Novel inhaled pulmonary vasodilators in adult cardiac surgery: a scoping review.

PURPOSE: Pulmonary hypertension (PH) is a common cause of postoperative mortality in cardiac surgery that is commonly treated with conventional inhaled therapies, specifically nitric oxide and prostacyclin. Alternative therapies include inhaled milrinone and levosimendan, which are receiving more research interest and are increasing in clinical use as they may cut costs while allowing for easier administration. We sought to conduct a scoping review to appraise the evidence base for the use of these two novel inhaled vasodilators as an intervention for PH in cardiac surgery. SOURCE: We searched Embase and MEDLINE for relevant articles from 1947 to 2022. PRINCIPAL FINDINGS: We identified 17 studies including 969 patients. The included studies show that inhaled milrinone and levosimendan are selective pulmonary vasodilators with potential benefits ranging from ease of weaning from cardiopulmonary bypass to reduction in ventricular dysfunction. Nevertheless, high-quality data are limited, and study design and comparators are extremely heterogeneous, limiting the potential validity and generalizability of findings. CONCLUSION: The findings of this scoping review suggest that milrinone and levosimendan may be effective alternatives to current inhaled therapies for cardiac dysfunction in the setting of PH. Nevertheless, randomized trials have focused on specific agents and consistent outcome measures are needed to better validate the early-stage promise of these agents. STUDY REGISTRATION: Open Science Framework ( https://osf.io/z3k6f/ ); first posted 21 July 2022.

RéSUMé: OBJECTIF: L'hypertension pulmonaire (HTP) est une cause fréquente de mortalité postopératoire en chirurgie cardiaque généralement traitée par des thérapies inhalées conventionnelles, en particulier le monoxyde d'azote et la prostacycline. Les thérapies alternatives comprennent la milrinone et le lévosimendan inhalés, qui suscitent de plus en plus d'intérêt dans la recherche et sont de plus en plus utilisés en clinique car ils peuvent réduire les coûts tout en permettant une administration plus facile. Nous avons cherché à réaliser une étude de portée afin d'évaluer la base de données probantes concernant l'utilisation de ces deux nouveaux vasodilatateurs inhalés comme intervention pour l'HTP en chirurgie cardiaque. SOURCES: Nous avons cherché des articles pertinents dans Embase et MEDLINE de 1947 à 2022. CONSTATATIONS PRINCIPALES: Nous avons identifié 17 études incluant 969 patient·es. Les études incluses montrent que la milrinone et le lévosimendan inhalés sont des vasodilatateurs pulmonaires sélectifs possédant des avantages potentiels allant de la facilité de sevrage de la circulation extracorporelle à la réduction de la dysfonction ventriculaire. Néanmoins, les données de haute qualité sont limitées, et la conception des études et les comparateurs sont extrêmement hétérogènes, ce qui limite la validité potentielle et la généralisabilité des résultats. CONCLUSION: Les résultats de cette étude de portée suggèrent que la milrinone et le lévosimendan pourraient être des solutions de rechange efficaces aux traitements inhalés actuels pour le dysfonctionnement cardiaque dans un contexte d'HTP. Néanmoins, les études randomisées se sont concentrées sur des agents spécifiques et des mesures cohérentes des résultats sont nécessaires pour mieux valider les promesses de ces agents à un stade précoce. ENREGISTREMENT DE L'éTUDE: Open Science Framework ( https://osf.io/z3k6f/ ); première publication le 21 juillet 2022.

Development of an Easily Reproducible Cough Simulator With Droplets and Aerosols for Rapidly Testing Novel Personal Protective Equipment.

INTRODUCTION: The current COVID-19 pandemic has produced numerous innovations in personal protective equipment, barrier devices, and infection mitigation strategies, which have not been validated. During high-risk procedures such as airway manipulation, coughs are common and discrete events that may expose healthcare workers to large amounts of viral particles. A simulated cough under controlled circumstances can rapidly test novel devices and protocols and thus aid in their evaluation and the development of implementation guidelines. Physiologic cough simulators exist but require significant expertise and specialized equipment not available to most clinicians. METHODS: Using components commonly found in healthcare settings, a cough simulator was designed for clinicians to easily assemble and use. Both droplet and aerosol particle generators were incorporated into a bimodal experimental system. High-speed flash photography was used for data collection. RESULTS: Using a gas flow analyzer, video recordings, and high-speed digital photography, the cough and particle simulators were quantitatively and qualitatively compared with known physiologic cough parameters and in vivo Schlieren imaging of human coughs. CONCLUSIONS: Based on our validation studies, this cough and particle simulator model approximates a physiologic, human cough in the context of testing personal protective equipment, barrier devices, and infection prevention measures.

Barrier Devices, Intubation, and Aerosol Mitigation Strategies: Personal Protective Equipment in the Time of Coronavirus Disease 2019.

BACKGROUND: Numerous barrier devices have recently been developed and rapidly deployed worldwide in an effort to protect health care workers (HCWs) from exposure to coronavirus disease 2019 (COVID-19) during high-risk procedures. However, only a few studies have examined their impact on the dispersion of droplets and aerosols, which are both thought to be significant contributors to the spread of COVID-19. METHODS: Two commonly used barrier devices, an intubation box and a clear plastic intubation sheet, were evaluated using a physiologically accurate cough simulator. Aerosols were modeled using a commercially available fog machine, and droplets were modeled with fluorescein dye. Both particles were propelled by the cough simulator in a simulated intubation environment. Data were captured by high-speed flash photography, and aerosol and droplet dispersion were assessed qualitatively with and without a barrier in place. RESULTS: Droplet contamination after a simulated cough was seemingly contained by both barrier devices. Simulated aerosol escaped the barriers and flowed toward the head of the bed. During barrier removal, simulated aerosol trapped underneath was released and propelled toward the HCW at the head of the bed. Usage of the intubation sheet concentrated droplets onto a smaller area. If no barrier was used, positioning the patient in slight reverse Trendelenburg directed aerosols away from the HCW located at the head of the bed. CONCLUSIONS: Our observations imply that intubation boxes and sheets may reduce HCW exposure to droplets, but they both may merely redirect aerosolized particles, potentially resulting in increased exposure to aerosols in certain circumstances. Aerosols may remain within the barrier device after a cough, and manipulation of the box may release them. Patients should be positioned to facilitate intubation, but slight reverse Trendelenburg may direct infectious aerosols away from the HCW. Novel barrier devices should be used with caution, and further validation studies are necessary.

Using Simulation to Develop Solutions for Ventilator Shortages From the Epicenter.

SUMMARY STATEMENT: The COVID-19 pandemic threatened to overwhelm the medical system of New York City, and the threat of ventilator shortages was real. Using high-fidelity simulation, a variety of solutions were tested to solve the problem of ventilator shortages including innovative designs for safely splitting ventilators, converting noninvasive ventilators to invasive ventilators, and testing and improving of ventilators created by outside companies. Simulation provides a safe environment for testing of devices and protocols before use on patients and should be vital in the preparation for emergencies such as the COVID-19 pandemic.

Intraoperative aerosol box use: does an educational visual aid reduce contamination?

BACKGROUND: The aerosol box was rapidly developed and disseminated to minimize viral exposure during aerosolizing procedures during the COVID-19 pandemic, yet users may not understand how to use and clean the device. This could potentially lead to increased viral exposure to subsequent patients and practitioners. We evaluated intraoperative contamination and aerosol box decontamination and the impact of a preoperative educational visual aid. METHODS: Using a double-blinded randomized design, forty-four anesthesiology trainees and faculty completed a simulated anesthetic case using an aerosol box contaminated with a fluorescent marker; half of the subjects received a visual aid prior to the simulation. Intraoperative contamination was evaluated at 10 standardized locations using an ultraviolet (UV) light. Next, subjects were instructed to clean the aerosol box for use on the next patient. Following cleaning, the box was evaluated for decontamination using an UV light. RESULTS: Median total contamination score was significantly reduced in the experimental group (5.0 vs. 10.0, P < 0.001). The aerosol box was completely cleaned by 36.4% of subjects in the experimental group compared to 4.5% in the control group (P = 0.009). CONCLUSIONS: The use of a visual aid significantly decreased intraoperative contamination and improved box cleaning. Despite these findings, a potentially clinically significant amount of viral exposure may exist. Thorough evaluation of the risks and benefits of the aerosol box should be completed prior to use. If an aerosol box is used, a visual aid should be considered to remind practitioners how to best use and clean the box.

Phase Composition Control in Microsphere-Supported Biomembrane Systems.

The popularization of studies in membrane protein lipid phase coexistence has prompted the development of new techniques to construct and study biomimetic systems with cholesterol-rich lipid microdomains. Here, microsphere-supported biomembranes with integrated α-helical peptides, referred to as proteolipobeads (PLBs), were used to model peptide/protein partitioning within DOPC/DPPC/cholesterol phase-separated membranes. Due to the appearance of compositional heterogeneity and impurities in the formation of model PLB assemblies, fluorescence-activated cell sorting (FACS) was used to characterize and sort PLB populations on the basis of disordered phase (Ld) content. In addition, spectral imaging was used to assess the partitioning of FITC-labeled α-helical peptide between fluorescently labeled Ld phase and unlabeled ordered phase (Lo) phase lipid microdomains. The apparent peptide partition coefficient, Kp,app, was measured to be 0.89 ± 0.06, indicating a slight preference of the peptide for the Lo phase. A biomimetic motif of the Lo phase concentration enhancement of the biotinyl-peptide ligand display in proteolipobeads was also observed. Finally, peptide mobility was measured by FRAP separately in each lipid phase, yielding diffusivities of 0.036 ± 0.005 and 0.014 ± 0.003 µm2/s in the Ld and Lo phases, respectively.

Biodegradable, Tethered Lipid Bilayer-Microsphere Systems with Membrane-Integrated α-Helical Peptide Anchors.

Supported lipid bilayers (SLBs) are ideally suited for the study of biomembrane-biomembrane interactions and for the biomimicry of cell-to-cell communication, allowing for surface ligand displays that contain laterally mobile elements. However, the SLB paradigm does not include three-dimensionality and biocompatibility. As a way to bypass these limitations, we have developed a biodegradable form of microsphere SLBs, also known as proteolipobeads (PLBs), using PLGA microspheres. Microspheres were synthesized using solvent evaporation and size selected with fluorescence activated cell sorting (FACS). Biomembranes were covalently tethered upon fusion to microsphere supports via short-chain PEG spacers connecting membrane-integrated α-helical peptides and the microsphere surface, affecting membrane diffusivity and mobility as indicated by confocal FRAP analysis. Membrane heterogeneities, which are attributed to PLGA hydrophobicity and rough surface topography, are curtailed by the addition of PEG tethers. This method allows for the presentation of tethered, laterally mobile biomembranes in three dimensions with functionally embedded attachment peptides for mobile ligand displays.

Impact of diblock copolymers on droplet coalescence, emulsification, and aggregation in immiscible homopolymer blends.

Using rheo-optical techniques, we investigated the impact of interfacial wetting of symmetric diblock copolymers (BCPs) on the coalescence and aggregation of polydimethylsiloxane (PDMS) droplets in immiscible polyethylene-propylene (PEP) homopolymers. Anionic polymerization was used to synthesize well-defined matrix homopolymers and symmetric 16 kg/mol-to-16 kg/mol PDMS-b-PEP diblock copolymers with low polydispersity (PDI ≈ 1.02) as characterized with size exclusion chromatography and nuclear magnetic resonance spectroscopy. Blends were formulated to match the viscosities between the droplets and the matrix. Moreover, molecular weights of these components were varied to ensure that the inner block of the copolymer inside the droplet was collapsed and dry, whereas the outer block of the copolymer outside of the droplet was stretched and wet. Droplet breakup and coalescence as well as interfacial tensions were measured using rheo-optical experiments with Linkam shearing stage and an optical microscope. Subsequent to droplet breakup at high shear rates, we found that the BCPs mitigated shear-induced coalescence at lower shear rates. Based on surface tension measurements, the stretching of the BCP increased in lower molecular weight matrices, causing the droplet surface to saturate at lower coverage in line with theoretical predictions. Droplet aggregation was detected with further reductions in shear rate, which was attributed to the dewetting or the expulsion of the matrix from a saturated brush. Ultimately, the regions of droplet coalescence and aggregation were scaled by balancing the forces of shear with those due to the attraction between BCP-coated droplets.