NIPPV after Surfactant Treatment for RDS Reduces the Need for Mechanical Ventilation at 7 Days of Age and BPD in Preterm Infants: Interpret Results with Caution.
NIPPV after Surfactant Treatment for RDS Reduces the Need for Mechanical Ventilation at 7 Days of Age and BPD in Preterm Infants: Interpret Results with Caution.
Project description:ObjectiveTo provide the best clinical practice guidance for surfactant use in preterm neonates with respiratory distress syndrome (RDS). The RDS-Neonatal Expert Taskforce (RDS-NExT) initiative was intended to add to existing evidence and clinical guidelines, where evidence is lacking, with input from an expert panel.Study designAn expert panel of healthcare providers specializing in neonatal intensive care was convened and administered a survey questionnaire, followed by 3 virtual workshops. A modified Delphi method was used to obtain consensus around topics in surfactant use in neonatal RDS.ResultStatements focused on establishing RDS diagnosis and indicators for surfactant administration, surfactant administration methods and techniques, and other considerations. After discussion and voting, consensus was achieved on 20 statements.ConclusionThese consensus statements provide practical guidance for surfactant administration in preterm neonates with RDS, with a goal to contribute to improving the care of neonates and providing a stimulus for further investigation to bridge existing knowledge gaps.
Project description:Background: Intratracheal budesonide mixed with surfactant has been investigated as an alternative to decrease lung injury and prevent bronchopulmonary dysplasia in preterm infants. However, possible systemic effects are not known. Our goal was identify systemic effects of intra-tracheal instilled budesonide by transcriptome analysis of the brain and lung in a preterm lamb model of mechanical ventilation. Methods: We performed RNA-sequencing of the fetal periventricular white matter and liver from preterm sheep after treatment with intratracheal budesonide mixed with surfactant or surfactant alone followed by mechanical ventilation. Unventilated animals were used as controls. mRNA profiles were generated from polyA selected RNA using Illumina platform. Read sequences were aligned to the sheep genome (Oar 4.0) using Bowtie2 followed read counts using featureCounts. We performed differential expression analysis using EdgeR. Results: We identified large and significant gene expression genes both in the liver and in the priventricular white matter in animals treated with budesonide+surfactant compared to surfactant alone and unventilated animals. There were complexes synergies and antagonism of effect of ventilation and budesonide on gene expression. Ventilation induced inflammatory signaling in the periventricular white matter and liver which was partially antagonized by budesonide. Budesonide also suppressed developmental pathways in the periventricular white matter. Conclusions: Intratracheal budesonide had systemic effects including suppression of developmental pathways in the brain. These effects could have clinical implication in affecting the neurodevelopmental outcomes of preterm newborns.
Project description:This study aimed to investigate whether using lung ultrasound (LUS) scores in premature newborns with respiratory distress syndrome (RDS) allows for earlier surfactant therapy (within the first 3 h of life) than using FiO2 criteria. This was a randomised, non-blinded clinical trial conducted in a neonatal intensive care unit. The inclusion criteria were newborns with a gestational age of ≤ 32 weeks and RDS. Patients meeting the inclusion criteria were randomly assigned to two groups: the ultrasound group, administered surfactant based on LUS score and/or FiO2 threshold, and the control group, guided by FiO2 only. Fifty-six patients were included. The ultrasound group received surfactant earlier (1 h of life vs. 6 h, p < 0.001), with lower FiO2 (25% vs. 30%, p = 0.016) and lower CO2 (48 vs. 54, p = 0.011). After surfactant treatment, newborns in the ultrasound group presented a greater SpO2 (p = 0.001) and SpO2/FiO2 ratio (p = 0.012).Conclusions: LUS score allowed an earlier surfactant therapy, reduced oxygen exposure early in life and a better oxygenation after the treatment. This early surfactant replacement may lead to reduced oxygen exposure. What is Known: • Lung ultrasound scores predict the need for surfactant therapy in premature newborns. What is New: • This study shows that using lung ultrasound scores improves the timeliness of surfactant replacement compared with using FiO2 alone.
Project description:Hemodynamic changes during neonatal transition increase the vulnerability of the preterm brain to injury. Real-time monitoring of brain function during this period would help identify the immediate impact of these changes on the brain. Neonatal EEG provides detailed real-time information about newborn brain function but can be difficult to interpret for non-experts; preterm neonatal EEG poses even greater challenges. An objective quantitative measure of preterm brain health would be invaluable during neonatal transition to help guide supportive care and ultimately protect the brain. Appropriate quantitative measures of preterm EEG must be calculated and care needs to be taken when applying the many techniques available for this task in the era of modern data science. This review provides valuable information about the factors that influence quantitative EEG analysis and describes the common pitfalls. Careful feature selection is required and attention must be paid to behavioral state given the variations encountered in newborn EEG during different states. Finally, the detrimental influence of artifacts on quantitative EEG analysis is illustrated.
Project description:High frequency oscillatory ventilation with volume-guarantee (HFOV-VG) is a promising lung protective ventilator mode for the treatment of respiratory failure in newborns. However, indicators of optimal ventilation during HFOV-VG mode are not identified yet. In this study, we aimed to evaluate optimal high-frequency tidal volume (VThf) and the dissociation coefficient of CO2 (DCO2) levels to achieve normocapnia during HFOV-VG after lung recruitment in very low birthweight infants with respiratory distress syndrome (RDS). Preterm babies under the 32nd postmenstrual week with severe RDS that received HFOV-VG using open-lung strategy between January 2014 and January 2019 were retrospectively evaluated. All included patients were treated with the Dräger Babylog VN500 ventilator in the HFOV-VG mode. In total, 53 infants with a mean gestational age of 26.8 ± 2.3 weeks were evaluated. HFOV mean optimal airway pressure (MAPhf) level after lung recruitment was found to be 10.2 ± 1.7 mbar. Overall, the mean applied VThf per kg was 1.64 ± 0.25 mL/kg in the study sample. To provide normocapnia, the mean VThf was 1.61 ± 0.25 mL/kg and the mean DCO2corr was 29.84 ± 7.88 [mL/kg]2/s. No significant correlation was found between pCO2 levels with VThf (per kg) or DCO2corr levels. VThf levels to maintain normocarbia were significantly lower with 12 Hz frequency compared to 10 Hz frequency (1.50 ± 0.24 vs. 1.65 ± 0.25 mL/ kg, p < 0.001, respectively). A weak but significant positive correlation was found between mean airway pressure (MAPhf) and VThf levels. To our knowledge, this is the largest study to evaluate the optimal HFOV-VG settings in premature infants with RDS, using the open-lung strategy. According to the results, a specific set of numbers could not be recommended to achieve normocarbia. Following the trend of each patient and small adjustments according to the closely monitored pCO2 levels seems logical.
Project description:Mechanical ventilation from birth with normal tidal volumes (VT) causes lung injury and systemic responses in preterm sheep. The addition of budesonide to surfactant therapy decreases these injury markers. Budesonide and surfactant will decrease the injury from injurious VT ventilation in preterm sheep. Lambs at 126 ± 1 day gestational age were ventilated from birth with either: 1) Normal VT [surfactant 200 mg/kg before ventilation, positive end expiratory pressure (PEEP) 5 cmH2O, VT 8 mL/kg] or 2) Injury VT (high pressure, 100% oxygen, no PEEP) for 15 min, then further randomized to surfactant + saline or surfactant + 0.25 mg/kg budesonide with Normal VT for 6 h. Lung function and lung, liver, and brain tissues were evaluated for indicators of injury. Injury VT + saline caused significant injury and systemic responses, and Injury VT + budesonide improved lung physiology. Budesonide decreased lung inflammation and decreased pro-inflammatory cytokine mRNA in the lung, liver, and brain to levels similar to Normal VT + saline. Budesonide was present in plasma within 15 min of treatment in both ventilation groups, and less than 5% of the budesonide remained in the lung at 6 h. mRNA sequencing of liver and periventricular white matter demonstrated multiple pathways altered by both Injury VT and budesonide and the combination exposure. In lambs receiving Injury VT, the addition of budesonide to surfactant improved lung physiology and decreased pro-inflammatory cytokine responses in the lung, liver, and brain to levels similar to lambs receiving Normal VT.
Project description:Preterm infants often require mechanical ventilation due to lung immaturity including reduced or abnormal surfactant. Since cyclic stretch with cycle-by-cycle variability is known to augment surfactant release by epithelial cells, we hypothesized that such in vivo mechanotransduction improves surfactant maturation and hence lung physiology in preterm subjects. We thus tested whether breath-by-breath variability in tidal volume (VT) in variable ventilation (VV) can be tuned for optimal performance in a preterm lamb model. Preterm lambs were ventilated for 3 h with conventional ventilation (CV) or two variants of VV that used a maximum VT of 1.5 (VV1) or 2.25 (VV2) times the mean VT. VT was adjusted during ventilation to a permissive pCO2 target range. Respiratory mechanics were monitored continuously using the forced oscillation technique, followed by postmortem bronchoalveolar lavage and tissue collection. Both VVs outperformed CV in blood gas parameters (pH, SaO2, cerebral O2 saturation). However, only VV2 lowered PaCO2 and had a higher specific respiratory compliance than CV. VV2 also increased surfactant protein (SP)-B release compared to VV1 and stimulated its production compared to CV. The production and release of proSP-C however, was increased with CV compared to both VVs. There was more SP-A in both VVs than CV in the lung, but VV2 downregulated SP-A in the lavage, whereas SP-D significantly increased in CV in both the lavage and lung. Compared to CV, the cytokines IL-1β, and TNFα decreased with both VVs with less inflammation during VV2. Additionally, VV2 lungs showed the most homogeneous alveolar structure and least inflammatory cell infiltration assessed by histology. CV lungs exhibited over-distension mixed with collapsed and interstitial edematous regions with occasional hemorrhage. Following VV1, some lambs had normal alveolar structure while others were similar to CV. The IgG serum proteins in the lavage, a marker of leakage, were the highest in CV. An overall combined index of performance that included physiological, biochemical and histological markers was the best in VV2 followed by VV1. Thus, VV2 outperformed VV1 by enhancing SP-B metabolism resulting in open alveolar airspaces, less leakage and inflammation and hence better respiratory mechanics.
Project description:BackgroundBovine surfactants are known to be clinically equivalent but it is unclear if porcine or bovine surfactants at their licensed dose should be preferred to treat respiratory distress syndrome in preterm neonates.MethodsWe performed a comprehensive review of biochemical and pharmacological features of surfactants to understand the biological plausibility of any clinical effect. We then performed a pragmatic meta-analysis comparing internationally marketed porcine and bovine surfactants for mortality and respiratory outcomes. Search for randomised controlled trials with no language/year restrictions and excluding "grey" literature, unpublished or non-peer reviewed reports was conducted, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and the most recent methodological recommendations.ResultsSixteen articles were included in the review and 14 in the meta-analysis (1491 neonates). 200 mg/kg poractant-α (a porcine surfactant) was associated with lower BPD/mortality (OR 0.632[95%CI:0.494, 0.809];p < 0.001),BPD (OR 0.688[95%CI:0.512, 0.925];p = 0.013), retreatment (OR 0.313[95%CI:0.187, 0.522];p < 0.0001), airleaks (OR 0.505[95%CI:0.308, 0.827];p = 0.006) and lung haemorrhage (OR 0.624[95%CI:0.388, 1];p = 0.051). Gestational age is associated with effect size for BPD (coefficient: 0.308 [95%CI:0.063, 0.554];p = 0.014) and surfactant retreatment (coefficient: -0.311 [95%CI:-0.595, - 0.028];p = 0.031).Conclusion200 mg/kg poractant-α is associated with better respiratory outcomes compared to bovine surfactants at their licensed dose. The effect of poractant-α on BPD and surfactant retreatment is greater at lowest and highest gestational ages, respectively.Trial registrationPROSPERO n.42017075251 .
Project description:BackgroundRetinopathy of prematurity is treated with laser photocoagulation under general anaesthesia with intubation using endotracheal tube (ETT), which carries a risk for postoperative mechanical ventilation (MV). Laryngeal mask airway (LMA) may provide a safe alternative. We assessed the need for postoperative MV in preterm infants who received LMA versus ETT.MethodsIn this single-centre, retrospective cohort study, preterm infants who underwent laser photocoagulation between 2014-2021 were enroled. For airway management, patients received either LMA (n = 224) or ETT (n = 47). The outcome was the rate of postoperative MV.ResultsPatients' age were 37 [35;39] weeks of postmenstrual age, median bodyweight of Group LMA was higher than Group ETT's (2110 [1800;2780] g versus 1350 [1230;1610] g, respectively, p < 0.0001). After laser photocoagulation, 8% of Group LMA and 74% of Group ETT left the operating theatre requiring MV. Multiple logistic regression revealed that the use of LMA and every 100 g increase in bodyweight significantly decreased the odds of mechanical ventilation (OR 0.21 [95% CI 0.07-0.60], and 0.73 [95% CI 0.63-0.84], respectively). Propensity score matching confirmed that LMA decreased the odds of postoperative MV (OR 0.30 [95% CI 0.11-0.70]).ConclusionThe use of LMA is associated with a reduced need for postoperative MV.ImpactUsing laryngeal mask airway instead of endotracheal tube for airway management in preterm infants undergoing general anaesthesia for laser photocoagulation for treating retinopathy of prematurity could significantly decrease the postoperative need for mechanical ventilation. According to our current understanding, this has been the largest study investigating the effect of laryngeal mask airway during general anaesthesia in preterm infants. Our study suggests that the use of laryngeal mask airway is a viable alternative to intubation in the vulnerable population of preterm infants in need of laser treatment.
Project description:ObjectiveTo evaluate the physiological impact of high CPAP (≥9 cmH2O) vs. NIPPV at equivalent mean airway pressures.Study designIn this cross-over study, preterm neonates on high CPAP or NIPPV were placed on the alternate mode. After 30 min, left and right ventricular cardiac output and work of breathing indices were assessed, following which patients were placed back on the original mode and a similar procedure ensued.ResultsFifteen infants with mean (SD) postmenstrual age 32.7 (3.0) weeks, and weight 1569 (564) grams were included. No differences in LVO [320 (63) vs. 331 (86) mL/kg/min, P = 0.46] or RVO [420 (135) vs. 437 (141) mL/kg/min, P = 0.19] were noted during high CPAP vs. NIPPV, along with no differences in work of breathing indices.ConclusionHigh CPAP pressures did not adversely impact cardiac output or work of breathing compared to NIPPV at equivalent mean airway pressure.