In a monocenter prospective observational study demographic, physiological and subjective data was collected from in-patients with severe COPD III-IV and chronic hypercapnic failure before, during and after use of an already established NIV.
Extended routine examinations included cardio-respiratory monitoring during and one hour after the nocturnal use of NIV, including ultrasonic diaphragm measurements. Subjective dyspnea was documented before and after use of NIV by use of the Borg scale and questionnaires were supplemented.
Being an observational study to document the Deventilation Syndrome, no study endpoints were defined. The authors refrained from power calculation due to the observational character of the study.
Between November 2016 and January 2019, 71 patients with severe COPD (Gold III°-IV°) and established long-term home NIV were included in the study. Sufficient data was collected from 67 patients. Inclusion criteria were: men and women with stable COPD disease, GOLD stage III-IV, regular use (≥ 4h/d) of NIV (prescription ≥ 1 year) and age > 18 years. Study participation required written consent and patients had to be able to follow the requirements of the project. The study protocol was granted permission by the ethics review board of the University of Heidelberg, Germany and all patients gave their written consent.
During the study any medically necessary concomitant therapy was allowed. Intercurrent diseases were treated according to the clinic standard.
Exclusion criteria were: Acute pulmonary impairment (e.g. pneumonia), other acute diseases such as acute pulmonary artery embolism, haemoptysis, internal bleeding, pneumothorax. In addition, serious neurological disorders (e.g. apoplex) or cardiovascular diseases with hemodynamic instability (e.g. heart failure NYHA≥ III, myocardial infarction < 1 month ago) were excluded, as also newly occurring hypoxemia or worsening of hypercapnia ≥ 20% compared to previous values. In addition, alcohol/drug/drug abuse made participation in the study impossible.
Deventilation Syndrome (DVS)
DVS is determined by dyspnea – a highly subjective symptom. Objectification is best done by use of the modified Borg scale  The minimal clinical importance difference for Borg is 1 point . Being a novel syndrome, there is no definition of DVS to this date. For this study and further use of this terminology, DVS was defined by an increase of subjective dyspnea by ≥ 2 points on the Borg scale during the first 30 minutes after NIV termination – thus stressing the symptomatic and chronologic context after use of NIV.
Survey examination timeline
Baseline (T0, day of admittance): anamnesis, PE, questionnaires, BGA w/wo NIV, pulmonary function tests, spO2, breath and heart rate, blood pressure, ultrasound measurement of diaphragm excursion
Tn (following morning, with NIV): dyspnea by Borg scale, spO2, tCO2, breath and heart rate, blood pressure
T1 (10 min post NIV): dyspnea by Borg scale (and every 10 min for the following hour), BGA, spO2, tCO2, breath and heart rate, blood pressure, ultrasound measurement of diaphragm excursion
T2 (60 min post NIV): dyspnea by Borg scale, BGA, spO2, tCO2, breath and heart rate, blood pressure
Pulmonary Function Diagnostics
These were carried out according to the internal standards of the lung function department of the University Thoraxklinik Heidelberg, using MasterScreenBody and PFT Body + Diff. by Care Fusion (Jaeger).
Documentation of body plethysmography (functional residual capacity (FRCpleth), specific airway resistance (sRaw), total lung capacity (TLC) and residual volume (RV), airway resistance was calculated by use of sRaw and FRC(pleth)) and spirometric data (vital capacity (VC), forced vital capacity (FVC), forced expiratory volume (FEV1) and percentage value Tiffeneau index. Furthermore, measurement of diffusion capacity (TLCO).
Reference values were calculated according to GLI for spirometric parameters and TLCO [11, 12], while ECSC was referenced for body plethysmography .
Respiratory muscle strength:
Exhaustion of respiratory muscle function was measured non-invasively by maximal inspiratory mouth pressure (Pimax), reflecting respiratory capacity. The respiratory load was documented by measurement of occlusion pressures (P0.1) .
Ultrasonic diaphragm measurement
Measurements of diaphragm excursion were performed using the Philips Ultrasound Sparq with an abdominal transducer C 6-2. Patients were examined during spontaneous breathing on admission day (T0) and the following morning after termination of NIV (T1). This was done in a dorsal lying position, the torso elevated at approx. 45°.The right diaphragm was located in B-Mode and then excursion measured in M-Mode subcostal, mid clavicular line [15, 16].
Measurement of carbon dioxide values and blood gas analysis
Carbon dioxide values were collected by two methods: continuous transcutaneous measurement and capillary blood draw (blood gas analysis, BGA), both examined on the earlobe.
BGA was assessed by arterialized capillary ear-lobe puncture earlobe skin . The ABL 800 flex from Radiometer GmbH was used as blood gas analyzer. Transcutaneous CO2 measurement was performed using TOSCA transcutaneous monitor TCM 4, Radiometer.
Nightly monitoring of patients undergoing long term home NIV is an essential part of NIV surveillance, reflecting the respiratory situation and efficiency of ventilation during sleep. This standardized procedure was performed during nocturnal use and extended one hour after termination of NIV on our ward using Philips IntelliVue MX550 monitors.
Borg perception of exertion CR10 Scale
Acquired by Modified Borg Scale (MBS) with 10-point dyspnea assessment . An increase of ≥ 2 points after NIV termination was defined by the authors as relevant for DVS.
CAT: COPD Assessment Test
Cut off: < 10 = low impairment to > 30 = very high impairment .
mMRC: Modified Medical Research Council
Score from 0 ("never breathless, except during intense exertion") to 4 ("too short of breath to leave the house or to dress and undress alone") .
Baseline characteristics are presented for the whole sample and stratified by group (DVS vs nDVS) by mean and standard deviation (SD) or median and interquartile range (IQR) or frequencies (n, %) as appropriate. Differences between groups were investigated by means of independent t-test, Mann-Whitney U test or chi-square test retrospectively. Continuous variables were explored graphically to justify parametric analysis.
Longitudinal models were applied to test for time x group effects for outcomes measured over time. Except for BORG (ordinal scale), a linear regression model with repeated measures statement was applied for each outcome with the explaining variables time, group, and interaction term. Group and time effects with confidence intervals and p-value were presented based on the contrast between groups at each visit and contrasts between the visits for each group.
For Borg, the total score was analyzed descriptively by median (IQR) at the four measurement points in time for each group (DVS and nDVS).
To analyze the relationship of Borg and FEV1, Spearman correlation coefficients were calculated.
This is an exploratory analysis so that p-values are interpreted descriptively. A p-value < 0.05 was considered statistically significant. All analyses were performed in SAS version 9.4.