Search

Aim: We explored whether subnormal forced expiratory volume within 1 s (FEV 1 ) at 5-9 years of age was lower in children born preterm who received less invasive surfactant administration (LISA) rather than surfactant via an endotracheal tube., Methods: The multi-centre, randomised Nonintubated Surfactant Application trial enrolled 211 preterm infants born at 23-26 weeks of gestation from 13 level III neonatal intensive care units from April 2009 to March 2012. They received surfactant via LISA (n = 107) or after conventional endotracheal intubation (n = 104). The follow-up assessments were carried out by a single team blinded to the group assignments. The main outcome was FEV 1  < 80% of predicted values., Results: Spirometry was successful in 102/121 children. The other children died or were lost to follow-up. Median FEV 1 was 93% (interquartile range 80%-113%) of predicted values in the LISA group and 86% (interquartile range 77-102%) in the control group (p = 0.685). Rates of FEV 1  < 80% were 11/57 (19%) and 15/45 (33%), respectively, which was an absolute risk reduction of 14% (95% confidence interval -3.1% to 31.2%, p = 0.235). There were no differences in other outcome measures., Conclusion: The proportion of children aged 5-9 years with subnormal FEV 1 was not significantly different between the groups., (© 2022 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)

Aim: The aim of this study was to evaluate neurocognitive outcome at 24 months of corrected age after less invasive surfactant application (LISA) in preterm infants born at 23-26 weeks of gestational age., Methods: Surviving participants of a LISA trial conducted in 13 German level III neonatal intensive care units were reviewed for assessment of developmental outcome, hearing and vision problems, growth and rehospitalisation days. Maternal depression, breastfeeding rates and socio-economic factors were evaluated as potentially confounding factors., Results: In total, 156/182 infants took part in the study, 78 had received surfactant via LISA and 78 via endotracheal intubation. 22% of LISA infants compared to 42% of intubated infants had a psychomotor development index (PDI) <70 (0.012). A significant difference in mental development index (MDI) was observed in the stratum of more mature infants (25 and 26 weeks of GA). For this group, MDI < 70 was observed in 4% of LISA infants vs 21% of intubated infants (P = 0.008)., Conclusion: At 24 months of age, the LISA-treated infants scored less often PDI < 70 and had similar results in MDI. Infants born at 25 and 26 weeks treated with LISA had lower rates of severe disability. LISA is safe and may be superior., (© 2020 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)

In a large cohort study of the German Neonatal Network (GNN) we aimed to evaluate whether less invasive surfactant administration (LISA) strategy is associated with complications of preterm birth. Within the observational period n = 7533 very-low-birth-weight infants (VLBWI) with gestational age 22 0/7 to 28 6/7 weeks were enrolled in GNN; n = 1214 VLBWI never received surfactant, n = 2624 VLBWI were treated according to LISA procedure, n = 3695 VLBWI had surfactant via endotracheal tube (ETT). LISA was associated with a reduced risk for adverse outcome measures including mortality [odds ratio (OR) 0.66 (95% CI: 0.51-0.84), p < 0.001] bronchopulmonary dysplasia [BPD; OR 0.55 (95% CI: 0.49-0.62), p < 0.001], intracerebral hemorrhage (ICH) grade II-IV [OR 0.55 (95% CI: 0.48-0.64), p < 0.001] and retinopathy of prematurity [ROP; OR 0.62 (95% CI: 0.45-0.85), p < 0.001]. Notably, LISA was associated with an increased risk for focal intestinal perforation [FIP; OR 1.49 (95% CI: 1.14-1.95), p = 0.002]. The differences in FIP rates were primarily observed in VLBWI born <26 weeks (LISA: 10.0 vs. ETT: 7.4%, p = 0.029). Our observational data confirm that LISA is associated with improved outcome. In infants <26 weeks we noted an increased risk for FIP. Future randomized controlled trials including LISA need to integrate safety analyses for this particular subgroup.

Importance: Treatment of respiratory distress syndrome in premature infants with continuous positive airway pressure (CPAP) preserves surfactant and keeps the lung open but is insufficient in severe surfactant deficiency. Traditional surfactant administration is related to short periods of positive pressure ventilation and implies the risk of lung injury. CPAP with surfactant but without any positive pressure ventilation may work synergistically. This randomized trial investigated a less invasive surfactant application protocol (LISA)., Objective: To test the hypothesis that LISA increases survival without bronchopulmonary dysplasia (BPD) at 36 weeks' gestational age in extremely preterm infants., Design, Setting, and Participants: The Nonintubated Surfactant Application trial was a multicenter, randomized, clinical, parallel-group study conducted between April 15, 2009, and March 25, 2012, in 13 level III neonatal intensive care units in Germany. The final follow-up date was June 21, 2012. Participants included 211 of 558 eligible (37.8%) spontaneously breathing preterm infants born between 23.0 and 26.8 weeks' gestational age with signs of respiratory distress syndrome. In an intention-to-treat design, infants were randomly assigned to receive surfactant either via a thin endotracheal catheter during CPAP-assisted spontaneous breathing (intervention group) or after conventional endotracheal intubation during mechanical ventilation (control group). Analysis was conducted from September 6, 2012, to June 20, 2013., Intervention: LISA via a thin catheter., Main Outcomes and Measures: Survival without BPD at 36 weeks' gestational age., Results: Of 211 infants who were randomized, 104 were randomized to the control group and 107 to the LISA group. Of the infants who received LISA, 72 (67.3%) survived without BPD compared with 61 (58.7%) of those in the control group. The reduction in absolute risk was 8.6% (95% CI, -5.0% to 21.9%; P = .20). Intervention group infants were less frequently intubated (80 infants [74.8%] vs 103 [99.0%]; P < .001) and required fewer days of mechanical ventilation. Significant reductions were seen in pneumothorax (5 of 105 intervention group infants [4.8%] vs 13 of 103 12.6%]; P = .04) and severe intraventricular hemorrhage (11 infants [10.3%] vs 23 [22.1%]; P = .02), and the combined survival without severe adverse events was increased in the intervention group (54 infants [50.5%] vs 37 [35.6%]; P = .02; absolute risk reduction, 14.9; 95% CI, 1.4 to 28.2)., Conclusions and Relevance: LISA did not increase survival without BPD but was associated with increased survival without major complications. Because major complications are related to lifelong disabilities, LISA may be a promising therapy for extremely preterm infants., Trial Registration: isrctn.org Identifier: ISRCTN64011614.

Aim: Providing less invasive surfactant administration (LISA) to spontaneously breathing preterm infants has been reported to reduce mechanical ventilation and bronchopulmonary dysplasia (BPD) in randomised controlled trials. This large cohort study compared these outcome measures between LISA-treated infants and controls., Methods: Infants receiving LISA, who were born before 32 gestational weeks and enrolled in the German Neonatal Network, were matched to control infants by gestational age, umbilical cord pH, Apgar-score at 5 min, small for gestational age status, antenatal treatment with steroids, gender and highest supplemental oxygen during the first 12 h of life. Outcome data were compared with chi-square and Mann-Whitney U-tests and adjusted for multiple comparisons., Results: Between 2009 and 2012, 1103 infants were treated with LISA at 37 centres. LISA infants had lower rates of mechanical ventilation (41% versus 62%, p < 0.001), postnatal dexamethasone treatment (2.5% versus 7%, p < 0.001), BPD (12% versus 18%, p = 0.001) and BPD or death (14% versus 21%, p < 0.001) than the controls., Conclusion: Surfactant treatment of spontaneously breathing infants was associated with lower rates of mechanical ventilation and BPD. Additional large-scale randomised controlled trials are needed to assess the possible long-term benefits of LISA., (©2014 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Objective: To determine whether bovine surfactant given in cases of severe pediatric acute respiratory distress syndrome (ARDS) improves oxygenation., Design: Single-center study with 19 patients, followed by a multicenter randomized comparison of surfactant with a standardized treatment algorithm. Primary endpoint PaO(2)/FIO(2) at 48 h, secondary endpoints: PaO(2)/FIO(2) at 2, 4, 12, and 24 h, survival, survival without rescue, days on ventilator, subgroups analyzed by analysis of variance to identify patients who might benefit from surfactant., Setting: Multicenter study in 19 reference centers for ARDS., Patients: Children after the 44th postconceptional week and under 14 years old, admitted for at least 4 h, ventilated for 12-120 h, and without heart failure or chronic lung disease. In the multicenter study 35 patients were recruited; 20 were randomized to the surfactant group and 15 to the nonsurfactant group. Decreasing recruitment of patients led to a preliminary end of this study., Interventions: Administration of 100 mg/kg bovine surfactant intratracheally under continuous ventilation and PEEP, as soon as the PaO(2)/FIO(2) ratio dropped to less than 100 for 2 h (in the pilot study increments of 50 mg/kg as long as the PaO(2)/FIO(2) did not increase by 20%). A second equivalent dose within 48 h was permitted., Results: In the pilot study the PaO(2)/FIO(2) increased by a mean of 100 at 48 h (n=19). A higher PaO(2)/FIO(2) ratio was observed in the surfactant group 2 h after the first dose (58 from baseline vs. 9), at 48 h there was a trend towards a higher ratio (38 from baseline vs. 22). The rate of rescue therapy was significantly lower in the surfactant group. Outcome criteria were not affected by a second surfactant dose (n=11). A significant difference in PaO(2)/FIO(2) in favor of surfactant at 48 h was found in the subgroup with an initial PaO(2)/FIO(2) ratio higher than 65 and in patients without pneumonia. CONCLUSIONS. Surfactant therapy in severe ARDS improves oxygenation immediately after administration. This improvement is sustained only in the subgroup of patients without pneumonia and that with an initial PaO(2)/FIO(2) ratio higher than 65

Background: Aim of this study was to assess whether the decrease in heart rate and oxygen saturation occurring acutely after bolus administration of surfactant is different from the effect of endotracheal suctioning and whether there are effects on cerebral haemodynamics and oxygenation., Methods: Twelve premature infants, birth weight 720-1560 g (Median 935 g), gestational age 25-30 weeks (Median 28 weeks), were investigated during surfactant administration (Curosurf) as a single bolus and a preceding endotracheal suctioning procedure. Using near infrared spectroscopy changes in cerebral blood volume and cerebral oxygenation index were assessed. Heart rate, arterial oxygen saturation, PCO2, and arterial blood pressure were registered continuously. Data were compared at 30, 60 and 120 seconds after the beginning of suctioning and surfactant administration., Results: Endotracheal suctioning and surfactant administration induced a similar decrease in heart rate (-29/min, SD 25, p < 0.01 and -30/min, SD 23, p < 0.001) during the first 30 seconds and in oxygen saturation at the 30 seconds datapoint (-3%, SD 2, p < 0.01 and -3%, SD 6, p < 0.05). The decrease in oxygen saturation persisted at 60 seconds after the start of suctioning (-4%, SD 5, p < 0.05). In contrast, oxygen saturation was no longer different from baseline levels 60 seconds after surfactant administration (+1%, SD 6, p = 0.5). After suctioning, cerebral oxygenation index had decreased significantly from baseline levels at 30, 60, and 120 seconds. In contrast, after surfactant administration, no significant difference from baseline was noted at 30 and 60 seconds and a significant increase occurred at 120 seconds. Mean arterial blood pressure, PCO2, and cerebral blood volume did not change significantly during endotracheal suctioning and during surfactant administration., Conclusions: Acute decreases in heart rate and oxygen saturation during bolus administration of surfactant are equal to effects occurring during endotracheal suctioning. However, the decrease in oxygen saturation is shorter and more importantly, no decrease in cerebral oxygenation occurs.

Objectives: The aim of this study was to assess changes in cerebral haemodynamics and oxygenation induced by surfactant administration using near infrared spectroscopy (NIRS)., Methods: Eighteen premature infants, mean birth weight 960 g (range 550-1560 g), mean gestation age 28 weeks (range 25-30 weeks), were studied during 27 surfactant administrations. Porcine surfactant was administered to treat respiratory distress syndrome in a bolus of 100 mg/kg. Manual bag ventilation was performed for one minute after instillation. Heart rate, arterial oxygen saturation measured by pulse oximetry, transcutaneous PO2 (TcPO2), and PCO2 (TcPCO2), blood pressure, and cerebral oxygenated (O2Hb), deoxygenated (HHb), and total haemoglobin (tHb) concentration changes obtained by NIRS were registered every second from 15 minutes before until 30 minutes after surfactant administration., Results: During surfactant administration, there was a short-lasting but significant drop in heart rate and arterial oxygen saturation. NIRS parameters remained constant during and up to 1 minute after administration. One to three minutes after administration, heart rate, oxygen saturation, and TcPO2 increased significantly concomitantly with an increase in O2Hb and a decrease in HHb. In 10 cases, TcPO2 increased above 100 mmHg. tHb--indicative of cerebral blood volume--did not change significantly. Five to 30 minutes after surfactant administration there was no difference of monitoring data from baseline levels. TcPCO2 and blood pressure remained unchanged during the measurement period., Conclusion: Cerebral blood volume remained constant in very-low-birth-weight infants when surfactant was administered by bolus administration followed by manual ventilation according to our protocol. Attention should be directed towards rapid adaptation of inspiratory oxygen concentrations after surfactant administration to avoid hyperoxaemia.

Unlabelled: Congenital alveolar proteinosis and misalignment of lung vessels are rare disorders. We report on five infants of consanguineous kindred. All infants were delivered at term after uneventful pregnancies. Shortly after birth they developed respiratory failure and severe persistent pulmonary hypertension. All died despite intensive care. Lung tissue of two infants was studied. Histological examination revealed combination of alveolar proteinosis and misalignment of lung vessels in one patient, alveolar proteinosis in the other. Immunostaining demonstrated surfactant protein B (SP-B) deficiency in both patients' lungs. In a further sibling, analysis of broncho-alveolar lavage fluid showed decreased surfactant protein. PCR and direct sequence analysis of the SP-B gene revealed three novel mutations. One of them, a single base deletion, shifts the reading frame at amino acid 122 and creates a premature termination of translation in exon 6. No mature SP-B protein is produced., Conclusion: Surfactant protein B deficiency caused by mutations of the respective gene and misalignment of lung vessels can concur. Both diseases may have a pathogenetic factor in common.

Aims: To compare treatment regimens of two widely used natural surfactant preparations Curosurf and Survanta in respiratory distress syndrome (RDS)., Methods: The effects of the two treatment regimens on gas exchange, ventilatory requirements, and 28 day outcome in infants with RDS were compared. Seventy five preterm infants (birth weight 700-1500 g) with RDS requiring artificial ventilation with an FIO2 of > or = 0.4, were randomly selected at 1-24 hours of age. One group received an initial dose of Curosurf (200 mg/kg); the other group Survanta (100 mg/kg). Patients who remained dependent on artificial ventilation with an FIO2 of > or = 0.3 received up to two additional doses of Curosurf (each of 100 mg/kg) after 12 and 24 hours or up to three additional doses of Survanta (each of 100 mg/kg) between six and 48 hours after the initial dose., Results: There was a rapid improvement in oxygenation and ventilatory requirements were reduced in both groups. However, infants treated with Curosurf had a higher arterial:alveolar oxygen tension ratio and required a lower peak inspiratory pressure and mean airway pressure at several time points within 24 hours of randomisation (p < 0.05-0.001). The incidences of pneumothorax in the Curosurf and Survanta groups were 6% and 12.5%, respectively; the corresponding figures for grades 3-4 intracerebral haemorrhage were 3% and 12.5%, respectively. Mortality was 3% in the Curosurf group and 12.5% in the Survanta group. However, these differences did not reach significance., Conclusion: The Curosurf treatment regimen resulted in a more rapid improvement in oxygenation than Survanta and reduced ventilatory requirements up to 24 hours after start of treatment. This was associated with a trend towards reduced incidence of serious pulmonary and non-pulmonary complications.