A recommendation for the use of electrical biosensing technology in neonatology.

Non-invasive cardiac output monitoring, via electrical biosensing technology (EBT), provides continuous, multi-parameter hemodynamic variable monitoring which may allow for timely identification of hemodynamic instability in some neonates, providing an opportunity for early intervention that may improve neonatal outcomes. EBT encompasses thoracic (TEBT) and whole body (WBEBT) methods. Despite the lack of relative accuracy of these technologies, as compared to transthoracic echocardiography, the use of these technologies in neonatology, both in the research and clinical arena, have increased dramatically over the last 30 years. The European Society of Pediatric Research Special Interest Group in Non-Invasive Cardiac Output Monitoring, a group of experienced neonatologists in the field of EBT, deemed it appropriate to provide recommendations for the use of TEBT and WBEBT in the field of neonatology. Although TEBT is not an accurate determinant of cardiac output or stroke volume, it may be useful for monitoring longitudinal changes of hemodynamic parameters. Few recommendations can be made for the use of TEBT in common neonatal clinical conditions. It is recommended not to use WBEBT to monitor cardiac output. The differences in technologies, study methodologies and data reporting should be addressed in ongoing research prior to introducing EBT into routine practice. IMPACT STATEMENT: TEBT is not recommended as an accurate determinant of cardiac output (CO) (or stroke volume (SV)). TEBT may be useful for monitoring longitudinal changes from baseline of hemodynamic parameters on an individual patient basis. TEBT-derived thoracic fluid content (TFC) longitudinal changes from baseline may be useful in monitoring progress in respiratory disorders and circulatory conditions affecting intrathoracic fluid volume. Currently there is insufficient evidence to make any recommendations regarding the use of WBEBT for CO monitoring in neonates. Further research is required in all areas prior to the implementation of these monitors into routine clinical practice.

Bioreactance-derived haemodynamic parameters in the transitional phase in preterm neonates: a longitudinal study.

Bioreactance (BR) is a novel, non-invasive technology that is able to provide minute-to-minute monitoring of cardiac output and additional haemodynamic variables. This study aimed to determine the values for BR-derived haemodynamic variables in stable preterm neonates during the transitional period. A prospective observational study was performed in a group of stable preterm (< 37 weeks) infants in the neonatal service of Tygerberg Children's Hospital, Cape Town, South Africa. All infants underwent continuous bioreactance (BR) monitoring until 72 h of life. Sixty three preterm infants with a mean gestational age of 31 weeks and mean birth weight of 1563 g were enrolled. Summary data and time series graphs were drawn for BR-derived heart rate, non-invasive blood pressure, stroke volume, cardiac output and total peripheral resistance index. All haemodynamic parameters were significantly associated with postnatal age, after correction for clinical variables (gestational age, birth weight, respiratory support mode). To our knowledge, this is the first paper to present longitudinal BR-derived haemodynamic variable data in a cohort of stable preterm infants, not requiring invasive ventilation or inotropic support, during the first 72 h of life. Bioreactance-derived haemodynamic monitoring is non-invasive and offers the ability to simultaneously monitor numerous haemodynamic parameters of global systemic blood flow. Moreover, it may provide insight into transitional physiology and its pathophysiology.

Healthcare professionals' knowledge of the systematic ABCDE approach: a cross-sectional study.

BACKGROUND: The Airway, Breathing, Circulation, Disability and Exposure (ABCDE) approach is a universal, priority-based approach for the assessment and treatment of critically ill patients. Although the ABCDE approach is widely recommended, adherence in practice appears to be suboptimal. The cause of this non-compliance is unknown. As knowledge is a prerequisite for adherence, the aim of this study was to assess healthcare professionals' knowledge of the ABCDE approach. METHODS: A cross-sectional study was conducted at the Radboud University Medical Center, the Netherlands. A digital multiple-choice assessment tool of the ABCDE approach was developed by an expert panel through a mini-Delphi method and validated by performing test item statistics and an expert-novice comparison. The validated test was sent to healthcare professionals (nurses, residents and medical specialists) of the participating departments: Anaesthesiology, Paediatrics, Emergency Department and the Neonatal, Paediatric and Adult Intensive Care Units. Primary outcome was the test score, reflecting individual level of knowledge. Descriptive statistics, regression analysis and ANOVA were used. RESULTS: Test validation showed a Cronbach's alpha of 0.71 and an expert-novice comparison of 91.9% (standard deviation (SD) 9.1) and 72.4% (15.2) respectively (p < 0.001). Of 954 eligible participants, 240 filled out the questionnaire. The mean (SD) test score (% of correct answers) was 80.1% (12.2). Nurses had significantly lower scores (74.9% (10.9)) than residents (92.3% (7.5)) and medical specialists (88.0% (8.6)) (p < 0.001). The Neonatal Intensive Care Unit (75.9% (12.6)) and Adult Intensive Care Unit (77.4% (11.2)) had significantly lower scores than Paediatric Intensive Care Unit (85.6% (10.6)), Emergency Department (85.5% (10.4)) and Anaesthesiology (85.3% (10.6)) (p < 0.05). Younger participants scored higher than older participants (-0.30% (-0.46;-0.15) in test score/year increase in age). CONCLUSION: Scores of a validated knowledge test regarding the ABCDE approach vary among healthcare professionals caring for critically ill patients. Type of department, profession category and age had a significant influence on the test score. Further research should relate theoretical knowledge level to clinical practice. Tailored interventions to increase ABCDE-related knowledge are recommended.

Accuracy and Trending Ability of Electrical Biosensing Technology for Non-invasive Cardiac Output Monitoring in Neonates: A Systematic Qualitative Review.

Background: Electrical biosensing technology (EBT) is an umbrella term for non-invasive technology utilizing the body's fluctuating resistance to electrical current flow to estimate cardiac output. Monitoring cardiac output in neonates may allow for timely recognition of hemodynamic compromise and allow for prompt therapy, thereby mitigating adverse outcomes. For a new technology to be safely used in the clinical environment for therapeutic decisions, it must be proven to be accurate, precise and be able to track temporal changes. The aim of this systematic review was to identify and analyze studies that describe the accuracy, precision, and trending ability of EBT to non-invasively monitor Left ventricular cardiac output and/or stroke volume in neonates. Methods: A qualitative systematic review was performed. Studies were identified from PubMed NCBI, SCOPUS, and EBSCOHost up to November 2021, where EBT technologies were analyzed in neonates, in comparison to a reference technology. Outcome measures were bias, limits of agreement, percentage error for agreement studies and data from 4-quadrant and polar plots for trending studies. Effect direction plots were used to present results. Results: Fifteen neonatal studies were identified, 14 for agreement and 1 for trending analysis. Only thoracic electrical biosensing technology (TEBT), with transthoracic echocardiography (TTE) as the comparator, studies were available for analyzes. High heterogeneity existed between studies. An equal number of studies showed over- and underestimation of left ventricular output parameters. All studies showed small bias, wide limits of agreement, with most studies having a percentage error >30%. Sub-analyses for respiratory support mode, cardiac anomalies and type of technology showed similar results. The single trending study showed poor concordance, high angular bias, and poor angular concordance. Discussion: Overall, TEBT shows reasonable accuracy, poor precision, and non-interchangeability with TTE. However, high heterogeneity hampered proper analysis. TEBT should be used with caution in the neonatal population for monitoring and determining therapeutic interventions. The use of TEBT trend monitoring has not been sufficiently studied and requires further evaluation in future trials.

Clinical review: Update on hemodynamic monitoring--a consensus of 16.

Hemodynamic monitoring plays a fundamental role in the management of acutely ill patients. With increased concerns about the use of invasive techniques, notably the pulmonary artery catheter, to measure cardiac output, recent years have seen an influx of new, less-invasive means of measuring hemodynamic variables, leaving the clinician somewhat bewildered as to which technique, if any, is best and which he/she should use. In this consensus paper, we try to provide some clarification, offering an objective review of the available monitoring systems, including their specific advantages and limitations, and highlighting some key principles underlying hemodynamic monitoring in critically ill patients.

Bioreactance Cardiac Output Trending Ability in Preterm Infants: A Single Centre, Longitudinal Study.

INTRODUCTION: It is unknown whether bioreactance (BR) can accurately track cardiac output (CO) changes in preterm neonates. METHODS: A prospective observational longitudinal study was performed in stable preterm infants (<37 weeks) during the first 72 h of life. Stroke volume (SV) and CO, as measured by BR and transthoracic echocardiography, were compared. RESULTS: The mean gestational age (GA) was 31.3 weeks and mean birth weight (BW) was 1,563 g. Overall, 690 measurements were analysed for trending ability by 4-quadrant and polar plots. For non-weight-indexed measurements, 377 (54.6%) lay outside the 5% exclusion zone, the concordance rate was poor (77.2%) with a high mean angular bias (28.6°), wide limits of agreement and a poor angular concordance rate (17.4%). Neither GA, BW nor respiratory support mode affected trending data. Patent ductus arteriosus, postnatal age, and CO level had variable effects on trending data. Trending data for 5 and 10% exclusion zones were also compared. CONCLUSION: The ability of BR to track changes in CO is not interchangeable with CO changes as measured by echocardiography. BR, as a trend monitor for changes in CO or SV to determine clinical decisions around interventions in neonatology, should be used with caution.

Advanced Hemodynamic Monitoring in the Neonatal Intensive Care Unit.

Clinical assessment of cardiac output by interpretation of indirect parameters has proven to be inaccurate, irrespective of the level of experience of the clinician. Objective cardiac output monitoring is feasible in newborn infants in intensive care. The most promising methods include transthoracic echocardiography, transcutaneous Doppler, electrical biosensing technologies, transpulmonary ultrasound dilution, and arterial pulse contour analysis. Simultaneous assessment of blood pressure and cardiac output enables the identification of the earliest stage of shock. Comprehensive hemodynamic monitoring is pivotal for an individualized pathophysiology-based hemodynamic management.

Agreement of Cardiac Output Measurements between Bioreactance and Transthoracic Echocardiography in Preterm Infants during the Transitional Phase: A Single-Centre, Prospective Study.

INTRODUCTION: Bioreactance cardiac output (CO) monitors are able to non-invasively and continuously monitor CO. However, as a novel tool to measure CO, it must be proven to be accurate and precise. OBJECTIVE: To determine the agreement between CO measured with a bioreactance monitor and transthoracic echocardiography-derived left ventricular output parameters in preterm infants. METHODS: This is a prospective observational study in 63 preterm neonates with non-invasive respiratory support, not requiring inotrope support. The infants underwent continuous bioreactance monitoring of CO and stroke volume (SV) and simultaneous transthoracic echocardiography every 6 h until 72 h of life. RESULTS: The agreement between bioreactance and transthoracic echocardiography, for both SV and CO, was poor. The percentage error was 67.5% for SV and 71.6% for CO. The mean error was 60.4% for SV and 69.8% for CO. Bias was affected by numerous variables. After correcting for time, CO and SV bias were significantly affected by the presence of an open patent ductus arteriosus and the level of CO. CONCLUSION: Bioreactance cannot be considered interchangeable with transthoracic echocardiography to measure CO in preterm infants during the transition phase. Agreement between bioreactance and other CO metrics should be assessed before concluding its accuracy or inaccuracy in neonates.

Ventilator-induced pulse pressure variation in neonates.

During positive pressure ventilation, arterial pressure variations, like the pulse pressure variation (PPV), are observed in neonates. However, the frequency of the PPV does not always correspond with the respiratory rate. It is hypothesized that PPV is caused by cardiopulmonary interaction, but that this mismatch is related to the low respiratory rate/heart rate ratio. Therefore, the goal of this study is to investigate the relation between PPV and ventilation in neonates. A prospective observational cross-sectional study was carried out in a third-level neonatal intensive care unit in a university hospital. Neonates on synchronized intermittent mandatory ventilation (SIMV) or high-frequency ventilation (HFV) participated in the study. The arterial blood pressure was continuously monitored in 20 neonates on SIMV and 10 neonates on HFV. In neonates on SIMV the CO2 waveform and neonates on HFV the thorax impedance waveform were continuously monitored and defined as the respiratory signal. Correlation and coherence between the respiratory signal and pulse pressure were determined. The correlation between the respiratory signal and pulse pressure was -0.64 ± 0.18 and 0.55 ± 0.16 and coherence at the respiratory frequency was 0.95 ± 0.11 and 0.76 ± 0.4 for SIMV and HFV, respectively. The arterial pressure variations observed in neonates on SIMV or HFV are related to cardiopulmonary interaction. Despite this relation, it is not likely that PPV will reliably predict fluid responsiveness in neonates due to physiological aliasing.

Clinical monitoring of systemic hemodynamics in critically ill newborns.

Circulatory failure is a major cause of mortality and morbidity in critically ill newborn infants. Since objective measurement of systemic blood flow remains very challenging, neonatal hemodynamics is usually assessed by the interpretation of various clinical and biochemical parameters. An overview is given about the predictive value of the most used indicators of circulatory failure, which are blood pressure, heart rate, urine output, capillary refill time, serum lactate concentration, central-peripheral temperature difference, pH, standard base excess, central venous oxygen saturation and colour.

Cardiac output monitoring in newborns.

There is an increased interest in methods of objective cardiac output measurement in critically ill patients. Several techniques are available for measurement of cardiac output in children, although this remains very complex in newborns. Cardiac output monitoring could provide essential information to guide hemodynamic management. An overview is given of various methods of cardiac output monitoring with advantages and major limitations of each technology together with a short explanation of the basic principles.

Null mutations and lethal congenital form of glycogen storage disease type IV.

Glycogen branching enzyme deficiency (glycogen storage disease type IV, GSD-IV) is a rare autosomal recessive disorder of the glycogen synthesis with high mortality. Two female newborns showed severe hypotonia at birth and both died of cardiorespiratory failure, at 4 and 12 weeks, respectively. In both patients, muscle biopsies showed deposits of PAS-positive diastase-resistant material and biochemical analysis in cultured fibroblasts showed markedly reduced glycogen branching enzyme activity. Direct sequencing of GBE1 gene revealed that patient 1 was homozygous for a novel c.691+5 g>c in intron 5 (IVS5+5 g>c). RT-PCR analysis of GBE1 transcripts from fibroblasts cDNA showed that this mutation produce aberrant splicing. Patient 2 was homozygous for a novel c.1643G>A mutation leading to a stop at codon 548 in exon 13 (p.W548X). These data underscore that in GSD-IV a severe phenotype correlates with null mutations, and indicate that RNA analysis is necessary to characterize functional consequences of intronic mutations.

Normal serum alanine concentration differentiates transient neonatal lactic acidemia from an inborn error of energy metabolism.

BACKGROUND: Elevated blood lactate levels are common in the critically ill neonate; however, sometimes they are difficult to interpret. Persistent or recurrent lactic acidemia might point to an inborn error of metabolism, like disturbances of the oxidative phosphorylation. Chronic lactic acidemia results in increased serum alanine levels. Serum alanine levels in newborns with transient lactic acidemia have not yet been studied. OBJECTIVE: We designed a pilot study to evaluate the use of serum alanine levels as an additional metabolic marker to differentiate the transient effect of circulatory failure from a possible mitochondrial dysfunction. METHODS: We prospectively evaluated 10 newborns with transient lactic acidemia after mild dysoxia, and 10 newborns with recurrent lactic acidemia consecutively diagnosed with a disorder in oxidative phosphorylation. RESULTS: No significant serum alanine level elevation was found in transient lactic acidemia. Increased serum alanine was a sensitive marker in mitochondrial dysfunction. CONCLUSIONS: We propose to measure the serum alanine level in hypotonic newborns with lactic acidemia to facilitate the decision making in further diagnostics and management.