Dynamic positive end-expiratory pressure strategies using time and pressure recruitment at birth reduce early expression of lung injury in preterm lambs.

Positive end-expiratory pressure (PEEP) is critical to the preterm lung at birth, but the optimal PEEP level remains uncertain. The objective of this study was to determine the effect of maximum PEEP levels at birth on the physiological and injury response in preterm lambs. Steroid-exposed preterm lambs (124-127 days gestation; n = 65) were randomly assigned from birth to either 1) positive pressure ventilation (PPV) at 8 cmH2O PEEP or 3-min dynamic stepwise PEEP strategy (DynPEEP), with either 2) 20 cmH2O maximum PEEP (10 PEEP second steps) or 3) 14 cmH2O maximum PEEP (20-s steps), all followed by standardized PPV for 90 min. Lung mechanics, gas exchange, regional ventilation and aeration (electrical impedance tomography), and histological and molecular measures of lung injury were compared between groups. Dynamic compliance was greatest using a maximum 20 cmH2O (DynPEEP). There were no differences in gas exchange, end-expiratory volume, and ventilator requirements. Regional ventilation became more uniform with time following all PEEP strategies. For all groups, gene expression of markers of early lung injury was greater in the gravity nondependent lung, and inversely related to the magnitude of PEEP, being lowest in the 20 cmH2O DynPEEP group overall. PEEP levels had no impact on lung injury in the dependent lung. Transient high maximum PEEP levels using dynamic PEEP strategies may confer more lung protection at birth.

Gradual Aeration at Birth Is More Lung Protective Than a Sustained Inflation in Preterm Lambs.

Rationale: The preterm lung is susceptible to injury during transition to air breathing at birth. It remains unclear whether rapid or gradual lung aeration at birth causes less lung injury.Objectives: To examine the effect of gradual and rapid aeration at birth on: 1) the spatiotemporal volume conditions of the lung; and 2) resultant regional lung injury.Methods: Preterm lambs (125 ± 1 d gestation) were randomized at birth to receive: 1) tidal ventilation without an intentional recruitment (no-recruitment maneuver [No-RM]; n = 19); 2) sustained inflation (SI) until full aeration (n = 26); or 3) tidal ventilation with an initial escalating/de-escalating (dynamic) positive end-expiratory pressure (DynPEEP; n = 26). Ventilation thereafter continued for 90 minutes at standardized settings, including PEEP of 8 cm H2O. Lung mechanics and regional aeration and ventilation (electrical impedance tomography) were measured throughout and correlated with histological and gene markers of early lung injury.Measurements and Main Results: DynPEEP significantly improved dynamic compliance (P < 0.0001). An SI, but not DynPEEP or No-RM, resulted in preferential nondependent lung aeration that became less uniform with time (P = 0.0006). The nondependent lung was preferential ventilated by 5 minutes in all groups, with ventilation only becoming uniform with time in the No-RM and DynPEEP groups. All strategies generated similar nondependent lung injury patterns. Only an SI caused greater upregulation of dependent lung gene markers compared with unventilated fetal controls (P < 0.05).Conclusions: Rapidly aerating the preterm lung at birth creates heterogeneous volume states, producing distinct regional injury patterns that affect subsequent tidal ventilation. Gradual aeration with tidal ventilation and PEEP produced the least lung injury.

Time to lung aeration during a sustained inflation at birth is influenced by gestation in lambs.

BackgroundCurrent sustained lung inflation (SI) approaches use uniform pressures and durations. We hypothesized that gestational-age-related mechanical and developmental differences would affect the time required to achieve optimal lung aeration, and resultant lung volumes, during SI delivery at birth in lambs.Methods49 lambs, in five cohorts between 118 and 139 days of gestation (term 142 d), received a standardized 40 cmH2O SI, which was delivered until 10 s after lung volume stability (optimal aeration) was visualized on real-time electrical impedance tomography (EIT), or to a maximum duration of 180 s. Time to stable lung aeration (Tstable) within the whole lung, gravity-dependent, and non-gravity-dependent regions, was determined from EIT recordings.ResultsTstable was inversely related to gestation (P<0.0001, Kruskal-Wallis test), with the median (range) being 229 (85,306) s and 72 (50,162) s in the 118-d and 139-d cohorts, respectively. Lung volume at Tstable increased with gestation from a mean (SD) of 20 (17) ml/kg at 118 d to 56 (13) ml/kg at 139 d (P=0.002, one-way ANOVA). There were no gravity-dependent regional differences in Tstable or aeration.ConclusionsThe trajectory of aeration during an SI at birth is influenced by gestational age in lambs. An understanding of this may assist in developing SI protocols that optimize lung aeration for all infants.

Effect of Minimally Invasive Surfactant Therapy on Lung Volume and Ventilation in Preterm Infants.

OBJECTIVE: To assess the changes in (regional) lung volume and gas exchange during minimally invasive surfactant therapy (MIST) in preterm infants with respiratory distress syndrome. STUDY DESIGN: In this prospective observational study, infants requiring a fraction of inspired oxygen (FiO2) ≥ 0.30 during nasal continuous positive airway pressure of 6 cmH2O were eligible for MIST. Surfactant (160-240 mg/kg) was administered in supine position in 1-3 minutes via an umbilical catheter placed 2 cm below the vocal cords. Changes in end-expiratory lung volume (EELV), tidal volume, and its distribution were recorded continuously with electrical impedance tomography before and up to 60 minutes after MIST. Changes in transcutaneous oxygen saturation (SpO2) and partial carbon dioxide pressure, FiO2, respiratory rate, and minute ventilation were recorded. RESULTS: A total of 16 preterm infants were included. One patient did not finish study protocol because of severe apnea 10 minutes after MIST. In the remaining infants (gestational age 29.8 ± 2.8 weeks, body weight 1545 ± 481 g) EELV showed a rapid and sustained increase, starting in the dependent lung regions, followed by the nondependent regions approximately 5 minutes later. Oxygenation, expressed as the SpO2/FiO2 ratio, increased from 233 (IQR 206-257) to 418 (IQR 356-446) after 60 minutes (P < .001). This change was significantly correlated with the change in EELV (ρ = 0.70, P < .01). Tidal volume and minute volume decreased significantly after MIST, but transcutaneous partial carbon dioxide pressure was comparable with pre-MIST values. Ventilation distribution remained unchanged. CONCLUSIONS: MIST results in a rapid and homogeneous increase in EELV, which is associated with an improvement in oxygenation.

Changes in lung volume and ventilation following transition from invasive to noninvasive respiratory support and prone positioning in preterm infants.

BACKGROUND: To minimize secondary lung injury, ventilated preterm infants are extubated as soon as possible. To maximize extubation success, they are often placed in prone position. The effect of extubation and subsequent prone positioning on lung volumes is currently unknown. METHODS: Changes in end-expiratory lung volume (ΔEELV), tidal volume (VT), and ventilation distribution were monitored during transition from endotracheal to nasal continuous positive airway pressure and following prone positioning using electrical impedance tomography. In addition, the continuous distending pressure (CDP) and oxygen need (FiO2) were recorded. RESULTS: Twenty preterm infants (GA 28.7 ± 1.7 wk) were included. Following extubation, the CDP decreased from 7.9 ± 0.5 to 6.0 ± 0.2 cmH2O, while the FiO2 remained stable. Both ΔEELV and VT increased significantly (P < 0.05) after extubation, without changing ventilation distribution. Prone positioning resulted in a further increase in ΔEELV (P < 0.01) and a decrease in respiratory rate. VT remained stable but its distribution clearly shifted toward the ventral lung regions. CONCLUSION: Infants who are transitioned from invasive to noninvasive respiratory support are able to maintain their EELV and increase their VT. Prone positioning increases EELV and shifts tidal ventilation to the ventral lung regions. The latter suggests that infants should preferably be placed in prone position after extubation.

Cross-sectional changes in lung volume measured by electrical impedance tomography are representative for the whole lung in ventilated preterm infants.

OBJECTIVE: Electrical impedance tomography measures lung volume in a cross-sectional slice of the lung. Whether these cross-sectional volume changes are representative of the whole lung has only been investigated in adults, showing conflicting results. This study aimed to compare cross-sectional and whole lung volume changes using electrical impedance tomography and respiratory inductive plethysmography. DESIGN: A prospective, single-center, observational, nonrandomized study. SETTING: The study was conducted in a neonatal ICU in the Netherlands. PATIENTS: High-frequency ventilated preterm infants with respiratory distress syndrome. INTERVENTIONS: Cross-sectional and whole lung volume changes were continuously and simultaneously measured by, respectively, electrical impedance tomography and respiratory inductive plethysmography during a stepwise recruitment procedure. End-expiratory lung volume changes were assessed by mapping the inflation and deflation limbs using both the pressure/impedance and pressure/inductance pairs and characterized by calculating the inflection points. In addition, oscillatory tidal volume changes were assessed at each pressure step. MEASUREMENTS AND MAIN RESULTS: Twenty-three infants were included in the study. Of these, eight infants had to be excluded because the quality of the registration was insufficient for analysis (two electrical impedance tomography and six respiratory inductive plethysmography). In the remaining 15 infants (gestational age 28.0 ± 2.6 wk; birth weight 1,027 ± 514 g), end-expiratory lung volume changes measured by electrical impedance tomography were significantly correlated to respiratory inductive plethysmography measurements in 12 patients (mean r = 0.93 ± 0.05). This was also true for the upper inflection point on the inflation (r = 0.91, p < 0.01) and deflation limb (r = 0.83, p < 0.01). In 13 patients, impedance and inductance data also correlated significantly on oscillatory tidal volume/pressure relationships (mean r = 0.81 ± 0.18). CONCLUSIONS: This study shows that cross-sectional lung volume changes measured by electrical impedance tomography are representative for the whole lung and that this concept also applies to newborn infants.

Effect of nasal continuous and biphasic positive airway pressure on lung volume in preterm infants.

OBJECTIVE: To monitor regional changes in end-expiratory lung volume (EELV), tidal volumes, and their ventilation distribution during different levels of nasal continuous positive airway pressure (nCPAP) and nasal biphasic positive airway pressure (BiPAP) in stable preterm infants. STUDY DESIGN: By using electrical impedance tomography and respiratory inductive plethysmography, we measured changes in EELV and tidal volumes in 22 preterm infants (gestational age 29.7 ± 1.5 weeks) during 3 nCPAP levels (2, 4, and 6 cmH2O) and unsynchronized BiPAP (nCPAP = 6 cmH2O; pressure amplitude = 3 cmH2O; frequency = 50/min; inspiration time = 0.5 seconds) at 10-minute intervals. We assessed the distribution of these volumes in ventral and dorsal chest regions by using electrical impedance tomography. RESULTS: EELV increased with increasing nCPAP with no difference between the ventral and dorsal lung regions. Tidal volume also increased, and a decrease in phase angle and respiratory rate was noted by respiratory induction plethysmography. At the regional level, electrical impedance tomography data showed a more dorsally oriented ventilation distribution. BiPAP resulted in a small increase in EELV but without changes in tidal volume or its regional distribution. CONCLUSION: Increasing nCPAP in the range of 2 to 6 cmH2O results in a homogeneous increase in EELV and an increase in tidal volume in preterm infants with a more physiologic ventilation distribution. Unsynchronized BiPAP does not improve tidal volume compared with nCPAP.

Clinical prediction models for bronchopulmonary dysplasia: a systematic review and external validation study.

BACKGROUND: Bronchopulmonary dysplasia (BPD) is a common complication of preterm birth. Very different models using clinical parameters at an early postnatal age to predict BPD have been developed with little extensive quantitative validation. The objective of this study is to review and validate clinical prediction models for BPD. METHODS: We searched the main electronic databases and abstracts from annual meetings. The STROBE instrument was used to assess the methodological quality. External validation of the retrieved models was performed using an individual patient dataset of 3229 patients at risk for BPD. Receiver operating characteristic curves were used to assess discrimination for each model by calculating the area under the curve (AUC). Calibration was assessed for the best discriminating models by visually comparing predicted and observed BPD probabilities. RESULTS: We identified 26 clinical prediction models for BPD. Although the STROBE instrument judged the quality from moderate to excellent, only four models utilised external validation and none presented calibration of the predictive value. For 19 prediction models with variables matched to our dataset, the AUCs ranged from 0.50 to 0.76 for the outcome BPD. Only two of the five best discriminating models showed good calibration. CONCLUSIONS: External validation demonstrates that, except for two promising models, most existing clinical prediction models are poor to moderate predictors for BPD. To improve the predictive accuracy and identify preterm infants for future intervention studies aiming to reduce the risk of BPD, additional variables are required. Subsequently, that model should be externally validated using a proper impact analysis before its clinical implementation.

Neonatal high-frequency oscillatory ventilation: where are we now?

High-frequency oscillatory ventilation (HFOV) is an established mode of respiratory support in the neonatal intensive care unit. Large clinical trial data is based on first intention use in preterm infants with acute respiratory distress syndrome. Clinical practice has evolved from this narrow population. HFOV is most often reserved for term and preterm infants with severe, and often complex, respiratory failure not responding to conventional modalities of respiratory support. Thus, optimal, and safe, application of HFOV requires the clinician to adapt mean airway pressure, frequency, inspiratory:expiratory ratio and tidal volume to individual patient needs based on pathophysiology, lung volume state and infant size. This narrative review summarises the status of HFOV in neonatal intensive care units today, the lessons that can be learnt from the past, how to apply HFOV in different neonatal populations and conditions and highlights potential new advances. Specifically, we provide guidance on how to apply an open lung approach to mean airway pressure, selecting the correct frequency and use of volume-targeted HFOV.

Effect of routine suction on lung aeration in critically ill neonates and young infants measured with electrical impedance tomography.

Endotracheal suctioning is a widely used procedure to remove secretions from the airways of ventilated patients. Despite its prevalence, regional effects of this maneuver have seldom been studied. In this study, we explore its effects on regional lung aeration in neonates and young infants using electrical impedance tomography (EIT) as part of the large EU-funded multicenter observational study CRADL. 200 neonates and young infants in intensive care units were monitored with EIT for up to 72 h. EIT parameters were calculated to detect changes in ventilation distribution, ventilation inhomogeneity and ventilation quantity on a breath-by-breath level 5-10 min before and after suctioning. The intratidal change in aeration over time was investigated by means of regional expiratory time constants calculated from all respiratory cycles using an innovative procedure and visualized by 2D maps of the thoracic cross-section. 344 tracheal suctioning events from 51 patients could be analyzed. They showed no or very small changes of EIT parameters, with a dorsal shift of the center of ventilation by 0.5% of the chest diameter and a 7% decrease of tidal impedance variation after suctioning. Regional time constants did not change significantly. Routine suctioning led to EIT-detectable but merely small changes of the ventilation distribution in this study population. While still a measure requiring further study, the time constant maps may help clinicians interpret ventilation mechanics in specific cases.

The effect of airway pressure and oscillation amplitude on ventilation in pre-term infants.

We determined the effect of lung recruitment and oscillation amplitude on regional oscillation volume and functional residual capacity (FRC) in high-frequency oscillatory ventilation (HFOV) used in pre-term infants with respiratory distress syndrome (RDS). Changes in lung volume, oscillation volume and carbon dioxide levels were recorded in 10 infants during a stepwise recruitment procedure, and an increase in pressure amplitude of 5 cmH(2)O was measured using electrical impedance tomography and transcutaneous monitoring. The pressures at maximal respiratory system compliance, maximal oscillation volume and minimal carbon dioxide levels were determined. Impedance data were analysed for the chest cross-section and predefined regions of interest. Despite the fixed pressure amplitude, the oscillation volume changed during the incremental pressure steps following a parabolic pattern, with an inverse relationship to the carbon dioxide pressures. The pressures corresponding with maximal compliance, maximal oscillation volume and minimal carbon dioxide were similar and highly correlated. Regional analysis showed similar findings. The increase in pressure amplitude resulted in increased oscillation volumes and decreased carbon dioxide levels, while FRC remained unchanged. In HFV pre-term infants with RDS, oscillation volumes are closely related to the position of ventilation in the pressure-volume envelope and the applied pressure amplitude. Changes in pressure amplitude do not seem to affect FRC.

Changes in lung volume and ventilation during surfactant treatment in ventilated preterm infants.

RATIONALE: The immediate and regional effects of exogenous surfactant in open lung high-frequency oscillatory ventilated (HFOV) preterm infants are unknown. OBJECTIVES: To assess regional changes in lung volume, mechanics, and ventilation during and after surfactant administration in HFOV preterm infants with respiratory distress syndrome (RDS). METHODS: Using electrical impedance tomography, changes in lung volume were continuously recorded during a stepwise recruitment procedure before, during, and after surfactant administration in 15 preterm infants (gestational age: 28.3 wk; birth weight: 1,000 g). Deflation limbs of the pressure-impedance curve before and after surfactant were mapped and the effect of surfactant on oscillation volumes and ventilation was determined. Data were analyzed for the whole cross-section and the left, right, ventral, and dorsal lung regions. MEASUREMENTS AND MAIN RESULTS: Surfactant increased lung volume by 61 ± 39% within a median time of 241 seconds. The ventral to dorsal ratio in lung volume changed significantly from 1.16 before to 0.81 after surfactant administration. The upper inflection point of the deflation limb after surfactant (10.4 ± 2.4 cm H(2)O) was significantly lower compared with before surfactant (16.4 ± 3.1 cm H(2)O). Surfactant increased maximal compliance of the respiratory system, and this effect was reached at lower airway pressures. Surfactant caused a transient decrease in oscillatory volume but did not alter its regional distribution. CONCLUSIONS: Surfactant treatment in HFOV preterm infants with RDS causes a rapid increase and subsequent stabilization of lung volume, which is most prominent in dependent lung regions. It increased maximal compliance, but this effect is only reached at lower airway pressures.

Prolonged Continuous Monitoring of Regional Lung Function in Infants with Respiratory Failure.

Rationale: Electrical impedance tomography (EIT) allows instantaneous and continuous visualization of regional ventilation and changes in end-expiratory lung volume at the bedside. There is particular interest in using EIT for monitoring in critically ill neonates and young children with respiratory failure. Previous studies have focused only on short-term monitoring in small populations. The feasibility and safety of prolonged monitoring with EIT in neonates and young children have not been demonstrated yet. Objectives: To evaluate the feasibility and safety of long-term EIT monitoring in a routine clinical setting and to describe changes in ventilation distribution and homogeneity over time and with positioning in a multicenter cohort of neonates and young children with respiratory failure. Methods: At four European University hospitals, we conducted an observational study (NCT02962505) on 200 patients with postmenstrual ages (PMA) between 25 weeks and 36 months, at risk for or suffering from respiratory failure. Continuous EIT data were obtained using a novel textile 32-electrode interface and recorded at 48 images/s for up to 72 hours. Clinicians were blinded to EIT images during the recording. EIT parameters and the effects of body position on ventilation distribution were analyzed offline. Results: The average duration of EIT measurements was 53 ± 20 hours. Skin contact impedance was sufficient to allow image reconstruction for valid ventilation analysis during a median of 92% (interquartile range, 77-98%) of examination time. EIT examinations were well tolerated, with minor skin irritations (temporary redness or imprint) occurring in 10% of patients and no moderate or severe adverse events. Higher ventilation amplitude was found in the dorsal and right lung areas when compared with the ventral and left regions, respectively. Prone positioning resulted in an increase in the ventilation-related EIT signal in the dorsal hemithorax, indicating increased ventilation of the dorsal lung areas. Lateral positioning led to a redistribution of ventilation toward the dependent lung in preterm infants and to the nondependent lung in patients with PMA > 37 weeks. Conclusions: EIT allows continuous long-term monitoring of regional lung function in neonates and young children for up to 72 hours with minimal adverse effects. Our study confirmed the presence of posture-dependent changes in ventilation distribution and their dependency on PMA in a large patient cohort. Clinical trial registered with www.clinicaltrials.gov (NCT02962505).

Changes in lung volume and ventilation during lung recruitment in high-frequency ventilated preterm infants with respiratory distress syndrome.

OBJECTIVES: To assess global and regional changes in lung volume and ventilation during lung recruitment in preterm infants with respiratory distress syndrome. STUDY DESIGN: Using electrical impedance tomography, changes in lung volume and ventilation were measured in 15 high-frequency oscillatory ventilated preterm infants during oxygenation-guided recruitment maneuvers. The inflation and deflation limbs were mapped, and the lower and upper inflection points were calculated using both oxygenation and impedance data. The impedance data were also used to determine recruitment-related changes in oscillation volume and distribution. RESULTS: During inflation, lower and upper inflection points were identified in the majority of infants. The deflation limb showed clear lung hysteresis in all infants. The upper inflection point was significantly lower when comparing the pressure/oxygenation and pressure/impedance curves. Lung volume changes differed between the ventral and dorsal regions, but did not show a consistent pattern. Optimal recruitment increased the oscillation volume, but the distribution of ventilation was relatively homogeneous along the ventral-dorsal axis. CONCLUSIONS: Lung hysteresis is present in preterm infants with respiratory distress syndrome. Regional differences in lung volume changes and ventilation during high-frequency oscillatory ventilation with lung recruitment are relatively modest and do not follow a gravity-dependent distribution.

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.

Electrical impedance tomography identifies a distinct change in regional phase angle delay pattern in ventilation filling immediately prior to a spontaneous pneumothorax.

Pneumothoraxes are common in preterm infants and are a major cause of morbidity. Early detection and treatment of pneumothoraxes are vital to minimize further respiratory compromise. Electrical impedance tomography (EIT) has been suggested as a method of rapidly detecting pneumothoraxes at the bedside. Our objective was to define the EIT-derived regional phase angle differences in filling characteristics before and during spontaneous pneumothoraxes in preterm lambs. Preterm lambs (124-127-day gestation) were ventilated with high-frequency oscillatory ventilation for 120 min. EIT data and cardiorespiratory parameters were monitored continuously and recorded for 3 min every 15 min. Six animals spontaneously developed a pneumothorax within a gravity-nondependent quadrant of the lung and were included for this analysis. Changes in end-expiratory lung impedance (EELI), ventilation, and phase angle delay were calculated in the four lung quadrants at the onset of the pneumothorax and 15 and 30 min prior. At the onset of the pneumothorax, all animals showed a clear increase in EELI in the affected lung quadrant. Fifteen and thirty minutes before the pneumothorax there was a significant phase angle delay between the nondependent and dependent lung. At 1 min before pneumothorax this phase angle delay was isolated just to the affected quadrant (nondependent). These findings are the first description of the events within the lung at initiation of a pneumothorax, demonstrating distinct predictive changes in air-filling characteristics before the occurrence of pneumothorax. This suggests that EIT may be able to accurately identify the onset of a pneumothorax.NEW & NOTEWORTHY In this article we describe for the first time predictive changes in electrical impedance tomography-based regional filling characteristics of the lung before the onset of a one-sided pneumothorax in six preterm lambs ventilated with high-frequency oscillatory ventilation. This can give clinicians bedside information to change treatment of preterm infants and prevent pneumothorax as life-threatening event from happening.

Initial Observations on the Effect of Repeated Surfactant Dose on Lung Volume and Ventilation in Neonatal Respiratory Distress Syndrome.

BACKGROUND: Exogenous surfactant administration is an essential part of respiratory distress syndrome treatment in preterm infants. Current guidelines recommend the first dose to be given as early as possible, followed by an additional dose if symptoms persist. The effect of additional dosing on regional ventilation and lung volume has not been investigated so far. OBJECTIVES: The aim of this study was to assess changes in ventilation distribution, lung volume, and gas exchange following repeated surfactant dosing in invasively ventilated neonates. METHOD: Preterm infants requiring invasive ventilation and repeated surfactant treatment, and participating in the prospective observational multicenter trial "Continuous Regional Analysis Device for neonate Lung (CRADL)" were included in this analysis. Ventilation distribution, end-expiratory lung impedance (EELZ), and tidal impedance variation were determined by electrical impedance tomography together with clinical parameters before and after repeat endotracheal surfactant treatment. RESULTS: Nine neonates (gestational age 32.7 ± 2.7 weeks, weight 1,724 ± 691 g) received an additional dose of surfactant at a median postnatal age of 33.5 h (IQR 9.1-46.6). One patient was excluded from the analysis due to simultaneous interventions confounding data analysis. Repeated surfactant dose did not significantly affect ventilation distribution. There were no significant changes in EELZ or tidal impedance variation. SpO2/FiO2 increased from 248 ± 104 to 367 ± 92 (p = 0.001), while FiO2 was reduced from 0.41 ± 0.20 to 0.27 ± 0.10 (p = 0.004). Expiratory tidal volume fell from 4.3 ± 0.6 to 3.0 ± 1.2 mL/kg (p = 0.03), while other ventilator and clinical parameters remained stable. CONCLUSIONS: Repeated surfactant dose during invasive ventilation improves oxygenation without measurable changes in EELZ or ventilation distribution.