Nasal versus oronasal masks for home non-invasive ventilation in patients with chronic hypercapnia: a systematic review and individual participant data meta-analysis.

BACKGROUND: The optimal interface for the delivery of home non-invasive ventilation (NIV) to treat chronic respiratory failure has not yet been determined. The aim of this individual participant data (IPD) meta-analysis was to compare the effect of nasal and oronasal masks on treatment efficacy and adherence in patients with COPD and obesity hypoventilation syndrome (OHS). METHODS: We searched Medline and Cochrane Central Register of Controlled Trials for prospective randomised controlled trials (RCTs) of at least 1 month's duration, published between January 1994 and April 2019, that assessed NIV efficacy in patients with OHS and COPD. The main outcomes were diurnal PaCO2, PaO2 and NIV adherence (PROSPERO CRD42019132398). FINDINGS: Of 1576 articles identified, 34 RCTs met the inclusion criteria and IPD were obtained for 18. Ten RCTs were excluded because only one type of mask was used, or mask data were missing. Data from 8 RCTs, including 290 IPD, underwent meta-analysis. Oronasal masks were used in 86% of cases. There were no differences between oronasal and nasal masks for PaCO2 (0.61 mm Hg (95% CI -2.15 to 3.38); p=0.68), PaO2 (-0.00 mm Hg (95% CI -4.59 to 4.58); p=1) or NIV adherence (0·29 hour/day (95% CI -0.74 to 1.32); p=0.58). There was no interaction between the underlying pathology and the effect of mask type on any outcome. INTERPRETATION: Oronasal masks are the most used interface for the delivery of home NIV in patients with OHS and COPD; however, there is no difference in the efficacy or tolerance of oronasal or nasal masks.

Pulmonary rehabilitation and noninvasive ventilation in patients with hypercapnic interstitial lung disease.

BACKGROUND: Pulmonary rehabilitation (PR) has a positive impact on functional status and quality of life in patients with interstitial lung disease (ILD). OBJECTIVES: This study investigated the effects of PR in hypercapnic ILD patients receiving nighttime noninvasive positive pressure ventilation (NPPV). METHODS: Consecutive ILD patients referred to a specialized inpatient PR center were included. All participated in a PR program. Those with hypercapnia received NPPV (NPPV group; n = 29); the remaining patients served as comparison group (n = 319). RESULTS: PR improved the 6-min walk distance by 64.4 ± 67.1 m versus baseline (p < 0.0001) in NPPV patients and by 43.2 ± 55.1 m (p < 0.0001) in the comparison group (difference 21.1 m, 95% confidence interval 0.5-41.8; p = 0.045). There was no change in total lung capacity during PR in NPPV recipients or the comparison group. Forced vital capacity significantly increased from baseline in the comparison, but not the NPPV group. NPPV recipients were significantly more likely than the comparison group to have improved dyspnea during PR (p = 0.049). There was no improvement in the 36-item Short Form (SF-36) physical component score in the NPPV group after PR, but there was in the comparison group. PR improved the SF-36 mental component score versus baseline in both groups. CONCLUSION: An individually tailored PR plus nighttime NPPV appears feasible in hypercapnic ILD patients and significantly improves exercise capacity and quality of life.

Spot check analysis of gas exchange: invasive versus noninvasive methods.

BACKGROUND: Correct measurement of PO2 and PCO2 is essential to establish appropriate therapy such as long-term oxygen therapy (LTOT) in patients suffering from respiratory failure. OBJECTIVES: We aimed to compare common invasive and noninvasive methods for assessing blood gas components for spot check analysis. METHODS: Arterial (PaO2, PaCO2) and capillary blood gas (PCBGO2, PCBGCO2) measurements were taken consecutively in a randomized order and were compared with noninvasive measurements obtained from the transcutaneous monitoring of PO2 and PCO2 (PtcOv, PtcCO2, sensor-temperature 44°C). Capillary samples were taken from both arterialized earlobes, where samples of right earlobes were defined as a reference value. Pain assessment of all measurements was evaluated by each subject using the 100-mm visual analogue scale. RESULTS: 83 patients and 17 healthy subjects were included. The mean difference between PaO2 and PtcO2 was 11.9 ± 15.0 mm Hg, with lower limits of agreement (LLA) of -17.4 mm Hg (95% confidence interval (CI) -22.5 to -12.3 mm Hg), and upper limits of agreement (ULA) of 41.1 mm Hg (95% CI 36.0-46.2 mm Hg). The comparison of PaO2 with PCBGO2 showed a mean difference of 5.6 ± 7.2 mm Hg (LLA -11.0; ULA 19.6 mm Hg). The mean difference between PaCO2 and PtcCO2 was 1.1 ± 4.9 mm Hg (LLA -8.6; ULA 10.8 mm Hg) and that between PaCO2 and PCBGCO2 was 0.7 ± 2.0 mm Hg (LLA -3.3; ULA 4.8 mm Hg). The analysis of capillary blood gases (36.2 ± 22.3 mm) was rated as more painful than the analysis of arterial blood gases (26.1 ± 20.6 mm), while transcutaneous measurement was rated as the least painful method (1.9 ± 7.4 mm; all p < 0.0001). CONCLUSIONS: The comparison of different methods for blood gas measurements showed substantial differences between capillary and arterial PO2 and between transcutaneous and arterial PO2. Therefore, arterial PO2 analysis is the essential method evaluating indication for LTOT. Nevertheless, comparative analysis further indicated capillary PCO2 as an adequate surrogate for arterial PCO2.

Walking with Non-Invasive Ventilation Does Not Prevent Exercise-Induced Hypoxaemia in Stable Hypercapnic COPD Patients.

BACKGROUND: Non-invasive positive pressure ventilation (NPPV) in addition to supplemental oxygen improves arterial oxygenation, walking distance and dyspnea when applied during exercise in stable hypercapnic COPD patients. The aim of the current study was to investigate whether NPPV without supplemental oxygen is capable of preventing severe exercise-induced hypoxemia in these patients when applied during walking. METHODS AND RESULTS: 15 stable hypercapnic COPD patients (FEV1 29.9 ± 15.9%) performed two 6-minute walk tests (6MWT) with a rollator in a randomized cross-over design: using either supplemental oxygen (2.4 ± 0.7 L/min) or NPPV (inspiratory/expiratory positive airway pressure of 28.2 ± 2.8 / 5.5 ± 1.5 mbar) without supplemental oxygen. RESULTS: 10 patients were able to complete both 6MWT. 6MWT with supplemental oxygen resulted in no changes for PO2 (pre: 67.3 ± 11.2 mmHg vs. post: 65.6 ± 12.0 mmHg, p = 0.72) whereas PCO2 increased (pre: 50.9 ± 8.1 mmHg vs. post: 54.3 ± 10.0 mmHg (p < 0.03). During 6MWT with NPPV PO2 significantly decreased from 66.8 ± 7.2 mmHg to 55.5 ± 10.6 mmHg (p < 0.02) whereas no changes occurred in PCO2 (pre: 50.6 ± 7.5 mmHg vs. post: 53.0 ± 7.1 mmHg; p = 0.17). Walking distance tended to be lower in 6MWT with NPPV compared to 6MWT with supplemental oxygen alone (318 ± 160 m vs. 377 ± 108 m; p = 0.08). CONCLUSION: The use of NPPV during walking without the application of supplemental oxygen does not prevent exercise-induced hypoxemia in patients with stable hypercapnic COPD.

Impact of intelligent volume-assured pressure support on sleep quality in stable hypercapnic chronic obstructive pulmonary disease patients: a randomized, crossover study.

BACKGROUND: Noninvasive positive-pressure ventilation (NPPV) using intelligent volume-assured pressure support (iVAPS) combines volume- and pressure-preset NPPV and therefore uses a variation of inspiratory positive airway pressures. OBJECTIVES: The effect of iVAPS on sleep quality in stable hypercapnic patients with chronic obstructive pulmonary disease (COPD) has not been determined. METHODS: In this randomized, open-label, two-treatment, two-period, crossover study, patients were randomized to receive high-intensity (HI)-NPPV and then iVAPS or iVAPS and then HI-NPPV. Patients were studied in hospital for 2 consecutive nights, employing full polysomnography (PSG), transcutaneous partial pressure of CO2 (PtcCO2) monitoring, blood gas analysis and a visual analog scale (VAS)-based sleep questionnaire. After discharge, patients used HI-NPPV and iVAPS at home, each for 6 weeks. They had to answer a VAS question concerning sleep every morning, and were telephoned weekly and asked additional questions. At the end of each treatment period, they were visited at home for the determination of blood gases and treatment adherence, and to change the NPPV mode. RESULTS: Fourteen patients were enrolled. In-hospital PSG measurements showed no difference in sleep quality between iVAPS and HI-NPPV. At home, patients reported more restful sleep during iVAPS than HI-NPPV (p = 0.04). Blood gases during spontaneous breathing at home did not differ with iVAPS and HI-NPPV, and there was a greater decrease in PtcCO2 during iVAPS than during HI-NPPV (p = 0.003). CONCLUSION: Although sleep quality in hospital was not different between iVAPS and HI-NPPV, COPD patients with chronic hypercapnic respiratory failure reported a trend towards more restful sleep at home with iVAPS. In addition, nocturnal hypercapnia was effectively treated with iVAPS.

Minute ventilation during spontaneous breathing, high-intensity noninvasive positive pressure ventilation and intelligent volume assured pressure support in hypercapnic COPD.

BACKGROUND: High-intensity noninvasive positive pressure ventilation (HI-NPPV) is an effective treatment option in patients with stable hypercapnic chronic obstructive pulmonary disease (COPD). However, the effect of HI-NPPV compared with spontaneous breathing (SB) on minute ventilation (MV) in patients receiving long-term treatment remains to be determined. This study compared MV during HI-NPPV and SB. In addition, the ability of intelligent volume assured pressure support (iVAPS) to increase MV to the same extent as HI-NPPV was determined. METHODS: Daytime pneumotachographic measurements were performed during SB, HI-NPPV and iVAPS. RESULTS: Twenty-seven stable hypercapnic COPD patients (mean FEV1 34 ± 15% predicted) who had been treated with HI-NPPV for a median of 22 months (interquartile range 8.5-84 months) were enrolled. Mean MV was 9.5 ± 1.7 L/min during SB and 12.1 ± 2.8 L/min during HI-NPPV, an increase of 2.5 L/min (95% CI [1.5-3.6] p < 0.001), or 26%. MV during iVAPS was 11.7 ± 3.6 L/min, an increase of 1.8 L/min (95%CI [0.7-3.0], p = 0.003) compared with SB. There was no difference in MV between HI-NPPV and iVAPS (p = 0.25). CONCLUSION: Long-term HI-NPPV increased MV by an average of 26% compared with SB in stable hypercapnic COPD patients. A similar increase in MV was observed during use of iVAPS.

Sedation during flexible bronchoscopy in patients with pre-existing respiratory failure: Midazolam versus Midazolam plus Alfentanil.

BACKGROUND: The use of sedation during flexible bronchoscopy (FB) is undisputed; however, the combination of benzodiazepines and opiates, although reasonable, is suggested to cause hypoventilation, particularly in patients with pre-existing respiratory failure. OBJECTIVES: To assess respiratory function during FB. METHODS: Transcutaneous PCO(2 )(PtcCO(2)), oxygen saturation, patients' tolerance, time after FB until recovery and application of drug dosage were assessed in patients receiving either midazolam with alfentanil (n = 15) or midazolam alone (n = 15) for sedation for FB. RESULTS: There were no differences in PtcCO(2) values during FB between the two groups (all p > 0.05). However, PtcCO(2 )significantly increased over time in both groups (both p < 0.001; RM-ANOVA on ranks). Minimum oxygen saturation (SaO(2)) [89 (interquartile range 79.8/92.8) vs. 86 (interquartile range 82.3/87.8)%; p = 0.46] and the duration until recovery, i.e., achieving an ALDRETE score of > or =9 [30 (interquartile range 10/90) vs. 10 (interquartile range 10/105) min; p = 0.68] were comparable for monosedation and combined sedation, respectively. The total amount of midazolam [4.0 (interquartile range 4.0/4.0) vs. 2.0 (interquartile range 2.0/2.0) mg; p < 0.001] was lower in patients receiving combined sedation. Significantly lower scores for pain and asphyxia, and a clear tendency to less nausea and cough were reported by patients receiving combined sedation. CONCLUSIONS: Combined sedation during FB produced a comparable degree of desaturation and hypoventilation, and is associated with a comparable time to full recovery compared to monosedation in patients with pre-existing respiratory failure. Importantly, FB using combined sedation is better tolerated by patients despite only 50% midazolam consumption.

Influence of effective noninvasive positive pressure ventilation on inflammatory and cardiovascular biomarkers in stable hypercapnic COPD patients.

BACKGROUND: Noninvasive positive pressure ventilation (NPPV) using effective pressure levels to reduce chronic hypercapnia improves survival in stable hypercapnic COPD. However, the underlying mechanisms remain unclear. This study investigated the influence of effective NPPV on a panel of cytokines and established cardiovascular biomarkers. METHODS: Peripheral blood samples were drawn before and three months after the initiation of NPPV and analyzed by flow cytometric bead array and ELISA. RESULTS: Twenty COPD patients (forced expiratory volume in 1 s 31 ± 17% predicted) were included. NPPV (inspiratory positive airway pressure 23 ± 4 mbar; breathing frequency 17 ± 2/min) significantly improved arterial carbon dioxide pressure (PaCO2), both during daytime spontaneous breathing (p = 0.005) and nighttime ventilation (p < 0.001). Serum interleukin (IL)-10 levels were slightly reduced (p = 0.016), whereas IL-1 (p = 0.073) and IL-12 (p = 0.089) showed only a tendency towards change over time. Pro-brain natriuretic peptide (proBNP) significantly decreased by a mean of 578 ± 1332 ng/L after three months' NPPV (p = 0.017 vs baseline). No other significant changes in cardiovascular biomarkers occurred. The decrease in PaCO2 during daytime spontaneous breathing was positively correlated with the reduction in proBNP (correlation coefficient 0.613; p = 0.0197). CONCLUSION: Effective NPPV impacts on systemic inflammation in COPD patients. Furthermore, reductions in PaCO2 during NPPV were associated with decreases in proBNP levels. Future studies are needed to clarify these findings in a larger cohort of COPD patients. CLINICAL TRIAL REGISTRATION: DRKS00007644 (German Clinical Trials Register; https://drks-neu.uniklinik-freiburg.de/drks_web/navigate.do?navigationId=resultsExt).

Oxygen supplementation in noninvasive home mechanical ventilation: the crucial roles of CO2 exhalation systems and leakages.

BACKGROUND: When supplemental oxygen is added to noninvasive ventilation using a non-ICU ventilator, it is usually introduced with a preset flow into the circuit near the ventilator; however, the impact of different CO2 exhalation systems and leaks on the actual FIO2 and gas exchange has not been elucidated. METHODS: In a randomized, open-label, 4-treatment (2-by-2), 4-period crossover design, 4 daytime measurements (60 min each) were performed in 20 subjects receiving home mechanical noninvasive ventilation plus supplemental oxygen (≥ 2 L/min) inserted near the ventilator: active valve circuit or leak port circuit with or without artificial leakage (4 mm inner diameter). Oxygen concentration near the ventilator, oxygen concentration at the mask, and blood gases were measured. RESULTS: Overall, oxygen concentration at the mask (29 ± 5%) was lower than oxygen concentration at the ventilator (34 ± 4%), with a mean difference of 5.1% (95% CI 4.2-5.9%, P < .001)%. With the leak port circuit, oxygen concentration at the mask decreased by 3.2% (95% CI 2.6 to 3.9%, P < .001), compared to the active valve circuit. When artificial leakage was introduced into the circuit, oxygen concentration at the mask decreased by 5.7% (95% CI 5.1 to 6.4%, P < .001)%, PaO2 by 10.4 mm Hg (95% CI 3.1 to 17.7 mm Hg, P = .006), and PaCO2 increased by 1.8 mm Hg (95% CI 0.5 to 3.1 mm Hg, P = .008). CONCLUSIONS: The use of a leak port circuit and the occurrence of leak around the interface significantly reduced oxygen concentration at the mask and negatively impacted gas exchange in subjects receiving home noninvasive ventilation and supplemental oxygen. (German Clinical Trials Registry, www.drks.de, DRKS00000449).

Home mechanical ventilation for COPD: high-intensity versus target volume noninvasive ventilation.

BACKGROUND: High-intensity noninvasive ventilation (HI-NIV) is the most effective means of improving several physiological and clinical parameters in subjects with chronic hypercapnic COPD. Whether the newer hybrid mode using target tidal volume noninvasive ventilation (target V(T) NIV) provides additional benefits remains unclear. METHODS: Subjects with COPD successfully established on long-term HI-NIV were switched to target V(T) NIV. Optimal target V(T) settings according to nocturnal transcutaneous P(CO2) measurements were achieved following a randomized crossover trial using 8 mL/kg ideal body weight and 110% of individual V(T) during HI-NIV, respectively. The following parameters were compared at the beginning of the trial while subjects were on HI-NIV, and after 3 months on optimal target V(T) NIV: sleep quality by polysomnography, overnight gas exchange, subjects' tolerance, overnight pneumotachygraphic measurements during NIV, health-related quality of life (severe respiratory insufficiency questionnaire), exercise capacity (6-min walk test), and lung function. RESULTS: Ten of 14 subjects completed the study. There were no differences between HI-NIV and target V(T) NIV in any of the above-mentioned parameters. Specifically, the mean overnight transcutaneous P(CO2) was equivalent under each form of ventilation (both 45 ± 5 mm Hg, P = .75). CONCLUSIONS: Switching subjects from well-established HI-NIV to target V(T) NIV shows no clinical benefits in chronic hypercapnic COPD. In particular, sleep quality, the control of nocturnal hypoventilation, daytime hypercapnia, overnight ventilation patterns, subjects' tolerance, health-related quality of life, lung function, and exercise capability were all similar in subjects who underwent HI-NIV and target V(T) NIV. Nevertheless, target V(T) NIV might offer some physiological advantages in breathing pattern and might be beneficial in some individual patients. (German Clinical Trials Register [www.drks.de] Registration DRKS00000450.).

Noninvasive ventilation in COPD: impact of inspiratory pressure levels on sleep quality.

BACKGROUND: Although high-intensity noninvasive positive pressure ventilation (HI-NPPV) is superior to low-intensity noninvasive positive pressure ventilation (LI-NPPV) in controlling nocturnal hypoventilation in stable hypercapnic patients with COPD, it produces higher amounts of air leakage, which, in turn, could impair sleep quality. Therefore, the present study assessed the difference in sleep quality during HI-NPPV and LI-NPPV. METHODS: A randomized, controlled, crossover trial comparing sleep quality during HI-NPPV (mean inspiratory positive airway pressure 29 ± 4 mbar) and LI-NPPV (mean inspiratory positive airway pressure 14 mbar) was performed in 17 stable hypercapnic patients with COPD who were already familiar with HI-NPPV. RESULTS: Thirteen patients (mean FEV(1) 27% ± 11% predicted) completed the trial; four patients refused to sleep under LI-NPPV. There was no significant difference in sleep quality between the treatment groups (all P > .05), with a mean difference of -3.0% (95% CI, -10.0 to 3.9; P = .36) in the primary outcome, namely non-rapid eye movement sleep stages 3 and 4. However, nocturnal Paco(2) was lower during HI-NPPV compared with LI-NPPV, with a mean difference of -6.4 mm Hg (95% CI, -10.9 to -1.8; P = .01). CONCLUSIONS: In patients with COPD, high inspiratory pressures used with long-term HI-NPPV produce acceptable sleep quality that is no worse than that produced by lower inspiratory pressures, which are more traditionally applied in conjunction with LI-NPPV. In addition, higher pressures are more successful in maintaining sufficient alveolar ventilation compared with low pressures. Thus, HI-NPPV is a very promising new approach, but still requires large, longer-term trials to determine the impact on outcomes such as exacerbation rates and longevity. TRIAL REGISTRY: German Clinical Trials Register (DRKS); No.: DRKS00000520; URL: www.drks.de.