Kurt Rasche

Neuropsychological investigations and event-related potentials in obstructive sleep apnea syndrome before and during CPAP-therapy

Patients with obstructive sleep apnea syndrome (OSAS) suffer from daytime sleepiness and a decline of cognitive functions. The study evaluated whether special cognitive disabilities predominate in OSAS. Besides the number connection test (ZVT), judging information processing and working velocity, computer-assisted (Wiener Testsystem and Zimmermann Testbatterie) neuropsychological testing was performed in 31 OSAS patients (50.1 +/- 9.4 years) before starting nasal continuous positive airway pressure (nCPAP) therapy. Identical test battery was performed in 10 male healthy volunteers (48 +/- 9.9 years). In addition visual evoked event-related potentials (ERPs) were recorded, the P3-component was evaluated. Impairment of alertness (P < 0.001), selective attention (P < 0.001) and continuous attention (P < 0.001) could be revealed, vigilance was not altered. Cognitive deficits were correlated with the degree of nocturnal hypoxemia. They were not linked to the apnea/hypopnea-index (AHI), arousal index or vigilance parameters. During 6 months of nCPAP-therapy (15 patients) alertness and continuous attention improved significantly (P < 0.01), intra-individual different pathological results persisted however. P3 latencies also remained prolonged. Chronic intermittent nocturnal hypoxemia in OSAS-patients obviously leads to cognitive deficits. ERP partially generated in subcortical cerebral structures represent a neurophysiological tool indicating brain dysfunction which cannot be evaluated by neuropsychological tests. Objective neuropsychological testing is needed in revealing therapeutic effects in OSAS-patients. Remaining deficits during sufficient nCPAP-therapy may reflect irreversible hypoxic cerebral damage.

Oxidant scavenger function of ambroxol in vitro: a comparison with N-acetylcysteine.

Highly reactive oxygen metabolites play an important role in inflammatory processes in the lung. Ambroxol (2-amino-3,5-dibromo-N-[trans-4-hydroxycyclohexyl]benzylamine) has been shown to reduce oxidant-mediated cell damage. However, the mechanism of this effect remains unclear. In order to evaluate oxidant scavenger function increasing concentrations of ambroxol (0–10−3 mol/l) were compared with equimolar concentrations ofN-acetylcysteine (NAC) and glutathione (GSH) in vitro to reduce OH• (hydroxyl radical), HOCl (hypochlorous acid), O2− (superoxide anion) and H2O2 (hydrogen peroxide). OH• was measured spectrophotometrically (deoxyribose assay); O2− (xanthine/x-oxidase), H2O2 and HOCl (HOCl/OCl−) were determined by chemiluminescence. Ambroxol, NAC and reduced GSH scavenged OH• significantly at 10−3 mol/l, while HOCl was inhibited at concentrations ≥10−4 mol/l completely (P<0.01). NAC and GSH had no anti-O2− function, while ambroxol (10−4 mol/l) reduced O2− by 14.3±6.7%. In contrast, GSH and NAC scavenged H2O2 at>10−6 mol/l (P<0.01), while ambroxol had no anti-H2O2 effect. Our data demonstrate direct oxidant-reducing capabilities of ambroxol, which may be directly related to the aromatic moiety of the molecule. However, high concentrations (micromolar concentrations) are needed. Due to differences in direct oxidant scavenger function, a combination of ambroxol and NAC could be beneficial in antioxidant therapy.

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.

Respiratory monitoring in neuromuscular disease — capnography as an additional tool?

Daytime complaints like fatigue, sleepiness and cognitive dysfunction in neuromuscular disease can be due to nocturnal hypercapnia and hypoxemia. Daytime respiratory diagnostics does not reflect sleep disordered breathing. Nocturnal pulse oxymetry and capnography were performed in 11 patients (15-75 years old) with different slowly progressive neuromuscular diseases. Only four patients complained of dyspnea. Pulmonary function was abnormal in three patients. Blood gas samples showed a hypoxemia in three patients. Pulse oxymetry results were pathological in six patients. Nine patients presented abnormal capnographies. According to these results either nocturnal oxygen application was initiated or ventilatory parameters were modified. Daytime symptoms and muscular strength improved markedly. Capnography and pulse oxymetry should be performed during the course of neuromuscular disease to detect respiratory insufficiency. Capnography seems to be a more sensitive indicator for respiratory impairment especially when artificial ventilation has been initiated.

Left Ventricular Geometry in Patients with Obstructive Sleep Apnea Coexisting with Treated Systemic Hypertension

Background: Left ventricular (LV) hypertrophy is a common consequence of systemic hypertension (SH) and obstructive sleep apnea (OSA). However, little is known about the degree of LV involvement in patients with OSA coexisting with treated SH. Objectives: Our study was designed in order to assess the prevalence of distinct types of LV geometry in treated hypertensive OSA patients. Methods: Patients: 183 patients with treated SH were enrolled to the study. Group 1 consisted of 38 patients with newly-diagnosed OSA and ineffectively treated SH. The remaining 145 patients with effectively treated SH were divided into three groups: group 2 – 70 patients with newly-diagnosed OSA, group 3 – 31 patients with OSA treated with continuous positive airway pressure (CPAP), and group 4 – 44 patients without OSA.Overnight sleep studies and M-mode echocardiography were performed. Results: LV mass index did not differ between the study groups. Mean values of LV end-diastolic diameter (LVED) were 55.4 ± 6.8 mm in group 1 and 53.6 ± 6.9 mm in group 2 and were significantly increased in comparison to subjects treated with CPAP and controls (49.8 ± 6.8 mm and 50.1 ± 64.7 mm, respectively; p = 0.001). LVED correlated positively with the apnea-hypopnea index and desaturation index. LV eccentric hypertrophy was the commonest type of LV geometry in newly-diagnosed OSA patients. Conclusions: The major finding of our study is the predominance of LV eccentric hypertrophy in newly-diagnosed OSA patients. We suggest that a relatively moderate degree of LV involvement in hypertensive OSA patients may depend on the cardioprotective effect of concomitant antihypertensive therapy, ameliorating OSA-dependent neurohumoral abnormalities.

Das obstruktive Schlafapnoe-Syndrom: Ein kardiovaskulärer Risikofaktor?

Introduction Obstructive sleep apnea syndrome (OSAS) is frequently associated with cardiovascular disease. We investigated endothelium-dependent and endothelium-independent nitric oxide-mediated vasodilatory function in normotensive patients with OSAS using the hand vein compliance technique. Patients and methods Dose-response curves to the endothelium-dependent vasodilator bradykinin were obtained in 23 male subjects with OSAS and 12 male control subjects of comparable age, height, and weight. Results Mean (±SD) maximum dilation (Emax) to bradykinin was significantly lower in OSAS patients than in controls (59.8±26.0 vs. 94.8±9.5%, p<0.0001). Mean vasodilation with nitroglycerin was not diminished in the OSAS group (90.7±30.5 vs. 100.3±12.9% in controls; n.s.). In 11 OSAS patients, a follow-up investigation was performed after at least 2 months of treatment with nasal continuous positive airway pressure (CPAP): Emax to bradykinin rose from 54.5±19.2% to 111.5±25.1% after treatment (p<0.001). Mean vasodilation to nitroglycerin was unchanged. Conclusions These results suggest that endothelium-dependent nitric oxide-mediated vasodilation is impaired in patients with OSAS due to an impaired function in the endothelial cells. This impairment is reversible with CPAP treatment. Einleitung Das obstruktive Schlafapnoe-Syndrom (OSAS) ist häufig mit kardiovaskulären Erkrankungen assoziiert. Zur Erkennung möglicher pathophysiologischer Zusammenhänge zwischen OSAS und kardiovaskulären Erkrankungen untersuchten wir daher die Gefäßreagibilität bei normotensiven OSAS-Patienten. Patienten und Methodik Bei 23 männlichen OSAS-Patienten und 12 gesunden männlichen Kontrollprobanden mit vergleichbarem Alter, Größe und Gewicht wurden Dosis-Wirkungskurven nach Gabe des endothelabhängigen Vasodilatators Bradykinin und einer Einzeldosis des endothelunabhängig wirkenden Nitroglycerins mit der Handvenen-Compliancetechnik in vivo bestimmt. Ergebnisse Die mittlere (±Standardabweichung) maximale Gefäßdilatation (Emax) nach Gabe von Bradykinin war bei den OSAS-Patienten signifikant niedriger als in der Kontrollgruppe (59,8±26,0 vs. 94,8±9,5%, p<0,0001). Hingegen war die mittlere Gefäßdilatation nach Gabe von Nitroglycerin in der OSAS-Gruppe nicht signifikant erniedrigt (90,7±30,5 vs. 100,3±12,9% in der Kontrollgruppe; n.s.). Bei 11 der OSAS-Patienten konnte eine Verlaufsuntersuchung nach mindestens zweimonatiger Behandlung mit einer nasalen Überdruck (CPAP)- Therapie durchgeführt werden. Bei diesen Patienten wurde eine Verbesserung der Emax-Werte nach Bradykiningabe von initial 54,5±19,2% auf 111,5±25,1% unter CPAP-Therapie erreicht (p<0,001). Die Vasodilatation nach Nitroglycerin blieb hingegen im Mittel unverändert. Schlussfolgerungen Es konnte gezeigt werden, dass die endothelabhängige Vasodilatation bei Patienten mit OSAS aufgrund einer Dysfunktion der Gefäßendothelzellen gestört ist. Diese endotheliale Dysfunktion ist unter nCPAP-Therapie reversibel.

Konsensuspapier zur Diagnostik und Therapie schlafbezogener Atmungsstörungen bei Erwachsenen

ZusammenfassungDie Diagnostik und Therapie schlafbezogener Atmungsstörungen (SBAS) unterliegt wesentlichen Veränderungen sowohl in medizinisch-wissenschaftlicher Hinsicht als auch in Bezug auf die Versorgungssituation der Patienten und sozioökonomische Aspekte. Die Relevanz der SBAS für die Morbidität und Mortalität Betroffener ist neben der besseren Differenzierung und Phänotypisierung der Untertypen der SBAS Gegenstand intensiver Forschungsaktivitäten. Diese differenzierte Betrachtung verändert die Vorgehensweise beim Verdacht auf SBAS erheblich. Dem stehen Trends zur Simplifizierung des diagnostischen Prozederes und der Therapieeinleitung, der Verlagerung medizinischer Leistungen auf nicht-medizinisches Personal und Fragen der Kostenminimierung entgegen. In diesem Konsensuspapier werden daher vor dem Hintergrund der aktuellen Situation die Prinzipien der Diagnostik, Therapieeinleitung und Versorgung, sowie die Rolle der verschiedenen Beteiligten am Gesundheitssystem und die Bewertung der Therapieangebote vorgestellt. Zu den Kernstücken gehören die Differenzierung der Diagnostik in Screening, Bestätigungsdiagnostik und Differenzialdiagnostik, der Zugang zum Patienten nach der Vortestwahrscheinlichkeit und ein therapeutischer Algorithmus.AbstractDiagnosis and treatment of sleep disordered breathing (SDB) undergo substantial changes, both in terms of increasing scientific knowledge and also in terms of patient provision and socio-economic aspects. Increasing evidence shows the relevance of SDB on morbidity and mortality of affected patients. The precise differentiation of different phenotypes of SDBs has improved substantially in recent years. These proceedings influence the approach to the patients suspected of suffering from SDB. The scientific advances on the one hand are facing intentions to simplify diagnostical processes and treatment initiation and intentions to translate duties of physicians to non-medical personnel on the other hand. This consensus paper presents the principals of diagnosis, treatment initiation and provision, including the role of different participants of the healthcare system, and compares different treatment options. Major aspects include the differentiation of the diagnostical process in screening, affirmation of diagnosis and differential diagnosis. In addition, it focusses on the relevance of the pretest probability and describes a therapeutical algorithm.

Obstructive Sleep Apnea and Hypopnea Efficacy and Safety of a Long-Acting β2-Agonist

The effect of inhaled long-acting β2-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· 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 μg 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 Student’s 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) ≤ 90% (placebo 13.1 ± 14.5 vs. verum 19.5 ± 20.8%; p = 0.02), and 3) a significant increase in heart rate (placebo 63.1 ± 9.2 vs. verum 65.6 ± 9.3 h-1; p = 0.01). In patients with OSAS, salmeterol had no adverse effect on quality of sleep, AI or AHI. The slight increase in heart rate and the deterioration of oxygen saturation probably have no clinical relevance; the latter condition might be due to ventilation-perfusion-mismatch. This study excluded any influence of salmeterol on obstructive sleep apnea and hypopnea; on the other hand, salmeterol turned out to be safe in terms of OSAS. This might be of special importance in patients suffering from both OSAS and obstructive airway disease.

Der schwere Asthmaanfall im Erwachsenenalter

ZusammenfassungDie Ursachen für einen schweren bzw. lebensbedrohlichen Asthmaanfall sind Infektionen mit pneumotropen Viren oder Mycoplasma pneumoniae, weniger häufig bakterielle Infekte, darüber hinaus Allergene, unspezifische Reize, Medikamente sowie eine inadäquate Langzeittherapie. Die Basistherapie des schweren Asthmaanfalls stellen hochdosierte inhalative β2-Agonisten, systemische Glukokortikosteroide und Sauerstoff dar. Bei unzureichender Wirkung ist eine Krankenhauseinweisung erforderlich. Hier sind eine kontinuierlich überwachte intravenöse Medikamentenapplikation möglich, notfalls eine Gabe von Sedativa, bei zunehmender Störung der Atempumpfunktion mit alveolärer Hypoventilation auch eine nicht-invasive oder invasive Beatmung. Ist letztere erforderlich, reduziert die Anwendung einer permissiven Hyperkapnie die Komplikationsrate. Die Bronchoskopie einschließlich Bronchiallavage findet im Falle steigender Beatmungsdrucke sowie bei Atelektasenbildung Anwendung.AbstractThe underlying causes of acute severe or life threatening asthma are infections with respiratory viruses or Mycoplasma pneumoniae, rather than bacterial infections. In addition, exposure to various agents such as allergens, non-specific irritants or drugs, and inadequate long-term treatment may be responsible. High flow oxygen therapy, high dose topic β2-agonists and systemic glucocorticosteroids should be used as baseline therapy in outpatients. In hospital, intravenous therapy—eventually including sedatives—can be administered under controlled or intensive care conditions. In patients with increasing respiratory pump weakness and alveolar hypoventilation, non-invasive and/or invasive mechanical ventilation may be required. In ventilated asthma patients permissive hypercarbia has been shown to reduce complications such as pneumothorax. Bronchoscopy and bronchial lavage are recommended for patients ventilated with increasing pressures or when atelectasis occurs.

CHRONISCHES COR PULMONALE: EPIDEMIOLOGIE, PATHOPHYSIOLOGIE UND KLINIK

Zum ThemaDem Cor pulmonale mit den typischen klinischen Symptomen Dyspnoe, Müdigkeit, Herzrhythmusstörungen, retrosternalen Schmerzen, Oberbauchbeschwerden durch Leberschwellung, vermehrter Jugularvenenfüllung, Beinödemen und Zyanose liegen verschiedene pulmonale Krankheitsbilder mit meist jahrelangem chronischen Verlauf zugrunde. Im Rahmen dieser Übersicht wird deren Pathogenese eingehend erläutert, nachdem zunächst die Physiologie der pulmonalen Zirkulation erörtert wird.Die epidemiologischen Zahlen unterstreichen die Bedeutung des Krankheitsbildes Cor pulmonale, das bei 5–10% aller Herzkrankheiten und 10–30% aller stationär mit Herzinsuffizienz behandelten Patienten vorliegt. In fast der Hälfte aller Fälle mit chronisch obstruktiver Atemwegserkrankung (COPD) findet sich ein Cor pulmonale.Komplementär zu dieser Übersicht sind andere Arbeiten dieses Hefts, besonders aber die von Ch. Perings et al. zur Diagnostik und D. Köhler zur Therapie des Cor pulmonale.