulmonary blood flow (or no change), rather than a rise, indicating that the dominant haemodynamic effect was ductal constriction rather than pulmonary vasodilation.

Effects of inhaled nitric oxide on pulmonary edema and lung neutrophil accumulation in severe experimental hyaline membrane disease.

To determine the effects of inhaled NO (iNO) on pulmonary edema and lung inflammation in experimental hyaline membrane disease (HMD), we measured the effects of iNO on pulmonary hemodynamics, gas exchange, pulmonary edema, and lung myeloperoxidase (MPO) activity in extremely premature lambs (115 d of gestation, 0.78 term). In protocol 1, we measured the effects of iNO (20 ppm) on lung vascular endothelial permeability to 125I-labeled albumin (indexed to blood volume using 57Cr-tagged red blood cells) during 1 h (n = 10) and 3 h (n = 14) of conventional mechanical ventilation with FiO2 = 1.00. In comparison with controls, iNO improved pulmonary hemodynamics and gas exchange, but did not alter lung weight-to-dry weight ratio or vascular permeability to albumin after 1 or 3 h of mechanical ventilation. To determine whether low dose iNO (5 ppm) would decrease lung neutrophil accumulation in severe HMD, we measured lung MPO activity after 4 h of mechanical ventilation with or without iNO (protocol 2). Low dose iNO improved gas exchange during 4 h of mechanical ventilation (PaO2 at 4 h: 119 +/- 35 mm Hg iNO versus 41 +/- 7 mm Hg control, p < 0.05), and reduced MPO activity by 79% (p < 0.05). We conclude that low dose iNO increases pulmonary blood flow, without worsening pulmonary edema, and decreases lung neutrophil accumulation in severe experimental HMD. We speculate that in addition to its hemodynamic effects, low dose iNO decreases early neutrophil recruitment and may attenuate lung injury in severe HMD.

Surfactant therapy prior to the interhospital transport of preterm infants.

The risk-to-benefit ratio of surfactant treatment of outborn preterm infants prior, as opposed to after, transportation to a perinatal center is not known. The objective of this study was to document current practice and to examine clinical outcomes in North America. In phase I (December, 1991 to January, 1992) questionnaires were distributed to 114 perinatal centers in the United States and Canada. The centers returned 98 surveys. Over half (50.5%) of the centers report giving surfactant rescue prior to infant transport, but only a minority (9.5%) of the centers report doing so for prophylaxis. In phase II (January, 1992 to December, 1992), clinical outcomes of surfactant-eligible babies requiring interhospital transport at a university hospital were evaluated to determine which infants ultimately received surfactant and when. The infants were compared between groups and did not differ significantly in gestational age, birthweight, sex type, number of multiple births, five-minute Apgar scores, or whether antenatal steroids were used. In phase II, the 66 consecutive, ventilator-dependent, outborn infants with average, and median, gestational age of 28 weeks were compared. The infants receiving surfactant prior to transport, when compared to the infants that got it after transport (9 hours later), did not do any better. There was 6% more survival without bronchopulmonary dysplasia in the group receiving surfactant after transport (65.2% versus 59.3%, p = 0.665). The infants receiving surfactant after transport were off the ventilator sooner (95% C.I. 6.0-28.7 versus 11.8-25.9 days) and discharged from the perinatal center earlier (95% C.I. 37.8-70.8 versus 47.9-69.0 days). Furthermore, arterial blood gases before and after transport reveals that there were no short-term advantages in administering surfactant prior to transport when compared to waiting for reevaluation at the perinatal center. These findings suggest that surfactant can be used safely prior to the interhospital transport of preterm infants, but this treatment does not seem to confer benefit over waiting for reevaluation, and possible surfactant treatment, at the tertiary perinatal center.

Extravascular coagulation and fibrin deposition in acute lung injury.

Extravascular fibrin deposition is characteristic of the acute inflammatory response and is, for example, prominent in the alveolar compartment of patients with the adult respiratory distress syndrome. Fibrin deposition in the injured lung is regulated by a balance of locally expressed pathways of coagulation and fibrin clearance, called fibrinolysis. These pathways comprise part of the interactive network of responses that influence local inflammatory cell traffic, microvascular permeability, and repair mechanisms. In this sense, fibrin turnover in the lung extends beyond traditional hemostasis and may influence the acute inflammatory response and resolution. Within the injured alveolar compartment, fibrin deposition is initiated by increased activity of the extrinsic coagulation pathway-tissue factor associated with factor VII. Activation of the contact and intrinsic coagulation pathways also occurs. Local fibrinolysis is generally impaired, which may potentiate extravascular fibrin deposition. Fibrin turnover in the adult mammalian lung is similarly disrupted in several forms of injury but differs from the injury that occurs in the lungs of premature infants with respiratory distress.

Plasma cysteine concentrations in infants with respiratory distress.

Because factors that predispose infants to persistent pulmonary hypertension of the newborn (PPHN) may cause oxidant stress, which in turn may increase demands for cysteine and glutathione, we investigated the availability of cysteine and its precursors in PPHN and related disorders. Plasma concentrations of four sulfur-containing and two non-sulfur-containing amino acids were measured by gas chromatography-mass spectrometry in blood from infants with PPHN, both those managed conventionally (PPHN group) and those treated with extracorporeal membrane oxygenation, as well as from infants with hyaline membrane disease. Concentrations also were measured in umbilical venous cord blood samples from a healthy control population, in venous plasma from infants receiving only intravenously administered glucose-containing solutions because they had noncardiopulmonary illnesses ("fasted" group), and from otherwise healthy, orally fed infants ("fed" group). The plasma total cyst(e)ine concentration was markedly lower in the three groups (PPHN, PPHN and extracorpeal membrane oxygenation, and hyaline membrane disease) receiving an elevated inspired oxygen concentration (0.6 to 1.0) than in fasted or fed control infants. In contrast, levels of plasma methionine, the other major sulfur amino acid, were low in the three groups receiving an elevated inspired oxygen concentration, as well as in fasted infants. Glycine and serine, two non-sulfur-containing amino acids, had a pattern similar to that of plasma methionine. Thus infants with PPHN and hyaline membrane disease have low plasma total cyst(e)ine levels, an effect that does not appear to result primarily from nutritional deprivation. We speculate that the role of cysteine in bioactivation of nitric oxide and as a precursor of glutathione may be relevant to the pathogenesis and evolution of PPHN and respiratory distress syndrome. Further studies are needed to determine whether increased demands for cysteine exist in these disorders.

Ventilation-perfusion relationships in preterm infants after surfactant treatment.

Arterial-alveolar partial pressure differences for oxygen, carbon dioxide, and nitrogen were measured before and after surfactant replacement therapy on 15 occasions in 14 ventilator-dependent preterm infants with hyaline membrane disease (HMD). Eight treatments resulted in a significant improvement in arterial partial pressure of oxygen (PaO2) 2 hr after treatment; 7 did not. Neither group showed any significant change in arterial-alveolar partial pressure differences for oxygen, nitrogen, and carbon dioxide. This observation suggests that if surfactant replacement therapy produces an improvement in PaO2 it does so by recruitment of atelectatic alveoli with a balanced ventilation/perfusion ratio rather than by redistribution of ventilation within already ventilated alveoli.

Avoidance of red blood cell transfusion in an extremely preterm infant given recombinant human erythropoietin therapy.

To avoid red blood cell (RBC) transfusions, recombinant human erythropoietin (rHuEPO) was given to an infant born at a gestation of 26 weeks and a birthweight of 830 g to parents who were Jehovah's Witnesses. The infant had hyaline membrane disease and required 52 days of assisted ventilation and 19 days of oxygen therapy. He received theophylline therapy for 61 days for recurrent apnoea and bradycardia. He developed bilateral intraventricular haemorrhage (IVH) and left-sided periventricular leucomalacia (PVL). Intravenous rHuEPO was started on day 1 at 200 U/kg per day for 1 month followed by subcutaneous rHuEPO 400 U/kg three times a week for 6 more weeks, supplemented with Vitamin E, folic acid and iron. Blood sampling was kept to a minimum and non-invasive blood-gas monitoring was used consistently. Consequently, the estimated cumulative volume of blood loss from sampling was only 21 mL during his hospital stay. His haemoglobin (Hb) was 150 g/L at birth and this fell to below 100 g/L from day 25 onwards. His lowest leucocyte count was 3.6 x 10(9)/L. He was discharged on day 83 with a Hb of 95 g/L, Hct of 29%, reticulocyte count of 2.8% and weight of 2400 g. At a postnatal age of 3 months, he had a Hb of 113 g/L. At 6 months, investigations showed: Hb 121 g/L, haematocrit 33%, reticulocyte 1% and a weight of 4.4 kg. He was readmitted to hospital once for an episode of vomiting and follow up to date showed developmental delay.(ABSTRACT TRUNCATED AT 250 WORDS)

Randomised double-blind controlled trial of effect of morphine on catecholamine concentrations in ventilated pre-term babies.

A sick premature baby who requires intensive care will undergo many uncomfortable procedures. It is now accepted that such babies perceive pain and need adequate analgesia, but little is known about the effects of sedation in these patients. We investigated the use of morphine to provide analgesia and sedation for ventilated preterm babies in a randomised, double-blind, placebo-controlled trial. 41 mechanically ventilated babies who had been treated with surfactant (Curosurf) for hyaline membrane disease were randomly assigned morphine in 5% dextrose (100 micrograms/kg per h for 2 h followed by 25 micrograms/kg per h continuous infusion) or 5% dextrose (placebo). Plasma catecholamine concentrations were measured 1 h after the first dose of surfactant and 24 h later. Blood pressure was measured at study entry and after 6 h. The morphine and placebo groups showed no differences in method of delivery, Apgar scores, birthweight, gestation, or catecholamine concentrations at baseline. Morphine-treated babies showed a significant reduction in adrenaline concentrations during the first 24 h (median change -0.4 [95% CI -1.1 to -0.3] nmol/L p < 0.001), which was not seen in the placebo group (median change 0.2 [-0.6 to 0.6] nmol/L, p = 0.79). There was a non-significant reduction in noradrenaline concentration in the morphine group. Blood pressure showed a slight but non-significant fall (median -4 mm Hg) in morphine-treated babies. The incidence of intraventricular haemorrhage, patent ductus arteriosus, and pneumothorax, the number of ventilator days, and the numbers of deaths did not differ significantly between the groups. Morphine, in the dose regimen we used, is safe and effective in reducing adrenaline concentrations in preterm ventilated babies.

Elevated immunoreactive endothelin-1 levels in newborn infants with persistent pulmonary hypertension.

To study the potential role of endothelin-1, a potent endothelium-derived vasoconstrictor peptide, in the pathophysiology of persistent pulmonary hypertension of the newborn (PPHN), we measured arterial concentrations of immunoreactive endothelin-1 (irET-1) in 24 neonates with PPHN. Secondary diagnoses included meconium aspiration syndrome (13 patients), sepsis (2), congenital diaphragmatic hernia (1), asphyxia (1), pulmonary hemorrhage (1), aspiration of blood (1), and respiratory distress syndrome (1). Compared with irET-1 levels in umbilical cord blood in normal infants (15.1 +/- 4.1 pg/ml; mean +/- SEM) and in newborn infants with hyaline membrane disease who were supported by mechanical ventilation (11.8 +/- 1.2 pg/ml), infants with PPHN had markedly elevated circulating irET-1 levels (27.6 +/- 3.6 pg/ml; p < 0.01 vs cord blood, hyaline membrane disease). Infants with severe PPHN requiring extracorporeal membrane oxygenation (ECMO) therapy had higher irET-1 levels than infants with milder disease (31.0 +/- 4.7 for ECMO-treated infants vs 21.2 +/- 2.0 for non-ECMO-treated infants; p < 0.05). In patients treated without ECMO, irET-1 progressively decreased during the following 3 to 5 days, paralleling clinical improvement. In contrast, irET-1 concentrations remained elevated in infants with severe PPHN during ECMO therapy. We conclude that circulating irET-1 levels are elevated in newborn infants with PPHN, are positively correlated with disease severity, and decline with resolution of disease in patients who do not require ECMO therapy. Whether endothelin-1 contributes directly to the pathophysiology of PPHN or is simply a marker of disease activity remains speculative.

[The therapeutic use of pulmonary surfactant in neonatal hyaline membrane disease]. / Uso terapéutico del surfactante pulmonar en la enfermedad de membrana hialina neonatal.

Preliminary report of our experience with the therapeutic use of pulmonary surfactant in newborn infants of less than 30 weeks gestation with hyaline membrane disease. The use of pulmonary surfactant was held under the "rescue" modality, with up to 36 hours of postnatal life. The blood gas changes are described and the assisted ventilation progress, as well as the general response on the clinical condition of each case. Discussion in centered in the risk of use and in the criteria for prescribing the therapeutic pulmonary surfactant. It is concluded that meeting the recommended requirements for its use, the pulmonary surfactant is a therapeutic alternative in the treatment of hyaline membrane disease in newborn infants of less than 33 weeks gestation, being different the immediate ventilatory response in terms of therapeutic control, with one or other forms of pulmonary exogenous surfactant, without differences in the final result.

Evaluation of complement activation in premature newborn infants with hyaline membrane disease.

Fifteen premature newborns with hyaline membrane disease causing acute respiratory distress were evaluated for complement activation. A high intrapulmonary right-to-left shunt and marked arterial-alveolar oxygen difference indicated the severity of the respiratory failure. Twenty preterm healthy infants served as controls. Total haemolytic activity, plasma concentrations of complement components and regulatory proteins (C3, C4, C1-inhibitor, factors H and I) as well as activation products (C3a, C3dg, C1rsC1-inhibitor, C3b(Bb)P) gave no evidence of significant complement activation. Functional activity of the ubiquitous regulatory protein C1-inhibitor was significantly reduced without impact on classical pathway activation. These data suggest that, in contrast to the adult form of respiratory distress syndrome, the low-pressure pulmonary oedema characterising hyaline membrane disease is not mediated by activation of the complement system.

Acute changes in vasoactive lipid mediators in experimental hyaline membrane disease.

Endothelial release of the arachidonate derivative PGI2 may be increased in response to cyclic lung stretching. We therefore sought to determine if the stable metabolite of PGI2, 6-keto-PGF1 alpha, would be found in increased quantities in primates ventilated with conventional mechanical ventilation (CMV) compared to treatment with high frequency oscillatory ventilation (HFOV). We also sought to determine if other membrane-derived vasoactive substances such as LTC4, PAF and TXB2 would be elevated in plasma and lung tissue of animals developing hyaline membrane disease (HMD) and if the levels would correlate with the severity of the respiratory distress. Twenty prematurely delivered monkeys were treated with either CMV or HFOV from the first breath after Cesarean delivery until sacrifice at 6 h of age. We found a significant increase from birth to 5 min and from 5 min to 5 h in 6-keto-PGF1 alpha, and a significant increase from 5 min to 5 h in TXB2. We found a significant decline from cord blood to 5 min of LTC4, without further change by 5 h. PAF was present in all plasma samples but showed no upward or downward trend. There was no difference in the 5-h plasma level or in the lung homogenate level of any of the lipid mediators between the two types of assisted ventilation. There was no correlation between any lipid mediator level and severity of the HMD, as measured by gas exchange, radiographic or histologic criteria, when assessed by each ventilator group alone or with both groups combined. We conclude that the immediate postnatal increases in TXB2 and PGI2 and decrease in LTC4 are not altered substantially by use of HFOV.

Simultaneous measurement of preductal and postductal oxygen saturation by pulse oximetry in hyaline membrane disease.

Preductal and postductal oxygen saturation were compared in 20 ventilated preterm infants with hyaline membrane disease to establish the frequency of right to left shunting and to assess the accuracy of postductus arteriosus blood gas sampling. One hundred and thirty eight comparisons were made and the frequency of right to left shunting was 17% (95% confidence interval 12 to 25%). Shunting episodes with possible preductal hyperoxia occurred far less commonly on a maximum of 5% of occasions. The findings in infants under 1000 g and of 24-28 weeks' gestation were not significantly different from larger or more mature infants. Shunting occurred significantly more frequently in very ill infants who subsequently died as a result of respiratory disease.

High frequency oscillatory ventilation in neonates with respiratory distress.

High frequency oscillatory ventilation (HFOV) was attempted in ten infants with severe respiratory failure not responding to conventional ventilation (CV); it was, therefore, used as a rescue measure. HFOV was successful in improving the respiratory status of seven infants, all with hyaline membrane disease (HMD). Five of these infants survived, of the remaining two, one died of massive peri/intra-ventricular haemorrhage and the other of cholestasis associated with total parenteral nutrition. It was unsuccessful in three infants, one with meconium aspiration, the second died within two hours commencing HFOV and the third with severe depression and hypotonia.