Protecting brains and saving futures guidelines: A prospective, multicenter, and observational study on the use of telemedicine for neonatal neurocritical care in Brazil.

BACKGROUND: Management of high-risk newborns should involve the use of standardized protocols and training, continuous and specialized brain monitoring with electroencephalography (EEG), amplitude integrated EEG, Near Infrared Spectroscopy, and neuroimaging. Brazil is a large country with disparities in health care assessment and some neonatal intensive care units (NICUs) are not well structured with trained personnel able to provide adequate neurocritical care. To reduce this existing gap, an advanced telemedicine model of neurocritical care called Protecting Brains and Saving Futures (PBSF) Guidelines was developed and implemented in a group of Brazilian NICUs. METHODS: A prospective, multicenter, and observational study will be conducted in all 20 Brazilian NICUs using the PBSF Guidelines as standard-of-care. All infants treated accordingly to the guidelines during Dec 2021 to Nov 2024 will be eligible. Ethical approval was obtained from participating centers. The primary objective is to describe adherence to the PBSF Guidelines and clinical outcomes, by center and over a 3-year period. Adherence will be measured by quantification of neuromonitoring, neuroimaging exams, sub-specialties consultation, and clinical case discussions and videoconference meetings. Clinical outcomes of interest are detection of seizures during hospitalization, use of anticonvulsants, inotropes, and fluid resuscitation, death before hospital discharge, length of hospital stay, and referral of patients to specialized follow-up. DISCUSSION: The study will provide evaluation of PBSF Guidelines adherence and its impact on clinical outcomes. Thus, data from this large prospective, multicenter, and observational study will help determine whether neonatal neurocritical care via telemedicine can be effective. Ultimately, it may offer the necessary framework for larger scale implementation and development of research projects using remote neuromonitoring. TRIAL REGISTRATION: NCT03786497, Registered 26 December 2018, https://www.clinicaltrials.gov/ct2/show/NCT03786497?term=protecting+brains+and+saving+futures&draw=2&rank=1.

Natural evolution of the patent ductus arteriosus in the extremely premature newborn and respiratory outcomes.

OBJECTIVE: Evaluate spontaneous closure of the patent ductus arteriosus (PDA) in extremely preterm infants and their respiratory outcomes, especially at <26 weeks gestational age (GA). STUDY DESIGN: Retrospective study in <29 weeks, admitted within 24 h after birth (Feb 2015 and Dec 2019). Infants without any intervention to promote ductal closure, ≥1 echocardiography, and alive at discharge were included. RESULTS: Two hundred and fourteen infants (average GA 26.3 ± 1.5 weeks) were included; 84 (39%) <26 weeks. PDA closed spontaneously in 194 (91%); 76/84 (90%) for infants <26 weeks. PDA closure was ascertained on an echocardiography performed at a median age of 36.4 [34.4-40.1] weeks. Rate of moderate-to-severe bronchopulmonary dysplasia decreased throughout the study period (OR for year of birth: 0.70 [95% CI: 0.57-0.87], p = 0.001). CONCLUSION: Majority of extremely preterm infants, including <26 weeks, had spontaneous closure of the ductus before term corrected age. There was a concomitant improvement of respiratory outcomes.

Vagal Neuromodulation in Chronic Heart Failure With Reduced Ejection Fraction: A Systematic Review and Meta-Analysis.

Objectives: The aim of this study was to evaluate the effects of invasive vagal nerve stimulation (VNS) in patients with chronic heart failure (HF) and reduced ejection fraction (HFrEF). Background: Heart failure is characterized by autonomic nervous system imbalance and electrical events that can lead to sudden death. The effects of parasympathetic (vagal) stimulation in patients with HF are not well-established. Methods: From May 1994 to July 2020, a systematic review was performed using PubMed, Embase, and Cochrane Library for clinical trials, comparing VNS with medical therapy for the management of chronic HFrEF (EF ≤ 40%). A meta-analysis of several outcomes and adverse effects was completed, and GRADE was used to assess the level of evidence. Results: Four randomized controlled trials (RCT) and three prospective studies, totalizing 1,263 patients were identified; 756 treated with VNS and 507 with medical therapy. RCT data were included in the meta-analysis (fixed-effect distribution). Adverse effects related to VNS were observed in only 11% of patients. VNS was associated with significant improvement (GRADE = High) in the New York Heart Association (NYHA) functional class (OR, 2.72, 95% CI: 2.07-3.57, p < 0.0001), quality of life (MD -14.18, 95% CI: -18.09 to -10.28, p < 0.0001), a 6-min walk test (MD, 55.46, 95% CI: 39.11-71.81, p < 0.0001) and NT-proBNP levels (MD -144.25, 95% CI: -238.31 to -50.18, p = 0.003). There was no difference in mortality (OR, 1.24; 95% CI: 0.82-1.89, p = 0.43). Conclusions: A high grade of evidence demonstrated that vagal nerve stimulation improves NYHA functional class, a 6-min walk test, quality of life, and NT-proBNP levels in patients with chronic HFrEF, with no differences in mortality.

Predictors of extubation readiness in preterm infants: a systematic review and meta-analysis.

CONTEXT: A variety of extubation readiness tests have already been incorporated into clinical practice in preterm infants. OBJECTIVE: To identify predictor tests of successful extubation and determine their accuracy compared with clinical judgement alone. METHODS: MEDLINE, Embase, PubMed, Cochrane Library and Web of Science were searched between 1984 and June 2016. Studies evaluating predictors of extubation success during a period free of mechanical inflations in infants less than 37 weeks' gestation were included. Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. After identifying and describing all predictor tests, pooled sensitivity and specificity estimates for the different test categories were generated using a bivariate random-effects model. RESULTS: Thirty-five studies were included, showing wide heterogeneities in population characteristics, methodologies and definitions of extubation success. Assessments ranged from a few seconds to 24 hours, provided 0-6 cmH2O positive end-expiratory pressure and measured several clinical and/or physiological parameters. Thirty-one predictor tests were identified, showing good sensitivities but low and variable specificities. Given the high variation in test definitions across studies, pooling could only be performed on a subset. The commonly performed spontaneous breathing trials had pooled sensitivity of 95% (95% CI 87% to 99%) and specificity of 62% (95% CI 38% to 82%), while composite tests offered the best performance characteristics. CONCLUSIONS: There is a lack of strong evidence to support the use of extubation readiness tests in preterm infants. Although spontaneous breathing trials are attractive assessment tools, higher quality studies are needed for determining the optimal strategies for improving their accuracy.

Heart rate variability and extubation readiness in extremely preterm infants.

BACKGROUND: Mechanical ventilation (MV) is associated with changes in autonomic nervous system activity in preterm infants, which can be assessed by measurements of heart rate variability (HRV). Decreased HRV has been described in adults undergoing disconnection from MV; such information is not available in preterm infants. OBJECTIVE: To compare differences in HRV between infants successfully extubated and those who failed, and to evaluate the accuracy of HRV as a predictor of extubation readiness. METHODS: This is a prospective, observational study of infants with a birth weight ≤1,250 g undergoing their first extubation attempt. Heart rate was measured during a 60-min period immediately prior to extubation and HRV was calculated using the frequency domain analysis. RESULTS: A total of 47 infants were studied; 36 were successfully extubated and 11 reintubated. There were no differences in patient demographics, ventilator settings, blood gases or postextubation management between the groups. All components of the HRV analysis were significantly decreased in infants who failed, generating high areas under the receiver operating characteristic curve. The specificity and positive predictive values were 100, but with limited sensitivity and negative predictive values. CONCLUSIONS: Infants considered 'ready to be extubated' but who subsequently failed their first extubation attempt had decreased HRV prior to extubation. Though promising, the value of HRV as a predictor of extubation readiness requires further evaluation.

Cooling in the real world: therapeutic hypothermia in hypoxic-ischemic encephalopathy.

BACKGROUND AND AIM: The benefits of therapeutic hypothermia have not been assessed from the perspective of the neurology clinic. We aimed to report the impact of the implementation of a local regional therapeutic hypothermia program on the neurodevelopmental outcomes of surviving hypoxic-ischemic encephalopathy (HIE) infants who were followed in the neonatal neurology clinic. METHODS: Retrospective analysis of term infants referred to the neonatal neurology clinic after having been diagnosed with HIE and meeting eligibility criteria for therapeutic hypothermia between March 1999 and June 2010. Therapeutic hypothermia was implemented in September 2008. Outcome measures were dichotomously defined as: normal or adverse, which included cerebral palsy, global developmental delay, and epilepsy. RESULTS: Thirty infants were included in the pre-therapeutic hypothermia group. Thirty-one infants received therapeutic hypothermia and 27 were adequately followed and included in the post-therapeutic hypothermia group. The frequency of an adverse outcome was significantly higher in the pre-therapeutic hypothermia infants (19/30 [63%] versus 4/27 [15%]; OR = 0.10; 95% CI, 0.03-0.37; P < 0.001). Neonatal clinical seizures were more frequent in the pre-therapeutic hypothermia group (P = 0.012). There were no differences regarding frequency of fetal distress, rate of caesarean sections, Apgar scores, need of resuscitation, cord/initial blood gases, and degrees of encephalopathy between the two groups. CONCLUSIONS: The implementation of a regional therapeutic hypothermia program in our institution has vastly reduced the observed neurological morbidity of surviving HIE infants followed in our neonatal neurology clinic. A similar change in outcomes of infants with HIE can be anticipated by other centers and other clinics adopting this therapy.

Fluctuations in relative humidity provided to extremely low-birthweight infants (R1).

BACKGROUND: In extremely low-birthweight infants, the addition of relative humidity (RH) improves thermal stability, fluid and electrolyte balance. However, during routine care this microenvironment is frequently disturbed. The objective of this study was to determine the frequency, magnitude and direction of fluctuations in RH provided to extremely low-birthweight infants. METHODS: All infants in our study had ambient temperature and RH continuously recorded for 48 h using a datalogger device (RH32S-C2). A clinically acceptable range for RH was defined as the set point ± 10%. A secondary analysis was performed to compare outcomes between infants that spent > 50% of the time out-of-range (OOR) or inside the range (IR). A P-value < 0.05 was significant. RESULTS: A total of 20 infants were included. Important fluctuations were detected by the device with infants spending 40% and 14% of the time above and below the range, respectively. However, the RH set point did not differ from the mean levels measured over 48 h by the RH32S-C2 or the incubator. Infants in the OOR group spent significantly more time at values higher than the planned range when compared to IR infants. CONCLUSION: Although significant fluctuations in RH above the desired range were detected in more than half of the infants, the average values were similar to the set points. Nevertheless, knowledge of these dynamic changes may help to optimize individualized care.

Liver fluid collection in neonates and its association with the use of a specific umbilical vein catheter: Report of five cases.

In newborns, the presence of liver fluid collection is a rare event. The reported cases are isolated or described over long periods. Within four months, five neonates were diagnosed with liver fluid collection from safety occurrence reports. Clinical, laboratory and radiological data were extracted from medical records. The definite diagnosis was made by ultrasound. Four of the patients were preterm, male and had very low birth weights. The osmolality of the infused solution was within the acceptable range. Investigations revealed that the use of a new brand of umbilical vein catheter introduced in the neonatal intensive care unit, one month before the first case, was associated with this cluster. Low positioning of the umbilical vein catheter tip appeared to be a second contributory factor. Neonatal practitioners may benefit from the present report when facing the occurrence of similar lesions.

Implementation of a respiratory therapist-driven protocol for neonatal ventilation: impact on the premature population.

OBJECTIVE: The purpose of this work was to evaluate the impact of the implementation of a ventilation protocol driven by registered respiratory therapists on respiratory outcomes of premature infants with birth weight < or =1250 g. METHODS: A ventilation protocol driven by a registered respiratory therapist was developed by a multidisciplinary group and implemented in our unit in July 2004. A retrospective review of 301 inborn infants with birth weight < or =1250 g who were mechanically ventilated was performed. Ninety-three infants were ventilated before the ventilation protocol (before), 109 in the first year (after 1) and 99 during the second year (after 2) after the ventilation protocol implementation. Data were collected with a predefined form. RESULTS: The baseline characteristics of the population were similar among the 3 groups, except for a significant smaller number of male infants in the first year after the protocol implementation. The significant differences among the 3 periods were as follows: (1) time of first extubation attempt; (2) duration of mechanical ventilation; and (3) rate of extubation failure (40%, 26%, and 20%). There was no difference in the rate of air leaks, patent ductus arteriosus ligation, necrotizing enterocolitis, bronchopulmonary dysplasia, or death. There was a significant decrease in the combined rates of intraventricular hemorrhage grades III to IV and/or periventricular leukomalacia (31%, 18%, and 4%) after the protocol implementation. CONCLUSIONS: In this study, we were able to demonstrate for the first time a significant improvement on the weaning time and duration of mechanical ventilation with the implementation of a ventilation protocol driven by a registered respiratory therapist in the premature population. Based on our experience, other institutions can customize ventilation protocols to their local practice. However, a prospective, randomized, controlled study should be planned to evaluate long-term outcomes such as BPD and neurodevelopment.

Alterações do crescimento e do metabolismo após o nascimento: repercussões tardias sobre o controle da respiração e da termorregulação e o mecanismo de catch-up growth / Alterations of the growth and the metabolism after the delayed nascimento: repercussões on the control of the breath and the termorregulação and the mechanism of catch-up growth

Alterações do crescimento e do metabolismo durante o período de desenvolvimento pós-natal são eventos bastante comuns na natureza. Foram investigados alguns aspectos do controle da respiração e da termorregulação em ratos jovens, após alterações do crescimento e do metabolismo durante o período pós-natal, produzidas através de baixa ingesta calórica e exposição crônica ao frio. O controle da respiração foi avaliado através da medida do padrão ventilatório em repouso e a resposta ventilatória durante a exposição aguda a hipóxia e a hiperconia. No primeiro experimento foram realizadas medidas de mecânica pulmonar passiva. Ao final dos experimentos os ratos foram sacrificados e os pulmões e uma amostra do tecido gorduroso marrom foram retirado para avaliação do peso pulmonar e da concentração de proteína e DNA dos pulmões e de proteína e UCP do tecido gorduroso marrom. Os resultados demonstraram que alterações importantes do crescimento e do metabolismo durante o período logo após o nascimento não produzem modificações no estabelecimento das funções regulatórias testadas. Observou-se uma fase de crescimento acelerado ao final do insulto, numa tentativa de recolocar o animal nos canais de crescimento anteriores ao insulto. Este fenômeno é denominado de catch-up growth. O terceiro experimento avalia este fenomeno, descrito a cerca de 40 anos atras e ainda sem uma explicação mais clara quanto ao mecanismo responsável. Para avaliação do catch-up growth foram estudados 6 grupos de animais, que foram submetidos a baixa ingesta calórica e exposição a hipóxia durante a primeira semana de vida, além do grupo controle. O crescimento foi monitorizado através das medidas antropométricas de peso corporal total e do comprimento em 3 momentos. Para cada idade, após a medida do metabolismo gasoso em temperatura ambiente, os animais foram sacrificados e foram medidos os pesos de vários orgãos internos. Um índice de desigualdade entre os orgãos internos foi calculado através do coeficiente de variação da relação entre a média dos sete parâmetros do grupo experimental em relação aos controles. Uma correlação positiva entre este índice de desigualdade inter-orgãos e a taxa de crescimento mostrou-se significativa. Resultado suporta a possibilidade de que esta desigualdade inter-orgãos seja um fator adicional no controle da velocidade de crescimento observada durante o catch-up growth.