Acetazolamide improves central sleep apnea in heart failure: a double-blind, prospective study

RATIONALE: Acetazolamide is a mild diuretic and a respiratory stimulant. It is used to treat periodic breathing at high altitude. OBJECTIVES: To determine the therapeutic efficacy of acetazolamide on central sleep apnea associated with heart failure. METHODS: Twelve male patients with stable systolic heart failure whose initial polysomnograms showed more than 15 episodes per hour of apnea and hypopnea participated in the study. The patients were randomized to a double-blind cross-over protocol with acetazolamide or placebo, taken 1 h before bedtime for six nights with 2 wk of washout. Measurements: Polysomnography, pulmonary function tests, arterial blood gases, and left ventricular ejection fraction were obtained initially along with a sleep questionnaire, history, and physical examination. Baseline measurements were repeated at the end of each arm. MAIN RESULTS: There were no significant differences between parameters at baseline and placebo. In comparing placebo with acetazolamide, the hourly number of episodes of central apnea (49 +/- 28 vs. 23 +/- 21 [mean +/- SD]; p = 0.004) and the percentage of total sleep time spent below an arterial oxyhemoglobin saturation of 90% (19 +/- 32 vs. 6 +/- 13%; p = 0.01) decreased significantly. Acetazolamide improved subjective perception of overall sleep quality (p = 0.003), feeling rested on awakening (p = 0.007), daytime fatigue (p = 0.02), and falling asleep unintentionally during daytime (p = 0.002). CONCLUSIONS: In patients with heart failure, administration of a single dose of acetazolamide before sleep improves central sleep apnea and related daytime symptoms.     

Blunted peripheral chemoreceptor response to hyperoxia in a group of infants with bronchopulmonary dysplasia

Infants with BPD often suffer from chronic hypoxia and require supplemental oxygen (O₂). This might affect the sensitivity of peripheral chemoreceptors. Therefore, we assessed peripheral chemoreceptor function in 25 infants with bronchopulmonary dysplasia (BPD) of varying severity, using the hyperoxic test. These infants were compared with 35 preterm infants who did not develop BPD. All infants were tested during the 40th week of postconceptional age and their mean postnatal age was 81.5 ± 16.3 days. Sixty percent (15/25) of the BPD infants lacked a hyperoxic response, while the proportion of nonresponders to O₂, among the other groups was 20% (7/35). The intensity of this response was negatively correlated to time spent on a ventilator and positively to time without supplemental oxygen. The intensity of chemoreceptor function was closely related to the severity of BPD; none of the infants with the most severe form of BPD (grade 3) showed a ventilatory response to hyperoxia. Furthermore, infants with BPD needed significantly longer time to increase their saturation than did non-BPD infants (4.7 and 9.3 sec, respectively). We conclude that many infants with BPD, particularly those with the most severe form of the disease, have abnormally functioning peripheral chemoreceptors. Pediatr Pulmonol. 1995; 20:101–106 . © 1995 Wiley-Liss, Inc.     

稳定期慢性充血性心力衰竭患者睡眠呼吸障碍

目的了解稳定期、已得到良好治疗的慢性充血性心力衰竭(心衰)患者的睡眠呼吸障碍的发生情况及睡眠呼吸障碍对心衰的影响.方法应用多导睡眠监护仪(Polywin1000,RespironicsInc.)对稳定期充血性心衰患者进行监测.结果病人分为两组,Ⅰ组(21例)A-H指数≤15,Ⅱ组(15例,占41.7%)A-H指数》15.Ⅱ组A-H指数为16.8～78.8,平均42.6±15.5,其中阻塞性AHI为11.1±8.4,而中枢性AHI为31.5±9.6.同时,Ⅱ组有着显著多的醒觉指数,为36.8±21.3(Ⅰ组为19.4±11.2),这直接与呼吸暂停及低通气指数有关,并与睡眠中最低血氧饱和度[Ⅱ组(76.7±4.6)%,Ⅰ组(86.5±2.8)%、更低的左心室射血分数[Ⅱ组(24.2±8.8)%,Ⅰ组(31.5±10.6)%]有关.结论稳定期慢性充血性心衰患者有着很高的严重的睡眠呼吸障碍的发生率,主要为伴中枢性睡眠呼吸暂停的周期性呼吸.睡眠呼吸障碍的发生与严重的夜间氧合血红蛋白饱和度的下降及过多的觉醒有关.严重的未经治疗的睡眠呼吸障碍可能影响左心室功能,并能加剧充血性心衰患者的死亡.     

Polysomnographic values in children 2-9 years old: additional data and review of the literature

The establishment of normal pediatric polysomnographic parameters is important for both clinical and research interests. Our objectives were to describe respiratory events, paradoxical breathing, periodic limb movements, and sleep architecture of children at the age of peak incidence of obstructive sleep apnea syndrome. We performed a retrospective cross-sectional analysis of a prospective cohort study of 66 children, 2-9 years old, at the Sleep Disorders Center at the Children's Hospital of Philadelphia. Subjects screened by questionnaire underwent a standard polysomnogram. The percent of total sleep time spent in sleep stages 1, 2, 3, 4, and rapid eye movement (REM) were 4 +/- 3%, 44 +/- 10%, 10 +/- 6%, 22 +/- 8%, and 21 +/- 6%, respectively. The arousal and awakening index was 11.2 +/- 4.3/hr. Respiratory events included a central apnea index of 0.08 +/- 0.14/hr, obstructive apnea index of 0.01 +/- 0.03/hr, and obstructive hypopnea index of 0.3 +/- 0.5/hr. The baseline arterial oxygen saturation (SpO2) was 97 +/- 1%, with a nadir of 92 +/- 3%. The index of periodic limb movements in sleep (PLMS) was 1.3 +/- 2.2/hr. Paradoxical breathing appeared significantly more frequent with piezo crystal effort belts (40 +/- 24% of epochs) than with respiratory inductive plethysmography (1.5 +/- 3% of epochs). We describe the occurrence of hypopneas during sleep, arousals and awakenings, and PLMS. We illustrate how different technologies can vary the apparent amount of paradoxical breathing. We also confirm previous data on the frequency distribution of sleep stages, SpO2, and relative rarity of respiratory events in this age group.     

Heart rate response to breath-hold, valsalva and Mueller maneuvers in obstructive sleep apnea

We wished to assess the role of increased vagal tone and arterial oxygen saturation (SaO2) as determinants of HR response to voluntary respiratory maneuvers in OSAS. The changes in HR and SaO2 during breath-hold (B), Valsalva (V) and Mueller (M) maneuvers were determined in nine male subjects with OSAS while breathing RA or O2. Oxygen saturation was significantly lower breathing RA than O2 at the end of B (92.6 +/- 1.6 vs 97.2 +/- 0.8 percent), V (92.9 +/- 1.3 vs 95.2 +/- 1.7 percent), and M (92.7 +/- 1.2 vs 95.3 +/- 1.9 percent). Despite this, there was no significant difference between the HR change while breathing RA and O2 during B (12 +/- 18 vs 7 +/- 15 beats/minute), V (-2 +/- 12 vs -5 +/- 17 beats/minute), and M (5 +/- 16 vs 1 +/- 8 beats/minute). The change in HR was not related to the duration of B, V, or M or to the mouth pressure generated during V and M. In order to determine if awake HR response to the maneuvers reflected HR response to obstructive apnea, we examined the relationship between the HR response to B, V, and M during wakefulness and the response to obstructive apnea of similar duration while asleep. A significant correlation was found between the HR response to obstructive sleep apnea during sleep and the response to awake B (r = 0.67, p less than 0.001), V (r = 0.51, p less than 0.05), and M (r = 0.75, p less than 0.001). We conclude that in OSAS, increased vagal tone is a major determinant of HR response to voluntary respiratory maneuvers, that bradycardia can occur in the absence of hypoxemia, and that HR response to these maneuvers, especially to M, during wakefulness predicts HR response to obstructive apnea while asleep.     

The effects of oxygen in patients with sleep apnea

The effects of 6 h of continuous low flow, nasally administered oxygen were compared with the effects of breathing air in 10 men and 2 women with obstructive sleep apnea and daytime hypersomnolence. The overall quality of sleep, sleep fragmentation, the pattern of breathing, nocturnal oxygenation, and the clinical effects on daytime hypersomnolence determined by multiple sleep latency testing were evaluated. We found that in non-REM sleep, breathing 3 L/min of oxygen increased baseline percent arterial oxyhemoglobin saturation and decreased both the rate of sleep-disordered breathing from 69 +/- 36 to 56 +/- 39 (mean +/- SD) (p less than 0.02) episodes per hour and the peak fall in arterial oxyhemoglobin saturation from 11.5 +/- 5.6% to 6.5 +/- 4.0% (p less than 0.001). In addition, oxygen significantly reduced the percentage of central and mixed sleep-disordered breathing events, thus increasing the percentage of obstructive sleep-disordered breathing events. In contrast, during REM sleep, neither the baseline nor the peak fall in oxyhemoglobin saturation during disordered breathing improved; however, there was a significant reduction in hourly sleep-disordered breeathing rate from 70 +/- 17 to 56 +/- 23 (p less than 0.02) episodes. These improvements in oxygenation and pattern of breathing were associated with improved sleep architecture characterized by a decrease in the number of awakenings from sleep and an increased total sleep time from 335 +/- 72 to 369 +/- 68 min (p less than 0.05). Although 7 of 12 patients felt more alert after oxygen therapy, there was no overall improvement in multiple sleep latency test results.(ABSTRACT TRUNCATED AT 250 WORDS)     

Nasal oxygen alleviates hypoxemia in colonoscopy patients sedated with midazolam and meperidine

A randomized study was carried out to determine whether the administration of oxygen (3 liter/min) via nasal prongs significantly affects arterial oxygenation during colonoscopy in patients sedated with intravenous midazolam (2.6 +/- 0.2 mg, means +/- SE) and meperidine (48 +/- 3 mg). Patients who received supplemental oxygen were less likely to become hypoxic (pulse oximeter reading, SpO2 less than 90%) than those who breathed room air (10 of 28 vs. 22 of 28, p less than 0.005). Similarly, the total time during which SpO2 was below 90% was significantly less in patients receiving nasal oxygen (0.7 +/- 0.3 min) than in patients breathing room air (9.7 +/- 1.9 min, p less than 0.001). Minimum oxygen saturations were significantly higher in patients receiving oxygen (90.6 +/- 0.8%) than in patients breathing air (86.5 +/- 0.8%, p less than 0.001). In patients breathing air, there was a significant negative correlation between the dose of meperidine and the minimum observed oxygen saturation; conversely, midazolam dose did not correlate with indices of hypoxemia. The authors conclude that administration of oxygen via nasal prongs can reduce the risk of hypoxemia during colonoscopy. However, since hypoxemia may occur even when nasal oxygen is given, continuous monitoring of arterial oxygenation is recommended.     

Balloon Post-Dilatation Improves Long-Term Valve Performance After Balloon-Expandable Valve Implantation

BackgroundThe impact of balloon post-dilatation (BPD) on short- and long-term valve performance after Sapien 3 (S3) implantation is unknown. This study aimed to evaluate the impact of balloon post-dilatation (BPD) on short- and long-term valve performance after the implantation of S3.MethodsA total of 846 patients implanted with S3 from the OCEAN-TAVI registry were included in this study. The patients were divided into BPD and non-BPD groups. The clinical outcomes and valve functions were compared.ResultsThe BPD group included 173 (20.4%) patients and the non-BPD group comprised 673 (79.6%) patients. The prosthesis-patient mismatch (PPM) rates were significantly lower in the BPD group than in the non-BPD group before and after propensity score matching at in-hospital follow-up (before matching: 12 [7.1%] vs. 108 [16.3%], p = 0.002; after matching: 8 [6.3%] vs. 19 [14.8%], p = 0.027) and at 1-year follow-up (before matching: 14 [12.5%] vs. 112 [23.6%], p = 0.010; after matching: 9 [10.5%] vs. 19 [22.1%], p = 0.039). The rates of acute kidney injury, cardiac tamponade, and in-hospital cardiovascular death were significantly higher in the BPD group than in the non-BPD group (acute kidney injury: 22 [12.7%] vs. 33 [4.9%], p < 0.001; cardiac tamponade: 3 [1.7%] vs. 2 [0.3%], p = 0.028; in-hospital cardiovascular death: 4 [2.3%] vs. 3 [0.4%], p = 0.016). After matching, these clinical outcomes were similar between the BPD and non-BPD groups.ConclusionsThe BPD group demonstrated better short- and long-term valve performance. Caution is needed to avoid procedure-related complications in patients undergoing BPD.     

Incidence of nocturnal desaturation while breathing oxygen in COPD patients undergoing long-term oxygen therapy

STUDY OBJECTIVE: It is suggested that oxygen flow be increased by 1 L/min during sleep in COPD patients undergoing long-term oxygen therapy (LTOT) in order to avoid nocturnal desaturations. The purpose of this study was to investigate the occurrence of nocturnal desaturations while breathing oxygen in COPD patients receiving LTOT. SETTING: Inpatient/university hospital. PATIENTS: We studied 82 consecutive COPD patients. Their functional characteristics were as follows (mean +/- SD): FVC, 2.15 +/- 0.69 L; FEV(1), 0.87 +/- 0.33 L; PaO(2), 51.6 +/- 5 mm Hg; and PaCO(2), 47 +/- 8 mm Hg. MEASUREMENTS: Overnight pulse oximetry (PO) was performed twice: (1) while breathing air and (2) while breathing supplemental oxygen assuring satisfactory diurnal resting oxygenation (mean PaO(2) during oxygen breathing, 67 +/- 6 mm Hg; mean arterial oxygen saturation [SaO(2)] during oxygen breathing, 93%). RESULTS: PO performed while patients were breathing air showed a mean overnight SaO(2) of 82.7 +/- 6.7%. Patients spent 90% of the recording time with an SaO(2) of < 90%. While breathing oxygen, 43 patients (52.4%) remained well oxygenated. Their mean overnight SaO(2) while breathing oxygen was 94.4 +/- 2.1%, and time spent with saturation < 90% was 6.9 +/- 8.6%. Thirty-nine patients (47.6%) spent > 30% of the night with an SaO(2) of < 90% while breathing supplemental oxygen. Their mean overnight SaO(2) while breathing oxygen was 87.1 +/- 4.5%, and time spent with an SaO(2) of < 90% was 66.1 +/- 24.7% of the recording time. Comparison of ventilatory variables and daytime blood gases between both groups revealed statistically significantly higher PaCO(2) on air (p < 0.001) and on oxygen (p < 0. 05), and lower PaO(2) on oxygen (p < 0.05) in the group of patients demonstrating significant nocturnal desaturation. CONCLUSIONS: We conclude that about half of COPD patients undergoing LTOT need increased oxygen flow during sleep. Patients with both hypercapnia (PaCO(2) > or = 45 mm Hg) and PaO(2) < 65 mm Hg while breathing oxygen are most likely to desaturate during sleep.     

The effect of oxygen on respiration and sleep in patients with congestive heart failure

STUDY OBJECTIVE: To determine the effect of supplemental oxygen on Cheyne-Stokes respiration, nocturnal oxygen saturation (SaO2), and sleep in male patients with severe, stable congestive heart failure. DESIGN: Randomized, single-blind, placebo-controlled crossover study. SETTING: Patients referred from outpatient cardiology clinics of two teaching hospitals. PATIENTS: Sequential sample of nine outpatients with severe, stable congestive heart failure. INTERVENTIONS: For each patient, sleep studies (after an adaptation night) from two consecutive randomized nights were compared; one study was done while the patient breathed compressed air and the other while the patient breathed oxygen (O2). Compressed air and oxygen were both administered through nasal cannulae at 2 to 3 L/min. MEASUREMENTS AND MAIN RESULTS: Cheyne-Stokes respiration, defined as periodic breathing with apnea or hypopnea, was found in all patients. Low-flow oxygen significantly reduced the duration of Cheyne-Stokes respiration (50.7% +/- 12.0% to 24.2% +/- 5.4% total sleep time), mainly during stage 1 NREM (non-rapid eye movement) sleep (21.3% +/- 7.1% to 6.7% +/- 2.3% total sleep time) with no significant change during stage 2 sleep, slow-wave sleep, or REM (rapid eye movement) sleep. Although patients had normal SaO2 (96.0% +/- 1.7%) while awake, severe sleep hypoxemia was common; breathing oxygen reduced the amount of time that SaO2 was less than 90% from 22.3% +/- 8.0% to 2.41% +/- 1.93% of total sleep time. Sleep, disrupted to a variable extent in all patients, improved with oxygen therapy: There was an increase in total sleep time from 275.3 min +/- 36.6 to 324.6 min +/- 23.3; a reduction in the proportion of stage 1 sleep (27.6% +/- 5.8% total sleep time to 15.2% +/- 2.6% total sleep time); and a reduction in the number of arousals (30.4/h +/- 8.0 to 13.8/h +/- 1.9). The apnea-hypopnea index was reduced from 30.0 +/- 4.7 to 18.9 +/- 2.4 with oxygen breathing. CONCLUSION: In severe, stable congestive heart failure, nocturnal oxygen therapy reduces Cheyne-Stokes respiration, corrects hypoxemia, and consolidates sleep by reducing arousals caused by the hyperpneic phase of Cheyne-Stokes respiration. Correction of nocturnal hypoxemia and sleep disruption may improve the clinical status of these patients.     

Possibility of close relationship between sleep disorder breathing and acute coronary syndrome

OBJECTIVES: Sleep apnea syndrome and acute coronary syndrome (ACS) are related, but any further association with congestive heart failure (CHF) remains unclear. METHODS: Sixty-five patients with ACS (ACS group) and 48 patients with CHF (CHF group)underwent Holter electrocardiography and respiratory monitoring to identify sleep apnea. RESULTS: There were significant differences in age, sex, frequency of smoking, and ejection fraction between the two groups. The apnea hypopnea index showed similar high values in both ACS group (21.7 +/- 17.0/hr) and CHF group (19.4 +/- 17.9/hr). In the ACS group, 24 patients (37%) had central sleep apnea syndrome and 29 patients (45%) had obstructive sleep apnea syndrome. There were no significant differences in the incidences of central and obstructive sleep apnea syndromes between the two groups. Sympathetic nerve activity was significantly higher in ACS group than in CHF group (low/high frequency power ratio in overall study, 2.64 +/- 2.43 vs 1.24 +/- 1.05, p = 0.0003; in asleep study, 2.64 +/- 2.35 vs 1.23 +/- 1.04, p = 0.0002; in awake study, 2.73 +/- 2.36 vs 1.50 +/- 1.46, p = 0.002). CONCLUSIONS: Sleep apnea was observed at the same frequency in the ACS group and the CHF group including higher sympathetic nerve activity, and there was no significant difference in frequency of desaturation. This study suggested that sleep disorder breathing is frequently and similarly associated with both CHF and ACS.     

Cardiorespiratory effects of added dead space in patients with heart failure and central sleep apnea

BACKGROUND: Inhaled CO(2) has been shown to stabilize the breathing pattern of patients with central sleep apnea (CSA) with and without congestive heart failure (CHF). Added dead space (DS) as a form of supplemental CO(2) was effective in eliminating idiopathic CSA. The efficacy and safety of DS has not yet been evaluated in patients with CHF and CSA. METHODS: We examined the respiratory and cardiovascular effects of added DS in eight patients with CHF and CSA. The DS consisted of a facemask attached to a cylinder of adjustable volume. During wakefulness, the cardiorespiratory response to 200 to 600 mL of DS was tested. Cardiac output and stroke volume were measured using echocardiography with and without DS. During the nocturnal study, patients slept with and without DS, alternating at approximately 1-h intervals. RESULTS: Values are expressed as the mean +/- SE. The wakefulness study revealed a plateau in the partial pressure of end-tidal CO(2) (PETCO(2)) and the partial pressure of end-tidal O(2) between DS amounts of 400 and 600 mL. The mean stroke volume index (33 +/- 7 vs 34 +/- 7 mL/m(2), respectively) and the mean cardiac index (1.9 +/- 0.3 vs 1.9 +/- 0.4 L/min/m(2), respectively) were not affected by DS. Neither heart rate nor BP showed a significant change in response to DS of < or = 600 mL. During sleep, DS increased the PETCO(2) (40.7 +/- 2.7 vs 38.9 +/- 2.6 mm Hg, respectively; p < 0.05), reduced apnea (1 +/- 1 vs 29 +/- 7 episodes per hour, respectively; p < 0.01) and arousal (21 +/- 8 vs 30 +/- 8 arousals per hour, respectively; p < 0.05), increased the mean arterial oxygen saturation (SaO(2)) [94.4 +/- 1.0% vs 93.5 +/- 1.1%, respectively; p < 0.01), and reduced SaO(2) oscillations (DeltaSaO(2) from maximum to minimum, 1.8 +/- 0.4% vs 5.5 +/- 0.9%, respectively; p < 0.01). CONCLUSION: DS stabilized CSA and improved sleep quality in patients with CHF without significant acute adverse effects on the cardiovascular function.     

Prolonged apnea and oxyhemoglobin desaturation in asymptomatic premature infants.

Seventy-eight longitudinal four-channel recordings of heart rate, thoracic impedance, nasal thermistry, and pulse oximetry were performed on 26 asymptomatic premature infants (gestational age, 29.9 +/- 1.58 weeks; birth weight, 1,753 +/- 226 grams; postconceptional age, 34.3 +/- 2.0 weeks; postnatal age, 4.41 +/- 2.40 weeks; all values mean +/- SD). Tracings were scored for central and obstructive apnea, bradycardia, periodic breathing, apnea density, and prolonged apnea. The studies demonstrated 585 episodes (7.41/recording) of oxyhemoglobin desaturation with less than 90%. Recordings had a mean of 16.1 episodes of central apnea, 3.04 episodes of obstructive apnea, and 2.34 episodes of bradycardia. Periodic breathing and short obstructive apneas correlated significantly with the total number of oxyhemoglobin desaturations of less than 80% and 90%. Episodes of prolonged apnea were seen in 20 of 78 recordings. In the latter a significantly higher number of total desaturations (less than 90%), desaturations less than 80% and 90% in association with apnea and with bradycardia, longer desaturations, desaturations during sleep, and isolated bradycardia were observed. Variations in heart rate, thoracic impedance, nasal air flow, and pulse oximetry are associated with episodes of oxyhemoglobin desaturation in asymptomatic premature infants. These infants, although asymptomatic, may be at risk for impaired tissue oxygenation.     

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.     

Cerebrovascular response to carbon dioxide in patients with congestive heart failure

RATIONALE: Cerebrovascular reactivity to CO(2) provides an important counterregulatory mechanism that serves to minimize the change in H(+) at the central chemoreceptor, thereby stabilizing the breathing pattern in the face of perturbations in Pa(CO(2)). However, there are no studies relating cerebral circulation abnormality to the presence or absence of central sleep apnea in patients with heart failure. OBJECTIVES: To determine whether patients with congestive heart failure and central sleep apnea have an attenuated cerebrovascular responsibility to CO(2). METHODS: Cerebral blood flow velocity in the middle cerebral artery was measured in patients with stable congestive heart failure with (n = 9) and without (n = 8) central sleep apnea using transcranial ultrasound during eucapnia (room air), hypercapnia (inspired CO(2), 3 and 5%), and hypocapnia (voluntary hyperventilation). In addition, eight subjects with apnea and nine without apnea performed a 20-second breath-hold to investigate the dynamic cerebrovascular response to apnea. MEASUREMENTS AND MAIN RESULTS: The overall cerebrovascular reactivity to CO(2) (hyper- and hypocapnia) was lower in patients with apnea than in the control group (1.8 +/- 0.2 vs. 2.5 +/- 0.2%/mm Hg, p < 0.05), mainly due to the prominent reduction of cerebrovascular reactivity to hypocapnia (1.2 +/- 0.3 vs. 2.2 +/- 0.1%/mm Hg, p < 0.05). Similarly, brain blood flow demonstrated a smaller surge after a 20-second breath-hold (peak velocity, 119 +/- 4 vs. 141 +/- 8% of baseline, p < 0.05). CONCLUSION: Patients with central sleep apnea have a diminished cerebrovascular response to PET(CO(2)), especially to hypocapnia. The compromised cerebrovascular reactivity to CO(2) might affect stability of the breathing pattern by causing ventilatory overshooting during hypercapnia and undershooting during hypocapnia.     

A double-blind, placebo-controlled, crossover study of sildenafil in obstructive sleep apnea

BACKGROUND: Sildenafil prolongs the action of cyclic guanosine monophosphate and nitric oxide by inhibiting cyclic guanosine monophosphate-specific phosphodiesterase 5. It is largely used for erectile dysfunction, a highly prevalent condition in obstructive sleep apnea. Because nitric oxide promotes upper airway congestion, muscle relaxation, and pulmonary vasodilation, the aim of this study was to establish the impact of a single 50-mg dose of sildenafil on the sleep of patients with severe obstructive sleep apnea. METHODS: Thirteen [corrected] middle-aged men with severe obstructive sleep apnea were consecutively selected for this double-blind, placebo-controlled, crossover study. Exclusion criteria were obesity, cardiovascular and/or respiratory disease, and conditions that interfere with sleep. All-night polysomnography was preceded by a single 50-mg dose of sildenafil or matching placebo randomly administered at bedtime, after a washout period of 1 week. RESULTS: In comparison to placebo, a single 50-mg dose of sildenafil significantly increased the percentage of total sleep time with an arterial oxygen saturation of less than 90% (mean +/- SD, 15.6% +/- 9.6% vs 7.9% +/- 3.3%, [corrected] P < .01), without a difference in the nadir of oxygen desaturation. The mean arterial oxygen saturation also decreased (92.1% +/- 1.9% vs 93.8% +/- 1.3%, P = .03), [corrected] and the desaturation index increased (30.3 +/- 14.5 [corrected] events per hour vs 18.5 +/- 9.1 [corrected] events per hour, P < .001). There was an increase in apnea-hypopnea index (48.1 +/- 20.8 [corrected] events per hour vs 32.3 +/- 11.3 [corrected] events per hour, P = .001), [corrected] involving mostly obstructive events. CONCLUSION: In patients with severe obstructive sleep apnea, a single 50-mg dose of sildenafil at bedtime worsens respiratory and desaturation events.     

A shift from central and mixed sleep apnea to obstructive sleep apnea resulting from low-flow oxygen

Low-flow oxygen decreases the frequency of the 3 types of apnea (central, mixed, and obstructive) in patients with predominantly obstructive sleep apnea. The decrease in frequency appears to be accompanied by a shift in apnea distribution, consisting of a decrease in the proportion of central and mixed apneas and an increase in that of obstructive apneas. To determine whether this shift represents a greater inhibitory effect on central and mixed apneas or an increased tendency toward obstructive apneas, we administered low-flow oxygen during sleep to 9 patients who demonstrated predominantly central and mixed sleep apnea (51 +/- 33% and 33 +/- 21% of apneic events, respectively, mean +/- SD) and had resting, room air, oxygen tensions of 83 +/- 11 mmHg. During non-REM sleep, oxygen increased the baseline oxyhemoglobin saturation while reducing the average peak fall in oxyhemoglobin saturation during each apneic event. Oxygen reduced the overall apnea frequency from 66 +/- 7.8 (mean +/- SE) to 43.0 +/- 10.7 episodes per hour (p less than 0.02). Central and mixed apneas decreased markedly from 31.4 +/- 0.6 to 6.4 +/- 4.3 episodes per hour (p less than 0.02) and from 20.9 +/- 5.0 to 4.9 +/- 1.5 episodes per hour (p less than 0.02), respectively. However, obstructive apnea frequency more than doubled from 13.9 +/- 7.0 to 32.1 +/- 9.2 episodes per hour (p less than 0.02). We conclude that in these patients oxygen tension altered both the frequency and distribution of sleep-induced apnea, with a lower oxygen tension increasing the frequency of central and mixed apneas and a higher oxygen tension increasing the frequency of obstructive apneas.(ABSTRACT TRUNCATED AT 250 WORDS)     

Association between hemodynamic impairment and Cheyne-Stokes respiration and periodic breathing in chronic stable congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy.

Irregular breathing occurs frequently in patients with congestive heart failure (CHF) both during daytime and nighttime. Many factors are involved in the genesis of these breathing abnormalities, but the role of the hemodynamic impairment remains controversial. This study investigated the relation between worsening ventricular function and the frequency of respiratory disorders in patients with mild to severe CHF. One hundred fifty patients with CHF (mean age 53 +/- 8 years, left ventricular (LV) ejection fraction 26 +/- 7, in New York Heart Association [NYHA] classes II to IV, and who underwent stable therapy for > or =2 weeks) were studied. Analysis of instantaneous lung volume signal and arterial oxygen saturation during awake daytime revealed a normal respiratory pattern in 63 patients, whereas 87 had a persistent alteration of breathing, with a typical Cheyne-Stokes respiration (CSR) in 42 and periodic breathing (PB [oscillation of tidal volumes without apnea]) in 45 patients. Patients with PB and CSR showed a more pronounced hemodynamic impairment with a significantly reduced cardiac index, an increased pulmonary arterial wedge pressure, and a longer lung-to-ear circulation time (LECT) compared with patients with normal respiratory patterns. In a logistic regression model that included all of the variables significantly associated with breathing disorders, cardiac index and LECT emerged as the major determinants of CSR. In those patients with LECT > or =30 seconds (upper quartile) and cardiac index < or =1.9 L/min/m2 (lower quartiles), the incidence of CSR was significantly higher (69%) than in patients with lower LECT and higher cardiac index (14%, p <0.001). In conclusion, abnormalities of breathing activity during daytime are significantly associated with a prolonged circulation time and a more severe impairment of systolic and diastolic LV indexes.     

Incidence of respiratory syncytial virus-related hospitalizations in high-risk children: follow-up of a national cohort of infants treated with Palivizumab as RSV prophylaxis

Somatic and pulmonary growth coincide with resolution of hypoxemia by 2 years of age in most children with bronchopulmonary dysplasia (BPD). However, a distinct subgroup of children with BPD continue to require mechanical ventilation and/or supplemental oxygen beyond 2 years of age. This study tested the hypothesis that indices of pulmonary function would be significantly worse in children with BPD 2 years and older who remained technology-dependent secondary to hypoxemia, compared to those of age-matched children with BPD who were normoxemic. We measured pulmonary mechanics in 21 oxygen- or ventilator-dependent children with BPD 2 years and older (BPDO2 group; mean age+/-SD, 30.2+/-6.5 months) and in 19 children with BPD who had been weaned off mechanical ventilation and supplemental oxygen for at least 6 months (control group; mean age, 30.1+/-5.5 months). Respiratory rate and tidal volume were measured after sedation with chloral hydrate, and dynamic compliance and expiratory conductance were calculated using the esophageal catheter technique. Maximal flow at FRC (V'(maxFRC)) and ratio of forced-to-tidal flows at midtidal volume were obtained by the rapid thoracic compression technique. FRC was determined by nitrogen washout. There were no statistically significant differences in most measured indices of pulmonary mechanics between the BPDO2 and control groups. However, V'(maxFRC)/FRC was higher in controls compared to subjects in the BPDO2 group (0.81+/-0.40 sec(-1) vs. 0.34+/-0.21 sec(-1), P<0.003). We conclude that most indices of pulmonary function in children with BPD 2 years and older do not reflect the need for mechanical ventilation or supplemental oxygen. We speculate that measurements of lung elastic recoil and tests of distribution of ventilation and pulmonary perfusion may be more sensitive in differentiating normoxemic and hypoxemic children with BPD 2 years and older.     

Oxygen supplementation and cardiac-autonomic modulation in COPD

STUDY OBJECTIVES: Patients with COPD have an increased sympathetic modulation and reduced baroreflex sensitivity (BRS). Therefore, we studied the effects of breathing 31% supplemental oxygen (SuppO(2)) on autonomic modulation in a group of COPD patients. DESIGN: We measured autonomic modulation before and during the administration of SuppO(2) on 51 patients with COPD using time-frequency analysis of R-R intervals and BP before and after intervention. This was done via a counterbalanced crossover design. The BRS index was determined using the sequence method. RESULTS: Significant differences were seen in oxygen saturation levels following breathing with SuppO(2) ([mean +/- SD] 96.4+/-1.5%) when compared to those seen after breathing with compressed air (CA) (92.8+/-2.9%; p<0.0001). Significant increases were seen in the natural log-transformed high-frequency modulation (HFln) (SuppO(2), 10.8+/-1.3 natural logarithm [ln] ms(2)/Hz; CA, 10.6+/-1.3 ln ms(2)/Hz; p<0.028) and BRS (SuppO(2), 3.3+/-2.2 ms/mm Hg; CA, 2.8+/-1.8 ms/mm Hg) following the supplemental oxygen treatment (p<0.015). The low-frequency/high-frequency ratio of heart rate variability revealed significant differences between the two treatments (SuppO(2), 2.7 +/-1.2; CA, 3.1+/-1.3; p<0.008). The analysis of BP variability data revealed significant decreases in the HFln (CA, 6.9+/-1.0 mm Hg(2)/Hz; SuppO(2), 6.5+/-1.2 mm Hg(2)/Hz; p<0.0001). Hemodynamic data also revealed a decrease in mean heart rate after breathing SuppO(2) compared with that after breathing CA (CA, 87.3+/-13.3 beats/min; SuppO(2), 85.0+/-12.4 beats/min; p<0.0004). The arterial pulse pressure significantly decreased when breathing SuppO(2) compared with that when breathing CA (CA, 57.2+/-13.5 mm Hg; SuppO(2), 53.3+/-13.0 mm Hg; p<0.0023). CONCLUSION: Oxygen supplementation in COPD patients significantly and favorably alters autonomic modulation.