Respiratory muscle activity and patient–ventilator asynchrony during different settings of noninvasive ventilation in stable hypercapnic COPD: does high inspiratory pressure lead to respiratory muscle unloading?

Figures & data

Table 1 Patient characteristics

Characteristics
Age, year, mean ± SD	66±8
Years on home NIV, median (range)	5 (1.3–9.2)
LTOT, % of patients	50
FEV1, L, mean ± SD	0.85±0.31
FVC, L, mean ± SD	2.65±0.79
FEV1/FVC, %	30±7
PaCO2 before NIV, kPa, mean ± SD	7.9±1.3
PaO2 before NIV, kPa, mean ± SD	8.3±1.7
PaCO2 at last control visit, kPa, mean ± SD	6.9±1.3
PaO2 at last control visit, kPa, mean ± SD	9.5±2.1

Abbreviations: SD, standard deviation; NIV, noninvasive ventilation; LTOT, long-term oxygen therapy; FEV₁, postbronchodilator forced expiratory volume in 1 s in liters (L); FVC, forced vital capacity in liters (L); PaO₂, arterial oxygen pressure at daytime without ventilation; PaCO₂, arterial carbon dioxide pressure at daytime without ventilation; kPa, kilopascal.

Table 2 The different ventilatory settings investigated and the breathing frequency adopted by the patients

Ventilatory setting	IPAP, cm H2O, median (range)	EPAP, cm H2O, median (range)	Ventilator BF, breaths/min median (range)	Patient BF, breaths/min median (range)
Own home settings	28 (25–30)	6 (4–9)	18 (13–22)
LPLF	18 (18–20)	6 (4–9)	10	20 (12–25)
HPLF	30 (28–34)	6 (4–9)	10	16 (10–26)
LPHF	18 (18–20)	6 (4–9)	22.5 (16–25)	25 (16–27)
HPHF	30 (28–34)	6 (4–9)	22.5 (16–25)	23 (15–27)

Abbreviations: LPLF, low-pressure/low-frequency setting; HPLF, high-pressure/low-frequency setting; LPHF, low-pressure/high-frequency setting; HPHF, high-pressure/high-frequency setting; IPAP, inspiratory positive airway pressure; EPAP, expiratory airway pressure; ventilator BF, breathing frequency set by the ventilator; patient BF, breathing frequency adopted by the patient, calculated as the number of patient efforts per minute on the EMG tracings.

Table 3 EMG activity per breath (average over 10 breaths) and total EMG activity in 1 min during the spontaneous breathing period before the NIV setting and during the selected NIV settings

EMG activity (microvolts)	SB	LPLF	SB	HPLF	SB	LPHF	SB	HPHF
Int – per breath	1.98 (1.3–4.1)	1.22 (0.6–2.1)*	2.19 (1.4–3.5)	1.18 (0.3–2.5)**	1.80 (1.4–2.7)	1.38 (0.5–2.8)**	2.36 (1.4–3.4)	0.64 (0.10–1.9)**
Int – total 1 min	43.7 (34–59)	24.1 (15–31)**	42.4 (30–48)	17.7 (4–41)**	42.4 (34–49)	31.5 (11–65)	40.7 (33–57)	13.6 (6–35)**
Dia – per breath	9.86 (5.9–14.1)	6.52 (2.9–7.9)**	8.67 (5.9–13.7)	4.07 (2.4–6.7)*	8.17 (6.2–12.1)	7.57 (3.6–11.5)**	9.51 (5.9–12.6)	2.94 (1.0–4.9)**
Dia – total 1 min	180.8 (134–210)	103.8 (67–144)**	186.7 (153–215)	69.5 (38–125)*	169.5 (129–216)	150.9 (100–261)	178.0 (117–205)	75.3 (36–129)**
Sc – per breath	2.07 (0.9–3.6)	1.38 (0.6–2.8)	2.52 (1.1–3.9)	1.27 (0.5–2.0)	2.19 (0.7–3.8)	1.84 (0.7–3.9)	3.01 (1.4–3.9)	1.31 (0.4–2.4)**
Sc – total 1 min	40.8 (21–77)	21.8 (15–52)	38.6 (27–69)	16.9 (11–62)	43.3 (17–72)	37.6 (17–85)	40.2 (17–79)	27.5 (11–46)
BF (breaths/min)	21.5 (11–28)	19.8 (12–25)	18.2 (15–23)	15.8 (12–21)	20.3 (17–23)	24.6 (22–26)**	17.8 (15–21)	23.4 (22–24)**

Notes: Raw EMG data were not normally distributed, therefore median and interquartile ranges are shown.

* P<0.001 and

** P<0.05 compared with a Mann–Whitney U-test.

Abbreviations: EMG, electromyography; Int, intercotal EMG activity; Dia, diaphragm EMG activity; Sc, scalene EMG activity; BF, breathing frequency; SB, spontaneous breathing; LPLF, low-pressure, low-frequency setting; HPLF, high-pressure, low-frequency setting; LPHF, low-pressure, high-frequency setting; HPHF, high-pressure, high-frequency setting.

Figure 1 EMG activity ratios (EMGARs) with the different settings are shown per breath (A) and per minute (B).

Notes: Entries shown are medians and interquartile ranges. Low-frequency settings are shown in black (●: LPLF setting; ■: HPLF setting), High-frequency settings are shown in gray (▲: LPHF setting; ▼ HPHF setting). EMGAR is the ratio between the EMG activity during NIV divided by the resting breathing EMG activity. For example, an EMGAR of 0.29 for the diaphragm during the HPHF setting means a decrease in EMG activity with a factor 1/0.29=3.4 with this setting compared to resting breathing. *P<0.05, **P<0.01, and ***P<0.001.
Abbreviations: EMG, electromyography; LPLF, low-pressure, low-frequency setting; HPLF, high-pressure, low-frequency setting; LPHF, low-pressure, high-frequency setting; HPHF, high-pressure, high-frequency setting; NIV, noninvasive ventilation.

Table 4 Patient-ventilator asynchrony during different settings

Control of breath and asynchrony event	LPLF	HPLF	LPHF	HPHF
Breaths counted per measurement (requested and delivered) mean (range)	218 (110–325)	184 (73–325)	277 (137–284)	275 (160–361)
Pressure-supported, % of breaths* (range)	97 (83–100)	88 (39–100)	39* (2–99)	25 (0–100)
Pressure-controlled, % of breaths* (range)	2 (0–13)	10 (0–56)**	61 (1–98)*	74 (0–99)
Ineffective breaths
% of patients with at least 1 event	75	75	65	55
% of counted breaths, mean (range)	1.5 (0–9)	5.3 (0–26)	0.9 (0–3)	0.9 (0–9)
Patients with >10% of the asynchrony event, n	0	3#	0	0
Autotriggering
% of patients with at least 1 event	70	65	40	45
% of counted breaths, mean (range)	1.9 (0–8)##	1.8 (0–9)###	0.4 (0–3)	0.9 (0–9)
Patients with >10% of the asynchrony event, n	0	0	0	0
Double or multiple triggering
% of patients with at least 1 event	20	60	30	25
% of counted breaths, mean (range)	0.3 (0–4)##	0.9 (0–5)	0.6 (0–6)	0.4 (0–4)
Patients with >10% of the asynchrony event, n	0	0	0	0
Total triggering asynchrony
% of patients with at least 1 event	95	90	70	55
% of counted breaths, mean (range)	3.7 (0–14)	8.0 (0–29)	1.8 (0–9)	2.2 (0–10)
Patients with >10% of the asynchrony event, n	2	6	0	0
Premature cycling
% of patients with at least 1 event	2	5	6	3
% of counted breaths, mean (range)	0.1 (0–1)	0.3 (0–3)	0.8 (0–6)	0.1 (0–1)
Patients with >10% of the asynchrony event, n	0	0
Delayed cycling
% of patients with at least 1 event	2	6	0	5
% of counted breaths, mean (range)	0.2 (0–2)	1.7 (0–16)	0 (0–0)	0.2 (0–3)
Patients with >10% of the asynchrony event, n	0	1	0	0
Total cycling asynchrony
% of patients with at least 1 event	4	10	7	7
% of counted breaths, mean (range)	0.3 (0–2)	2.0 (0–16)	0.7 (0–6)	0.5 (0–3)
Patients with >10% of the asynchrony event, n	0	2	0	0

Notes: Differences between the settings were tested with a Friedman test for multiple comparisons and pairwise comparisons with Mann–Whitney U-tests.

* HF versus LF: P<0.001;

** LPLF vs HPLF: P=0.001;

# HPLF vs high-frequency settings: P=0.017;

## LPLF vs LPHF: P=0.001; and

### HPLF vs HPHF: P=0.036.

Abbreviations: LPLF, low-pressure/low-frequency setting; HPLF, high-pressure/low-frequency setting; LPHF, low-pressure/high-frequency setting; HPHF, high-pressure/high-frequency setting.

Figure 2 Transcutaneous carbon dioxide pressure (PtCO₂) during spontaneous breathing and with the different settings.

Notes: Shown are the PtCO₂ values during the last minute of the prior spontaneous breathing period and during the last minute of the particular setting. *P<0.05.
Abbreviations: LPLF, low-pressure/low-frequency setting; HPLF, high-pressure/low-frequency setting; LPHF, low-pressure/high-frequency setting; HPHF, high-pressure/high-frequency setting.

Figure 3 Reproducibility of the EMG of the intercostal muscles (A), diaphragm (B), and scalene muscles (C).

Notes: Bland & Altman plots. Shown are mean EMGAR measurements 1 and 2 on the x-axis and the difference (Diff) between those EMGARs on the y-axis. The mean difference is shown with a straight line, with 95% CI with dashed lines (●: LPLF setting; ■: HPLF setting; ▲: LPHF setting; ▼: HPHF setting).
Abbreviations: EMG, electromyography; EMGAR, EMG activity ratio; LPLF, low-pressure/low-frequency setting; HPLF, high-pressure/low-frequency setting; LPHF, low-pressure/high-frequency setting; HPHF, high-pressure/high-frequency setting.

Figure S1 The QRS removal process.

Notes: The averaged EMG (EMGa) shows respiratory activity. As control the signal from the abdominal magnetometer band (Band) is shown. From the diaphragmatic EMG signal (EMGd), the QRS complex was detected and stretched into a standard QRS pulse with a duration of 100 ms (QRS). During the QRS pulse a cut was made in the slightly delayed (40 ms) EMG signal to completely filter out the QRS complex (EMGg). Next, the gated EMG was rectified and averaged with a moving time window of 200 ms. Finally, the missing signal in the gate was filled with the running average resulting in a fairly good interpolation during the gate and an almost QRS-free averaged EMG signal (EMGa).

Abbreviation: EMG, electromyography.

Figure S2 A pressure-supported (PS) breath.

Notes: Shown are (from top to bottom) the raw intercostal signal (Int raw), the raw frontal diaphragm signal (F Dia raw), the raw dorsal diaphragm signal (D Dia raw), the pressure wave (Paw), the average intercostal signal (Interc), the average frontal diaphragm (F Dia) signal, and the average dorsal diaphragm signal (D Dia). Two PS breaths are shown, as electromyography activity (the dotted red line) precedes the pressure wave (the straight blue line). A low backup frequency of 10 breaths/min was set on the ventilator, therefore a 2.6 s time in-between the breaths confirms that breaths were PS and not pressure-controlled (PC).

Abbreviation: EMG, electromyography.

Figure S3 A pressure-controlled (PC) breath.

Notes: Shown are (from top to bottom) the raw intercostal signal (Int raw), the raw frontal diaphragm signal (F Dia raw), the raw dorsal diaphragm signal (D Dia raw), the pressure wave (Paw), the average intercostal signal (Interc), the average frontal diaphragm (F Dia) signal, and the average dorsal diaphragm signal (D Dia). Two PC breaths are shown, electromyography activity (the dotted red line) appears but after the pressure wave (the straight blue line) started. This is a tracing during a high-pressure, high-frequency setting, with a backup frequency of 22 breaths/min, so that an in-between breath time of 2.7 s means that the ventilator delivers a breath at the moment it is supposed to do according to the set-up backup frequency. Of note, electromyography activity was much lower with this setting.

Figure S4 An ineffective effort.

Notes: Shown are (from top to bottom) the raw intercostal signal (Int raw), the raw frontal diaphragm signal (F Dia raw), the raw dorsal diaphragm signal (D Dia raw), the pressure wave (Paw), the average intercostal signal (Interc), the average frontal diaphragm (F Dia) signal, and the average dorsal diaphragm signal (D Dia). An electromyography signal (dotted red line) was not followed by a breath delivered by the ventilator (straight arrow blue line).

Figure S5 Autotriggering.

Notes: Shown are (from top to bottom) the raw intercostal signal (Int raw), the raw frontal diaphragm signal (F Dia raw), the raw dorsal diaphragm signal (D Dia raw), the pressure wave (Paw), the average intercostal signal (Interc), the average frontal diaphragm (F Dia) signal, and the average dorsal diaphragm signal (D Dia). During this low-frequency setting (backup frequency 10 breaths/min), the two breaths denoted by arrows come too soon to be PC. As it is not preceded by EMG activity, these are defined as inappropriate autotriggered breaths (straight blue lines).

Abbreviations: EMG, electromyography; PC, pressure-controlled.

Figure S6 Double triggering.

Notes: Shown are (from top to bottom) the raw intercostal signal (Int raw), the raw frontal diaphragm signal (F Dia raw), the raw dorsal diaphragm signal (D Dia raw), the pressure wave (Paw), the average intercostal signal (Interc), the average frontal diaphragm (F Dia) signal, and the average dorsal diaphragm signal (D Dia). A single electromyography wave (dotted red line) is followed by two ventilator delivered breaths (nr.1 and nr.2 straight blue lines).

Figure S7 Premature cycling.

Notes: Shown are (from top to bottom) the raw intercostal signal (Int raw), the raw frontal diaphragm signal (F Dia raw), the raw dorsal diaphragm signal (D Dia raw), the pressure wave (Paw), the average intercostal signal (Interc), the average frontal diaphragm (F Dia) signal, and the average dorsal diaphragm signal (D Dia). Electromyography activity (the maximum of the electromyography is depicted by the red dotted line) continues, while the pressure returns to baseline again (the end of the inspiratory pressure delivering is depicted by the blue dotted line).

Figure S8 Delayed cycling.

Notes: Shown are (from top to bottom) the raw intercostal signal (Int raw), the raw frontal diaphragm signal (F Dia raw), the raw dorsal diaphragm signal (D Dia raw), the pressure wave (Paw), the average intercostal signal (Interc), the average frontal diaphragm (F Dia) signal, and the average dorsal diaphragm signal (D Dia). The electromyography activity has already ceased (end of the electromyography activity depicted by the red dotted line), while the pressure wave continues, (end of the breaths depicted by the straight blue line).