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Background: Arterial pressure measurements are important to monitor vital function in neonates, and values are known to be dependent of gestational and postnatal age. Current reference ranges for mean arterial pressure in neonates have been derived from small samples and combined data of noninvasive and invasive measurements. We aimed to define reference values for noninvasive mean, systolic, and diastolic blood pressure during the first week of life in otherwise healthy preterm and term neonates defined by gestational and postnatal age. Methods: In this retrospective cohort study in a neonatal intensive care unit (NICU) in a Dutch tertiary paediatric hospital, we included the noninvasive blood pressures of neonates admitted between 2016 and 2018, with exclusion of those with severe comorbidities (major cardiac malformations, intracerebral haemorrhage, and tracheal intubation >6 h). We defined the median (P50) with −2 standard deviations (SD) (P0.23), −1 SD (P16), +1 SD (P84), and +2 SD (P97.7) for gestational age and postnatal age using quantile regression, percentiles provided online (http://bloodpressure-neonate.com/). Results: A total of 607 neonates, with 5885 measurements, fulfilled the inclusion criteria. The P50 values of mean noninvasive arterial blood pressure in extreme preterm infants steeply increased during the first day after birth and gradually increased within a week from 27 to 49 mm Hg at 24 h of gestational age, and from 49 to 61 mm Hg at 41 weeks of gestational age. Conclusions: These reference values for noninvasive blood pressure in neonates in the NICU for various gestational age groups provide guidance for clinical decision-making in healthy and diseased neonates during anaesthesia and sedation.

Background: An oxygen saturation (SpO2) histogram classification system has been shown to enable quantification of SpO2 instability into five types, based on histogram distribution and time spent at SpO2 ≤ 80%. We aimed to investigate this classification system as a tool to describe response to doxapram treatment in infants with severe apnea of prematurity. Methods: This retrospective study included 61 very-low-birth-weight infants who received doxapram. SpO2 histograms were generated over the 24-h before and after doxapram start. Therapy response was defined as a decrease of ≥1 histogram types after therapy start. Results: The median (IQR) histogram type decreased from 4 (3–4) before to 3 (2–3) after therapy start (p < 0.001). The median (IQR) FiO2 remained constant before (27% [24–35%]) and after (26% [22–35%]) therapy. Thirty-six infants (59%) responded to therapy within 24 h. In 34/36 (94%) of the responders, invasive mechanical ventilation (IMV) was not required during the first 72 h of therapy, compared to 15/25 (60%) of non-responders (p = 0.002). Positive and negative predictive values of the 24-h response for no IMV requirement within 72 h were 0.46 and 0.94, respectively. Conclusions: Classification of SpO2 histograms provides an objective bedside measure to assess response to doxapram therapy and can serve as a tool to detect changes in oxygenation status around respiratory interventions. Impact: The SpO2 histogram classification system provides a tool for quantifying response to doxapram therapy.The classification system allowed estimation of the probability of invasive mechanical ventilation requirement, already within a few hours of treatment.The SpO2 histogram classification system allows an objective bedside assessment of the oxygenation status of the preterm infant, making it possible to assess the changes in oxygenation status in response to respiratory interventions.

Background: In neonates with post-asphyxial neonatal encephalopathy, further neuronal damage is prevented with therapeutic hypothermia (TH). In addition, fluctuations in carbon dioxide levels have been associated with poor neurodevelopmental outcome, demanding close monitoring. This study investigated the accuracy and clinical value of transcutaneous carbon dioxide (tcPCO2) monitoring during TH. Methods: In this retrospective cohort study in neonates, agreement between arterial carbon dioxide (PaCO2) values and tcPCO2 measurements during TH was determined. TcPCO2 levels during the first 24 h of hypothermia were tested for an association with ischemic brain injury on magnetic resonance imaging (MRI). Results: Thirty-four neonates were included. Agreement (bias (95% limits of agreement)) between tcPCO2 and PaCO2 levels was 3.9 (−12.4–20.2) mm Hg. No relation was found between the body temperature and tcPCO2 levels. TcPCO2 levels differed significantly between patients with considerable and minimal damage on MRI; after 6 h (P = 0.02) and 9 h (P = 0.04). Conclusions: Although tcPCO2 provided a limited estimation of PaCO2, it can be used for trend monitoring during TH. TcPCO2 levels after birth could provide an early indicator of ischemic brain injury. This relation should be investigated in large prospective studies, in which adjustments for confounders can be made. Impact: Transcutaneous carbon dioxide measurements during therapeutic hypothermia in neonates show limited accuracy similar to measurements reported in normothermic neonates and can be used for trend monitoring.Low transcutaneous carbon dioxide levels during the first 24 h were associated with considerable ischemic brain injury on MRI.The value of transcutaneous carbon dioxide measurements during the first 24 h as an indicator of considerable ischemic brain injury on MRI should be investigated in future studies, adjusting for confounders.Transcutaneous oxygen measurements during therapeutic hypothermia showed an inaccuracy that could not be related to a low body temperature.

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.

OBJECTIVE: To develop a realistic simulation model for laparotomy-assisted fetoscopic spina bifida aperta (SBa) surgery, to be used for training purposes and preoperative planning.METHODS: The predefined general requirement was a realistic model of an exteriorized uterus, allowing all neurosurgical steps of the intervention. The uterus was modelled using ultrasound and MRI images of a 25 weeks' gravid uterus, consisting of flexible polyurethane foam coated with pigmented silicone. The fetal model, contained an opening on the dorsal side for a customizable spinal insert with all the aspects of a SBa, including a cele, placode, and myofascial and skin layer. The model was assessed in a series of validation experiments.RESULTS: Production costs are low, uterus and fetus are reusable. Placental localization and the level and size of the spinal defect are adjustable, enabling case-specific adaptations. All aspects of the simulator were scored close to realistic or higher for both appearance and functional capacities.CONCLUSIONS: This innovative model provides an excellent training opportunity for centers that are starting a fetoscopic SBa repair program. It is the first simulation model with adjustable spinal defect and placental localisation. Further objective validation is required, but the potential for using this model in preoperative planning is promising.

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 2 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 2 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 2. Perfusion index increased significantly after RBC transfusion (p Conclusions: RBC transfusions in preterm newborns could help decrease the incidence of desaturations and the area 2 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.

Background Abdominal compliance describes the ease of expansion of the abdominal cavity. Several studies highlighted the importance of monitoring abdominal compliance (Cab) during the creation of laparoscopic workspace to individualize the insufflation pressure. The lack of validated clinical monitoring tools for abdominal compliance prevents accurate tailoring of insufflation pressure. Oscillometry, also known as the forced oscillation technique (FOT), is currently used to measure respiratory mechanics and has the potential to be adapted for monitoring abdominal compliance. This study aimed to define, develop and evaluate a novel approach which can monitor abdominal compliance during laparoscopy using endoscopic oscillometry. Materials and methods Endoscopic oscillometry was evaluated in a porcine model for laparoscopy. A custom-built insufflator was developed for applying an oscillatory pressure signal superimposed onto a mean intra-abdominal pressure. This insufflator was used to measure the abdominal compliance at insufflation pressures ranging from 5 to 20 hPa (3.75 to 15 mmHg). The measurements were compared to the static abdominal compliance, which was measured simultaneously with computed tomography imaging. Results Endoscopic oscillometry recordings and CT images were obtained in 10 subjects, resulting in 76 measurement pairs for analysis. The measured dynamic Cab ranged between 0.0216 and 0.261 L/hPa while the static Cab based on the CT imaging ranged between 0.0318 and 0.364 L/hPa. The correlation showed a polynomial relation and the adjusted R-squared was 97.1%. Conclusions Endoscopic oscillometry can be used to monitor changes in abdominal compliance during laparoscopic surgery, which was demonstrated in this study with a comparison with CT imaging in a porcine laparoscopy model. Use of this technology to personalize the insufflation pressure could reduce the risk of applying excessive pressure and limit the drawbacks of insufflation.

Arterial blood gas analysis is the gold standard for monitoring of PWe conducted a study in children undergoing general anesthesia to validate the use and to determine the accuracy of continuous transcutaneous measurements of the partial pressures of PCOA prospective observational study in a tertiary care pediatric hospital in The Netherlands, from April to October 2018, in children aged 0-18 years undergoing general anesthesia. Patients were included when endotracheally intubated and provided with an arterial catheter for regular blood sampling. Patients with a gestational age31 weeks, burn victims, and patients with skin disease were excluded. TcPCOWe included 53 patients (median age 4.1 years, IQR 0.7-14.4 years) and retrieved 175 samples. TcPCOThis study showed good agreement between P

An oxygen saturation (SpOThis retrospective study included 61 very-low-birth-weight infants who received doxapram. SpOThe median (IQR) histogram type decreased from 4 (3-4) before to 3 (2-3) after therapy start (p 0.001). The median (IQR) FiOClassification of SpOThe SpO

In neonates with post-asphyxial neonatal encephalopathy, further neuronal damage is prevented with therapeutic hypothermia (TH). In addition, fluctuations in carbon dioxide levels have been associated with poor neurodevelopmental outcome, demanding close monitoring. This study investigated the accuracy and clinical value of transcutaneous carbon dioxide (tcPCOIn this retrospective cohort study in neonates, agreement between arterial carbon dioxide (PaCOThirty-four neonates were included. Agreement (bias (95% limits of agreement)) between tcPCOAlthough tcPCOTranscutaneous carbon dioxide measurements during therapeutic hypothermia in neonates show limited accuracy similar to measurements reported in normothermic neonates and can be used for trend monitoring. Low transcutaneous carbon dioxide levels during the first 24 h were associated with considerable ischemic brain injury on MRI. The value of transcutaneous carbon dioxide measurements during the first 24 h as an indicator of considerable ischemic brain injury on MRI should be investigated in future studies, adjusting for confounders. Transcutaneous oxygen measurements during therapeutic hypothermia showed an inaccuracy that could not be related to a low body temperature.

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.

This study investigated the accuracy, drift, and clinical usefulness of a new optical transcutaneous oxygen tension (tcPO2) measuring technique, combined with a conventional electrochemical transcutaneous carbon dioxide (tcPCO2) measurement and reflectance pulse oximetry in the novel transcutaneous OxiVenT™ Sensor. In vitro gas studies were performed to measure accuracy and drift of tcPO2and tcPCO2. Clinical usefulness for tcPO2and tcPCO2monitoring was assessed in neonates. In healthy adult volunteers, measured oxygen saturation values (SpO2) were compared with arterially sampled oxygen saturation values (SaO2) during controlled hypoxemia. In vitro correlation and agreement with gas mixtures of tcPO2(r= 0.999, bias 3.0 mm Hg, limits of agreement − 6.6 to 4.9 mm Hg) and tcPCO2(r= 0.999, bias 0.8 mm Hg, limits of agreement − 0.7 to 2.2 mm Hg) were excellent. In vitro drift was negligible for tcPO2(0.30 (0.63 SD) mm Hg/24 h) and highly acceptable for tcPCO2(− 2.53 (1.04 SD) mm Hg/12 h). Clinical use in neonates showed good usability and feasibility. SpO2-SaO2correlation (r= 0.979) and agreement (bias 0.13%, limits of agreement − 3.95 to 4.21%) in healthy adult volunteers were excellent. The investigated combined tcPO2, tcPCO2, and SpO2sensor with a new oxygen fluorescence quenching technique is clinically usable and provides good overall accuracy and negligible tcPO2drift. Accurate and low-drift tcPO2monitoring offers improved measurement validity for long-term monitoring of blood and tissue oxygenation.

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 analyzed. Sixty infants with 112 RBC transfusions, median GA of 26.7 weeks, were included. The number of desaturations and area 2 limit, as a measure of the hypoxic burden, were calculated in 24h before and after RBC transfusion. A mixed effects model was used to account for repeated measurements. Overall, mean (SE) number of desaturations per hour decreased from 3.28(0.55) to 2.25(0.38; p2 limit decreased from 0.14(0.04) to 0.08(0.02) %/sec (p=0.02). These outcomes were stratified for number of desaturations in 24h 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) (p2. Perfusion index increased significantly after RBC transfusion (pConclusions: RBC transfusions in preterm newborns decrease the incidence of desaturations and the hypoxic burden. The higher the number of desaturations prior to the RBC transfusion, the larger the effect observed.

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% SpO

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.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.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.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.

Introduction: Evaluation of pharmacotherapy during intensive care treatment is commonly based on subjective, intermittent interpretations of physiological parameters. Real-time visualization and analysis may improve drug effect evaluation. We aimed to evaluate the effects of the respiratory stimulant doxapram objectively in preterm infants using continuous physiological parameters. Methods: In this longitudinal observational study, preterm infants who received doxapram therapy were eligible for inclusion. Physiological data (1 Hz) were used to assess respiration and to evaluate therapy effects. The oxygen saturation (SpO2)/fraction of inspired oxygen (FiO2) ratio and the area under the 89% SpO2 curve (duration × saturation depth below target) were calculated as measures of hypoxemia. Regression analyses were performed in 1-h timeframes to discriminate therapy failure (intubation or death) from success (no intubation). Results: Monitor data of 61 patients with a median postmenstrual age (PMA) at doxapram initiation of 28.7 (IQR 27.6–30.0) weeks were available. The success rate of doxapram therapy was 56%. Doxapram pharmacodynamics were reflected in an increased SpO2 and SpO2/FiO2 ratio as well as a decrease in episodes with saturations below target (SpO2 2/FiO2 ratio, corrected for PMA and mechanical ventilation before therapy start, discriminated best between therapy failure and success (highest AUC ROC of 0.83). Conclusion: The use of continuous physiological monitor data enables objective and detailed interpretation of doxapram in preterm infants. The SpO2/FiO2 ratio is the best predictive parameter for therapy failure or success. Further implementation of real-time data analysis and treatment algorithms would provide new opportunities to treat newborns.

Neonates with congenital diaphragmatic hernia are among the more complex patients to support with mechanical ventilation. They have particular features that add to the difficulties already present in the neonatal patient. A ventilation strategy tailored to the patient's underlying physiology rather than mode of ventilation is a crucial issue for clinicians treating these delicate patients.

Background: 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.

Background: Drug effect evaluation is often based on subjective interpretation of a selection of patient data. Continuous analyses of high frequency patient monitor data are a valuable source to measuring drug effects. However, these have not yet been fully explored in clinical care. We aim to evaluate the usefulness and applicability of high frequency physiological data for analyses of pharmacotherapy. Methods: As a proof of principle, the effects of doxapram, a respiratory stimulant, on the oxygenation in preterm infants were studied. Second-to-second physiological data were collected from 12 hours before until 36 hours after start of doxapram loading dose plus continuous maintenance dose in seven preterm infants. Besides physiological data, plasma concentrations of doxapram and keto-doxapram were measured. Results: Arterial oxygen saturation (SpO2) increased after the start of doxapram treatment alongside an increase in heart rate. The respiratory rate remained unaffected. The number of saturation dips and the time below a saturation of 80%, as well as the area under the 80%-saturation-time curve (AUC), were significantly lowered after the start of doxapram. The AUC under 90% saturation also significantly improved after start of doxapram. Plasma concentrations of doxapram and keto-doxapram were measured. Conclusion: Using high-frequency monitoring data, we showed the detailed effects over time of pharmacotherapy. We could objectively determine the respiratory condition and the effects of doxapram treatment in preterm infants. This type of analysis might help to develop individualized drug treatments with tailored dose adjustments based on a closed-loop algorithm.