[Sequels of lung diseases on cardiac function]. / Auswirkungen von Lungenerkrankungen auf die Herzfunktion.

The most severe cardiac sequel of lung diseases is the load of the right ventricle due to pulmonary hypertension with the development of a cor pulmonale. This is characterized by hypertrophy and/or dilatation of the right ventricle because of a primary impairment of lung function and/or lung structure. The most important pathomechanisms of the development of pulmonary hypertension are vessel obliteration, mechanical lesions, primary vascular or extravascular inflammation and hypoxic vasoconstriction. Chronic obstructive pulmonary disease (COPD) is one of the most important reasons of chronic cor pulmonale. A further very common reason is obstructive sleep apnea syndrome (OSAS), especially, if combined with a COPD. In this case prevalence of cor pulmonale rises up to 80%. The development of a chronic cor pulmonale is the most striking negative prognostic factor for these patients. Just 30% of COPD patients with cor pulmonale survive longer than 5 years. Only the early detection of respiratory disturbances, which potentially might lead to cor pulmonale, and their consequent therapy are able to improve the patients' prognosis.

[Cardiac structure and function in patients with obstructive sleep apnea syndrome and co-prevalent arterial hypertension. Influence of CPAP therapy]. / Kardiale Funktion bei Patienten mit obstruktivem Schlafapnoesyndrom und behandelter arterieller Hypertonie Vorteile durch CPAP-Therapie?

BACKGROUND AND PURPOSE: 30% of patients with arterial hypertension (AH) are supposed to have a co-prevalent obstructive sleep apnea syndrome (OSAS). Hence, the influence of CPAP (continuous positive airway pressure) therapy on cardiac structure and function was investigated in medically treated patients with AH and co-prevalent OSAS. PATIENTS AND METHODS: In all patients AH was treated for at least 5 years. Matched pairs concerning anthropometric data, medical therapy and duration of AH, and severity of OSAS were investigated: 20 patients with untreated OSAS were compared to 20 patients with CPAP therapy for at least 6 months. Further cardiopulmonary diseases were excluded. Cardiac structure and function were assessed echocardiographically. RESULTS: Patients under CPAP therapy had significantly better diastolic left ventricular function, a lower left ventricular mass index, and significantly less frequent signs of left ventricular (eccentric) hypertrophy than patients with untreated OSAS. Furthermore, differences were significant concerning right ventricular wall thickness and mean pulmonary artery pressure. CONCLUSION: CPAP therapy positively influences left and right cardial structure and function in addition to antihypertensive medication in patients with AH and co-prevalent OSAS.

[Improvement of cardiopulmonary exercise capacity in patients with obstructive sleep apnea syndrome under CPAP therapy]. / Verbesserung der kardiopulmonalen Leistungsfähigkeit bei Patienten mit obstruktivem Schlafapnoesyndrom unter CPAP-Langzeittherapie.

BACKGROUND AND PURPOSE: Obstructive sleep apnea syndrome (OSAS) is regarded as a cardiovascular risk factor. Therefore, cardiopulmonary exercise capacity in patients with OSAS before and under treatment with continuous positive airway pressure (CPAP) was investigated. PATIENTS AND METHODS: Cardiopulmonary exercise capacity was investigated in 36 patients with untreated OSAS using spiroergometry. A follow-up after at least 6 months was performed in 17 of these patients being treated with CPAP and in eight CPAP-neglecting patients, who served as controls. RESULTS: Maximum oxygen uptake ( O(2max)) was significantly reduced in all 36 patients with untreated OSAS (17.68 +/- 6.1 ml/min/kg) compared with reference values (30.72 +/- 4.9 ml/min/kg; p < 0.001). After an average of 305.7 +/- 104.8 nights of CPAP therapy, O(2max) rose from 15.33 +/- 4.8 to 18.53 +/- 6.9 ml/min/kg, whereas O(2max) remained unchanged in controls. Further spirometric parameters of exercise capacity as well as arterial blood pressure were also significantly improved under CPAP therapy. CONCLUSION: Cardiopulmonary exercise capacity is markedly reduced in patients with OSAS. Long-term CPAP therapy leads to a significant improvement of reduced cardiopulmonary exercise capacity in these patients.

Short-term effects of oral theophylline in addition to CPAP in mild to moderate OSAS.

Theophylline is effective in the treatment of central apneas and periodic breathing. In obstructive sleep apnea syndrome (OSAS), results of pharmacological monotherapy with theophylline are inconsistent. The present study investigates whether additional theophylline in patients with OSAS and continuous positive airway pressure (CPAP) therapy might improve ventilation, lower effective CPAP pressure levels or affect sleep architecture. Patients with mild to moderate OSAS (mean apnea index [AI] 12.8+/-11.7) and CPAP therapy (Autoset system; n=16, all male) received either 900 mg of oral sustained-release theophylline (T) or placebo (P) on two separate nights, 3 days apart, using a randomized double-blind crossover study design. There was no change in AI (T: 0.7+/-1.4 vs. P: 0.7+/-0.6/h; P=0.3) or apnea-hypopnea index (AHI; T: 4.3+/-3.3 vs. P: 4.5+/-3.7/h; P=0.84) when theophylline was added to CPAP therapy. We observed no difference in mean CPAP pressure (T: 6.9+/-2.1 vs. P: 6.7+/-1.9 cm H2O; P=0.7) or 95% pressure percentiles (T: 9.7+/-2.7 vs. P: 9.3+/-2.1cm H2O; P=0.3) when nights with theophylline were compared to placebo nights. Theophylline reduced significantly total sleep time (T: 290.6+/-58.9 vs. P: 338.0+/-40.1 min; P=0.02) and thus sleep efficiency (SE; T: 70.5+/-14.9%, P: 82.0+/-70.5%; P=0.005). Rapid eye movement and slow wave sleep were not affected. Oral theophylline did not show any additional effects on ventilation parameters or pressures in patients with mild to moderate OSAS once CPAP therapy has been successfully installed. SE was reduced with theophylline with unchanged sleep architecture. The role of oral theophylline may be in patients with predominately central apneas not eligible for ventilation therapy or severe cases.

Long-term effects of nasal continuous positive airway pressure on vasodilatory endothelial function in obstructive sleep apnea syndrome.

Obstructive sleep apnea syndrome (OSAS) is associated with a dysfunction of vascular endothelial cells. The aim of this study was to investigate long-term improvement of endothelial dysfunction in OSAS with nasal continuous positive airway pressure (nCPAP) treatment. We investigated endothelium-dependent and endothelium-independent vasodilatory function in patients with OSAS using the hand vein compliance technique. Dose-response curves to endothelium-dependent vasodilator bradykinin were obtained in 16 subjects with OSAS before and after 6 months of nCPAP therapy and in 12 control subjects without OSAS. Maximum dilation (Emax) to bradykinin, being impaired in all OSAS patients, was completely restored with nCPAP. Mean Emax to bradykinin rose from 54.9+/-18.5 to 108.2+/-28.7% with 164.4+/-90.0 nights of nCPAP therapy (p<0.0001; Emax healthy controls, 94.8+/-9.5%). At treatment follow-up, endothelium-dependent vasodilatory capacity was not significantly different in nCPAP-treated OSAS patients vs healthy controls. Mean vasodilation with endothelium independently acting nitroglycerin was not altered initially and did not change with nCPAP therapy indicating that nCPAP restored endothelial cell function and not unspecific, endothelium-independent factors. These results suggest that regular nocturnal nCPAP treatment leads to a sustained restoration of OSAS-induced impaired endothelium-dependent nitric oxide-mediated vasodilation, suggesting an improvement of systemic endothelial dysfunction in patients studied.

[Quality of life in restless legs syndrome. Influence of daytime sleepiness and fatigue]. / Lebensqualität beim Restless-Legs-Syndrom Einfluss von Tagesschläfrigkeit und Fatigue.

BACKGROUND AND PURPOSE: Restless legs syndrome (RLS) is a frequent neurologic disorder characterized by leg paresthesia and motor restlessness. It is still under debate to which amount the disease affects quality of life as it causes daytime sleepiness and fatigue. The presented study evaluates the daytime problems by different scales. PATIENTS AND METHODS: 28 patients (19 women, nine men, aged 58.6 +/- 11.9 years) with RLS (78% with a severe form) were evaluated with the Epworth Sleepiness Scale (ESS), the Fatigue Severity Scale (FSS) and the SF-36 to judge quality of life. Subscales of the SF-36 contain either rather physical or mental components. RESULTS: 17/28 patients showed an increased daytime sleepiness (ESS) and 17/28 increased fatigue (FSS), whereby these symptoms did not correlate. With regard to the SF-36 scores higher values of fatigue caused a greater limitation of the physical health, daytime sleepiness correlated with limitation of the mental health. CONCLUSION: The study clearly demonstrates an impairment by fatigue and daytime sleepiness in RLS patients. Daytime symptoms worsen quality of life. Different scales have to be used to measure the different daytime symptoms. Therapy must be adjusted to the leading symptoms (e. g., stimulants in daytime sleepiness).

[Early polysomnographic detection of congestive heart failure caused by aortic valve stenosis]. / Polysomnographische Früherkennung einer kardialen Dekompensation infolge hochgradiger Aortenklappenstenose.

BACKGROUND: Obstructive sleep apnea (OSAS) is assumed to be an independent cardiovascular risk factor, whereas central sleep apnea with Cheyne-Stokes breathing occurs in congestive heart failure and has a prognostic value. CASE REPORT: The case of a 74-year-old man with long-term continuous positive airway pressure treatment due to OSAS is reported. In a routine polysomnography central apneas and Cheyne-Stokes breathing without any clinical signs of heart failure were seen. Further investigations revealed a newly diagnosed aortic valve stenosis with good left ventricular function. Clinical signs of congestive heart failure came up 2 weeks after first diagnosed Cheyne-Stokes breathing. CONCLUSION: Cheyne-Stokes breathing can be observed in acute heart failure before occurrence of any clinical signs of congestive heart failure and should always lead to further investigations. The current understanding of pathophysiological pathways in Cheyne-Stokes breathing is reviewed.

Evidence and consensus based guideline for the management of delirium, analgesia, and sedation in intensive care medicine. Revision 2015 (DAS-Guideline 2015) - short version.

In 2010, under the guidance of the DGAI (German Society of Anaesthesiology and Intensive Care Medicine) and DIVI (German Interdisciplinary Association for Intensive Care and Emergency Medicine), twelve German medical societies published the "Evidence- and Consensus-based Guidelines on the Management of Analgesia, Sedation and Delirium in Intensive Care". Since then, several new studies and publications have considerably increased the body of evidence, including the new recommendations from the American College of Critical Care Medicine (ACCM) in conjunction with Society of Critical Care Medicine (SCCM) and American Society of Health-System Pharmacists (ASHP) from 2013. For this update, a major restructuring and extension of the guidelines were needed in order to cover new aspects of treatment, such as sleep and anxiety management. The literature was systematically searched and evaluated using the criteria of the Oxford Center of Evidence Based Medicine. The body of evidence used to formulate these recommendations was reviewed and approved by representatives of 17 national societies. Three grades of recommendation were used as follows: Grade "A" (strong recommendation), Grade "B" (recommendation) and Grade "0" (open recommendation). The result is a comprehensive, interdisciplinary, evidence and consensus-based set of level 3 guidelines. This publication was designed for all ICU professionals, and takes into account all critically ill patient populations. It represents a guide to symptom-oriented prevention, diagnosis, and treatment of delirium, anxiety, stress, and protocol-based analgesia, sedation, and sleep-management in intensive care medicine.

Comparison of driving simulator performance and neuropsychological testing in narcolepsy.

Daytime sleepiness and cataplexy can increase automobile accident rates in narcolepsy. Several countries have produced guidelines for issuing a driving license. The aim of the study was to compare driving simulator performance and neuropsychological test results in narcolepsy in order to evaluate their predictive value regarding driving ability. Thirteen patients with narcolepsy (age: 41.5+/-12.9 years) and 10 healthy control patients (age: 55.1+/-7.8 years) were investigated. By computer-assisted neuropsychological testing, vigilance, alertness and divided attention were assessed. In a driving simulator patients and controls had to drive on a highway for 60 min (mean speed of 100 km/h). Different weather and daytime conditions and obstacles were presented. Epworth Sleepiness Scale-Scores were significantly raised (narcolepsy patients: 16.7+/-5.1, controls: 6.6+/-3.6, P < or = 0.001). The accident rate of the control patients increased (3.2+/-1.8 versus 1.3+/-1.5, P < or = 0.01). Significant differences in concentration lapses (e.g. tracking errors and deviation from speed limit) could not be revealed (9.8+/-3.5 versus 7.1+/-3.2, pns). Follow-up investigation in five patients after an optimising therapy could demonstrate the decrease in accidents due to concentration lapses (P < or = 0.05). Neuropsychological testing (expressed as percentage compared to a standardised control population) revealed deficits in alertness (32.3+/-28.6). Mean percentage scores of divided attention (56.9+/-25.4) and vigilance (58.7+/-26.8) were in a normal range. There was, however, a high inter-individual difference. There was no correlation between driving performance and neuropsychological test results or ESS Score. Neuropsychological test results did not significantly change in the follow-up. The difficulties encountered by the narcolepsy patient in remaining alert may account for sleep-related motor vehicle accidents. Driving simulator investigations are closely related to real traffic situations than isolated neuropsychological tests. At the present time the driving simulator seems to be a useful instrument judging driving ability especially in cases with ambiguous neuropsychological results.

Obstructive Sleep Apnea and Hypopnea Efficacy and Safety of a Long-Acting beta2-Agonist.

The effect of inhaled long-acting beta2-agonists in obstructive sleep apnea syndrome (OSAS) is unknown, although from the pharmacological point of view both therapeutic and adverse effects need to be considered. The purpose of this study was to obtain data on the efficacy and safety of salmeterol in patients with OSAS. In a randomized, double-blind, placebo-controlled, cross-over study, effects of salmeterol on respiration during sleep and sleep quality were investigated in 20 patients with OSAS. Of these, 4 patients were female, 16 male; the average age was 53.0 +/- 7.8 years, with average body mass index 28.0 +/- 3.0 kg small middle dot m(-2) and average apnea hypopnea index 35.6 +/- 17.8 h(-1). Patients with asthma, chronic obstructive pulmonary disease (COPD), and left heart failure were excluded. Placebo or verum (50 &mgr;g salmeterol) was administered at 7 pm by meter dose inhaler and spacer device. All patients underwent full polysomnography during baseline, placebo, and verum night. Statistical analysis was performed by StudentOs t-test (p > 0.05). Between the placebo and verum there were no differences in total sleep time, sleep stages, apnea index (AI), apnea hypopnea index (AHI), and nadir oxygen saturation. There was, however, 1) a significant deterioration of mean oxygen saturation (SaO2m; placebo 93.1 +/- 2.0 vs. verum 92.5 +/- 2.2%; p = 0.01), 2) of percent of time spent with an oxygen saturation (SaO2)

[Improvement of health-related quality of life in patients with obstructive sleep apnea syndrome under CPAP therapy]. / Verbesserung der gesundheitsspezifischen Lebensqualität unter CPAP-Therapie bei Patienten mit obstruktivem Schlafapnoesyndrom.

BACKGROUND: Only poor data regarding changes in quality of life in patients with obstructive sleep apnea syndrome (OSAS) under continuous positive airway pressure (CPAP) therapy concerning long-term effects are available. PATIENTS AND METHODS: In this study, 85 patients were evaluated before and under CPAP therapy using the Visual Analog Scale (VAS) Quality of Life, the Nottingham Health Profile (NHP), and the Quality of Life Index (QL-Index). The results of patients with continuous usage of CPAP (n = 66) were compared with a control group of patients who discontinued CPAP therapy (n = 19). RESULTS: VAS (before CPAP 56.9 +/- 27.0, under CPAP 67.2 +/- 21.8 mm; p = 0.027) as well as the NHP dimensions "Energy" (before CPAP 44.2 +/- 39.5, under CPAP 25.0 +/- 34.2 points; p < 0.001), "Emotional reactions" (before CPAP 24.7 +/- 22.5, under CPAP 11.8 +/- 18.8 points; p < 0,001), and "Sleep problems" (before CPAP 32.0 + 30.0, under CPAP 21.5 + 27.2 points; p = 0.005) showed a significant improvement after 16 +/- 9-month follow-up. In the control group, none of the instruments displayed a significant change. A correlation between CPAP compliance (mask hours) and changes in quality of life was not detected. CONCLUSION: Thus, even suboptimal CPAP usage might bring benefit regarding quality of life. As not all health-related instruments or dimensions were able to display the effects on quality of life, there is a need to translate and validate disease-specific instruments into the German language.

Antihypertensive treatment and endothelium-dependent venodilation in sleep-disordered breathing.

Sleep-disordered breathing (SDB) is associated with nitric oxide-mediated endothelial dysfunction and increased risk and prevalence of cardiovascular disease, namely, arterial hypertension. A substantial number of patients do not comply with nasal continuous positive airway pressure (nCPAP) treatment. These individuals have a persisting increased cardiovascular risk. Antihypertensive drugs have shown to improve nitric oxide-mediated endothelial dysfunction. We therefore designed a study to test the hypothesis that antihypertensive drug treatment in hypertensive patients with SDB can have beneficial effects on nitric oxide-mediated endothelial function in the absence of treatment with nCPAP. Six patients with SDB and treated arterial hypertension, six normotensive patients with SDB, and six healthy controls received sleep studies and an assessment of venodilation using the dorsal hand vein technique. Polygraphic measures using standard overnight sleep studies and dose-response curves to the endothelium-dependent vasodilator bradykinin were obtained. Maximum nitric-oxide-mediated dilation to bradykinin was significantly higher in patients with SDB who had received antihypertensive drug treatment compared to normotensive SDB patients. Nitric oxide-mediated dilation in hypertensive patients with SDB was similar to nitric oxide-mediated dilation in healthy controls. After treatment of normotensive patients with SDB using nCPAP, nitric oxide-mediated dilation in normotensive SDB patients was comparable to nitric oxide-mediated dilation in SDB patients with antihypertensive drug treatment and normal controls. Hypertensive patients with SDB present a normal nitric oxide-mediated endothelial function under antihypertensive treatment.

Vascular endothelial dysfunction in patients with mild obstructive sleep apnea syndrome.

BACKGROUND: We investigated endothelial dysfunction, an early manifestation of atherosclerosis, in patients with mild obstructive sleep apnea syndrome (OSAS) (5/h < AHI < 15/h). PATIENTS AND METHODS: Endothelium-dependent and -independent vasodilatory function was tested in 10 patients with mild OSAS, 12 healthy controls and 20 subjects with moderate to severe OSAS using the hand vein compliance technique. RESULTS: Maximum endothelium-dependent vasodilation to bradykinin (Emax) was significantly blunted in patients with mild OSAS (68.6 +/- 30.2 %) compared to healthy controls (94.8 +/- 9.5 %; p < 0.05; moderate to severe OSAS: 57.1 +/- 23.4 %; p = 0.33). Mean endothelium-independent venodilation was not altered. After 160.7 +/- 82.2 nights of CPAP therapy, mean Emax was significantly improved to 90.8 +/- 23.8 % (p < 0.01 vs. baseline; p = 0.7 vs. healthy controls) in 7 patients with mild OSAS. CONCLUSIONS: Systemic endothelium-dependent venodilation is markedly reduced in subjects with mild OSAS, which may imply adverse cardiovascular consequences. CPAP-treatment leads to a sustained restoration of endothelial dysfunction in these patients and is thus highly recommended.

Driving after cerebral ischemia--a driving simulator investigation.

UNLABELLED: Stroke patients with relevant deficits are not allowed to drive. This study tended to assess driving abilities in an early stage after cerebral ischemia with a driving simulator. METHODS: 32 patients (aged 54.9 +/- 14.8 years) with acute ischemia in the middle cerebral artery (MCA) (n = 24) and in the vertebral artery (VA) (n = 8) were investigated with reaction tests and a driving simulator. Controls were 12 healthy volunteers (aged 50.0 +/- 13.9 years). RESULTS: Compared to controls, the accident rate was increased only in patients with MCA-ischemia (2.9 +/- 3.6 vs. 1.3 +/- 1.4, p < 0.05). These patients also had poorer results in the driving simulator (p < 0.05) than patients with VA-ischemia. Driving simulator performance and neuropsychological test results did not correlate. CONCLUSION: All patients had only mild deficits and stated themselves able to drive. We could demonstrate the need to focus on driving skills especially in patients with MCA-infarctions. The driving simulator assesses various physical and neuropsychological functions influencing driving. It may especially be used for expert opinions regarding driving licence. It can also serve as a pre-driver evaluation before on road driving tests.

Assessment of driving performance in patients with relapsing-remitting multiple sclerosis by a driving simulator.

OBJECTIVE: To compare the driving performance using a driving simulator with physical and cognitive functions as measured by the Expanded Disability Status Scale (EDSS) and the Multiple Sclerosis Functional Composite (MSFC) in patients suffering from the relapsing-remitting form of multiple sclerosis (RRMS). METHODS: 31 RRMS patients (18 women, 13 men, mean age 35.6 +/- 8.3 years, EDSS 2.8 +/- 1.4) were compared with 10 healthy controls (8 men, 2 woman, age 45.1 +/- 7.8 years). RESULTS: Compared with controls, the accident rate (5.3 +/- 3.8 vs. 1.3 +/- 1.5, p < 0.001) and concentration faults (21.1 +/- 15.5 vs. 7.1 +/- 2.6, p < 0.01) of RRMS patients using the driving simulator were increased. While there was no correlation with the EDSS score, the accident rate was correlated with the MSFC (r = -0.5, p < 0.05). Regarding the three dimensions of the MSFC, accidents were related to the number of correct answers and Z-score in the paced auditory serial addition test (PASAT) as a measure for cognitive function (r = -0.33, p < 0.05). CONCLUSION: The current study demonstrates the need to focus also on driving skills in MS patients. The risk of accidents should be evaluated after relapses in particular. However, there are great interindividual differences. In the MSFC, most deficits could be evaluated in the PASAT. As there was a significant correlation between the accident rate in the driving simulator and the PASAT results, accidents seem to be more influenced by cognitive decline than by physical impairment. This indicates that the MSFC is a broader, more dimensional scale than the EDSS and should be preferred in the case of driving assessment. At the present time, the driving simulator seems to be a useful instrument judging driving ability, especially in cases with ambiguous neuropsychological results.