Characteristics of the deventilation syndrome in COPD patients treated with non-invasive ventilation: a prospective, controlled, non-blinded study

doi:10.21203/rs.3.rs-861025/v1

Download PDF

Research Article

Characteristics of the deventilation syndrome in COPD patients treated with non-invasive ventilation: a prospective, controlled, non-blinded study

https://doi.org/10.21203/rs.3.rs-861025/v1

This work is licensed under a CC BY 4.0 License

You are reading this latest preprint version

Background

Non-invasive ventilation (NIV) is a recommended treatment for COPD patients suffering from chronic hypercapnic respiratory failure. Prolonged dyspnea after mask removal in the morning, often referred to as deventilation syndrome, is a common side effect but has been poorly characterized yet. This study aimed to explore the pathomechanism, identify risk factors and possible treatment strategies for the deventilation syndrome.

Methods

A prospective, controlled, non-blinded study was conducted. After a night with established NIV therapy, the patients underwent spirometry, blood gas analyses and 6-minute walking tests (6MWT) directly, at two and four hours after mask removal. Dyspnea was measured by the modified Borg scale. Bodyplethysmography and health-related quality of life (HRQoL) questionnaires were used. Patients suffering from deventilation syndrome (defined as dyspnea of at least three points on the Borg scale after mask removal) were treated with non-invasive pursed lip breathing ventilation (PLBV) during the second night of the study.

Results

Eleven of 31 patients included (35%) met the given criteria for a deventilation syndrome. They reported significantly more dyspnea on the Borg scale directly after mask removal (mean: 7.2 ± 1.0) compared to measurement after two hours (4.8 ± 2.6; p = 0.003). Initially, mean inspiratory vital capacity was significantly reduced (VCmax: 46 ± 16%) compared to two hours later (54 ± 15%; p = 0.002), while no changes in pulse oximetry or blood gas analysis were observed. Patients who suffered from a deventilation syndrome had a significantly higher mean airway resistance (Reff: 320 ± 88.5%) than the patients in the control group (253 ± 147%; p = 0.021). They also scored significantly lower on the Severe Respiratory Insufficiency Questionnaire (SRI; mean: 37.6 ± 10.1 vs 50.6 ± 16.7, p = 0.027). After one night of ventilation in PLBV mode, mean morning dyspnea decreased significantly to 5.6 ± 2.0 compared to 7.2 ± 1.0 after established treatment (p = 0.019) and mean inspiratory vital capacity increased from 44 ± 16.0% to 48 ± 16.3 (p = 0.040).

Conclusions

The deventilation syndrome is a serious side effect of NIV in COPD patients, associated with lower HRQoL. Our data suggests that it is most likely caused by dynamic hyperinflation. Patients with high airway resistance are at greater risk of suffering from morning dyspnea. Ventilation in PLBV mode may prevent or improve the deventilation syndrome.

Trial registration

The study was registered in the German Clinical Trials Register (DRKS00016941) at 04 April 2019, https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS

Pulmonology

Deventilation syndrome

morning dyspnea

non-invasive ventilation

NIV

ventilatory insufficiency

hypercapnic respiratory failure

COPD

high-intensity NIV

PLBV

COPD is one of the leading causes of death worldwide (1). In severe disease, patients often suffer from hypercapnic respiratory failure and treatment with non-invasive ventilation (NIV) is strongly recommended (2). Studies have shown that among other benefits, NIV can reduce mortality, improve blood gases, and improve quality of life (3, 4, 5). However, positive effects of NIV are proven in patients with stable hypercapnia who are ventilated with high-intensity NIV (HINIV). HINIV uses high inspiratory pressures up to 30mmHg to achieve a maximum of pCO₂ reduction. It is often combined with high respiratory rate back-up rates (2, 6). A common side-effect of HINIV is the so-called deventilation syndrome, i.e. morning dyspnea immediately after removing the ventilation mask that can last several hours. This impairs the patient’s daily activities, reduces HRQoL and therapy compliance. Although approximately 30% of NIV-patients with COPD may suffer from the deventilation syndrome (7), the underlying mechanism remains unclear. A correlation between patient-ventilator-asynchrony, Auto-PEEP-phenomena and morning dyspnea has been described (7, 8). This suggests that dynamic hyperinflation, exacerbated by high inspiratory pressure may cause the deventilation syndrome (7). Other explanations discussed are chronic muscle fatigue after rapid cessation of positive ventilation pressure or poor sleeping patterns (9). In addition to optimizing ventilation settings (7), a potential therapy for morning dyspnea could be ventilation in pursed-lips-breathing-ventilation (PLBV) (8). This ventilation mode is characterized by a dynamic increase in pressure during the expiratory phase followed by a slow pressure decay, which could prevent airway collapse and thus lead to more adequate expiration and less air trapping. The aim of this study was to characterize the deventilation syndrome by further exploring the underlying mechanisms, identifying risk factors and possible strategies which may prevent its occurrence.

Study design

We conducted a prospective, controlled, single centre, non-randomized, descriptive trial with an interventional element (PLBV) during the second night. Investigations were performed from August 2019 until February 2021 but were interrupted for four months due to the COVID-19 pandemic. The deventilation syndrome was defined by two criteria: 1) subjective complaints of worsening dyspnea after ventilator mask removal and 2) patient reports three or more points on the Borg scale after ventilator mask removal. The patients were stratified into two groups during the study: 1) patients with deventilation syndrome, 2) patients without deventilation syndrome (control group).

Approval was obtained from the Ethics Committee of the University of Lübeck, Germany, reference 19–025. The study was registered in the German Clinical Trials Register (DRKS00016941).

Patients

Patients were enrolled when the following criteria were fulfilled: 1) bilevel mode (inspiratory pressure > expiratory pressure) was applied, 2) patient understood the study requirements, 3) patient was physically able to participate in the study examinations. Exclusion criteria were: 1) acute exacerbations of COPD, 2) pneumothorax 3) invasive ventilation 4) patient is unable to perform the study investigations.

Study protocol

The investigations were performed on two and three consecutive days in patients without and with deventilation syndrome, respectively. Study subjects spent all nights in the sleep laboratory. On the first day, baseline measurements were performed in the afternoon. On the second and third day, the investigations were conducted immediately when the patients took off their ventilation masks. Patients were therefore asked to wear the mask until the study personnel arrived. Dyspnea and pulse oximetry were reported every 30 minutes starting directly after mask removal. Spirometry and inspiratory flow were measured directly, after two and four hours. 6-minute walking test and blood gas analysis were conducted directly and after four hours. If no deventilation syndrome was reported, the study was terminated on the second day, as no changes in respiratory quality were suspected. If the patient reported a deventilation syndrome, ventilation was switched to PLBV mode for the second night and investigations were repeated thereafter.

Measurements

Demographic data, COPD stage according to the Global Initiative on Lung Disease (GOLD), comorbidities, current medication, long-term oxygen therapy and ventilation parameter were documented. Pulse rate and oxygen saturation were measured by pulse oximetry. Capillary blood gas analyses were taken and measured using the ABL 90 blood gas analyzer (Radiometer, Germany). Patients received their usual rate of oxygen supply during blood sampling. Spirometry was performed with the mobile spirometer Flowscreen V2.2.4 (Jaeger, Germany). Inspiratory airflow was measured by the In-Check-Dial G16 ® (Clement Clarke, UK) which was originally developed to measure the capability of inhalator-use. With one forced inspiration breath, patients can move a plastic sail on a scale from 0 to 120ml in variable difficulty levels. Only the easiest level was used for our examinations, requiring the least inspiratory flow. Bodyplethysmography was performed with the Masterscreen (Jäger/CareFusion, Germany). The 6-minute walking test was performed on a straight horizontal 30-meter track. Oxygen saturation and dyspnea on the Borg scale were reported before and after exercise. Muscle strength was measured using a 3kg dumbbell. Patients lifted and lowered it with their dominant arm in sitting position from their knee to their shoulder following the beat of a metronome at 40 bpm for as long as possible. The total time and the reason for stopping (dyspnea, muscle or joint pain) were documented. At night, patients underwent polysomnography, with recording of EEG, EMG, EKG, oxygen saturation, pulse, breathing rate, respiratory flow and ventilator pressure. Dyspnea was assessed using the modified Borg scale. Lastly, the patients answered the validated SRI (10) and CAT (11) questionnaires.

Intervention

In patients suffering from deventilation syndrome in the morning of the second day, pursed-lip-breathing ventilation (PLBV) using the Vigaro® ventilator (FLO Medical Technologies, Germany) was established for the second night. The ventilation parameters were chosen according to experience and requirements as established in the work of Jünger et al. (8)

Sample size

Due to a lack of data about the deventilation syndrome, the sample size was calculated based on clinical experience. For an estimated change from seven points on the Borg scale to four points with a standard deviation of three points, at least ten patients were needed at a two-sided level alpha of 0.05 with a power of at least 80%. About 30% of all non-invasively ventilated patients suffer from a deventilation syndrome (7), resulting in a total of at least 30 patients that had to be enrolled.

Statistical analysis

Normal distribution was measured by the Shapiro-Wilk test. An unpaired t-test was performed to compare the means of the two groups. A paired t-test was performed to compare the means of the morning measurements and the means of the two ventilation modes. If no normal distribution was given, a Mann-Whitney U test was performed for unpaired samples or a Wilcoxon rank test for paired samples. The measurements directly after mask removal were compared to the following measurement that was performed after two hours (dyspnea, spirometry) or four hours (blood gas analysis, 6-minute walking test). Further, the measurements after established ventilation were compared to ventilation after ventilation in PLBV mode. The significance level was set at p = 0.05.

Drop-outs

Forty-two long-term non-invasively ventilated COPD patients were screened (Fig. 1). Ten did not meet the inclusion criteria or declined consent. Thirty-two patients underwent the baseline examination, of whom one experienced a panic attack in the first night due to massive dyspnea and discontinued the study. Of the 31 remaining, 11 patients had a deventilation syndrome according to the above criteria, 20 did not. Of the 11 patients with deventilation syndrome, one patient refused further NIV therapy. The ventilation of 10 was switched to PLBV mode and examined on day three.

Baseline measurements

Baseline data for the two groups were measured in the afternoon (Table 1). There were no group differences in age, medication, comorbidities, sleep, dependence of long-term-oxygen, oxygen saturation at rest, and severity or number of exacerbations of COPD in the last year. Patients who suffered from morning dyspnea had a significantly lower mean body mass index (BMI) (22.5 ± 5.1) than those who did not (27.6 ± 6.5; p = 0.032). In addition, patients with deventilation syndrome had significantly lower mean inspiratory vital capacity (VCmax: 51 ± 16.9% vs 67 ± 12.2%, p = 0.015), FEV1 (29 ± 14.6% vs 38 ± 11.8%, p = 0.001) and higher airway resistance (Reff: 320 ± 88.5% vs 253 ± 147%, p = 0.021). No significant difference in inspiratory flow was observed. Functionally, patients with deventilation syndrome had a worse exercise tolerance than the control group, with a significantly shorter mean walking distance in the 6MWT (149.9 ± 112.4m vs 236.7 ± 112.8, p = 0.049). The muscular exercise capacity also tended to be reduced, but was not significantly different. They reported more dyspnea at the BORG scale at baseline (mean: 3.9 ± 2.7) than the control group (2.1 ± 1.9; p = 0.042). There were no significant differences in the CAT questionnaire. In the SRI questionnaire, significant differences were reported in the summary score and the subcategories ‘respiratory complaints’ and ‘physical functioning’.

Table 1: Baseline demographic data and clinical characteristics.
	Patients with deventilation syndrome (n = 11)	Patient without deventilation syndrome (n = 20)	p
Baseline data
Sex m/f (%)	55/45	35/65
Age, years	68.5 (6.5)	69.9 (6.6)	0.573
BMI (kg/m²)	22.5 (5.1)	27.6 (6.5)	0.032
Ventilator settings
Duration of NIV (months)	30.7 (38.0)	21.3 (23.6)	0.509
Inspiratory pressure (mmHg)	16.7 (4.9)	16.7 (3.3)	0.999
Expiratory pressure (mmHg)	5.6 (1.2)	6.7 (1.4)	0.051
Blood gas analysis
pH	7.41 (0.02)	7.40 (0.03)	0.302
pO₂ (mmHg)	63.3 (12.0)	63.8 (13.2)	0.914
pCO₂ (mmHg)	47.0 (9.7)	46.7 (7.0)	0.913
Pulmonary function (n = 28)	n = 10	n = 18
VCmax (l)	1.56 (0.37)	1.98 (0.50)	0.016
VCmax (%)	51 (16.9)	67 (12.2)	0.015
FVC (%)	48 (16.3)	62 (12.8)	0.032
FEV1 (%)	29 (14.6)	38 (11.8)	0.001
FEV1/FVC	58 (10.2)	66 (14.2)	0.148
TLC (%)	136 (20.1)	124 (31.8)	0.089
RV (%)	276 (61.8)	218 (81.5)	0.060
RV/TLC	78 (5.5)	69 (7.1)	0.001
Reff (%)	320 (88.5)	253 (147)	0.021
SReff (%)	627 (165.6)	395 (165.6)	0.006
Rtot (%)	412 (138.3)	299 (169.4)	0.012
Inspiratory flow (ml)	68.2 (16.6)	72.0 (12.8)	0.516
Exercises
6MWT, distance (m)	149.9 (112.4)	236.7 (112.8)	0.049
Muscle strength, time (s)	60 (48)	82 (47)	0.094
Questionnaires
Borg scale	3.9 (2.7)	2.1 (1.9)	0.042
CAT	31.7 (5.7)	28.1 (7.5)	0.144
SRI Summary Score	37.6 (10.1)	50.6 (16.7)	0.027
SRI Respiratory Complaints	38.4 (14.3)	56.5 (23.8)	0.030
SRI Physical Functioning	24.2 (17.5)	40.0 (18.5)	0.029
SRI Attendant Symptoms and Sleep	52.6 (19.6)	56.7 (22.6)	0.617
SRI Social Relationships	49.6 (17.8)	61.3 (18.6)	0.146
SRI Anxiety	37.3 (15.2)	50.8 (26.5)	0.133
SRI Psychological Well Being	35.9 (17.4)	48. 5 (21.1)	0.106
SRI Social Functioning	26.4 (19.0)	40.2 (20.6)	0.081
Data were collected in the afternoon. Data are mean (SD). m: male, f: female, BMI: Body Mass Index, pCO₂: capillary carbon dioxide pressure, pO₂: capillary oxygen pressure, 6MWT: 6-minute walking test, VCmax: maximum vital capacity, FVC: forced vital capacity, FEV1: forced expiratory volume in 1 second, TLC: total lung capacity, RV: residual volume, sReff: specific resistance, Rtot: total resistance, SRI: Severe Respiratory Insufficiency Questionnaire, CAT: COPD Assessment Test

Changes during the deventilation syndrome

Immediately after mask removal, the patients who reported a deventilation syndrome experienced dyspnea with a mean Borg scale of 7.2 ± 1.0, that decreased significantly to 4.0 ± 2.2 in the following hours (p < 0.001). The patients in the control group reported dyspnea of 1.9 ± 1.6 on the Borg scale after ventilation that remained stable in the next hours (2.1 ± 1.6 after 4h; p = 0.5). The mean vital capacity of the patients with morning dyspnea was 46 ± 16% immediately after mask removal and 54 ± 15% after two hours (p = 0.002). Between the second (two hours) and the third measurement (four hours), no changes were observed. In the control group, no significant changes were observed. The initial inspiratory flow did not change significantly. The deventilation syndrome patients achieved a mean walking distance of 109 ± 111m in 6MWT immediately and 163 ± 131m four hours after mask removal (p = 0.007). In the control group, changes were non-significant. No significant changes in pCO₂ were observed. There were also no changes and differences in oxygen saturation or heart rate in both groups immediately after ventilation. Detailed results are shown in Table 2 and Fig. 2.

Table 2

Deventilation syndrome
	baseline (mask removal)	after 2h	after 4h	p *
Patients with deventilation syndrome (n = 11)
Borg Scale	7.18 (0.98)	4.82 (2.64)	4.00 (2.19)	0.003
pCO₂(mmHg)	47.42 (5.60)		46.71 (7.92)	0.492
6MWT walking distance (m)	109.00 (111.45)		163.09 (130.75)	0.007
VCmax (%)	46.00 (16.08)	54.86 (14.65)	54.55 (14.56)	< 0.001
Inspiratory flow (ml)	59.00 (19.12)	66.50 (13.55)	69.50 (12.13)	0.067
Patients without deventilation syndrome (n = 20)
Borg Scale	1.9 (1.64)	2.10 (1.58)	2.05 (1.64)	0.330
pCO₂(mmHg)	49.05 (6.85)		49.58 (6.70)	0.510
6MWT walking distance (m)	238.95 (110.33)		238.45 (110.36)	0.789
VCmax (%)	61.70 (10.04)	65.25 (12.98)	66.65 (11.17)	0.079
Inspiratory flow (ml)	68.25 (12.49)	69.75 (12.92)	71.00 (12.90)	0.316
Data are mean (SD). pCO₂: capillary carbon dioxide pressure, 6MWT: 6-minute walking test, VCmax: maximum vital capacity. *If available, baseline values were compared to measurement after two hours otherwise to measurement after four hours.

Established NIV mode compared to PLBV mode

Compared to established treatment, the inspiratory pressure could be reduced from 17.5 ± 4.4 to 14.6 ± 3.0mmHg in PLBV mode (p = 0.002) with no changes in blood gas analysis results. Reported dyspnea immediately after ventilation decreased significantly from 7.2 ± 1.0 to 5.6 ± 2.0 points on the Borg scale (p = 0.019). VCmax immediately after ventilation was higher on PLBV with 44.4 ± 16.0 versus 47.7 ± 16.2 (p = 0.040) with the established NIV. The walking distance in 6MWT after ventilation increased from 114.9 ± 115.7m to 129.8 ± 132.2m when treatment was switched to PLBV, but the difference was not significant (p = 0.087). Detailed results are shown in Table 3.

Table 3: Patients with deventilation syndrome under PLBV compared to established NIV
	established NIV	PLBV mode	p
Ventilator settings
Inspiratory pressure	17.5 (4.4)	14.6 (3.0)	0.002
Expiratory pressure	5.8 (1.1)	6.1 (1.3)	0.343
Borg scale	7.2 (1.0)	5.6 (2.0)	0.019
Blood gas analysis
pH	7.419 (0.49)	7.418 (0.37)	0.849
pCO₂(mmHg)	47.2 (5.9)	47.4 (6.3)	0.821
pO₂ (mmHg)	64.6 (12.7)	67.9 (16.4)	0.326
BE (mmHg)	5.3 (5.5)	5.1 (4.8)	0.696
HCO₃- (mmHg)	30.5 (6.1)	30.4 (5.4)	0.873
6-minute walking test
Distance (m)	114.9 (115.7)	129.8 (132.2)	0.087
Pulmonary function
VCmax (%)	44 (16.0)	48 (16.3)	0.040
FVC (%)	41 (19.0)	47 (18.4)	0.032
FEV1 (%)	20 (9.5)	21 (8.2)	0.415
FEV1/FVC (%)	37 (8.3)	34 (5.4)	0.051
Inspiratory flow (ml)	59.5 (19.2)	63.5 (15.6)	0.085
Measurements immediately after mask removal after a single night in PLBV mode. Data are mean (SD). n = 10. pCO₂: capillary carbon dioxide pressure, pO₂: capillary oxygen pressure, BE: base excess, HCO₃-: bicarbonate, VCmax: maximum vital capacity, FVC: forced vital capacity, FEV1: forced expiratory volume in 1 second

In this study, we describe parameters associated with early morning dyspnea after mask removal following nightly NIV. We focused on clinically relevant parameters used to describe pulmonary function and exercise tolerance as no concrete definition of the deventilation syndrome was available in the literature. The main finding of this study is the significant decrease of vital capacity during the occurrence of the deventilation syndrome in non-invasively ventilated COPD patients. Together with the significantly higher airway resistance found in patients with a deventilation syndrome, our findings support the hypothesis that morning dyspnea after NIV-therapy is the result of dynamic hyperinflation during ventilation (7, 12). COPD patients usually adapt a longer expiratory phase to achieve adequate expiration despite high airway resistance. During NIV therapy, they possibly inhale a volume that cannot be exhaled before the next inspiratory phase is triggered, especially in controlled modes with short expiratory time. This can lead to massive hyperinflation with an increase of intrinsic positive end expiratory pressure (PEEP). Especially a chronically weakened diaphragm can struggle in overcoming that, leading to dyspnea after NIV therapy. We could not find any differences in muscle strength that may suggest a generalized muscle weakness causing morning dyspnea. Furthermore, muscle weakness should have led to a decrease in inspiratory flow, which we did not find. With a mean inspiratory pressure of 16,7mmHg in our cohort, the mean pressure level was relatively low, probably due to a lack of tolerance of higher pressures by the patients. In our pathogenic model, a higher inspiratory pressure would lead to an exacerbation of morning dyspnea. In our study, dyspnea persisted for one hour after removal of the ventilation mask. Accordingly, performance in the 6MWT was significantly worse immediately after ventilator mask removal compared to later exercise tests. Interestingly, no changes in blood gas analysis or pulse oximetry were observed, suggesting that the patients can cope with the resulting acute increase in respiratory workload and NIV therapy can effectively reduce CO₂ despite the deventilation syndrome.

We observed that the patients who suffered from a deventilation syndrome in the morning had worse results in 6MWT, lung function and reported more severe dyspnea on the Borg scale at all times of the day. They also reported poorer HRQoL in the SRI compared to the control group. In addition to the higher airway resistance, we also found an increased RV/TLC. This indicates that hyperinflation is not a problem confined to NIV periods but all day. This may explain the poorer exercise tolerance and dyspnea at any time during the day. It has been postulated, that NIV can reduce hyperinflation in COPD patients (13), but in a group of patients, who experience severe acute hyperinflation during and after NIV therapy, the therapy might also exacerbate persisting hyperinflation.

The gold standard to determine hyperinflation requires bodyplethysmography that is not available on the bedside. Thus, direct measurement of intrathoracic gas-volume (ITGV) was not possible in our patients who were investigated in their bed immediately after mask removal in the morning. Furthermore, the strongly impaired physical condition of most patients after mask removal only allowed bedside spirometry. Therefore, we can only hypothesize, that the decrease in vital capacity is caused by hyperinflation. Measurement of intrathoracic pressure to prove this hypothesis would again require invasive investigations.

Our observations in patients treated with PLBV also support the notion that hyperinflation is causing morning dyspnea in deventilation syndrome. After the patients were switched to PLBV, morning dyspnea decreased and this was associated with an increased inspiratory vital capacity. This confirms results of our previous retrospective study on PLBV (8). It can be assumed that an increase in airway pressure during exhalation results in better airflow control allowing a harmonization of alveolar filling pressure and prevention of small airway collapse. In PLBV mode, no respiratory rate was adjusted and the inspiratory pressure was decreased in some patients who had very severe morning dyspnea. Capillary blood CO₂ levels were unchanged compared to their established NIV. This suggests that PLBV may be a potential treatment to reduce hyperinflation and morning dyspnea while maintaining stable CO₂ levels. However, due to the small number of patients treated with PLBV, this study was not designed to evaluate therapeutic effects.

We are aware of the limitations of our study. The number of patients included is small, explained by the advanced morbidity of the patients and the decreasing inpatient numbers during the COVID-19 pandemic. Furthermore, the subjects were classified into “deventilation syndrome” and “no deventilation” syndrome according to their subjective assessments on the Borg scale. However, given the lack of a published definition of this disabling condition this approach appears to represent the real-life setting best. The number and type of examinations, especially lung function and 6MWT can be very exhausting for patients with ventilatory failure. As some patients were unable to complete the full set of diagnostic tests, smaller case numbers in some investigations had to be taken into account. The intervention (change of ventilation mode in the deventilation syndrome group) could not be blinded.

The deventilation syndrome in COPD patients can be defined as acute morning dyspnea after removal of the ventilator mask, most likely caused by hyperinflation under NIV therapy. Patients with high airway resistance are at increased risk of developing a deventilation syndrome. With a prevalence of 35% in our study, it is a common side effect in COPD patients undergoing NIV therapy. Adjusting high inspiratory pressures, as recommended in international guidelines (6), while maintaining patient comfort during ventilation remains a clinical challenge. Apart from optimizing ventilator settings (7), ventilation in PLBV mode may be a potential strategy to prevent morning dyspnea. Although a reduction of hypercapnia was achieved in our study despite the occurrence of the deventilation syndrome, the long-term effects of ventilator-induced hyperinflation remain unclear and should be further elucidated.

Ethics approval and consent to participate

Ethical commitment was obtained from the Ethical Committee of the University of Lübeck, AZ: 19-025. All patients gave written consent to participate.

Consent for publication

Not applicable.

Availability of data and materials

The dataset used and analyzed during the current study are available from the corresponding author on reasonable request.

Competing interests

SR invented the PLBV and co-developed the Vigaro® within the scope of a consulting contract with FLO medical. CH and ML have no conflicts of interests to declare.

Funding

Not applicable.

Authors’ contributions

All authors contributed substantially to the study design, data analysis and interpretation. CH supervised the project, ML collected the data, SR set the Vigaro® ventilator. ML and CH wrote the manuscript. All authors read and approved the final manuscript.

Acknowledgements

The authors would like to thank Petra Hein and Regina Morwinski from the sleep laboratory of the Medical Clinic Borstel and Andrea Glaewe, Lenka Krabbe, Johanna Döhling and Vanessa Pingel from the Center for Clinical Studies, Borstel for their constant support and advices in all kind of organizational matters.

BE base excess

BMI body mass index

CAT COPD assessment test

CO₂ carbon dioxide

COPD chronic obstructive pulmonary disease

DVS deventilation syndrome

HCO₃- bicarbonate

FEV1 first second of forced expiration

FVC forced vital capacity

IGTV intrathoracic gas-volume

NIV non-invasive ventilation

O₂ oxygen

PEEP positive end-expiratory pressure

PLBV pursed-lips-breathing-ventilation

Reff effective airway resistance

Rtot total airway resistance

SRI Severe Respiratory Insufficiency Questionnaire

sReff specific effective airway resistance

VCmax maximum vital capacity

6MWT 6-minute walking test

World Health Organization. The top 10 causes of death. 2020. https://www.who.int/news-room/fact-sheets/detail/the-top-10-causes-of-death. Accessed 26 Mar 2021.
Ergan B, Oczkowski S, Rochwerg B, Carlucci A, Chatwin M, Clini E, Elliott M, Gonzalez-Bermejo J, Hart N, Lujan M, Nasilowski J, Nava S, Pepin J, Pisani L, Storre JH, Wijkstra P, Tonia T, Boyd J, Scala R, Windisch W. European Respiratory Society guidelines on long-term home non-invasive ventilation for management of COPD. Eur Respir J. 2019;54(3):e1901003.
Clini E, Sturani C, Rossi A, Viaggi S, Corrado A, Donner CF, Ambrosino N. The Italian multicentre study on noninvasive ventilation in chronic obstructive pulmonary disease patients. Eur Respir J. 2002;20(3):529–38.
Köhnlein T, Windisch W, Köhler D, Drabik A, Geiseler J, Hartl S, Karg O, Laier-Groeneveld G, Nava S, Schönhofer B, Schucher B, Wegschneider K, Criée C, Welte T. Non-invasive positive pressure ventilation for the treatment of severe stable chronic obstructive pulmonary disease: a prospective, multicentre, randomised, controlled clinical trial. The Lancet Respiratory Medicine. 2014;2(9):698–705.
Duiverman ML, Wempe JB, Bladder G, Vonk JM, Zijlstra JG, Kerstjens HA, Wijkstra PJ. Two-year home-based nocturnal noninvasive ventilation added to rehabilitation in chronic obstructive pulmonary disease patients: A randomized controlled trial. Respir Res. 2011;12(1):112.
Dreher M, Storre JH, Schmoor C, Windisch W. High-intensity versus low-intensity non-invasive ventilation in patients with stable hypercapnic COPD: a randomised crossover trial. Thorax. 2010;65(4):303–8.
Adler D, Perrig S, Takahashi H, Espa F, Rodenstein D, Pépin JL, Janssens JP. Polysomnography in stable COPD under non-invasive ventilation to reduce patient–ventilator asynchrony and morning breathlessness. Sleep Breath. 2012;16(4):1081–90.
Jünger C, Reimann M, Krabbe L, Gaede KI, Lange C, Herzmann C, Rüller S. Non-invasive ventilation with pursed lips breathing mode for patients with COPD and hypercapnic respiratory failure: A retrospective analysis. PLOS ONE. 2020;15(9):e0238619.
Esquinas AM, Ucar ZZ, Kirakli C. Deventilation syndrome in severe COPD patients during long-term noninvasive mechanical ventilation: poor sleep pattern, hyperinflation, or silent chronic muscular fatigue? Sleep Breathing. 2014;18(2):225–6.
Windisch W, Freidel K, Schucher B, Baumann H, Wiebel M, Matthys H, Petermann F. The Severe Respiratory Insufficiency (SRI) Questionnaire: a specific measure of health-related quality of life in patients receiving home mechanical ventilation. J Clin Epidemiol. 2003;56(8):752–9.
Jones PW, Harding G, Berry P, Wiklund I, Chen W-H. Kline Leidy N. Development and first validation of the COPD Assessment Test. Eur Respir J. 2009;34(3):648–54.
Lukácsovits J, Carlucci A, Hill N, Ceriana P, Pisani L, Schreiber A, Pierucci P, Losonczy G, Nava S. Physiological changes during low- and high-intensity noninvasive ventilation. Eur Respir J. 2012;39(4):869–75.
Budweiser S, Heinemann F, Fischer W, Dobroschke J, Pfeifer M. Long-term reduction of hyperinflation in stable COPD by non-invasive nocturnal home ventilation. Respir Med. 2005;99(8):976–84.

Download PDF

Review #2 received at journal
03 Nov, 2021
Reviewer #3 agreed at journal
25 Oct, 2021
Reviewer #2 agreed at journal
24 Oct, 2021
Reviews received at journal
24 Oct, 2021
Reviewers invited by journal
24 Oct, 2021
Reviewer #1 agreed at journal
23 Oct, 2021
Editor assigned by journal
30 Aug, 2021
First submitted to journal
30 Aug, 2021
Submission checks completed at journal
29 Aug, 2021
Editor invited by journal
29 Aug, 2021

You are reading this latest preprint version

Characteristics of the deventilation syndrome in COPD patients treated with non-invasive ventilation: a prospective, controlled, non-blinded study

Status:

Version 1

Abstract

Background

Methods

Results

Conclusions

Trial registration

Figures

Background

Methods

Study design

Patients

Study protocol

Measurements

Intervention

Sample size

Statistical analysis

Results

Drop-outs

Baseline measurements

Changes during the deventilation syndrome

Discussion

Conclusions

Declarations

Abbreviations

References

Status:

Version 1