Environmental And Genetic Risk Factors For Bronchopulmonary Dysplasia In Neonates

We hypothesized that early intubation would decrease the hazard of BPD and BPD/death in premature infants regardless of need for reintubation. Specific aims included assessing rates of BPD and BPD/death in infants first extubated between day of life (DOL)1-3 versus 4-7, 8+ and impact of re-intubation. We included infants with gestational age ≤28weeks, birth weight ≤1000g, and intubation on DOL1. Proportional hazards regression modeled time to BPD and BPD/death, adjusting for potential confounders. Of 262 infants, 101 (38.55%), 41 (15.65%) and 120 (45.80%) were extubated between DOL1-3, 4-7, and 8+, respectively. Extubation between DOL4-7 versus DOL1-3 was associated with an increased hazard of developing BPD (HR 1.7; 95%CI 1.0-2.8; p\u3c0.05). Extubation on DOL 8+ was associated with a significantly increased hazard compared to extubation between DOL1-3 (16.9; 10.5-27.1; \u3c0.0001) or DOL4-7 (10.0; 6.1-16.3; \u3c 0.0001). Similar results were noted with BPD/death. Re-intubation did not affect BPD and BPD/death. Delaying extubation beyond the first 3 and 7 days was associated with an increased risk of BPD and BPD/death. Re-intubation did not impact outcomes

Artificial Intelligence for the prediction of weaning readiness outcome in a multi-centrical clinical cohort of mechanically ventilated patients

Quando un paziente soffre di insufficienza respiratoria acuta, viene praticata la ventilazione meccanica (VM) finché questa non riesce a respirare di nuovo in autonomia. Il medico di Terapia Intensiva verifica ogni giorno se la VM può essere interrotta. Questo screening consiste in una prima fase, il Readiness Test (RT), che è composta da vari parametri clinici. Se questo test ha esito positivo, si sottopone il paziente a 30 minuti di respirazione spontanea (SBT). Se anche l'SBT viene superato con successo, la VM viene interrotta. Al contrario, se l’RT o l’SBT falliscono, il paziente rimane in VM e verrà rivalutato il giorno successivo. Quindi ogni giorno possono verificarsi tre scenari mutuamente esclusivi: l’SBT non verrà tentato, l’SBT fallirà o l’SBT avrà successo (portando quindi all’estubazione del paziente). Il modello di intelligenza artificiale sviluppato, è progettato per dedurre fin dalle prime ore del mattino quale dei tre scenari si verificherà probabilmente nel corso della giornata, partendo dai dati clinici del paziente, dalle informazioni raccolte nel diario clinico dei giorni precedenti e dall'intera storia di registrazione minuto-per-minuto dei vari parametri del ventilatore meccanico, provenienti da uno studio osservazionale retrospettivo multicentrico, condotto in Italia nel corso di 27 mesi. Questi dati vengono elaborati con un approccio di Deep Learning, attraverso una topologia di rete neurale multi-sorgente, alimentata da architetture ricorrenti multiple. Gli iper-parametri sono ottimizzati per selezionare il modello desiderato attraverso la convalida incrociata, riservando 36 pazienti su 182 per testare le prestazioni finali del modello su una serie di metriche, tra cui uno score personalizzato progettato per evidenziare l'impatto clinico. Il modello di intelligenza artificiale finale mostra un'accuratezza del 79% [74, 83%], uno score personalizzato di 0,01 [-0,04, 0,05], un MCC di 0,28 [0,17, 0,39], ottenendo un punteggio migliore rispetto agli altri modelli di confronto, tra cui XG Boost, addestrato solo sui dati clinici giornalieri del giorno precedente, che ha avuto un'accuratezza del 61% [56%, 66%], un MCC di 0,14 [0,06, 0,2] e uno score personalizzato di -0,05 [-0,08, -0,01]. Complessivamente, il modello di intelligenza artificiale è in grado di approssimare bene l'attuale gestione clinica giorno per giorno, fornendo suggerimenti al mattino presto. Inoltre, c'è ancora spazio per migliorare l'utilità clinica del modello considerando ulteriori dati di addestramento personalizzati.When someone suffers from acute respiratory failure, mechanical ventilation (MV) is performed until they can breathe on their own again. The doctor checks every day whether the MV can be stopped. This screening consists of a first phase, the Readiness Testing (RT), which includes various clinical parameters. If this test is successful, 30 minutes of spontaneous breathing (SBT) is attempted. If also the SBT is passed successfully, the VM is stopped. On the contrary, if RT or SBT fails, the patient will be re-evaluated the next day. So, every day three mutually exclusive scenarios may happen: SBT will not be attempted, SBT will fail, or SBT will succeed. Our artificial intelligence model is designed to infer early in the morning which of the three scenarios will probably occur during the day, starting from the patient's clinical data, from the information collected in the previous day’s clinical diary, and from whole minute-by-minute recording history of the various parameters of the mechanical ventilator, coming from a retrospective observational multi-centrical study, conducted in Italy over a course of 27 months. Those data are processed with a deep learning approach, through a multi-source neural network topology, powered by multiple recurrent architectures. Hyper-parameters are optimized to select the purposed model through cross-validation, setting aside 36 out of 182 patients for testing final model performance over a variety of metrics, including a custom score designed to highlight clinical impact. The final AI model had an accuracy of 79% [74, 83%], a custom score of 0.01 [-0.04, 0.05], a MCC of 0.28 [0.17, 0.39], scoring better than the other comparison models, including XG Boost that was trained on daily and baseline clinical data of the previous day only, which had an accuracy of 61% [56%, 66%], a MCC of 0.14 [0.06, 0.2] and a custom score of -0.05 [-0.08, -0.01]. Overall, AI model could approximate well what is the current clinical management throughout day-by-day providing suggestions early in the morning. Moreover, there are still space to improve the model clinical utility considering additional tailored training data

A randomised controlled trial comparing two methods of providing volume targeted ventilation in preterm infants :volume guarantee versus volume-controlled ventilation, The VoluVent Trial

M.D. ThesisBackground: Many preterm infants require mechanical ventilation via an endotracheal tube for the treatment of neonatal respiratory distress (RDS). A side effect of mechanical ventilation is lung injury. VTV aims to reduce lung injury by controlling the tidal volumes delivered to the infant by the ventilator. Many VTV modes are widely in use but have not been compared using clinically relevant outcomes. Aim: This was the first trial to compare two modes of VTV in preterm infants with RDS. We aimed to compare volume-controlled ventilation (VCV) with volume guarantee (VG) using clinically relevant outcomes. Hypothesis: We hypothesised that, in preterm infants with RDS, the time taken to be ready for extubation would be shorter in the VG group compared with VCV. The initial sample size calculation indicated that 102 infants were needed to show a 33% reduction in the time taken to be ready for extubation with a significance level of 0.05 and a power of 80%. Methods: This single centre, randomised controlled pilot trial was undertaken in a tertiary neonatal unit from July 2013 – December 2015. Infants were stratified into two groups according to gestational age at birth (<28 weeks’ gestation and 28 – 33+6 weeks’ gestation). The primary outcome was the duration of time from starting the trial mode until being ready for extubation. Readiness for extubation was defined using pre-determined ‘success’ criteria. Secondary outcomes included important clinical outcomes. After four months the consent method was changed from prospective to deferred parental consent. A trial oversight review of data from the first 50 infants identified that the primary outcome data were not likely to be normally distributed. The statistical analysis plan was therefore updated prior to any data analysis. We planned to present data as descriptive summary statistics including survival probabilities, hazard ratios (HRs) and odds ratios (ORs). In addition, using early phase trials statistical methods, a difference of 15% between groups in the numbers of infants reaching the ‘success’ criteria at 48 hours would indicate a potentially significant difference between groups. iv An ancillary study was undertaken using mechanistic data downloaded from ventilators to validate one of the ‘success’ criteria (mean airway pressure). Results: One hundred and thirteen infants were enrolled. One infant was subsequently withdrawn due to a diagnosis consistent with exclusion criteria. The median time to ‘success’ criteria was 23 hours (95% CI 10.78 – 35.22 hours) in the VG group and 36 hours (95% CI 18.03 – 53.97) in the VCV group. The HR was 0.93 (95% CI 0.63 – 1.37). Thirty four infants in the VG group and 33 infants in the VCV group had met the ‘success’ criteria by 48 hours. Subgroup analyses showed that, in infants born at 28 – 33+6 weeks’ gestation, the median time to reach the primary outcome faster in the VG group. The pneumothorax rates and duration of ventilation were lower in the VG group. The use of deferred consent appeared to be more acceptable to parents and led to an improvement in the recruitment rate. The ancillary study showed very good correlation between the mean airway pressure values recorded manually once every hour and the values downloaded with every breath. This validated the use of manual recordings of mean airway pressure as part of the primary outcome. Conclusions: There was a clinical important difference between VG and VCV in the time taken for infants to be ready for extubation. This difference favoured VG but a larger trial is needed to show a definitive result. This trial also highlights current gaps in knowledge regarding short-term clinical outcomes and the use of VTV modes in different subgroups of infants. Deferred consent appears to be acceptable to parents of newborn infants but qualitative research is needed to explore this further. This thesis describes The VoluVent Trial (ISRCTN 04448562), the first clinical trial to compare two types of volume-targeted ventilation (VTV) in preterm infants. One of the known side effects of mechanical ventilation is lung injury. VTV aims to minimise ventilator-associated lung injury and different types of VTV are used widely. However, there is no evidence to confirm whether one type of VTV is better than another for preterm infant

INTERMITTENT HYPOXEMIA IN PRETERM INFANTS

Intermittent hypoxemia (IH) is defined as episodic drops in oxygen saturation (SpO2). Virtually all preterm infants have IH events. Extremely preterm infants have hundreds of IH events per day. The extent of IH is not apparent clinically as accurately documenting cardiorespiratory events for day-to-day patient care management is challenging. High resolution pulse oximeters with 2 second averaging time are currently the ideal methods to measure IH. We have developed novel methods and processes to accurately and efficiently calculate an IH profile that reflects to spectrum of the problem. The natural progression of IH is dynamic. There is low incidence of IH in the few 2 weeks of life, followed by a progressive increase until peak IH at 4-5 week after which IH plateaus. Multiple factors place preterm infants at high risk for increased IH. These factors include respiratory immaturity, lung disease, and anemia. We also show that preterm infants prenatally exposed to opioids or inflammation (due to maternal chorioamnionitis) have increased IH measures compared to unexposed infants. Interestingly, the increased IH in the exposed groups persists beyond the immediate postnatal period. Brief episodes of oxygen desaturations may seem clinically insignificant; however, these events may have a cumulative effect on neonatal outcomes. There is mounting evidence from both animal models and clinical studies suggesting that IH is associated with injury and poor outcomes such as impaired growth, retinopathy of prematurity and neurodevelopmental impairment. In addition data from neonatal animal models and adults with obstructive sleep apnea suggest that IH is pro inflammatory itself. We demonstrate in this document for the first time in preterm infants that IH is associated with increased serum inflammatory marker, C-reactive protein. Finally, a valuable experience throughout this process is working with a talented and dedicated multidisciplinary team. We are a solid example of the value of team science during this new era of clinical and translational research. Our respiratory control research program is one of handful programs nationwide able to perform such high-fidelity studies related to cardiorespiratory events in preterm infants. We will continue to tackle complex questions involving health of infants

Mechanical Ventilation

Mechanical ventilation, ventilator management, and weaning from mechanical ventilation vary based on location within the hospital, type of lung injury, and medical condition of the patient. Understanding the types of lung injury and various methods of achieving ventilation expand the armamentarium of the practitioner and allow for the best management decisions. This book begins with the use of a high-flow nasal cannula (HFNC) and a detailed description of the advanced modes of ventilation. The information on the types of ventilation can then be applied to the ventilation approaches in different populations of patients: the trauma patients, the obese patients, and the patients under neurocritical care. The conclusion contains a discussion of the mechanisms on how to wean from mechanical ventilation and how certain medical conditions affect the weaning process

Comparison of oxygen supplementation in very preterm infants: Variations of oxygen saturation features and their application to hypoxemic episode based risk stratification

BackgroundOxygen supplementation is commonly used to maintain oxygen saturation (SpO2) levels in preterm infants within target ranges to reduce intermittent hypoxemic (IH) events, which are associated with short- and long-term morbidities. There is not much information available about differences in oxygenation patterns in infants undergoing such supplementations nor their relation to observed IH events. This study aimed to describe oxygenation characteristics during two types of supplementation by studying SpO2 signal features and assess their performance in hypoxemia risk screening during NICU monitoring.Subjects and methodsSpO2 data from 25 infants with gestational age &lt;32 weeks and birthweight &lt;2,000 g who underwent a cross over trial of low-flow nasal cannula (NC) and digitally-set servo-controlled oxygen environment (OE) supplementations was considered in this secondary analysis. Features pertaining to signal distribution, variability and complexity were estimated and analyzed for differences between the supplementations. Univariate and regularized multivariate logistic regression was applied to identify relevant features and develop screening models for infants likely to experience a critically high number of IH per day of observation. Their performance was assessed using area under receiver operating curves (AUROC), accuracy, sensitivity, specificity and F1 scores.ResultsWhile most SpO2 measures remained comparable during both supplementations, signal irregularity and complexity were elevated while on OE, pointing to more volatility in oxygen saturation during this supplementation mode. In addition, SpO2 variability measures exhibited early prognostic value in discriminating infants at higher risk of critically many IH events. Poincare plot variability at lag 1 had AUROC of 0.82, 0.86, 0.89 compared to 0.63, 0.75, 0.81 for the IH number, a clinical parameter at observation times of 30 min, 1 and 2 h, respectively. Multivariate models with two features exhibited validation AUROC &gt; 0.80, F1 score &gt; 0.60 and specificity &gt;0.85 at observation times ≥ 1 h. Finally, we proposed a framework for risk stratification of infants using a cumulative risk score for continuous monitoring.ConclusionAnalysis of oxygen saturation signal routinely collected in the NICU, may have extensive applications in inferring subtle changes to cardiorespiratory dynamics under various conditions as well as in informing clinical decisions about infant care