Early Blood Clot Detection Using Forward Scattering Light Measurements Is Not Superior to Delta Pressure Measurements.

The occurrence of thrombus formation within an extracorporeal membrane oxygenator is a common complication during extracorporeal membrane oxygenation therapy and can rapidly result in a life-threatening situation due to arterial thromboembolism, causing stroke, pulmonary embolism, and limb ischemia in the patient. The standard clinical practice is to monitor the pressure at the inlet and outlet of oxygenators, indicating fulminant, obstructive clot formation indicated by an increasing pressure difference (ΔP). However, smaller blood clots at early stages are not detectable. Therefore, there is an unmet need for sensors that can detect blood clots at an early stage to minimize the associated thromboembolic risks for patients. This study aimed to evaluate if forward scattered light (FSL) measurements can be used for early blood clot detection and if it is superior to the current clinical gold standard (pressure measurements). A miniaturized in vitro test circuit, including a custom-made test chamber, was used. Heparinized human whole blood was circulated through the test circuit until clot formation occurred. Four LEDs and four photodiodes were placed along the sidewall of the test chamber in different positions for FSL measurements. The pressure monitor was connected to the inlet and the outlet to detect changes in ΔP across the test chamber. Despite several modifications in the LED positions on the test chamber, the FSL measurements could not reliably detect a blood clot within the in vitro test circuit, although the pressure measurements used as the current clinical gold standard detected fulminant clot formation in 11 independent experiments.

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.

Treatment of children with hyperbaric oxygenation (HBOT): a Europe-wide survey.

BACKGROUND: Hyperbaric oxygenation therapy (HBOT) is used as emergency treatment for decompression sickness, gas embolism, carbon monoxide intoxication, and necrotizing fasciitis. There is low evidence and little clinical knowledge about the treatment of children with HBOT. METHODS: We sent an internet-based questionnaire to HBO centers in Europe to gain information about their experience with children and HBOT. RESULTS: Out of all HBO-centers who participated in the questionnaire 90% treat children analogue to adults about indication and HBOT protocol. Most treated children had life-threatening indications or the risk of organ loss. The reported rate of side effects was: 6.8% anxiety, 2.4% barotrauma, 0.9% seizure, 0.2% retinopathy and no case of pulmonary barotrauma or oxygen toxicity. CONCLUSIONS: HBO therapy for children is present in European HBO centers. The rate of severe side effects is as low to the rates in adults; apart from this, oxygen-related seizures and anxiety are more frequent. A special focus seems necessary on the psychological management of the children, because anxiety is common depending on the age of the children. Especially for smaller children, an adequate psychological support seems essential. Prospective observational or controlled studies in children seem necessary to create relevant clinical evidence for HBOT and to observe the rate of side-effects.

Algorithmic surveillance of ICU patients with acute respiratory distress syndrome (ASIC): protocol for a multicentre stepped-wedge cluster randomised quality improvement strategy.

INTRODUCTION: The acute respiratory distress syndrome (ARDS) is a highly relevant entity in critical care with mortality rates of 40%. Despite extensive scientific efforts, outcome-relevant therapeutic measures are still insufficiently practised at the bedside. Thus, there is a clear need to adhere to early diagnosis and sufficient therapy in ARDS, assuring lower mortality and multiple organ failure. METHODS AND ANALYSIS: In this quality improvement strategy (QIS), a decision support system as a mobile application (ASIC app), which uses available clinical real-time data, is implemented to support physicians in timely diagnosis and improvement of adherence to established guidelines in the treatment of ARDS. ASIC is conducted on 31 intensive care units (ICUs) at 8 German university hospitals. It is designed as a multicentre stepped-wedge cluster randomised QIS. ICUs are combined into 12 clusters which are randomised in 12 steps. After preparation (18 months) and a control phase of 8 months for all clusters, the first cluster enters a roll-in phase (3 months) that is followed by the actual QIS phase. The remaining clusters follow in month wise steps. The coprimary key performance indicators (KPIs) consist of the ARDS diagnostic rate and guideline adherence regarding lung-protective ventilation. Secondary KPIs include the prevalence of organ dysfunction within 28 days after diagnosis or ICU discharge, the treatment duration on ICU and the hospital mortality. Furthermore, the user acceptance and usability of new technologies in medicine are examined. To show improvements in healthcare of patients with ARDS, differences in primary and secondary KPIs between control phase and QIS will be tested. ETHICS AND DISSEMINATION: Ethical approval was obtained from the independent Ethics Committee (EC) at the RWTH Aachen Faculty of Medicine (local EC reference number: EK 102/19) and the respective data protection officer in March 2019. The results of the ASIC QIS will be presented at conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: DRKS00014330.

Cold Preflush of Porcine Kidney Grafts Prior to Normothermic Machine Perfusion Aggravates Ischemia Reperfusion Injury.

Normothermic machine perfusion (NMP) of kidney grafts is a promising new preservation method to improve graft quality and clinical outcome. Routinely, kidneys are washed out of blood remnants and cooled using organ preservation solutions prior to NMP. Here we assessed the effect of cold preflush compared to direct NMP. After 30 min of warm ischemia, porcine kidneys were either preflushed with cold histidine-tryptophan-ketoglutarate solution (PFNMP group) prior to NMP or directly subjected to NMP (DNMP group) using a blood/buffer solution. NMP was performed at a perfusion pressure of 75 mmHg for 6 h. Functional parameters were assessed as well as histopathological and biochemical analyses. Renal function as expressed by creatinine clearance, fractional excretion of sodium and total output of urine was inferior in PFNMP. Urine protein and neutrophil gelatinase-associated lipocalin (NGAL) concentrations as markers for kidney damage were significantly higher in the PFNMP group. Additionally, increased osmotic nephropathy was found after PFNMP. This study demonstrated that cold preflush prior to NMP aggravates ischemia reperfusion injury in comparison to direct NMP of warm ischemia-damaged kidney grafts. With increasing use of NMP systems for kidneys and other organs, further research into graft flushing during retrieval is warranted.

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.

Smart Medical Information Technology for Healthcare (SMITH).

INTRODUCTION: This article is part of the Focus Theme of Methods of Information in Medicine on the German Medical Informatics Initiative. "Smart Medical Information Technology for Healthcare (SMITH)" is one of four consortia funded by the German Medical Informatics Initiative (MI-I) to create an alliance of universities, university hospitals, research institutions and IT companies. SMITH's goals are to establish Data Integration Centers (DICs) at each SMITH partner hospital and to implement use cases which demonstrate the usefulness of the approach. OBJECTIVES: To give insight into architectural design issues underlying SMITH data integration and to introduce the use cases to be implemented. GOVERNANCE AND POLICIES: SMITH implements a federated approach as well for its governance structure as for its information system architecture. SMITH has designed a generic concept for its data integration centers. They share identical services and functionalities to take best advantage of the interoperability architectures and of the data use and access process planned. The DICs provide access to the local hospitals' Electronic Medical Records (EMR). This is based on data trustee and privacy management services. DIC staff will curate and amend EMR data in the Health Data Storage. METHODOLOGY AND ARCHITECTURAL FRAMEWORK: To share medical and research data, SMITH's information system is based on communication and storage standards. We use the Reference Model of the Open Archival Information System and will consistently implement profiles of Integrating the Health Care Enterprise (IHE) and Health Level Seven (HL7) standards. Standard terminologies will be applied. The SMITH Market Place will be used for devising agreements on data access and distribution. 3LGM2 for enterprise architecture modeling supports a consistent development process.The DIC reference architecture determines the services, applications and the standardsbased communication links needed for efficiently supporting the ingesting, data nourishing, trustee, privacy management and data transfer tasks of the SMITH DICs. The reference architecture is adopted at the local sites. Data sharing services and the market place enable interoperability. USE CASES: The methodological use case "Phenotype Pipeline" (PheP) constructs algorithms for annotations and analyses of patient-related phenotypes according to classification rules or statistical models based on structured data. Unstructured textual data will be subject to natural language processing to permit integration into the phenotyping algorithms. The clinical use case "Algorithmic Surveillance of ICU Patients" (ASIC) focusses on patients in Intensive Care Units (ICU) with the acute respiratory distress syndrome (ARDS). A model-based decision-support system will give advice for mechanical ventilation. The clinical use case HELP develops a "hospital-wide electronic medical record-based computerized decision support system to improve outcomes of patients with blood-stream infections" (HELP). ASIC and HELP use the PheP. The clinical benefit of the use cases ASIC and HELP will be demonstrated in a change of care clinical trial based on a step wedge design. DISCUSSION: SMITH's strength is the modular, reusable IT architecture based on interoperability standards, the integration of the hospitals' information management departments and the public-private partnership. The project aims at sustainability beyond the first 4-year funding period.

Decentralized safety concept for closed-loop controlled intensive care.

This paper presents a decentralized safety concept for networked intensive care setups, for which a decentralized network of sensors and actuators is realized by embedded microcontroller nodes. It is evaluated for up to eleven medical devices in a setup for automated acute respiratory distress syndrome (ARDS) therapy. In this contribution we highlight a blood pump supervision as exemplary safety measure, which allows a reliable bubble detection in an extracorporeal blood circulation. The approach is validated with data of animal experiments including 35 bubbles with a size between 0.05 and 0.3 ml. All 18 bubbles with a size down to 0.15 ml are successfully detected. By using hidden Markov models (HMMs) as statistical method the number of necessary sensors can be reduced by two pressure sensors.

Physiological closed-loop control of mechanical ventilation and extracorporeal membrane oxygenation.

A new concept is presented for cooperative automation of mechanical ventilation and extracorporeal membrane oxygenation (ECMO) therapy for treatment of acute respiratory distress syndrome (ARDS). While mechanical ventilation is continuously optimized to promote lung protection, extracorporeal gas transfer rates are simultaneously adjusted to control oxygen supply and carbon dioxide removal using a robust patient-in-the-loop control system. In addition, the cooperative therapy management uses higher-level algorithms to adjust both therapeutic approaches. The controller synthesis is derived based on the introduced objectives, the experimental setup and the uncertain models. Finally, the autonomous ARDS therapy system capabilities are demonstrated and discussed based on in vivo data from animal experiments.

Automatic Control of Veno-Venous Extracorporeal Lung Assist.

Veno-venous extracorporeal lung assist (ECLA) can provide sufficient gas exchange even in most severe cases of acute respiratory distress syndrome. Commercially available systems are manually controlled, although an automatically controlled ECLA could allow individualized and continuous adaption to clinical requirements. Therefore, we developed a demonstrator with an integrated control algorithm to keep continuously measured peripheral oxygen saturation and partial pressure of carbon dioxide constant by automatically adjusting extracorporeal blood and gas flow. The "SmartECLA" system was tested in six animal experiments with increasing pulmonary hypoventilation and hypoxic inspiratory gas mixture to simulate progressive acute respiratory failure. During a cumulative evaluation time of 32 h for all experiments, automatic ECLA control resulted in a peripheral oxygen saturation ≥90% for 98% of the time with the lowest value of 82% for 15 s. Partial pressure of venous carbon dioxide was between 40 and 49 mm Hg for 97% of the time with no value <35 mm Hg or >49 mm Hg. With decreasing inspiratory oxygen concentration, extracorporeal oxygen uptake increased from 68 ± 25 to 154 ± 34 mL/min (P < 0.05), and reducing respiratory rate resulted in increasing extracorporeal carbon dioxide elimination from 71 ± 37 to 92 ± 37 mL/min (P < 0.05). The "SmartECLA" demonstrator allowed reliable automatic control of the extracorporeal circuit. Proof of concept could be demonstrated for this novel automatically controlled veno-venous ECLA circuit.

A physiological model for extracorporeal oxygenation controller design.

Long term extracorporeal membrane oxygenation can be used in cases of severe lung failure to maintain sufficient gas exchange without the need to apply higher ventilation pressures which damage the lung additionally. The use of cardiopulmonary bypass devices is well established inside the operating room. The usage of such devices as long-term support in the intensive care unit is still experimental and limited to few cases. This is because neither machine architecture nor staff situation provides for the long term application scenario. In the joint research Project "smart ECLA" we target an advanced ECMO device featuring an automation system capable of maintaining gas concentrations automatically. One key requirement for systematic controller design is the availability of a process model, which will be presented in this article.

[Automatic control and safety concepts for extracorporeal lung support]. / Regelungs- und Sicherheitskonzepte für extrakorporale Systeme zur Lungenunterstützung.

In some cases of severe acute respiratory distress syndrome, hypoxemia occurs despite optimized conservative therapy; however, extracorporeal membrane oxygenation (ECMO) can assure sufficient gas exchange. To increase safety and reliability of devices, the oxygenator design was optimized integrating new plasma-resistant composite membranes and new blood pumps are used with longer durability and reduced blood cell damage. Another approach is the use of an arterio-venous pumpless extracorporeal lung assist (pECLA) using an oxygenator with reduced pressure drop to simplify management and to avoid pump-related complications. First attempts were made to integrate basic control and safety concepts in ECMO circuits, but this does not seem to be sufficient to overcome the specific problems of ECMO (long-term use and limited supervision of the intensive care unit). The integration of sophisticated automated control and safety concepts in combination with revised ECMO circuits could allow a more reliable application of ECMO of the intensive care unit without continuous observation by a perfusionist. Easier intra- and interhospital transfer of patients with running ECMO would be another advantage.