Frank Zorick

Surgical Correction of Anatomic Abnormalities in Obstructive Sleep Apnea Syndrome: Uvulopalatopharyngoplasty:

Excessive daytime sleepiness and loud snoring are the major symptoms of obstructive sleep apnea, often leading to serious medical complications if unrecognized and untreated. Tracheostomy has been the only effective treatment in most adult cases. This paper reports on a new surgical approach to treat obstructive sleep apnea by uvulopalatopharyngoplasty designed to enlarge the potential airspace in the oropharynx. Twelve patients underwent this operation. In nine there was relief of symptoms and in eight there was objective improvement in nocturnal respiration and sleep pattern, demonstrated by polysomnography.

Disturbed sleep in patients complaining of chronic pain.

Polygraphic recordings of the sleep of patients complaining of insomnia has led to recognition of specific patterns of disturbed sleep corresponding to different etiologies of insomnia. This study presents results of polygraphic recordings of the sleep of 26 patients with chronic pain for which no physical cause can be found. All 26 also complained of insomnia. Sleep parameters of this group were compared with those of two other groups also complaining of insomnia: 12 patients whose disturbed sleep was judged secondary to psychiatric disorder, and 16 patients with the subjective complaint of insomnia in whom no objective evidence of sleep disturbance could be demonstrated. The three groups differed significantly in terms of their sleep parameters. The pain patients slept less than the subjective insomnia patients. The sleep disturbance of the psychiatric patients was more severe than that of the chronic pain patients. Several chronic pain patients showed evidence of nocturnal myoclonus; several also showed alpha rhythm intrusions into their sleeping electroencephalograms. The study verifies that chronic pain patients do experience significant sleep disturbance and raises several questions concerning relationships among chronic pain, sleep disturbance, and psychiatric illness, particularly depression.

Experimental sleep fragmentation in normal subjects

Recent research has suggested that sleep fragmentation in the absence of sleep loss is an important cause of excessive daytime sleepiness in certain clinical populations (e.g., sleep apnea syndrome or periodic leg movements). This study experimentally varied the number and rate of arousals in sleep to define more clearly the relation of sleep fragmentation and daytime sleepiness. Five male subjects participated in the study. Data from each were recorded for three consecutive nights (one baseline followed by two experimental nights) under three experimental conditions. All nocturnal polysomnograms were followed by a Multiple Sleep Latency Test (MSLT) the next day. The experimental conditions consisted of three different schedules of arousal produced by series of tones presented to subjects over headphones. The MSLT showed statistically significant changes after two nights of fragmented sleep, but the three fragmentation schedules did not differ from each other. Arousal threshold also changed significantly with sleep fragmentation from night one to night two.

Characteristics of Individuals Who Do or Do Not Seek Treatment for Chronic Insomnia

Survey data have shown that a minority of people who complain of insomnia receive medical treatment for this problem. Patients who seek treatment for insomnia at medical clinics and sleep disorders centers are a self-selected group who may not be representative of all individuals with insomnia. Fifty patients presenting to a sleep disorders center with an insomnia complaint were compared to 50 subjects with insomnia recruited through the newspaper for psychopharmacological studies. No differences in sleep parameters were found, but significant differences on psychometric measures and in daytime alertness were present. The implications of these differences are discussed.

Sedative, memory, and performance effects of hypnotics

The sedative, amnestic, and performance disruptive effects of benzodiazepine (Bz) receptor selective and non-selective hypnotics were studied in 23 healthy, normal subjects, aged 26.8±1.0 years. Triazolam (0.25 and 0.50 mg), zolpidem (10 and 20 mg) and placebo were administered, double-blind, at bedtime in a repeated measures design. During an awakening 90 min later (at approximate peak concentration of each drug) a 30-min performance battery which included memory, vigilance, and psychomotor tasks was completed. Each drug and dose impaired memory (both immediate and delayed), vigilance, and psychomotor performance relative to placebo. Among active drugs impairment was greatest with zolpidem 20 mg, next triazolam 0.50 mg, then zolpidem 10 mg, and finally triazolam 0.25 mg. Next morning delayed recall was also impaired by all drugs and doses (i.e. anterograde amnesia). The amnestic and performance-disruptive effects paralleled the relative hypnotic effects of the drugs and doses. No receptor selectivity in these pharmacodynamic effects was observed.

The dose effects of zolpidem on the sleep of healthy normals.

This study determined the dose effects of zolpidem in 12 healthy males with normal sleep patterns. Subjects spent 7 weeks, 3 consecutive nights per week, in the laboratory and had a 4-night washout between treatments. The first week was a screening and adaptation week. Then subjects received zolpidem (2.5, 5.0, 7.5, 10.0, or 20.0 mg) or placebo on the first two nights for each of the next 6 consecutive weeks. Treatments were organized in a Latin square design and administered in a double-blind fashion. On the third night of each treatment, subjects always received placebo. The 5.0 mg and larger doses of zolpidem significantly decreased latency to persistent sleep and wake before sleep. Sleep maintenance measures were not affected by zolpidem. The 7.5 mg and higher doses of zolpidem significantly increased total sleep time. The only significant sleep stage effect was a decrease in percent of rapid eye movement sleep at only the 20 mg dose. No consistent discontinuation effects were found. Zolpidem was hypnotically active at doses as low as 5.0 and 7.5 mg, and sleep stage effects occurred only at the 20 mg dose, thus separating the dose range of hypnotic and sleep stage effects.

Narcolepsy and disturbed nocturnal sleep.

Disturbed nocturnal sleep is considered a symptom of narcolepsy. Polysomnographic recordings of 57 consecutive narcoleptic patients were reviewed for evidence of disturbed sleep. When disrupted sleep was present, it was attributable to recognized sleep disorders: nocturnal myoclonus and sleep apnea. Comparison of standard polysomnographically derived parameters of patients who had narcolepsy without sleep apnea or nocturnal myoclonus with those of a normal control group, showed no evidence of disturbed sleep in the patient population. The narcoleptics that also had nocturnal myoclonus or upper airway sleep apnea did have disturbed sleep in comparison with the normals. Our data suggest disturbed sleep tends to develop in narcolpetic patients with age, but is not an inherent element of the narcolepsy syndrome.

Pharmacological Effects of Sedative-Hypnotics, Narcotic Analgesics, and Alcohol During Sleep

This article briefly reviews the well known effects of sedative-hypnotics, alcohol and narcotics on sleep. These drugs also have respiratory depressant effects, and the limited information about their effects on sleep-related breathing disturbances is reviewed. They exacerbate obstructive sleep apnea syndrome and have moderate to minimal effects on occasional apnea or hypopnea, but do not induce breathing disturbances de novo.

Anatomic abnormalities in obstructive sleep apnea.

Both muscular hypotonia and anatomic abnormalities have been implicated in the pathogenesis of the obstructive sleep apnea syndrome (OSAS). The upper airways of 25 patients with OSAS were evaluated to determine potential sites of obstruction. Significant airway compromise was found in all patients with some patients having multiple sites of airway narrowing.

Efficacy of a reduced triazolam dose in elderly insomniacs.

Elderly persons with insomnia are unique because the cause of their insomnia differs from that of younger people and their metabolism of benzodiazepine hypnotics differs as well. This study used nocturnal polysomnography and daytime sleep/wake tendency measures (Multiple Sleep Latency Test, MSLT) to assess the efficacy and safety of a reduced triazolam dosage (0.125 mg) in elderly subjects with insomnia. After 2 nights and an intervening day of screening each subject received triazolam and placebo for 2 consecutive nights presented in a counter-balanced design. Compared to placebo the reduced triazolam dose induced and maintained sleep thereby increasing total sleep time. Sleep stage distribution and the frequency of apneas and periodic leg movements was not altered. The improved sleep was associated with a restoration of the normal pattern of daytime alertness. The correspondence of this clinical data to known pharmacokinetic data is discussed.