Intermittent feeding with an overnight fast versus 24-h feeding in critically ill neonates, infants, and children:An open-label, single-centre, randomised controlled trial

Background &amp; aims: Critically ill children are fed day and night, assuming this improves enteral tolerance and the probability of achieving nutritional goals. It was previously shown that a fasting response, reflected by increased ketosis, at least partly explained the beneficial outcome of delayed initiation of supplemental parenteral nutrition. This study aims to investigate whether an overnight fast increases ketosis and is feasible and safe in critically ill children. Methods: The Continuous versus Intermittent Nutrition in Paediatric Intensive Care (ContInNuPIC) study is a randomised controlled trial in a tertiary referral Paediatric Intensive Care Unit (PICU) in the Netherlands. Critically ill children (term newborn-18 years) with an expected PICU stay ≥48 h, dependent on artificial nutrition, were eligible. Participants were randomly assigned (1:1, stratified for age group) to intermittent feeding, with interruption of feedings during an age-dependent overnight period of eight to 12 h, or to continuous feeding, with the administration of feedings day and night. In both groups, similar daily caloric targets were pursued. For children younger than one year, mandatory minor glucose infusions were provided during fasting. The primary outcome was the feasibility, defined as two conditions (1): a significant difference in the patients’ highest daily ketone (3-β-hydroxybutyrate, BHB) levels during each overnight period, and (2): non-inferiority regarding daily caloric intake, examined using a two-part mixed-effects model with a predefined non-inferiority margin of 33%, in an intention-to-treat analysis. The study is registered in the Netherlands Trial Register (NL7877). Results: Between May 19, 2020, and July 13, 2022, 140 critically ill children, median (first quartile; third quartile) age 0.3 (0.1; 2.7) years, were randomised to intermittent (n = 67) or continuous feeding (n = 73). In the intermittent feeding group, BHB levels were significantly higher (median 0.4 (0.2; 1.0) vs. 0.3 (0.1; 0.7) mmol/L, p &lt; 0.001). The ratio of total caloric intake in the intermittent feeding group to the intake in the continuous feeding group was not consistently significantly more than 0.67, thus not proving non-inferiority. No severe, resistant hypoglycaemic events, nor severe gastrointestinal complications related to the intervention occurred, and feeding intolerance did not occur more often in the intermittent than in the continuous feeding group. Conclusion: Compared with day and night feeding, intermittent feeding with an overnight fast and mandatory glucose infusion for children younger than one year marginally increased ketosis and did not lead to more hypoglycaemic incidents in critically ill children. Because non-inferiority regarding daily caloric intake was not proven, the feasibility of an overnight fast could not be shown in the current study. However, as feeding intolerance did not increase during the condensed feeding periods, the nutritional intake was probably limited by the prescription of nutrition and interruptions. More research is needed to determine the optimal level and duration of clinically relevant ketosis and the best method to achieve this.</p

Transcutaneous Microcirculatory Imaging in Preterm Neonates

Microcirculatory imaging (MI) is a relatively new research tool mainly used in the intensive care setting. MI provides a clear view of the smallest capillaries, arterioles and venules. The magnifying effect visualizes the flow pattern of erythrocytes through these vessels. It's non-invasive character makes it suitable to apply in (preterm) neonates, even in cardiorespiratory unstable patients. In adults and children, MI is mainly performed sublingually, but this is not possible in preterm infants as these cannot cooperate and the size of the probe is problematic. In preterm infants, MI is therefore performed transcutaneously. Their thin skin makes it possible to obtain high quality images of peripheral microcirculation. In this manuscript we will demonstrate the method of transcutaneous MI in preterm infants. We will focus on the different techniques and provide tips to optimize image quality. The highlights of software settings, safety and offline analysis are also addressed

Improving the Clinical Interpretation of Transcutaneous Carbon Dioxide and Oxygen Measurements in the Neonatal Intensive Care Unit

Introduction: Transcutaneous blood gas monitoring allows for continuous non-invasive evaluation of carbon dioxide and oxygen levels. Its use is limited as its accuracy is dependent on several factors. We aimed to identify the most influential factors to increase usability and aid in the interpretation of transcutaneous blood gas monitoring. Methods: In this retrospective cohort study, transcutaneous blood gas measurements were paired to arterial blood gas withdrawals in neonates admitted to the neonatal intensive care unit. The effects of patient-related, microcirculatory, macrocirculatory, respiratory, and sensor-related factors on the difference between transcutaneously and arterially measured carbon dioxide and oxygen values (ΔPCO2 and ΔPO2) were evaluated using marginal models. Results: A total of 1,578 measurement pairs from 204 infants with a median [interquartile range] gestational age of 273/7 [261/7-313/7] weeks were included. ΔPCO2 was significantly associated with the postnatal age, arterial systolic blood pressure, body temperature, arterial partial pressure of oxygen (PaO2), and sensor temperature. ΔPO2 was, with the exception of PaO2, additionally associated with gestational age, birth weight Z-score, heating power, arterial partial pressure of carbon dioxide, and interactions between sepsis and body temperature and sepsis and the fraction of inspired oxygen. Conclusion: The reliability of transcutaneous blood gas measurements is affected by several clinical factors. Caution is recommended when interpreting transcutaneous blood gas values with an increasing postnatal age due to skin maturation, lower arterial systolic blood pressures, and for transcutaneously measured oxygen values in the case of critical illness. </p

No structural cerebral differences between children with a history of bacterial meningitis and healthy siblings

Aim: After bacterial meningitis, about one-third of children develops academic and/or behavioural limitations. The aim of our study was to search for structural differences in the brain, with a special focus on the hippocampus, between childhood survivors of bacterial meningitis with and without academic and/or behavioural limitations and healthy siblings. Patients and methods: A selection of a cohort, compiled in an earlier performed retrospective study, was used in this case-control study. Magnetic Resonance Imaging scans of the brain were performed in 43 post-meningitis children, of whom 18 had learning and/or behavioural limitations and 25 had no problems, and 18 controls. Voxel-based morphometry investigated the brain for structural changes. Hippocampal volume and lateral ventricle width were measured. Results: No structural differences between the groups, in any area of the brain, were found. There were no significant differences in hippocampal volume or lateral ventricle width. The group with limitations had three children with a right hippocampal volume smaller than two standard deviations below the mean of the control group. Conclusion: Despite hippocampus lesions found in experimental studies, we found no anatomical differences of the brain or hippocampus related to bacterial meningitis in children, nor to the academic and/or behavioural limitations seen after bacterial meningitis

Blunted cortisol response to a psychosocial stressor in schizophrenia

Schizophrenia is considered a neurodevelopmental disorder in which vulnerability to stress may be a contributing factor. Coping is an important psychological component of stress processing, and the hypothalamic-pituitary- adrenal system (HPA system) is one of the biological components of stress adaptation. Disturbances of either of these components may make schizophrenic patients more vulnerable to develop a psychosis under stressful circumstances. In this study, 10 schizophrenic men were compared with 10 healthy male controls in their response to a psychosocial stressor, consisting of a public-speaking task. Heart rate was monitored as a measure of autonomic arousal. HPA responses were assessed by measuring salivary cortisol. Coping skills were measured by using the Utrecht Coping List and the Ways of Coping Checklist. The stress of speaking in public increased the heart rate in both patients and controls; however, a significant cortisol response was found in the controls, but not in the schizophrenic patients. The patients used more passive and avoidant coping strategies than controls. The findings provide support for the notion that schizophrenic patients have an impaired ability to adapt, both psychologically and biologically, to their environment

Cardiorespiratory monitoring of red blood cell transfusions in preterm infants

Clinical improvement after red blood cell (RBC) transfusions in preterm infants remains debated. This study aims to investigate the effect of RBC transfusion on the occurrence of desaturations and hypoxia, and other cardiorespiratory outcomes in preterm infants. In this longitudinal observational study, prospectively stored cardiorespiratory parameters of preterm infants who received at least one RBC transfusion between July 2016 and June 2017 were retrospectively analyzed. Sixty infants with 112 RBC transfusions, median GA of 26.7 weeks, were included. The number of desaturations and area < 80% SpO2 limit, as a measure of the hypoxic burden, were calculated in 24 h before and after RBC transfusion. A mixed effects model was used to account for repeated measurements. Overall, the mean (SE) number of desaturations per hour decreased from 3.28 (0.55) to 2.25 (0.38; p < 0.001), and area < 80% SpO2 limit decreased from 0.14 (0.04) to 0.08 (0.02) %/s (p = 0.02). These outcomes were stratified for the number of desaturations in 24 h prior to RBC transfusion. The largest effect was observed in the group with the highest mean number of desaturations (≥ 6) prior to RBC transfusion, with a decrease from 7.50 (0.66) to 4.26 (0.38) (p < 0.001) in the number of desaturations and 0.46 (0.13) to 0.20 (0.06) in the area < 80% SpO2. Perfusion index increased significantly after RBC transfusion (p < 0.001). No other significant effects of RBC transfusion on cardiorespiratory data were observed. Conclusions: RBC transfusions in preterm newborns could help decrease the incidence of desaturations and the area < 80% SpO2 as a measure of the hypoxic burden. The higher the number of desaturations prior to the RBC transfusion, the larger the effect observed.What is Known:•Red blood cell transfusions potentially prevent hypoxia in anemic preterm infants by increasing the circulatory hemoglobin concentration and improving tissue oxygenation.•There is not a predefined hemoglobin concentration cut-off for the occurrence of symptomatic anemia in preterm infants.What is New:•Oxygen desaturations and hypoxia in anemic preterm infants can be improved by RBC transfusions, especially if more desaturations have occurred before transfusion.•Cardiorespiratory monitor data may help identify infants who will benefit most from red blood cell transfusions

Dynamic Light Scattering: A New Noninvasive Technology for Neonatal Heart Rate Monitoring

Heart rate (HR) detection in premature infants using electrocardiography (ECG) is challenging due to a low signal amplitude and the fragility of the premature skin. Recently, the dynamic light scattering (DLS) technique has been miniaturized, allowing noninvasive HR measurements with a single sensor. Objective: The aim was to determine the accuracy of DLS for HR measurement in infants, compared to ECG-derived HR. Methods: Stable infants with a gestational age of ≥26 weeks, monitored with ECG, were eligible for inclusion. HR was measured with the DLS sensor at 5 different sites for 15 min each. We recorded every 10th second of the DLS-derived HR and the DLS signal-to-noise ratio (SNR), and the ECG-derived HR was extracted for analysis. Patients were randomly divided into 2 groups. In the first group, the optimal SNR cut-off value was determined and then applied to the second group to assess agreement. Results: HR measurements from 31 infants were analyzed. ECG-DLS paired data points were collected at the forehead, an upper extremity, the thorax, a lower extremity, and the abdomen. When applying the international accuracy standard for HR detection, DLS accuracy in the first group (n = 15) was optimal at the forehead (SNR cut-off 1.66). Application of this cut-off to the second group (n = 16) showed good agreement between DLS-derived HR and ECG-derived HR (bias –0.73 bpm; 95% limits of agreement –15.46 and 14.00 bpm) at the forehead with approximately 80% (i.e., 1,066/1,310) of all data pairs remaining. Conclusion: The investigated DLS sensor was sensitive to movement, overall providing less accurate HR measurements than ECG and pulse oximetry. In this study population, specific measurement sites provided excellent signal quality and good agreement with ECG-derived HR.Medical Instruments & Bio-Inspired Technolog

Validation of a New Transcutaneous tcPO₂/tcPCO₂Sensor with an Optical Oxygen Measurement in Preterm Neonates

Introduction: Traditional transcutaneous oxygen (tcPO2) measurements are affected by measurement drift, limiting accuracy and usability. The new potentially drift-free oxygen fluorescence quenching technique has been combined in a single sensor with conventional transcutaneous carbon dioxide (tcPCO2) monitoring. This study aimed to validate optical tcPO2 and conventional tcPCO2 against arterial blood gas samples in preterm neonates and determine measurement drift. Methods: In this prospective observational study, during regular care, transcutaneous measurements were paired to arterial blood gases from preterm neonates aged 24-31 weeks of gestational age (GA) with an arterial catheter. Samples were included based on stability criteria and stratified for sepsis status. Agreement was assessed using the Bland-Altman analysis. Measurement drift per hour was calculated. Results: Sixty-eight premature neonates were included {median (interquartile range [IQR]) GA of 26 4/7 [25 3/7-27 5/7] weeks}, resulting in 216 stable paired samples. Agreement of stable samples in neonates without sepsis (n = 38) and with suspected sepsis (n = 112) was acceptable for tcPO2 and good for tcPCO2. However, in stable samples of neonates with sepsis (n = 66), tcPO2 agreement (bias and 95% limits of agreement) was -32.6 (-97.0 to 31.8) mm Hg and tcPCO2 agreement was 4.2 (-10.5 to 18.9) mm Hg. The median (IQR) absolute drift values were 0.058 (0.0231-0.1013) mm Hg/h for tcPO2 and 0.30 (0.11-0.64) mm Hg/h for tcPCO2. Conclusion: The accuracy of optical tcPO2 in premature neonates was acceptable without sepsis, while electrochemically measured tcPCO2 remained accurate under all circumstances. Measurement drift was negligible for tcPO2 and highly acceptable for tcPCO2. Medical Instruments & Bio-Inspired Technolog

Comparison of frequency-domain and continuous-wave near-infrared spectroscopy devices during the immediate transition

Background: Non-invasive monitoring of cerebral tissue oxygen saturation (rcSO2) during transition is of growing interest. Different near-infrared spectroscopy (NIRS) techniques have been developed to measure rcSO2. We compared rcSO2 values during the immediate transition in preterm neonates measured with frequency-domain NIRS (FD-NIRS) with those measured with continuous-wave NIRS (CW-NIRS) devices in prospective observational studies. Methods: We compared rcSO2 values measured with an FD-NIRS device during the first 15 min after birth in neonates with a gestational age ≥ 30 weeks but &lt; 37 weeks born at the Erasmus MC- Sophia Children's Hospital, Rotterdam, the Netherlands, with similar values measured with a CW-NIRS device in neonates born at the Medical University of Graz, Austria. Mixed models were used to adjust for repeated rcSO2 measurements, with fixed effects for time (non-linear), device, respiratory support and the interaction of device and respiratory support with time. Additionally, parameters such as total haemoglobin concentration and oxygenated and deoxygenated haemoglobin concentrations measured by FD-NIRS were analysed. Results: Thirty-eight FD-NIRS measurements were compared with 58 CW-NIRS measurements. The FD-NIRS rcSO2 values were consistently higher than the CW-NIRS rcSO2 values in the first 12 min, irrespective of respiratory support. After adjustment for respiratory support, the time-dependent trend in rcSO2 differed significantly between techniques (p &lt; 0.01). Conclusion: As cerebral saturation measured with the FD-NIRS device differed significantly from that measured with the CW-NIRS device, differences in absolute values need to be interpreted with care. Although FD-NIRS devices have technical advantages over CW-NIRS devices, FD-NIRS devices may overestimate true cerebral oxygenation and their benefits might not outweigh the usability of the more clinically viable CW-NIRS devices.Medical Instruments & Bio-Inspired Technolog

Reproducibility of the Pleth Variability Index in premature infants

The aim was to assess the reproducibility of the Pleth Variability Index (PVI), developed for non-invasive monitoring of peripheral perfusion, in preterm neonates below 32 weeks of gestational age. Three PVI measurements were consecutively performed in stable, comfortable preterm neonates in the first 48 h of life. On each occasion, pulse oximeter sensors were attached to two different limbs for 5 min. Reproducibility was assessed with the intra-class correlation coefficient (ICC) and Bland–Altman analysis. A total of 25 preterm neonates were included. Inter-limb comparison showed fair to moderate ICC’s with 95%-confidence intervals (95%-CI). Left hand–right hand ICC = 0.498, 95%-CI (0.119–0.753); right foot–right hand ICC = 0.314 (−0.088–0.644); right foot–left foot ICC = 0.315 (−0.089–0.628). Intra-limb comparison showed fair to moderate ICC for right foot–right foot ICC = 0.380 (−0.014–0.677); and good ICC for right hand–right hand ICC = 0.646 (0.194–0.852). Bland–Altman plots showed moderate reproducibility of measurements between different limbs and of the same limb in consecutive time periods, with large biases and wide limits of agreement. The findings from this study indicate that PVI measurement is poorly reproducible when measured on different limbs and on the same limb in stable and comfortable preterm neonates.Medical Instruments & Bio-Inspired Technolog