Severity of nocturnal cardiac arrhythmias correlates with intensity of sleep apnea in men.

Various cardiac arrhythmias frequently occur in patients with sleep apnea, but complex analysis of the relationship between their severity and the probable arrhythmogenic risk factors is conflicting. The question is what cardiovascular risk factors and how strongly they are associated with the severity of cardiac arrhythmias in sleep apnea. Adult males (33 with and 16 without sleep apnea), matched for cardiovascular co-morbidity were studied by polysomnography with simultaneous ECG monitoring. Arrhythmia severity was evaluated for each subject by a special 7-degree scoring system. Laboratory, clinical, echocardiographic, carotid ultrasonographic, ambulatory blood pressure, and baroreflex sensitivity values were also assessed. Moderate sleep apnea patients had benign, but more exaggerated cardiac arrhythmias than control subjects (2.53 ± 2.49 vs. 1.13 ± 1.64 degrees of cumulative severity, p < 0.05). We confirmed strong correlations between the arrhythmia severity and known arrhythmogenic risk factors (left ventricular ejection fraction and dimensions, right ventricular diameter, baroreflex sensitivity, carotid intima-media thickness, age, previous myocardial infarction, and also apnea-hypopnea index). In multivariate modelling only the apnea-hypopnea index indicating the sleep apnea intensity remained highly significantly correlated with the cumulative arrhythmia severity (beta = 0.548, p < 0.005). In conclusion, sleep apnea modifying cardiovascular risk factors and structures or functions provoked various nocturnal arrhythmias. The proposed scoring system allowed a complex analysis of the contribution of various triggers to arrhythmogenesis and confirmed the apnea-hypopnea index as an independent risk for nocturnal cardiac arrhythmia severity in sleep apnea.

An Obstructive Sleep Apnea - A Novel Public Health Threat.

In patients with obstructive sleep apnea (OSA) during obstructive events, episodes of hypoxia and hypercapnia may modulate the autonomic nervous system (ANS) by increasing sympathetic tone and irritability, which contributes to sympathovagal imbalance and ultimately dysautonomia. Because OSA can alter ANS function through biochemical changes, we can assume that heart rate variability (HRV) will be altered in patients with OSA. Most studies show that in both the time and frequency domains, patients with OSA have higher sympathetic components and lower parasympathetic dominance than healthy controls. These results confirm autonomic dysfunction in these patients, but also provide new therapeutic directions. Respiratory methods that modulate ANS, e.g., cardiorespiratory biofeedback, could be beneficial for these patients. Heart rate variability assessment can be used as a tool to evaluate the effectiveness of OSA treatment due to its association with autonomic impairment.

Heart rate variability in hypertension caused by sleep disordered breathing and its modification by CPAP.

OBJECTIVES: 1) To analyze heart rate variability (HRV) changes, reflecting the sympathovagal balance with secondary hypertension caused by sleep disordered breathing (SDB), compared to healthy controls and essential hypertension without SDB; 2) to compare HRV changes between various degrees of SDB severity; and 3) to test the modification of HRV indices by continuous positive airway pressure (CPAP) in SDB patients. BACKGROUND: Differentiation of secondary hypertension caused by SDB from essential hypertension and healthy controls by ambulatory blood pressure measurement (ABPM) and its modification by CPAP, requires an analysis of HRV changes, as frequently used for the prediction of cardiovascular risk. METHODS: HRV changes were analyzed in 48 adults divided into six groups according to the apnoea/hypopnoea index (AHI), i.e. three groups with various degrees of SDB, a group with severe SDB after CPAP application, a group with essential hypertension without SDB, and a group of healthy controls. Night-time and daytime values of low frequency (LF) and high frequency (HF) bands and the LF/HF ratio were compared in the six groups. RESULTS: The night-time values of LF bands were higher in severe than in moderate and mild degrees of SDB, and the correlation of LF/HF ratio with AHI (r = 0.3511) suggests the gradual increase of sympathetic predominance with the severity of SDB. The high sympathetic activity substantially decreased after application of CPAP in severe SDB. CONCLUSION: The increased nocturnal values of the LF band and the LF/HF ratio, caused by frequent apnoea/ hypopnoea episodes, support the usefulness of HRV spectral analysis for the prediction of cardiovascular risk in patients with SDB (Tab. 1, Fig. 3, Ref. 36).

Severe nocturnal cardiac arrhythmias caused by sleep apnea-induced hypoxemia in males.

Nocturnal cardiac arrhythmias (NCA) were analyzed in patients with sleep apnea/hypopnea syndrome (SAHS) and controls. Occurrence and severity of NCA were compared in 33 SAHS patients and 16 control subjects, matched for cardiovascular risk factors. Continuous overnight polysomnography provided ECG, respiratory and sleep parameters for a comparative analysis. Various types and severity of NCA were detected already in moderate SAHS (apnea/hypopnea index = 26 ±15.6/h), reflecting the respiratory and atherosclerotic changes. Moderately severe arrhythmias, represented with benign and 2 complex types were caused by hypoxemia characterized by AHI, minimal SaO2, and lower values after desaturation. Three-time higher prevalence of complex arrhythmias in SAHS patients was not significantly different by usual statistical comparison, likely due to a low number of controls and a joint occurrence of various types and complex severity of arrhythmias in some patients. Therefore, a complex assessment of different types and varying severity of arrhythmias would require a scale specifically constructed for their evaluation.

Minute ventilation stabilization during all pressure-control / support mechanical ventilation modes.

The main goal of our prospective randomized study was comparing compare the effectiveness of ventilation control method "Automatic proportional minute ventilation (APMV) "versus manually set pressure control ventilation modes in relationship to lung mechanics and gas exchange. 80 patients undergoing coronary artery bypass grafting (CABG) were randomized into 2 groups. 40 patients in the first group No.1 (APMV group) were ventilated with pressure control (PCV) or pressure support ventilation (PSV) mode with APMV control. The other 40 patients (control group No.2) were ventilated with synchronized intermittent mandatory ventilation (SIMV-p) or pressure control modes (PCV) without APMV. Ventilation control with APMV was able to maintain minute ventilation more precisely in comparison with manual control (p<0.01), similarly deviations of ETCO(2) were significantly lower (p<0.01). The number of manual corrections of ventilation settings was significantly lower when APMV was used (p<0.01). The differences in lung mechanics and hemodynamics were not statistically significant. Ventilation using APMV is more precise in maintaining minute ventilation and gas exchange compared with manual settings. It required less staff intervention, while respiratory system mechanics and hemodynamics are comparable. APMV showed as effective and safe method applicable on top of all pressure control ventilation modes.

Strong coincidence between slow wave sleep and low AHI is explainable by the high instability of slow wave sleep to obstructive apnea exposure.

It is well known that in patients with obstructive sleep apnea syndrome (OSAS) the apnea-hypopnea index (AHI) is significantly decreased during slow wave sleep (SWS). It used to be explained by the ability of SWS to stabilize the upper airways against collapse. Another explanation, which is the focus of the current study, is that it is just a result of high instability of SWS to obstructive apnea exposure, i.e. high susceptibility of SWS to transition into lighter sleep stages during exposure to obstructive apneas. A retrospective chart review was performed on 560 males who underwent an overnight polysomnography. Two hundred and eighty-seven patients were eligible for the study. They were divided into 3 groups according to different AHI level. All three groups had a higher SWS occurrence in the lateral position than in the supine position. A special fourth group of patients was created with severe OSAS in the supine position but with very mild OSAS in the lateral position. This group had, in the lateral position, (A) higher AHI in NREM sleep (4.1+/-3.1/h vs. 0.7+/-1.2/h, p<0.001) as well as (B) higher SWS occurrence (27.7+/-15.0 % vs. 21.4+/-16.2 % of NREM sleep, p<0.05), than the group with the lowest AHI in the study, i.e. AHI<5/h in NREM sleep. These data suggest that strong coincidence between SWS and low AHI is the result of the high instability of SWS to obstructive apnea exposure. The data also support the presence of SWS-rebound in OSAS patients in the lateral body position.

Medico-legal implications of sleep apnoea syndrome: driving license regulations in Europe.

BACKGROUND: Sleep apnoea syndrome (SAS), one of the main medical causes of excessive daytime sleepiness, has been shown to be a risk factor for traffic accidents. Treating SAS results in a normalized rate of traffic accidents. As part of the COST Action B-26, we looked at driving license regulations, and especially at its medical aspects in the European region. METHODS: We obtained data from Transport Authorities in 25 countries (Austria, AT; Belgium, BE; Czech Republic, CZ; Denmark, DK; Estonia, EE; Finland, FI; France, FR; Germany, DE; Greece, GR; Hungary, HU; Ireland, IE; Italy, IT; Lithuania, LT; Luxembourg, LU; Malta, MT; Netherlands, NL; Norway, EC; Poland, PL; Portugal, PT; Slovakia, SK; Slovenia, SI; Spain, ES; Sweden, SE; Switzerland, CH; United Kingdom, UK). RESULTS: Driving license regulations date from 1997 onwards. Excessive daytime sleepiness is mentioned in nine, whereas sleep apnoea syndrome is mentioned in 10 countries. A patient with untreated sleep apnoea is always considered unfit to drive. To recover the driving capacity, seven countries rely on a physician's medical certificate based on symptom control and compliance with therapy, whereas in two countries it is up to the patient to decide (on his doctor's advice) to drive again. Only FR requires a normalized electroencephalography (EEG)-based Maintenance of Wakefulness Test for professional drivers. Rare conditions (e.g., narcolepsy) are considered a driving safety risk more frequently than sleep apnoea syndrome. CONCLUSION: Despite the available scientific evidence, most countries in Europe do not include sleep apnoea syndrome or excessive daytime sleepiness among the specific medical conditions to be considered when judging whether or not a person is fit to drive. A unified European Directive seems desirable.

Relationship between dynamic expiratory time constant tau(edyn) and parameters of breathing cycle in pressure support ventilation mode.

Study of the relationship between ventilation parameters: monitored expiratory time constant - tau(edyn) and breathing - trigger frequency (f(trig)) and time of breathing cycle (T(cy)) are main goals of this article. Parameters were analyzed during last 4+/-2 h before weaning from ventilation in 66 patients ventilated in pressure support mode (PSV). We have found out, that there exist mathematical relationships, observed during adequate gas exchange, yet not described. Monitored parameters are represented by tau(edyn), f(trig) and T(cy). The analysis showed close negative correlation between T(cy) and f(trig) (R(2)=0.903). This implies that each increasing of tau(edyn) causes decreasing of f(trig) and vice versa. The calculation of regression equation between tau(edyn) and T(cy) outlined that T(cy) = 5.2625 * tau(edyn) + 0.1242 (R(2)=0.85). Regulation of respiratory cycles by the respiratory center in the brain is probably based on evaluation of tau(edyn) as the tau(edyn) probably represents a regulatory element and T(cy) regulated element. It can be assumed, that respiratory center can optimize the work of breathing in order to minimize energy in system patient + ventilator. The unique relationship, described above could be useful in clinical practice for development of new ventilation modes.

Sleep apnoea inducing hypoxemia is associated with early signs of carotid atherosclerosis in males.

The intima-media thickness (IMT) of carotid arteries as a marker of preclinical atherosclerosis was measured by ultrasonography in 49 subjects to determine, how strongly the obstructive sleep apnoea (OSA) syndrome is associated with atherosclerosis. Maximal IMT was higher in patients with cardiovascular diseases and with or without risk factors of atherosclerosis, presenting also OSA (apnoea-hypopnoea index=26.1+/-15.6/h) compared to controls without OSA (0.91+/-0.21 mm versus 0.77+/-0.18 mm, p<0.05). The prevalence of IMT > or = 0.85 mm was also higher in patients with cardiovascular pathology presenting OSA than without it (p<0.05). IMT(max) was increased in subjects with mild to moderate OSA alone (AHI=20.4+/-8.7/h) versus healthy controls (0.83+/-0.14 mm versus 0.63+/-0.08 mm, p<0.01). Regression analysis revealed a correlation of IMT(max) with the frequency, intensity and duration of intermittent hypoxemia reflected by AHI (p<0.01), minimal oxygen saturation (p<0.01) and time spent with Sa(O2) < 90% (p<0.05) in patients presenting OSA. The results indicate clear association between early signs of carotid atherosclerosis and moderate OSA in males with and without concomitant cardiovascular pathology.

Is ionized oxygen negatively or positively charged more effective for carboxyhemoglobin reduction compare to medical oxygen at atmospheric pressure?

Carbon monoxide (CO) reversibly binds to hemoglobin forming carboxyhemoglobin (COHb). CO competes with O(2) for binding place in hemoglobin leading to tissue hypoxia. Already 30 % saturation of COHb can be deadly. Medical oxygen at atmospheric pressure as a therapy is not enough effective. Therefore hyperbaric oxygen O(2) inhalation is recommended. There was a question if partially ionized oxygen can be a better treatment at atmospheric pressure. In present study we evaluated effect of partially ionized oxygen produced by device Oxygen Ion 3000 by Dr. Engler in elimination of COHb in vitro experiments and in smokers. Diluted blood with different content of CO was purged with 5 l/min of either medicinal oxygen O(2), negatively ionized O(2) or positively ionized O(2) for 15 min, then the COHb content was checked. In vivo study, 15 smokers inhaled of either medicinal oxygen O(2) or negatively ionized O(2), than we compared CO levels in expired air before and after inhalation. In both studies we found the highest elimination of CO when we used negatively ionized O(2). These results confirmed the benefit of short inhalation of negatively ionized O(2), in frame of Ionized Oxygen Therapy (I O(2)Th/Engler) which could be used in smokers for decreasing of COHb in blood.

Hypoxic apnoea induced by N2 inhalation can be reversed by the aspiration reflex in anaesthetized cats.

Various cardiorespiratory and electrophysiological parameters were analysed in a model of acute respiratory failure induced by inhalation of pure nitrogen in approximately 150 anaesthetized cats. Initial hyperventilation leading to apnoea was characterized by extreme hypoxaemia, marked bradycardia and flattening of electrocortical (ECoG) activity. Artificial ventilation applied at the stage of marked mydriasis usually spontaneously prevented cardiovascular failure and normalized vital functions. Up to seven successive apnoeic attacks could be induced in the same cat. During the first 30 or 60 s of apnoea, nasopharyngeal stimulation usually elicited a typical gasp-like aspiration reflex, while tracheobronchial stimulation provoked a weak cough only in 28 and 34% of cases for 30- and 60-s apnoea, respectively. The aspiration reflex could be elicited at very low and even isoelectric ECoG activity, and its periodic provocation (without artificial ventilation) resulted, more frequently than did gasping, in recovery from hypoxic apnoea. Arousal and resuscitation induced by the aspiration reflex can provide a useful model to study the mechanisms of reversible respiratory failure and restitution of vital functions.

Contribution of upper airway reflexes to apnoea reversal, arousal, and resuscitation.

Cardiorespiratory decompensation or even death may result from dysfunction of upper airway reflexes during sleep. This could manifest, for example, as a lack of pharyngeal dilation in obstructive sleep apnoea or failure of autoresuscitation by gasping in sudden infant death syndrome. Data obtained from experiments in anaesthetized cats suggest several clinicophysiological applications for upper airway reflexes possessing important pathogenetic and therapeutic potentials. Such reflex effects include: 1. Pharyngeal dilation as additional treatment in obstructive sleep apnoea. 2. Bronchodilation after deep nasal breathing in asthmatic attacks. 3. Oesophageal sphincter relaxation alleviating gastro-oesophageal reflux. 4. Provocation of sniff- and gasp-like aspiration for reversal of central apnoea. 5. Arousal from sleep increasing the general reactivity. 6. Increase in muscle tone underlying behavioural defence reactions. 7. Increase in sympathetic activity contributing to powerful cardiopulmonary-cerebral resuscitation. 8. Adrenergic reaction mediated by catecholamine secretion.

[Sleep-related breathing disorders--an interdisciplinary topic in undergraduate and postgraduate medical education]. / Spánkové poruchy dýchania--aktuálny interdisciplinárny problém pregraduálnej a postgraduálnej výchovy lekárov.

Sleep-related breathing disorders (SRBD) include several disorders gradually developing from simple and loud snoring through upper airway resistance syndrome and sleep apnoea up to the Pickwickian syndrome. They are manifestant as a respiratory distress and apnoeic episodes, desaturation of oxygen in the blood and interruption of sleep. These symptoms are demonstrated in a case of a patient with the Pickwickian syndrome. SRBD may result in severe secondary life-threatening cardiovascular complications (nocturnal arrhythmias, sudden cardiac death, stroke and pulmonary oedema). They may contribute also to the development of important disorders of public health such as hypertension, obesity, and traffic accidents resulting from hypersomnolence and fatigue. (Tab. 1, Fig. 3, Ref. 46.)

Interaction of sleep apnoea syndrome with various diseases.

Sleep disordered breathing (SDB), particularly their clinically most serious and at the same time common form-sleep apnoea syndrome-caused by structural or functional abnormalities in the area of upper airways, are frequently linked with other diseases. The accompanying respiratory, cardiovascular, neuropsychic, sympathoadrenal and endocrine-metabolic disorders and their variable intensity determine the character and severity of patients complaints. The coincidence of SDB with alteration in one or another system produces mutual potentiation of their negative effects appearing as serious, not rarely even life threatening acute complications or chronic consequences manifesting exactly in the area of the afflicted system. The paper illustrates on several examples the development of pathological signs of SDB concerning practically all medical branches and at the same time demonstrating the multidisciplinary character of sleep medicine. (Fig. 1, Ref. 27.)

[Disorders of heart rhythm and ECG changes in experimental apneic states]. / Poruchy srdcového rytmu a zmeny EKG pri apnoických stavoch v experimente.

BACKGROUND: Apnoeic events are often accompanied by various disturbances in electric cardiac activity, the character and development as well as mechanism of which remain broadly unknown suggesting both direct metabolic defects as well as neurogenous autonomic influences. METHODS: Changes in ECG and heart rate induced by repeated short-lasting inhalation of hypoxic poikilocapnic mixtures (100% N2 and/or 0.5-1% CO2 or 6% CO2 in N2) were analyzed in 17 spontaneously breathing cats anaesthetized with sodium pentobarbitone (40 mg.kg-1i.p.). RESULTS: N2 inhalation evokes hypoxaemic hyperventilation progressing into apnoea and bradycardia with secondary low-level atrioventricular conduction block and ischaemic changes in ECG. Contrary to this reversible respiratory failure, hypoxaemic hypercapnic hyperventilation and apnoea evoked by inhalation of 6% CO2 in N2 or 100% CO2 were accompanied by very marked additional effects of hypercapnia and acidosis. They appeared earlier and were more severe (high-level AV conduction block and premature contractions) suggesting direct myocardial alteration due to acidosis. CONCLUSIONS: The results provide experimental data for better understanding the dynamics, intensity and development of dysrhythmias and ECG changes occurring in two different types of cardiorespiratory failure in animal experiments as well as in central and obstructive types of sleep apnoea and other apnoeic events in humans. (Fig. 3, Ref. 27.)

[Obstructive sleep apnea as a cause of dysrhythmia in sudden cardiac death]. / Obstrukcné spánkové apnoe ako prícina dysrytmií a náhlej srdcovej smrti.

BACKGROUND: Sleep apnoea is often accompanied by severe disturbances in heart rate and cardiac rhythm. SUBJECTS AND METHODS: Various respiratory parameters were continuously recorded 6-9 hours during sleep in ten patients with sleep apnoea syndrome, paralley with direct ECG recording (8 cases) or Holter monitoring (2 cases). The rate, development and reversibility of various dysrrhythmias were evaluated. RESULTS: Obstructive, central and mixed sleep apnoeas (OSA, CSA, MSA) and hypopnoea occurred in each patient (52.5%, 3.5%, 10% and 34%, respectively). Lighter dysrrhythmias (sinus arrest, atrioventricular block and occasional supraventricular premature contractions) were in patients with frequent CSA, whereas the most severe ones (higher degrees of AVCB, premature ventricular contractions and tachyarrhythmias) occurred during OSA. Stronger hypoxaemia and myocardial acidosis, as well as severe alteration in sympathetic and vagal tone probably contributed to the development of life-threatening brady- and tachyarrhythmias in OSA, based on alteration in effective refractory period and reentry phenomenon. CONCLUSION: Dysrrhythmias often occur during OSA and they may result in acute cardiovascular complications. Due to their functional character and reversibility, the development of nocturnal dysrrhythmias can be prevented by early diagnosis and effective treatment of sleep related breathing disorders, which at the same time decreases, the risk of both cardiovascular complications and diseases.

[Computer evaluation of respiratory changes during acute hypoxia in an experimental model]. / Pocítacové hodnotenie zmien dýchania pocas akútnej hypoxie v modelovom pokuse.

Experiences are presented concerning the use of a computer system in analyzing the dynamics of respiratory changes during reversible respiratory failure induced by inhalation of nitrogen in anesthetized cats. The main focus is on semiautomatic evaluation of the air flow signal during experimentally induced hypoxia in model experiment. On the basis of experience with computer aided evaluation of respiratory changes in over 40 animals and regarding the analysis of actual data obtained from 29 hypoxic episodes leading to reversible respiratory failure in 9 cats, advantages and pitfalls of evaluating respiration parameters by the breath-by-breath method are highlighted. Besides demonstrating the applied computer processing of data, the paper evaluates the most important of the 30 respiratory parameters studied, i.e. tidal volume (VT), minute ventilation (VE), inspiratory time (TI), and the ratios VI/TI and TI/TTOT. The results allow to quantify well the dynamics of development of changes of the respiratory model particularly during the first phase of acute hypoxic hypoxia. (Tab. 1, Fig. 5, Ref. 21).

Does obstructive sleep apnea worsen during REM sleep?

Although it is thought that obstructive sleep apnea (OSA) is worse during rapid eye movement (REM) sleep than in non-REM (NREM) sleep there are some uncertainties, especially about apnoe-hypopnoe-index (AHI). Several studies found no significant difference in AHI between both sleep stages. However, REM sleep is associated more with side sleeping compared to NREM sleep, which suggests that body position is a possible confounding factor. The main purpose of this study was to compare the AHI in REM and NREM sleep in both supine and lateral body position. A retrospective study was performed on 422 consecutive patients who underwent an overnight polysomnography. Women had higher AHI in REM sleep than NREM sleep in both supine (46.05+/-26.26 vs. 23.91+/-30.96, P<0.01) and lateral (18.16+/-27.68 vs. 11.30+/-21.09, P<0.01) body position. Men had higher AHI in REM sleep than NREM sleep in lateral body position (28.94+/-28.44 vs. 23.58+/-27.31, P<0.01), however, they did not reach statistical significance in supine position (49.12+/-32.03 in REM sleep vs. 45.78+/-34.02 in NREM sleep, P=0.50). In conclusion, our data suggest that REM sleep is a contributing factor for OSA in women as well as in men, at least in lateral position.

Management of obstructive sleep apnea in Europe.

OBJECTIVES: In Europe, the services provided for the investigation and management of obstructive sleep apnoea (OSA) varies from country to country. The aim of this questionnaire-based study was to investigate the current status of diagnostic pathways and therapeutic approaches applied in the treatment of OSA in Europe, qualification requirements of physicians involved in diagnosis and treatment of OSA, and reimbursement of these services. METHODS: Two questionnaires were sent to 39 physicians in 22 countries in Europe. In order to standardize the responses, the questionnaire was accompanied by an example. RESULTS: Sleep centers from 21 countries (38 physicians) participated. A broad consistency among countries with respect to the following was found: pathways included referral to sleep physicians/sleep laboratories, necessity for objective diagnosis (primarily by polysomnography), use of polygraphic methods, analysis of polysomnography (PSG), indications for positive airway pressure (PAP) therapy, application of standard continuous PAP (CPAP) therapy (100% with an CPAP/APAP ratio of 2.24:1), and the need (90.5%) and management of follow-up. Differences were apparent in reimbursement of the diagnostic procedures and follow-up, in the procedures for PAP titration from home APAP titration with portable sleep apnea monitoring (38.1%) up to hospital monitoring with PSG and APAP (85.7%), and in the qualification requirements of sleep physicians. CONCLUSIONS: Management of OSA in different European countries is similar except for reimbursement rules, qualification of sleep specialists and procedures for titration of the CPAP treatment. A European network (such as the one accomplished by the European Cooperation in Science and Technology [COST] B26 Action) could be helpful for implementing these findings into health-service research in order to standardize management in a cost effective perspective.