Evolution of sleep-disordered breathing and blood pressure during menopausal transition.

The purpose of this study was to investigate how the blood pressure increase observed during menopausal transition is affected by sleep-disordered breathing and the menopause itself. Further, we aimed to find new sleep-disordered breathing related markers that would predict the development of hypertension. Sixty-four community-dwelling premenopausal women aged 45-47 years were studied. Polysomnography, serum follicle stimulating hormone, forced expiratory volume in 1 s, and a physical examination were performed at baseline and again after 10 years of follow-up. Indices for sleep apnea/hypopnea and inspiratory flow-limitation were determined. Regression models were used to study the relationships between variables. Changes in the apnea-hypopnea index or serum follicle stimulating hormone were not significant for blood pressure change. An increase in morning blood pressure during the follow-up period was associated with a body mass-index increase. An increase in evening blood pressure was associated with an increase in inspiratory flow-limitation during non-rapid eye movement sleep. Incident hypertension during the follow-up was associated with hypopnea (median hypopnea index 7.6/h, p = 0.048) during rapid eye movement sleep at baseline. Users of menopausal hormone therapy had a lower rapid eye movement sleep apnea-hypopnea index (1.6/h vs. 6.9/h, p = 0.026) at baseline whereas at follow-up users and non-users did not differ in any way. The progression of menopause or the use of menopausal hormone therapy had a minimal effect on blood pressure in our population. The effects of inspiratory flow-limitation on blood pressure profile should be studied further.

Upper-airway flow limitation and transcutaneous carbon dioxide during sleep in normal pregnancy.

OBJECTIVE: Sleep during pregnancy involves a physiological challenge to provide sufficient gas exchange to the fetus. Enhanced ventilatory responses to hypercapnia and hypoxia may protect from deficient gas exchange, but sleep-disordered breathing (SDB) may predispose to adverse events. The aim of this study was to analyze sleep and breathing in healthy pregnant women compared to non-pregnant controls, with a focus on CO2 changes and upper-airway flow limitation. METHODS: Healthy women in the third trimester and healthy non-pregnant women with normal body mass index (BMI) were recruited for polysomnography. Conventional analysis of sleep and breathing was performed. Transcutaneous carbon dioxide (TcCO2) was determined for each sleep stage. Flow-limitation was analyzed using the flattening index and TcCO2 values were recorded for every inspiration. RESULTS: Eighteen pregnant women and 12 controls were studied. Pregnancy was associated with shorter sleep duration and more superficial sleep. Apnea-hypopnea index, arterial oxyhemoglobin desaturation, flow-limitation, snoring or periodic leg movements were similar in the two groups. Mean SaO2 and minimum SaO2 were lower and average heart rate was higher in the pregnant group. TcCO2 levels did not differ between groups but variance of TcCO2 was smaller in pregnant women during non-rapid eye movement (NREM). TcCO2 profiles showed transient TcCO2 peaks, which seem specific to pregnancy. CONCLUSIONS: Healthy pregnancy does not predispose to SDB. Enhanced ventilatory control manifests as narrowing threshold of TcCO2 between wakefulness and sleep. Pregnant women have a tendency for rapid CO2 increases during sleep which might have harmful consequences if not properly compensated.

Prolonged partial upper airway obstruction during sleep - an underdiagnosed phenotype of sleep-disordered breathing.

Obstructive sleep apnea syndrome (OSAS) is a well-recognized disorder conventionally diagnosed with an elevated apnea-hypopnea index. Prolonged partial upper airway obstruction is a common phenotype of sleep-disordered breathing (SDB), which however is still largely underreported. The major reasons for this are that cyclic breathing pattern coupled with arousals and arterial oxyhemoglobin saturation are easy to detect and considered more important than prolonged episodes of increased respiratory effort with increased levels of carbon dioxide in the absence of cycling breathing pattern and repetitive arousals. There is also a growing body of evidence that prolonged partial obstruction is a clinically significant form of SDB, which is associated with symptoms and co-morbidities which may partially differ from those associated with OSAS. Partial upper airway obstruction is most prevalent in women, and it is treatable with the nasal continuous positive pressure device with good adherence to therapy. This review describes the characteristics of prolonged partial upper airway obstruction during sleep in terms of diagnostics, pathophysiology, clinical presentation, and comorbidity to improve recognition of this phenotype and its timely and appropriate treatment.

Transcutaneous carbon dioxide during sleep-disordered breathing.

Respiratory drive is tightly controlled by the carbon dioxide levels. We tested the hypothesis that sequences of sleep apnoea (obstructive, central or mixed), hypopnoea and flow limitation are characterized by different levels of transcutaneous CO2 (PtcCO2). Polygraphic recordings (n=555) from patients with suspected sleep-disordered breathing (SDB) were retrospectively screened to find sequences (5 min or 10 events) of both SDB and steady breathing. Eighty-eight SDB sequences from 44 patients were included and PtcCO2 and SpO2 values were collected. PtcCO2 values during sequences were normalized by setting wakefulness level as 100%. In terms of PtcCO2, apnoea sequences with central component (central (n=7) and mixed (n=3) apnoea) did not differ from wakefulness (102.0% vs 100%, p=0.122) whereas obstructive apnoea (105.8%, p<0.001) and hypopnoea did (105.4%, p<0.001). PtcCO2 during flow limitation was higher than that during any other sequence, including steady breathing (112.2% vs 108.4%, p=0.022). Continuous PtcCO2 monitoring during sleep adds to the understanding of different SDB phenotypes.

Pramipexole alters thermoregulation in restless legs syndrome.

STUDY OBJECTIVES: Previous studies have associated restless legs syndrome (RLS) with peripheral hypoxia and impaired thermoregulation in the lower extremities. We performed long-term monitoring of skin temperatures in order to investigate whether these findings could be explained by reduced blood flow to the peripheral tissues. METHODS: 96-hour continuous measurements of skin temperature were performed both in the distal and proximal parts of the body of 15 patients with RLS and 14 healthy controls. During the recording, the patients participated in suggested immobilization tests both with and without pramipexole medication. RESULTS: We found no baseline differences in distal or proximal skin temperature between patients and controls in daytime or during immobilization. However, pramipexole significantly increased distal skin temperature in the patient group during immobilization (31.1°C vs. 32.9°C, p < 0.05). Daytime temperatures were not affected by therapy or disease status. CONCLUSIONS: The data suggest that patients with RLS and healthy controls have similar blood flow to the peripheral skin tissue. Pramipexole, however, alters thermoregulation and the previous studies might have been biased by medication. Dopaminergic medication is a major confounding factor when assessing peripheral phenomena in RLS and should be controlled for in the future studies.

Peripheral hypoxia in restless legs syndrome (Willis-Ekbom disease).

OBJECTIVE: A case-control study to measure oxygen and carbon dioxide partial pressures in the legs in order to assess the involvement of peripheral hypoxia or hypercapnia in the pathogenesis of restless legs syndrome (RLS). METHODS: RLS severity was assessed with a standard questionnaire. Suggested immobilization tests were performed twice in 15 patients with RLS and 14 healthy controls. Patients with RLS participated in the tests with and without pramipexole medication. During the tests, peripheral oxygen and carbon dioxide partial pressures were measured noninvasively on the skin of the legs and the chest. RESULTS: During immobilization, the patients with RLS had lower partial pressure of oxygen in their legs (5.54 vs 7.19 kPa, p < 0.01) but not on the chest (8.75 vs 8.20 kPa, p = 0.355). More severe RLS correlated with high chest-to-foot oxygen gradient (ρ = 0.692, p < 0.01). Carbon dioxide levels did not differ between the groups. Pramipexole corrected the peripheral hypoxia toward the levels observed in the controls (from 5.54 to 6.65 kPa, p < 0.05). CONCLUSIONS: Peripheral hypoxia is associated with the appearance of RLS symptoms. Strong correlation with RLS severity suggests a close pathophysiologic link between peripheral hypoxia and the symptoms of RLS. This is further supported by the simultaneous reversal of hypoxia and discomfort by dopaminergic treatment.

Transcutaneous CO(2) plateau as set-point for respiratory drive during upper airway flow-limitation.

Upper airway flow-limitation is often but not always associated with prolonged gradually increasing respiratory effort. We investigated the changes in transcutaneous carbon dioxide tension (tcCO(2)) during episodes of upper airway flow limitation during sleep with or without respiratory effort response. Seventy-seven episodes of progressive flow-limitation were analyzed in 36 patients with sleep-disordered breathing. TcCO(2) and arterial oxyhaemoglobin saturation (SaO2) were measured during steady breathing and during episodes of flow-limitation with and without effort response. After lights-off tcCO(2) increased and leveled-off at plateau, when breathing stabilized. During flow-limitation tcCO(2) increased at rate of 4.0kPa/h. Flow-limitation with increasing respiratory effort associated with tcCO(2) increase above the plateau (terminating at 105.2%, p<0.001), whereas flow-limitation without effort response associated with tcCO(2) increase starting below the plateau (95.8%, p<0.001). We conclude that the nocturnal tcCO(2) plateau indicates the level above which the increasing respiratory effort is triggered as response to upper airway flow-limitation. We propose that flow-limitation below the tcCO(2) plateau is an event related to stabilization of sleep and breathing.

Disconnection between periodic leg movements and cortical arousals in spinal cord injury.

OBJECTIVE: In this study we examine the temporal connection between periodic leg movements (PLMs) and cortical arousals, as well as the treatment effect of pramipexole, in a clinical case with spinal cord lesion. METHODS: A patient with complete cervical spinal cord injury and PLMs during sleep underwent two baseline sleep recordings, one recording with dopaminergic treatment, and one recording with adaptive servoventilation. RESULTS: The PLMs were temporally dissociated from cortical arousals as well as from respiratory or heart rate events. PLMs were suppressed by pramipexole and persisted after treatment of apnea. CONCLUSION: The disconnection of PLMs from arousals supports a spinal generator or peripheral trigger mechanism for PLMs. The suppression of movements by a dopamine agonist suggests that its site of action is caudal to the cervical lesion and outside of the brain. Our observation provides significant new knowledge about the pathogenesis of PLMs and warrants studies in larger populations.