Predictors of early nasal CPAP failure and effects of various intubation criteria on the rate of mechanical ventilation in preterm infants of <29 weeks gestational age

Abstract Background Mechanical ventilation is still needed in most preterm newborns, even in the non-invasive ventilation era. Ventilator-induced lung injury is one of the known pathogenetic factors of bronchopulmonary dysplasia (BPD) in preterm newborns. Lung injury has several patterns including surfactant dysfunction. Some recent trials have showed that a late surfactant administration can improve respiratory outcome in preterm babies still on invasive ventilation after the first week of life. Unfortunately, these results are still not conclusive. Moreover, giving surfactant after a recruitment manoeuvre in High Frequency Oscillatory Ventilation (HFOV) was shown to be safe and to reduce mortality in extremely preterm infants in a recent RCT. Our aim is to test the hypothesis that endotracheal administration of poractant-alfa preceded by a recruitment manoeuvre in HFOV in preterm infants still requiring mechanical ventilation at 7-10 days of life could facilitate extubation. Methods/Design: This will be an unblinded monocentric pilot trial that will be conducted in a III level Neonatal Intensive Care Unit at Fondazione Policlinico Agostino Gemelli IRCCS in Rome - Italy. Preterm newborns with a gestational age < 28 weeks still requiring invasive mechanical ventilation at 7-10 days of life with a fraction of inspired oxygen (FiO2) of more than 0.30 and/or an oxygenation index of 8 or more for at least 6 hours will be eligible for the study. Patients will be randomly assigned to intervention or to standard care. Intervention group infants will receive up to 4 doses of Poractant-alfa every 12 hours, each dose preceded by a recruitment manoeuvre in HFOV, until extubation. Primary endpoint will be the first successful extubation. Discussion Surfactant therapy is nowadays recommended in case of RDS in the first days of life but little is known about its effects in ventilator-dependant preterm newborns. Late administration of surfactant could help healing the lung of preterm babies in which RDS is evolving in a chronic pulmonary insufficiency of prematurity. The findings of this pilot trial will permit evaluation of the study design for a full-scale RCT. Trial registration: Clinicaltrials.gov – ID NCT04825197. Registered 12 April 2021, https://clinicaltrials.gov/ct2/home

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Duration of mechanical ventilation and neurodevelopment in preterm infants

Archives of Disease in Childhood - Fetal and Neonatal Edition ◽

10.1136/archdischild-2018-315993 ◽

2019 ◽

Vol 104 (6) ◽

pp. F631-F635 ◽

Cited By ~ 8

Author(s):

Roos J S Vliegenthart ◽

Anton H van Kaam ◽

Cornelieke S H Aarnoudse-Moens ◽

Aleid G van Wassenaer ◽

Wes Onland

Keyword(s):

Mechanical Ventilation ◽

Regression Analysis ◽

Preterm Infants ◽

Bronchopulmonary Dysplasia ◽

Gestational Age ◽

Invasive Mechanical Ventilation ◽

Multivariate Logistic Regression Analysis ◽

Neurodevelopmental Outcomes ◽

Respiratory Management ◽

Increased Risk

ObjectiveTo investigate the association between invasive mechanical ventilation (IMV) duration and long-term neurodevelopmental outcomes in preterm infants in an era of restricted IMV.DesignRetrospective cohort study.SettingSingle neonatal intensive care unit in Amsterdam.PatientsAll ventilated patients with a gestational age between 24 and 30 weeks born between 2010 and 2015.Main outcome measuresNeurodevelopmental impairment (NDI) at 24 months corrected age (CA). Data on patient characteristics, respiratory management, neonatal morbidities, mortality and bronchopulmonary dysplasia were collected. The relationship between IMV duration and NDI was determined by multivariate logistic regression analysis.ResultsDuring the study period, 368 admitted infants received IMV for a median duration of 2 days. Moderate and severe bronchopulmonary dysplasia was diagnosed in 33% of the infant. Multivariate regression analysis with adjustment for gestational age, small for gestational age and socioeconomic status showed a significant association between every day of IMV and NDI at 24 months CA (adjusted OR [aOR] 1.08, 95% CI 1.004 to 1.16, p=0.04). This association only reached borderline significance when also adjusting for severe neonatal morbidity (aOR 1.08, 95% CI 1.00 to 1.17, p=0.05).ConclusionEven in an era of restricted IMV, every additional day of IMV in preterm infants is strongly associated with an increased risk of NDI at 24 months CA. Limiting IMV should be an important focus in the treatment of preterm infants.

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Predictor Factors of Continuous Positive Airway Pressure Failure in Preterm Infants with Respiratory Distress

Global Pediatric Health ◽

10.1177/2333794x211007464 ◽

2021 ◽

Vol 8 ◽

pp. 2333794X2110074

Author(s):

Winda Intan Permatahati ◽

Amalia Setyati ◽

Ekawaty Lutfia Haksari

Keyword(s):

Birth Weight ◽

Continuous Positive Airway Pressure ◽

Respiratory Distress ◽

Preterm Infants ◽

Airway Pressure ◽

Positive Airway Pressure ◽

Multivariate Logistic Regression Analysis ◽

Mortality And Morbidity ◽

Nasal Cpap ◽

Cpap Failure

Respiratory distress contributes significantly to mortality, and morbidity in preterm infants. The incidence of nasal continuous positive airway pressure (CPAP) failure is remarkably high. There are limited data available regarding nasal CPAP failure in Indonesia, and this study is expected to be a reference in taking preventive measures to reduce mortality and morbidity in preterm infants. To determine predictive factors of nasal CPAP failure in preterm infants with respiratory distress. A retrospective cohort study was conducted in preterm infants with respiratory distress at the Neonatology ward of Dr. Sardjito Hospital during January 2017-July 2019. Chi-square or Fisher’s exact tests, followed by multivariate logistic regression analysis with backward method, was used to identify factors contributing to nasal CPAP failure. A total of 150 infants were included in this study. Fifty-three (37.8%) infants had nasal CPAP failure. Bivariate analysis showed birth weight <1000 g, singleton, APGAR score 4-7, premature rupture of membrane (PROM), Downes score, and initiation of fractional concentration of inspired (FiO2) requirement were all risk factors of nasal CPAP failure. However, only birth weight <1000 g ( P = .022; OR 2.69; CI 95% 1.34-5.44), initial Downes score ( P = .035; OR 2.68; CI 95% 3.10-24.11), and initiation of FiO2 requirement ≥30% ( P = .0001; OR 3.03; CI 95% 2.04-4.50) were significant predictors for nasal CPAP failure by multivariate analysis. Birth weight <1000 g, singleton, initial Downes score, and initiation of FiO2 requirement >30% were significant predictors of nasal CPAP failure in preterm infants with respiratory distress.

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SENTINEL1: Two-Season Study of Respiratory Syncytial Virus Hospitalizations among U.S. Infants Born at 29 to 35 Weeks' Gestational Age Not Receiving Immunoprophylaxis

American Journal of Perinatology ◽

10.1055/s-0039-1681014 ◽

2019 ◽

Vol 37 (04) ◽

pp. 421-429 ◽

Cited By ~ 7

Author(s):

Evan J. Anderson ◽

John P. DeVincenzo ◽

Eric A. F. Simões ◽

Leonard R. Krilov ◽

Michael L. Forbes ◽

...

Keyword(s):

Intensive Care Unit ◽

Mechanical Ventilation ◽

Intensive Care ◽

Respiratory Syncytial Virus ◽

Observational Study ◽

Preterm Infants ◽

Gestational Age ◽

Invasive Mechanical Ventilation ◽

Syncytial Virus ◽

Birth Hospitalization

Objective The SENTINEL1 observational study characterized confirmed respiratory syncytial virus hospitalizations (RSVH) among U.S. preterm infants born at 29 to 35 weeks' gestational age (wGA) not receiving respiratory syncytial virus (RSV) immunoprophylaxis (IP) during the 2014 to 2015 and 2015 to 2016 RSV seasons. Study Design All laboratory-confirmed RSVH at participating sites during the 2014 to 2015 and 2015 to 2016 RSV seasons (October 1–April 30) lasting ≥24 hours among preterm infants 29 to 35 wGA and aged <12 months who did not receive RSV IP within 35 days before onset of symptoms were identified and characterized. Results Results were similar across the two seasons. Among infants with community-acquired RSVH (N = 1,378), 45% were admitted to the intensive care unit (ICU) and 19% required invasive mechanical ventilation (IMV). There were two deaths. Infants aged <6 months accounted for 78% of RSVH observed, 84% of ICU admissions, and 91% requiring IMV. Among infants who were discharged from their birth hospitalization during the RSV season, 82% of RSVH occurred within 60 days of birth hospitalization discharge. Conclusion Among U.S. preterm infants 29 to 35 wGA not receiving RSV IP, RSVH are often severe with almost one-half requiring ICU admission and about one in five needing IMV.

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Application of two different nasal CPAP levels for the treatment of respiratory distress syndrome in preterm infants—“The OPTTIMMAL-Trial”—Optimizing PEEP To The IMMAture Lungs: study protocol of a randomized controlled trial

Trials ◽

10.1186/s13063-020-04660-0 ◽

2020 ◽

Vol 21 (1) ◽

Author(s):

Markus Waitz ◽

Corinna Engel ◽

Rolf Schloesser ◽

Ulrich Rochwalsky ◽

Sascha Meyer ◽

...

Keyword(s):

Respiratory Distress Syndrome ◽

Respiratory Distress ◽

Preterm Infants ◽

Distress Syndrome ◽

Very Low Birth Weight ◽

Peep Level ◽

Low Birth Weight Infants ◽

Nasal Cpap ◽

Inspired Oxygen ◽

Cpap Failure

Abstract Background Nasal continuous positive airway pressure (CPAP) applies positive end-expiratory pressure (PEEP) and has been shown to reduce the need for intubation and invasive mechanical ventilation in very low birth weight infants with respiratory distress syndrome. However, CPAP failure rates of 50% are reported in large randomized controlled trials. A possible explanation for these failure rates is the application of insufficient low levels of PEEP during nasal CPAP treatment to maintain adequate functional residual capacity shortly after birth. The optimum PEEP level to treat symptoms of respiratory distress in very low birth weight infants has not been assessed in clinical studies. The aim of the study is to compare two different PEEP levels during nasal CPAP treatment in preterm infants. Methods In this randomized multicenter trial, 216 preterm infants born at 26 + 0–29 + 6 gestational weeks will be allocated to receive a higher (6–8 cmH2O) or a lower (3–5 cmH2O) PEEP during neonatal resuscitation and the first 120 h of life. The PEEP level within each group will be titrated throughout the intervention based on the FiO2 (fraction of inspired oxygen concentration) requirements to keep oxygenation within the target range. The primary outcome is defined as the need for intubation and mechanical ventilation for > 1 h or being not ventilated but reaching one of the two pre-defined CPAP failure criteria (FiO2 > 0.5 for > 1 h or pCO2 ≥ 70 mmHg in two consecutive blood gas analyses at least 2 h apart). Discussion Based on available data from the literature, the optimum level of PEEP that most effectively treats respiratory distress syndrome in preterm infants is unknown, since the majority of large clinical trials applied a wide range of PEEP levels (4–8 cmH2O). The rationale for our study hypothesis is that the early application of a higher PEEP level will more effectively counteract the collapsing properties of the immature and surfactant-deficient lungs and that the level of inspired oxygen may serve as a surrogate marker to guide PEEP titration. Finding the optimum noninvasive continuous distending pressure during early nasal CPAP is required to improve CPAP efficacy and as a consequence to reduce the exposure to ventilator-induced lung injury and the incidence of chronic lung disease in this vulnerable population of very preterm infants. Trial registration drks.de DRKS00019940. Registered on March 13, 2020

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The association between clinical and biochemical characteristics of late-onset sepsis and bronchopulmonary dysplasia in preterm infants

European Journal of Pediatrics ◽

10.1007/s00431-021-03981-9 ◽

2021 ◽

Author(s):

Melania E. Ebrahimi ◽

Michelle Romijn ◽

Roos J. S. Vliegenthart ◽

Douwe H. Visser ◽

Anton H. van Kaam ◽

...

Keyword(s):

Mechanical Ventilation ◽

Preterm Infants ◽

Bronchopulmonary Dysplasia ◽

Gestational Age ◽

Late Onset ◽

Multivariate Logistic Regression Analysis ◽

Biochemical Characteristics ◽

Late Onset Sepsis ◽

Early Onset Sepsis ◽

Increased Risk

AbstractStudies in preterm infants have shown an association between late-onset sepsis (LOS) and the development of bronchopulmonary dysplasia (BPD). It is unknown whether clinical or biochemical characteristics during sepsis modulate the risk for BPD. This single-center retrospective cohort study included all patients with a gestational age < 30 weeks, born between 2009 and 2015, in whom empiric antimicrobial treatment was initiated > 72 h after birth and continued for at least 5 days, independent on microbiological results. The association between clinical and biochemical characteristics of LOS and the development of BPD in survivors were assessed with multivariate logistic regression analysis adjusted for early-onset sepsis, small for gestational age, and gestational age. Of the 756 admitted infants, 256 infants (mean GA: 27.0 weeks; birthweight: 924 grams) had at least one LOS episode, of whom 79 (30.9%) developed BPD. Analyses showed that only the need for and duration of mechanical ventilation during LOS were independently associated with an increased risk for BPD (adjusted OR 2.62, 95% CI 1.38, 4.96, p value 0.003, and OR 1.004, 95% CI 1.00, 1.007, p value 0.045, respectively).Conclusion: During a LOS, the need for and duration of mechanical ventilation are independently associated with the risk of developing BPD in preterm infants. What is Known:• Premature infants diagnosed with a late-onset sepsis are at higher risk of developing bronchopulmonary dysplasia• This association is mainly shown in infants with a positive blood culture What is New:• This study investigates the clinical and biochemical characteristics of late-onset sepsis and the development of bronchopulmonary dysplasia• The need for mechanical ventilation and duration of mechanical ventilation during late-onset sepsis are associated with an increased risk of developing bronchopulmonary dysplasia.

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Nasal CPAP vs. mechanical ventilation in 28-32 weeks preterm infants with early surfactant administration

Biomédica ◽

10.7705/biomedica.v34i4.2163 ◽

2014 ◽

Vol 34 (4) ◽

Cited By ~ 1

Author(s):

Luis Alfonso Pérez ◽

Diana Marcela González ◽

Karen Margarita de Jesús Álvarez ◽

Luis Alfonso Díaz-Martínez

Keyword(s):

Mechanical Ventilation ◽

Preterm Infants ◽

Nasal Cpap ◽

Surfactant Administration

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Risk factors for the development of intraventricular hemorrhage in preterm infants with respiratory distress syndrome

Rossiyskiy Vestnik Perinatologii i Pediatrii (Russian Bulletin of Perinatology and Pediatrics) ◽

10.21508/1027-4065-2021-66-5-49-55 ◽

2021 ◽

Vol 66 (5) ◽

pp. 49-55

Author(s):

A. V. Andreev ◽

N. V. Kharlamova ◽

N. A. Shilova ◽

A. A. Pesenkina

Keyword(s):

Risk Factors ◽

Mechanical Ventilation ◽

Respiratory Distress Syndrome ◽

Respiratory Distress ◽

Preterm Infants ◽

Gestational Age ◽

Intraventricular Hemorrhage ◽

Distress Syndrome ◽

Significant Risk ◽

Group I

Intraventricular hemorrhage remains a serious complication in infants and especially in preterm infants with gestational age up to 27 weeks.Objective. To assess the risk factors for the development of intraventricular hemorrhage in deeply preterm infants with respiratory distress syndrome.Materials and methods. We carried out a prospective controlled comparative study. The study included 104 newborns with respiratory distress syndrome with a gestational age of less than 32 weeks and a birth weight of less than 1500 g. Depending on the presence of intraventricular hemorrhage the patients were divided into groups: Group I : 56 preterm infants with intraventricular hemorrhage verified during the observation; Group II: 48 preterm infants without intraventricular hemorrhageResults. The groups at birth were comparable in terms of weight and height. We identified the risk factors contributing to the development of intraventricular hemorrhage: the absence of antenatal prophylaxis of fetal respiratory distress syndrome (odds ratio (OR) 2.728; 95% CI 1.218–6.109), tracheal intubation in the delivery room (OR 5.714; 95% CI 1.610–20.28), the need for mechanical ventilation on the first day life (OR 2.713; 95% CI 1.154–6.377), forced mechanical ventilation (OR 9.818; 95% CI 1.039–92.86), > 20 manipulations in the first day of life (OR 2.747; 95% CI 1.240–6.089). Also, the authors determined the factors contributing to a decrease in the development of intraventricular hemorrhage: complete antenatal prevention of fetal respiratory distress syndrome (OR 0.35; 95% CI 0.149–0.825), less invasive administration of poractant-alpha at a dosage of 200 mg/kg (OR 0.161; 95% CI 0.033–0.787), ventilation with double control during inspiration (OR 0.159; 95% CI 0.032–0.784), chronic arterial hypertension in the mother during the present pregnancy (OR 0.185; 95% CI 0.037–0.919).Conclusion. According to the results of the study the authors identified significant risk factors for the development of intraventricular hemorrhage in deeply preterm infants with respiratory distress syndrome.

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RAM cannula with Cannulaide versus Hudson prongs for delivery of nasal continuous positive airway pressure in preterm infants: an RCT

Scientific Reports ◽

10.1038/s41598-021-02988-4 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Shravani Maram ◽

Srinivas Murki ◽

Sidharth Nayyar ◽

Sandeep Kadam ◽

Tejo Pratap Oleti ◽

...

Keyword(s):

Mechanical Ventilation ◽

Continuous Positive Airway Pressure ◽

Respiratory Distress ◽

Preterm Infants ◽

Gestational Age ◽

Airway Pressure ◽

Positive Airway Pressure ◽

Open Label ◽

Non Invasive ◽

Nasal Injury

AbstractNasal continuous positive airway pressure (nCPAP) is the standard non-invasive respiratory support for newborns with respiratory distress. Nasal injury is a common problem with the interfaces used. To compare the incidence and severity of nasal injury in neonates with respiratory distress and supported on nCPAP with Hudson prong or RAM cannula with Cannulaide, a semipermeable membrane. This is an open-label, parallel-arm, gestational age-stratified, bi-centric, randomized control trial including neonates between 28 and 34 weeks gestational age and birth weight > 1000 g needing nCPAP. The size of the interface was chosen as per the manufacturer’s recommendation. Of the 229 neonates enrolled, 112 were randomized to RAM cannula with Cannulaide and 117 to Hudson prong. The baseline characteristics were similar. Any nasal injury at CPAP removal was significantly lower in the RAM cannula with Cannulaide group [6 (5.4%) vs. 31 (26.4%); risk ratio—0.77 (95% CI 0.69–0.87); p = 0.0001]. The incidence of moderate to severe nasal injury, need for mechanical ventilation within 72 h of age, duration of oxygen, and requirement of nCPAP for > 3 days were similar. For preterm infants on nCPAP, RAM cannula with Cannulaide, compared to Hudson prongs, decreases nasal injury without increasing the need for mechanical ventilation.Trail registration: CTRI/2019/03/018333, http://www.ctri.nic.in.

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