Influence of neonatal endotracheal tube dimensions on oscillometry-acquired reactance: a bench study.

Objective.To examine the influence of the endotracheal tube (ETT) on respiratory reactance (Xrs) measured with the forced oscillation technique (FOT) and develop a correction method for it.Approach.In a bench study, the reactance of ETTs (Xtube) with different dimensions was measured on a breathing test lung in various respiratory settings.Main results.Xtubecan be accurately predicted by a fitted formula, with an R2of 0.97, with negligible effects due to changes in respiratory pattern and lung volume.Significance.The developed formula offers the ability to measure ETT-independent Xrsvalues of patients, improving the potential of FOT for lung function testing in mechanically ventilated newborns.

The Effect of Initial Oxygen Exposure on Diaphragm Activity in Preterm Infants at Birth.

Background: The initial FiO2 that should be used for the stabilization of preterm infants in the delivery room (DR) is still a matter of debate as both hypoxia and hyperoxia should be prevented. A recent randomized controlled trial showed that preterm infants [gestational age (GA) < 30 weeks] stabilized with an initial high FiO2 (1.0) had a significantly higher breathing effort than infants stabilized with a low FiO2 (0.3). As the diaphragm is the main respiratory muscle in these infants, we aimed to describe the effects of the initial FiO2 on diaphragm activity. Methods: In a subgroup of infants from the original bi-center randomized controlled trial diaphragm activity was measured with transcutaneous electromyography of the diaphragm (dEMG), using three skin electrodes that were placed directly after birth. Diaphragm activity was compared in the first 5 min after birth. From the dEMG respiratory waveform several outcome measures were determined for comparison of the groups: average peak- and tonic inspiratory activity (dEMGpeak and dEMGton, respectively), inspiratory amplitude (dEMGamp), area under the curve (dEMGAUC) and the respiratory rate (RR). Results: Thirty-one infants were included in this subgroup, of which 29 could be analyzed [n = 15 (median GA 28.4 weeks) and n = 14 (median GA 27.9 weeks) for the 100 and 30% oxygen group, respectively]. Tonic diaphragm activity was significantly higher in the high FiO2-group (4.3 ± 2.1 µV vs. 2.9 ± 1.1 µV; p = 0.047). The other dEMG-parameters (dEMGpeak, dEMGamp, dEMGAUC) showed consistently higher values in the high FiO2 group, but did not reach statistical significance. Average RR showed similar values in both groups (34 ± 9 vs. 32 ± 10 breaths/min for the high and low oxygen group, respectively). Conclusion: Preterm infants stabilized with an initial high FiO2 showed significantly more tonic diaphragm activity and an overall trend toward a higher level of diaphragm activity than those stabilized with an initial low FiO2. These results confirm that a high initial FiO2 after birth stimulates breathing effort, which can be objectified with dEMG.

Modes and strategies for providing conventional mechanical ventilation in neonates.

Neonatal respiratory failure is a common and serious clinical problem which in a considerable proportion of infants requires invasive mechanical ventilation. The basic goal of mechanical ventilation is to restore lung function while limiting ventilator-induced lung injury, which is considered an important risk factor in the development of bronchopulmonary dysplasia (BPD). Over the last decades, new conventional mechanical ventilation (CMV) modalities have been introduced in clinical practice, aiming to assist clinicians in providing lung protective ventilation strategies. These modalities use more sophisticated techniques to improve patient-ventilator interaction and transfer control of ventilation from the operator to the patient. Knowledge on how these new modalities work and how they interact with lung physiology is essential for optimal and safe use. In this review, we will discuss some important basic lung physiological aspects for applying CMV, the basic principles of the old and new CMV modalities, and the evidence to support their use in daily clinical practice.

Precision Medicine in Neonates: Future Perspectives for the Lung.

Bronchopulmonary dysplasia (BPD) is the most common complication of pre-term birth with long lasting sequelae. Since its first description more than 50 years ago, many large randomized controlled trials have been conducted, aiming to improve evidence-based knowledge on the optimal strategies to prevent and treat BPD. However, most of these intervention studies have been performed on a population level without regard for the variation in clinical and biological diversity (e.g., gestational age, ethnicity, gender, or disease progression) between patients that is driven by the complex interaction of genetic pre-disposition and environmental exposures. Nevertheless, clinicians provide daily care such as lung protective interventions on an individual basis every day despite the fact that research supporting individualized or precision medicine for monitoring or treating pre-term lungs is immature. This narrative review summarizes four potential developments in pulmonary research that might facilitate the process of individualizing lung protective interventions to prevent development of BPD. Electrical impedance tomography and electromyography of the diaphragm are bedside monitoring tools to assess regional changes in lung volume and ventilation and spontaneous breathing effort, respectively. These non-invasive tools allow a more individualized optimization of invasive and non-invasive respiratory support. Investigation of the genomic variation in caffeine metabolism in pre-term infants can be used to optimize and individualize caffeine dosing regimens. Finally, volatile organic compound analysis in exhaled breath might accurately predict BPD at an early stage of the disease, enabling clinicians to initiate preventive strategies for BPD on an individual basis. Before these suggested diagnostic or monitoring tools can be implemented in daily practice and improve individualized patient care, future research should address and overcome their technical difficulties, perform extensive external validation and show their additional value in preventing BPD.

The Effect of Initial High vs. Low FiO2 on Breathing Effort in Preterm Infants at Birth: A Randomized Controlled Trial.

Background: Infants are currently stabilized at birth with initial low FiO2 which increases the risk of hypoxia and suppression of breathing in the first minutes after birth. We hypothesized that initiating stabilization at birth with a high O2 concentration, followed by titration, would improve breathing effort when compared to a low O2 concentration, followed by titration. Methods: In a bi-center randomized controlled trial, infants <30 weeks gestation were stabilized at birth with an initial O2 concentration of 30 or 100%, followed by oxygen titration. Primary outcome was minute volume of spontaneous breathing. We also assessed tidal volumes, mean inspiratory flow rate (MIFR) and respiratory rate with a respiratory function monitor in the first 5 min after birth, and evaluated the duration of mask ventilation in the first 10 min after birth. Pulse oximetry was used to measure heart rate and SpO2 values in the first 10 min. Hypoxemia was defined as SpO2 < 25th percentile and hyperoxemia as SpO2 >95%. 8-iso-prostaglandin F2α (8iPGF2α) was measured to assess oxidative stress in cord blood and 1 and 24 h after birth. Results: Fifty-two infants were randomized and recordings were obtained in 44 infants (100% O2-group: n = 20, 30% O2-group: n = 24). Minute volumes were significantly higher in the 100% O2-group (146.34 ± 112.68 mL/kg/min) compared to the 30% O2-group (74.43 ± 52.19 mL/kg/min), p = 0.014. Tidal volumes and MIFR were significantly higher in the 100% O2-group, while the duration of mask ventilation given was significantly shorter. Oxygenation in the first 5 min after birth was significantly higher in infants in the 100% O2-group [85 (64-93)%] compared to the 30% O2-group [58 (46-67)%], p < 0.001. The duration of hypoxemia was significantly shorter in the 100% O2-group, while the duration of hyperoxemia was not different between groups. There was no difference in oxidative stress marker 8iPGF2α between the groups. Conclusion: Initiating stabilization of preterm infants at birth with 100% O2 led to higher breathing effort, improved oxygenation, and a shorter duration of mask ventilation as compared to 30% O2, without increasing the risk for hyperoxia or oxidative stress. Clinical Trial Registration: This study was registered in www.trialregister.nl, with registration number NTR6878.

Mortality and causes of death of end-stage renal disease in children: a Dutch cohort study.

BACKGROUND: To establish mortality rates, causes of death, and determinants of mortality in children with end-stage renal disease (ESRD), we performed a national long-term follow up study. METHODS: Mortality rate was determined in all Dutch patients with onset of ESRD at ages 0 to 14 years in the period between 1972 and 1992. Causes of death and mortality determinants were investigated in all patients of this cohort who were born before 1979. Data were derived from the Dutch Registry for patients on renal replacement therapy (RRT), medical charts and National Health Database. RESULTS: Of all 381 patients 85 had died. The overall mortality rate (MR) was 1.57/100 patient-years, and the standardized mortality rate (SMR) was 31.0. The MR for patients 0 to 5 and 6 to 10 years old at onset of ESRD decreased from, respectively, 7.0 (range 0-14.9) to 3.9 (1.2-6.7) and 4.3 (1.1-7.5) to 1.6 (0.3-2.8) between the periods 1972-1981 and 1982-1992. The mortality hazard ratio of relatively long standing dialysis and of long standing hypertension were, respectively, 7.2 (4.4-11.8) and 3.1 (2.1-4.6), of cyclosporine-introduction in transplanted patients 0.3 (0.1-0.4). Overall cerebrovascular accidents (24%) and infections (21%) were the most common causes of death; after 10 years of RRT cardiac death (7/21) was most prevalent. Cardiovascular death was most prominent in dialysis as well as transplanted patients. CONCLUSION: Survival in children with ESRD has increased over the last 20 years, but the SMR remains high. Early transplantation and a more vigorous approach toward hypertension and infection may be mandatory in order to further reduce mortality.