Factors that impact second attempt success for neonatal intubation following first attempt failure: a report from the National Emergency Airway Registry for Neonates.

OBJECTIVE: To determine the factors associated with second attempt success and the risk of adverse events following a failed first attempt at neonatal tracheal intubation. DESIGN: Retrospective analysis of prospectively collected data on intubations performed in the neonatal intensive care unit (NICU) and delivery room from the National Emergency Airway Registry for Neonates (NEAR4NEOS). SETTING: Eighteen academic NICUs in NEAR4NEOS. PATIENTS: Neonates requiring two or more attempts at intubation between October 2014 and December 2021. MAIN OUTCOME MEASURES: The primary outcome was successful intubation on the second attempt, with severe tracheal intubation-associated events (TIAEs) or severe desaturation (≥20% decline in oxygen saturation) being secondary outcomes. Multivariate regression examined the associations between these outcomes and patient characteristics and changes in intubation practice. RESULTS: 5805 of 13 126 (44%) encounters required two or more intubation attempts, with 3156 (54%) successful on the second attempt. Second attempt success was more likely with changes in any of the following: intubator (OR 1.80, 95% CI 1.56 to 2.07), stylet use (OR 1.65, 95% CI 1.36 to 2.01) or endotracheal tube (ETT) size (OR 2.11, 95% CI 1.74 to 2.56). Changes in stylet use were associated with a reduced chance of severe desaturation (OR 0.74, 95% CI 0.61 to 0.90), but changes in intubator, laryngoscope type or ETT size were not; no changes in intubator or equipment were associated with severe TIAEs. CONCLUSIONS: Successful neonatal intubation on a second attempt was more likely with a change in intubator, stylet use or ETT size.

Factors that determine first intubation attempt success in high-risk neonates.

BACKGROUND: Approximately 50% of all neonatal endotracheal intubation attempts are unsuccessful and associated with airway injury and cardiorespiratory instability. The aim of this study was to describe intubation practice at a high-risk Neonatal Intensive Care Unit (NICU) and identify factors associated with successful intubation at the first attempt. METHODS: Retrospective cohort study of all infants requiring intubation within the Royal Children's Hospital NICU over three years. Data was collected from the National Emergency Airway Registry for Neonates (NEAR4NEOS). Outcomes were number of attempts, level of operator training, equipment used, difficult airway grade, and clinical factors. Univariate and multivariate analysis were performed to determine factors independently associated with first attempt success. RESULTS: Three hundred and sixty intubation courses, with 538 attempts, were identified. Two hundred and twenty-five (62.5%) were successful on first attempt, with similar rates at subsequent attempts. On multivariate analysis, increasing operator seniority increased the chance of first attempt success. Higher glottic airway grades were associated with lower chance of first attempt success, but neither a known difficult airway nor use of a stylet were associated with first attempt success. CONCLUSION: In a NICU with a high rate of difficult airways, operator experience rather than equipment was the greatest determinant of intubation success. IMPACT: Neonatal intubation is a high-risk lifesaving procedure, and this is the first report of intubation practices at a quaternary surgical NICU that provides regional referral services for complex medical and surgical admissions. Our results showed that increasing operator seniority and lower glottic airway grades were associated with increased first attempt intubation success rates, while factors such as gestational age, weight, stylet use, and known history of difficult airway were not. Operator factors rather than equipment factors were the greatest determinants of first attempt success, highlighting the importance of team selection for neonatal intubations in a high-risk cohort of infants.

Lung ultrasound detects regional aeration inhomogeneity in ventilated preterm lambs.

BACKGROUND: Inhomogeneous lung aeration is a significant contributor to preterm lung injury. EIT detects inhomogeneous aeration in the research setting. Whether LUS detects inhomogeneous aeration is unknown. The aim was to determine whether LUS detects regional inhomogeneity identified by EIT in preterm lambs. METHODS: LUS and EIT were simultaneously performed on mechanically ventilated preterm lambs. LUS images from non-dependent and dependent regions were acquired and reported using a validated scoring system and computer-assisted quantitative LUS greyscale analysis (Q-LUSMGV). Regional inhomogeneity was calculated by observed over predicted aeration ratio from the EIT reconstructive model. LUS scores and Q-LUSMGV were compared with EIT aeration ratios using one-way ANOVA. RESULTS: LUS was performed in 32 lambs (~125d gestation, 128 images). LUS scores were greater in upper anterior (non-dependent) compared to lower lateral (dependent) regions of the left (3.4 vs 2.9, p = 0.1) and right (3.4 vs 2.7, p < 0.0087). The left and right upper regions also had greater LUS scores compared to right lower (3.4 vs 2.7, p < 0.0087) and left lower (3.7 vs 2.9, p = 0.1). Q-LUSMGV yielded similar results. All LUS findings corresponded with EIT regional differences. CONCLUSION: LUS may have potential in measuring regional aeration, which should be further explored in human studies. IMPACT: Inhomogeneous lung aeration is an important contributor to preterm lung injury, however, tools detecting inhomogeneous aeration at the bedside are limited. Currently, the only tool clinically available to detect this is electrical impedance tomography (EIT), however, its use is largely limited to research. Lung ultrasound (LUS) may play a role in monitoring lung aeration in preterm infants, however, whether it detects inhomogeneous lung aeration is unknown. Visual LUS scores and mean greyscale image analysis using computer assisted quantitative LUS (Q-LUSMGV) detects regional lung aeration differences when compared to EIT. This suggests LUS reliably detects aeration inhomogeneity warranting further investigation in human trials.

Inflating Pressure and Not Expiratory Pressure Initiates Lung Injury at Birth in Preterm Lambs.

Rationale: Inflation is essential for aeration at birth, but current inflating pressure settings are without an evidence base. Objectives: To determine the role of inflating pressure (ΔP), and its relationship with positive end-expiratory pressure (PEEP), in initiating early lung injury pathways in the preterm lamb lung. Methods: Preterm (124 to 127 d) steroid-exposed lambs (n = 45) were randomly allocated (8-10 per group) to 15 minutes of respiratory support with placental circulation and 20 or 30 cm H2O ΔP, with an initial high PEEP (maximum, 20 cm H2O) recruitment maneuver known to facilitate aeration (dynamic PEEP), and compared with dynamic PEEP with no ΔP or 30 cm H2O ΔP and low (4 cm H2O) PEEP. Lung mechanics and aeration were measured throughout. After an additional 30 minutes of apneic placental support, lung tissue and bronchoalveolar fluid were analyzed for regional lung injury, including proteomics. Measurements and Main Results: The 30 cm H2O ΔP and dynamic PEEP strategies resulted in quicker aeration and better compliance but higher tidal volumes (often >8 ml/kg, all P < 0.0001; mixed effects) and injury. ΔP 20 cm H2O with dynamic PEEP resulted in the same lung mechanics and aeration, but less energy transmission (tidal mechanical power), as ΔP 30 cm H2O with low PEEP. Dynamic PEEP without any tidal inflations resulted in the least lung injury. Use of any tidal inflating pressures altered metabolic, coagulation and complement protein pathways within the lung. Conclusions: Inflating pressure is essential for the preterm lung at birth, but it is also the primary mediator of lung injury. Greater focus is needed on strategies that identify the safest application of pressure in the delivery room.

Lung ultrasound of the dependent lung detects real-time changes in lung volume in the preterm lamb.

BACKGROUND: Effective lung protective ventilation requires reliable, real-time estimation of lung volume at the bedside. Neonatal clinicians lack a readily available imaging tool for this purpose. OBJECTIVE: To determine the ability of lung ultrasound (LUS) of the dependent region to detect real-time changes in lung volume, identify opening and closing pressures of the lung, and detect pulmonary hysteresis. METHODS: LUS was performed on preterm lambs (n=20) during in vivo mapping of the pressure-volume relationship of the respiratory system using the super-syringe method. Electrical impedance tomography was used to derive regional lung volumes. Images were blindly graded using an expanded scoring system. The scores were compared with total and regional lung volumes, and differences in LUS scores between pressure increments were calculated. RESULTS: Changes in LUS scores correlated moderately with changes in total lung volume (r=0.56, 95% CI 0.47-0.64, p<0.0001) and fairly with right whole (r=0.41, CI 0.30-0.51, p<0.0001), ventral (r=0.39, CI 0.28-0.49, p<0.0001), central (r=0.41, CI 0.31-0.52, p<0.0001) and dorsal (r=0.38, CI 0.27-0.49, p<0.0001) regional lung volumes. The pressure-volume relationship of the lung exhibited hysteresis in all lambs. LUS was able to detect hysteresis in 17 (85%) lambs. The greatest changes in LUS scores occurred at the opening and closing pressures. CONCLUSION: LUS was able to detect large changes in total and regional lung volume in real time and correctly identified opening and closing pressures but lacked the precision to detect small changes in lung volume. Further work is needed to improve precision prior to translation to clinical practice.

Aeration strategy at birth does not impact carotid haemodynamics in preterm lambs.

BACKGROUND: The impact of different respiratory strategies at birth on the preterm lung is well understood; however, concerns have been raised that lung recruitment may impede cerebral haemodynamics. This study aims to examine the effect of three different ventilation strategies on carotid blood flow, carotid artery oxygen content and carotid oxygen delivery. METHODS: 124-127-day gestation apnoeic intubated preterm lambs studied as part of a larger programme primarily assessing lung injury were randomised to positive pressure ventilation with positive end-expiratory pressure (PEEP) 8 cmH2O (No-RM; n = 12), sustained inflation (SI; n = 15) or dynamic PEEP strategy (DynPEEP; maximum PEEP 14 or 20 cmH2O, n = 41) at birth, followed by 90 min of standardised ventilation. Haemodynamic data were continuously recorded, with intermittent arterial blood gas analysis. RESULTS: Overall carotid blood flow measures were comparable between strategies. Except for mean carotid blood flow that was significantly lower for the SI group compared to the No-RM and DynPEEP groups over the first 3 min (p < 0.0001, mixed effects model). Carotid oxygen content and oxygen delivery were similar between strategies. Maximum PEEP level did not alter cerebral haemodynamic measures. CONCLUSIONS: Although there were some short-term variations in cerebral haemodynamics between different PEEP strategies and SI, these were not sustained. IMPACT: Different pressure strategies to facilitate lung aeration at birth in preterm infants have been proposed. There is minimal information on the effect of lung recruitment on cerebral haemodynamics. This is the first study that compares the effect of sustained lung inflation and dynamic and static positive end-expiratory pressure on cerebral haemodynamics. We found that the different ventilation strategies did not alter carotid blood flow, carotid oxygen content or carotid oxygen delivery. This preclinical study provides some reassurance that respiratory strategies designed to focus on lung aeration at birth may not impact cerebral haemodynamics in preterm neonates.

Quantitative lung ultrasound detects dynamic changes in lung recruitment in the preterm lamb.

BACKGROUND: Lung ultrasound (LUS) may not detect small, dynamic changes in lung volume. Mean greyscale measurement using computer-assisted image analysis (Q-LUSMGV) may improve the precision of these measurements. METHODS: Preterm lambs (n = 40) underwent LUS of the dependent or non-dependent lung during static pressure-volume curve mapping. Total and regional lung volumes were determined using the super-syringe technique and electrical impedance tomography. Q-LUSMGV and gold standard measurements of lung volume were compared in 520 images. RESULTS: Dependent Q-LUSMGV moderately correlated with total lung volume (rho = 0.60, 95% CI 0.51-0.67) and fairly with right whole (rho = 0.39, 0.27-0.49), central (rho = 0.38, 0.27-0.48), ventral (rho = 0.41, 0.31-0.51) and dorsal regional lung volumes (rho = 0.32, 0.21-0.43). Non-dependent Q-LUSMGV moderately correlated with total lung volume (rho = 0.57, 0.48-0.65) and fairly with right whole (rho = 0.43, 0.32-0.52), central (rho = 0.46, 0.35-0.55), ventral (rho = 0.36, 0.25-0.47) and dorsal lung volumes (rho = 0.36, 0.25-0.47). All correlation coefficients were statistically significant. Distinct inflation and deflation limbs, and sonographic pulmonary hysteresis occurred in 95% of lambs. The greatest changes in Q-LUSMGV occurred at the opening and closing pressures. CONCLUSION: Q-LUSMGV detected changes in total and regional lung volume and offers objective quantification of LUS images, and may improve bedside discrimination of real-time changes in lung volume. IMPACT: Lung ultrasound (LUS) offers continuous, radiation-free imaging that may play a role in assessing lung recruitment but may not detect small changes in lung volume. Mean greyscale image analysis using computer-assisted quantitative LUS (Q-LUSMGV) moderately correlated with changes in total and regional lung volume. Q-LUSMGV identified opening and closing pressure and pulmonary hysteresis in 95% of lambs. Computer-assisted image analysis may enhance LUS estimation of lung recruitment at the bedside. Future research should focus on improving precision prior to clinical translation.

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.

Imaging the Respiratory Transition at Birth: Unraveling the Complexities of the First Breaths of Life.

Rationale: The transition to air breathing at birth is a seminal respiratory event common to all humans, but the intrathoracic processes remain poorly understood. Objectives: The objectives of this prospective, observational study were to describe the spatiotemporal gas flow, aeration, and ventilation patterns within the lung in term neonates undergoing successful respiratory transition. Methods: Electrical impedance tomography was used to image intrathoracic volume patterns for every breath until 6 minutes from birth in neonates born by elective cesearean section and not needing resuscitation. Breaths were classified by video data, and measures of lung aeration, tidal flow conditions, and intrathoracic volume distribution calculated for each inflation. Measurements and Main Results: A total of 1,401 breaths from 17 neonates met all eligibility and data analysis criteria. Stable FRC was obtained by median (interquartile range) 43 (21-77) breaths. Breathing patterns changed from predominantly crying (80.9% first min) to tidal breathing (65.3% sixth min). From birth, tidal ventilation was not uniform within the lung, favoring the right and nondependent regions; P < 0.001 versus left and dependent regions (mixed-effects model). Initial crying created a unique volumetric pattern with delayed midexpiratory gas flow associated with intrathoracic volume redistribution (pendelluft flow) within the lung. This preserved FRC, especially within the dorsal and right regions. Conclusions: The commencement of air breathing at birth generates unique flow and volume states associated with marked spatiotemporal ventilation inhomogeneity not seen elsewhere in respiratory physiology. At birth, neonates innately brake expiratory flow to defend FRC gains and redistribute gas to less aerated regions.

Skin-to-skin care alters regional ventilation in stable neonates.

OBJECTIVE: Skin-to-skin care (SSC) has proven psychological benefits; however, the physiological effects are less clearly defined. Regional ventilation patterns during SSC have not previously been reported. This study aimed to compare regional ventilation indices and other cardiorespiratory parameters during prone SSC with supine and prone position cot-nursing. DESIGN: Prospective observational study. SETTING: Single quaternary neonatal intensive care unit in Australia. PATIENTS: 20 infants spontaneously breathing (n=17) or on non-invasive ventilation (n=3), with mean (SD) gestational age at birth of 33 (5) weeks. INTERVENTIONS: Thirty-minute episodes of care in each position: supine cot care, prone SSC and prone cot care preceding a 10 min period of continuous electrical impedance tomography measurements of regional ventilation. MAIN OUTCOME MEASURES: In each position, ventral-dorsal and right-left centre of ventilation (CoV), percentage of whole lung ventilation by region and percentage of apparent unventilated lung regions were determined. Heart and respiratory rates, oxygen saturation and axillary temperature were also measured. RESULTS: Heart and respiratory rates, oxygen saturation, temperature and right-left lung ventilation did not differ between the three positions (mixed-effects model). Ventilation generally favoured the dorsal lung, but the mean (95% CI) ventrodorsal CoV was -2.0 (-0.4 to -3.6)% more dorsal during SSC compared with prone. Supine position resulted in 5.0 (1.5 to 5.3)% and 4.5 (3.9 to 5.1)% less apparently unventilated lung regions compared with SSC and prone, respectively. CONCLUSIONS: In clinically stable infants, SSC generates a distinct regional ventilation pattern that is independent of prone position and results in greater distribution of ventilation towards the dorsal lung.

Regional ventilation characteristics during non-invasive respiratory support in preterm infants.

OBJECTIVES: To determine the regional ventilation characteristics during non-invasive ventilation (NIV) in stable preterm infants. The secondary aim was to explore the relationship between indicators of ventilation homogeneity and other clinical measures of respiratory status. DESIGN: Prospective observational study. SETTING: Two tertiary neonatal intensive care units. PATIENTS: Forty stable preterm infants born <30 weeks of gestation receiving either continuous positive airway pressure (n=32) or high-flow nasal cannulae (n=8) at least 24 hours after extubation at time of study. INTERVENTIONS: Continuous electrical impedance tomography imaging of regional ventilation during 60 min of quiet breathing on clinician-determined non-invasive settings. MAIN OUTCOME MEASURES: Gravity-dependent and right-left centre of ventilation (CoV), percentage of whole lung tidal volume (VT) by lung region and percentage of lung unventilated were determined for 120 artefact-free breaths/infant (4770 breaths included). Oxygen saturation, heart and respiratory rates were also measured. RESULTS: Ventilation was greater in the right lung (mean 69.1 (SD 14.9)%) total VT and the gravity-non-dependent (ND) lung; ideal-actual CoV 1.4 (4.5)%. The central third of the lung received the most VT, followed by the non-dependent and dependent regions (p<0.0001 repeated-measure analysis of variance). Ventilation inhomogeneity was associated with worse peripheral capillary oxygen saturation (SpO2)/fraction of inspired oxygen (FiO2) (p=0.031, r2 0.12; linear regression). In those infants that later developed bronchopulmonary dysplasia (n=25), SpO2/FiO2 was worse and non-dependent ventilation inhomogeneity was greater than in those that did not (both p<0.05, t-test Welch correction). CONCLUSIONS: There is high breath-by-breath variability in regional ventilation patterns during NIV in preterm infants. Ventilation favoured the ND lung, with ventilation inhomogeneity associated with worse oxygenation.

Respiratory mechanics during initial lung aeration at birth in the preterm lamb.

Despite recent insights into the dynamic processes during lung aeration at birth, several aspects remain poorly understood. We aimed to characterize changes in lung mechanics during the first inflation at birth and their relationship to changes in lung volume. Intubated preterm lambs (gestational age, 124-127 days; n = 17) were studied at birth. Lung volume changes were measured by electrical impedance tomography (VLEIT). Respiratory system resistance (R5) and oscillatory compliance (Cx5) were monitored with the forced oscillation technique at 5 Hz. Lambs received 3-7 s of 8 cmH2O of continuous distending pressure (CDP) before delivery of a sustained inflation (SI) of 40 cmH2O. The SI was then applied until either Cx5 or the VLEIT or the airway opening volume was stable. CDP was resumed for 3-7 s before commencement of mechanical ventilation. The exponential increases with time of Cx5 and VLEIT from commencement of the SI were characterized by estimating their time constants (τCx5 and τVLEIT, respectively). During SI, a fast decrease in R5 and an exponential increase in Cx5 and VLEIT were observed. Cx5 and VLEIT provided comparable information on the dynamics of lung aeration in all lambs, with τCx5 and τVLEIT being highly linearly correlated (r2 = 0.87, P < 0.001). Cx5 and VLEIT decreased immediately after SI. Despite the standardization of the animal model, changes in Cx5 and R5 both during and after SI were highly variable. Lung aeration at birth is characterized by a fast reduction in resistance and a slower increase in oscillatory compliance, the latter being a direct reflection of the amount of lung aeration.

Aeration strategy at birth influences the physiological response to surfactant in preterm lambs.

BACKGROUND: The influence of pressure strategies to promote lung aeration at birth on the subsequent physiological response to exogenous surfactant therapy has not been investigated. OBJECTIVES: To compare the effect of sustained inflation (SI) and a dynamic positive end-expiratory pressure (PEEP) manoeuvre at birth on the subsequent physiological response to exogenous surfactant therapy in preterm lambs. METHODS: Steroid-exposed preterm lambs (124-127 days' gestation; n=71) were randomly assigned from birth to either (1) positive-pressure ventilation (PPV) with no recruitment manoeuvre; (2) SI until stable aeration; or (3) 3 min dynamic stepwise PEEP strategy (maximum 14-20 cmH2O; dynamic PEEP (DynPEEP)), followed by PPV for 60 min using a standardised protocol. Surfactant (200 mg/kg poractant alfa) was administered at 10 min. Dynamic compliance, gas exchange and regional ventilation and aeration characteristics (electrical impedance tomography) were measured throughout and compared between groups, and with a historical group (n=38) managed using the same strategies without surfactant. RESULTS: Compliance increased after surfactant only in the DynPEEP group (p<0.0001, repeated measures analysis of variance), being 0.17 (0.10, 0.23) mL/kg/cmH2O higher at 60 min than the SI group. An SI resulted in the least uniform aeration, and unlike the no-recruitment and DynPEEP groups, the distribution of aeration and tidal ventilation did not improve with surfactant. All groups had similar improvements in oxygenation post-surfactant compared with the corresponding groups not treated with surfactant. CONCLUSIONS: A DynPEEP strategy at birth may improve the response to early surfactant therapy, whereas rapid lung inflation with SI creates non-uniform aeration that appears to inhibit surfactant efficacy.

Gestational Age Influences the Early Microarchitectural Changes in Response to Mechanical Ventilation in the Preterm Lamb Lung.

Background: Preterm birth is associated with abnormal lung architecture, and a reduction in pulmonary function related to the degree of prematurity. A thorough understanding of the impact of gestational age on lung microarchitecture requires reproducible quantitative analysis of lung structure abnormalities. The objectives of this study were (1) to use quantitative histological software (ImageJ) to map morphological patterns of injury resulting from delivery of an identical ventilation strategy to the lung at varying gestational ages and (2) to identify associations between gestational age-specific morphological alterations and key functional outcomes. Method: Lung morphology was compared after 60 min of a standardized ventilation protocol (40 cm H2O sustained inflation and then volume-targeted positive pressure ventilation with positive end-expiratory pressure 8 cm H2O) in lambs at different gestations (119, 124, 128, 133, 140d) representing the spectrum of premature developmental lung states and the term lung. Age-matched controls were compared at 124 and 128d gestation. Automated and manual functions of Image J were used to measure key histological features. Correlation analysis compared morphological and functional outcomes in lambs aged ≤128 and >128d. Results: In initial studies, unventilated lung was indistinguishable at 124 and 128d. Ventilated lung from lambs aged 124d gestation exhibited increased numbers of detached epithelial cells and lung tissue compared with 128d lambs. Comparing results from saccular to alveolar development (120-140d), lambs aged ≤124d exhibited increased lung tissue, average alveolar area, and increased numbers of detached epithelial cells. Alveolar septal width was increased in lambs aged ≤128d. These findings were mirrored in the measures of gas exchange, lung mechanics, and molecular markers of lung injury. Correlation analysis confirmed the gestation-specific relationships between the histological assessments and functional measures in ventilated lambs at gestation ≤128 vs. >128d. Conclusion: Image J allowed rapid, quantitative assessment of alveolar morphology, and lung injury in the preterm lamb model. Gestational age-specific patterns of injury in response to delivery of an identical ventilation strategy were identified, with 128d being a transition point for associations between morphological alterations and functional outcomes. These results further support the need to develop individualized respiratory support approaches tailored to both the gestational age of the infant and their underlying injury response.

A dedicated respiratory function monitor to improve tidal volume delivery during neonatal anesthesia.

BACKGROUND: Tight control of tidal volume using accurate monitoring may improve neonatal outcomes. However, respiratory function monitors incorporated in current anesthetic workstations are generally inaccurate at tidal volumes used for infants. AIMS: To determine if a specific respiratory function monitor for neonatal infants improved expired tidal volume delivery during anesthesia. METHOD: Infants <3 months old requiring intubation for surgery in the operating theater were studied. After intubation a Phillips NM3, Acutronic Florian, or Novametrix Ventcheck Respiratory Function Monitor was integrated into the circuit, and clinicians given access to the display for the duration of anesthesia. Breath-to-breath expired tidal volume delivery, leak, and delivered pressure were recorded, with cardiorespiratory parameters. These were compared with a matched control group with clinicians blinded to respiratory function monitor display. RESULTS: A total of 10 055 and 2569 inflations were measured in the respiratory function monitor visible (n = 32) and masked (n = 33) groups, respectively, with mean (standard deviation) delivered expired tidal volume 7.5 (2.4) mL/kg and 7.7 (3.0) mL/kg, respectively; mean difference (95% confidence interval) -0.2 (-1.1, 0.8) mL/kg (Welch's t test). In the visible group, 55.6% of expired tidal volumes were between 4 and 8 mL/kg compared to 51.7% in the masked group; relative benefit (95% confidence interval), 1.08 (1.03, 1.12). Expired tidal volume was less likely to be <4 mL/kg in the visible group compared to masked group; 6.4% vs 9.8%, 1.53 (1.33, 1.76). The use of a respiratory function monitor also reduced the number of inflations >10 mL/kg; 13.0% vs 22.0%, 1.11 (1.09, 1.14). CONCLUSION: Tidal volumes <4 mL/kg and >10 mL/kg are frequently delivered during neonatal anesthesia. The inclusion of an accurate respiratory function monitor may reduce the risk of exposure to potentially harmful tidal volumes.

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.

Preterm Lung Exhibits Distinct Spatiotemporal Proteome Expression at Initiation of Lung Injury.

The development of regional lung injury in the preterm lung is not well understood. This study aimed to characterize time-dependent and regionally specific injury patterns associated with early ventilation of the preterm lung using a mass spectrometry-based proteomic approach. Preterm lambs delivered at 124-127 days gestation received 15 or 90 minutes of mechanical ventilation (positive end-expiratory pressure = 8 cm H2O, Vt = 6-8 ml/kg) and were compared with unventilated control lambs. At study completion, lung tissue was taken from standardized nondependent and dependent regions, and assessed for lung injury via histology, quantitative PCR, and proteomic analysis using Orbitrap-mass spectrometry. Ingenuity pathway analysis software was used to identify temporal and region-specific enrichments in pathways and functions. Apoptotic cell numbers were ninefold higher in nondependent lung at 15 and 90 minutes compared with controls, whereas proliferative cells were increased fourfold in the dependent lung at 90 minutes. The relative gene expression of lung injury markers was increased at 90 minutes in nondependent lung and unchanged in gravity-dependent lung. Within the proteome, the number of differentially expressed proteins was fourfold higher in the nondependent lung than the dependent lung. The number of differential proteins increased over time in both lung regions. A total of 95% of enriched canonical pathways and 94% of enriched cellular and molecular functions were identified only in nondependent lung tissue from the 90-minute ventilation group. In conclusion, complex injury pathways are initiated within the preterm lung after 15 minutes of ventilation and amplified by continuing ventilation. Injury development is region specific, with greater alterations within the proteome of nondependent lung.

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.

Plasma proteomics reveals gestational age-specific responses to mechanical ventilation and identifies the mechanistic pathways that initiate preterm lung injury.

The preterm lung is particularly vulnerable to ventilator-induced lung injury (VILI) as a result of mechanical ventilation. However the developmental and pathological cellular mechanisms influencing the changing patterns of VILI have not been comprehensively delineated, preventing the advancement of targeted lung protective therapies. This study aimed to use SWATH-MS to comprehensively map the plasma proteome alterations associated with the initiation of VILI following 60 minutes of standardized mechanical ventilation from birth in three distinctly different developmental lung states; the extremely preterm, preterm and term lung using the ventilated lamb model. Across these gestations, 34 proteins were differentially altered in matched plasma samples taken at birth and 60 minutes. Multivariate analysis of the plasma proteomes confirmed a gestation-specific response to mechanical ventilation with 79% of differentially-expressed proteins altered in a single gestation group only. Six cellular and molecular functions and two physiological functions were uniquely enriched in either the extremely preterm or preterm group. Correlation analysis supported gestation-specific protein-function associations within each group. In identifying the gestation-specific proteome and functional responses to ventilation we provide the founding evidence required for the potential development of individualized respiratory support approaches tailored to both the developmental and pathological state of the lung.