Emelie Ekkernkamp

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.

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 PCO2 (PtcCO2), 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 PtcCO2 values during FB between the two groups (all p > 0.05). However, PtcCO2 significantly increased over time in both groups (both p < 0.001; RM-ANOVA on ranks). Minimum oxygen saturation (SaO2) [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 ≧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.

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.

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 (P_aO₂, P_aCO₂) and capillary blood gas (P_CBGO₂, P_CBGCO₂) measurements were taken consecutively in a randomized order and were compared with noninvasive measurements obtained from the transcutaneous monitoring of PO₂ and PCO₂ (P_tcO₂, P_tcCO₂, 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 P_aO₂ and P_tcO₂ 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 P_aO₂ with P_CBGO₂ showed a mean difference of 5.6 ± 7.2 mm Hg (LLA -11.0; ULA 19.6 mm Hg). The mean difference between P_aCO₂ and P_tcCO₂ was 1.1 ± 4.9 mm Hg (LLA -8.6; ULA 10.8 mm Hg) and that between P_aCO₂ and P_CBGCO₂ 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.

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).

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

Abstract 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.