Diaphragm

BackgroundDiaphragm ultrasonography is rapidly evolving in both critical care and research. Nevertheless, methodologically robust guidelines on its methodology and acquiring expertise do not, or only partially, exist. Therefore, we set out to provide consensus-based statements towards a universal measurement protocol for diaphragm ultrasonography and establish key areas for research.MethodsTo formulate a robust expert consensus statement, between November 2020 and May 2021, a two-round, anonymous and online survey-based Delphi study among experts in the field was performed. Based on the literature review, the following domains were chosen: "Anatomy and physiology", "Transducer Settings", "Ventilator Impact", "Learning and expertise", "Daily practice" and "Future directions". Agreement of ≥ 68% (≥ 10 panelists) was needed to reach consensus on a question.ResultsOf 18 panelists invited, 14 agreed to participate in the survey. After two rounds, the survey included 117 questions of which 42 questions were designed to collect arguments and opinions and 75 questions aimed at reaching consensus. Of these, 46 (61%) consensus was reached. In both rounds, the response rate was 100%. Among others, there was agreement on measuring thickness between the pleura and peritoneum, using > 10% decrease in thickness as cut-off for atrophy and using 40 examinations as minimum training to use diaphragm ultrasonography in clinical practice. In addition, key areas for research were established.ConclusionThis expert consensus statement presents the first set of consensus-based statements on diaphragm ultrasonography methodology. They serve to ensure high-quality and homogenous measurements in daily clinical practice and in research. In addition, important gaps in current knowledge and thereby key areas for research are established. Trial registration The study was pre-registered on the Open Science Framework with registration digital object identifier https://doi.org/10.17605/OSF.IO/HM8UG .

BackgroundInsufficient or excessive respiratory effort during acute hypoxemic respiratory failure (AHRF) increases the risk of lung and diaphragm injury. We sought to establish whether respiratory effort can be optimized to achieve lung- and diaphragm-protective (LDP) targets (esophageal pressure swing - 3 to - 8 cm H2O; dynamic transpulmonary driving pressure ≤ 15 cm H2O) during AHRF.MethodsIn patients with early AHRF, spontaneous breathing was initiated as soon as passive ventilation was not deemed mandatory. Inspiratory pressure, sedation, positive end-expiratory pressure (PEEP), and sweep gas flow (in patients receiving veno-venous extracorporeal membrane oxygenation (VV-ECMO)) were systematically titrated to achieve LDP targets. Additionally, partial neuromuscular blockade (pNMBA) was administered in patients with refractory excessive respiratory effort.ResultsOf 30 patients enrolled, most had severe AHRF; 16 required VV-ECMO. Respiratory effort was absent in all at enrolment. After initiating spontaneous breathing, most exhibited high respiratory effort and only 6/30 met LDP targets. After titrating ventilation, sedation, and sweep gas flow, LDP targets were achieved in 20/30. LDP targets were more likely to be achieved in patients on VV-ECMO (median OR 10, 95% CrI 2, 81) and at the PEEP level associated with improved dynamic compliance (median OR 33, 95% CrI 5, 898). Administration of pNMBA to patients with refractory excessive effort was well-tolerated and effectively achieved LDP targets.ConclusionRespiratory effort is frequently absent under deep sedation but becomes excessive when spontaneous breathing is permitted in patients with moderate or severe AHRF. Systematically titrating ventilation and sedation can optimize respiratory effort for lung and diaphragm protection in most patients. VV-ECMO can greatly facilitate the delivery of a LDP strategy.Trial registrationThis trial was registered in Clinicaltrials.gov in August 2018 (NCT03612583).

Time-lapse mechanical properties of stem cell derived cardiac organoids are important biological cues for understanding contraction dynamics of human heart tissues, cardiovascular functions and diseases. However, it remains difficult to directly, instantaneously and accurately characterize such mechanical properties in real-time and in situ because cardiac organoids are topologically complex, three-dimensional soft tissues suspended in biological media, which creates a mismatch in mechanics and topology with state-of-the-art force sensors that are typically rigid, planar and bulky. Here, we present a soft resistive force-sensing diaphragm based on ultrasensitive resistive nanocracked platinum film, which can be integrated into an all-soft culture well via an oxygen plasma-enabled bonding process. We show that a reliable organoid-diaphragm contact can be established by an 'Atomic Force Microscope-like' engaging process. This allows for instantaneous detection of the organoids' minute contractile forces and beating patterns during electrical stimulation, resuscitation, drug dosing, tissue culture, and disease modelling.

BACKGROUND: Positive pressure ventilation has multiple adverse cardiopulmonary effects leading to impaired lung mechanics and hemodynamic performance. Controlled levels of diaphragm activity may mitigate these. The objectives of the study were to assess the effect of varying levels of diaphragm neurostimulation on respiratory mechanics and hemodynamics during positive pressure ventilation and to establish whether these effects depend on the level of applied positive end-expiratory pressure (PEEP). METHODS: Patients enrolled in a clinical trial of diaphragm neurostimulation underwent a nested randomized cross-over study assessing the effect of passive ventilation alone or in combination with three levels of diaphragm neurostimulation, performed at two levels of PEEP. Respiratory mechanics, distribution of ventilation, and hemodynamics were assessed. RESULTS: Sixteen patients were included. Diaphragm neurostimulation increased ventilation to the dorsal lung regions in a dose-dependent fashion (median 63% vs. 43% of tidal volume, p < 0.001) whereas increasing PEEP had a much more limited effect (median 43% vs. 43%, p = 0.05). Diaphragm neurostimulation increased end-expiratory lung volume by 617 mL and decreased respiratory system elastance from 1.4 to 1.2 cm H2O/(mL/kg), but only at higher PEEP (p = 0.025 and 0.021 for interaction, respectively). Neurostimulation significantly increased cardiac index (2.4 vs. 2.7 L/min/m2, p = 0.031) without increasing pulmonary artery transmural pressure (p = 0.26). In the absence of neurostimulation, increasing PEEP tended to decrease cardiac index (2.4 vs. 2.1 L/min/m2, p = 0.28). CONCLUSIONS: Diaphragm neurostimulation can mitigate the adverse cardiopulmonary effects of positive pressure ventilation. When combined with higher PEEP, diaphragm neurostimulation enhances dorsal lung recruitment without impairing hemodynamics. TRIAL REGISTRATION: The STIMULUS trial (NCT05465083) was prospectively registered at clinicaltrials.gov (July 2022).