Research ArticleOriginal Research

Effects of Mechanical Insufflation-Exsufflation With Different Pressure Settings on Respiratory Mucus Displacement During Invasive Ventilation

Joan-Daniel Martí, Roberto Martínez-Alejos, Xabier Pilar-Diaz, Hua Yang, Francesco Pagliara, Denise Battaglini, Andrea Meli, Milan Yang, Joaquim Bobi, Monsterrat Rigol, Oystein Tronstad, Marcia Souza Volpe, Marcelo Britto Passos Amato, Gianluigi Li Bassi and Antoni Torres
Respiratory Care December 2022, 67 (12) 1508-1516; DOI: https://doi.org/10.4187/respcare.10173

Abstract

BACKGROUND: Mechanical insufflation-exsufflation (MI-E) has been proposed as a potential strategy to generate high expiratory flows and simulate cough in the critically ill. However, efficacy and safety of MI-E during invasive mechanical ventilation are still to be fully elucidated. This study in intubated and mechanically ventilated pigs aimed to evaluate the effects of 8 combinations of insufflation-exsufflation pressures during MI-E on mucus displacement, respiratory flows, as well as respiratory mechanics and hemodynamics.

METHODS: Six healthy Landrace-Large White female pigs were orotracheally intubated, anesthetized, and invasively ventilated for up to 72 h. Eight combinations of insufflation-exsufflation pressures (+40/−40, +40/−50, +40/−60, +40/−70, +50/−40, +50/−50, +50/−60, +50/−70 cm H2O) were applied in a randomized order. The MI-E device was set to automatic mode, medium inspiratory flow, and an inspiratory-expiratory time 3 and 2 s, respectively, with a 1-s pause between cycles. We performed 4 series of 5 insufflation-exsufflation cycles for each combination of pressures. Velocity and direction of movement of a mucus simulant containing radio-opaque markers were assessed through sequential lateral fluoroscopic images of the trachea. We also evaluated respiratory flows, respiratory mechanics, and hemodynamics before, during, and after each combination of pressures.

RESULTS: In 3 of the animals, experiments were conducted twice; and for the remaining 3, they were conducted once. In comparison to baseline mucus movement (2.85 ± 2.06 mm/min), all insufflation-exsufflation pressure combinations significantly increased mucus velocity (P = .01). Particularly, +40/−70 cm H2O was the most effective combination, increasing mucus movement velocity by up to 4.8-fold (P < .001). Insufflation pressure of +50 cm H2O resulted in higher peak inspiratory flows (P = .004) and inspiratory transpulmonary pressure (P < .001) than +40 cm H2O.

CONCLUSIONS: MI-E appeared to be an efficient strategy to improve mucus displacement during invasive ventilation, particularly when set at +40/−70 cm H2O. No safety concerns were identified although a transient significant increase of transpulmonary pressure was observed.

Introduction

Ineffective cough and/or mucociliary clearance impairment is highly prevalent in patients receiving invasive mechanical ventilation,1-2 resulting in retention of airway secretions, increased work of breathing, lung collapse, and pulmonary infections.3-5 Physiotherapy and airway clearance techniques are commonly implemented for these patients to maintain airway patency and improve morbidity.6-7 However, the efficacy and safety of several physiotherapy techniques used during invasive ventilation are yet to be fully elucidated.

Mechanical insufflation-exsufflation (MI-E) is a noninvasive technique aimed to improve clearance of proximal airway secretions.8 The technique is implemented through a dedicated electromechanical device that gradually applies positive pressure to hyperinflate the lungs, before rapidly shifting to a negative pressure that creates high expiratory flows simulating a cough. MI-E has been associated with encouraging outcomes in patients with respiratory pump failure (ie, neuromuscular diseases),9,10 with +40/−40 cm H2O described and recommended as the most comfortable and effective insufflation-exsufflation pressures.11 However, higher pressures may be necessary in patients with pathologies involving increased respiratory resistance or decreased compliance.12 Additionally, in critically ill patients receiving invasive ventilation, the endotracheal tube (ETT) or tracheostomy tube may impact the delivery of insufflation-exsufflation pressures by substantially increasing resistance to air flow.13

To date, only a few studies14-18 have evaluated efficacy and/or safety of MI-E in critically ill patients receiving invasive ventilation, with these studies reporting promising results. However, extrapolation of published results is limited by use of surrogate measures to assess mucus clearance (eg, volume/weight of mucus) and heterogeneity in pressure settings used during MI-E. Therefore, considering the lack of robust evidence and limitations of previous studies, we designed this experimental animal study to objectively evaluate the effects of different pressure combinations of MI-E on mucus displacement and respiratory flows and safety of using MI-E during invasive ventilation.

QUICK LOOK

Current Knowledge

Invasive mechanically ventilated patients often present with airway secretion retention and ineffective cough. In this context, mechanical insufflation-exsufflation (MI-E) is a medical device that propels retained airway secretions similar to a simulated cough and has been recently suggested as a potential strategy to clear airway secretions in mechanically ventilated patients. However, extrapolation of published results is limited by heterogeneity in pressure settings used during MI-E.

What This Paper Contributes to Our Knowledge

In this experimental randomized clinical trial in mechanically ventilated pigs, mechanical insufflation-exsufflation set at +40/−70 cm H2O led to a greater displacement of secretions. No safety concerns were identified although a transient significant increase of transpulmonary pressure was observed when insufflation pressure was set at +50 cm H2O.

Methods

This study was conducted at the animal research laboratories of University of Barcelona, Spain, after approval by the Hospital Clinic and University of Barcelona Animal Care and Use Committee (2013/8069). Animals were managed according to National Institutes of Health guidelines for use and care of animals.19

We evaluated effects of 8 different combinations of insufflation-exsufflation pressures (+40/−40, +40/−50, +40/−60, +40/−70, and +50/−40, +50/−50, +50/−60, +50/−70 cm H2O) on artificial mucus displacement. The study was performed on healthy pigs receiving invasive ventilation for up to 72 h included in a concomitant experimental investigation. The order of delivered insufflation-exsufflation pressures was randomized. We also assessed air flows, respiratory mechanics, and hemodynamics.

Animal Preparation

Large White-Landrace pigs were orotracheally intubated with a 7.5 mm internal diameter Hi-Lo ETT (Mallinckrodt, Dublin, Ireland) and ventilated by a Servo-i mechanical ventilator (Getinge, Solna, Sweden). Ventilatory parameters were initially set as follows: volume control mode, tidal volume (VT): 8 mL/kg; pressure trigger sensitivity: −2 cm H2O; FIO2: 0.4; duty cycle: 0.33; inspiratory rise time: 5%; inspiratory pause: 10%; PEEP: 3 cm H2O; and breathing frequency adjusted to maintain normocapnia. The animals were placed in horizontal position; inspiratory gases were conditioned through a heated humidifier, and internal ETT cuff pressure was continuously maintained at 28 cm H2O. Midazolam and fentanyl were administered as previously reported.20 We surgically cannulated the femoral artery for systemic arterial pressure monitoring and collection of blood samples.

Secretion Simulant

We used an iso-osmotic 2% polyethylene oxide polymer (Polyox, Union Carbide, Houston, Texas) in a solution of 133 mL phosphate-buffered saline solution and 33 mL radiologic contrast (Visipaque, GE Healthcare, Madison, Wisconsin) to simulate bronchial secretions. Five tantalum disks were introduced into the solution and homogenously distributed through gentle shaking. The weight of each tantalum disk was 0.8 mg, and thickness and diameter were 0.1 mm and 0.6 mm, respectively. Polyethylene oxide polymer solution has been commonly used in previous in vitro21-23 and in vivo24 studies to simulate bronchial secretions.

Mechanical Insufflation-Exsufflation

Prior to commencement of the study, FIO2 was increased to 1.0; administered doses of midazolam and fentanyl were increased by 20%, and lack of cough reflex was confirmed. Tracheal suctioning was performed (following international guidelines25) 1 h before start of protocol and after each intervention to ensure elimination of natural and simulant mucus within airways. Before each experiment, internal cuff pressure was increased beyond randomized inspiratory pressure to avoid air leaks (ie, 40 or 50 cm H2O). Then, the animal was disconnected from ventilator, and 4 mL of mucus simulant containing 5 tantalum disks were instilled through a 12-Fr suction catheter on the ventral (dependent) part of the trachea. The suction catheter was marked to ensure the mucus simulant was always deposited at same distance from the carina. MI-E was delivered by CoughAssist E70 device (Philips, Amsterdam, the Netherlands) set to automatic mode, medium inspiratory flow, with insufflation-exsufflation time of 3 and 2 s, respectively, and a 1-s pause (total time of 30 s per set). Insufflation-exsufflation pressures were set at +40/−40, +40/−50, +40/−60, +40/−70, and +50/−40, +50/−50, +50/−60, and +50/−70 cm H2O in a randomized fashion. Four sets of 5 insufflation-exsufflation cycles were applied for each combination of pressures before the animals were quickly reconnected to ventilator. A period of 30 s of invasive ventilation was applied between sets and a 15-min washout period between each combination of pressures (Fig. 1).

Fig. 1.
Fig. 1.

Study protocol. A physiotherapist randomly and consecutively applied a 5-min treatment of 8 different combinations of insufflation-exsufflation pressures (+40/−40, +40/−50, +40/−60, +40/−70, +50/−40, +50/−50, +50/−60, +50/−70 cm H2O). Fluoroscopic images to track artificial mucus movement were obtained 5 min before beginning of intervention and after each set of 5 insufflation-exsufflations. A 15-min period was allowed between interventions. MI-E = mechanical insufflation-exsufflation.

Tracheal Mucus Velocity

Tracheal mucus velocity was assessed through fluoroscopic images of the lateral trachea to track radio-opaque tantalum disks placed into the trachea as previously reported.20 Fluoroscopic images were obtained 5 min before interventions to establish baseline movement of mucus simulant and immediately after each cycle of MI-E (Fig. 1). Measurement of tracheal mucus velocities was made and averaged by 2 independent observers blinded to treatment applied. The direction of movement of each tantalum disk was described by a positive vector (toward the glottis) or negative vector (toward the lungs) (Fig. 2).

Fig. 2.
Fig. 2.

Artificial mucus tracking. Fluoroscopic image taken at beginning of an MI-E set shows 4 tantalum disks, readily visible within artificial secretions on dependent part of trachea (A). Fluoroscopic image taken at end of the same MI-E set shows outward movement of disks, displaced between point 1 and 2 (B). ETT = endotracheal tube.

Respiratory and Hemodynamic Measurements

Respiratory flows, airway pressures, and esophageal pressure were measured before, during, and after application of MI-E (Fig. 1) as described earlier.19 Flow and pressure signals were recorded for subsequent analysis with dedicated software (Colligo, Elekton, Milan, Italy). We measured mean inspiratory flow (MIF), mean expiratory flow (MEF) from beginning of expiration up to zero flow, peak inspiratory flow (PIF), and peak expiratory flow (PEF). PEF-MIF and MEF-MIF differences were also calculated. Static chest wall and lung elastances, inspiratory air flow resistances, and additional inspiratory tissue resistances were computed as previously reported.20 Heart rate and arterial blood pressure were assessed and recorded prior, during, and after each combination of insufflation-exsufflation pressures (Fig. 1).

Statistical Analysis

Continuous variables were described as means and SD, unless otherwise specified. Air flow and airway pressures were analyzed using a restricted maximum likelihood (REML) analysis, comprising MI-E settings as repeated interventions. Heart rate and mean arterial pressure were monitored before, during, and after MI-E intervention; hence, we used a modified REML analysis based on a repeated measures approach, including MI-E settings, times of assessment, and their interaction as factors. As for variables assessed before and after MI-E, that is elastance and inspiratory resistances, δ parameters were computed as difference between values prior to and after intervention. A compound symmetry (co)variance structure was used to model within-patient errors and Kenward-Roger or between-within approximations to estimate denominator degrees of freedom. Then, the effects of MI-E settings were appraised using REML analysis as described above. Mucus movement was also analyzed using a REML analysis, comprising MI-E settings and day of assessment as repeated interventions. For each model, normality of residuals was confirmed through visual inspection of distribution of residuals. Two-sided comparisons between MI-E settings or times of assessment were performed, and a given comparison was considered significant if its P was ≤ .05. Each pair-wise comparison was corrected using Bonferroni test to control for experiment-wise error rate. Linear simple regression analysis and multiple regression analysis with a backward-selection model were undertaken to assess correlation between air flows and mucus displacement rate. Finally, to explore the effects of tracheal suctioning on respiratory variables, comparisons were made through Wilcoxon signed-rank sum test. Data are reported as mean ± SD or median [25–75% interquartile range]. All statistical analyses were performed using SAS software (version 9.4, SAS Institute, Cary, North Carolina).

Results

Overall, 6 animals were studied (average weight 31.1 ± 3.6 kg). The MI-E protocol was performed only once in 3 animals, twice in 2 animals, and in one animal the protocol was applied 3 times, but during the first day of assessment only 2 MI-E interventions were performed (+40–50 and +40–60).

Mucus Displacement

Overall, movement of median 4 [3–5] tantalum disks was tracked within the airways, with no difference between MI-E settings (P = .98). Baseline mucus movement rate was 2.85 ± 2.29 mm/min in cephalad direction (toward the glottis). All MI-E pressure combinations increased the velocity of mucus movement, with maximal and minimal being 4.8- and 1.7-fold increase in velocity during the most (+40–70) and least effective (+50−50) combination of pressures. There was a statistically significant difference in mucus velocity between various MI-E settings (no. = 81, P < .001) (Fig. 3). In univariate analyses, mucus displacement rate was linearly correlated with MIF (no. = 61, P = .047; r2 0.06, adjusted r2 0.05) and PIF (no. = 61, P = .03; r2 0.07, adjusted r2 0.06) but lacked linear associations with PEF (no. = 61, P = .85; r2 < 0.001, adjusted r2 −0.016), MEF (no. = 61, P = .40; r2 0.012, adjusted r2 −0.004), PEF-PIF (no. = 61, P = .31; r2 < 0.001, adjusted r2 < −0.001), PEF-MIF (no. = 61, P = .42; r2 0.015, adjusted r2 −0.005), and MEF-MIF (no. = 61, P = .5; r2 0.007, adjusted r2 −0.009). Multivariate regression analysis confirmed mild association of MIF with mucus displacement (Fig. 4), with reduction of mucus displacement rate by 0.23 ± 0.08 mm/min per each unit (L/min) increase in MIF (no. = 60, P = .006; r2 0.12, adjusted r2 0.10) (Table 1. Supplemental Digital Content, see related supplementary materials at http://www.rcjournal.com).

Fig. 3.
Fig. 3.

Mucus displacement (mm/min). Scattered plot of mucus movement velocity during baseline assessments and 8 combinations of insufflation-exsufflation pressures: +40/−40, +40/−50, +40/−60, +40/−70, +50/−40, +50/−50, +50/−60, and +50/−70 cm H2O (P < .001). For each intervention, continuous line depicts median value. #Post hoc analysis, P = .002, and P = .002 versus baseline and +50/−50, respectively. MI-E = mechanical insufflation-exsufflation.

Fig. 4.
Fig. 4.

Multivariate regression analysis. Scattered plot of multivariate regression analysis model between mean inspiratory flow and mucus displacement. Scattered plot is overlaid by the fit continuous dark-blue line, the 95% CI limits within the blue light lines, and 95% prediction limits depicted by dashed lines.

Respiratory Air Flows

On average, VT 1.70 ± 0.43 L were delivered during MI-E to achieve preset insufflation pressures, with no significant differences between applied combinations of pressures (no. = 68, P = .34). Similarly, MIF and MEF were 29.2 ± 8.7 L/min (no. = 67, P = .50) and 92.8 ± 32.6 L/min (no. = 67, P = .26), respectively, with no difference between MI-E settings (Fig. 5). MEF-MIF did not vary between pressure combinations and was on average 63.5 ± 29.4 L/min (no. = 66, P = .35). The average PIF was 92.7 ± 14.1 L/min, with a statistical difference between pressure combinations (no. = 65, P = .004). The highest values (108.5 ± 22.9 L/min) were measured during delivery of +50/−70 cm H2O pressures. PEF was on average 142.6 ± 28.5 L/min, which did not reach statistically significant variations between MI-E settings (no. = 67, P = .066). Similarly, the average expiratory flow bias (PEF-PIF) was 51.8 ± 16.8 L/min, suggesting MI-E combinations of +40/−70 cm H2O and +50/−70 cm H2O were most effective (no. = 54, P = .065) (Fig. 5).

Fig. 5.
Fig. 5.

Respiratory air flows (L/min). Scattered plots displaying effects of 8 different combinations of insufflation-exsufflation pressures (+40/−40, +40/−50, +40/−60, +40/−70, +50/−40, +50/−50, +50/−60, and +50/−70 cm H2O) on (A) mean inspiratory flow (MIF), (B) mean expiratory flow (MEF), (C) MEF-MIF bias, (D) peak inspiratory flow (PIF), (E) peak expiratory flow (PEF), and (F) PEF–PIF bias. For each intervention, continuous line depicts median value. # P = .02 and P = .01 versus +50–40 and +50–50, respectively. MI-E = mechanical insufflation-exsufflation.

Respiratory Mechanics and Hemodynamics

Overall, after MI-E interventions, chest wall elastance was reduced by an average 0.76 ± 2.41 cm H2O/L (no. = 63, P = .92), and lung elastance reduced by 1.33 ± 4.24 cm H2O/L (no. = 63, P = .13), with no significant differences between the various MI-E settings (Fig. 2 Supplemental Digital Content, see related supplementary materials at http://www.rcjournal.com). Expiratory transpulmonary pressure was on average 22.3 ± 9.9 cm H2O and did not change significantly between pressure combinations (no. = 59 P = .97), whereas inspiratory transpulmonary pressure was 32.0 ± 5.4 cm H2O and significantly changed across tested MI-E settings (no. = 60, P < .001) (Fig. 6).

Fig. 6.
Fig. 6.

Transpulmonary pressure. Scattered plots displaying effects of 8 different combinations of insufflation-exsufflation pressures (+40/−40, +40/−50, +40/−60, +40/−70, +50/−40, +50/−50, +50/−60, and +50/−70 cm H2O) on (A) inspiratory transpulmonary pressure (cm H2O) and (B) expiratory transpulmonary pressure (cm H2O). # P = .04, P = .01, P = .007, and P = .006 versus +40–40, +40–50, +40–60 and +40–70, respectively; ^ P = .02, P = .001, P = .002, and P = .002 versus +40–40, +40–50, +40–60, and +40–70, respectively; $ P = .04, P = .02, and P = .02 versus +40–50, +40–60, and +40–70, respectively; ∼ P = .04, P = .02, and P = 0.02 versus +40–50, +40–60, and +40–70, respectively. For each intervention, continuous line depicts median value. MI-E = mechanical insufflation-exsufflation.

MI-E interventions marginally increased air flow resistance by an average 0.66 ± 1.84 cm H2O/L/s (no. = 71, P = .82), and tissue resistance increased post intervention by 0.34 ± 2.73 cm H2O/L/s (no. = 71, P = .68), with no significant differences between varying combinations of pressures (Fig. 2 Supplemental Digital Content). Interestingly, tracheal suctioning significantly increased lung elastance 2.11 ± 4.74 cm H2O/L (no. = 72, P < .001) and marginally decreased air flow resistance 0.24 ± 1.89 cm H2O/L/s, (no. = 72, P = .006) (Fig. 3 Supplemental Digital Content, see related supplementary materials at http://www.rcjournal.com).

Finally, heart rate statistically differed before (79.2 ± 28.2 beats/min), during (76.1 ± 31.5 beats/min), and after (75.4 ± 29.5 beats/min) MI-E intervention (no. = 214, P = .048) (Fig. 4A Supplemental Digital Content, see related supplementary materials at http://www.rcjournal.com), but there was no difference between interventions (no. = 214, P = .14). Conversely, mean arterial pressure was 79.8 ± 13.8, 82.3 ± 13.6, and 83.9 ± 13.5 mm Hg, respectively, and also did not differ either across times of assessment (no. = 214, P = .09) or MI-E interventions (no. = 214, P = .064) (Fig. 4B Electronic Supplemental content, see related supplementary materials at http://www.rcjournal.com).

Discussion

This study is the first to objectively demonstrate beyond in vitro scenarios that MI-E set at different insufflation-exsufflation pressures (+40/−40, +40/−50, +40/−60, +40/−70, and +50/−40, +50/−50, +50/−60, +50/−70 cm H2O) improves mucus displacement in comparison with no intervention, particularly when set at +40/−70 cm H2O. Moreover, the technique appears to be safe as no significant adverse effects on respiratory mechanics or hemodynamics occurred during the procedure.

Growing evidence on MI-E advocates for potential of the technique to clear airway secretions in critically ill patients receiving invasive ventilation, presenting positive but heterogeneous results. The heterogeneity of previous studies is mainly explained by the fact that most studies applied different insufflation-exsufflation pressures, ranging from +30–+50 and −30 to −60 cm H2O, with mucus displacement assessed via different methods.14-18 For instance, Sanchez-García et al14 and Ferreira de Camillis et al15 reported MI-E set at +50/−45 cm H2O and +40/−40 cm H2O, respectively, to be effective in clearing respiratory secretions in sedated subjects on invasive ventilation. However, efficacy of the technique was assessed through visible secretions within artificial airway or weight of aspirated secretions. In a recent crossover randomized trial in 26 subjects mechanically ventilated for > 48 h, we found that MI-E set at +40/−40 cm H2O significantly increased retrieved volume of mucus, oxygenation, and respiratory mechanics when added to a combination of respiratory physiotherapy techniques.18 Conversely, Coutinho et al16 found no significant differences in volume of mucus retrieved when comparing use of MI-E set at +40/−40 to conventional tracheal suctioning.

In the present study, we found that +40/−70 cm H2O was the most effective MI-E combination to improve mucus displacement, which could be explained by several reasons. Early in vitro21-23 and in vivo24 studies elegantly demonstrated that air flow interacts with the cilial mucus layer and moves secretions toward the direction of the highest air flow (ie, outward movement with expiratory flow bias and inward movement with inspiratory flow bias). Later, Volpe et al26 found a linear correlation between PEF-PIF bias and mucus simulant transport, with greater difference between PEF and PIF correlating with increased movement of mucus. Recently, in another bench study,27 the same authors found MI-E to significantly move mucus outward when the device was set to maximize PEF-PIF bias in comparison to a conventional setting. Thus, our study corroborates previous in vitro findings where greater difference between exsufflation and insufflation pressure and, therefore, subsequent greater difference between PEF and PIF cause improved mucus displacement. Moreover, we also found an association between inspiratory flow and mucus displacement toward the lungs, suggesting that insufflation pressure is a key factor to consider for enhancing mucus displacement and should be kept as low as possible when optimizing PEF-PIF bias. Of note, although we set the MI-E device to medium inspiratory flow instead of conventional rapid inspiratory flow, slower inspiratory flow options on the device should be considered to further optimize PEF-PIF bias.

In our current study, none of the combined insufflation-exsufflation pressures had a significant impact on lung elastance or resistance, neither immediately after the procedure nor 15 min after interventions. Impact of MI-E on respiratory mechanics has mainly been assessed as a secondary outcome with contradictory results. Martinez-Alejos et al18 and Ferreira de Camillis et al15 found a short-term improvement in lung compliance after implementation of MI-E set at +40/−40 cm H2O, and Nunes et al17 showed that insufflation-exsufflation pressures of 50 cm H2O improved lung compliance immediately after intervention and 10 min thereafter. However, all other studies assessing respiratory mechanics during MI-E failed to demonstrate any significant positive or negative effects.14,16

Importantly, we found a significant increase in inspiratory transpulmonary pressure during all settings with insufflation pressure of 50 cm H2O, without this having any clinical importance. Our study was performed in healthy animals with intact lung parenchyma; thus, considering potential detrimental effects that MI-E set at higher insufflation pressures might generate in a damaged lung parenchyma, the technique should be used with caution in critically ill patients with underlying pulmonary pathologies. Finally, heart rate increased during interventions, with no significant differences between pressure combinations and without any impact on mean arterial pressure. This concurs with previous studies in which heart rate increased, without clinical consequences, during manual chest physiotherapy with or without additional MI-E.18 Therefore, it is recommended to closely monitor critically ill patients during chest physiotherapy including MI-E, particularly when hemodynamic lability is present.

Some limitations of our study merit consideration. First, the protocol was developed in a porcine model; and although our animal model has been conceived to mimic a real clinical setting, the present results cannot be extrapolated to a clinical scenario with human patients. Second, to ensure consistency between experiments, we used healthy animals with unaffected lung parenchyma, and our results would probably differ in scenarios with pulmonary pathologies entailing lung damage or altered pulmonary mechanics. Thus, this study confirms potential role of MI-E to clear retained secretions in the critically ill without pulmonary affections, but effects of the technique in patients with altered lung parenchyma need to be further elucidated. Finally, we used artificial respiratory secretions with identical characteristics for all the animals, whereas, in humans, mucus rheology may differ from one patient to another and also within patients over time, ultimately influencing the effects of MI-E.

Conclusions

In a swine model of invasive mechanical ventilation, MI-E enhanced artificial mucus displacement regardless of the combinations of insufflation-exsufflation pressures used. Particularly, MI-E at +40/−70 cm H2O was the most effective combination, increasing artificial mucus velocity by nearly 5-fold. No relevant adverse events were associated with the technique, despite a transient significant increase in inspiratory transpulmonary pressure when the insufflation pressure was set at +50 cm H2O. These findings call for larger clinical trials to evaluate effects of MI-E in intubated critically ill patients with or without pulmonary pathologies and to further elucidate indications and contraindications of MI-E in these patients.

Footnotes

  • Correspondence: Antoni Torres MD PhD, Servei de Pneumologia i Al·lèrgia Respiratòria, Hospital Clínic, Calle Villarroel 170, Esc 6/8 Planta 2, 08036 Barcelona, Spain. E-mail: atorres{at}clinic.ub.es

  • See the Original Study on Page 1637

  • The authors have disclosed no conflicts of interest.

  • Drs Marti and Martínez-Alejos equally contributed to this work.

  • Supplementary material related to this paper is available at http://rcjournal.com.

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