Wolfram Windisch

Non-invasive positive pressure ventilation for the treatment of severe stable chronic obstructive pulmonary disease: a prospective, multicentre, randomised, controlled clinical trial

BACKGROUND Evidence is weak for the ability of long-term non-invasive positive pressure ventilation (NPPV) to improve survival in patients with stable hypercapnic chronic obstructive pulmonary disease (COPD). Previous prospective studies did not target a reduction in hypercapnia when adjusting ventilator settings. This study investigated the effect of long-term NPPV, targeted to markedly reduce hypercapnia, on survival in patients with advanced, stable hypercapnic COPD. METHODS This investigator-initiated, prospective, multicentre, randomised, controlled clinical trial enrolled patients with stable GOLD stage IV COPD and a partial carbon dioxide pressure (PaCO2) of 7 kPa (51.9 mm Hg) or higher and pH higher than 7.35. NPPV was targeted to reduce baseline PaCO2 by at least 20% or to achieve PaCO2 values lower than 6.5 kPa (48.1 mm Hg). Patients were randomly assigned (in a 1:1 ratio) via a computer-generated randomisation sequence with a block size of four, to continue optimised standard treatment (control group) or to receive additional NPPV for at least 12 months (intervention group). The primary outcome was 1-year all-cause mortality. Analysis was by intention to treat. The intervention was unblinded, but outcome assessment was blinded to treatment assignment. This study is registered with ClinicalTrials.gov, number NCT00710541. FINDINGS Patients were recruited from 36 respiratory units in Germany and Austria, starting on Oct 29, 2004, and terminated with a record of the vital status on July 31, 2011. 195 patients were randomly assigned to the NPPV group (n=102) or to the control group (n=93). All patients from the control group and the NPPV group were included in the primary analysis. 1-year mortality was 12% (12 of 102 patients) in the intervention group and 33% (31 of 93 patients) in the control group; hazard ratio 0.24 (95% CI 0.11-0.49; p=0.0004). 14 (14%) patients reported facial skin rash, which could be managed by changing the type of the mask. No other intervention-related adverse events were reported. INTERPRETATION The addition of long-term NPPV to standard treatment improves survival of patients with hypercapnic, stable COPD when NPPV is targeted to greatly reduce hypercapnia. FUNDING German Lung Foundation; ResMed, Germany; Tyco Healthcare, Germany; and Weinmann, Germany.

The Severe Respiratory Insufficiency (SRI) Questionnaire A specific measure of health-related quality of life in patients receiving home mechanical ventilation

BACKGROUND AND OBJECTIVE The objective of this study was to develop a specific instrument for measuring health-related quality of life (HRQL) in patients receiving home mechanical ventilation (HMV). METHODS The Severe Respiratory Insufficiency (SRI) Questionnaire was developed and tested for its psychometric properties following a multicentric clinical trial including 226 patients receiving HMV (mean age 57.3+/-14.0 years). RESULTS Forty-nine items passed the selection process and were allocated to seven subscales: Respiratory Complaints, Physical Functioning, Attendant Symptoms and Sleep, Social Relationships, Anxiety, Psychologic Well-Being, and Social Functioning. Cronbachs alpha was >0.7 in all subscales and >0.8 in four subscales indicating high internal consistency reliability. Construct validity was confirmed by factor analysis, indicating one summary scale that accounts for 59.8% of the variance. Concurrent validity was confirmed by correlating subscales of the SRI and the SF-36 (0.21<r<0.79). Item-scale correlations revealed a high item discriminant validity. In addition, different diagnostic groups could be discriminated by the SRI. Here, the overall best HRQL was measured in the following order: patients with kyphoscoliosis, miscellaneous disorders, neuromuscular diseases, post-tuberculosis, and chronic obstructive pulmonary disease (P<.05). CONCLUSION The SRI is a new multidimensional instrument with high psychometric properties designed to measure specific HRQL in patients with SRI receiving HMV.

Knowledge and attitude regarding organ donation among medical students and physicians.

Background. There is a discrepancy between demand and supply of donor organs for kidney transplantation. Health care providers can influence the willingness to donate or hold an organ donor card. It is unclear how educated current and future health care professionals are about organ donation and what constitutes their attitude toward this topic. Methods. The authors conducted a cross-sectional survey among 1,136 medical students and physicians to evaluate the knowledge about and attitude toward organ donation and transplantation at a large academic medical center in Germany. The authors used a 28-item questionnaire that included items on knowledge, attitude, and demographics. Results. Only 8% of the respondents felt sufficiently prepared for approaching relatives of potential organ donors. Knowledge about and attitude toward organ donation were highly associated with increasing level of medical education. In multivariate analyses, knowledge (odds ratio [OR], 1.17; 95% confidence interval [CI], 1.08–1.25), attitude (OR, 1.03; 95% CI, 1.02–1.04), and level of education (OR for preclinical students, 0.39; 95% CI, 0.20–0.76 compared with physicians) were significantly associated with the likelihood of holding an organ donor card, whereas age, gender, and personal experience with renal replacement therapy were not. Conclusions. Higher medical education is associated with greater knowledge about and a more positive attitude toward organ donation. Health care professionals with a higher education level are more likely to hold an organ donor card and also feel more comfortable in approaching relatives of potential organ donors. Educating health care professionals about the organ donation process appears to be an important factor in maximizing the benefits from the limited organ donor pool.

Noninvasive ventilation during walking in patients with severe COPD: a randomised cross-over trial

It was hypothesised that noninvasive positive-pressure ventilation (NPPV) applied during walking prevents exercise-induced hypoxaemia and improves exercise performance in severe chronic obstructive pulmonary disease (COPD) patients already receiving long-term NPPV. A total of 20 COPD patients (mean±sd age 65.1±8.7 yrs, forced expiratory volume in one second 27±8% predicted and total lung capacity 116±27% pred) reporting dyspnoea, even during mild exertion, underwent two 6-min walking tests with a rollator and supplemental oxygen (2.1±0.9 L·min−1) in a randomised cross-over design: with and without pressure-limited NPPV as used at home (inspiratory:expiratory pressure 2.9±0.44:0.4±0.1 kPa (29±4:4±1 mbar), respiratory frequency 20±2 breaths·min−1). The arterial oxygen tension significantly increased by 1.39±1.43 kPa (95% confidence interval (CI) 0.71–2.07 kPa) after walking with NPPV, but significantly decreased by 1.43±1.06 kPa (95% CI −1.92 – −0.94 kPa) without NPPV. Dyspnoea, as assessed by the Borg dyspnoea scale, significantly decreased from 6 (interquartile range (IQR) 4.5–10) to 4 (1.5–4.5) and walking distance significantly increased from 209 (IQR 178–279) to 252 (203–314) m when walking was NPPV-aided. In chronic hypercapnic chronic obstructive pulmonary disease, high-intensity noninvasive positive-pressure ventilation can also be administered during walking with unchanged ventilator settings compared with settings used at rest, thus resulting in improved oxygenation, decreased dyspnoea and increased walking distance. Therefore, noninvasive positive-pressure ventilation during walking could prevent hypoxia-induced complications and could, in future, play a role in palliative care.

Guidelines for Non-Invasive and Invasive Mechanical Ventilation for Treatment of Chronic Respiratory Failure * Published by the German Society for Pneumology (DGP)

Martina Bogel, Weinmann GmbH, Hamburg Andreas Bosch, Heinen & Lowenstein GmbH, Bad Ems Jorg Brambring, Heimbeatmungsservice Brambring Jaschke GmbH, Unterhaching Stephan Budweiser, Klinik Donaustauf Dominic Dellweg, Fachkrankenhaus Kloster Grafschaft GmbH, Schmallenberg Peter Demmel, MDK Bayern, Munchen Rolf Dubb, Klinikum Stuttgart – Katharinenhospital Jens Geiseler, Asklepios Fachkliniken Munchen-Gauting Frank Gerhard, isb Ambulante Dienste gGmbH, Wuppertal Uwe Janssens, St.-Antonius-Hospital Eschweiler Thomas Jehser, Gemeinschaftskrankenhaus Havelhohe, Berlin Anne Kreiling, Deutsche Gesellschaft fur Muskelkranke e.V., Baunatal Thomas Kohnlein, Medizinische Hochschule Hannover Uwe Mellies, Universitatsklinikum Essen F. JoachimMeyer, Medizinische Universitatsklinik Heidelberg Winfried Randerath, Krankenhaus Bethanien gGmbH, Solingen Bernd Schonhofer, Klinikum Hannover Oststadt Bernd Schucher, Krankenhaus Groshansdorf Karsten Siemon, Fachkrankenhaus Kloster Grafschaft GmbH, Schmallenberg Helmut Sitter, Universitatsklinikum Giesen und Marburg GmbH (Vertreter der AWMF) Jan Hendrik Storre, Universitatsklinik Freiburg Stephan Walterspacher, Universitatsklinik Freiburg Steffen Weber-Carstens, Charite – Universitatsmedizin Berlin Wolfram Windisch, Universitatsklinik Freiburg MartinWinterholler, Krankenhaus Rummelsberg, Schwarzenbruck KurtWollinsky, Universitatsund Rehabilitationskliniken Ulm

Evaluation of health-related quality of life using the MOS 36-Item Short-Form Health Status Survey in patients receiving noninvasive positive pressure ventilation

ObjectiveTo collect benchmark data on the MOS 36-Item Short-Form Health Status Survey (SF-36) in patients receiving noninvasive positive pressure ventilation and to examine whether health-related quality of life is influenced by the underlying disease or by physical parameters.Design and settingMulticentric clinical cross-sectional trial in four general wards specialized in noninvasive positive pressure ventilation.Patients and participants226 patients (78 chronic obstructive pulmonary disease, 57 kyphoscoliosis, 20 posttuberculosis sequelae, 17 Duchenne muscular dystrophy, 13 polyneuropathy, 13 myopathy, 6 amyotrophic lateral sclerosis, 12 obesity-hypoventilation syndrome, 4 poliomyelitis sequelae, 3 phrenic nerve lesion, 3 central hypoventilation syndrome) who used noninvasive positive pressure ventilation for home mechanical ventilation.Measurements and resultsHealth-related quality of life as assessed by the SF-36 was lower than in the general population. Overall the Physical Component Summary (PCS) was significantly lower than the general population norm; the Mental Component Summary (MCS) was also reduced but less markedly. Patients with chronic obstructive pulmonary disease were more impaired in MCS than those with kyphoscoliosis. PCS was significantly associated with age. Gender, lung function, and arterial blood gas values were not significant predictors of health-related quality of life.ConclusionsBenchmark SF-36 data in patients receiving noninvasive positive pressure ventilation are given. Although physical health is significantly impaired in these patients, this does not necessarily lead to mental limitation, and mental health is influenced by the underlying disease, but not by physical parameters.

Nocturnal non-invasive positive pressure ventilation: Physiological effects on spontaneous breathing

The dynamic process of how non-invasive positive pressure ventilation (NPPV) improves spontaneous ventilation is unclear. Therefore, daytime trends of blood gases and breathing pattern were assessed by measurements 0, 0.5, 1, 3, 7, 11 and 15 h after cessation of nocturnal controlled NPPV in patients with chronic hypercapnic respiratory failure. Twelve patients (six COPD/six restrictive) who were established on NPPV and 12 controls (six COPD/six restrictive) completed. PaCO2 decreased during controlled NPPV (P < 0.02). PaCO2 additionally decreased step by step during the first 3 h of spontaneous breathing after switching from NPPV to spontaneous breathing (P < 0.05), but remained unchanged in controls. The PaCO2 decrease was due to a stepwise increase in tidal volume (P < 0.05) at an unchanged breathing frequency. Accordingly, minute ventilation also stepwise increased (P < 0.03). There were no significant changes in controls. Improvements of PaCO2 and tidal volume occurred even after 5.7 +/- 3.1 days following first NPPV trials, but became more evident after 2 months. Maximal inspiratory mouth pressures increased in chronic obstructive pulmonary disease (COPD) patients (P < 0.05), and respiratory drive increased in restrictive patients (P < 0.05) following 2 months of NPPV. Lung function parameters and inspiratory impedance remained unchanged. Improvements in health-related quality of life were evident and were correlated to the decline of elevated bicarbonate levels (r = 0.72, P < 0.01). In conclusion, there is a stepwise adaptation process lasting 3h when switching from nocturnal controlled NPPV to daytime spontaneous breathing in which tidal volume increases and PaCO2 drops after an initial PaCO2 decrease while on NPPV.

Impairment of respiratory muscle function in pulmonary hypertension

It has been suggested that impaired respiratory muscle function occurs in patients with PH (pulmonary hypertension); however, comprehensive investigations of respiratory muscle function, including the application of non-volitional tests, needed to verify impairment of respiratory muscle strength in patients with PH have not yet been performed. In the present study, respiratory muscle function was assessed in 31 patients with PH (20 females and 11 males; mean pulmonary artery pressure, 51+/-20 mmHg; median World Health Organization class 3.0+/-0.5; 25 patients with pulmonary arterial hypertension and six patients with chronic thromboembolic PH) and in 31 control subjects (20 females and 11 males) well-matched for gender, age and BMI (body mass index). A 6-min walking test was performed to determine exercise capacity. Volitionally assessed maximal inspiratory (7.5+/-2.1 compared with 6.2+/-2.8 kPa; P=0.04) and expiratory (13.3+/-4.2 compared with 9.9+/-3.4 kPa; P<0.001) mouth pressures, sniff nasal (8.3+/-1.9 compared with 6.6+/-2.2 kPa; P=0.002) and transdiaphragmatic (11.3+/-2.5 compared with 8.7+/-2.5 kPa; P<0.001) pressures, non-volitionally assessed twitch mouth (1.46+/-0.43 compared with 0.97+/-0.41 kPa; P<0.001) and transdiaphragmatic (2.08+/-0.55 compared with 1.47+/-0.72 kPa; P=0.001) pressures during bilateral anterior magnetic phrenic nerve stimulation were markedly lower in patients with PH compared with control subjects. Maximal inspiratory mouth (r=0.58, P<0.001) and sniff transdiaphragmatic (r=0.43, P=0.02) pressures were correlated with the 6-min walking distance in patients with PH. In conclusion, the present study provides strong evidence that respiratory muscle strength is reduced in patients with PH compared with well-matched control subjects. Furthermore, the 6-min walking distance is significantly linked to parameters assessing inspiratory muscle strength.

The Severe Respiratory Insufficiency Questionnaire was valid for COPD patients with severe chronic respiratory failure

OBJECTIVES The Severe Respiratory Insufficiency (SRI) Questionnaire has recently been developed and validated for the assessment of health-related quality of life (HRQL) in patients with severe chronic respiratory failure resulting from a broad spectrum of underlying disorders. The present study was aimed at reexamining the internal structure of the SRI specifically for chronic obstructive pulmonary disease (COPD) patients. STUDY DESIGN AND SETTING Cross-validation was performed in two COPD groups (N=78 and N=84), each receiving home mechanical ventilation in addition to long-term oxygen therapy. The internal consistency reliability was calculated using Cronbachs alpha coefficient. Explorative Factor Analysis was performed followed by Confirmatory Factor Analysis to establish construct validity. RESULTS In the total group (N=162) Cronbachs alpha ranged from 0.73 to 0.88. Only one factor could be established which explained 58.5% of the total variance confirming one Summary Scale (SRI-SS). For each of the seven subscales, Confirmatory Factor Analysis revealed two factors, which were substantially correlated (r=0.43-0.80). All scale scores covered a broad range of the questionnaires scaling range (0-100). The mean SRI-SS score was 52+/-17 indicating a homogenous scaling distribution. CONCLUSION The SRI is a multidimensional and highly specific tool with high psychometric properties for HRQL assessment in COPD patients with severe chronic respiratory failure.

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.