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BACKGROUND: Methacholine bronchoprovocation or challenge testing (MCT) is commonly performed to assess airway hyper-responsiveness in the setting of suspected asthma. Nebulization is an aerosol-generating procedure, but little is known about the risks of MCT in the context of the ongoing coronavirus disease 2019 (COVID-19) pandemic. We aimed to quantify and characterize aerosol generation during MCT by using different delivery methods and to assess the impact of adding a viral filter. METHODS: Seven healthy subjects performed simulated MCT in a near particle-free laboratory space with 4 different nebulizers and with a dosimeter. Two devices continuously sampled the ambient air during the procedure, which detected ultrafine particles, from 0.02–1 μm, and particles of sizes 0.3, 0.5, 1.0, 2.0, 5.0, and 10 µm, respectively. Particle generation was compared among all the devices, with and without viral filter placement. RESULTS: Ultrafine-particle generation during simulated MCT was significant across all the devices. Ultrafine-particle (0.02–1 μm) concentrations decreased 77%–91% with the addition of a viral filter and varied significantly between unfiltered (P < .001) and filtered devices (P < .001). Ultrafine-particle generation was lowest when using the dosimeter with filtered Hudson nebulizer (1,258 ± 1,644 particle/mL). Ultrafine-particle concentrations with the filtered nebulizer devices using a compressor were higher than particle concentrations detected when using the dosimeter: Monaghan (3,472 ± 1,794 particles/mL), PARI (4,403 ± 2,948), Hudson (6,320 ± 1,787) and AirLife (9,523 ± 5,098). CONCLUSIONS: The high particle concentrations generated during MCT pose significant infection control concerns during the COVID-19 pandemic. Particle generation during MCT was significantly reduced by using breath-actuated delivery and a viral filter, which offers an effective mitigation strategy.

Methacholine challenge testing (MCT) is a common bronchoprovocation technique used to assess airway hyper-responsiveness. We previously demonstrated that the addition of a viral filter to the nebulizer exhalation limb substantially reduced expelled particles during MCT. Our aim was to evaluate whether this modification affects the delivered dose of methacholine.A mechanical ventilator was connected to a lung simulator with breathing frequency 15 breaths/min, tidal volume 500 mL, inspiratory-expiratory ratio 1:1, with a sinusoidal waveform. We compared methacholine dose delivery using the Hudson Micro Mist or AeroEclipse II BAN nebulizers powered by either a dry gas source or a compressor system. A filter placed in line between the nebulizer and test lung was weighed before and after 1 min of nebulized methacholine delivery. Mean inhaled mass was measured with and without a viral filter on the exhalation limb. Dose delivery was calculated by multiplying the mean inhaled mass by the respirable fraction (particles5 μm) and inhalation time. UnpairedThe addition of a viral filter did not significantly affect methacholine dose delivery across all devices tested. Using a 50-psi dry gas source, dose delivered with or without a viral filter did not differ with the Hudson (422.3 μg vs 282.0 μg,The addition of a viral filter to the nebulizer exhalation limb did not affect methacholine dose during bronchoprovocation testing. Routine use of a viral filter should be considered to improve pulmonary function technician safety and infection control measures during the ongoing COVID-19 pandemic.

To explore the impact of digoxin on hemodynamic parameters in patients with sepsis and tachycardia admitted to the intensive care unit.Retrospective review of adult patients admitted to the medical and mixed ICU at Mayo Clinic Rochester, Minnesota from March 2008 to February 2018, initiated on digoxin within 24 h of ICU stay. Hemodynamic parameters were reviewed before digoxin administration and at 6, 12 and 24 h after. Adverse events including new onset conduction abnormalities or arrhythmias during the first 48 h after digoxin administration were reviewed by a critical care cardiologist.Study included 180 patients. We observed significant decrease in heart rate from 124 (115-138) beats/min 1 h before digoxin to 101 (87-117) 6 h after digoxin and 94 (84-112) 12 h after (p .01). Median systolic blood pressure increased from 100 (91-112) mm Hg 1 h before to 110 (100-122) (p .01) and 111 (103-124) at 6 and 12 h respectively after digoxin.Early digoxin administration in patients with sepsis and tachycardia is uncommon but associated with improvements of hemodynamic parameters. These preliminary results will help formulate future hypotheses for focused trials on utility, efficacy and safety of digoxin in sepsis.

BACKGROUND: Peak flow testing is a common procedure performed in ambulatory care. There are currently no data regarding aerosol generation during this procedure. Given the ongoing debate regarding the potential for aerosol transmission of SARS-CoV-2, we aimed to quantify and characterize aerosol generation during peak flow testing. METHODS: Five healthy volunteers performed peak flow maneuvers in a particle-free laboratory space. Two devices continuously sampled the ambient air during the procedure. One device can detect ultrafine particles 0.02–1 μm in diameter, while the second device can detect particles 0.3, 0.5, 1.0, 2.0, 5.0, and 10 μm in diameter. Five different peak flow meters were compared to ambient baseline during masked and unmasked tidal breathing. RESULTS: Ultrafine particles (0.02–1 μm) were generated during peak flow measurement. There was no significant difference in ultrafine particle mean concentration between peak flow meters (P = .23): Respironics (1.25 ± 0.47 particles/mL), Philips (3.06 ± 1.22), Clement Clarke (3.55 ± 1.22 particles/mL), Respironics Low Range (3.50 ± 1.52 particles/mL), and Monaghan (3.78 ± 1.31 particles/mL). Ultrafine particle mean concentration with peak flow testing was significantly higher than masked (0.22 ± 0.29 particles/mL) and unmasked tidal breathing (0.15 ± 0.18 particles/mL, P = .01), but the ultrafine particle concentrations were small compared to ambient particle concentrations in a pulmonary function testing room (89.9 ± 8.95 particles/mL). CONCLUSIONS: In this study, aerosol generation was present during peak flow testing, but concentrations were small compared to the background particle concentration in the ambient clinical environment. Surgical masks and eye protection are likely sufficient infection control measures during peak expiratory flow testing in asymptomatic patients with well controlled respiratory symptoms, but COVID-19 testing remains prudent in patients with acute respiratory symptoms prior to evaluation and peak expiratory flow assessment while the community prevalence of SARS-CoV-2 cases remains high.

Objectives Critically ill surgical patients may receive concomitant aspirin and therapeutic anticoagulation postoperatively, yet the safety of this practice remains unknown. We evaluated the risk of major bleeding with concomitant therapy compared with anticoagulation alone. Design Observational cohort study. Inverse probability of treatment weighting was used to assess the association between concomitant therapy and a primary outcome of major bleeding. Setting Postoperative ICUs at an academic medical center. Patients Adults (≥ 18 yr old) receiving anticoagulation during postoperative ICU admission between 2007 and 2016. Interventions None. Measurements and main results Nine thousand five hundred eighteen anticoagulated patients were included, including 3,237 (34%) receiving aspirin. A total of 1,874 unique patients (19.7%) experienced a major bleeding event. In inverse probability of treatment weighting analyses, concomitant therapy was associated with increased odds for major bleeding (odds ratio, 1.20; 95% CI, 1.05-1.36; p = 0.006) compared with anticoagulation alone. An interaction test suggested a differential relationship between aspirin use and major bleeding based on aspirin use in the 7 days prior to anticoagulation, such that a strong association between aspirin and major bleeding was observed for recent initiators of aspirin (1.40; 1.13-1.72;p = 0.002) but not for those continuing prior aspirin use. Aspirin use prior to anticoagulation did not modify the relationship between concomitant therapy and new myocardial infarction or stroke (i.e., rates were not increased with aspirin discontinuation prior to anticoagulation). Conclusions Concomitant aspirin and anticoagulation in critically ill surgical patients was associated with an increased rate of major bleeding. Future investigations are warranted to further define optimal management of antiplatelet therapy during anticoagulation in surgical patients.

Background We aimed to evaluate the risk of major bleeding in non-surgical critically ill patients who received aspirin in conjunction with therapeutic anticoagulation (concomitant therapy) compared to those who received therapeutic anticoagulation alone. Methods This is a retrospective cohort study of critically ill patients initiated on therapeutic anticoagulation at a large academic medical center from 2007 to 2016. The exposure of interest was aspirin therapy during anticoagulation. The primary outcome was the incidence of major bleeding during hospitalization. Secondary outcomes included in-hospital mortality, hospital free days, and new myocardial infarction or stroke. Results 5507 (73.2%) patients received anticoagulation alone and 2014 (26.8%) received concomitant therapy; major bleeding occurred in 19.0% and 22.2%, respectively. There was no increased risk of major bleeding [OR 1.10 (95% CI: 0.93–1.30); p = .27] or mortality [OR 0.93 (95% CI: 0.77–1.11); p = .43] with concomitant therapy. Patients receiving concomitant therapy had fewer hospital-free days (mean decrease of 0.73 [1.36, 0.09]; p = .03) and were more likely to experience new myocardial infarction or stroke [OR 2.61 (95% CI: 1.72–3.98); p Conclusions In non-surgical critically ill patients receiving therapeutic anticoagulation, concomitant use of aspirin was not associated with an increased risk of bleeding or in-hospital mortality.

TOPIC: Respiratory Care TYPE: Original Investigations PURPOSE: Methacholine challenge testing (MCT) is a common bronchoprovocation technique used to assess airway hyperresponsiveness. Current ERS guidelines recommend that measures should be taken to minimize technician exposure to methacholine aerosol, with added infection control concerns in the context of the ongoing COVID-19 pandemic. We previously demonstrated that the addition of a viral filter to the nebulizer exhalation limb reduced expelled particle concentrations by 77-91% during MCT. Our aim was to evaluate whether this modification resulted in a change in the delivered dose of methacholine. METHODS: Following published industry testing standards for MCT, we connected a Hamilton-G5 mechanical ventilator and Michigan lung simulator in series with respiratory rate 15 breaths/min, tidal volume (VT) 500 mL, I:E ratio 1:1 with a sinusoidal waveform. We compared methacholine dose delivery using the Hudson MicroMist and AeroEclipse II BAN nebulizers powered by either a dry gas source at 50 psi and 4.5 L/min or the Ombra compressor system, in addition to our current MCT protocol which utilizes Hudson MicroMist nebulizer with KoKo dosimeter (3 breaths). A filter placed in line between the nebulizer and test lung was weighed before and after 1 minute of nebulized methacholine delivery. Mean inhaled mass was calculated from three trials of each method with and without a viral filter on the exhalation limb. Dose delivery was calculated by multiplying the mean inhaled mass by the respirable fraction (particles < 5 µm) and inhalation time. Unpaired t-test was used to compare methacholine dose delivery with and without viral filter placement. Due to multiple independent comparisons, Bonferroni correction was used and alpha level was set at 0.01. RESULTS: The addition of a viral filter did not significantly affect methacholine dose delivery across all devices tested. Using the 50 psi dry gas source, dose delivered with the Hudson MicroMist did not differ with (461.0 µg) or without (307.8 µg) a viral filter (P=0.11) or with the AeroEclipse II BAN with (580.8 µg) or without (678.4) a viral filter (P=0.59). Using the Ombra compressor, dose delivered with the Hudson MicroMist did not differ with (1063.3 µg) or without (947.5 µg) a viral filter (P=0.026) or with AeroEclipse II BAN with (843.8 µg) or without (648.3) viral filter (P=0.42). Dose delivery did not differ significantly when using the KoKo dosimeter and Hudson MicroMist with or without a viral filter (P=0.20) using a 3-breath protocol. CONCLUSIONS: The addition of a viral filter to the nebulizer expiratory limb did not result in a significant change in the in the delivered dose of methacholine. CLINICAL IMPLICATIONS: Based on these findings, use of a viral filter to limit the concentration of expelled aerosol during MCT should be considered to improve pulmonary function technician safety and potentially reduce the risk of infectious exposure during the ongoing COVID-19 pandemic. DISCLOSURES: No relevant relationships by Kaiser Lim, source=Web Response no disclosure submitted for todd meyer;No relevant relationships by Alexander Niven, source=Web Response No relevant relationships by Paul Scanlon, source=Web Response No relevant relationships by Yosuf Subat, source=Web Response No relevant relationships by Keith Torgerud, source=Web Response

OBJECTIVEThe primary goal of the treatment of cerebral arteriovenous malformations (AVMs) is angiographic occlusion to eliminate future hemorrhage risk. Although multimodal treatment is increasingly used for AVMs, periprocedural hemorrhage after transarterial embolization is a potential endovascular complication that is only partially understood and merits quantification.METHODSSearching the period between 1990 and 2019, the authors of this meta-analysis queried the PubMed and Embase databases for studies reporting periprocedural hemorrhage (within 30 days) after liquid embolization (using cyanoacrylate or ethylene vinyl alcohol copolymer) of AVMs. Random effects meta-analysis was used to evaluate the pooled rate of flow-related hemorrhage (those attributed to alterations in AVM dynamics), technical hemorrhage (those related to procedural complications), and total hemorrhage. Meta-regression was used to analyze the study-level predictors of hemorrhage, including patient age, Spetzler-Martin grade, hemorrhagic presentation, embolysate used, intent of treatment (adjuvant vs curative), associated aneurysms, endovascular angiographic obliteration, year of study publication, and years the procedures were performed.RESULTSA total of 98 studies with 8009 patients were included in this analysis, and the mean number of embolization sessions per patient was 1.9. The pooled flow-related and total periprocedural hemorrhage rates were 2.0% (95% CI 1.5%–2.4%) and 2.6% (95% CI 2.1%–3.0%) per procedure and 3.4% (95% CI 2.6%–4.2%) and 4.8% (95% CI 4.0%–5.6%) per patient, respectively. The mortality and morbidity rates associated with hemorrhage were 14.6% and 45.1%, respectively. Subgroup analyses revealed a pooled total hemorrhage rate per procedure of 1.8% (95% CI 1.0%–2.5%) for adjuvant (surgery or radiosurgery) and 4.6% (95% CI 2.8%–6.4%) for curative intent. The treatment of aneurysms (p = 0.04) and larger patient populations (p < 0.001) were significant predictors of a lower hemorrhage rate, whereas curative intent (p = 0.04), angiographic obliteration achieved endovascularly (p = 0.003), and a greater number of embolization sessions (p = 0.03) were significant predictors of a higher hemorrhage rate. There were no significant differences in periprocedural hemorrhage rates according to the years evaluated or the embolysate utilized.CONCLUSIONSIn this study-level meta-analysis, periprocedural hemorrhage was seen after 2.6% of transarterial embolization procedures for cerebral AVMs. The adjuvant use of endovascular embolization, including in the treatment of associated aneurysms and in the presurgical or preradiosurgical setting, was a study-level predictor of significantly lower hemorrhage rates, whereas more aggressive embolization involving curative intent and endovascular angiographic obliteration was a predictor of a significantly higher total hemorrhage rate.