The CoDiNOS trial protocol: an international randomised controlled trial of intravenous sildenafil versus inhaled nitric oxide for the treatment of pulmonary hypertension in neonates with congenital diaphragmatic hernia

INTRODUCTION: Congenital diaphragmatic hernia (CDH) is a developmental defect of the diaphragm that impairs normal lung development, causing pulmonary hypertension (PH). PH in CDH newborns is the main determinant for morbidity and mortality. Different therapies are still mainly based on 'trial and error'. Inhaled nitric oxide (iNO) is often the drug of first choice. However, iNO does not seem to improve mortality. Intravenous sildenafil has reduced mortality in newborns with PH without CDH, but prospective data in CDH patients are lacking. METHODS AND ANALYSIS: In an open label, multicentre, international randomised controlled trial in Europe, Canada and Australia, 330 newborns with CDH and PH are recruited over a 4-year period (2018-2022). Patients are randomised for intravenous sildenafil or iNO. Sildenafil is given in a loading dose of 0.4 mg/kg in 3 hours; followed by continuous infusion of 1.6 mg/kg/day, iNO is dosed at 20 ppm. Primary outcome is absence of PH on day 14 without pulmonary vasodilator therapy and/or absence of death within the first 28 days of life. Secondary outcome measures include clinical and echocardiographic markers of PH in the first year of life. We hypothesise that sildenafil gives a 25% reduction in the primary outcome from 68% to 48% on day 14, for which a sample size of 330 patients is needed. An intention-to-treat analysis will be performed. A p-value (two-sided) <0.05 is considered significant in all analyses. ETHICS AND DISSEMINATION: Ethics approval has been granted by the ethics committee in Rotterdam (MEC-2017-324) and the central Committee on Research Involving Human Subjects (NL60229.078.17) in the Netherlands. The principles of the Declaration of Helsinki, the Medical Research Involving Human Subjects Act and the national rules and regulations on personal data protection will be used. Parental informed consent will be obtained. TRIAL REGISTRATION NUMBER: NTR6982; Pre-results

Delivery room management of extremely low birth weight infants in Italy: Comparison between academic and non-academic birth centres

Objective: International Guidelines provide a standardised approach to newborn resuscitation in the DR and, in their most recent versions, recommendations dedicated to management of ELBWI were progressively increased. It is expected that introduction in clinical practice and dissemination of the most recent evidence should be more consistent in academic than in non-academic hospitals. The aim of the study was to compare adherence to the International Guidelines and consistency of practice in delivery room management of extremely low birth weight infants between academic and non-academic institutions.Methods: A questionnaire was sent to the directors of all Italian level III centres between April and August 2012.Results: There was a 92% (n = 98/107) response rate. Apart from polyethylene wrapping to optimise thermal control, perinatal management approach was comparable between academic and non-academic centres.Conclusions: There were minor differences in management of extremely low birth weight infants between Italian academic and non-academic institutions, apart from thermal management. Although there was a good, overall adherence to the International Guidelines for Neonatal Resuscitation, temperature management was not in accordance with official recommendations and every effort has to be done to improve this aspect

Delivery room management of ELBW infants in Italy

In this article we evaluated the consistency of practice and the adherence to the International Guidelines in early delivery room management of ELBW infants in Italy. A polyethylene bag/wrap was used by 54 centres (55.1%). In Northern regions, one centre (2.5%) reported to use oxygen concentrations >40% to initiate positive pressure ventilation in ELBW infants. These proportions were higher in the Central (14.3%) and Southern (16.2%) areas. A T-piece device for positive pressure ventilation was widely used (77/97, 79.4%). A median of 13% (IQR: 5%-30%) of ELBW infants received chest compressions at birth in Italy. Forty-seven out of 98 (47.9%) centres declared to administer prophylactic surfactant in delivery room. Although there were geographic differences in the country, our results showed a good general adherence to the International Guidelines for Neonatal Resuscitation

Start a Neonatal Extracorporeal Membrane Oxygenation Program: A Multistep Team Training

Background: Extracorporeal membrane oxygenation (ECMO) is a complex life-saving support for acute cardio-respiratory failure, unresponsive to medical treatment. Emergency events on ECMO are rare but require immediate and proficient management. Multidisciplinary ECMO team members need to acquire and maintain over time cognitive, technical and behavioral skills, to safely face life-threatening clinical scenarios.Methods: A multistep educational program was delivered in a 4-year period to 32 ECMO team members, based on guidelines from the Extracorporeal Life Support Organization. A first traditional module was provided through didactic lectures, hands-on water drills, and laboratory animal training. The second phase consisted of a multi-edition high-fidelity simulation-based training on a modified neonatal mannequin (SimNewB®). In each session, participants were called to face, in small groups, ten critical scenarios, followed by debriefing time. Trainees underwent a pre-test for baseline competency assessment. Once completed the full training program, a post-test was administered. Pre- and post-test scores were compared. Trainees rated the educational program through survey questionnaires.Results: 28 trainees (87.5%) completed the full educational program. ECMO staff skills improved from a median pre-test score of 7.5/18 (IQR = 6–11) to 14/18 (IQR = 14–16) at post-test (P &lt; 0.001, Wilcoxon rank test). All trainees highly rated the educational program and its impact on their practice. They reported high-fidelity simulations to be beneficial to novice learners as it increased self-confidence in ECMO-emergencies (according to 100% of surveyed), theoretical knowledge (61.5%) and team-work/communicative skills (58%).Conclusions: The multistep ECMO team training increased staff' knowledge, technical skills, teamwork, and self-confidence, allowing the successful development of a neonatal respiratory ECMO program. Conventional training was perceived as relevant in the early phase of the program development, while the active learning emerged to be more beneficial to master ECMO knowledge, specific skills, and team performance

Delivery room management of ELBW infants in Italy

In this article we evaluated the consistency of practice and the adherence to the International Guidelines in early delivery room management of ELBW infants in Italy. A polyethylene bag/wrap was used by 54 centres (55.1%). In Northern regions, one centre (2.5%) reported to use oxygen concentrations >40% to initiate positive pressure ventilation in ELBW infants. These proportions were higher in the Central (14.3%) and Southern (16.2%) areas. A T-piece device for positive pressure ventilation was widely used (77/97, 79.4%). A median of 13% (IQR: 5%-30%) of ELBW infants received chest compressions at birth in Italy. Forty-seven out of 98 (47.9%) centres declared to administer prophylactic surfactant in delivery room. Although there were geographic differences in the country, our results showed a good general adherence to the International Guidelines for Neonatal Resuscitation

Data_Sheet_1_Start a Neonatal Extracorporeal Membrane Oxygenation Program: A Multistep Team Training.docx

<p>Background: Extracorporeal membrane oxygenation (ECMO) is a complex life-saving support for acute cardio-respiratory failure, unresponsive to medical treatment. Emergency events on ECMO are rare but require immediate and proficient management. Multidisciplinary ECMO team members need to acquire and maintain over time cognitive, technical and behavioral skills, to safely face life-threatening clinical scenarios.</p><p>Methods: A multistep educational program was delivered in a 4-year period to 32 ECMO team members, based on guidelines from the Extracorporeal Life Support Organization. A first traditional module was provided through didactic lectures, hands-on water drills, and laboratory animal training. The second phase consisted of a multi-edition high-fidelity simulation-based training on a modified neonatal mannequin (SimNewB®). In each session, participants were called to face, in small groups, ten critical scenarios, followed by debriefing time. Trainees underwent a pre-test for baseline competency assessment. Once completed the full training program, a post-test was administered. Pre- and post-test scores were compared. Trainees rated the educational program through survey questionnaires.</p><p>Results: 28 trainees (87.5%) completed the full educational program. ECMO staff skills improved from a median pre-test score of 7.5/18 (IQR = 6–11) to 14/18 (IQR = 14–16) at post-test (P < 0.001, Wilcoxon rank test). All trainees highly rated the educational program and its impact on their practice. They reported high-fidelity simulations to be beneficial to novice learners as it increased self-confidence in ECMO-emergencies (according to 100% of surveyed), theoretical knowledge (61.5%) and team-work/communicative skills (58%).</p><p>Conclusions: The multistep ECMO team training increased staff' knowledge, technical skills, teamwork, and self-confidence, allowing the successful development of a neonatal respiratory ECMO program. Conventional training was perceived as relevant in the early phase of the program development, while the active learning emerged to be more beneficial to master ECMO knowledge, specific skills, and team performance.</p

The CoDiNOS trial protocol: an international randomised controlled trial of intravenous sildenafil versus inhaled nitric oxide for the treatment of pulmonary hypertension in neonates with congenital diaphragmatic hernia

INTRODUCTION: Congenital diaphragmatic hernia (CDH) is a developmental defect of the diaphragm that impairs normal lung development, causing pulmonary hypertension (PH). PH in CDH newborns is the main determinant for morbidity and mortality. Different therapies are still mainly based on 'trial and error'. Inhaled nitric oxide (iNO) is often the drug of first choice. However, iNO does not seem to improve mortality. Intravenous sildenafil has reduced mortality in newborns with PH without CDH, but prospective data in CDH patients are lacking. METHODS AND ANALYSIS: In an open label, multicentre, international randomised controlled trial in Europe, Canada and Australia, 330 newborns with CDH and PH are recruited over a 4-year period (2018-2022). Patients are randomised for intravenous sildenafil or iNO. Sildenafil is given in a loading dose of 0.4 mg/kg in 3 hours; followed by continuous infusion of 1.6 mg/kg/day, iNO is dosed at 20 ppm. Primary outcome is absence of PH on day 14 without pulmonary vasodilator therapy and/or absence of death within the first 28 days of life. Secondary outcome measures include clinical and echocardiographic markers of PH in the first year of life. We hypothesise that sildenafil gives a 25% reduction in the primary outcome from 68% to 48% on day 14, for which a sample size of 330 patients is needed. An intention-to-treat analysis will be performed. A p-value (two-sided) <0.05 is considered significant in all analyses. ETHICS AND DISSEMINATION: Ethics approval has been granted by the ethics committee in Rotterdam (MEC-2017-324) and the central Committee on Research Involving Human Subjects (NL60229.078.17) in the Netherlands. The principles of the Declaration of Helsinki, the Medical Research Involving Human Subjects Act and the national rules and regulations on personal data protection will be used. Parental informed consent will be obtained. TRIAL REGISTRATION NUMBER: NTR6982; Pre-results.status: publishe