Escape of surgical smoke particles, comparing conventional and valveless trocar systems.

BACKGROUND: During minimal access surgery, surgical smoke is produced which can potentially be inhaled by the surgical team, leading to several health risks. This smoke can escape from the abdominal cavity into the operating room due to trocar leakage. The trocars and insufflator that are used during surgery influence gas leakage. Therefore, this study compares particle escape from a valveless (Conmed AirSeal iFS), and a conventional (Karl Storz Endoflator) system. MATERIALS AND METHODS: Using an in vitro model, a conventional and a valveless trocar system were compared. A protocol that simulated various surgical phases was defined to assess the surgical conditions and particle leakage. Insufflation pressures and instrument diameters were varied as these are known to affect gas leakage. RESULTS: The conventional trocar leaked during two distinct phases. Removal of the obturator caused a sudden release of particles. During instrument insertion, an average of 211 (IQR 111) particles per second escaped when using the 5 mm diameter instrument. With the 10 mm instrument, 50 (IQR 13) particles per second were measured. With the conventional trocar, a higher abdominal pressure increased particle leakage. The valveless trocar demonstrated a continuously high particle release during all phases. After the obturator was removed, particle escape increased sharply. Particle escape decreased to 1276 (IQR 580) particles per second for the 5 mm instrument insertion, and 1084 (IQR 630) particles per second for 10 mm instrument insertion. With the valveless trocar system, a higher insufflation pressure lowered particle escape. CONCLUSIONS: This study shows that a valveless trocar system releases more particles into the operating room environment than a conventional trocar. During instrument insertion, the leakage through the valveless system is 6 to 20 times higher than the conventional system. With a valveless trocar, leakage decreases with increasing pressure. With both trocar types leakage depends on instrument diameter.

Automated control for investigation of the insufflation-ventilation interaction in experimental laparoscopy.

In laparoscopic surgery the abdominal cavity is insufflated with pressurized carbon dioxide gas to create workspace. This pressure is exerted through the diaphragm onto the lungs, competing with ventilation and hampering it. In clinical practice the difficulty of optimizing this balance can lead to the application of harmfully high pressures. This study set out to create a research platform for the investigation of the complex interaction between insufflation and ventilation in an animal model. The research platform was constructed to incorporate insufflation, ventilation and relevant hemodynamic monitoring devices, controlling insufflation and ventilation from a central computer. The core of the applied methodology is the fixation of physiological parameters by applying closed-loop control of specific ventilation parameters. For accurate volumetric measurements the research platform can be used in a CT scanner. An algorithm was designed to keep blood carbon dioxide and oxygen values stable, minimizing the effect of fluctuations on vascular tone and hemodynamics. This design allowed stepwise adjustment of insufflation pressure to measure the effects on ventilation and circulation. A pilot experiment in a porcine model demonstrated adequate platform performance. The developed research platform and protocol automation have the potential to increase translatability and repeatability of animal experiments on the biomechanical interactions between insufflation and ventilation.

Age-dependent changes in arterial blood pressure in neonates during the first week of life: reference values and development of a model.

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.

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.

Development of a simulator for training of fetoscopic myelomeningocele surgery.

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.

Oxygen saturation histogram classification system to evaluate response to doxapram treatment in preterm infants.

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.

A novel method for monitoring abdominal compliance to optimize insufflation pressure during laparoscopy.

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.

A novel non-invasive method of measuring microcirculatory perfusion and blood velocity in infants: a pilot study.

Current haemodynamic monitoring is mainly aimed at the macrocirculation. Multiple studies have demonstrated the importance of the microcirculation in relation to the patient's condition and impact of treatment strategies. However, continuous monitoring of the microcirculation is not yet possible in the neonatal field. A novel dynamic light scattering (DLS) sensor technology for continuous monitoring of the microcirculation was investigated in the neonatal population. Thirty-one haemodynamically stable infants were included. Sequential measurements at the forehead, upper extremity, thorax, abdomen and lower extremity were conducted with the DLS sensor. For analyses stable measurements were selected. The DLS parameters, total blood flow (TBF) and relative blood velocity (RBV), were compared between measurement locations. Changes in relative haemodynamic indices (relHIs), indicating the distribution of blood flow in the microcirculatory blood vessels, were associated with heart rate decelerations. Measurements performed at the forehead had significantly lower TBF levels, compared to measurements at other locations. Early changes in relHIs around a heart rate deceleration were recorded a median (IQR) of 22.0 (13.5-27.0) s before the onset. Measurement of the currently unavailable parameters TBF, RBV and relHIs is possible with DLS technology. Validation of the DLS technology is needed for clinical implementation.

Transcutaneous carbon dioxide monitoring during therapeutic hypothermia for neonatal encephalopathy.

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.

Characterisation of trocar associated gas leaks during laparoscopic surgery.

BACKGROUND: During laparoscopy, the abdominal cavity is insufflated with carbon dioxide (CO2) that could become contaminated with viruses and surgical smoke. Medical staff is potentially exposed when this gas leaks into the operating room through the instruments and past trocar valves. No detailed studies currently exist that have quantified these leakage pathways. Therefore, the goal of this study was to quantify the gas leakages through trocars and instruments, during minimally invasive procedures. METHODS: A model of the surgical environment was created, consisting of a rigid container with an interface for airtight clamping of laparoscopic equipment such as trocars and surgical instruments. The model was insufflated to 15 mm Hg using a pressure generator and a pneumotachograph measured the equipment gas leak. A protocol of several use cases was designed to simulate the motions and forces the surgeon exerts on the trocar during surgery. RESULTS: Twenty-three individual trocars and twenty-six laparoscopic instruments were measured for leakage under the different conditions of the protocol. Trocar leakages varied between 0 L/min and more than 30 L/min, the instruments revealed a range of leakages between 0 L/min and 5.5 L/min. The results showed that leakage performance varied widely between trocars and instruments and that the performance and location of the valves influenced trocar leakage. CONCLUSIONS: We propose trocar redesigns to overcome specific causes of gas leaks. Moreover, an international testing standard for CO2 leakage for all new trocars and instruments is needed so surgical teams can avoid this potential health hazard when selecting new equipment.

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.

Validation of a new combined transcutaneous tcPCO2 and tcPO2 sensor in children in the operating theater.

BACKGROUND: Arterial blood gas analysis is the gold standard for monitoring of Pa CO2 and PaO2 during mechanical ventilation. However, continuous measurements would be preferred. Transcutaneous sensors continuously measure blood gases diffusing from the locally heated skin. These sensors have been validated in children mostly in intensive care settings. Accuracy in children during general anesthesia is largely unknown. AIMS: We 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 PCO2 (tcPCO2 ) and PO2 (tcPO2 ). METHODS: A 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 age <31 weeks, burn victims, and patients with skin disease were excluded. TcPCO2 and tcPO2  measurements were performed with a SenTec OxiVenT™ sensor (SenTec AG). Accuracy was determined with an agreement analysis between arterial and transcutaneous PCO2 and PO2  values, and between arterial and endtidal PCO2 (etCO2 ) values, according to Bland and Altman, accounting for multiple measurements per subject. RESULTS: We included 53 patients (median age 4.1 years, IQR 0.7-14.4 years) and retrieved 175 samples. TcPCO2 -Pa CO2 agreement analysis provided a bias of 0.06 kPa (limits of agreement (LOA) -1.18 to 1.31), the etCO2 -Pa CO2 agreement showed a bias of -0.31 kPa (LOA -1.38 to 0.76). Results of the tcPO2 -PaO2 agreement showed a bias of 3.40 to 0.86* (mean tension) kPa. CONCLUSIONS: This study showed good agreement between Pa CO2 and tcPCO2 in children of all ages during general anesthesia. Both transcutaneous and endtidal CO2  measurements showed good accuracy. TcPO2 is only accurate under 6 months of age.

Dynamics of the QTc interval over a 24-h dose interval after start of intravenous ciprofloxacin or low-dose erythromycin administration in ICU patients.

QTc interval prolongation is an adverse effect associated with the use of fluoroquinolones and macrolides. Ciprofloxacin and erythromycin are both frequently prescribed QTc-prolonging drugs in critically ill patients. Critically ill patients may be more vulnerable to developing QTc prolongation, as several risk factors can be present at the same time. Therefore, it is important to know the QTc-prolonging potential of these drugs in the intensive care unit (ICU) population. The aim of this study was to assess the dynamics of the QTc interval over a 24-hour dose interval during intravenous ciprofloxacin and low-dose erythromycin treatment. Therefore, an observational study was performed in ICU patients (≥18 years) receiving ciprofloxacin 400 mg t.i.d. or erythromycin 100 mg b.i.d. intravenously. Continuous ECG data were collected from 2 h before to 24 h after the first administration. QT-analyses were performed using high-end holter software. The effect was determined with a two-sample t-test for clustered data on all QTc values. A linear mixed model by maximum likelihood was applied, for which QTc values were assessed for the available time intervals and therapy. No evident effect over time on therapy with ciprofloxacin and erythromycin was observed on QTc time. There was no significant difference (p = 0.22) in QTc values between the ciprofloxacin group (mean 393 ms) and ciprofloxacin control group (mean 386 ms). The erythromycin group (mean 405 ms) and erythromycin control group (mean 404 ms) neither showed a significant difference (p = 0.80). In 0.6% of the registrations (1.138 out of 198.270 samples) the duration of the QTc interval was longer than 500 ms. The index groups showed slightly more recorded QTc intervals over 500 ms. To conclude, this study could not identify differences in the QTc interval between the treatments analyzed.

Validation of a New Transcutaneous tcPO2/tcPCO2 Sensor 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.

Use of Continuous Physiological Monitor Data to Evaluate Doxapram Therapy in Preterm Infants.

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 <89%). The SpO2/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.

Precision Dosing of Doxapram in Preterm Infants Using Continuous Pharmacodynamic Data and Model-Based Pharmacokinetics: An Illustrative Case Series.

INTRODUCTION: Current drug dosing in preterm infants is standardized, mostly based on bodyweight. Still, covariates such as gestational and postnatal age may importantly alter pharmacokinetics and pharmacodynamics. Evaluation of drug therapy in these patients is very difficult because objective pharmacodynamic parameters are generally lacking. By integrating continuous physiological data with model-based drug exposure and data on adverse drug reactions (ADRs), we aimed to show the potential benefit for optimized individual pharmacotherapy. MATERIALS AND METHODS: Continuous data on oxygen saturation (SpO2), fraction of inspired oxygen (FiO2) and composite parameters, including the SpO2/FiO2 ratio and the cumulative oxygen shortage under the 89% SpO2 limit, served as indicators for doxapram effectiveness. We analyzed these continuous effect data, integrated with doxapram exposure and ADR parameters, obtained in preterm infants around the start of doxapram therapy. The exposures to doxapram and the active metabolite keto-doxapram were simulated using a population pharmacokinetic model. Infants were selected and retrospectively compared on the indication to start doxapram, the first response to doxapram, a potential dose-response relationship, and the administered dosage over time. Recommendations were made for individual improvements of therapy. RESULTS: We provide eight cases of continuous doxapram administration that illustrate a correct and incorrect indication to start doxapram, responders and non-responders to therapy, and unnecessary over-exposure with ADRs. Recommendations for improvement of therapy include: objective evaluation of added effect of doxapram after start, prevention of overdosing by earlier down-titration or termination of therapy, and the prevention of hypoxia and agitation by measuring specific parameters at strategical time-points. CONCLUSION: Real-time and non-invasive effect monitoring of drug therapy combined with model-based exposure provides relevant information to clinicians and can importantly improve therapy. The variability between and within patients emphasizes the importance of individual, objective evaluation of pharmacotherapy. These measurements, together with data on ADRs, allow for precision medicine in neonatology that should be brought to the bedside.

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

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.

Novel transcutaneous sensor combining optical tcPO2 and electrochemical tcPCO2 monitoring with reflectance pulse oximetry.

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 tcPO2 and tcPCO2. Clinical usefulness for tcPO2 and tcPCO2 monitoring 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-SaO2 correlation (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 SpO2 sensor with a new oxygen fluorescence quenching technique is clinically usable and provides good overall accuracy and negligible tcPO2 drift. Accurate and low-drift tcPO2 monitoring offers improved measurement validity for long-term monitoring of blood and tissue oxygenation. Graphical abstract.

Ventilation modalities in infants with congenital diaphragmatic hernia.

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.