[Show abstract][Hide abstract] ABSTRACT: Purpose:
Unlike in the outpatient setting, delivery of aerosols to critically ill patients may be considered complex, particularly in ventilated patients, and benefits remain to be proven. Many factors influence aerosol delivery and recommendations exist, but little is known about knowledge translation into clinical practice.
Two-week cross-sectional study to assess the prevalence of aerosol therapy in 81 intensive and intermediate care units in 22 countries. All aerosols delivered to patients breathing spontaneously, ventilated invasively or noninvasively (NIV) were recorded, and drugs, devices, ventilator settings, circuit set-up, humidification and side effects were noted.
A total of 9714 aerosols were administered to 678 of the 2808 admitted patients (24 %, CI95 22-26 %), whereas only 271 patients (10 %) were taking inhaled medication before admission. There were large variations among centers, from 0 to 57 %. Among intubated patients 22 % (n = 262) received aerosols, and 50 % (n = 149) of patients undergoing NIV, predominantly (75 %) inbetween NIV sessions. Bronchodilators (n = 7960) and corticosteroids (n = 1233) were the most frequently delivered drugs (88 % overall), predominantly but not exclusively (49 %) administered to patients with chronic airway disease. An anti-infectious drug was aerosolized 509 times (5 % of all aerosols) for nosocomial infections. Jet-nebulizers were the most frequently used device (56 %), followed by metered dose inhalers (23 %). Only 106 (<1 %) mild side effects were observed, despite frequent suboptimal set-ups such as an external gas supply of jet nebulizers for intubated patients.
Aerosol therapy concerns every fourth critically ill patient and one-fifth of ventilated patients.
Full-text · Article · Nov 2015 · Intensive Care Medicine
[Show abstract][Hide abstract] ABSTRACT: Background:
Jet nebulizers constitute the aerosolization devices most frequently used during mechanical ventilation. Continuous nebulization can influence the delivered tidal volume (V(T)) and lead to significant medication loss during expiration. Ventilators thus provide integrated jet nebulization systems that are synchronized during inspiration and ostensibly keep VT constant.
This was a bench study of systems integrated in the Evita XL, Avea, Galileo, and G5 ventilators. The VT delivered with and without nebulization, the inspiratory synchronization of nebulization, and the aerosol deposition were measured with 2 locations of the nebulizer.
Changes in V(T) with the nebulizer were below 20 mL and below 10% of set V(T) for all ventilators. Synchronization was good at the beginning of insufflation, but prolonged nebulization was observed with all ventilators at the end of insufflation, until up to 1 s during expiration: 5-80% of nebulization occurred during expiration with significant aerosol loss in the expiratory limb. Synchrony could be improved by (1) reducing gas compression/decompression phenomena proximal to the jet nebulizer and (2) increasing inspiratory time, which reduced the amount of nebulization occurring during expiration. Placing the nebulizer upstream in the inspiratory limb did not affect inspiratory synchrony but allowed reduction of the amount of aerosol lost in the expiratory limb.
Jet nebulizer systems integrated in the tested ventilators are reliable in terms of V(T) control. Gas compression in tubing driving gas to the nebulizer delays synchronization and reduces nebulization yield if the nebulizer is placed close to the Y-piece. Increasing inspiratory time with no end-inspiratory pause reduces the expiratory loss of medication if placement of the nebulizer upstream in the inspiratory limb is not feasible.
[Show abstract][Hide abstract] ABSTRACT: INTRODUCTION. Aerosol-therapy is appealing as it may enable to deliver high drug concentrations at the site of action while limiting systemic side effects. In the intensive care unit, a great number of molecules have been reported to be nebulized. However, technical implementation may be challenging, particularly during mechanical ventilation and only little data is available concerning current practice in the intensive care environment.
OBJECTIVES. To prospectively describe the practice of aerosol-therapy in intensive care and intermediate care unit in terms of frequency, technical implementation and tolerance.
METHODS. Prospective non-interventional cross-section descriptive study. All patients admitted to 83 centers over a two weeks observational study period (staggered over March and April 2013) were included. We here present preliminary results for the 55 first participating centers.
RESULTS. 1857 patients (Median SAPSII 34[21-48] were present in the participating centers over the study period (8225 patients.days of which 6951 [84%] were spent in the ICU]). 468 (25%) patients received at least one inhaled medication during the study. Overall 6361 aerosols were analyzed. 3117 (49%), 253 (4%) and 2988 (47%) were performed during invasive-, non-invasive mechanical ventilation and spontaneous breathing respectively.
2528 (40%) nebulization concerned more than one molecule delivered as an association. The most frequently drugs delivered were bronchodilators (n=7418 [75%]), followed by steroids (n=1561[16%]). Among other nebulized drugs, anti-infective molecules were delivered 278 times (3%): Colistin (87%), Amphotericine B (11%), Ceftazidime (2%). The aerosolization devices used were jet-nebulizers (n=3646 [58%]), metered dose inhalers (1600 [25%]), ultrasonic nebulizers (774 [12%]) and vibrating mesh nebulizers (247 [4%]). Overall, for aerosol-therapy during mechanical ventilation, the nebulizer was mostly placed immediately distal or immediately proximal of the Y piece (75% of aerosols), heated humidification pursued (83%) and ventilator settings not changed (< 1%). Of note, when nebulizing anti-infective drugs, heated humidification was interrupted in 57% of the cases.
No side effects of aerosol-therapy were observed for the large majority of deliveries (98%). Reported side effects were: tachycardia (33%), cough (26%), hypotension (19%), hypoxemia (14%), and bronchospasm (4%).
CONCLUSIONS. Aerosol-therapy is very frequent in intensive and intermediate care units as it concerns about one quarter of patients. Half of the aerosols are delivered to mechanically ventilated patients mostly using jet-nebulizer. Ventiltor settings are almost never changed during aerosolization. Aerosol-therapy of anti-infective drugs is rare and mostly concerns colistin. Overall side effects are infrequent.
GRANT ACKNOWLEDGMENT. Agence Nationale de la Recherche (ANR-2010 BLAN 1119 05).
[Show abstract][Hide abstract] ABSTRACT: Purpose:
To describe the practice, knowledge and beliefs about aerosol therapy during mechanical ventilation in an international sample of physicians working in intensive care units (ICU).
A self-administered survey was emailed to physicians who worked regularly in ICUs. The physicians were identified from the databases of the European and French societies of intensive care medicine and the REVA network.
Of the 1,192 responses (15 % response rate), 854 were analyzed. Of the respondents, who represented 611 departments in 70 countries, 99 % reported using aerosol therapy during mechanical ventilation (including non-invasive), 43 % exclusively used nebulizers and 55 % also used metered dose inhalers. Nebulization relied on jet, ultrasonic and vibrating mesh nebulizers (55 %, 44 % and 14 % of respondents, respectively). Bronchodilators and steroids were the most frequently delivered drugs, and 80 % of respondents had a positive opinion concerning nebulized colistin and 30 % reported the use of nebulized antibiotics at least every other month. During nebulization, ventilator settings were never changed by 77 % of respondents, 65 % reported placing a filter on the expiratory limb, and of these 28 % never changed it. Only 22 % of respondents using heated humidifiers reported turning them off during nebulization. Specific knowledge about droplet size and nebulization yield was poor. A majority of respondents (87 %) thought that ultrasonic nebulizers outperform jet nebulizers, while 69 % had no opinion concerning mesh nebulizers.
Aerosol therapy during mechanical ventilation is used by over 95 % of intensivists, mostly for bronchodilator and steroid administration, but also frequently for antibiotics. The current scientific knowledge about optimal implementation seemed infrequently applied, suggesting the need for educational programs and research focusing on a better bench-to-bedside transfer of knowledge.
Full-text · Article · Mar 2013 · Intensive Care Medicine
[Show abstract][Hide abstract] ABSTRACT: Interest in bioequivalence (BE) of inhaled drugs derives largely from the desire to offer generic substitutes to successful drug products. The complexity of aerosol dosage forms renders them difficult to mimic and raises questions regarding definitions of similarities and those properties that must be controlled to guarantee both the quality and the efficacy of the product. Despite a high level of enthusiasm to identify and control desirable properties there is no clear guidance, regulatory or scientific, for the variety of aerosol dosage forms, on practical measures of BE from which products can be developed. As more data on the pharmaceutical and clinical relevance of various techniques, as described in this review, become available, it is likely that a path to the demonstration of BE will become evident. In the meantime, debate on this topic will continue.
Full-text · Article · Mar 2013 · Therapeutic delivery
[Show abstract][Hide abstract] ABSTRACT: Computer modeling is used widely to predict inhaled aerosol deposition in the human lung based on definition of the input conditions describing the aerosol characteristics, the breathing pattern and the airway anatomy of the subject. Validation of the models is limited by the lack of detailed experimental data. Three dimensional imaging data provides an opportunity to address this unmet need. Radioactive aerosol was administered to each of 11 healthy male subjects on two occasions under carefully monitored input conditions. Input parameters varied were particle size, depth of breathing, carrier gas and posture. The aerosol distribution was measured by combined single photon emission computed tomography and X-ray computer tomography (SPECT/CT). Airway anatomy was determined by high resolution CT imaging. The distribution of deposition was determined by a combination of 2D and 3D analysis and described in terms of the percentage of inhaled aerosol deposited in sections of the respiratory tract and in both spatial and anatomical sub-divisions within each lung. The percentage deposition in the conducting airways was also assessed by 24 h clearance. A set of imaging data of aerosol deposition has been produced in which the input parameters of inhalation are well described. The parameters were varied in a controlled manner to allow the sensitivity of predictive models to different factors to be tested. An initial analysis of the data is presented which will act as a guide that other centers can use to compare their own methodology. This data is considered to be of great potential value to computer modelers of aerosol deposition in validating their models.
Full-text · Article · Oct 2012 · Journal of Aerosol Science
[Show abstract][Hide abstract] ABSTRACT: To evaluate the efficacy of delivering a mixture of helium and oxygen gas (He–O2) in spontaneous ventilation. Three high oxygen flow reservoir masks were tested: the Heliox21, specifically designed for helium; the Hi-Ox80 mask, with an inspiratory and an expiratory valve; and a standard high-concentration face mask.
This prospective randomized crossover study was performed in six healthy volunteers in a laboratory setting. Volunteers breathed a mixture of 78% He/22% O2 through each of the masks under two different breathing conditions (rest and hyperventilation: minute ventilation of 14.9 ± 6.1 and 26.7 ± 8.7 L min(−1), respectively) and four different He–O2 flow rates (7, 10, 12, and 15 L min(−1)).
A nasopharyngeal catheter was used to estimate He pharyngeal concentration (Fp [He]) in the airways in order to determine the percentage of contamination with room air (% air cont) at end-expiration. Under all testing conditions, the Hi-Ox80 mask presented a significantly lower % air cont. During resting breathing pattern, a Fp [He] higher than 50% was achieved in 54% of the tests performed with the Hi-Ox80 mask compared to 29% for the Heliox21 mask and only 17% for the standard mask. At hyperventilation, a Fp [He] higher than 50% was achieved in 17% of the tests performed with the Hi-Ox mask compared to 4% for the other two masks.
He–O2 administration via the usual high-concentration reservoir masks results in significant dilution by room air. The Hi-Ox80 mask minimized room air contamination and much more frequently achieved a pharyngeal He concentration higher than 50%.
No preview · Article · Nov 2011 · Intensive Care Medicine
[Show abstract][Hide abstract] ABSTRACT: Gamma camera imaging is widely used to assess pulmonary aerosol deposition. Conventional planar imaging provides limited information on its regional distribution. In this study, single photon emission computed tomography (SPECT) was used to describe deposition in three dimensions (3D) and combined with X-ray computed tomography (CT) to relate this to lung anatomy. Its performance was compared to planar imaging.
Ten SPECT/CT studies were performed on five healthy subjects following carefully controlled inhalation of radioaerosol from a nebulizer, using a variety of inhalation regimes. The 3D spatial distribution was assessed using a central-to-peripheral ratio (C/P) normalized to lung volume and for the right lung was compared to planar C/P analysis. The deposition by airway generation was calculated for each lung and the conducting airways deposition fraction compared to 24-h clearance.
The 3D normalized C/P ratio correlated more closely with 24-h clearance than the 2D ratio for the right lung [coefficient of variation (COV), 9% compared to 15% p < 0.05]. Analysis of regional distribution was possible for both lungs in 3D but not in 2D due to overlap of the stomach on the left lung. The mean conducting airways deposition fraction from SPECT for both lungs was not significantly different from 24-h clearance (COV 18%). Both spatial and generational measures of central deposition were significantly higher for the left than for the right lung.
Combined SPECT/CT enabled improved analysis of aerosol deposition from gamma camera imaging compared to planar imaging. 3D radionuclide imaging combined with anatomical information from CT and computer analysis is a useful approach for applications requiring regional information on deposition.
Full-text · Article · Feb 2011 · Journal of Aerosol Medicine and Pulmonary Drug Delivery
[Show abstract][Hide abstract] ABSTRACT: Experimental and theoretical aspects of targeted drug delivery have been addressed several times in this journal. Herein, a computational study of particle deposition patterns within healthy and diseased lungs has been performed, using a validated aerosol dosimetry model and a flow-resistance model.
To evaluate to what extent the uneven flow distributions produced by the physical manifestations of respiratory diseases affect the deposition patterns of inhaled aerosolized drugs.
Diseases were simulated by constrictions and blockages, which caused uneven flow distributions. Respiratory conditions of sedentary and pronounced activities, and of particle sizes ranging from 0.1 microm to 10 microm, were used as the basis for the calculated deposition patterns.
Findings are presented that describe flow as a function of airway disease state (eg, flow redistribution). Data on the effects of lung morphologies, healthy and diseased, on compartmental (tracheobronchial and pulmonary) and local (airway generation) aerosol deposition are also given. By formulating these related factors, modeling results show that aerosolized drugs can be effectively targeted to appropriate sites within lungs to elicit positive therapeutic effects.
We have addressed the complexities involved when taking into account interactive effects between diseased airway morphologies and redistributed air flows on the transport and deposition of inhaled particles. Our results demonstrate that respiratory diseases may influence the deposition of inhaled drugs used in their treatment in a systematic and predictable manner. We submit this work as a first step in establishing the use of mathematical modeling techniques as a sound scientific basis to relate airway diseases and aerosolized drug delivery protocols.
[Show abstract][Hide abstract] ABSTRACT: In order to compare the effects of using helium–oxygen and air in assisted breathing and inhalation therapies, flow and particle deposition results were obtained in a realistic model of human oral extrathoracic (ET) airways using computational fluid dynamics (CFD) and pressure loss measurements. As the main deposition mechanism for pharmaceutical aerosols in the ET is inertial impaction, the ET model was reconstructed from medical images to take into account the complexity of realistic morphological features. Calculations were performed with the CFD software Fluent®, and pressure losses were measured on a cast based on a stereolithographic fabrication of the model. Results show that ET pressure loss and particle deposition are lower with helium–oxygen as compared to air. Moreover, further simulations were performed with various particle sizes and inspiratory flow rates, which indicate that particle deposition in the ET depends on both the Stokes and Reynolds number.
No preview · Article · Mar 2010 · Journal of Aerosol Science
[Show abstract][Hide abstract] ABSTRACT: This study presents a method for quantification of convective transport of a bolus (particle cloud) in the alveolar region.
A computational fluid dynamics calculation was performed using a model of a single alveolus connected to a bronchiole. Moving
wall boundary conditions and oscillating flow rates in the bronchiole were imposed to mimic breathing conditions. A passive
scalar representing the aerosol bolus, injected at the inlet of the bronchiole, is tracked in the course of breathing cycles.
The amount of scalar penetrating in the alveolus characterizes convective dispersion of bolus in the acinar airways. The amount
of scalar remaining in the alveolus after several breaths may be used to estimate the residence time of bolus in the alveolus.
The ratio QA/QD (QA and QD are respectively the flow rates entering the alveolus and the bronchiole) appears a key parameter to describe the variation
in bolus dispersion and the bolus residence time. The peak value of bolus dispersion is observed for QA/QD=2.5(10− 3. Bolus residence time also depends on the flow ratio QA/QD. These results emphasize the influence of specific alveolar flow patterns on convective dispersion in the alveolar region
of the aerosol bolus in the alveolar region of the lungs. Such a data could be integrated into the existing models of particle
deposition in the human airways.
No preview · Article · Jan 2010 · IFMBE proceedings
[Show abstract][Hide abstract] ABSTRACT: This work describes the development of an experimental setup that allows rapid determination of deposition characteristics of aerosols in different carrier gases and different geometries, based on particle size distribution measurements using the laser diffraction method. Isotonic saline solution was nebulized by a vibrating mesh nebulizer. The aerosol was introduced to a humidified gas stream of air or helium-oxygen. The particle size distributions at the inlet and outlet of a mouth-throat model were measured by laser diffractometry. Additionally, the nebulizer output and the deposition mass in the model were determined gravimetrically. The deposited percentage of the nebulizer output was highest in air. The laser diffractometry data showed increasing deposition of larger particles; in the given model particles larger than 9 mum in diameter deposited completely. Compared to the entering particle size distribution, however, the mass fraction in small particles was increased in the distribution leaving the model. The developed setup can be used for a rapid determination of deposition characteristics in different geometries and different gases. The shift towards small particles should be investigated further. Particle shrinkage via evaporation could be one of the reasons despite the humidification of the carrier gas.
[Show abstract][Hide abstract] ABSTRACT: The control of the temperature increase is an important issue in retinal laser treatments. Within the fundus of the eye heat, generated by absorption of light, is transmitted by diffusion in the retinal pigment epithelium and in the choroid and lost by convection due to the choroidal blood flow. The temperature can be spatially and temporally determined by solving the heat equation. In a former analytical model this was achieved by assuming uniform convection for the whole fundus of the eye. A numerical method avoiding this unrealistic assumption by considering convective heat transfer only in the choroid is used here to solve the heat equation. Numerical results are compared with experimental results obtained by using a novel method of noninvasive optoacoustic retinal temperature measurements in rabbits. Assuming global convection the perfusion coefficient was evaluated to 0.07 s(-1), whereas a value of 0.32 s(-1)--much closer to values found in the literature (between 0.28 and 0.30 s(-1))--was obtained when choroidal convection was assumed, showing the advantage of the numerical method. The modelling of retinal laser treatment is thus improved and could be considered in the future to optimize treatments by calculating retinal temperature increases under various tissues and laser properties.
Full-text · Article · Mar 2008 · Journal of Biophotonics
[Show abstract][Hide abstract] ABSTRACT: In most retinal laser treatments the therapeutic effect is initiated by a transient temperature increase at and around the retinal pigment epithelium (RPE). Especially in long exposure time treatments like Transpupillary Thermotherapy (TTT) choroidal perfusion has a strong influence on the realized temperature at the fundus. The fundus blood circulation and therefore the heat dissipation is influenced by the intraocular pressure (IOP), which is investigated in the study presented here. In order to reduce the choroidal perfusion, the IOP is increased by injection of physiological saline solution into the eye of anaesthetized rabbits. The fundus is irradiated with 3.64 W/cm2 by means of a TTT-laser (lambda = 810 nm) for t = 20 s causing a retinal temperature increase. Realtime temperature determination at the irradiated spot is achieved by a non invasive optoacoustic technique. Perfusion can be reduced by increasing IOP, which leads to different temperature increases when irradiating the retina. This should be considered for long time laser treatments.
Full-text · Article · Jun 2007 · Proceedings of SPIE - The International Society for Optical Engineering
[Show abstract][Hide abstract] ABSTRACT: Tumor thermo treatment such as photodynamic therapy (PDT) or transpupillary thermotherapy (TTT) deal with long term and large laser spot exposures. The induced temperature increase is not exactly known . Under these conditions convective heat transfers due to the blood flow in the choroid and the choriocapillaris must be considered in addition to the usually calculated heat conduction. From an existing analytical model defining a unique convective term for the whole fundus irradiated with Gaussian irradiance distribution lasers , we developed a numerical one allowing a precise modelling of convection and calculating heating evolution and temperature profiles of the fundus of the eye. The aim of this study is to present the modelling and several comparisons between experimental results  and numerical ones concerning the convective heat transfers inside the fundus of the eye.
No preview · Article · Mar 2006 · Proceedings of SPIE - The International Society for Optical Engineering