Protecting Brains and Saving Futures - the PBSF Protocol

Summary

Participation Requirements

Description

METHODS Objectives The aim of this multicenter, prospective, cohort study is to describe the use of the PBSF protocol and clinical outcomes, by center and over a 3 years period (2021 to 2023) in the NICUs that have adopted it. We hypothesize that the use of the PBSF protocol will increase over time ...

METHODS Objectives The aim of this multicenter, prospective, cohort study is to describe the use of the PBSF protocol and clinical outcomes, by center and over a 3 years period (2021 to 2023) in the NICUs that have adopted it. We hypothesize that the use of the PBSF protocol will increase over time with improvement of some specific short-term outcomes (see methods below). Results of this study may provide the necessary background information for larger studies and initiatives aiming to protect neonatal brains and save futures. Study Design and Setting This will be a multicenter, prospective, observational study in a cohort of high-risk neonates treated at 20 different NICU's in Brazil. The intended period of patient recruitment and data collection will be 3 years (January 2021 to December 2023). The study followed the precepts of good clinical practice and was approved by the Research Ethics Committee of the Irmandade da Santa Casa de Misericórdia de São Paulo. In addition, the project has received formal authorization from the Clinical and Administrative Board of each center. When selecting a participant, the principal investigator of the study or one of the co-investigators will contact the parents or guardians and obtain informed consent. All data will be treated anonymously and confidentially, and in no phase of the study any name, image, or data that allows participants identification will be disclosed. Participants In this cohort study, all the infants admitted to any of the 20 NICUs from birth up to three months of life and receiving the PBSF protocol are eligible. Indications for the use of the protocol are provided on Box 1. Patients with genetic syndromes or malformation incompatible with life, or older than three months old will be excluded. Details on the PBSF protocol are provided in supplemental material. Briefly, the protocol includes provision of equipment and resources, connection between the associated NICU and the remote monitoring center called the Central of Surveillance and Intelligence (CSI), training and teaching of all health care professional team of each NICU, and customized multiparametric recordings of biological signals of each patient monitoring. At the CSI, a team is available 24 hours a day all year around, allowing for case discussions and simplified reports of brain monitoring information on the patient monitor's display every 6 hours. Variables Population demographics: gender, gestational age at birth, gestational age ? 32 weeks and < 37 weeks, Apgar score at 1 min, 5 min and 10 min, birth weight, current weight, inborn or outborn, use of antenatal steroids and magnesium sulfate, type of birth. Primary diagnosis: seizure, anoxia/mild HIE, moderate or severe HIE/cooling, neurologic abnormalities without specific diagnosis, congenital central nervous system (CNS) anomalies, grade III or IV intraventricular hemorrhage (IVH) or hydrocephalus, periventricular leukomalacia, meningitis, neural tube defects, stroke, cyanotic congenital heart defect (CHD), prematurity, gestational age ? 32 weeks, meconium aspiration syndrome, cardiorespiratory instability, necrotizing enterocolitis, metabolic disease, extracorporeal membrane oxygenation (ECMO)/pre-ECMO and any other medical conditions not listed here. For descriptive analysis of the 2 main outcomes (use of the PBSF protocol and clinical outcomes) patients will be them divided into two groups accordingly to their primary diagnosis: neurological or clinical. Data sources / measurement Patient demographics, diagnosis and clinical outcomes will be extracted from the medical charts of each patient enrolled and entered in the PBSF database. The use of the PBSF protocol will be measured with the data collected by the CSI center continuously. Details of these recordings are provided on Appendix 2. Bias To address potential source of bias related to financial availability, the 2 main outcomes of interest will be also adjusted based on the unit primary profile: private, foundation or public. Study size Based on our current experience, there are an average of 5 patients per month with criteria for neurocritical care on each center, making a total of 3,240 eligible patients during a three years period. Considering a 30% loss due to refusal to consent, non-availability of the research team or missing data, we expect to recruit 2,268 infants from all study centers (around 756 patients per year). Statistical methods Categorical variables will be analyzed by descriptive statistics and presented as number of valid cases and percentage (%). Numeric variables will be analyzed as mean and standard deviation, median and interquartile ranges, or coefficient intervals. Chi-square test (or Fisher's exact test) will be performed to analyze categorical variables and the Student's t test, or Wilcoxon rank sum test will be used to check for significant differences between the two groups. A p value of <0.05 will be considered statistically significant. The confidence interval considered will be 95%. Analysis of variability (distribution) per site for each variable of the 2 main outcomes will also be performed. ANOVA with post hoc Bonferroni will be used to compare outcomes over time, i.e. between years 1, 2 and 3 and Kaplan Meier curves will be generated to follow the evolution of outcomes over time for the 2 groups of patients: neurologic and clinical. Results Participants. A flow chart of all eligible and enrolled patients will be produced, and the total number of patients will be reported, overall and per center. Descriptive data Population demographics: male, n (%); gestational age at birth, weeks, mean (SD); gestational age ? 32 wk, n(%); Gestational age < 37 wk, n (%); Apgar score at 1 min, at 5 min, and at 10min, median (IQR); birth weight, grams, mean (SD); current weight, grams, mean (SD); Inborn, n (%); use of antenatal steroids and magnesium sulfate, n (%); Caesarean, n(%). Primary outcomes: Use of the PBSF protocol Use of aEEG/EEG monitoring Duration of aEEG/EEG monitoring Number primary neurologic or medical patients with aEEG or EEG monitoring and the duration of the monitoring (hours) Number of primary neurologic or medical patients with NIRS monitoring and the duration of the NIRS monitoring (hours) Number of primary neurologic or medical patients with brain MRI, neurology consult, and neurosurgery consult. Number of clinical case discussions and videoconference meetings Clinical outcomes Length of hospital stay Number of electroencephalographic seizures during hospitalization Use and types of anticonvulsants administered Number and types of anticonvulsants prescribed at discharge Use and types of inotropes administered during NICU stay Use and types of fluid resuscitation administered during NICU stay Death before hospital discharge Number of patients referred to neurology or neurosurgery Number of patients referred to high-risk infant follow-up* Secondary outcomes: Use of the PBSF protocol Number of remote communications between CSI and local team Number of reports issued for aEEG / EEG exams with or without the use of NIRS Number of patients who performed Therapeutic Hypothermia Association of pathological brain monitoring findings (aEEG/EEG and NIRS) and alterations in imaging exams including brain magnetic resonance imaging (brain MRI) and cranial ultrasonography (cranial US) performed during hospitalization Association of pathological brain monitoring findings with morbi-mortality and length of hospital stay Adverse effects of therapeutic hypothermia measured by cardiac arrhythmia, thrombocytopenia and coagulation disorders in general, skin lesion and pulmonary hypertension Adverse effects of brain monitoring expressed by skin lesion due to electrode / sensor positioning Association of pathological brain monitoring findings with evaluation of neurodevelopment by application of the Bayley test between 18 and 24 months of life

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