A physiological model of phrenic nerve excitation by electrical stimulation.

Mechanical ventilation is essential in intensive care treatment but leads to diaphragmatic atrophy, which in turn contributes to prolonged weaning and increased mortality. One approach to prevent diaphragmatic atrophy while achieving pulmonary ventilation is electrical stimulation of the phrenic nerve. To automize phrenic nerve stimulation resulting in lung protective tidal volumes with lowest possible currents, mathematical models are required. Nerve stimulation models are often complex, so many parameters have to be identified prior to implementation. This paper presents a novel, simplified approach to model phrenic nerve excitation to obtain an individualized patient model using a few data points. The latter is based on the idea that nerve fibers are excited when the electric field exceeds a threshold. The effect of the geometry parameter on the model output was analyzed, and the model was validated with measurement data from a pig trial (RMSE in between 0.44 × 10-2and 1.64 × 10-2for parameterized models). The modeled phrenic nerve excitation behaved similarly to the measured tidal volumes, and thus could be used to develop automated phrenic nerve stimulation systems for lung protective ventilation.

Breath-by-breath comparison of a novel percutaneous phrenic nerve stimulation approach with mechanical ventilation in juvenile pigs: a pilot study.

About one in three critically ill patients requires mechanical ventilation (MV). Prolonged MV, however, results in diaphragmatic weakness, which itself is associated with delayed weaning and increased mortality. Inducing active diaphragmatic contraction via electrical phrenic nerve stimulation (PNS) not only provides the potential to reduce diaphragmatic muscular atrophy but also generates physiological-like ventilation and therefore offers a promising alternative to MV. Reasons why PNS is not yet used in critical care medicine are high procedural invasiveness, insufficient evidence, and lack of side-by-side comparison to MV. This study aims to establish a minimal-invasive percutaneous, bilateral electrode placement approach for sole PNS breathing and thereby enable, for the first time, a breath-by-breath comparison to MV. Six juvenile German Landrace pigs received general anesthesia and orotracheal intubation. Following the novel ultrasound-guided, landmark-based, 4-step approach, two echogenic needles per phrenic nerve were successfully placed. Stimulation effectiveness was evaluated measuring tidal volume, diaphragmatic thickening and tomographic electrical impedance in a breath-by-breath comparison to MV. Following sufficient bilateral phrenic nerve stimulation in all pigs, PNS breaths showed a 2.2-fold increase in diaphragmatic thickening. It induced tidal volumes in the lung-protective range by negative pressure inspiration and improved dorso-caudal regional ventilation in contrast to MV. Our study demonstrated the feasibility of a novel ultrasound-guided, percutaneous phrenic nerve stimulation approach, which generated sufficient tidal volumes and showed more resemblance to physiological breathing than MV in a breath-by-breath comparison.

Standardized pharmacological management of delirium after on-pump cardiac surgery reduces ICU stay and ventilation in a retrospective pre-post study.

Cardiac surgery patients not only undergo a highly invasive procedure but are at risk for a diversity of postoperative complications. Up to 53% of these patients suffer from postoperative delirium (POD). This severe and common adverse event increases mortality and prolonged mechanical ventilation and extends the intensive care unit stay. The objective of this study was to test the hypothesis that standardized pharmacological management of delirium (SPMD) may reduce the length of stay in the intensive care unit (ICU), duration of postoperative mechanical ventilation, and the incidence of postoperative complications such as pneumonia or bloodstream infections in on-pump cardiac surgery ICU patients. In this retrospective, single-center observational cohort study, 247 patients were examined between May 2018 to June 2020, who underwent on-pump cardiac surgery, suffered from POD, and received pharmacological POD treatment. 125 were treated before and 122 after SPMD implementation in the ICU. The primary endpoint was a composite outcome, including the length of ICU stay, postoperative mechanical ventilation time, and ICU survival rate. The secondary endpoints were complications including postoperative pneumonia and bloodstream infections. Although the ICU survival rate was not significantly different between both groups, the length of ICU stay (control group: 23 ± 27 days; SPMD group: 16 ± 16 days; p = 0.024) and the duration of mechanical ventilation were significantly reduced in the SPMD-cohort (control group: 230 ± 395 h; SPMD group: 128 ± 268 h; p = 0.022). Concordantly, the pneumonic risk was reduced after SPMD introduction (control group: 44.0%; SPMD group: 27.9%; p = 0.012) as well as the incidence for bloodstream infections (control group: 19.2%; SPMD group: 6.6%; p = 0.004). Standardized pharmacological management of postoperative delirium in on-pump cardiac surgery ICU patients reduced the length of ICU stay and duration of mechanical ventilation significantly, leading to a decrease in pneumonic complications and bloodstream infections.

Evaluation of electric phrenic nerve stimulation patterns for mechanical ventilation: a pilot study.

Diaphragm atrophy is a common side effect of mechanical ventilation and results in prolonged weaning. Electric phrenic nerve stimulation presents a possibility to avoid diaphragm atrophy by keeping the diaphragm conditioned in sedated patients. There is a need of further investigation on how to set stimulation parameters to achieve sufficient ventilation. A prototype system is presented with a systematic evaluation for stimulation pattern adjustments. The main indicator for efficient stimulation was the tidal volume. The evaluation was performed in two pig models. As a major finding, the results for biphasic pulses were more consistent than for alternating pulses. The tidal volume increased for a range of pulse frequency and pulse width until reaching a plateau at 80-120 Hz and 0.15 ms. Furthermore, the generated tidal volume and the stimulation pulse frequency were significantly correlated (0.42-0.84, [Formula: see text]). The results show which stimulation parameter combinations generate the highest tidal volume. We established a guideline on how to set stimulation parameters. The guideline is helpful for future clinical applications of phrenic nerve stimulation.

Post-Mortem Extracorporeal Membrane Oxygenation Perfusion Rat Model: A Feasibility Study.

The development of biomedical soft- or hardware frequently includes testing in animals. However, large efforts have been made to reduce the number of animal experiments, according to the 3Rs principle. Simultaneously, a significant number of surplus animals are euthanized without scientific necessity. The primary aim of this study was to establish a post-mortem rat perfusion model using extracorporeal membrane oxygenation (ECMO) in surplus rat cadavers and generate first post vivo results concerning the oxygenation performance of a recently developed ECMO membrane oxygenator. Four rats were euthanized and connected post-mortem to a venous-arterial ECMO circulation for up to eight hours. Angiographic perfusion proofs, blood gas analyses and blood oxygenation calculations were performed. The mean preparation time for the ECMO system was 791 ± 29 s and sufficient organ perfusion could be maintained for 463 ± 26 min, proofed via angiographic imaging and a mean femoral arterial pressure of 43 ± 17 mmHg. A stable partial oxygen pressure, a 73% rise in arterial oxygen concentration and an exponentially increasing oxygen extraction ratio up to 4.75 times were shown. Considering the 3Rs, the established post-mortal ECMO perfusion rat model using surplus animals represents a promising alternative to models using live animals. Given the preserved organ perfusion, its use could be conceivable for various biomedical device testing.

[Onboarding of young professionals in the intensive care unit : Nationwide online survey by young DIVI - an initiative of the German interdisciplinary association for intensive and emergency medicine (DIVI)]. / Einarbeitung junger Fachkräfte auf der Intensivstation : Eine bundesweite Onlineumfrage der Jungen DIVI ­ einer Initiative der Deutschen Interdisziplinären Vereinigung für Intensiv- und Notfallmedizin (DIVI).

BACKGROUND: Onboarding of junior staff in the intensive care unit is vital to ensure high-quality critical care treatment. This process depends on beginner's training. AIM: We aimed to determine structure and duration of intensive care onboarding and the job satisfaction of junior professionals in German intensive care units. MATERIALS AND METHODS: We conducted an anonymous, interprofessional online survey regarding quality of onboarding and job satisfaction among young professionals. RESULTS: A total of 554 young professionals participated, about two thirds were physicians. A written concept was used in 59% of the nurse's and 27% of physicians' training. Median duration of training before taking full charge of patient treatment was 30 days among nurses and 7 days among physicians. About one third of nurses and 17% of physicians stated that they were sufficiently prepared after the training period, whereby 49% of physicians often felt overwhelmed. More than 42% can imagine working in critical care longer than the next 3 years. CONCLUSION: Fundamental methods for training of critical care professionals starting their intensive care career are underused in Germany and the duration of training blatantly differs from national guideline recommendations. Although there seem to be deficits concerning material and staff resources, participants are satisfied with learning progress and teamwork.

Recommendations on the structure, personal, and organization of intensive care units.

Background: Intensive care units (ICU) are central facilities of medical care in hospitals world-wide and pose a significant financial burden on the health care system. Objectives: To provide guidance and recommendations for the requirements of (infra)structure, personal, and organization of intensive care units. Design and setting: Development of recommendations based on a systematic literature search and a formal consensus process from a group of multidisciplinary and multiprofessional specialists from the German Interdisciplinary Association of Intensive Care and Emergency Medicine (DIVI). The grading of the recommendation follows the report from an American College of Chest Physicians Task Force. Results: The recommendations cover the fields of a 3-staged level of intensive care units, a 3-staged level of care with respect to severity of illness, qualitative and quantitative requirements of physicians and nurses as well as staffing with physiotherapists, pharmacists, psychologists, palliative medicine and other specialists, all adapted to the 3 levels of ICUs. Furthermore, proposals concerning the equipment and the construction of ICUs are supplied. Conclusion: This document provides a detailed framework for organizing and planning the operation and construction/renovation of ICUs.

[DIVI-Recommendations on the infrastruture of adult intensive care units]. / DIVI-Empfehlung zur Struktur und Ausstattung von Intensivstationen 2022 (Erwachsene).

This document on the Structure and Equipment for Intensive Care Units of the German Association for Intensive and Emergency Care (DIVI) aims at providing guidance and recommendations for the requirements of (infra)structure, personal, and organization of intensive care units. The recommendations are based on a systematic literature search and a formal consensus process from a group of multi-disciplinary and multiprofessional specialists from the DIVI. The recommendations comprise a 3-staged level of intensive care units, a 3-staged level of care with respect to severity of illness, the staffing requirement of physicians, nurses, physiotherapists, pharmacists, psychologists, and other specialists. Furthermore, proposals concerning the equipment and the construction of ICUs are supplied.

Direct addition of poly-lysine or poly-ethylenimine to the medium: A simple alternative to plate pre-coating.

For most cell culture experiments, it is indispensable that the cells are firmly anchored to culture plates, withstanding rinsing steps that can create shear forces and tolerating temperature changes without detaching. For semi-adherent cells such as the common HEK 293 or PC-12 cells, this could so far be obtained by time-consuming plate pre-coating with cationic polymer solutions. We report here, that i) pre-coating with the cheaper poly-ethylenimine (PEI) works as well as the commonly used poly-D-lysine (PDL), but more importantly and novel ii) that simple direct addition of either PEI (1.5 µg/ml) or PDL (2 µg/ml) to the cell culture medium results in strongly anchored HEK 293 cells, indistinguishable from ones seeded on pre-coated plates. Therefore, the replacement of plate pre-coating by direct addition of either PEI or PDL gives comparable excellent results, but is highly labour-, time-, and cost-efficient. Moreover, we could show that addition of PDL or PEI also works similarly well in animal-free culture using human platelet lysate instead of fetal bovine serum. Interestingly, additional experiments showed that strong cell attachment requires only cationic polymers but not fetal bovine serum or human platelet lysate added to the medium.

Identification of the Tidal Volume Response to Pulse Amplitudes of Phrenic Nerve Stimulation Using Gaussian Process Regression.

While mechanical ventilation (MV) can lead to ventilator-induced diaphragmatic atrophy due to diaphragm inactivity, electrical phrenic nerve stimulation (PNS) can keep the diaphragm active and therefore prevent diaphragmatic weakness. To quantify the effectivity of PNS, an identification experiment during PNS is presented, and its data is used in Gaussian process regression (GPR) of the tidal volume based on the constant voltage amplitude of the stimulation pulses. The measurements were split into training data of variable size and test data for cross validation. For variable training sizes and different PNS settings, the GPR had a root mean square deviation (RMSD) between 0.39 and 0.91 mL/kg. An identification experiment as short as one and a half minutes was able to characteristically capture the relationship between tidal volume and voltage amplitude. The proposed method needs to be validated in further experiments.