ASSESSMENT OF AEROSOL DRUG DELIVERY DURING THE ESCALATION OF TREATMENT FOR A SIMULATED COVID-19 ADULT PATIENT

The effect of the various COVID-19 clinical interventions on aerosol delivery is not well known. This study investigated the use of a vibrating mesh nebuliser to deliver aerosolised drugs during mouthpiece-mediated aerosol drug delivery, high flow nasal therapy and invasive mechanical ventilation employing a low tidal volume ventilation strategy. Simulated adult healthy and mild adult COVID-19 breathing patterns were used for spontaneous breathing assessments. A mechanical ventilator delivered standard and low tidal volume ventilation parameters. The results presented represent the percentage drug delivered to a simulated healthy adult and mild adult COVID-19 patient during concurrent aerosol therapy during these interventions. The highest delivered drug dose was measured during mouthpiece-mediated aerosol therapy with a result of 57.93 %- 1.05 % for mild COVID-19, 56.64 %- 2.94 % for healthy, as a comparator. Use of HFNT resulted in the lowest percentage drug delivered (2.33 %- 0.99 % for 30 LPM;1.80 %- 0.61 % for 60 LPM), with no significant difference between the flow rates (p=0.6220). For mechanical ventilation, there was a significant difference in adopting a LTV ventilation strategy (13.66 %- 0.75 %) in comparison to a standard ventilation (30.34 %- 0.27 %) (p < 0.0001). It can be concluded that the choice of clinical intervention in the oxygenation and ventilatory support of the COVID-19 patient influences aerosol delivery to the lung. This variability may be significant and therefore should be noted in the design of dosing strategies, and de-risking of clinical trial programs. Key Message: The choice of clinical intervention in the oxygenation and ventilatory support of the COVID-19 patient influences aerosol delivery to the lung. This variability may be significant and therefore should be noted in the design of dosing strategies, and derisking of clinical trial programs.

Effective removal of exhaled virus using a viral filter on the aerogen ultra nebuliser system

Introduction: In response to the ongoing COVID-19 pandemic, expert consensus suggests that connection of a filter to nebulisers has the potential to mitigate the risk of bystander exposure to patient-derived bioaerosol. Here we assess the feasibility of removing exhaled virus using a viral filter and determine its effect on nebuliser performance. Materials and Methods: Simulated exhaled breath, containing Adenovirus (Ad5-GFP) as a tracer bioaerosol was generated during normal adult breathing (15BPM, Vt 500mL, I:E 1:1). At ∼100nm, Ad5-GFP is similar size to SARS-CoV-2. Two viral filters (303EU;Vyaire, US) were connected to the mouthpiece of the Aerogen Ultra (Aerogen, Galway, Ireland). The primary filter was used to capture exhaled aerosol, the secondary to assess if virus escaped from the primary filter. Inhaled dose was assessed using salbutamol (2.5mL of 2.5mg/mL). No supplemental oxygen was used. QPCR was used to determine presence of viral plasmid on the filter. UV spectrophotometry was used to quantify salbutamol. Testing was completed in triplicate. Results: For all tests, virus was detected on the primary filter with none detected on the secondary filter. Inhaled dose was recorded as 65.22 ± 1.2 % versus 65.98 ± 2.01 % (p > 0.05), unfiltered and filtered, respectively. Conclusion: Connection of a viral filter was seen to effectively remove virus from the simulated exhaled breath, with the use of the filter not having a significant effect on nebuliser performance.

Evaluation of ventilation parameters on Aerosol delivery during mechanical Ventilation of covid-19 patients

Introduction and Objectives COVID-19 can cause serious respiratory complications. One form of treatment utilises aerosolised therapeutics concurrently with mechanical ventilation (MV). Clinicians have adopted low tidal volume ventilation (LTV) strategies (4-6 mL/kg body weight)1 in these patients. Nebuliser performance is typically characterised in accordance with international ventilatory standard ISO274272 (ISO ventilation). The objective of this study was to compare the aerosol dose delivered to a simulated adult model with either LTV ventilation or ISO ventilation settings. Methods A 2.5 ml dose of 1 mg/ml of salbutamol (GlaxoSmithKline Ltd., Ireland) was aerosolised with a vibrating mesh nebuliser (VMN) (Aerogen Ltd., Ireland) positioned on the dry side of the humidifier within a dual limb circuit (Fisher & Paykel, New Zealand) during simulated MV (Servo-I, Maquet, Sweden). Two adult breath patterns were generated: 1) ISO ventilation, Tidal Volume VT: 500 mL, Breathing Rate BR = 15 BPM, Inhalation Exhalation ratio I:E: 1:1, and 2) LTV, VT: 400 mL, BR = 20 BPM, I:E: 1:2. A capture filter (Respirgard, Baxter, Ireland) was placed between the ETT (8.0 mm, Flexicare Medical Inc., UK) and the test lung. The mass of drug was determined using UV spectrophotometry (276 nm). Results are expressed as the percentage of the nominal dose placed in the nebuliser's medication cup. All testing was performed in triplicate. Results The results of this study, presented in figure 1, highlight the difference in the aerosol dose delivered to the simulated patient at the two different ventilatory settings. Conclusions Study results confirm that a simulated adult patient undergoing MV utilising LTV ventilation strategy would receive approximately half of the aerosol dose delivered in comparison with the ISO ventilation parameters typically used in reporting nebuliser performance. These findings should provide clinicians with an approximation of the administered dose that is delivered. This may be useful when optimising aerosol dosing strategies during LTV ventilation in COVID-19 patients.

An in vitro investigation into the release of fugitive medical aerosols into the environment during manual ventilation.

BACKGROUND: During manual resuscitation, nebulizer therapy may be used to deliver therapeutics to patients in respiratory distress. However, the devices used to generate and deliver these medical aerosols have the potential to release these therapeutics into the local environment and expose caregivers to unwanted medical aerosols. AIM: To quantify the levels of fugitive medical aerosol released into the environment during aerosol drug delivery using a manual resuscitation bag with and without filtration. METHODS: Time-varying fugitive aerosol concentrations were measured using an aerodynamic particle sizer placed at a position designed to mimic a caregiver. Two nebulizer types were assessed, a vibrating mesh nebulizer and a jet nebulizer. The aerosol dose delivered to the simulated patient lung was also quantified. FINDINGS: Filtration of the exhalation port of the manual resuscitation bag was seen to reduce fugitive medical aerosols to ambient levels for both nebulizer types. The vibrating mesh nebulizer delivered the greatest quantity of aerosol to the simulated adult patient (18.44 ± 1.03% versus 3.64 ± 0.26% with a jet nebulizer). CONCLUSIONS: The results highlight the potential for exposure to fugitive medical aerosols released during the delivery of aerosol therapy with a manual resuscitation bag and also the potential for significant variation in patient lung dose depending on nebulizer type.