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Assessment of Respiratory System Resistance during High-Frequency Oscillatory Ventilation Based on In Vitro Experiment

Assessment of Respiratory System Resistance during High-Frequency Oscillatory Ventilation Based... applied sciences Article Assessment of Respiratory System Resistance during High-Frequency Oscillatory Ventilation Based on In Vitro Experiment Jan Matejka , Martin Rozanek * and Jakub Rafl Department of Biomedical Technology, Faculty of Biomedical Engineering, Czech Technical University in Prague, nam. Sitna 3105, 272 01 Kladno, Czech Republic; jan.matejka@fbmi.cvut.cz (J.M.); rafl@fbmi.cvut.cz (J.R.) * Correspondence: rozanek@fbmi.cvut.cz Abstract: High-frequency oscillatory ventilation (HFOV) is a type of mechanical ventilation with a protective potential characterized by a small tidal volume. Unfortunately, HFOV has limited monitoring of ventilation parameters and mechanical parameters of the respiratory system, which makes it difficult to adjust the continuous distension pressure (CDP) according to the individual patient’s airway status. Airway resistance R is one of the important parameters describing the aw mechanics of the respiratory system. The aim of the presented study was to verify in vitro whether the resistance of the respiratory system R can be reliably determined during HFOV to evaluate R rs aw in pediatric and adult patients. An experiment was performed with a 3100B high-frequency oscillator, a physical model of the respiratory system, and a pressure and flow measurement system. The physical model with different combinations of resistance and compliance was ventilated during the experiment. The resistance R was calculated from the impedance of the physical model, which was rs determined from the spectral density of the pressure at airway opening and the spectral cross-density Citation: Matejka, J.; Rozanek, M.; of the gas flow and pressure at airway opening. R of the model increased with an added resistor rs Rafl, J. Assessment of Respiratory and did not change significantly with a change in compliance. The method is feasible for monitoring System Resistance during respiratory system resistance during HFOV and has the potential to optimize CDP settings during High-Frequency Oscillatory Ventilation Based on In Vitro HFOV in clinical practice. Experiment. Appl. Sci. 2021, 11, 11279. https://doi.org/10.3390/ Keywords: high-frequency oscillatory ventilation; continuous distending pressure; respiratory app112311279 system resistance; rigid respiratory system model; forced oscillation technique Academic Editor: Thorsten Schwerte Received: 15 September 2021 1. Introduction Accepted: 23 November 2021 High-frequency oscillatory ventilation (HFOV) is one of the unconventional methods Published: 29 November 2021 of mechanical lung ventilation. It is characterized by a small tidal volume, approaching an anatomical dead space, with a protective potential [1]. Attenuation of pressure amplitude Publisher’s Note: MDPI stays neutral along the bronchial tree may contribute to less mechanical stress on lung tissue during with regard to jurisdictional claims in HFOV compared with conventional mechanical ventilation (CMV) [2]. The patients with published maps and institutional affil- severe acute respiratory distress syndrome (ARDS) that do not tolerate CMV may be the iations. target group for HFOV [3] if an alternative rescue therapy to ECMO is considered. With a number of etiologies and subtypes, ARDS is manifested by noncardiogenic pulmonary edema and hypoxia. Although new personalized pharmacological therapies for ARDS subtypes are being sought, also in the context of the COVID-19 pandemic, targeted treat- Copyright: © 2021 by the authors. ment is lacking and ARDS is still the leading cause of death in critically ill patients [4,5]. Licensee MDPI, Basel, Switzerland. Continuous distension pressure (CDP) and a set fraction of inspired oxygen determine the This article is an open access article oxygenation of the ventilated subject in HFOV. Carbon dioxide is eliminated from the lungs distributed under the terms and by pressure oscillations that are added to CDP [6]. Recently, there have been studies that conditions of the Creative Commons emphasize the need for an individualized approach in setting the ventilation parameters Attribution (CC BY) license (https:// of HFOV [7,8]. It has also been shown that other monitoring and computational methods, creativecommons.org/licenses/by/ including electrical impedance tomography (EIT) [9], optoelectronic plethysmography [10], 4.0/). Appl. Sci. 2021, 11, 11279. https://doi.org/10.3390/app112311279 https://www.mdpi.com/journal/applsci Appl. Sci. 2021, 11, 11279 2 of 8 or impedance analysis of the respiratory system [11], can lead to optimization of HFOV set- tings. The results of previous studies conducted with HFOV may have been influenced by settings that were not sufficiently individualized to the needs of individual patients [12,13]. Currently, there is no unified approach on how to properly set up CDP with respect to the respiratory status of individual patients. Airway resistance R is one of the important aw parameters describing the mechanics of the respiratory system. Besides tissue resistance, airway resistance R is a substantial part of respiratory system resistance R . Elevated R aw rs aw can lead to air trapping and hyperinflation, which can result in pulmonary barotrauma [14]. R depends on lung volume [15,16], which is directly related to the CDP value [17]. Both aw ventilation at low lung volumes (CDP is too low for the patient) and ventilation at high lung volumes (CDP is too high) lead to an increase in R . Moreover, the increase in resistance at aw low lung volumes is accompanied by a significant increase in peripheral resistance, which can account for 15% of R . The contribution of peripheral resistance to R is otherwise aw aw negligible [15]. However, the possibilities for monitoring ventilation parameters are small for HFOV. The high-frequency oscillatory ventilators 3100A and 3100B (Vyaire Medical, Mettawa, IL, USA) also lack monitoring of respiratory system mechanics, such as R . The aw 3100B ventilator, designed for adult patients, was used in this study. The forced oscillation technique (FOT) can be used to evaluate the mechanics of the respiratory system including total respiratory system resistance R [18,19]. In FOT, rs pressure oscillations with typical frequency f = 5 Hz are applied at the airway opening and R is assessed from the induced flow. Pressure oscillations at 5 Hz can penetrate the rs peripheral airways and detect changes in resistance in this region of the lung, allowing the assessment of R [18]. In a conventional FOT configuration, an external tool with rs an oscillator is used to generate high-frequency oscillations. The flow caused by the external oscillations is measured at the airway opening. However, some studies have demonstrated that a high-frequency ventilator itself can be used as a generator of the pressure oscillations utilized by FOT [20,21]. The studies used small animal models whose respiratory mechanics are consistent with neonatal patients. On the contrary, we have not found a study describing the use of the method in larger physical or animal models that correspond to pediatric or adult patients. Recently, FOT has been integrated into commercially available neonatal ventilator Fabian (Acutronic, Hirzel, Switzerland) to determine the reactance of the respiratory system of a neonatal patient. Studies described the usefulness of reactance analysis in ventilated [22] or spontaneously breathing neonatal patients [23]. In general, there is no information about the analysis of R in HFOV. As the method of assessing reactance of the rs respiratory system by FOT becomes clinically available, we suppose that monitoring of R might have similar clinical potential and could provide an early warning to elevated rs airway resistance. The aim of the presented study is to verify whether it is possible, under stable and well- defined laboratory conditions, to use pressure oscillations generated by the high-frequency oscillatory ventilator to determine the resistance of the respiratory system R from the rs measured proximal airway pressure and flow. We hypothesize that this method could be used to assess R at the bedside in neonatal, pediatric, and adult patients ventilated by aw HFOV similarly as reactance of the respiratory system. The presented method could be used also with ventilators 3100A and 3100B. 2. Materials and Methods The configuration of the experiment is shown in Figure 1 [24]. The high-frequency oscillatory ventilator 3100B with standard accessories was used for the experiment. The patient circuit was connected via an endotracheal tube to a model of the respiratory system that consisted of a glass demijohn. At one phase of the experiment, an Rp5 parabolic resistor (Michigan Instruments, Grand Rapids, MI, USA) was added to the circuit. The Rp5 simulated the increased resistance of the respiratory system and the glass demijohn simulated the compliance of the lungs. Measurements performed without and with Rp5 Appl. Sci. 2021, 11, x FOR PEER REVIEW 3 of 8 system that consisted of a glass demijohn. At one phase of the experiment, an Rp5 parabolic resistor (Michigan Instruments, Grand Rapids, MI, USA) was added to the Appl. Sci. 2021, 11, 11279 3 of 8 circuit. The Rp5 simulated the increased resistance of the respiratory system and the glass demijohn simulated the compliance of the lungs. Measurements performed without and with Rp5 were repeated for three glass demijohns of 54, 35, and 25 L. Values of wer corresp e repeated onding for com thrpee lianc glass es were demijohns 37, 24of , and 17 54, 35, m andL/25 cmH L.2O, respectively Values of corresponding [24]. The compliances following ve wer ntilat e 37, ion24, paand ramet 17emL/cmH rs were us O, edr in espectively the experiment [24]. The : bias following flow = ventilation 30 L/min, parameters were used in the experiment: bias flow = 30 L/min, ventilatory frequency ventilatory frequency f = 5 Hz, CDP = 12 cmH2O, and pressure oscillation amplitude ΔP = f = 5 Hz, CDP = 12 cmH O, and pressure oscillation amplitude DP = 20 cmH O. Inspiration 20 cmH2O. Inspiration to expiration time was set as I:E = 1:1. The ventilation parameters 2 2 to expiration time was set as I:E = 1:1. The ventilation parameters were set according to [25]. were set according to [25]. Pressure paw and flow qaw were recorded at the inlet of the model Pressure p and flow q were recorded at the inlet of the model of the respiratory system of the respiratory sy aw stem aw using a measurement system specifically designed for HFOV using a measurement system specifically designed for HFOV monitoring [26]. The flow monitoring [26]. The flow was calculated based on the pressure difference measured was calculated based on the pressure difference measured across an orifice. Both the signals across an orifice. Both the signals paw and qaw were recorded at a sampling frequency f = p and q were recorded at a sampling frequency f = 1000 Hz. aw aw 1000 Hz. Figure 1. Setup of in vitro experiment [24]. Figure 1. Setup of in vitro experiment [24]. The respiratory system resistance R measured at a pressure oscillation frequency of The respiratory system resistance R rs rs measured at a pressure oscillation frequency of f = 5 Hz was calculated from the respiratory system impedance Z following the spectral f = 5 Hz was calculated from the respiratory system impedance Z rsrs following the spectral density method described in [24]. R was obtained from Z by converting from polar to density method described in [24]. R rs rs was obtained from Zrs rs by converting from polar to Cartesian coordinates according to Equation (1): Cartesian coordinates according to Equation (1): 𝑅 =𝑍 ⋅𝑐𝑜𝑠𝑍 , (1) R = Z  cos Z , (1) rs mag ang where Zmag stands for the amplitude of the respiratory system impedance and Zang stands where Z stands for the amplitude of the respiratory system impedance and Z stands mag ang for the angle of the respiratory system impedance. for the angle of the respiratory system impedance. 3. Results 3. Results The measurements of Rrs in our experiment are summarized in Figure 2 and Table 1. The measurements of R in our experiment are summarized in Figure 2 and Table 1. rs Measurements 1–3 correspond to no added resistor and measurements 4–6 correspond to Measurements 1–3 correspond to no added resistor and measurements 4–6 correspond the phase of the experiment with the added resistor Rp. Three demijohns representing to the phase of the experiment with the added resistor Rp. Three demijohns represent- different compliances (37, 24, and 17 mL/cmH2O) were used in both phases of the ing different compliances (37, 24, and 17 mL/cmH O) were used in both phases of the experiment. The resistance R substantially increased by more than 100 cmH Os/L (over rs 220% increase) after the addition of the resistor to the model of the respiratory system (the change between Sections 3 and 4). The change in the compliance value did not have a substantial effect on the measured R values as the mean R did not differ for more than rs rs 4 cmH Os/L (less than 10%) when Rp remained unchanged. Appl. Sci. 2021, 11, x FOR PEER REVIEW 4 of 8 Appl. Sci. 2021, 11, x FOR PEER REVIEW 4 of 8 experiment. The resistance Rrs substantially increased by more than 100 cmH2O∙s/L (over 220% increase) after the addition of the resistor to the model of the respiratory system (the experiment. The resistance Rrs substantially increased by more than 100 cmH2O∙s/L (over change between Sections 3 and 4). The change in the compliance value did not have a 220% increase) after the addition of the resistor to the model of the respiratory system (the substantial effect on the measured Rrs values as the mean Rrs did not differ for more than change between Sections 3 and 4). The change in the compliance value did not have a 4 cmH2O∙s/L (less than 10%) when Rp remained unchanged. substantial effect on the measured Rrs values as the mean Rrs did not differ for more than Appl. Sci. 2021, 11, 11279 4 of 8 4 cmH2O∙s/L (less than 10%) when Rp remained unchanged. Rp = 5 cmH O∙s/L 120 140 Rp = 5 cmH O∙s/L 100 120 100 80 60 80 Rp = 0 cmH O∙s/L 40 60 Rp = 0 cmH O∙s/L Measurement (-) Figure 2. The computed Rrs during ventilation of the respiratory system model without an added Measurement (-) resistor (measurement sections 1, 2, and 3) and with added resistor Rp (measurement sections 4, 5, Figure 2. The computed Rrs during ventilation of the respiratory system model without an added Figure 2. The computed R during ventilation of the respiratory system model without an added rs and 6). To investigate the effect of compliance on the measured resistance of the respiratory system, resistor (measurement sections 1, 2, and 3) and with added resistor Rp (measurement sections 4, 5, resistor (measurement sections 1, 2, and 3) and with added resistor Rp (measurement sections 4, three glass demijohns with different compliance (37, 24, and 17 mL/cmH2O) were ventilated. and 6). To investigate the effect of compliance on the measured resistance of the respiratory system, 5, and 6). To investigate the effect of compliance on the measured resistance of the respiratory Negligible change in Rrs signal amplitude during measurement and a small change in Rrs when three glass demijohns with different compliance (37, 24, and 17 mL/cmH2O) were ventilated. system, three glass demijohns with different compliance (37, 24, and 17 mL/cmH O) were ventilated. compliance changed contrast with a large change in Rrs when the resistance 2 increased. Negligible change in Rrs signal amplitude during measurement and a small change in Rrs when Negligible change in R signal amplitude during measurement and a small change in R when rs rs compliance changed contrast with a large change in Rrs when the resistance increased. compliance changed contrast with a large change in R when the resistance increased. rs Table 1. Values of computed Rrs (cmH2O∙s/L) in both phases of the experiment (without/with the resistor) for glass demijohns of three different compliances C. Table 1. Values of computed Rrs (cmH2O∙s/L) in both phases of the experiment (without/with the Table 1. Values of computed R (cmH Os/L) in both phases of the experiment (without/with the rs resistor) for glass demijohns of three different compliances C. C Rrs with No Resistor Rrs with Resistor Rp5 resistor) for glass demijohns of three different compliances C. 1 1 (mL/cmH2O) Mean SD Mean SD C Rrs with No Resistor Rrs with Resistor Rp5 C R with No Resistor R with Resistor Rp5 rs rs 37 41.5 0.2 147.8 0.5 1 1 1 1 (mL/cmH2O) Mean SD Mean SD (mL/cmH O) Mean SD Mean SD 24 44.7 0.2 146.6 0.3 37 41.5 0.2 147.8 0.5 37 41.5 0.2 147.8 0.5 17 44.3 0.1 144.7 0.3 24 44.7 0.2 146.6 0.3 24 44.7 0.2 146.6 0.3 SD stands for standard deviation. 17 44.3 0.1 144.7 0.3 17 44.3 0.1 144.7 0.3 SD stands for standard deviation. SD stands for standard deviation. Figures 3 and 4 describe in more detail the measured signal of Rrs without and with Figures 3 and 4 describe in more detail the measured signal of R without and with the added resistor Rp5, respectively. It can be seen in the figure rs s that Rrs decreased over Figures 3 and 4 describe in more detail the measured signal of Rrs without and with the added resistor Rp5, respectively. It can be seen in the figures that R decreased over rs time. However, the decay of Rrs is negligible compared to the Rrs value. The decay over 40 the added resistor Rp5, respectively. It can be seen in the figures that Rrs decreased over time. However, the decay of R is negligible compared to the R value. The decay over 40 rs rs s, estimated from the linear interpolation of Rrs signals, was 3.8% of Rrs without the resistor time. However, the decay of Rrs is negligible compared to the Rrs value. The decay over 40 s, estimated from the linear interpolation of R signals, was 3.8% of R without the resistor rs rs and 1.8% with the resistor. s, est and 1.8% imatwith ed frthe om t resistor he line . ar interpolation of Rrs signals, was 3.8% of Rrs without the resistor and 1.8% with the resistor. 0 20 40 0 20 40 0 20 40 41 Relative Time (s) 0 20 40 0 20 40 0 20 40 Figure 3. The course of computed Rrs during ventilation of the respiratory system model without an Figure 3. The course of computed R during ventilation of the respiratory system model without rs Relative Time (s) added an added resist resistor or (three 40 (three 40 s l so long ng measurements measurements corr corre espond spond t to measur o measurement sections 1, 2 ement sections 1, 2, and, 3and 3 in Figure 3. The course of computed Rrs during ventilation of the respiratory system model without an Fi ingure 2). Figure Three gl 2). Three glass ass demi demijohns johns wi withth di differ ffent erent complia compliance nce (37, 24, a (37, 24, and 17 n mL/cmH d 17 mL/cm O) wer H2eO) were added resistor (three 40 s long measurements correspond to measurement sections 1, 2, and 3 in ventilated to investigate the effect of compliance on the measured resistance of the respiratory system. Figure 2). Three glass demijohns with different compliance (37, 24, and 17 mL/cmH2O) were Appl. Sci. 2021, 11, x FOR PEER REVIEW 5 of 8 Appl. Sci. 2021, 11, 11279 5 of 8 ventilated to investigate the effect of compliance on the measured resistance of the respiratory system. 0 20 40 0 20 40 0 20 40 Relative Time (s) Figure 4. The course of computed Rrs during ventilation of the respiratory system model with added Figure 4. The course of computed R during ventilation of the respiratory system model with rs resistor Rp5 (three 40 s long measurements correspond to measurement sections 4, 5, and 6 in Figure added resistor Rp5 (three 40 s long measurements correspond to measurement sections 4, 5, and 2). Three glass demijohns with different compliance (37, 24, and 17 mL/cmH2O) were ventilated to 6 in Figure 2). Three glass demijohns with different compliance (37, 24, and 17 mL/cmH O) were investigate the effect of compliance on the measured resistance of the respiratory system. ventilated to investigate the effect of compliance on the measured resistance of the respiratory system. It can also be seen from Figures 3 and 4 in detail that change of the compliance of the It can also be seen from Figures 3 and 4 in detail that change of the compliance of the respiratory system model does not affect substantially measured R . For a measurement rs respiratory system model does not affect substantially measured Rrs. For a measurement without an added resistor (Figure 3), a small increase in R of 3.2 cmH Os/L (7.7%) was rs 2 without an added resistor (Figure 3), a small increase in Rrs of 3.2 cmH2O∙s/L (7.7%) was observed with the change of compliance from 37 to 24 mL/cmH O and a very small change observed with the change of compliance from 37 to 24 mL/cmH2O and a very small change in R of about 0.4 cmH Os/L (1.0%) was observed with the change of compliance from 24 rs 2 in Rrs of about 0.4 cmH2O∙s/L (1.0%) was observed with the change of compliance from 24 to 17 mL/cmH O. A decrease in R about 1.2 cmH Os/L and 1.8 cmH Os/L (0.8% and rs 2 2 2 to 17 mL/cmH2O. A decrease in Rrs about 1.2 cmH2O∙s/L and 1.8 cmH2O∙s/L (0.8% and 1.3%, respectively) was observed for measurements with the resistor. 1.3%, respectively) was observed for measurements with the resistor. 4. Discussion The presented results show that changes in R can be monitored during HFOV by 4. Discussion aw measuring the resistance R at an oscillation frequency of 5 Hz, when the basic mechanical rs The presented results show that changes in Raw can be monitored during HFOV by properties of the respiratory system are consistent with larger animals or pediatric and measuring the resistance Rrs at an oscillation frequency of 5 Hz, when the basic mechanical adult patients. A physical model of the respiratory system was designed and an in vitro properties of the respiratory system are consistent with larger animals or pediatric and lab experiment was performed using different combinations of resistance and airway adult patients. A physical model of the respiratory system was designed and an in vitro compliance values. It was shown that R increases when R increases. The results of this rs aw lab exper in vitro study imealso nt was per suggest that formed us it is possible ing dif to f follow erent com the trb end inat ofions R of under resi conditions stance anof d airway aw changing lung compliance. compliance values. It was shown that Rrs increases when Raw increases. The results of this The low standard deviations of R summarized in Table 1 indicate sufficient robust- rs in vitro study also suggest that it is possible to follow the trend of Raw under conditions of ness of the algorithm used in signal processing. In Figures 3 and 4, small oscillations of the changing lung compliance. calculated R values can be seen. The oscillations are due to the processing of the noisy rs The low standard deviations of Rrs summarized in Table 1 indicate sufficient pressure and flow signals. The addition of a resistor to the ventilated system increased robustness of the algorithm used in signal processing. In Figures 3 and 4, small oscillations the standard deviation of R . The flow was more turbulent with the added resistor and rs of the calculated Rrs values can be seen. The oscillations are due to the processing of the this resulted in an increase in the noise in the flow signal [24]. However, the increased noisy pressure and flow signals. The addition of a resistor to the ventilated system turbulence did not degrade the evaluation of R . rs increOur ased the in vitr stand o study ard de has some viation o limitations. f Rrs. The fl First, aow wa single ventilatio s more tnufr rb equency ulent wi ofth the a 5 Hz dded was investigated. The choice of ventilation frequency as the most appropriate was based on resistor and this resulted in an increase in the noise in the flow signal [24]. However, the previous studies [18,19,24,27,28]. Second, we did not vary the CDP during the test, as this increased turbulence did not degrade the evaluation of Rrs. would be of little importance in a physical model with rigid walls. Animal studies [20,29,30], Our in vitro study has some limitations. First, a single ventilation frequency of 5 Hz which mimicked immature patients and used the same FOT measurement method, reported was investigated. The choice of ventilation frequency as the most appropriate was based a significant increase in R during lung derecruitment because of the low CDP applied rs on previous studies [18,19,24,27,28]. Second, we did not vary the CDP during the test, as during HFOV or the low positive end-expiratory pressure (PEEP) applied during CMV. this would be of little importance in a physical model with rigid walls. Animal studies The results are in agreement with the findings presented in [15], where the decrease in [20,29,30], which mimicked immature patients and used the same FOT measurement airway diameter was explained by a decrease in mean airway pressure. In contrast, only small changes in R are observed at CDP or PEEP values that are sufficient to maintain method, reported a significant increase in Rrs during lung derecruitment because of the rs lung inflation. This is consistent with our simulation performed on a rigid model. Third, low CDP applied during HFOV or the low positive end-expiratory pressure (PEEP) the results show that when the Rp5 resistor was added to the model, the measured R rs applied during CMV. The results are in agreement with the findings presented in [15], increased by more than 100 cmH Os/L on average, but the physical properties of the Rp5 where the decrease in airway diameter was explained by a decrease in mean airway pressure. In contrast, only small changes in Rrs are observed at CDP or PEEP values that are sufficient to maintain lung inflation. This is consistent with our simulation performed Appl. Sci. 2021, 11, 11279 6 of 8 resistor may have contributed to such a large increase in R . Resistor Rp5 is designed as rs parabolic, which means that the actual resistance value depends on gas flow rate. Moreover, the resistance of Rp5 is determined by its sudden and short decrease in airway diameter, a mechanism that is not present in vivo. The choke point created by the addition of Rp5 may cause the part of pressure-flow oscillation to be reflected into the glass demijohn and not return to the measuring system, resulting in an apparently more pronounced increase in resistance. It should also be taken into account that the physical properties of the glass demijohns used differ from the actual lungs. Pressure and flow oscillations could be deflected on the wall of the glass demijohn such that the oscillations could not return to the measuring system and would instead be damped within the glass demijohn. Such deflection does not occur in the airway tree in the lungs and could explain the difference between the actual resistance and the measured R . Finally, small changes in the shape of rs the patient circuit and endotracheal tube between measurements could also account for some of the inaccuracies in the calculation of R . rs The presented method of measuring R during HFOV is suitable for bedside patient rs monitoring because only a pressure and flow orifice is added to the patient circuit. In our study, a custom-made system consisting of an orifice, sensors, digitizing hardware, and a laptop with evaluation software was used [14]. In a real clinical scenario, any monitoring device capable of measuring proximal pressure and flow during HFOV and transmitting data in real time could be used. The disadvantage of the presented method may be the increased flow resistance and dead space caused by the addition of an orifice to the patient’s circuit. Assessment of respiratory mechanics using FOT in mechanical ventilators is now available to physicians with the Fabian neonatal ventilator [22,23]. However, the Fabian currently only determines the respiratory system reactance measured at an oscillation frequency of f = 10 Hz, which is typical for neonates. Besides the fact that in our study both parameters were measured at a frequency of f = 5 Hz, we believe that there is no significant difference between the method investigated in our study and the FOT method used by the Fabian ventilator. Therefore, no additional hardware would be required to simultaneously measure reactance and R at the patient’s bedside. Based on our study, we propose that rs not only reactance [24] but also R could be assessed during HFOV. rs 5. Conclusions In this study, for the first time, the feasibility of monitoring respiratory system resis- tance using the FOT method during HFOV under stable well-defined laboratory conditions was verified in a physical model whose properties correspond to a large laboratory animal. The FOT method used is simple enough to be applied at the patient’s bedside in clinical practice, requires no circuit disconnection, and can be used for long-term monitoring. Ventilator operators could have information on the resistance of the respiratory system, which could facilitate an early response to an increase in resistance and thus prevent pulmonary barotrauma. As the FOT method is already used in a commercially available neonatal ventilator to determine respiratory system reactance, simultaneous measurement of resistance could be readily available in clinical practice. Author Contributions: Conceptualization, M.R.; methodology, J.M.; software, J.M., J.R.; formal analy- sis, J.M.; investigation, M.R.; curation, J.M.; writing—original draft preparation, J.M.; writing—review and editing, M.R., J.R.; visualization, J.M.; supervision, M.R.; project administration, M.R.; funding acquisition, M.R. All authors have read and agreed to the published version of the manuscript. Funding: This work was supported by the project SGS19/202/OHK4/3T/17 and SGS20/202/ OHK4/3T/17. Data Availability Statement: The data presented in this study are available on request from the corresponding author. Conflicts of Interest: The authors declare no conflict of interest. Appl. Sci. 2021, 11, 11279 7 of 8 References 1. Meade, M.O.; Young, D.; Hanna, S.; Zhou, Q.; Bachman, T.E.; Bollen, C.; Slutsky, A.S.; Lamb, S.E.; Adhikari, N.K.; Mentzelopoulos, S.D.; et al. Severity of Hypoxemia and Effect of High-Frequency Oscillatory Ventilation in Acute Respiratory Distress Syndrome. Am. 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Lavizzari, A.; Veneroni, C.; Ottaviani, V.; Francesco, B.; Fumagalli, C.; Colnaghi, M.; Mosca, F.; Dellacà, R.L. Respiratory reactance (Xrs) by Forced Oscillation Technique (FOT) during the first 24h of life in non-intubated preterm infants. Eur. Respir. J. 2019, 54, PA1032. [CrossRef] 23. Zannin, E.; Dellacà, R.L.; Neumann, R.; Schulzke, S. Assessment of lung mechanics for the prediction and evaluation of pulmonary outcome in preterm infants. Eur. Respir. J. 2018, 52, OA306. [CrossRef] 24. Matejka, J.; Rozanek, M.; Rafl, J.; Kudrna, P.; Roubik, K. In Vitro Estimation of Relative Compliance during High-Frequency Oscillatory Ventilation. Appl. Sci. 2021, 11, 899. [CrossRef] Appl. Sci. 2021, 11, 11279 8 of 8 25. Fessler, H.E.; Derdak, S.; Ferguson, N.D.; Hager, D.N.; Kacmarek, R.M.; Thompson, B.T.; Brower, R.G. A protocol for high- frequency oscillatory ventilation in adults: Results from a roundtable discussion. Crit. Care Med. 2007, 35, 1649–1654. [CrossRef] 26. Roubik, K. 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Optimizing positive end-expiratory pressure by oscillatory mechanics minimizes tidal recruitment and distension: An experimental study in a lavage model of lung injury. Crit. Care 2012, 16, R217. [CrossRef] http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Applied Sciences Multidisciplinary Digital Publishing Institute

Assessment of Respiratory System Resistance during High-Frequency Oscillatory Ventilation Based on In Vitro Experiment

Applied Sciences , Volume 11 (23) – Nov 29, 2021

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applied sciences Article Assessment of Respiratory System Resistance during High-Frequency Oscillatory Ventilation Based on In Vitro Experiment Jan Matejka , Martin Rozanek * and Jakub Rafl Department of Biomedical Technology, Faculty of Biomedical Engineering, Czech Technical University in Prague, nam. Sitna 3105, 272 01 Kladno, Czech Republic; jan.matejka@fbmi.cvut.cz (J.M.); rafl@fbmi.cvut.cz (J.R.) * Correspondence: rozanek@fbmi.cvut.cz Abstract: High-frequency oscillatory ventilation (HFOV) is a type of mechanical ventilation with a protective potential characterized by a small tidal volume. Unfortunately, HFOV has limited monitoring of ventilation parameters and mechanical parameters of the respiratory system, which makes it difficult to adjust the continuous distension pressure (CDP) according to the individual patient’s airway status. Airway resistance R is one of the important parameters describing the aw mechanics of the respiratory system. The aim of the presented study was to verify in vitro whether the resistance of the respiratory system R can be reliably determined during HFOV to evaluate R rs aw in pediatric and adult patients. An experiment was performed with a 3100B high-frequency oscillator, a physical model of the respiratory system, and a pressure and flow measurement system. The physical model with different combinations of resistance and compliance was ventilated during the experiment. The resistance R was calculated from the impedance of the physical model, which was rs determined from the spectral density of the pressure at airway opening and the spectral cross-density Citation: Matejka, J.; Rozanek, M.; of the gas flow and pressure at airway opening. R of the model increased with an added resistor rs Rafl, J. Assessment of Respiratory and did not change significantly with a change in compliance. The method is feasible for monitoring System Resistance during respiratory system resistance during HFOV and has the potential to optimize CDP settings during High-Frequency Oscillatory Ventilation Based on In Vitro HFOV in clinical practice. Experiment. Appl. Sci. 2021, 11, 11279. https://doi.org/10.3390/ Keywords: high-frequency oscillatory ventilation; continuous distending pressure; respiratory app112311279 system resistance; rigid respiratory system model; forced oscillation technique Academic Editor: Thorsten Schwerte Received: 15 September 2021 1. Introduction Accepted: 23 November 2021 High-frequency oscillatory ventilation (HFOV) is one of the unconventional methods Published: 29 November 2021 of mechanical lung ventilation. It is characterized by a small tidal volume, approaching an anatomical dead space, with a protective potential [1]. Attenuation of pressure amplitude Publisher’s Note: MDPI stays neutral along the bronchial tree may contribute to less mechanical stress on lung tissue during with regard to jurisdictional claims in HFOV compared with conventional mechanical ventilation (CMV) [2]. The patients with published maps and institutional affil- severe acute respiratory distress syndrome (ARDS) that do not tolerate CMV may be the iations. target group for HFOV [3] if an alternative rescue therapy to ECMO is considered. With a number of etiologies and subtypes, ARDS is manifested by noncardiogenic pulmonary edema and hypoxia. Although new personalized pharmacological therapies for ARDS subtypes are being sought, also in the context of the COVID-19 pandemic, targeted treat- Copyright: © 2021 by the authors. ment is lacking and ARDS is still the leading cause of death in critically ill patients [4,5]. Licensee MDPI, Basel, Switzerland. Continuous distension pressure (CDP) and a set fraction of inspired oxygen determine the This article is an open access article oxygenation of the ventilated subject in HFOV. Carbon dioxide is eliminated from the lungs distributed under the terms and by pressure oscillations that are added to CDP [6]. Recently, there have been studies that conditions of the Creative Commons emphasize the need for an individualized approach in setting the ventilation parameters Attribution (CC BY) license (https:// of HFOV [7,8]. It has also been shown that other monitoring and computational methods, creativecommons.org/licenses/by/ including electrical impedance tomography (EIT) [9], optoelectronic plethysmography [10], 4.0/). Appl. Sci. 2021, 11, 11279. https://doi.org/10.3390/app112311279 https://www.mdpi.com/journal/applsci Appl. Sci. 2021, 11, 11279 2 of 8 or impedance analysis of the respiratory system [11], can lead to optimization of HFOV set- tings. The results of previous studies conducted with HFOV may have been influenced by settings that were not sufficiently individualized to the needs of individual patients [12,13]. Currently, there is no unified approach on how to properly set up CDP with respect to the respiratory status of individual patients. Airway resistance R is one of the important aw parameters describing the mechanics of the respiratory system. Besides tissue resistance, airway resistance R is a substantial part of respiratory system resistance R . Elevated R aw rs aw can lead to air trapping and hyperinflation, which can result in pulmonary barotrauma [14]. R depends on lung volume [15,16], which is directly related to the CDP value [17]. Both aw ventilation at low lung volumes (CDP is too low for the patient) and ventilation at high lung volumes (CDP is too high) lead to an increase in R . Moreover, the increase in resistance at aw low lung volumes is accompanied by a significant increase in peripheral resistance, which can account for 15% of R . The contribution of peripheral resistance to R is otherwise aw aw negligible [15]. However, the possibilities for monitoring ventilation parameters are small for HFOV. The high-frequency oscillatory ventilators 3100A and 3100B (Vyaire Medical, Mettawa, IL, USA) also lack monitoring of respiratory system mechanics, such as R . The aw 3100B ventilator, designed for adult patients, was used in this study. The forced oscillation technique (FOT) can be used to evaluate the mechanics of the respiratory system including total respiratory system resistance R [18,19]. In FOT, rs pressure oscillations with typical frequency f = 5 Hz are applied at the airway opening and R is assessed from the induced flow. Pressure oscillations at 5 Hz can penetrate the rs peripheral airways and detect changes in resistance in this region of the lung, allowing the assessment of R [18]. In a conventional FOT configuration, an external tool with rs an oscillator is used to generate high-frequency oscillations. The flow caused by the external oscillations is measured at the airway opening. However, some studies have demonstrated that a high-frequency ventilator itself can be used as a generator of the pressure oscillations utilized by FOT [20,21]. The studies used small animal models whose respiratory mechanics are consistent with neonatal patients. On the contrary, we have not found a study describing the use of the method in larger physical or animal models that correspond to pediatric or adult patients. Recently, FOT has been integrated into commercially available neonatal ventilator Fabian (Acutronic, Hirzel, Switzerland) to determine the reactance of the respiratory system of a neonatal patient. Studies described the usefulness of reactance analysis in ventilated [22] or spontaneously breathing neonatal patients [23]. In general, there is no information about the analysis of R in HFOV. As the method of assessing reactance of the rs respiratory system by FOT becomes clinically available, we suppose that monitoring of R might have similar clinical potential and could provide an early warning to elevated rs airway resistance. The aim of the presented study is to verify whether it is possible, under stable and well- defined laboratory conditions, to use pressure oscillations generated by the high-frequency oscillatory ventilator to determine the resistance of the respiratory system R from the rs measured proximal airway pressure and flow. We hypothesize that this method could be used to assess R at the bedside in neonatal, pediatric, and adult patients ventilated by aw HFOV similarly as reactance of the respiratory system. The presented method could be used also with ventilators 3100A and 3100B. 2. Materials and Methods The configuration of the experiment is shown in Figure 1 [24]. The high-frequency oscillatory ventilator 3100B with standard accessories was used for the experiment. The patient circuit was connected via an endotracheal tube to a model of the respiratory system that consisted of a glass demijohn. At one phase of the experiment, an Rp5 parabolic resistor (Michigan Instruments, Grand Rapids, MI, USA) was added to the circuit. The Rp5 simulated the increased resistance of the respiratory system and the glass demijohn simulated the compliance of the lungs. Measurements performed without and with Rp5 Appl. Sci. 2021, 11, x FOR PEER REVIEW 3 of 8 system that consisted of a glass demijohn. At one phase of the experiment, an Rp5 parabolic resistor (Michigan Instruments, Grand Rapids, MI, USA) was added to the Appl. Sci. 2021, 11, 11279 3 of 8 circuit. The Rp5 simulated the increased resistance of the respiratory system and the glass demijohn simulated the compliance of the lungs. Measurements performed without and with Rp5 were repeated for three glass demijohns of 54, 35, and 25 L. Values of wer corresp e repeated onding for com thrpee lianc glass es were demijohns 37, 24of , and 17 54, 35, m andL/25 cmH L.2O, respectively Values of corresponding [24]. The compliances following ve wer ntilat e 37, ion24, paand ramet 17emL/cmH rs were us O, edr in espectively the experiment [24]. The : bias following flow = ventilation 30 L/min, parameters were used in the experiment: bias flow = 30 L/min, ventilatory frequency ventilatory frequency f = 5 Hz, CDP = 12 cmH2O, and pressure oscillation amplitude ΔP = f = 5 Hz, CDP = 12 cmH O, and pressure oscillation amplitude DP = 20 cmH O. Inspiration 20 cmH2O. Inspiration to expiration time was set as I:E = 1:1. The ventilation parameters 2 2 to expiration time was set as I:E = 1:1. The ventilation parameters were set according to [25]. were set according to [25]. Pressure paw and flow qaw were recorded at the inlet of the model Pressure p and flow q were recorded at the inlet of the model of the respiratory system of the respiratory sy aw stem aw using a measurement system specifically designed for HFOV using a measurement system specifically designed for HFOV monitoring [26]. The flow monitoring [26]. The flow was calculated based on the pressure difference measured was calculated based on the pressure difference measured across an orifice. Both the signals across an orifice. Both the signals paw and qaw were recorded at a sampling frequency f = p and q were recorded at a sampling frequency f = 1000 Hz. aw aw 1000 Hz. Figure 1. Setup of in vitro experiment [24]. Figure 1. Setup of in vitro experiment [24]. The respiratory system resistance R measured at a pressure oscillation frequency of The respiratory system resistance R rs rs measured at a pressure oscillation frequency of f = 5 Hz was calculated from the respiratory system impedance Z following the spectral f = 5 Hz was calculated from the respiratory system impedance Z rsrs following the spectral density method described in [24]. R was obtained from Z by converting from polar to density method described in [24]. R rs rs was obtained from Zrs rs by converting from polar to Cartesian coordinates according to Equation (1): Cartesian coordinates according to Equation (1): 𝑅 =𝑍 ⋅𝑐𝑜𝑠𝑍 , (1) R = Z  cos Z , (1) rs mag ang where Zmag stands for the amplitude of the respiratory system impedance and Zang stands where Z stands for the amplitude of the respiratory system impedance and Z stands mag ang for the angle of the respiratory system impedance. for the angle of the respiratory system impedance. 3. Results 3. Results The measurements of Rrs in our experiment are summarized in Figure 2 and Table 1. The measurements of R in our experiment are summarized in Figure 2 and Table 1. rs Measurements 1–3 correspond to no added resistor and measurements 4–6 correspond to Measurements 1–3 correspond to no added resistor and measurements 4–6 correspond the phase of the experiment with the added resistor Rp. Three demijohns representing to the phase of the experiment with the added resistor Rp. Three demijohns represent- different compliances (37, 24, and 17 mL/cmH2O) were used in both phases of the ing different compliances (37, 24, and 17 mL/cmH O) were used in both phases of the experiment. The resistance R substantially increased by more than 100 cmH Os/L (over rs 220% increase) after the addition of the resistor to the model of the respiratory system (the change between Sections 3 and 4). The change in the compliance value did not have a substantial effect on the measured R values as the mean R did not differ for more than rs rs 4 cmH Os/L (less than 10%) when Rp remained unchanged. Appl. Sci. 2021, 11, x FOR PEER REVIEW 4 of 8 Appl. Sci. 2021, 11, x FOR PEER REVIEW 4 of 8 experiment. The resistance Rrs substantially increased by more than 100 cmH2O∙s/L (over 220% increase) after the addition of the resistor to the model of the respiratory system (the experiment. The resistance Rrs substantially increased by more than 100 cmH2O∙s/L (over change between Sections 3 and 4). The change in the compliance value did not have a 220% increase) after the addition of the resistor to the model of the respiratory system (the substantial effect on the measured Rrs values as the mean Rrs did not differ for more than change between Sections 3 and 4). The change in the compliance value did not have a 4 cmH2O∙s/L (less than 10%) when Rp remained unchanged. substantial effect on the measured Rrs values as the mean Rrs did not differ for more than Appl. Sci. 2021, 11, 11279 4 of 8 4 cmH2O∙s/L (less than 10%) when Rp remained unchanged. Rp = 5 cmH O∙s/L 120 140 Rp = 5 cmH O∙s/L 100 120 100 80 60 80 Rp = 0 cmH O∙s/L 40 60 Rp = 0 cmH O∙s/L Measurement (-) Figure 2. The computed Rrs during ventilation of the respiratory system model without an added Measurement (-) resistor (measurement sections 1, 2, and 3) and with added resistor Rp (measurement sections 4, 5, Figure 2. The computed Rrs during ventilation of the respiratory system model without an added Figure 2. The computed R during ventilation of the respiratory system model without an added rs and 6). To investigate the effect of compliance on the measured resistance of the respiratory system, resistor (measurement sections 1, 2, and 3) and with added resistor Rp (measurement sections 4, 5, resistor (measurement sections 1, 2, and 3) and with added resistor Rp (measurement sections 4, three glass demijohns with different compliance (37, 24, and 17 mL/cmH2O) were ventilated. and 6). To investigate the effect of compliance on the measured resistance of the respiratory system, 5, and 6). To investigate the effect of compliance on the measured resistance of the respiratory Negligible change in Rrs signal amplitude during measurement and a small change in Rrs when three glass demijohns with different compliance (37, 24, and 17 mL/cmH2O) were ventilated. system, three glass demijohns with different compliance (37, 24, and 17 mL/cmH O) were ventilated. compliance changed contrast with a large change in Rrs when the resistance 2 increased. Negligible change in Rrs signal amplitude during measurement and a small change in Rrs when Negligible change in R signal amplitude during measurement and a small change in R when rs rs compliance changed contrast with a large change in Rrs when the resistance increased. compliance changed contrast with a large change in R when the resistance increased. rs Table 1. Values of computed Rrs (cmH2O∙s/L) in both phases of the experiment (without/with the resistor) for glass demijohns of three different compliances C. Table 1. Values of computed Rrs (cmH2O∙s/L) in both phases of the experiment (without/with the Table 1. Values of computed R (cmH Os/L) in both phases of the experiment (without/with the rs resistor) for glass demijohns of three different compliances C. C Rrs with No Resistor Rrs with Resistor Rp5 resistor) for glass demijohns of three different compliances C. 1 1 (mL/cmH2O) Mean SD Mean SD C Rrs with No Resistor Rrs with Resistor Rp5 C R with No Resistor R with Resistor Rp5 rs rs 37 41.5 0.2 147.8 0.5 1 1 1 1 (mL/cmH2O) Mean SD Mean SD (mL/cmH O) Mean SD Mean SD 24 44.7 0.2 146.6 0.3 37 41.5 0.2 147.8 0.5 37 41.5 0.2 147.8 0.5 17 44.3 0.1 144.7 0.3 24 44.7 0.2 146.6 0.3 24 44.7 0.2 146.6 0.3 SD stands for standard deviation. 17 44.3 0.1 144.7 0.3 17 44.3 0.1 144.7 0.3 SD stands for standard deviation. SD stands for standard deviation. Figures 3 and 4 describe in more detail the measured signal of Rrs without and with Figures 3 and 4 describe in more detail the measured signal of R without and with the added resistor Rp5, respectively. It can be seen in the figure rs s that Rrs decreased over Figures 3 and 4 describe in more detail the measured signal of Rrs without and with the added resistor Rp5, respectively. It can be seen in the figures that R decreased over rs time. However, the decay of Rrs is negligible compared to the Rrs value. The decay over 40 the added resistor Rp5, respectively. It can be seen in the figures that Rrs decreased over time. However, the decay of R is negligible compared to the R value. The decay over 40 rs rs s, estimated from the linear interpolation of Rrs signals, was 3.8% of Rrs without the resistor time. However, the decay of Rrs is negligible compared to the Rrs value. The decay over 40 s, estimated from the linear interpolation of R signals, was 3.8% of R without the resistor rs rs and 1.8% with the resistor. s, est and 1.8% imatwith ed frthe om t resistor he line . ar interpolation of Rrs signals, was 3.8% of Rrs without the resistor and 1.8% with the resistor. 0 20 40 0 20 40 0 20 40 41 Relative Time (s) 0 20 40 0 20 40 0 20 40 Figure 3. The course of computed Rrs during ventilation of the respiratory system model without an Figure 3. The course of computed R during ventilation of the respiratory system model without rs Relative Time (s) added an added resist resistor or (three 40 (three 40 s l so long ng measurements measurements corr corre espond spond t to measur o measurement sections 1, 2 ement sections 1, 2, and, 3and 3 in Figure 3. The course of computed Rrs during ventilation of the respiratory system model without an Fi ingure 2). Figure Three gl 2). Three glass ass demi demijohns johns wi withth di differ ffent erent complia compliance nce (37, 24, a (37, 24, and 17 n mL/cmH d 17 mL/cm O) wer H2eO) were added resistor (three 40 s long measurements correspond to measurement sections 1, 2, and 3 in ventilated to investigate the effect of compliance on the measured resistance of the respiratory system. Figure 2). Three glass demijohns with different compliance (37, 24, and 17 mL/cmH2O) were Appl. Sci. 2021, 11, x FOR PEER REVIEW 5 of 8 Appl. Sci. 2021, 11, 11279 5 of 8 ventilated to investigate the effect of compliance on the measured resistance of the respiratory system. 0 20 40 0 20 40 0 20 40 Relative Time (s) Figure 4. The course of computed Rrs during ventilation of the respiratory system model with added Figure 4. The course of computed R during ventilation of the respiratory system model with rs resistor Rp5 (three 40 s long measurements correspond to measurement sections 4, 5, and 6 in Figure added resistor Rp5 (three 40 s long measurements correspond to measurement sections 4, 5, and 2). Three glass demijohns with different compliance (37, 24, and 17 mL/cmH2O) were ventilated to 6 in Figure 2). Three glass demijohns with different compliance (37, 24, and 17 mL/cmH O) were investigate the effect of compliance on the measured resistance of the respiratory system. ventilated to investigate the effect of compliance on the measured resistance of the respiratory system. It can also be seen from Figures 3 and 4 in detail that change of the compliance of the It can also be seen from Figures 3 and 4 in detail that change of the compliance of the respiratory system model does not affect substantially measured R . For a measurement rs respiratory system model does not affect substantially measured Rrs. For a measurement without an added resistor (Figure 3), a small increase in R of 3.2 cmH Os/L (7.7%) was rs 2 without an added resistor (Figure 3), a small increase in Rrs of 3.2 cmH2O∙s/L (7.7%) was observed with the change of compliance from 37 to 24 mL/cmH O and a very small change observed with the change of compliance from 37 to 24 mL/cmH2O and a very small change in R of about 0.4 cmH Os/L (1.0%) was observed with the change of compliance from 24 rs 2 in Rrs of about 0.4 cmH2O∙s/L (1.0%) was observed with the change of compliance from 24 to 17 mL/cmH O. A decrease in R about 1.2 cmH Os/L and 1.8 cmH Os/L (0.8% and rs 2 2 2 to 17 mL/cmH2O. A decrease in Rrs about 1.2 cmH2O∙s/L and 1.8 cmH2O∙s/L (0.8% and 1.3%, respectively) was observed for measurements with the resistor. 1.3%, respectively) was observed for measurements with the resistor. 4. Discussion The presented results show that changes in R can be monitored during HFOV by 4. Discussion aw measuring the resistance R at an oscillation frequency of 5 Hz, when the basic mechanical rs The presented results show that changes in Raw can be monitored during HFOV by properties of the respiratory system are consistent with larger animals or pediatric and measuring the resistance Rrs at an oscillation frequency of 5 Hz, when the basic mechanical adult patients. A physical model of the respiratory system was designed and an in vitro properties of the respiratory system are consistent with larger animals or pediatric and lab experiment was performed using different combinations of resistance and airway adult patients. A physical model of the respiratory system was designed and an in vitro compliance values. It was shown that R increases when R increases. The results of this rs aw lab exper in vitro study imealso nt was per suggest that formed us it is possible ing dif to f follow erent com the trb end inat ofions R of under resi conditions stance anof d airway aw changing lung compliance. compliance values. It was shown that Rrs increases when Raw increases. The results of this The low standard deviations of R summarized in Table 1 indicate sufficient robust- rs in vitro study also suggest that it is possible to follow the trend of Raw under conditions of ness of the algorithm used in signal processing. In Figures 3 and 4, small oscillations of the changing lung compliance. calculated R values can be seen. The oscillations are due to the processing of the noisy rs The low standard deviations of Rrs summarized in Table 1 indicate sufficient pressure and flow signals. The addition of a resistor to the ventilated system increased robustness of the algorithm used in signal processing. In Figures 3 and 4, small oscillations the standard deviation of R . The flow was more turbulent with the added resistor and rs of the calculated Rrs values can be seen. The oscillations are due to the processing of the this resulted in an increase in the noise in the flow signal [24]. However, the increased noisy pressure and flow signals. The addition of a resistor to the ventilated system turbulence did not degrade the evaluation of R . rs increOur ased the in vitr stand o study ard de has some viation o limitations. f Rrs. The fl First, aow wa single ventilatio s more tnufr rb equency ulent wi ofth the a 5 Hz dded was investigated. The choice of ventilation frequency as the most appropriate was based on resistor and this resulted in an increase in the noise in the flow signal [24]. However, the previous studies [18,19,24,27,28]. Second, we did not vary the CDP during the test, as this increased turbulence did not degrade the evaluation of Rrs. would be of little importance in a physical model with rigid walls. Animal studies [20,29,30], Our in vitro study has some limitations. First, a single ventilation frequency of 5 Hz which mimicked immature patients and used the same FOT measurement method, reported was investigated. The choice of ventilation frequency as the most appropriate was based a significant increase in R during lung derecruitment because of the low CDP applied rs on previous studies [18,19,24,27,28]. Second, we did not vary the CDP during the test, as during HFOV or the low positive end-expiratory pressure (PEEP) applied during CMV. this would be of little importance in a physical model with rigid walls. Animal studies The results are in agreement with the findings presented in [15], where the decrease in [20,29,30], which mimicked immature patients and used the same FOT measurement airway diameter was explained by a decrease in mean airway pressure. In contrast, only small changes in R are observed at CDP or PEEP values that are sufficient to maintain method, reported a significant increase in Rrs during lung derecruitment because of the rs lung inflation. This is consistent with our simulation performed on a rigid model. Third, low CDP applied during HFOV or the low positive end-expiratory pressure (PEEP) the results show that when the Rp5 resistor was added to the model, the measured R rs applied during CMV. The results are in agreement with the findings presented in [15], increased by more than 100 cmH Os/L on average, but the physical properties of the Rp5 where the decrease in airway diameter was explained by a decrease in mean airway pressure. In contrast, only small changes in Rrs are observed at CDP or PEEP values that are sufficient to maintain lung inflation. This is consistent with our simulation performed Appl. Sci. 2021, 11, 11279 6 of 8 resistor may have contributed to such a large increase in R . Resistor Rp5 is designed as rs parabolic, which means that the actual resistance value depends on gas flow rate. Moreover, the resistance of Rp5 is determined by its sudden and short decrease in airway diameter, a mechanism that is not present in vivo. The choke point created by the addition of Rp5 may cause the part of pressure-flow oscillation to be reflected into the glass demijohn and not return to the measuring system, resulting in an apparently more pronounced increase in resistance. It should also be taken into account that the physical properties of the glass demijohns used differ from the actual lungs. Pressure and flow oscillations could be deflected on the wall of the glass demijohn such that the oscillations could not return to the measuring system and would instead be damped within the glass demijohn. Such deflection does not occur in the airway tree in the lungs and could explain the difference between the actual resistance and the measured R . Finally, small changes in the shape of rs the patient circuit and endotracheal tube between measurements could also account for some of the inaccuracies in the calculation of R . rs The presented method of measuring R during HFOV is suitable for bedside patient rs monitoring because only a pressure and flow orifice is added to the patient circuit. In our study, a custom-made system consisting of an orifice, sensors, digitizing hardware, and a laptop with evaluation software was used [14]. In a real clinical scenario, any monitoring device capable of measuring proximal pressure and flow during HFOV and transmitting data in real time could be used. The disadvantage of the presented method may be the increased flow resistance and dead space caused by the addition of an orifice to the patient’s circuit. Assessment of respiratory mechanics using FOT in mechanical ventilators is now available to physicians with the Fabian neonatal ventilator [22,23]. However, the Fabian currently only determines the respiratory system reactance measured at an oscillation frequency of f = 10 Hz, which is typical for neonates. Besides the fact that in our study both parameters were measured at a frequency of f = 5 Hz, we believe that there is no significant difference between the method investigated in our study and the FOT method used by the Fabian ventilator. Therefore, no additional hardware would be required to simultaneously measure reactance and R at the patient’s bedside. Based on our study, we propose that rs not only reactance [24] but also R could be assessed during HFOV. rs 5. Conclusions In this study, for the first time, the feasibility of monitoring respiratory system resis- tance using the FOT method during HFOV under stable well-defined laboratory conditions was verified in a physical model whose properties correspond to a large laboratory animal. The FOT method used is simple enough to be applied at the patient’s bedside in clinical practice, requires no circuit disconnection, and can be used for long-term monitoring. Ventilator operators could have information on the resistance of the respiratory system, which could facilitate an early response to an increase in resistance and thus prevent pulmonary barotrauma. As the FOT method is already used in a commercially available neonatal ventilator to determine respiratory system reactance, simultaneous measurement of resistance could be readily available in clinical practice. 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Journal

Applied SciencesMultidisciplinary Digital Publishing Institute

Published: Nov 29, 2021

Keywords: high-frequency oscillatory ventilation; continuous distending pressure; respiratory system resistance; rigid respiratory system model; forced oscillation technique

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