Abstract
BACKGROUND: The effect of single- and dual-limb circuits on aerosol delivery during noninvasive ventilation (NIV) in adult models is unclear.
METHODS: A noninvasive ventilator equipped with a single-limb circuit or an ICU ventilator equipped with a dual-limb circuit was connected to a simulated lung. Ventilator parameters were adjusted to maintain a tidal volume at ∼500 mL. Aerosol deposition with different placements of a vibrating mesh nebulizer and humidification conditions were compared. Additional experiments by using a non-vented mask or a vented mask were compared in the single-limb circuit only. Aerosol was collected by a disposable filter placed between the simulated lung and the head model (n = 3), and measured by ultraviolet spectrophotometry (276 nm).
RESULTS: The aerosol deposition varied between 4.12 ± 0.22% and 20.75 ± 0.95%. The greatest aerosol delivery during NIV when using a non-vented mask was found when a vibrating mesh nebulizer was placed between the mask and 15 cm from the exhalation port in the humidified single-limb circuit, and 15 cm from the Y-piece in the inspiratory limb of the humidified dual-limb circuit, and no significant difference of aerosol deposition was found between the two optimal positions (20.03 ± 1.48% vs 18.04 ± 0.93%, respectively; P =.042). There was no difference of aerosol delivery in dry versus humidified circuits, except when a vibrating mesh nebulizer was placed at the humidifier inlet in a dual-limb circuit. When using a vented mask, the aerosol deposition was poor (6.56 ± 0.41 ∼ 8.02 ± 0.39%), regardless of vibrating mesh nebulizer positions and humidification types.
CONCLUSIONS: During NIV, the aerosol delivery was optimal when a vibrating mesh nebulizer was placed between the non-vented mask and 15 cm from the exhalation port in the single-limb circuit or 15 cm from the Y-piece in the inspiratory limb of the dual-limb circuit; no significant difference was found between the two optimal placements. Humidification had little effect on aerosol delivery. Aerosol delivery was poor in the single-limb circuit with a vented mask.
- noninvasive ventilation
- aerosol delivery
- single limb circuit
- dual limb circuit
- humidification
- vibrating mesh nebulizer
Introduction
Noninvasive ventilation (NIV) is widely used in patients with acute and chronic respiratory failure. It can effectively reduce the intubation rate, hospital length of stay, and mortality, and the risk of respiratory failure after extubation in selected patients.1–5 Many of these patients who are receiving NIV also need to receive aerosolized medication, such as bronchodilators, glucocorticoids, mucolytics, and antibiotics. Nebulization in conjunction with NIV has been proven to be a feasible and effective method, and is widely used in acute settings.6 Early studies found that many factors can impact aerosol delivery during NIV and may influence the clinical effects.7 These influential factors include an aerosol generator, the inspiratory and expiratory pressures, the exhalation port, and the nebulizer position. To our knowledge, little is known about the effect of different breathing circuits (a single limb or a dual limb) on aerosol delivery during NIV in an adult model.
NIV can be delivered via a noninvasive ventilator with a single-limb circuit and a critical care ventilator equipped with a dual-limb circuit.8 Clinically, both types of ventilators are commonly used for NIV, depending on clinicians' preference and equipment availability.9 When using a pediatric model, Berlinski and Velasco10 and Velasco and Berlinski11 conducted 2 separate in vitro studies with the use of single- and dual-limb circuits, respectively; they found that aerosol deposition was highest when a vibrating mesh nebulizer was placed after the exhalation port in the single-limb circuit and at the mask or before the Y-piece in the dual-limb circuit. Aerosol deposition with the 2 optimal positions seems to be similar; however, they did not directly compare them in the same study. In addition, in the single-limb circuit, both non-vented masks (exhalation port in the circuit) and vented masks (exhalation port in the mask) are often used during NIV,12,13 a previous study found that aerosol delivery with non-vented masks was higher than with vented masks12; however, no data are available on the optimal nebulizer position with the use of a vented mask.
Moreover, the vibrating mesh nebulizer has been broadly used in clinical practice due to its advantages of little to no residual volume and no need for an external gas resource to drive the nebulizer. Recently, Saeed et al14 reported no significant differences of humidification on aerosol deposition during NIV when using a single-limb circuit; however, the effect of humidification on aerosol delivery is unclear in NIV with a dual-limb circuit. Therefore, we aimed to investigate the effect of a single-limb circuit with a non-vented mask or a vented mask and of a dual-limb circuit with a non-vented mask on aerosol delivery, with different nebulizer positions in both dry and humidified circuits.
QUICK LOOK
Current Knowledge
During noninvasive ventilation, aerosol delivery can be effected by the type of circuit, single limb vs dual limb and the use of a vented vs a non-vented mask. Humidification may also alter aerosol delivery. Within a combination of circuit and mask types, the optimal position of the nebulizer is likely different with each combination.
What This Paper Contributes to Our Knowledge
The aerosol delivery was optimal when a vibrating mesh nebulizer was placed between a non-vented mask and 15 cm from an exhalation port in the single-limb circuit or 15 cm from a Y-piece in the inspiratory limb of the dual-limb circuit, and no significant difference was found between the 2 placements. Aerosol delivery was poor in the single-limb circuit with a vented mask. Humidification had little effect on aerosol delivery.
Methods
Ventilator Settings
A noninvasive ventilator (V60, Philips Respironics, Murrysville, Pennsylvania) was connected to a humidifier (MR850, Fisher & Paykel Healthcare, Auckland, New Zealand) and a single limb heated-wire circuit (RT319, Fisher & Paykel). A non-vented mask (K1, Philips Respironics) or a vented mask (mirage Quattro, ResMed, France) was connected to the exhalation port (Philips Respironics) in the single-limb circuit. Spontaneous/Timed mode was used, with inspiratory positive airway pressure set at 15 cm H2O and expiratory positive airway pressure at 4 cm H2O to achieve a tidal volume () of 500 mL, an inspiratory time of 0.9 s, and an increased pressure gradient of 2.
An ICU ventilator (Servo-s, Maquet Critical Care, Solna, Sweden) was connected to a humidifier (MR850, Fisher & Paykel) and an adult-size dual-limb heated-wire circuit (RT100, Fisher & Paykel). The Y-piece was connected to a non-vented mask. The pressure support ventilation mode was used, with a pressure support of 13 cm H2O and PEEP of 4 cm H2O to maintain a of ∼500 mL, expiratory sensitivity of 34%, increased pressure time of 0.1 s, and trigger sensitivity of 2. When the humidifier was used with filling water, the noninvasive mode (31 ± 1°C) was set, the pass-over humidifier was turned on for a minimum of 20 min before the start of the experiment. For experiments with a dry circuit, a new circuit and a new humidifier chamber were used, without filling water.
Simulated Lung Settings
The active servo lung simulation system (ASL5000, Ingmar, Pittsburgh, Pennsylvania) is a precise breathing simulator that contains a piston that moves inside a cylinder and can simulate different breathing patterns of patients, such as COPD, asthma, or interstitial lung diseases. The following parameters, adapted from previous literature, were applied for the simulated COPD lung model15–17: compliance of 60 mL/cm H2O, inspiratory resistance of 10 cm H2O/L/s, expiratory resistance of 15 cm H2O/L/s, and a maximum inspiratory pressure drop of –8 cm H2O. To simulate the profile of the negative pressure created by respiratory muscles, 5% of the respiratory cycle time was active inspiration, 3% was an end-inspiratory hold, and 15% was for the return of pressure to baseline. Breathing frequency was set at 15 breaths/min.
In Vitro Model and Study Procedure
The ventilator was connected to the mask, which was placed on the face of a head model,18,19 which had a mouth port and tubing to be attached to the simulated lung. To avoid an unintentional leak, plasticine was used to seal the space between the mask and the face (Fig. 1). In the single-limb ventilator, a nebulizer was placed at 5 positions with a non-vented mask, including before the mask (position SN 1), 15 cm from the distal end of the exhalation valve (position SN 2), immediately after the exhalation valve (position SN 3), 15 cm from the proximal end of the exhalation valve (position SN 4), and at the humidifier inlet (position SN 5) (Fig. 1A). When a vented mask was used, the nebulizer was placed at 3 locations: before the mask (position SV 3), 15 cm from the mask (position SV 4), and at the humidifier inlet (position SV 5) (Fig. 1B). In the dual-limb circuit with a non-vented mask, a nebulizer was placed at 4 positions: before the mask (position D 1), at the Y-piece in the inspiratory limb (position D 3), 15 cm from the Y-piece in the inspiratory limb (position D 4), and at the humidifier inlet (position D 5) (Fig. 1C).
Schematic diagram of the experimental setup and aerosol delivery of the 3 ventilator settings (in a humidified noninvasive ventilation [NIV] circuit). A: Position SN = a nebulizer position in a single-limb circuit with a non-vented mask; B: Position SV = a nebulizer position in a single-limb circuit with a vented mask; and C: Position D = a nebulizer position in a dual-limb circuit.
Aerosol Delivery and Measurement
A 1-mL solution of 0.5% salbutamol (Ventolin, GlaxoSmithKline, Boronia, Australia) was diluted with 3 mL of normal saline solution, and the solution was placed into a vibrating mesh nebulizer (Aeroneb Pro, Aerogen, Galway, Ireland). The aerosol particles were captured by a disposable filter (DAA120, Chongren Medical Instrument Co. Ltd., Xiamen, China) that was placed between the head model and the simulated lung. A stopwatch was used to record the nebulization time; nebulization was considered completed when there was no visible aerosol for 30 s. The ventilator and the simulated lung were turned off for at least 1 min after each nebulization was completed. Vibrating mesh nebulizer was then washed with 5 mL of normal saline solution and nebulization with 1 mL of normal saline solution, per manufacturer's recommendation. Experiments were performed 3 times under each experimental condition.
After each nebulization, the filter was eluted by using 10 mL normal saline solution to collect the aerosol. The filter was shaken by using a vortex shaker (XW-80A, Huxi Medical Co. Ltd., Shanghai, China) for 1 min to fully mix the normal saline solution and salbutamol aerosol particles. The elution was placed into a 1-mL quartz glass cup, and an ultraviolet spectrophotometer (DU500, Beckman Instruments, Fullerton, California) was used to measure the absorbance of the solution at a wavelength of 276 nm. Absorbance at this wavelength had a linear relationship with the concentration of the salbutamol solution over the concentration range of 0 to 0.1 mg/mL, and the slope of the standard curve was 0.1426 (r2 = 0.99). The standard curve was then used to calculate the corresponding salbutamol concentration and amount. All the experiments were performed by the same investigator (Dong-Yang Xu).
Statistical Analysis
All statistical analysis was performed by using SPSS software (SPSS version 22.0, SPSS, Chicago, Illinois). Aerosol delivery was presented as a percentage of the aerosol. The Kruskal-Wallis test was used to analyze the difference of aerosol delivery with different nebulizer positions by using the same ventilator circuit, whereas the Mann Whitney test was used to compare the aerosol delivery of the optimal nebulizer positions within the single- and dual-limb circuits, and to compare the aerosol delivery of dry versus humidified circuits within the same ventilator setting. P < .05 indicated statistical significance for comparisons of aerosol delivery. For ventilator performance, a 2-tailed P < .05 and clinically important differences > 10% indicated statistical and clinical importance, respectively.15
Results
The aerosol delivery time varied from 11.6 ± 0.5 min to 12.4 ± 0.2 min with the 3 breathing circuit setups. The monitoring parameters, including , inspiratory time, expiratory time, breathing frequency, and total leak volume, are shown in Table 1.
The Ventilation Parameters and Aerosol Delivery Time With Single- and Dual-Limb Circuits
Different Nebulizer Positions in the Humidified Single-Limb Ventilator With a Non-Vented Mask or a Vented Mask
The aerosol delivery was higher with the nebulizer placed at position SN 2 (15 cm from the distal end of the exhalation valve) (20.03 ± 1.48%) than other positions in the single-limb ventilator with a non-vented mask, whereas the aerosol delivery was the lowest at position SN 3 (immediately after the exhalation valve) (4.34 ± 0.33%) (P < .001) (Fig. 1A, Table 2). With the use of a vented mask in the single-limb ventilator, aerosol deposition was generally low (6.56 ± 0.41 ∼ 8.02 ± 0.39%) at all 3 nebulizer positions (P = .54) (Fig. 1B, Table 2).
Comparison of Aerosol Delivery in Dry Versus Humidified Noninvasive Ventilation Circuit
Different Nebulizer Positions in the Humidified Dual-Limb Ventilator With a Non-Vented Mask
In the dual-limb ventilator with a non-vented mask, the aerosol delivery was higher when the nebulizer was placed at position D 4 (15 cm from the Y-piece in the inspiratory limb) (18.04 ± 0.93%) than in other positions. Compared with aerosol deposition at this optimal position, aerosol delivery was lower with the nebulizer placed at position D 3 (at the Y-piece in the inspiratory limb) (12.31 ± 0.47%, P<.001) and at position D 5 (humidifier inlet) (8.0 ± 0.30%, P < .001) (Fig. 1C, Table 2). Compared with the highest aerosol deposition in the single-limb circuit with a non-vented mask (position SN 2), the aerosol deposition with the optimal deposition in the dual-limb circuit (position D 4) was similar (20.03 ± 1.48% vs 18.04 ± 0.93%, respectively; P = .042).
Comparison of Aerosol Delivery in a Dry Versus Humidified NIV Circuit
There was no difference in aerosol delivery in a dry versus humidified single-limb circuit at different nebulizer positions. Only when the nebulizer was placed at the humidifier inlet in the dual-limb circuit (position D 5), the aerosol delivery with humidification was lower than the dry circuit (8.0 ± 0.30% vs 12.46 ± 0.23%; P < .001) (Fig. 2, Table 2).
Comparison of aerosol delivery (%) in dry versus humidified noninvasive ventilation circuit. *A significant difference was found between dry and humidified dual-limb circuits (P < .001). Position SN = a nebulizer position in a single-limb circuit with a non-vented mask, position SV = a nebulizer position in a single-limb circuit with a vented mask; and position D = a nebulizer position in a dual-limb circuit.
Discussion
In this study, we found that, with the use of a non-vented mask during NIV, the optimal aerosol delivery was achieved with the nebulizer placed between the mask and 15 cm from the exhalation port in the single-limb circuit and 15 cm from the Y-piece in the inspiratory limb of the dual-limb circuit, and the aerosol deposition with optimal delivery in the single- and dual-limb circuits was similar. Aerosol delivery with a vented mask during NIV was poor, regardless of nebulizer positions. Humidification has little effect on aerosol delivery in almost all conditions, except when the nebulizer was placed at the humidifier inlet in the dual-limb circuit.
Early studies found that many factors may impact aerosol delivery during NIV, including the type of delivery device, the interface, NIV settings, the nebulizer placement, and exhalation port.7,10–12,20 Most of these studies7,10,12,20 investigated aerosol delivery during NIV with a single-limb circuit. Clinically, both single- and dual-limb circuits are widely used for NIV, even in the same institution, and they are often switched from one to the other. Berlinski and Velasco10 and Velasco and Berlinski11 compared the aerosol delivery of different nebulizer positions in single- and dual-limb circuits in a pediatric model in 2 separate studies, but they did not compare the aerosol deposition in both circuits. In our study, we investigated the effect of single- and dual-limb circuits on the aerosol delivery by using the same adult model and the same settings, and no difference was found in aerosol deposition between the single- and dual-limb circuits with a non-vented mask, when a vibrating mesh nebulizer was placed at its optimal position with each circuit type.
Moreover, we compared more nebulizer positions and the impact of humidification on aerosol delivery. The comprehensive results in our study could help identify the key influential factors of aerosol delivery via NIV. Real-life clinical practice varied, and the nebulizer was not always placed at the optimal position.9 Therefore, our findings would be meaningful to guide clinical practice, especially when the ventilator is switched from one to the other; it is important for clinicians to understand where to place the nebulizer to achieve similar effects. If the optimal position is not feasible, then clinicians need to know the extent of reduction in aerosol deposition with the nebulizer placed at alternative positions.
In the dual-limb circuit, we found that a vibrating mesh nebulizer placed at the mask or before the Y-piece provided higher aerosol delivery than a vibrating mesh nebulizer placed at the humidifier inlet; this agrees with the findings with a pediatric model.11 In addition, adding an extra 15 cm of tubing before the Y-piece was found to further increase aerosol delivery, which might be explained by the reservoir effects of the extra 15 cm of tubing, which reduced aerosol waste during the exhalation phase. Similarly, we found that the optimal placement for a vibrating mesh nebulizer in the single-limb ventilator was 15 cm away from the exhalation valve; this finding was consistent with our previous study when using a small-volume jet nebulizer.21 The 15-cm extension tube adds ∼60 mL of dead space to the breathing circuit, which might result in CO2 rebreathing. For patients with severe hypercapnia, adding the 15 cm of tubing might increase the risk of CO2 rebreathing. However, CO2 rebreathing is also associated with some factors, such as the type and location of the exhalation port as well as the inspiratory and expiratory pressure settings.22 Hence, whether adding a 15-cm extension tube has significant impact on CO2 rebreathing remains to be further studied.
A previous study found that aerosol delivery in a single-limb circuit with a non-vented mask (an exhalation valve located in the circuit) was higher than with a vented mask12; however, the effects of different nebulizer positions in the single-limb circuit with a vented mask on aerosol delivery are still unclear. In our study, no significant difference of aerosol delivery was found among the different nebulizer positions, and the aerosol delivery was generally poor. This may be explained that little or no reservoir is available with a vented mask because the exhalation port is located on the mask and the gas is constantly leaking via the port. Therefore, if possible, a vented mask should be avoided during aerosol delivery via NIV; otherwise, if tolerated, discontinuing NIV so to use a high-efficient nebulizer with a mask or mouthpiece might help improve aerosol delivery.
Previous in vitro studies reported that humidification without a heated-wire circuit during invasive ventilation reduced aerosol delivery23,24; however, two clinical trials demonstrated that there were no significant differences in lung deposition and clinical outcomes with and without humidification of invasive ventilation.25,26 In addition, dry gas might cause airway irritation, a mucus plug, and airway membrane injury, thus the humidifier should not be turned off during aerosol therapy.24 To our knowledge, little is known about the effect of humidification on aerosol delivery during NIV. Only one study found that humidification had an insignificant effect on aerosol delivery during single-limb NIV.14 In our study, humidification with a heated-wire circuit had little effect on aerosol delivery in almost all conditions, except when a nebulizer was placed at the humidifier inlet in a dual-limb circuit. This might be explained by the lower temperature (31 ± 1°C) and heated-wire circuit we used in our study, which is different from the invasive ventilation study that used a higher temperature setting (35 ± 1°C) or non-heated–wire circuit.23,24
Our study had several limitations. First, The aerosol delivery was likely to be overestimated because aerosol particles captured at the collected filter included both the inhaled and part of the exhaled lung dose. Second, it is difficult to control the unintentional leak around the mask to be the same in different scenarios, thus we sealed the mask with the purpose to simplify the study model, but this did not accurately reflect the typical clinical conditions. In a recent study, Haw et al27 found that the incorporation of a mask leak in NIV changes the dynamics of aerosol delivery. Third, in our study, we found that, with the same pressure settings, was variable with different ventilators (V60 and Servo-s). Thus, inspiratory pressures with the two ventilators were adjusted to maintain the same
. In addition, expiratory positive airway pressure was set at 4 cm H2O, which might be lower than clinically common expiratory positive airway pressure settings, future studies with higher expiratory positive airway pressure settings are warranted. Also, the findings from the in vitro study should be validated in a clinical study.
Conclusions
There was no difference in the optimal aerosol delivery between single- and dual-limb circuits with a non-vented mask, and aerosol delivery was generally poor in the single-limb circuit with a vented mask. Humidification has little effect on aerosol delivery, except when a nebulizer was placed at the humidifier inlet in a dual-limb circuit during NIV.
Footnotes
- Correspondence: Jie Li PhD RRT RRT-NPS RRT-ACCS FAARC, Division of Respiratory Care, Department of Cardiopulmonary Sciences, Rush University, Chicago, Illinois 60612. E-mail: Jie_Li{at}rush.edu
Drs Tan and Dai are co-first authors.
Dr J Li discloses relationships with Fisher & Paykel Healthcare, Aerogen, the Rice Foundation, the American Association for Respiratory Care, and Hyer; she is Section Editor for Respiratory Care. The other authors have disclosed no conflicts of interest.
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