Autonomic function in sleep apnea patients: increased heart rate variability except during REM sleep in obese patients.

The objective of this study was to examine heart rate variability (HRV) among sleep stages in obstructive sleep apnea (OSA) patients. The study was retrospective within subjects and examined the sleep stages and HRV in relation to OSA, age, body mass index (BMI), and sex. Data collected during diagnostic polysomnograms were used in this study. There were 105 clinical patients undergoing polysomnography for suspected OSA. We sampled the electrocardiogram (ECG) from wakefulness, stage 2, and REM sleep and analyzed for frequency domain HRV. Sampled epochs were free of apnea and arousals. Heart rate variability decreased with age. Total frequency variability (TF) and low frequency variability (LF) in wakefulness and REM sleep increased as apnea severity increased. Measures of TF, LF, and the LF/HF ratio were greatest in REM sleep. There was less LF and TF in Stage REM sleep in patients with higher BMI. In conclusion, the decrease in HRV with aging is a robust finding that occurs even in a clinical sleep apnea population. However, apnea does not mimic aging effects on the heart because HRV increased as apnea severity increased. The decrease in HRV during REM sleep in the obese apnea patients suggests the possibility of an autonomic dysfunction in this subgroup.

Sleep dysfunction in patients with gastro-oesophageal reflux disease: prevalence and response to GERD therapy, a pilot study.

BACKGROUND: There is little information on the prevalence of pathological sleep disorders in patients with gastro-oesophageal reflux disease and whether pharmacological treatment of patients with gastro-oesophageal reflux disease will lead to improvement in sleep. AIMS: This pilot study determined the prevalence of sleep disorder in patients with erosive gastro-oesophageal reflux disease, correlated subjective (questionnaire) and objective (actigraphy - a watch worn on the wrist that monitors motion to help differentiate sleep from awake states) assessment of sleep dysfunction and determined whether therapeutic resolution of oesophageal symptoms was associated with an improvement in sleep. METHODS: Eighteen patients with erosive gastro-oesophageal reflux disease received esomeprazole 40 mg once daily for 8 weeks. Assessments at 0, 4 and 8 weeks included: Gastrointestinal Symptoms Rating Scale, Pittsburgh Sleep Quality Index questionnaire and ambulatory wrist actigraphy. RESULTS: Unrecognized sleep disturbance occurred in 81% of this cohort of patients with gastro-oesophageal reflux disease and erosive oesophagitis. Median reflux syndrome score (heartburn and acid regurgitation) on Gastrointestinal Symptoms Rating Scale decreased from 2 at baseline to 0 at weeks 4 and 8 (P

Update on nonapnea sleep disorders.

Much of the attention in the field of sleep disorders focuses on the obstructive sleep apnea syndrome. However, for the pulmonary physician interested in a wider breadth of sleep knowledge, important and interesting developments have been witnessed in the area of nonapneic sleep disorders. Exciting new breakthroughs have illuminated the pathogenesis of narcolepsy and are expected to lead to new treatment options for narcoleptic patients. For the surprisingly common but poorly understood restless legs syndrome (RLS), an expanding armamentarium of medications aids the knowledgeable physician in caring for his or her patients. The physiology of circadian rhythms is better understood due to basic scientific advances. Finally, new drugs used to treat insomnia offer more flexible treatment options and an old and previously vilified drug may allow sleep specialists to better understand the mechanisms of sleep.

Driving simulation with EEG monitoring in normal and obstructive sleep apnea patients.

STUDY OBJECTIVES: To measure simulated driving performance in obstructive sleep apnea patients and its relationship with EEG defined attention lapses. DESIGN: Prospective, mixed design comparing apnea patients and control subjects over a 60-minute driving simulation task while continuously recording both driving performance and EEG measures. SETTING: Sleep disorders center. PARTICIPANTS: 15 polysomnographically diagnosed obstructive sleep apnea patients (mean age 42 +/- 6 yrs.) and 15 healthy volunteers (mean age 38 +/- 6 yrs.). INTERVENTIONS: NA. MEASUREMENTS AND RESULTS: A computer based driving simulator recorded lane position variability, speed variability, steering rate variability, and crash frequency. The frequency and duration of EEG-defined attention lapses were also measured. The results demonstrated that the apnea group had significantly greater variability in lane position, steering rate, and speed than the control group. The apnea group also had more crashes. In addition, the apnea group had more EEG-defined attention lapses of longer duration. Except for speed and steering rate variability, these differences increased over the 60-minute task. Measures of lane position variability and crash frequency had a significant positive correlation with attention lapse frequency and duration. CONCLUSIONS: The driving simulation task unmasked and quantified marked performance impairments in the sleep apnea group that increased over time. The poor performance appeared related to the EEG-defined attention lapses. Lane position variability appeared to be the most sensitive measure for assessing and quantifying impairment. This study suggests that poorer driving performance and crashes are not entirely due to overt sleep, but inattention due to sleepiness.

Influence of sex and age on duration and frequency of sleep apnea events.

OBJECTIVES: Differences between men and women potentially provide insight into the regulation sleep apnea events. This study, therefore, examined how apnea frequency and duration varied according to age, sex, and sleep stage in a clinical population. DESIGN: NA SETTING: NA PATIENTS: Patients were 215 women and 215 men referred to a sleep disorders center with symptoms of obstructive sleep apnea and matched for BMI. Apnea events were compared across three age groups (18-39, 40-59, and 60-88 years) in stage 2 and in REM sleep. INTERVENTIONS: NA RESULTS: In stage 2 sleep, young and middle aged women were similar averaging 15 and 13 apnea events per hour respectively. Men had significantly more events averaging 27 and 30 events per hour for the corresponding age groups. The apnea frequency doubled from middle age to older women, and the sex difference narrowed between the older males and females to a non significant difference (26 events per hour for women versus 34 events per hour for men). Apnea duration was significantly longer in men than in women. Stage 2 apnea duration increased significantly with age for men (20.1, 21.5, 23.8 s) and women (16.7, 18.3, 20.6 s) across the three age groups. This also occurred in REM sleep in for men (22.8, 26.5, 29.8 s) and women (19.3, 22.4, 26.6 s). CONCLUSIONS: Duration did not demonstrate the marked "menopausal effect" that there was for apnea frequency. Female gender and younger age conferred benefit primarily by preventing airway collapse (reduced apnea frequency) with less of an effect on apnea duration, i.e., the ability to end the apnea. Compared to stage 2 sleep, REM sleep reduced the differences between men and women in apnea frequency. One explanation may be that differences in muscle tone of the upper airway account for the sex differences in apnea frequency.

Eight weeks of non-nightly use of zolpidem for primary insomnia.

CONTEXT: Intermittent use (i.e., a few nights per week) of hypnotic medication is often recommended for the treatment of chronic insomnia despite an absence of efficacy and safety data using this regimen. STUDY OBJECTIVES: To evaluate the clinical efficacy and safety of intermittent pharmacotherapy for chronic insomnia. DESIGN AND SETTING: Randomized, double-blind, placebo-controlled, parallel groups, clinical trial at six sleep research sites. PATIENTS: One hundred-sixty-three (115 women, 48 men; mean age 44.1+ SE. 0.9 years), DSM-IV-defined primary insomnia patients were randomized, 134 patients completed the study. INTERVENTIONS: Eight weeks of treatment with either zolpidem 10 mg or placebo. Patients were instructed to take medication when they felt they needed it, but at least three and no more than five times per week. MAIN OUTCOME MEASURES: Investigator and Patient Global Ratings were the primary outcome variables. Secondary measures from daily questionnaires to assess efficacy, rebound insomnia and drug taking behavior. RESULTS: The Investigator's Global Rating indicated that intermittent use of zolpidem produced a significantly better therapeutic effect and significantly reduced insomnia severity throughout the 8-week study relative to placebo. Zolpidem was found to be effective in initiating and maintaining sleep on nights taken, as compared to placebo, based upon the Patient's Global Ratings and all subjective sleep variables. No evidence of rebound insomnia was found on nights that zolpidem was not taken. The number of nights a pill was taken did not differ between groups, nor did frequency of pill taking change in either group across the duration of the study. There were no significant effects of treatment upon quality of life or neurocognitive measures. CONCLUSIONS: Zolpidem 10 mg is effective in treating insomnia when used intermittently, without evidence of discontinuation effects or increased frequency of pill taking.

Antibiotic susceptibility profile of group B streptococcus acquired vertically.

OBJECTIVE: To determine the contemporary antibiotic susceptibility profile of vertically acquired group B streptococcal isolates. METHODS: Susceptibility to ampicillin, penicillin G, erythromycin, clindamycin, cefazolin, and gentamicin was assessed by two methods, minimal inhibitory concentration and disc diffusion. RESULTS: The susceptibility profiles of 119 colonizing and eight invasive strains of group B streptococcus isolated from January 1996 to September 1997 at two hospitals in Birmingham, Alabama-University of Alabama at Birmingham and Cooper Green-were studied. Minimal inhibitory concentration determinations indicated that all colonizing strains were susceptible or moderately susceptible to ampicillin and penicillin G. Resistance was noted by at least one strain to each of the other antibiotics; all were resistant to gentamicin, whereas 27 (21%) were resistant to erythromycin, five (4%) to clindamycin, and one (1%) to cefazolin. All of the eight invasive strains were susceptible or moderately susceptible to ampicillin, penicillin G, clindamycin, and cefazolin; one (13%) was resistant to erythromycin, and all were resistant to gentamicin. Disc diffusion results generally were concordant with minimal inhibitory concentration results, although by disc diffusion fewer isolates were classified as susceptible, and more as moderately susceptible, to ampicillin and penicillin G than by minimal inhibitory concentration. CONCLUSION: Universal susceptibility of group B streptococcus to members of the penicillin family supports the continued use of penicillin G or ampicillin for early onset neonatal group B streptococcal disease prevention. For patients allergic to beta-lactam agents, clindamycin (4% resistance) may be a better alternative than erythromycin (21% resistance).

Nasal patency and the effectiveness of nasal continuous positive air pressure in obstructive sleep apnea.

Nasal airway obstruction may exacerbate sleep apnea and is difficult to quantify on clinical examination. In this study, we examined the relationship among nasal patency, the frequency of sleep apnea events, and effective nasal continuous positive air pressures. Acoustic rhinometry was used as an objective measurement of nasal cross-sectional areas in 76 patients without nasal symptoms who underwent study with diagnostic polysomnography because of obstructive sleep apnea. Patients with persistent obstructive sleep apnea were titrated to nasal continuous positive air pressure in a split night study. All subjects had a mean apnea/hypopnea index of 28, and those with obstructive sleep apnea had a mean apnea/hypopnea index of 43. Mean cross-sectional areas 1 to 4 cm into the nose were 1.7, 1.1, 2.1, and 2.8 cm2, respectively (F = 39, p < 0.001). However, there was no correlation between the apnea/hypopnea index and the cross-sectional area at the four distances (r = 0.03, 0.06, 0.02, and 0.02, respectively, p = not significant). Correlations between nasal continuous positive air pressures and cross-sectional areas did not reveal a significant relationship at any of the four sites (r = 0.09, 0.07, -0.03, 0.00, respectively). Findings in patients with apnea were also compared with those in patients without apnea and significant differences were not found (F = 0.019, p = not significant). Although it would seem intuitive that increased nasal obstruction is associated with the severity of obstructive sleep apnea and difficulty with the use of nasal continuous positive air pressure, this study shows that nasal patency, as measured by acoustic rhinometry, does not correlate with the severity of obstructive sleep apnea, as determined by the apnea/hypopnea index or the effective nasal continuous positive air pressure.

Sleep apnea in obese miniature pigs.

We postulated that three extremely obese Yucatan miniature pigs would have more sleep apnea than three nonobese Yucatan miniature pigs. Pigs were studied with the use of electroencephalograms, inductance plethysmography, oximetry, expired nasal CO2, or thermistors. All of the obese pigs, but none of the nonobese pigs, had both sleep apnea (8.5, 10.3, and 97.0 in obese pigs vs. O apnea + hypopnea/h in all nonobese pigs; P < 0.05) and oxyhemoglobin desaturation episodes during sleep [9.4 +/- 3.0 vs. 0 + 0.53 (SD) mean desaturation episodes/h in obese pigs vs. nonobese pigs, respectively; P < 0.05]. Two of the extremely obese pigs had obstructive sleep apnea, whereas the third obese pig had central sleep apnea. We conclude that sleep apnea occurs in extremely obese Yucatan minipigs and suggest that this animal can be used as a model for sleep apnea in obesity.

Sleep-related erections: absence of change following presleep sexual arousal.

We examined the effects of a brief period of sexual arousal before sleep on sleep-related erections (SREs) to add to our knowledge concerning those factors that affect SREs. Twelve subjects watched a 5 minute sexually explicit video before sleep. On other evenings they watched a dysphoric arousal video or a lecture (neutral) video. Sleep and SREs were recorded throughout the following night. Although the brief sexual arousal video produced a full or near full erection in all subjects, no significant effect on subsequent SREs occurred. We conclude that the control of SREs in young healthy subjects is insulated against the effect of a brief period of sexual arousal before sleep.

Minimal rebound insomnia after treatment with 10-mg zolpidem.

This study examined rebound insomnia after discontinuation of chronic use of zolpidem (10 mg), a short elimination half-life imidazopyridine. The zolpidem group was bracketed by a placebo group and a positive control group taking 0.5 mg of triazolam (twice the recommended dose), which is known to produce rebound insomnia. Ninety-nine patients with sleep complaints that were polysomnographically documented participated in the study. After randomization, patients completed a 2-night, single-blind, placebo baseline period, a 28-night double-blind treatment phase, and a 3-night, single-blind, placebo substitution period. Polysomnographic and subjective sleep variables indicated a lack of rebound insomnia for the zolpidem group. The positive triazolam control group had rebound insomnia only on the first discontinuation night. There was no significant correlation between rebound insomnia and the level of initial insomnia, the degree of response to treatment in week 4, or the amount of tolerance that developed during drug use. During the 4-week treatment period, efficacy diminished for both drugs. From these data, it cannot be determined whether the lack of rebound insomnia with zolpidem is a result of drug dose or some property of the drug such as receptor selectivity.

Narcolepsy.

Narcolepsy is a commonly under diagnosed or misdiagnosed problem that results in severe daytime sleepiness. There is a strong genetic component with some immune system involvement. It may occur in combination with other sleep disorders such as sleep apnea complicating its treatment. An objective diagnosis requires a polysomnogram and Multiple Sleep Latency Test. Management depends on the careful use of stimulant medication to control the sleepiness and other medications to control the auxiiliary symptom of cataplexy.

The acute effects of nefazodone, trazodone and buspirone on sleep and sleep-related penile tumescence in normal subjects.

This study examined the effects of nefazodone, trazodone and buspirone on sleep and sleep-related penile tumescence. Trazodone is a sedating antidepressant without anticholinergic properties. Nefazodone is a new antidepressant that is a structural analogue of trazodone but is less sedating. Buspirone is a nonsedating, nonbenzodiazepine anxiolytic with antidepressant properties. Nefazodone was compared to trazodone and buspirone in a double-blind, placebo-controlled crossover study in 12 normal healthy males. Nefazodone increased rapid eye movement (REM) sleep, whereas trazodone and buspirone suppressed REM sleep. The drugs only minimally affected other sleep stages. Trazodone increased total tumescence time by delaying the onset of detumescence; nefazodone increased total tumescence time only insofar as it increased REM sleep; buspirone did not change total tumescence time when compared to placebo. The results support a growing body of data indicating that not all antidepressants suppress REM sleep. The results also are consistent with the interpretation of an earlier study showing that trazodone prolongs penile tumescence during sleep as a result of its alpha-adrenergic blocking properties that suppress detumescence. Nefazodone, with less alpha-adrenergic blocking activity, did not abnormally penile tumescence beyond REM sleep.

Characteristics of penile erections during sleep recorded from normal subjects.

The results of penile tumescence recordings from first- and second-night polysomnograms from 146 normal subjects are presented for four age groups. The data are in close agreement with basic tumescence parameters that have been presented earlier. In addition, results from first and second nights are compared, and data are presented from base and coronal sulcus (tip) recordings locations. The results indicate that tumescence parameters that are most correlated with rapid-eye-movement sleep are those most likely to significantly differ from the first to the second night. Base and tip recordings closely paralleled each other. Additionally, tumescence periods were also divided into three phases that are likely to correspond to different physiological states. These three phases, Tup, Tmax, and Tdown, vary in their sensitivity to night and age effects. It is hypothesized that changes in different tumescence phases may reflect different pathophysiologies.

Diagnosis and treatment of insomnia and depression.

Disturbed sleep is a common problem particularly among depressed patients. Diagnostic and treatment considerations are reviewed for two of the more common insomnia problems, psychophysiological insomnia and insomnia associated with depression. Studies of the actual sleep patterns of patients with these disorders reveal reliable differences that are important to understand for optimized treatment outcome. As the differentiation of sleep disorders becomes more precise and the pharmacologic armamentarium becomes greater, emphasis needs to be placed on both understanding the etiology of the sleep complaint and selecting a drug that is best matched to correct the underlying problem.

Pathophysiology of prolonged penile erection associated with trazodone use.

Treatment with the antidepressant trazodone has been associated with the occurrence of prolonged penile erection and priapism. To evaluate the effect of trazodone on erection we monitored the periodic physiological sleep-related erections in 6 healthy volunteers in a double-blind crossover study comparing the effect of trazodone, trimipramine (a tricyclic antidepressant) and placebo. In addition, to determine the effects of trazodone on the neurovascular control of penile smooth muscle we performed in vitro studies on corpus cavernosum tissue obtained from patients undergoing penile prosthesis implantation. Trazodone significantly increased the total interval of nocturnal erectile activity, while trimipramine had no effect. During the high dose treatment (nights 4 and 5) the average duration of erectile activity per night with placebo was 158 +/- 41 minutes (mean +/- standard deviation) for night 4 and 177 +/- 21 minutes for night 5. During trazodone treatment the erectile activity per night was significantly prolonged to 285 +/- 115 minutes during night 4 and 232 +/- 86 during night 5 (p less than 0.01). Analysis of the erectile activity in relation to the rapid eye movement sleep period during which erectile activity usually occurs revealed that the detumescence phase of erection, under sympathetic control, was significantly prolonged an average of 2.4 times by trazodone compared to placebo (p less than 0.05). In vitro, trazodone at concentrations comparable to those reached in plasma significantly impaired corporeal smooth muscle contractions elicited by electrical stimulation of adrenergic nerves and antagonized contractions induced by exogenous norepinephrine. We conclude that trazodone can enhance penile erection in man and propose a mechanism related to the alpha-adrenoceptor blocking properties of trazodone by interference with the sympathetic control of penile detumescence.

Increased deep sleep after trazodone use: a double-blind placebo-controlled study in healthy young adults.

The effects of trazodone on sleep were compared with those of placebo and the sedating tricyclic antidepressant trimipramine in a double-blind crossover study in six healthy young men. Only trazodone significantly increased deep sleep without otherwise altering the normal architecture of sleep. The alpha-adrenergic receptor-blocking property of trazodone and a relative lack of noradrenergic reuptake blocking and the lack of anticholinergic effects are hypothesized to be responsible for the effects on sleep.

Estazolam and flurazepam: a multicenter, placebo-controlled comparative study in outpatients with insomnia.

A multicenter, double-blind placebo-controlled clinical trial was designed to compare the safety and efficacy of estazolam compared with flurazepam as hypnotics. Outpatients complaining of insomnia were randomized to receive either estazolam 2 mg, flurazepam 30 mg or placebo for 7 consecutive nights. The analysis of efficacy was based on the patients' daily assessments of sleep and the investigators' global evaluations. Adverse events which were considered by the investigator to be attributable to, or of unknown relationship to the test medication were analyzed. The patient subjective questionnaire indicated that estazolam and flurazepam significantly improved all parameters (P less than .05) as compared to placebo. A marked or moderate improvement in sleep was reported by 81% (58/72), 78% (63/81) and 36% (27/76) of estazolam, flurazepam, and placebo recipients, respectively. There were no significant differences in hypnotic effect between estazolam and flurazepam. All efficacy parameters of the investigators' global evaluation improved significantly more (P less than .05) for patients receiving estazolam or flurazepam (except quality of sleep) than for those receiving placebo. The percentage of patients reporting any adverse experience was greatest for flurazepam (72%), followed by estazolam (59%), and placebo (43%). Somnolence and hypokinesia were the most commonly reported adverse events. An analysis of the global evaluation of side effects showed that flurazepam had a significantly worse side effect profile than estazolam (P less than .05) or placebo (P = .001). Estazolam and flurazepam effectively, and comparably, relieved insomnia when administered for 7 nights in adult patients complaining of insomnia. Estazolam demonstrated a more favorable side effect profile than flurazepam.