Table 1.
Clinical trials investigating the effect of LT-NIV in chronic hypercapnic COPD on different outcomes.
| Study Name | Population | Primary Outcome | Favors NIV | Baseline PaCO2, kPa | AE Frequency at Baseline |
BMI | OSA | Normalizing Hypercapnia, Yes/No | NIV Mode |
|---|---|---|---|---|---|---|---|---|---|
| Casanova 2000 [127] | Stable | Number of AEs | No | 6.8 ± 1.1 | No data | 25 ± 4 | Excluded | No | Nasal BiPAP, S mode, EPAP: 4 cmH2O; IPAP: 12 cmH2O |
| Clini 2002 [128] | Stable | Arterial blood gas values, hospital and ICU admissions, total hospital and ICU length of stay, HRQL | Partly | 7.2 ± 0.6 | No data | 26 ± 5 | Excluded | Yes (5% decrease) | Nasal BiPAP, S/T mode, backup frequency: 8/min; EPAP: 2–5 cmH2O; IPAP: maximal tolerated pressure |
| Duiverman 2008 [134] | Stable | HRQL, functional status and gas exchange parameters | Yes | 6.89 ± 0.68 | No data | 27.1 ± 6.4 | Excluded | Yes (PaCO2 < 6.0 kPa) | BiPAP, S/T mode; IPAP: maximal tolerated pressure titrated towards an optimal correction of nocturnal arterial blood gases (PaCO2 6.0 kPa and PaO2 8.0 kPa) |
| Garrod 2000 [138] | Stable | Exercise capacity and health status | Yes | 5.9 ± 0.9 | No data | No data | Not excluded | No | Nasal BiPAP, S mode overnight or minimum 8 h/day, settings adjusted individually to obtain the maximal pressure tolerated; EPAP: 4 (4–6) cmH2O; IPAP: 16 (13–24) cmH2O |
| Köhnlein 2014 [93] | Stable | 1-year all-cause mortality | Yes | 7.8 ± 0.8 | No data | 24.8 ± 5.8 | Not excluded | Yes (>20% decrease or PaCO2 < 6.5 kPa) | Pressure support ventilation with high backup rates minimum 6 h/day, preferably during sleep (face or nasal mask). Aim: to reduce ≥20% baseline PaCO2 or PaCO2 < 6.5 kPa |
| Marquez-Martin 2014 [135] | Stable | Exercise capacity | Favors ventilation/training combined group over ventilation alone | NIV group: median 51, NIV-ET group: median 50 | No data | No data | Excluded | No | Nocturnal nasal BiPAP, S/T mode, backup frequency 12/min, 6–8 h/night; EPAP: 4 cmH2O; IPAP: initially 10 cmH2O and increased progressively to a maximum of 20 cmH2O, depending on patient tolerance, clinical response and SpO2 |
| McEvoy 2009 [129] | Stable | Survival | Yes | 7.01 [6.80–7.23] | No data | 25.5 [24.3–26.7] | Excluded | No | BiPAP, VPAP mode, EPAP: lowest possible level (~3 cm H2O); IPAP: gradually increased during daytime and night-time trials to the maximum tolerated with a target PS of ≥10 cm H2O |
| Cheung 2010 [148] | Post AE (>48 h after successful weaning of acute NIV) | Recurrent severe AE with AHRF requiring acute NIV, intubation or resulting in death in the first year | Yes | 7.7 ± 1.0 | Previous acute NIV: 1 [0–3], previous intubation: 0 (0–1), no other data | 19.2 ± 3.6 | Excluded | No | BiPAP, S/T mode, backup frequency: 14/min; EPAP: 5 cmH2O; IPAP: 10–20 cmH2O |
| De Backer 2011 [149] | Post AE (5–12 days after admission) | Arterial blood gas values and functional imaging of the lungs | Yes | 7.39 ± 1.03 | No data | No data | Excluded | Yes (5% decrease) | BiPAP for >5 h a day with a full face mask; modes were adapted until O2 saturation was >90% during 90% of the time, and PaCO2 was decreased 5% in 1 h |
| Funk 2011 [153] | Post AE (before discharge from the ICU or immediately after transfer to regular wards) | Time to clinical worsening Defined as an escalation of mechanical ventilation | Yes | 7.6 ± 1.7 | No data | 24.2 ± 4.3 | Excluded | No | BiPAP EPAP: ~5 cmH2O; IPAP: increasingly raised from 10 to ~20 cmH2O. The inspiratory time was limited to a maximum of 1.3 s |
| Murphy 2017 [150] | Post AE (2–4 weeks after resolution of respiratory acidemia) | Time to readmission or death within 12 months adjusted for the number of previous COPD admissions, previous use of long-term oxygen, age, and BMI | Yes | 7.87 ± 0.93 | ≥3 COPD-related readmissions within past year: NIV-LTOT group: N = 30 (53%) vs. LTOT group: N = 31 (53%) | 21.5 (18.8–24.5) | Excluded | Yes (reduce tcCO2 by at least 4 mmHg) | BiPAP, PS mode, recommended initial titration settings: IPAP 18 cmH2O, EPAP 4 cmH2O, backup rate 14–16/min; target IPAP ≥25 cmH2O. NIV settings and O2 flow rate were titrated to maintain SpO2 >88% and to reduce tcCO2 by ≥4 mmHg |
| Struik 2014 [151] | Post AE (>48 h after termination of ventilatory support) | Time to readmission for respiratory cause or death | No | 7.9 ± 1.2 | Median: 2, min–max: 1–9 | 24.6 ± 5.4 | Excluded | Yes (to achieve normocapnia) | BiPAP, S/T mode starting with a backup frequency of 12/min; IPAP: initial 14 cmH2O and gradually increased to a maximal tolerated level; EPAP: initial 4 cmH2O and increased if auto-PEEP was present or when patients used respiratory muscles to trigger the ventilator. Respiratory rate was set as close as possible to the that of the patient. I:E ratio was 1:3, with a short rise time and then titrated on comfort and effectiveness |
Abbreviations: AE, acute exacerbation; AHRF, acute hypercapnic respiratory failure; BiPAP, bilevel positive airway pressure; BMI, body mass index; COPD, chronic obstructive pulmonary disease; EPAP, expiratory positive airway pressure; I:E, ratio of inhalation to exhalation; IPAP, inspiratory positive airway pressure; LT, long-term; NIV, noninvasive ventilation; OSA, obstructive sleep apnea syndrome; PaCO2, partial arterial carbon dioxide pressure; PEEP, positive end-expiratory pressure; PS, pressure support; SpO2, arterial oxygen saturation; S/T mode, spontaneous/timed mode.