Effect of respiratory filter resistance on respiratory mechanics and human-machine synchrony during invasive jet atomization: a prospective self-controlled study
Highlight box
Key findings
• Jet nebulization and the use of respiratory filters during invasive ventilation can lead to human-machine asynchrony events. Additionally, increased respiratory filter resistance could further exacerbate these asynchrony events.
What is known and what is new?
• Respiratory filters increase airway resistance and dead space volume, while jet nebulization introduces additional airflow that may interfere with ventilator triggering.
• Our study demonstrated that the application of jet nebulization and respiratory filters increases abnormal triggering and asynchrony index. Furthermore, increasing respiratory filter resistance exacerbates asynchrony events.
What is the implication, and what should change now?
• The potential risk caused by respiratory filters during jet nebulization necessitates intervention. The use of filters during nebulization should be carefully considered for patients with invasive ventilation. Additionally, the filters should be replaced promptly after nebulization.
Introduction
Respiratory filters are widely used in invasive mechanical ventilation to reduce microbial contamination and ventilator-associated pneumonia (VAP) risk (1). These filters, typically composed of electrostatic or pleated hydrophobic materials, are designed to prevent microorganisms such as bacteria and viruses from entering the breathing circuit. Due to their structural characteristics and physiochemical properties, prolonged use of breathing filters may lead to increased resistance and dead space volume in the breathing circuit (2). Moreover, the actual performance of breathing filters can be influenced by various factors, such as the closure of flow trigger function, clogging of filter pores by certain large molecule nebulization drugs, and wetness of pores and filter membranes, which may increase breathing filter resistance (3). Other factors outside the filter, such as the patient’s respiratory pathophysiological state and additional airflow introduced during jet nebulization, may further alter the performance of the breathing filter (4). These factors can result in prolonged expiratory time (Te) and increased respiratory work, leading to human-machine asynchrony and ventilator-associated lung injury, thereby causing harm to the patient.
Although a few studies have investigated the effects of breathing filters on certain mechanical ventilation parameters, research on the effects of different filter resistances on human-machine synchronization is limited. Additionally, there is a need for further investigation into the influence of breathing filters on respiratory mechanics during jet nebulization.
This study aims to address these gaps by simulating varying filter resistances through the addition of multiple filters to the expiratory circuit. By continuously monitoring key respiratory mechanics and human-machine synchronization indicators before and during nebulization, this study provides valuable insights for optimizing filter usage during mechanical ventilation with nebulization, ultimately improving patient care and safety. We present this article in accordance with the TREND reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2024-2131/rc).
Methods
Jet nebulization and the increasing resistance of the breathing filters may exacerbate human-machine asynchronicity. Thus, we conducted the study according to the following process to explore the question above.
This study is a single-center prospective self-controlled study that included 12 invasively mechanically ventilated patients admitted to the Department of Critical Care Medicine at the First Affiliated Hospital of Guangzhou Medical University from June 2022 to December 2022. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Ethics Committee of the First Affiliated Hospital of Guangzhou Medical University (Medical Research Ethics Review No. 2022-129), and all enrolled patients provided their informed consent.
Recruitment
All enrolled patients were screened by the clinician based on the following inclusion and exclusion criteria.
- Inclusion criteria: (I) patients who were 18 years old and were receiving invasive mechanical ventilation for more than 72 hours; (II) patients receiving at least one type of nebulization medication during mechanical ventilation; and (III) patients whose family members agreed to participate in the study and signed an informed consent form.
- Exclusion criteria: (I) patients with an acute risk of respiratory filter obstruction as judged by the attending physician (coughing up a large number of airway secretions); (II) patients with contraindications for indwelling integrated pressure monitoring gastric tubes (gastroesophageal lesions and deformities, severe gastric retention, and post-pyloric feeding); (III) patients who cannot tolerate jet nebulization or the use of respiratory filters; or (IV) patients with unstable vital signs.
- Withdrawal criteria: (I) severe intolerance or unstable vital signs at any stage during the experiment; (II) patient’s family members request to withdraw from the study.
Experiment and data collecting procedures
All experiment and data collecting procedures were conducted at the bedside of the patients and the patients underwent invasive mechanical ventilation with Dräger XL ventilator (provided by Dräger Medical Equipment Co., Ltd., Frankfurt, Germany). Patients were equipped with a pressure-monitoring gastric tube (No. CN307246718S), esophageal balloon, gastric balloon, and a Y-tube (Dräger breathing circuit, provided by Dräger Medical Equipment Co., Ltd., Frankfurt, Germany) connected to a pressure sensor (DP15-34-N-1-S-4-A, provided by Validyne Engineering Co., Ltd., Los Angeles, CA, USA) and a flow sensor (MLT 300L, provided by HANS RUDOLPH Co., Ltd., Boston, MA, USA). The three-channel pressure signals were amplified using a pressure amplifier (CD280-4C, provided by Validyne Engineering Co., Ltd.). Electromyography (EMG) signals were amplified and integrated into Powerlab 16/35 data acquisition device and Signal Conditioners (provided by At ADInstruments International Trading Co., Ltd., New South Wales, Australia), and data was acquired using LabChart 8.0 physiological data analysis software (provided by At ADInstruments International Trading Co., Ltd.). Patients were then positioned supine with a 30-degree head elevation. Once respiratory stability was achieved, respiratory rate, esophageal pressure (Pes), gastric pressure (Pga), inspiratory trigger delay, and diaphragmatic electrical activity, were recorded for 3 minutes using Labchart 8.0. Also, the transdiaphragmatic pressure (Pdi), esophageal pressure swing (ΔPes), human-machine asynchrony index (AI), abnormal trigger index, and other respiratory mechanics and human-machine asynchrony indicators were calculated in real time.
When the patient’s respiratory status was stable, respiratory mechanics data mentioned above would be collected and recorded. The data were categorized as the baseline group (Group 1).
Then, 5 mL of saline was then given through the built-in nebulization function of the ventilator to the enrolled patients for jet nebulization for 2 minutes. After the patient’s respiratory status was deemed stable, the above-mentioned data were collected again for another 3 minutes. The data obtained were divided into Group 2.
The nebulization was then stopped, and after the patient had rested and the respiratory condition was stabilized, a respiratory filter (Breathing filters PT020, provided by Fisher & Paykel Healthcare Limited, Auckland, New Zealand) was installed at the connection between the breathing circuit and the ventilator exhalation valve with the following specifications: compliance of 0.13 mL/cmH2O, compressible volume of 38 mL and flow resistance of 1.08 cmH2O at 45 LPM, and another 5 mL of saline was again used for jet nebulization, during which the above mechanical data and human-machine asynchrony indicators were recorded for 3 minutes. The data obtained were divided into Group 3.
The nebulization was then stopped again and after the patient had rested and the respiratory condition was deemed stable, two respiratory filters were installed at the connection between the breathing circuit and the ventilator exhalation valve, and the above nebulization and data recording process was repeated (see Figures 1,2 for a schematic diagram). The data obtained were divided into Group 4.
The acquired data were statistically analyzed according to the aforementioned groups (the experimental procedure flowchart can be seen in Figure 3).
Outcome
The primary outcomes were human-machine synchronization indicators including the number of abnormal triggers per minute and AI. The secondary outcomes were respiratory mechanics including inspiratory time (Ti), Te, respiratory cycle time (Ttot), the respiratory time ratio (Ti/Te), Pga, Pes, ΔPes, airway pressure (Paw), Pdi, ratio of esophageal pressure to transdiaphragmatic pressure (Pes/Pdi), the mean value of the airway pressure-time product obtained by the PEAK module in LabChart 8.0 (PeakArea), and diaphragmatic electromyogram (EMGdi), inspiratory trigger delay, pressure-time product (PTP), esophageal pressure-time product (PTPes), gastric pressure-time product (PTPga), transdiaphragmatic pressure-time product (PTPdi), ratio of ransdiaphragmatic pressure-time product to esophageal pressure-time product (PTPdi/PTPes), esophageal pressure coefficient variation (CVes), diaphragmatic electromyogram coefficient variation (CVEMG) and respiratory work.
The calculation formulas are as follows:
Statistical analysis
Categorical variables were described as mean ± standard deviation, while continuous variables were presented as medians with interquartile ranges. Given the small sample sizes, we adopted conservative non-parametric tests. The Kruskal-Wallis test was employed to compare the differences between groups, and the Benjamini & Hochberg method was used for post hoc comparisons. A P value <0.05 was considered statistically significant. All statistical analyses were conducted using R software (version 4.2.2, R Foundation, Vienna, Austria), utilizing the compareGroups package for comprehensive descriptive statistics and comparative analyses.
Results
General information
A total of 20 patients admitted to the intensive care unit (ICU) between June and December 2022 were screened, with 12 meeting the inclusion criteria and completing the study protocol without attrition. Their Acute Physiology and Chronic Health Evaluation II (APACHE II) score (5) at the time of admission to ICU was 22±5.53. The most common diagnosis (50%) was acute exacerbation of chronic obstructive pulmonary disease (AECOPD) (further demographic and clinical characteristics are summarized in Table 1).
Table 1
| Characteristics | Values |
|---|---|
| Age (years) | 66±9 |
| Females | 2 (16.67) |
| BMI (kg/m2) | 21.53±3.98 |
| APACHE II | 22.00±5.53 |
| SOFA | 8.33±4.19 |
| Hospitalization duration (days) | 35±10 |
| Duration of ICU stay (days) | 13 [10, 22] |
| Duration of invasive mechanical ventilation (days) | 10 [8, 16] |
| Primary diagnosis | |
| AECOPD | 6 (50.00) |
| Myocardial infarction | 1 (8.33) |
| Primary graft dysfunction after lung transplantation (POMES syndrome) | 1 (8.33) |
| Postoperative lung transplantation | 2 (16.67) |
| Postoperative cardiac valve surgery | 1 (8.33) |
| Postoperative aortic dissection | 1 (8.33) |
| Weaning success rate (%) | 100 |
| RR (breaths/min) | 18.35±5.88 |
| R [cmH2O/(L·s)] | 10.86±3.94 |
| Paw (cmH2O) | 61.00 [59.38, 63.00] |
| P0.1 (cmH2O) | −1.35±0.71 |
| PEEPi (cmH2O) | 6.20 [5.00, 9.13] |
| RSBI | 43.91±24.18 |
| Cre (mL/cmH2O) | 46.10 [40.85, 61.00] |
Data are presented as mean ± standard deviation, median [interquartile range] or n (%). AECOPD, acute exacerbation of chronic obstructive pulmonary disease; APACHE II, Acute Physiology and Chronic Health Evaluation II; BMI, body mass index; Cre, compliance of the respiratory system; ICU, intensive care unit; P0.1, mouth occlusion pressure at 0.1 s after onset of inspiratory effort; Paw, airway pressure; PEEPi, intrinsic positive end-expiratory pressure; POEMS, polyneuropathy, organomegaly, endocrinopathy, m-protein, and skin changes; R, respiratory system resistance; RR, respiration rate; RSBI, rapid shallow breathing index; SOFA, Sequential Organ Failure Assessment.
Major outcome
The abnormal triggers per minute became more frequent with increased resistance and the using of jet nebulization (P=0.01). The asynchrony index (P=0.01) and Ti/Te (P=0.02) increased with increased resistance and the using of jet nebulization as well (detailed data are presented in Table 2).
Table 2
| Respiratory mechanics | G1 (n=12) | G2 (n=12) | G3 (n=12) | G4 (n=12) | Poverall | PG1 vs. G2 | PG1 vs. G3 | PG1 vs. G4 | PG2 vs. G3 | PG2 vs. G4 | PG3 vs. G4 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| △Pes (cmH2O) | 2.80 [2.37, 4.67] | 2.86 [2.67, 5.39] | 3.30 [2.62, 3.81] | 3.59 [2.78, 5.38] | 0.90 | 0.95 | 0.95 | 0.95 | 0.95 | 0.95 | 0.95 |
| Inspiratory trigger delay (ms) | 162.00 [115.50, 223.50] | 210.00 [129.00, 265.50] | 303.00 [124.50, 340.00] | 294.67 [186.50, 380.00] | 0.08 | 0.48 | 0.21 | 0.13 | 0.41 | 0.21 | 0.62 |
| Abnormal triggers (breathes/min) | 0.50 [0.00, 1.00] | 2.00 [0.50, 2.00] | 2.00 [0.50, 2.63] | 3.00 [0.88, 4.50] | 0.01 | 0.07 | 0.07 | 0.04 | 0.44 | 0.07 | 0.19 |
| Asynchrony index (%) | 2.72 [0.00, 4.98] | 7.75 [2.54, 9.89] | 9.65 [2.97, 12.92] | 13.97 [8.48, 20.85] | 0.01 | 0.12 | 0.09 | 0.02 | 0.39 | 0.09 | 0.24 |
| Paw (cmH2O) | 13.40 (1.10) | 12.81 (0.83) | 13.09 (0.83) | 13.24 (0.91) | 0.46 | 0.41 | 0.85 | 0.97 | 0.88 | 0.67 | 0.98 |
| Pes (cmH2O) | 9.60 [7.10, 10.69] | 11.45 [7.32, 14.05] | 10.91 [7.25, 15.11] | 10.04 [6.54, 18.36] | 0.83 | >0.99 | >0.99 | >0.99 | >0.99 | >0.99 | >0.99 |
| Pga (cmH2O) | 16.26 [8.26, 19.13] | 9.96 [5.83, 18.59] | 7.62 [4.56, 15.14] | 9.25 [6.78, 14.96] | 0.35 | 0.52 | 0.52 | 0.52 | 0.52 | 0.52 | 0.60 |
| Pdi (cmH2O) | 5.11 (6.96) | −0.62 (11.24) | −0.96 (10.06) | −1.48 (11.19) | 0.34 | 0.51 | 0.46 | 0.38 | >0.99 | >0.99 | >0.99 |
| PeakArea (cmH2O·s) | 9.08 [7.35, 11.55] | 9.37 [8.32, 11.27] | 9.75 [8.45, 11.18] | 10.11 [9.49, 10.82] | 0.91 | 0.95 | 0.95 | 0.95 | >0.99 | 0.95 | 0.95 |
| PTP (cmH2O·s/min) | 16.43 [14.45, 18.25] | 16.72 [13.36, 18.76] | 18.14 [13.94, 19.93] | 15.64 [14.28, 18.76] | 0.96 | 0.95 | 0.95 | 0.95 | 0.95 | 0.95 | 0.95 |
| PTPes (cmH2O·s/min) | 11.75 [5.70, 15.45] | 17.93 [9.06, 21.04] | 14.79 [10.64, 19.52] | 15.68 [8.85, 21.08] | 0.59 | 0.71 | 0.71 | 0.71 | 0.77 | 0.77 | 0.77 |
| PTPga (cmH2O·s/min) | 18.12 [7.70, 25.04] | 15.57 [7.84, 24.42] | 9.69 [6.78, 20.26] | 12.37 [10.47, 18.34] | 0.66 | 0.82 | 0.82 | 0.82 | 0.82 | 0.82 | 0.82 |
| PTPdi (cmH2O·s/min) | 4.74 [1.01, 8.94] | −2.45 [−7.49, 7.28] | −5.64 [−9.13, 6.32] | −3.03 [−12.17, 6.41] | 0.27 | 0.33 | 0.33 | 0.33 | 0.86 | 0.86 | 0.86 |
| EMGdi (μV) | 0.02 [0.02, 0.05] | 0.03 [0.02, 0.04] | 0.03 [0.02, 0.07] | 0.03 [0.02, 0.06] | 0.91 | 0.82 | 0.82 | 0.82 | 0.82 | 0.98 | 0.82 |
| CVes (%) | 5.86 [3.53, 7.77] | 7.15 [4.55, 13.23] | 5.32 [3.02, 9.46] | 5.71 [2.97, 8.61] | 0.82 | 0.91 | >0.99 | >0.99 | 0.91 | 0.91 | >0.99 |
| CVEMG (%) | 6.63 [4.69, 17.25] | 11.83 [3.75, 25.84] | 11.11 [4.93, 16.99] | 8.17 [3.76, 13.98] | 0.92 | 0.95 | 0.95 | 0.95 | 0.95 | 0.95 | 0.95 |
| Ti (s) | 1.25 [1.05, 1.35] | 1.35 [1.06, 1.48] | 1.40 [1.14, 1.57] | 1.17 [1.13, 1.48] | 0.78 | 0.86 | 0.86 | 0.86 | 0.86 | 0.86 | 0.86 |
| Te (s) | 2.40 [1.54, 3.08] | 1.32 [0.92, 1.68] | 1.70 [0.97, 2.14] | 1.63 [1.03, 2.08] | 0.13 | 0.10 | 0.33 | 0.33 | 0.63 | 0.56 | 0.89 |
| Ti/Te (%) | 49.57 [40.99, 69.69] | 77.27 [70.42, 148.49] | 80.90 [54.99, 129.97] | 76.26 [57.72, 102.11] | 0.02 | 0.02 | 0.054 | 0.15 | 0.64 | 0.51 | 0.64 |
| Ttot (s) | 3.38 [2.75, 4.42] | 2.45 [2.33, 2.86] | 2.64 [2.26, 3.63] | 2.79 [2.25, 3.46] | 0.17 | 0.15 | 0.28 | 0.41 | 0.93 | 0.76 | >0.99 |
| RR (breaths/min) | 20.57 [16.02, 23.68] | 22.80 [18.78, 24.25] | 24.65 [18.39, 26.37] | 21.32 [18.21, 24.28] | 0.44 | 0.52 | 0.52 | 0.52 | 0.52 | 0.84 | 0.52 |
| PTPdi/PTPes | 0.30 [0.08, 0.93] | −0.14 [−0.57, 0.67] | −0.28 [−0.65, 0.74] | −0.16 [−0.51, 0.78] | 0.36 | 0.45 | 0.45 | 0.45 | 0.82 | 0.91 | 0.82 |
| Pes/Pdi | 1.43 [0.43, 3.37] | −1.55 [−1.88, 0.57] | −1.31 [−2.07, 0.22] | −0.80 [−1.91, 0.65] | 0.051 | 0.09 | 0.07 | 0.09 | 0.91 | 0.91 | 0.79 |
| Respiratory work (kJ) | 175.81 [147.39, 207.84] | 201.46 [189.35, 212.97] | 220.48 [178.18, 273.50] | 200.52 [179.51, 233.52] | 0.40 | 0.45 | 0.45 | 0.45 | 0.89 | 0.89 | 0.89 |
Data are presented as mean (standard deviation) or median [interquartile range]. G1, G2, G3, and G4 represent baseline data, nebulization without filter data, nebulization with one filter data, and nebulization with two filters respectively. CVEMG, diaphragmatic electromyogram coefficient variation; CVes, esophageal pressure coefficient variation; ΔPes, esophageal pressure swings; EMGdi, diaphragmatic electromyogram; Paw, airway pressure; Pdi, transdiaphragmatic pressure; PeakArea, the mean value of the airway pressure-time product obtained by the PEAK module in LabChart 8.0; Pes, esophageal pressure; Pga, gastric pressure; PTP, pressure-time product; PTPdi, transdiaphragmatic pressure-time product; PTPes, esophageal pressure-time product; PTPga, gastric pressure-time product; RR, respiration rate; Te, expiratory time; Ti, inspiratory time; Ttot, respiratory cycle time.
Secondary outcome
There were no significant differences in all secondary indicators but some trends could still be observed. The ΔPes (P=0.90) and PeakArea (P=0.91) increased with increased resistance and the using of jet nebulization while the Pes/Pdi shifted to negative values with increased resistance and the using of jet nebulization although no significant difference was observed (P=0.051) (detailed data are presented in Table 2).
Discussion
This study found that using nebulization and respiratory filters increased the frequency of abnormal triggers and human-machine asynchrony compared to baseline conditions. These two indicators had statistical differences compared to the baseline group when patients used both nebulization and two respiratory filters (with higher resistance). Secondary indicators showed that patients using nebulization and respiratory filters had a higher median Ti/Te than the baseline group, indicating that the increase in resistance due to nebulization and respiratory filters significantly prolonged the Ti/Te in the respiratory cycle, increasing the occurrence of human-machine asynchrony events. The mechanism may be related to the increased filter resistance caused by nebulization: Turnbull et al. (6) found that respiratory filter resistance can increase by 70–480% under humid conditions, such as those encountered during nebulization. Cann et al. (7) studied 23 different filter types and found median water breakthrough pressures of 1.18 kPa (≈12 cmH2O) for electrostatic filters and 8.04 kPa (≈82 cmH2O) for pleated filters. Our previous study also demonstrated that larger molecular nebulized drugs (such as interferon-alpha and amphotericin B) can block filter membranes, further increasing resistance.
In addition to the increased filter resistance, other factors contribute to human-machine asynchrony in patients. Due to the thermal insulation and moisture retention of respiratory filters, condensation tends to accumulate in the circuit and fluctuates with the airflow. Jet nebulization requires high-speed airflow (up to 15 L/min), which can exacerbate turbulence through high-resistance filters. These factors can cause abnormal fluctuations in flow and pressure, increasing false triggering. It is worth noting that although other respiratory mechanics indicators monitored in this study, such as ΔPes values, respiratory work, and transdiaphragmatic pressure, did not show significant differences, the median values of these indicators in patients under nebulization and respiratory filters were higher than the baseline level (transdiaphragmatic pressure showed the opposite direction of the baseline group), which may imply a significant increase in respiratory effort in patients. The impact of using filters during nebulization on lung protective ventilation strategies warrants further exploration.
There has been controversy over routine filter use in mechanically ventilated patients. The Association of Anaesthetists of Great Britain and Ireland (AAGBI) recommends placing appropriate filters between the patient and the respiratory system (8), while the American Society of Anesthesiologists (ASA) (9) and the American Centers for Disease Control and Prevention (CDC) (10) do not recommend using bacterial filters in patient breathing circuits or anesthesia equipment. In addition, there is a lack of consensus on when to replace or remove filters for patients who already have respiratory filters installed. Branson (11) suggests weekly replacement, while Boyer et al. (12) recommend replacing them after 48 hours. Our study suggests cautious filter use during nebulization, with removal or replacement as soon as possible after completing nebulization treatment to mitigate human-machine asynchrony risk.
Limitations
There are several limitations in this study. First, the sample size is relatively small, and half of the included patients had a concurrent diagnosis of chronic obstructive pulmonary disease (COPD). For these patients, the human-machine asynchrony caused by nebulization combined with respiratory filters may be more significant. Further expansion of the sample size and inclusion of patients with more diverse diseases are needed in future studies. Additionally, in this study, we only used saline for nebulization and did not involve nebulized medications with larger molecular weights, which may have underestimated the actual impact of nebulization combined with respiratory filters on human-machine asynchrony and exhalation difficulties in patients.
Conclusions
This study confirms that the simultaneous use of nebulization and respiratory filters, as well as increased resistance in respiratory filters, increases the occurrence of human-machine asynchrony events and may lead to an enhancement of patients’ respiratory drive. This suggests that there are certain risks associated with the use of respiratory filters during jet nebulization, and clinicians need to pay attention to the quality and safety of mechanical ventilation treatment.
Acknowledgments
We thank LetPub (www.letpub.com.cn) for its linguistic assistance during the preparation of this manuscript.
Footnote
Reporting Checklist: The authors have completed the TREND reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2024-2131/rc
Data Sharing Statement: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2024-2131/dss
Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2024-2131/prf
Funding: This study was supported by
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2024-2131/coif). The authors have no conflicts of interest to declare.
Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Ethics Committee of the First Affiliated Hospital of Guangzhou Medical University (Medical Research Ethics Review No. 2022-129), and all enrolled patients provided their informed consent.
Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.
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