Is untreated sleep apnea a contributing factor for chronic hypertension?
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Humans↗
Biomedical subjects
C W Zwillich
Publications and source records attributed to C W Zwillich.
The control of breathing in clinical practice.
The control of breathing results from a complex interaction involving the respiratory centers, which feed signals to a central control mechanism that, in turn, provides output to the effector muscles. In this review, we describe the individual elements of this system, and what is known about their function in man. We outline clinically relevant aspects of the integration of human ventilatory control system, and describe altered function in response to special circumstances, disorders, and medications. We emphasize the clinical relevance of this topic by employing case presentations of active patients from our practice.
Animals↗
Salmeterol vs theophylline: sleep and efficacy outcomes in patients with nocturnal asthma.
STUDY OBJECTIVES: To compare the efficacy, safety, and effects on sleep quality of salmeterol and extended-release theophylline in patients with nocturnal asthma. DESIGN: Randomized, double-blind, double-dummy, three-period crossover. SETTING: Outpatients at a single center. Patients spent 1 night during screening and 2 nights during each study period in a sleep laboratory for completion of sleep studies. PATIENTS: Male and female patients who were at least 18 years old with nocturnal asthma (baseline FEV1, 50 to 90% of predicted) and who required regular bronchodilator therapy. Patients on inhaled corticosteroids, cromolyn, and nedocromil were allowed into the study if their dosing remained constant throughout the study. INTERVENTIONS: Inhaled salmeterol (42 microg per actuation), extended-release oral theophylline (titrated to serum levels of 10 to 20 microg/mL), and placebo taken twice daily. MEASUREMENTS AND RESULTS: Efficacy measurements included nocturnal spirometry, nocturnal polysomnography, sleep questionnaires, and daily measurements of lung function and symptoms. Salmeterol was superior to theophylline (p < or = 0.05) in maintaining nocturnal FEV1 levels and was superior to placebo (p < or = 0.05) in improving morning and evening peak expiratory flow (PEF) and in decreasing nighttime albuterol use. The use of salmeterol significantly increased the percentage of days and nights with no albuterol use and decreased daytime albuterol use compared with theophylline and placebo (p < or = 0.05). Sleep quality global scores significantly improved with salmeterol and placebo (p < 0.001) but not with theophylline. The effects on sleep architecture were similar across treatment groups. CONCLUSIONS: Salmeterol (but not theophylline) was associated with sustained improvements in morning PEF, protection from nighttime lung function deterioration, reductions in albuterol use, and improvements in patient perceptions of sleep. No differences were seen in polysomnographic measures of sleep quality.
Administration, Inhalation↗
Obstructive sleep apnoea causes transient and sustained systemic hypertension.
Apnoea with associated fall in arterial oxygen tension results in increased blood pressure and a striking surge in sympathetic activity, which can be measured as high catecholamine levels or increase in muscle sympathetic nerve activity. Following the termination of apnoea with resumption of breathing, sympathetic nerve activity decreases and blood pressure returns to lower values. Sympathetic mediated alternations in peripheral vascular resistance best explain these findings. Hypertension during wakefulness in untreated patients with apnoea is also associated with high sympathetic nervous system activity. Nasal continuous positive airway pressure (CPAP) has been shown to lower blood pressure in some hypertensive obstructive sleep apnoea (OSA) patients. Recently, previously untreated OSA patients exhibiting awake sympathetic hyperexcitation demonstrated striking attentuation of the response following initiation of effective CPAP therapy. Accordingly, the common problem of systemic hypertension found in untreated OSA appears to be mediated by sympathetic excitation and responds to effective CPAP therapy.
Adult↗
Sleep apnoea and autonomic function.
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Animals↗
Influence of treatment on muscle sympathetic nerve activity in sleep apnea.
Obstructive sleep apnea (OSA) is a common disorder associated with systemic hypertension, myocardial infarction, stroke, and premature death. Elevated sympathetic tone has been documented previously in OSA and may contribute to the cardiovascular risk. As OSA therapy appears to reduce mortality, we wondered if decreased apnea activity would attenuate the sympathetic hyperactivity of untreated patients. Muscle sympathetic nerve activity (MSNA) was measured during wakefulness via peroneal microneurography in seven patients with documented OSA before and at least 1 mo after compliance-monitored nasal continuous positive airway pressure (CPAP) therapy. Before institution of CPAP therapy, MSNA was high in all patients and decreased after CPAP therapy (baseline versus CPAP: 69.4 +/- 15.3 versus 53.9 +/- 10.5 bursts/min, mean +/- SD; p<0.01). However, the decrease in MSNA was limited to the four patients with the greatest nightly use of CPAP (> or = 4.5 h/night), whereas it remained unchanged in the three patients who were less compliant. There was a direct linear correlation between the decrease in MSNA (bursts/min) and the average hours of CPAP use per night (r = 0.87, p = 0.01). We conclude that in patients with OSA effective reduction in apnea activity with CPAP therapy diminishes the high sympathetic tone present during resting wakefulness.
Adult↗
OSA and cardiovascular morbidity: Will CPAP prove to be effective?
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Cardiovascular Diseases↗
Continuous versus bilevel positive airway pressure for obstructive sleep apnea.
Recent objective studies demonstrate relatively low hours of nightly use during nasal continuous positive airway pressure (CPAP) therapy for obstructive sleep apnea (OSA). Patients frequently complain of dyspnea or discomfort during CPAP use, especially during expiration (against the continuous pressure), which may be a reason for the low hours of use. We hypothesized that with decreased expiratory pressure, hours of nightly use would increase. Therefore, we randomized 83 OSA patients to receive either continuous or bilevel positive airway pressure when expiratory pressure is lower. To document objectively the effective use of either therapy, we built and installed elapsed-time and mask pressure sensors in the patients' positive airway pressure units. A total of 62 patients were evaluable and followed for 1 yr. Of these, 26 received bilevel and 36 CPAP pressures. The machine timers measured accumulated "machine-on" time, and the mask pressure sensor recorded the total time in which the mask pressure was within 2 cm H2O of the effective pressure (pressure shown to eliminate 95% of the obstructive apneas during a full night of polysomnography). The mean machine timer hours of CPAP were 5.0 +/- 0.19 SEM and 4.9 +/- 0.23 SEM during bilevel therapy (p NS) over a 12-mo period. The pressures required during CPAP or bilevel therapy were not different between high and low hourly users. Effective use, the percentage of time that the machine was running and the prescribed pressure was being delivered, was 80% in CPAP and 82% in the bilevel users (p NS). Both groups had equal complaints with regard to mask discomfort, machine noise, and nasal stuffiness.(ABSTRACT TRUNCATED AT 250 WORDS)
Female↗
Is an anticholinergic agent superior to a beta 2-agonist in improving dyspnea and exercise limitation in COPD?
STUDY OBJECTIVE: To evaluate the impact of a week-long course of inhaled albuterol compared with ipratropium on expiratory peak flow, exercise performance, and dyspnea in patients with stable COPD. DESIGN AND INTERVENTIONS: A double-blind, two-period, crossover evaluation, wherein the subjects inhaled albuterol, two puffs four times a day (qid) for 7 days, or ipratropium, two puffs quid for 7 days, in random sequence. SETTING: Outpatients of the Pennsylvania State University Hospital, Lebanon VA Medical Center, and local private office practices. PARTICIPANTS: A sample of 15 subjects with stable COPD with FEV1 < 55% predicted. MEASUREMENTS AND RESULTS: Variables measured at baseline (no inhaled bronchodilator) and/or on day 7 of each arm included FEV1 (liters), 12-min walk test distance (meters), "rescue" puffs of metaproterenol needed each week, and dyspnea scoring after walking, on the Borg Category Scale (0 to 10 = maximal). There was no significant difference in distance walked in 12 min (mean of 751.0 +/- 55.5 [+/- SE]) vs 755.7 +/- 61.3 m) or perceived dyspnea (mean 2.7 +/- 0.4 vs 3.3 +/- 0.4) during albuterol or ipratropium use. Seven patients preferred ipratropium, seven preferred albuterol, and one had no preference. CONCLUSION: We conclude that the effects of 1 week of albuterol or ipratropium have similar effects on exercise performance and subjective dyspnea in patients with stable COPD.
Administration, Inhalation↗
Obstructive sleep apnea.
The high prevalence of obstructive sleep apnea (OSA) has only recently been appreciated, in part because the symptoms and signs of chronic sleep disruption are often overlooked in spite of their debilitating consequences. They typically develop insidiously during a period of years. We now know that the lives of millions of people each year are significantly impaired by the sequelae of OSA. Many of these patients go unrecognized, with tremendous medical and economic consequences for individual patients and for society. Evidence indicates that chronic, heavy snoring may be associated with increased long-term cardiovascular and neurophysiologic morbidity. Therefore considerable interest lies in the study of the epidemiology and the natural history of these related disorders. The fundamental problem in OSA is the periodic collapse of the pharyngeal airway during sleep. The pathophysiology of this phenomenon is reviewed in some detail. During apneas caused by obstruction, airflow is impeded by the collapsed pharynx in spite of continued effort to breathe. This causes progressive asphyxia, which increasingly stimulates breathing efforts against the collapsed airway, typically until the person is awakened. Hypopneas predominate in some patients and are caused by partial pharyngeal collapse. The clinical sequelae of OSA relate to the cumulative effects of exposure to periodic asphyxia and to sleep fragmentation caused by apneas and hypopneas. Some patients with frequent, brief apneas and hypopneas and normal underlying cardiopulmonary function may have considerable sleep disruption without much exposure to nocturnal hypoxia. Patients with sleep apnea often have excessive daytime sleepiness. As the disorder progresses, sleepiness becomes increasingly irresistible and dangerous, and patients develop cognitive dysfunction, inability to concentrate, memory and judgment impairment, irritability, and depression. These problems may lead to family and social problems and job loss. Cardiac and vascular morbidity in OSA may include systemic hypertension, cardiac arrhythmias, pulmonary hypertension, cor pulmonale, left ventricular dysfunction, stroke, and sudden death. The challenge for the clinician is to routinely consider the diagnosis and to incorporate several basic questions in the historical review of systems regarding daytime or inappropriate sleepiness. The diagnosis of OSA is made with polysomnography, and the decision to treat is based on an overall assessment of the severity of sleep-disordered breathing, sleep fragmentation, and associated clinical sequelae. The therapeutic options for the management of OSA are reviewed. Recognition and appropriate treatment of OSA and related disorders will often significantly enhance the patient's quality of life, overall health, productivity, and safety on the highways.
Adult↗
Nasal CPAP: an objective evaluation of patient compliance.
Nasal continuous positive airway pressure (NCPAP) improves sleepiness and prognosis in obstructive sleep apnea (OSA). Our objective was to document NCPAP compliance and the percentage of time that the effective pressure shown to eliminate 95% of the obstructive apneas and hypopneas was maintained. We built and covertly installed an elapsed timer and mask pressure transducer recorder in NCPAP units of 47 OSA patients. Subjects were seen at 2- to 8-wk intervals over 6 months. Group mean age was 51 yr; 38 males, with mean body mass index of 42; all complained of daytime sleepiness. Initial full night polysomnography demonstrated a mean apnea-hypopnea index (AHI) of 58 +/- 2.6 SEM (range, 10 to 115). Nine subjects discontinued therapy within 3 months for various reasons. In the remaining subjects (n = 38) the actual mean nightly hours of use was 4.7 which represents 68% of the stated total sleep time (compliance). However, effective mean hours of use was 4.3 which represents 91% of the time that prescribed effective pressure was maintained at the mask. The AHI did not correlate with compliance, but did correlate with effective use (R = 0.27048, p = 0.0006). Subjective initial complaints of daytime sleepiness correlated with compliance only during the first visit (R = 0.38590, p = 0.05). No predictors for compliance were found.
Adult↗
The post-cardiac injury syndrome following blunt chest trauma: case report.
The case of a 53-year-old man is reported in which the patient developed post-cardiac injury syndrome 2 weeks after blunt trauma to the thorax. The patient failed to respond adequately to ibuprofen but improved on corticosteroids. He suffered relapses 8 and 15 months after the original injury following reductions in the corticosteroid dosage. The patient at last follow-up had been asymptomatic for over 4 years.
Heart Diseases↗
Ventilatory response to oxygen after eucapnic hypoxia in conscious dogs.
In humans the ventilatory [minute ventilation (VI)] response to sustained hypoxia is biphasic: an initial brisk increase followed by a decline is usually seen. However, in adult dogs, the ventilatory response to a similar stimulus shows no decline. To evaluate if central ventilatory drive is altered by sustained hypoxia, we measured the lowest ventilation (nadir) as the lowest moving average of seven sequential breaths within 200 s after transition to hyperoxia (100% O2) after 3 different exposures: room air, 4-min (brief) eucapnic hypoxia (arterial O2 saturation = approximately 80%), and 12-min (prolonged) eucapnic hypoxia. The nadir hyperoxic VI after brief hypoxia (2.7 +/- 0.2 l/min) was similar to that after room air (2.6 +/- 0.2 l/min; P > 0.05), with both less than prior room air mean VI (P < 0.05). The nadir after prolonged hypoxia (3.5 +/- 0.3 l/min) was significantly greater than that after brief hypoxia (P < 0.05). This suggests that central ventilatory drive increases in conscious dogs after sustained eucapnic hypoxia. The reason for the difference in central ventilatory response to hypoxia between conscious dogs and adult humans is unexplained.
Animals↗
Breathing route and resistive loading: influence on ventilatory response to hypoxia in conscious dogs.
Unlike normal humans, the tracheostomized conscious dog does not show ventilatory adaptation in response to sustained isocapnic hypoxia. To determine whether this phenomenon is a result of the breathing route or the relatively low airflow resistance of tracheostomy breathing, we evaluated the ventilatory response to sustained isocapnic hypoxia (20 min; arterial oxyhemoglobin saturation = 80%) in five awake dogs during nasal-oral (mask) breathing, tracheal breathing, and tracheal breathing with added matched resistance of upper airway breathing. Mask breathing, like unloaded tracheal breathing, was associated with a consistent level of hyperventilation during the entire hypoxic exposure period. However, mask breathing was always less (P < 0.05) than that found during unloaded tracheal breathing. Loaded tracheal breathing during hypoxia resulted in initial hyperventilation similar to that of unloaded tracheal breathing followed by a "roll off" to a lower minute ventilation similar to that of mask breathing. Our findings demonstrate that ventilatory adaptation is only present during loaded tracheal breathing in dogs and suggest that the breathing route and upper airway resistive loading may play roles in ventilatory adaptation.
Airway Resistance↗
Ventilatory response to sustained eucapnic hypoxia in the adult conscious dog.
The ventilatory response to 20 min sustained isocapnic hypoxia (SaO2, 80 +/- 2%) was examined in 5 trained unanesthetized adult dogs breathing through an endotracheal tube. End tidal PCO2 was maintained at the resting levels. The dogs' conscious status was monitored by recording EEG and EOG on a chart recorder. The room temperature was kept between 19 and 21 degrees C. All tests were repeated in each dog on 2 occasions: (1) unloaded tracheal breathing or (2) resistive loaded breathing. During unloaded tracheal breathing, the average ventilation in response to sustained hypoxia rose from a control of 5.1 +/- 0.3 L/min (mean +/- within-dog SE) to 19.2 +/- 1.1 L/min at the initial stage of hypoxia. Ventilation remained at 20.7 +/- 1.3 L/min at 10 min, and then 19.7 +/- 1.4 L/min at the completion of the 20 min hypoxic exposure. There was no ventilatory adaptation observed (P greater than 0.05). After release from hypoxia, the ventilation fell abruptly to 7.6 +/- 0.8 L/min, which was higher than the resting baseline level (P less than 0.05), and then gradually returned to the resting baseline within 10 min. Experiments exposing the dogs to 40 min sustained hypoxia also failed to elicit significant adaptation. During resistive loading, the pattern of average ventilation in response to sustained hypoxia was similar to that observed in unloaded breathing tests. But the ventilatory recovery was longer than unloaded breathing, returning to the resting baseline within 20 min. Again, there was no ventilatory adaptation observed.(ABSTRACT TRUNCATED AT 250 WORDS)
Adaptation, Physiological↗
Adenosine infusion and periodic breathing during sleep.
Intravenously administered adenosine may increase ventilation (VI) and the ventilatory response to CO2 (HCVR). Inasmuch as we have previously hypothesized that those with higher HCVR may be more prone to periodic breathing during sleep, we measured VI and HCVR and monitored ventilatory pattern in seven healthy subjects before and during an infusion of adenosine (80 micrograms.kg-1.min-1) during uninterrupted sleep. Adenosine increased the mean sleeping VI (7.6 +/- 0.4 vs. 6.5 +/- 0.4 l/min, P less than 0.05) and decreased mean end-tidal CO2 values (42.4 +/- 1.2 vs. 43.7 +/- 1.0 Torr, P = 0.06, paired t test) during stable breathing. In six of seven subjects, periodic breathing occurred during this infusion. The amplitude (maximum VI--mean VI) and period length of this periodic breathing was variable among subjects and not predicted by baseline HCVR [correlation coefficients (r) = 0.64, P = 0.17 and r = -0.1, P = 0.9, respectively]. Attempts to measure HCVR during adenosine infusion were unsuccessful because of frequent arousals and continued periodic breathing despite hyperoxic hypercapnia. We conclude that adenosine infusion increases VI and produces periodic breathing during sleep in most normal subjects studied.
Adenosine↗
Increased normoxic ventilation induced by repetitive hypoxia in conscious dogs.
To determine if a long-lasting increase in normoxic ventilatory drive is induced in conscious animals by repetitive hypoxia, we examined the normoxic [arterial O2 saturation (SaO2) > 93%] ventilatory response following successive episodes of 2-min eucapnic hypoxic challenges (SaO2 = 80%) in awake tracheotomized dogs. End-tidal CO2 was maintained at the resting level during and after repetitive hypoxia. The experimental protocol was performed twice in each of five dogs on separate days. To determine if changes in normoxic ventilation occurred between episodes of repetitive hypoxia, data were compared from six periods (epochs) for all experiments. The mean minute ventilation (VI) during three normoxic periods between episodes of intermittent hypoxia was 135, 154, and 169% of control (P < 0.05). VI during a 30-min recovery period was still higher at 183 and 172% of control (P < 0.05). Normoxic VI between hypoxic and recovery periods was significantly higher than the corresponding values in sham experiments. Our results indicate that a long-lasting increase in normoxic ventilation can be evoked in an awake unanesthetized dog by a short exposure to repetitive hypoxia.
Animals↗