Transferring an extremely premature infant to an extra-uterine life support system: a prospective view on the obstetric procedure.

To improve care for extremely premature infants, the development of an extrauterine environment for newborn development is being researched, known as Artificial Placenta and Artificial Womb (APAW) technology. APAW facilitates extended development in a liquid-filled incubator with oxygen and nutrient supply through an oxygenator connected to the umbilical vessels. This setup is intended to provide the optimal environment for further development, allowing further lung maturation by delaying gas exposure to oxygen. This innovative treatment necessitates interventions in obstetric procedures to transfer an infant from the native to an artificial womb, while preventing fetal-to-neonatal transition. In this narrative review we analyze relevant fetal physiology literature, provide an overview of insights from APAW studies, and identify considerations for the obstetric procedure from the native uterus to an APAW system. Lastly, this review provides suggestions to improve sterility, fetal and maternal well-being, and the prevention of neonatal transition.

Closed-Loop Control of Arterial CO2 in Mechanical Ventilation of Neonates.

During mechanical ventilation of the neonate the main goal is to stabilize respiratory function of the often premature lungs. Ventilating the patient without inflicting harm is then the subordinated next goal. Ideally the arterial partial pressure of CO2 lays within a normocapnic range and fluctuations are kept minimal. By closely monitoring CO2 and controlling ventilation parameters accordingly, CO2 levels in the blood can be managed. We present an approach consisting of a cascaded controller for arterial CO2 by approximating arterial partial pressure PaCO2 from end-tidal PetCO2. As a proof of concept, feasibility of the controller was first evaluated on a mathematical patient model and subsequently in-vivo in lamb experiments. The controller is able to regulate CO2 into a normocapnic range in both setups with satisfactory stationarity within the target range. Estimation of the arterial partial pressure of CO2 remains a critical aspect that needs to be further investigated. Clinical relevance-Closed-loop control of CO2 in mechanical ventilation aims to avoid PaC O2 extremes and to reduce fluctuations. Both are a relevant risk factors especially for neurological complications among preterm newborns.

Interprofessional Consensus Regarding Design Requirements for Liquid-Based Perinatal Life Support (PLS) Technology.

Liquid-based perinatal life support (PLS) technology will probably be applied in a first-in-human study within the next decade. Research and development of PLS technology should not only address technical issues, but also consider socio-ethical and legal aspects, its application area, and the corresponding design implications. This paper represents the consensus opinion of a group of healthcare professionals, designers, ethicists, researchers and patient representatives, who have expertise in tertiary obstetric and neonatal care, bio-ethics, experimental perinatal animal models for physiologic research, biomedical modeling, monitoring, and design. The aim of this paper is to provide a framework for research and development of PLS technology. These requirements are considering the possible respective user perspectives, with the aim to co-create a PLS system that facilitates physiological growth and development for extremely preterm born infants.

Evaluation to improve the quality of medication preparation and administration in pediatric and adult intensive care units.

PURPOSE: To determine the type, frequency, and factors associated with medication preparation and administration errors in adult intensive care units (ICUs) and neonatal ICUs (NICUs)/pediatric ICUs (PICUs). PATIENTS AND METHODS: We conducted a prospective direct observation study in an adult ICU and NICU/PICU in a tertiary university hospital. Between June 2012 and June 2013, a clinical pharmacist and medical student observed the nursing care staff on weekdays during the preparation and administration of intravenous drugs. We analyzed the frequency and type of preparation and administration errors and factors associated with errors. RESULTS: Six hundred and three preparations in the adult ICU and 281 in the NICU/PICU were observed. Three hundred and eighty-five errors occurred in the adult ICU and 38 in the NICU/PICU. There were 5,040 and 2,514 error opportunities, with overall error rates of 7.6% and 1.5%, respectively. The total opportunities for error meant each single step of preparation and administration that was relevant for the drug. Most errors applied to the category "uniform mixing" (adult ICU: n=227, 59%; NICU/PICU: n=14, 37%). The multivariate logistic regression results showed a significantly different influence of the "preparation type" for the adult ICU compared with the NICU/PICU with regard to the occurrence of an error. Preparations for adult patients of the LCD type (liquid concentrate with diluent into syringe or infusion bag) were more often associated with errors than the P (powder in a glass vial that must be reconstituted and diluted if necessary), P=0.012, and LC (liquid concentrate into syringe), P=0.002 type. CONCLUSION: "Uniform mixing" was the most erroneous preparation step in intravenous drug preparations in two ICUs. Improvement of nurse training and the preparation of prefilled syringes in the pharmacy might reduce errors and improve the quality and safety of drug therapy.

Spontaneous movements in the first four months of life: An accelerometric study in moderate and late preterm infants.

BACKGROUND: Moderate preterm infants (MPI) and late preterm infants (LPI) account for the majority of children born preterm. Up to 5% of MPI and LPI are estimated to manifest neurodevelopmental impairments. However, information about normal early motor development in these patients is lacking. AIM: To find characteristic patterns for motor development in the first four months of life among MPI and LPI without risk factors for developmental impairment by using accelerometry of spontaneous movements. STUDY DESIGN: Prospective and observational study. SUBJECTS: Twenty-three MPI and LPI (9 female, 14 male) without known risk factors for neurodevelopmental impairment were included in this study. Spontaneous movements were measured by accelerometry at the time of hospital discharge (mean: 36.6wks postmenstrual age (PMA)) and at the corrected age of three months (mean: 53.0wks PMA). OUTCOME MEASURES: Motor development was described by analyzing 36 parameters calculated from the acceleration signal. Normal neurodevelopmental outcome was confirmed by Bayley Scales of Infant Development at the corrected age of two years. RESULTS: Statistically significant differences (p < 0.05) between the two measurements could be shown in 26 out of the 36 parameters. Striking changes in motor development were an increase in acceleration and variability of the spontaneous movements, the main criterion for analyzing spontaneous movements. Furthermore, the regularity of spontaneous movements increased significantly. CONCLUSION: Characteristic patterns of normal motor development in MPI and LPI can be identified and provide a basis for future investigations aiming at the early detection of abnormal motor development for this specific patient group.

Aided Hand Detection in Thermal Imaging Using RGB Stereo Vision.

Thermal imaging is used in medical diagnosis and preventive screening, e.g. breast cancer, cardiovascular disease, and orthopedics. Segmentation algorithms fail to recognize body parts of interest when the temperature difference between the body parts and the background is insufficient. We propose to perform segmentation in two stereoscopically acquired RGB images and to triangulate corresponding points extracted from those images into world coordinates. The thereby acquired world coordinates are projected into the thermal image plane for a more robust segmentation result. Our worked example is the segmentation of human hands. The extension of the thermal setup with two additional RGB cameras improves segmentation in our particular case, but could also make segmentation of other body parts in thermal images more robust. Comparing significant points like fingertips and the junctions between the fingers and the metacarpus, we come up with an average deviation of 1.03 pixel ± 0.82 pixel in x-axis direction and 1.04 pixel ± 0.62 pixel in y-axis direction, roughly corresponding to a mean Euclidean distance of 1.4 mm on the hands.

Preterm Pulmonary Hemorrhage Is Associated with Multiple Births but Not with Intracytoplasmic Sperm Injection: A Cohort Study on Medical Records.

OBJECTIVE: Pulmonary hemorrhage (PH) is a severe complication in preterm neonates. This study aims to identify risk factors and comorbidities of PH. STUDY DESIGN: A single-center cohort study on medical records including all preterm neonates of <30 weeks' gestational age was conducted in the neonatal intensive care unit of Universitätsklinikum Aachen, Germany. The occurrence of PH served as a primary end point. Gestational age, birthweight, sex, multiple births, intracytoplasmic sperm injection (ICSI), intubation, surfactant, antenatal steroids, intraventricular hemorrhage (IVH), amniotic infection syndrome, and persistent ductus arteriosus were studied as risk factors. RESULTS: In this study, 344 preterm neonates were included, of whom 36 suffered from PH (10.5%). The mean time of the first occurrence was the third day of life (standard deviation [SD]: 1.2). On average, the patients suffered from 1.5 incidents (SD: 0.8) of PH, of whom 50% were severe. Preterm neonates born as multiples (95% confidence interval [CI]: 3.1, 26.9) and those who suffered from IVH (95% CI: 2.7, 18.9) had a significantly increased risk of PH. ICSI was not an independent risk factor. CONCLUSION: PH is significantly associated with IVH and multiple births but not with ICSI. The identification of patients at risk allows to apply prophylactic strategies of ventilation and pharmacological treatment.

Incidence and Severity of Prescribing Errors in Parenteral Nutrition for Pediatric Inpatients at a Neonatal and Pediatric Intensive Care Unit.

OBJECTIVES: Pediatric inpatients are particularly vulnerable to medication errors (MEs), especially in highly individualized preparations like parenteral nutrition (PN). Aside from prescribing via a computerized physician order entry system (CPOE), we evaluated the effect of cross-checking by a clinical pharmacist to prevent harm from PN order errors in a neonatal and pediatric intensive care unit (NICU/PICU). METHODS: The incidence of prescribing errors in PN in a tertiary level NICU/PICU was surveyed prospectively between March 2012 and July 2013 (n = 3,012 orders). A pharmacist cross-checked all PN orders prior to preparation. Errors were assigned to seven different error-type categories. Three independent experts from different academic tertiary level NICUs judged the severity of each error according to the National Coordinating Council for Medication Error Reporting and Prevention (NCC MERP) Index (categories A-I). RESULTS: The error rate was 3.9% for all 3,012 orders (118 prescribing errors in 111 orders). 77 (6.0%, 1,277 orders) errors occurred in the category concentration range, all concerning a relative overdose of calcium gluconate for peripheral infusion. The majority of all events (60%) were assigned to categories C and D (without major harmful consequences) while 28% could not be assigned due to missing majority decision. Potential harmful consequences requiring interventions (category E) could have occurred in 12% of assessments. CONCLUSION: Next to systematic application of clinical guidelines and prescribing via CPOE, order review by a clinical pharmacist is still required to effectively reduce MEs and thus to prevent minor and major adverse drug events with the aim to enhance medication safety.

Adult "termination-of-resuscitation" (TOR)-criteria may not be suitable for children - a retrospective analysis.

BACKGROUND: Only a small number of patients survive out-of-hospital-cardiac-arrest (OHCA). The duration of CPR varies considerably and transportation of patients under CPR is often unsuccessful. Termination-of-resuscitation (TOR)-criteria aim to preclude futile resuscitation efforts. Our goal was to find out to which extent existing TOR-criteria can be transferred to paediatric OHCA-patients with special regard to their prognostic value. METHODS: We performed a retrospective analysis of an eleven-year single centre patient cohort. 43 paediatric patients admitted to our institution after emergency-medical-system (EMS)-confirmed OHCA from 2003 to 2013 were included. Morrison's BLS- and ALS-TOR-rules as well as the Trauma-TOR-criteria by the American Association of EMS Physicians were evaluated for application in children, by calculating sensitivity, specificity, negative and positive predictive value for death-, as well as survival-prediction in our cohort. RESULTS: 26 patients achieved ROSC and 14 were discharged alive (n = 7 PCPC 1/2, n = 7 PCPC 5). Sensitivity for BLS-TOR-criteria predicting death was 48.3%, specificity 92.9%, the PPV 93.3% and the NPV 46.4%. ALS-TOR-criteria for death had a sensitivity of 10.3%, specificity of 100%, a PPV of 100% and an NPV of 35%. CONCLUSION: Retrospective application of the BLS-TOR-rule in our patient cohort identified the resuscitation of one later survivor as futile. ALS-TOR-criteria did not give false predictions of death. The proportion of CPRs that could have been abandoned is 48.2% for the BLS-TOR and only 10.3% for the ALS-TOR-rule. Both rules therefore appear not to be transferable to a paediatric population.

Miniaturization: the clue to clinical application of the artificial placenta.

The artificial placenta as a fascinating treatment alternative for neonatal lung failure has been the subject of clinical research for over 50 years. Pumpless systems have been in use since 1986. However, inappropriate dimensioning of commercially available oxygenators has wasted some of the theoretical advantages of this concept. Disproportional shunt fractions can cause congestive heart failure. Blood priming of large oxygenators and circuits dilutes fetal hemoglobin (as the superior oxygen carrier), is potentially infectious, and causes inflammatory reactions. Flow demands of large extracorporeal circuits require cannula sizes that are not appropriate for use in preterm infants. NeonatOx, a tailored low-volume oxygenator for this purpose, has proven the feasibility of this principle before. We now report the advances in biological performance of a refined version of this specialized oxygenator.

Fifty years of work on the artificial placenta: milestones in the history of extracorporeal support of the premature newborn.

The concept of an artificial placenta has been pursued in experimental research since the early 1960s. The principle has yet to be successfully implemented in neonatal care despite the constant evolution in extracorporeal life support technology and advancements in neonatal intensive care in general. For more than three decades, the physical dimensions of the required equipment necessitated pump-driven circuits; however, recent advances in oxygenator technology have allowed exploration of the simpler and physiologically preferable concept of pumpless arteriovenous oxygenation. We expect that further miniaturization of the extracorporeal circuit will allow the implementation of the concept into clinical application as an assist device. To this end, NeonatOx (Fig. 1), a custom-made miniaturized oxygenator with a filling volume of 20 mL, designed by our own group, has been successfully implemented with a preterm lamb model of less than 2000 g body weight as an assist device. We provide an overview of milestones in the history of extracorporeal membrane oxygenation of the preterm newborn juxtaposed against current and future technological advancements. Key limitations, which need to be addressed in order to make mechanical gas exchange a clinical treatment option of prematurity-related lung failure, are also identified.

NeonatOx: a pumpless extracorporeal lung support for premature neonates.

Gas exchange in premature neonates is regularly impaired by structural and functional immaturity of the lung. Mechanical ventilation, which is vitally important to sustain oxygenation and CO(2) elimination, causes, at the same time, mechanical and inflammatory destruction of lung tissue. To date, extracorporeal oxygenation is not a treatment option, one reason among others being the size of available oxygenators and cannulas. We hypothesized that a substantial improvement in gas exchange can be achieved by maintenance of the fetal cardiopulmonary bypass and interposition of a suitable passively driven (arteriovenous) membrane oxygenator. In close cooperation between engineers and neonatologists, we developed a miniaturized oxygenator and adapted cannulas to be used as a pumpless extracorporeal lung support that is connected to the circulation via cannulation of the umbilical cord vessels. First in vitro and in vivo studies show promising results. We regard this as one step on the way to clinical application of the artificial placenta.