Factors Determining Continuous Infusion Aerosol Delivery During Mechanical Ventilation

McPeck, Michael; Ashraf, Sunya; Cuccia, Ann D; Smaldone, Gerald C.

doi:10.4187/respcare.07715

Cited by 7 publications

(12 citation statements)

References 14 publications

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“…Use of a radioactive tracer coupled with the gamma camera provides a detailed assessment of inhaled drug delivery in a mechanical ventilation circuit. ( 7 , 9–11 ) However, in previous studies, analysis of an experiment could not begin until after it was completed, and IM separately measured. Nebulizer function and aerosol output of some nebulizers in a ventilator circuit may be difficult to observe, and if aerosol output differs from that expected, the question always remained “did the nebulizer function?” The effect of anomalies on the veracity of the experiment often could not be determined in real time.…”

Section: Discussionmentioning

confidence: 99%

“…Similarly, with this particular nebulizer, the heated humidifier did not present as a significant barrier to aerosol delivery as has been shown in other studies. ( 7 , 9 , 10 ) The mass balance is therefore an important aspect of in vitro aerosol delivery assessment because (i) it accounts for all the drug or tracer placed initially or infused into the nebulizer over time, and (ii) its distribution has the potential to vary depending on several factors, alone and in combination.…”

Section: Discussionmentioning

confidence: 99%

“…Technetium ( 99m Tc) pertechnetate dissolved in normal saline (NS, 0.9% NaCl) was used as a tracer and surrogate for albuterol and other drugs. (5)(6)(7) Preparation of the surrogate nebulizer solutions plus deposition of 99m Tc-NS on collection filters and other parts of the ventilator circuit was quantified by direct measurement in a radioisotope calibrator (AtomLab 100; Biodex, Inc., Shirley, NY) or regionally in the ventilator circuit using a calibrated gamma camera (Maxi Camera 400; General Electric, Horsholm, Denmark, Model 604/150/D; Power Computing, Austin, TX, Nuclear MAC OS, Version 4.2.2; Scientific Imaging, Inc., Thousand Oaks, CA).…”

Section: Methodsmentioning

confidence: 99%

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Real-Time In Vitro Assessment of Aerosol Delivery During Mechanical Ventilation

McPeck

Lee

Cuccia

et al. 2022

Journal of Aerosol Medicine and Pulmonary Drug Delivery

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Background: A new real-time method for assessing factors determining aerosol delivery is described. Methods: A breath-enhanced jet nebulizer operated in a ventilator/heated humidifier system was tested during bolus and continuous infusion aerosol delivery. 99m Tc (technetium)/saline was either injected (3 or 6 mL) or infused over time into the nebulizer. A shielded gamma ratemeter was oriented to count radioaerosol accumulating on an inhaled mass (IM) filter at the airway opening of a test lung. Radioactivity measured at 2-10-minute intervals was expressed as % nebulizer charge (bolus) or % syringe activity per minute infused. All circuit parts were measured and imaged by gamma camera to determine mass balance. Results: Ratemeter activity quantitatively reflected immediate changes in IM: 3 and 6 mL bolus IM% ¼ 16.1 and 18.8% in 6 and 14 minutes, respectively; infusion IM% ¼ 0.64 + 0.13 (run time, min), R 2 0.999. Effect of nebulizer priming and system anomalies were readily detected in real time. Mass balance (basis ¼ dose infused in 90 minutes): IM 39.2%, breath-enhanced jet nebulizer residual 35.5%, circuit parts including humidifier 23.4%, and total recovery 98.1%. Visual analysis of circuit component images identified sites of increased deposition. Conclusion:Real-time ratemeter measurement with gamma camera imaging provides operational feedback during in vitro testing procedures and yields a detailed analysis of the parameters influencing drug delivery during mechanical ventilation. This method of analysis facilitates assessment of device function and influence of circuit parameters on drug delivery.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Real-Time In Vitro Assessment of Aerosol Delivery During Mechanical Ventilation

McPeck

Lee

Cuccia

et al. 2022

Journal of Aerosol Medicine and Pulmonary Drug Delivery

Self Cite

View full text Add to dashboard Cite

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“…Up to now, there is no consensus on whether a nebulizer should be combined with a humidifier, and if the humidifier should be placed between nebulizer and patient or the other way around ( 32 , 33 ). Therefore, the effect of epoprostenol and iloprost was measured in relation to the nebulizer position.…”

Section: Discussionmentioning

confidence: 99%

The impact of nebulized epoprostenol and iloprost on hemoglobin oxygen affinity: an ex vivo experiment

Woyke

Mair

Haller

et al. 2022

American Journal of Physiology-Lung Cellular and Molecular Phys

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Background Inhalational prostacyclins act as strong vasodilators, potentially improving oxygenation by reducing shunt fraction and ventilation-perfusion mismatch. As prostacyclin receptors are known to be present on human erythrocytes, possible direct effects on oxygenation were further explored by examining the sole in-vitro influence of prostacyclins on hemoglobin oxygen (Hb-O2) affinity. Methods Venous blood samples from 20 healthy volunteers were exposed in-vitro to supramaximal doses of epoprostenol, iloprost, and control. By high-throughput measurements, hemoglobin oxygen dissociation curves (ODC) were derived. Hb-O2 affinity, expressed by P50 and hill coefficient, was determined, and analyzed for three subgroups: males (n= 10), females not taking (n= 4) and females taking oral contraceptives (n= 6). Results Epoprostenol significantly decreased P50 in all (27.5 (26.4 - 28.6) mmHg and 24.2 (22.7 - 25.3) mmHg; p<0.001) thereby increasing Hb-O2 affinity. Inversely, iloprost merely showed significant effects in females taking oral contraceptives where P50 was markedly increased and therefore Hb-O2 affinity decreased (28.4 (27.9 - 28.9) mmHg and 34.4 (32.2 - 36.0) mmHg; p<0.001). Conclusion Prostacyclin-receptor stimulation and subsequent cAMP mediated ATP release from erythrocytes might explain the effect of epoprostenol on Hb-O2 affinity but the reason for the sex hormone modified iloprost effect remains unclear. This finding is of great interest, as contraception is recommended for women taking iloprost. Being aware of potentially differing effects on Hb-O2 affinity might help select the right prostacyclin (epoprostenol vs. iloprost) depending on the patient and the underlying disease (e.g., acute respiratory distress syndrome vs. peripheral arterial disease).

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“…Failure of gravitational feed was noted as well as bubble formation on the mesh particularly when used during mechanical ventilation. ( 66 , 67 ) In the IASIS trial, an inline vibrating plate electronic nebulizer (eFlow Inline System; PARI GmbH) was used. ( 5 ) Rottier et al tested PARI eFlow devices and found >50% of the time the eflow switched off after 19 minutes.…”

Section: Designing Clinical Trials For Ventilator-associated Infectionmentioning

confidence: 99%

The Unfulfilled Promise of Inhaled Therapy in Ventilator-Associated Infections: Where Do We Go from Here?

Palmer

Smaldone

2022

Journal of Aerosol Medicine and Pulmonary Drug Delivery

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Respiratory infection is common in intubated/tracheotomized patients and systemic antibiotic therapy is often unrewarding. In 1967, the difficulty in treating Gram-negative respiratory infections led to the use of inhaled gentamicin, targeting therapy directly to the lungs. Fifty-three years later, the effects of topical therapy in the intubated patient remain undefined. Clinical failures with intravenous antibiotics persist and instrumented patients are now infected by many more multidrug-resistant Gram-negative species as well as methicillin-resistant Staphylococcus aureus . Multiple systematic reviews and meta-analyses suggest that there may be a role for inhaled delivery but “more research is needed.” Yet there is still no Food and Drug Administration (FDA) approved inhaled antibiotic for the treatment of ventilator-associated infection, the hallmark of which is the foreign body in the upper airway. Current pulmonary and infectious disease guidelines suggest using aerosols only in the setting of Gram-negative infections that are resistant to all systemic antibiotics or not to use them at all. Recently two seemingly well-designed large randomized placebo-controlled Phase 2 and Phase 3 clinical trials of adjunctive inhaled therapy for the treatment of ventilator-associated pneumonia failed to show more rapid resolution of pneumonia symptoms or effect on mortality. Despite evolving technology of delivery devices and more detailed understanding of the factors affecting delivery, treatment effects were no better than placebo. What is wrong with our approach to ventilator- associated infection? Is there a message from the large meta-analyses and these two large recent multisite trials? This review will suggest why current therapies are unpredictable and have not fulfilled the promise of better outcomes. Data suggest that future studies of inhaled therapy, in the milieu of worsening bacterial resistance, require new approaches with completely different indications and endpoints to determine whether inhaled therapy indeed has an important role in the treatment of ventilated patients.

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Factors Determining Continuous Infusion Aerosol Delivery During Mechanical Ventilation

Cited by 7 publications

References 14 publications

Real-Time In Vitro Assessment of Aerosol Delivery During Mechanical Ventilation

Real-Time In Vitro Assessment of Aerosol Delivery During Mechanical Ventilation

The impact of nebulized epoprostenol and iloprost on hemoglobin oxygen affinity: an ex vivo experiment

The Unfulfilled Promise of Inhaled Therapy in Ventilator-Associated Infections: Where Do We Go from Here?

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