Sleep disorders, sleepiness and traffic safety: a public health menace

Sleep disorders are not uncommon and have been widely reported throughout the world. They have a profound impact on industrialized 24-h societies. Consequences of these problems include impaired social and recreational activities, increased human errors, loss of productivity, and elevated risk of accidents. Conditions such as acute and chronic insomnia, sleep loss, excessive sleepiness, shift-work, jet lag, narcolepsy, and sleep apnea warrant public health attention, since residual sleepiness during the day may affect performance of daily activities such as driving a car. Benzodiazepine hypnotics and zopiclone promote sleep, both having residual effects the following day including sleepiness and reduced alertness. In contrast, the non-benzodiazepine hypnotics zolpidem and zaleplon have no significant next-day residual effects when taken as recommended. Research on the effects of wakefulness-promoting drugs on driving ability is limited. Countermeasures for excessive daytime sleepiness have a limited effect. There is a need for a social awareness program to educate the public about the potential consequences of various sleep disorders such as narcolepsy, sleep apnea, shift-work-related sleep loss, and excessive daytime sleepiness in order to reduce the number of sleep-related traffic accidents.

Repercussions of a sleep medicine outreach program

Despite the high prevalence of sleep disorders, many healthcare professionals and lay people have little knowledge of Sleep Medicine. Mindful of such a reality, in 2001 the Sleep Institute of the Associação Fundo de Incentivo à Psicofarmacologia launched a campaign to increase Sleep Medicine awareness. Media features, exhibitions, inserts, and classes were used to reach 2,000,000 people and 55,000 healthcare professionals during the period from 2001 to 2004. To evaluate this program, we compared data for polysomnography referrals to the Institute in 2000 and in 2004. A total of 8805 referrals were evaluated (2000: 2164; 2004: 6641). Over the 4 years of the program, the number of beds increased by 43%; more women were referred (31 vs 37%; P < 0.001), mainly with a diagnostic hypothesis of sleep-disorder breathing (SDB). SDB was the most frequent diagnostic hypothesis in 2000 and 2004. In 2004 there were fewer referrals without a diagnostic hypothesis (27 vs 21%; P < 0.001) and for controlling surgically treated SDB (2.3 vs 1.6%; P < 0.05), and an increase in the following diagnostic hypotheses: non-invasive treatment of SDB (8.3 vs 12.3%; P < 0.001) and insomnia (3.5 vs 6.5%; P < 0.001). Insomnia diagnostic hypothesis was better correlated with SDB on referral documents in 2004 and less with a diagnostic hypothesis of limb movement disturbance. The program helped increase polysomnography referrals, particularly among women. Healthcare professionals appear to have a more developed understanding of sleep disorders.

Obese obstructive sleep apnea patients with tonsil hypertrophy submitted to tonsillectomy

The physiopathology of obstructive sleep apnea-hypopnea syndrome (OSAHS) is multifactorial and obesity has been shown to be one of the main factors correlated with its occurrence. In obese patients with anatomical alterations of the upper airways it is often difficult to predict success for surgical correction since obesity is a limiting factor. Therefore, the aim of the present study was to evaluate the results of tonsillectomy in a specific group of patients, i.e., obese OSAHS patients with tonsil hypertrophy. Seven OSAHS patients with moderate obesity with obstructive palatine tonsil hypertrophy were submitted to tonsillectomy. All patients were submitted to pre- and postoperative appraisal of body mass index, otorhinolaryngology examination and polysomnography. Patients' average age was 36.4 ± 10.3 years and average preoperative body mass index was 36.6 ± 6.3 kg/m². Postoperative weight did not differ significantly from preoperative weight (P = 0.27). Average preoperative apnea and hypopnea index (AHI) was 81 ± 26/h and postoperative AHI was 23 ± 18/h (P = 0.0005). Average preoperative minimum oxyhemoglobin saturation (SaO2 min) was 69 ± 14% and the postoperative value was 83 ± 3% (P = 0.038). In relation to AHI, 6 (86%) of the 7 patients studied showed a reduction of 50% in relation to preoperative level and of these, 4 (57%) presented AHI of less than 20%. Only one patient presented a reduction of less than 50% in AHI, but even so showed improved SaO2 min. Tonsillectomy treatment for OSAHS in obese patients with obstructive palatine tonsil hypertrophy caused a significant reduction in AHI, with improvement in SaO2 min. This procedure could be eventually considered as an option of treatment for obese OSAHS patients with significant tonsil hypertrophy when continuous positive air pressure therapy is not possible as the first choice of treatment.

A double-blind comparison of the effect of the antipsychotics haloperidol and olanzapine on sleep in mania

The effects of haloperidol and olanzapine on polysomnographic measures made in bipolar patients during manic episodes were compared. Twelve DSM-IV mania patients were randomly assigned to receive either haloperidol (mean ± SD final dosage: 5.8 ± 3.8 mg) or olanzapine (mean ± SD final dosage: 13.6 ± 6.9 mg) in a 6-week, double-blind, randomized, controlled clinical trial. One-night polysomnographic evaluation was performed before and after the haloperidol or olanzapine treatment. Psychopathology and illness severity were rated respectively with the Young Mania Rating Scale (YMRS) and the Clinical Global Impressions - Bipolar version (CGI-BP). There was a significant improvement in the YMRS and CGI-BP scores at the end of the study for both groups. Mixed ANOVA used to compare the polysomnographic measures of both drugs demonstrated significant improvement in sleep measures with olanzapine. In the olanzapine group, statistically significant time-drug interaction effects on sleep continuity measures were observed: sleep efficiency (mean ± SEM pre-treatment value: 6.7 ± 20.3%; after-treatment: 85.7 ± 10.9%), total wake time (pre-treatment: 140.0 ± 92.5 min; after-treatment: 55.2 ± 44.2 min), and wake time after sleep onset (pre-treatment: 109.7 ± 70.8 min; after-treatment: 32.2 ± 20.7 min). Conversely, improvement of polysomnographic measures was not observed for the haloperidol group (P > 0.05). These results suggest that olanzapine is more effective than haloperidol in terms of sleep-promoting effects, although olanzapine is comparatively as effective as haloperidol in treating mania. Polysomnography records should provide useful information on how manic states can be affected by psychopharmacological agents.

Sleep deprivation reduces the lymphocyte count in a non-obese mouse model of type 1 diabetes mellitus

The objective of the present study was to determine whether sleep deprivation (SD) would promote changes in lymphocyte numbers in a type 1 diabetes model (non-obese diabetic, NOD, mouse strain) and to determine whether SD would affect female and male NOD compared to Swiss mice. The number of lymphocytes in peripheral blood after 24 and 96 h of SD (by multiple platform method) or equivalent period of time in home-cage controls was examined prior to the onset of diabetes. SD for 96 h significantly reduced lymphocytes in male Swiss mice compared to control (8.6 ± 2.1 vs 4.1 ± 0.7 10³/µL; P < 0.02). In male NOD animals, 24- and 96-h SD caused a significant decrease of lymphocytes compared to control (4.4 ± 0.3 vs 1.6 ± 0.5; P < 0.001 and 4.4 ± 0.3 vs 0.9 ± 0.1 10³/µL; P < 0.00001, respectively). Both 24- and 96-h SD induced a reduction in the number of lymphocytes in female Swiss (7.5 ± 0.5 vs 4.5 ± 0.5, 4.4 ± 0.6 10³/µL; P < 0.001, respectively) and NOD mice (4 ± 0.6 vs 1.8 ± 0.2, 1.2 ± 0.4 10³/µL; P < 0.01, respectively) compared to the respective controls. Loss of sleep induced lymphopenia in peripheral blood in both genders and strains used. Since many cases of autoimmunity present reduced numbers of lymphocytes and, in this study, it was more evident in the NOD strain, our results suggest that SD should be considered a risk factor in the onset of autoimmune disorders.

Sleep habits and complaints of adults in the city of São Paulo, Brazil, in 1987 and 1995

This study compares the prevalence of complaints of insomnia, excessive diurnal sleepiness, parasomnias, and sleep habits of the adult population in the city of São Paulo, Brazil, estimated in surveys carried out in 1987 and 1995. Representative samples of 1000 adult residents per survey were interviewed using a validated structured sleep questionnaire, the "UNIFESP Sleep Questionnaire". Difficulty maintaining sleep, difficulty initiating sleep and early morning awakening, occurring at least three times a week, were reported in 1987 and 1995, by 15.8/27.6, 13.9/19.1, and 10.6/14.2% of the interviewees, respectively, significantly increasing throughout time. These sleep problems were more often found among women. Frequencies of excessive diurnal sleepiness and sleep attacks were unchanged comparing 1987 with 1995 (4.5 vs 3.8 and 3.1 vs 3.0%, respectively). Parasomnia complaints remained unchanged, with the exception of leg cramps, which doubled in prevalence from 1987 to 1995 (2.6 to 5.8%). Snoring was the most common parasomnia (21.5% in 1995), reported more often by men than by women, and somnambulism was the least common (approximately 1%). Besides sleeping slightly less, interviewees went to bed and woke up later in 1995. Approximately 12% of the subjects in both surveys had consulted a physician due to sleep problems and 3.0% reported habitual use of sleep-promoting substances in 1995. Overall, there was a significant increase in insomnia complaints from 1987 to 1995 in the general population of the city of São Paulo. This major change over a little under a decade should be considered as an important public health issue.

Effect of sildenafil (Viagra®) on the genital reflexes of paradoxical sleep-deprived male rats

Since there is evidence that paradoxical sleep deprivation (PSD) elicits penile erection (PE) and ejaculation (EJ), and that the erectile response of rats is mediated by nitric oxide, the present study sought to extend the latter finding by assessing the effects of sildenafil on the genital reflexes of male Wistar rats subjected to PSD. We also determined the influence of sildenafil on hormone concentrations. In the first experiment, sildenafil at doses ranging from 0.08 to 0.32 mg/kg was administered intraperitoneally to rats that had been deprived of sleep for 4 days and to home cage controls (N = 8-10/group). The frequency of PE and EJ was measured for 60 min. PSD alone induced PE in 50% of the animals; however, a single injection of sildenafil did not significantly increase the percentage of rats displaying PE compared to PSD-saline or to home cage groups. PSD alone also induced spontaneous EJ, but this response was not potentiated by sildenafil in the dose range tested. Testosterone concentrations were significantly lower in PSD rats (137 ± 22 ng/dL) than in controls (365 ± 38 ng/dL), whereas progesterone (0.9 ± 0.1 vs 5.4 ± 1 ng/mL) and plasma dopamine (103.4 ± 30 vs 262.6 ± 77 pg/mL) increased. These changes did not occur after sildenafil treatment. The data show that although sildenafil did not alter the frequency of genital reflexes, it antagonized hormonal (testosterone and progesterone) and plasma dopamine changes induced by PSD. The stimulation of the genital reflexes by sildenafil did not result in potentiating effects in PSD rats.

The reciprocal interaction between sleep and type 2 diabetes mellitus: facts and perspectives

Type 2 diabetes mellitus is a systemic disease characterized by intolerance to glucose and peripheral resistance to insulin. This endocrine disease affects fundamental mechanisms of the central nervous system and jeopardizes the balance of vital functions such as the cardiovascular and circadian rhythm. The increased prevalence of metabolic disorders in our society is aggravated by endemic voluntary postponement of bedtime and by the current sedentary lifestyle, leading to epidemic proportions of obese people. Diabetes and chronic loss of sleep share the fact that both affect millions and one is detrimental to the other. Indeed, sleep deficits have marked modulatory effects on glucose metabolism and insulin sensitivity and foster metabolic syndrome that culminates in sleep disorders like restless syndrome and sleep apnea, which in turn lead to poor sleep quality. We examine the hypothesis that these two worldwide emerging disorders are due to two interlinked cycles. In our paradigm, we establish an intimate relationship between diabetes and sleep disturbances and postulate possible mechanisms that provide support for this conjecture. In addition, we propose some perspectives about the development of the reciprocal interaction between predictor components of metabolic syndrome and sleep disturbances that lead to poor sleep quality. The ability to predict the development and identify or associate a given mode of sleep disturbance to diabetes would be a valuable asset in the assessment of both. Furthermore, major advances in care coupled with healthy lifestyles can ensure a higher quality of life for people with diabetes.

Effects of cocaine, methamphetamine and modafinil challenge on sleep rebound after paradoxical sleep deprivation in rats

Sleep loss is both common and critically relevant to our society and might lead to the abuse of psychostimulants such as amphetamines, cocaine and modafinil. Since psychoactive substance abuse often occurs within a scenario of sleep deficit, the purpose of this investigation was to compare the sleep patterns of rats challenged with cocaine (7 mg/kg, ip), methamphetamine (7 mg/kg, ip), or modafinil (100 mg/kg, ip) subsequent to paradoxical sleep deprivation (PSD) for 96 h. Our results show that, immediately after 96 h of PSD, rats (10 per group) that were injected with a psychostimulant presented lower percentages of paradoxical sleep compared to those injected with saline (P < 0.01). Regarding slow wave sleep (SWS), rats injected with psychostimulants after PSD presented a late rebound (on the second night subsequent to the injection) in the percentage of this phase of sleep when compared to PSD rats injected with saline (P < 0.05). In addition, the current study has produced evidence of the characteristic effect of each drug on sleep architecture. Home cage control rats injected with modafinil and methamphetamine showed a reduction in SWS compared with the saline group. Methamphetamine affected sleep patterns most, since it significantly reduced paradoxical sleep, SWS and sleep efficiency before and after PSD compared to control (P < 0.05). Cocaine was the psychostimulant causing the least changes in sleep pattern in relation to those observed after saline injection. Therefore, our results suggest that abuse of these psychostimulants in a PSD paradigm aggravates their impact on sleep patterns.

Hemodialysis improves endothelial venous function in end-stage renal disease

The objective of the present study was to determine the acute effect of hemodialysis on endothelial venous function and oxidative stress. We studied 9 patients with end-stage renal disease (ESRD), 36.8 ± 3.0 years old, arterial pressure 133.8 ± 6.8/80.0 ± 5.0 mmHg, time on dialysis 55.0 ± 16.6 months, immediately before and after a hemodialysis session, and 10 healthy controls matched for age and gender. Endothelial function was assessed by the dorsal hand vein technique using graded local infusion of acetylcholine (endothelium-dependent venodilation, EDV) and sodium nitroprusside (endothelium-independent venodilation). Oxidative stress was evaluated by measuring protein oxidative damage (carbonyls) and antioxidant defense (total radical trapping antioxidant potential - TRAP) in blood samples. All patients were receiving recombinant human erythropoietin for at least 3 months and were not taking nitrates or a-receptor antagonists. EDV was significantly lower in ESRD patients before hemodialysis (65.6 ± 10.5) vs controls (109.6 ± 10.8; P = 0.010) and after hemodialysis (106.6 ± 15.7; P = 0.045). Endothelium-independent venodilation was similar in all comparisons performed. The hemodialysis session significantly decreased TRAP (402.0 ± 53.5 vs 157.1 ± 28.3 U Trolox/µL plasma; P = 0.001). There was no difference in protein damage comparing ESRD patients before and after hemodialysis. The magnitude of change in the EDV was correlated negatively with the magnitude of change in TRAP (r = -0.70; P = 0.037). These results suggest that a hemodialysis session improves endothelial venous function, in association with an antioxidant effect.

Effect of smoking habits on sleep

To evaluate the effect of smoking habits on sleep, data from 1492 adults referred to the Sleep Institute were accessed and divided into 3 categories of smoking status: current, former and non-smokers. Categories of pack-years (<15 and ≥15) defined smoking severity. The association of smoking status and smoking severity with sleep was analyzed for sleep parameters, especially apnea and hypopnea index (AHI) ≥5, more than 5% of total sleep time (TST) spent with oxyhemoglobin saturation (SaO2) <90%, and arousal index. The arousal index was higher among current (21 ± 17) and former smokers (20 ± 17) than non-smokers (17 ± 15; P < 0.04). Former smokers had a higher percent of TST at SaO2 <90% than non-smokers (9 ± 18 vs 6 ± 13; P < 0.04). Former smokers with pack-years ≥15 compared to <15 exhibited higher AHI (22 ± 24 vs 16 ± 21; P < 0.05) and arousal index (22 ± 19 vs 18 ± 15; P < 0.05). Current smokers with pack-years ≥15 compared to <15 exhibited higher arousal index (23 ± 18 vs 18 ± 16; P < 0.05) and percent of TST at SaO2 <90% (11 ± 17 vs 6 ± 13; P < 0.05). Smoking status and pack-years were not associated with AHI ≥5 on logistic regression analysis, but current smokers with pack-years ≥15 were 1.9 times more likely to spend more than 5% of TST at SaO2 <90% than non-smokers (95%CI = 1.21-2.97; P = 0.005). The variability of arousal index was influenced by gender, AHI and current smokers with pack-years ≥15 (all P < 0.01). Smoking habits seem to be associated with arousal and oxyhemoglobin desaturation during sleep, but not with AHI. The effect was more pronounced in current than former smokers.

Ethnicity as a risk factor for obstructive sleep apnea: comparison of Japanese descendants and white males in São Paulo, Brazil

Some studies showed that Asians with obstructive sleep apnea (OSA) are thinner than Caucasians. Because obesity is a major risk factor for OSA, it was concluded that Asians are predisposed to OSA. However, body fat composition varies for a same body mass index (BMI) according to ethnicity. We firstly compared anthropometric characteristics, symptoms and associated disorders in all consecutive male Japanese descendants and white males with OSA referred for polysomnography. In a second analysis, all Japanese descendants were compared to a subgroup of white males, matched for apnea/hypopnea index and age. In the first analysis, age, symptoms, OSA severity and co-morbidities were similar among Japanese descendants (N = 54) and white patients (N = 466). However, Japanese descendants had a lower BMI than white patients: 27.1 (25.5-28.4) vs 29.4 (26.5-33.0) kg/m², respectively (P < 0.001). In the second analysis, Japanese descendants had a lower BMI than white patients (P < 0.001). Multiple linear regression considering the entire group revealed that age, BMI, neck circumference, Epworth sleepiness scale, ethnicity and %REM sleep were independent predictors for apnea/hypopnea index (P < 0.001). Ethnicity was no longer significantly associated with OSA severity when we adopted the World Health Organization criteria for obesity (≥25 and 30 kg/m² among Japanese descendants and white males, respectively). Japanese descendants with OSA have a lower BMI than white subjects of similar severity. However, ethnicity was not associated with OSA severity when an ethnical difference in obesity criteria was respected. Our data suggest that Japanese descendants are not predisposed to OSA.

Relationship between the quality of life and the severity of obstructive sleep apnea syndrome

The effects of sleep disorders on the quality of life (QOL) have been documented in the literature. Excessive sleepiness and altered circadian rhythms may negatively affect ability to learn, employment, and interpersonal relations, and directly degrade QOL. The objective of the present study was to evaluate the impact of obstructive sleep apnea syndrome of varying severity on QOL. The study was conducted on 1892 patients aged 18 years or older referred by a physician to the Sleep Institute, São Paulo, with complaints related to apnea (snoring, excessive daytime sleepiness, hyperarousal, and fatigue). They were submitted to overnight polysomnography for the diagnosis of sleep disorders from August 2005 through April 2006. The patients completed the Epworth Sleepiness Scale and QOL SF-36 sleep questionnaires. They were classified as non-physically active and physically active and not-sleepy and sleepy and the results of polysomnography were analyzed on the basis of the apnea hypopnea index (AHI). The apneic subjects showed a reduction in QOL which was proportional to severity. There was a significant decrease in all domains (physical functioning, role physical problems, bodily pain, general health perceptions, vitality, social functioning, emotional problems, general mental health) for apneics with AHI >30, who generally were sleepy and did not participate in physical activities (P < 0.05). The present study provides evidence that the impact of sleep disorders on QOL in apneics is not limited to excessive daytime sleepiness and that physical activity can contribute to reducing the symptoms. Thus, exercise should be considered as an adjunct interventional strategy in the management of obstructive sleep apnea syndrome.

Influence of chronotype and social zeitgebers on sleep/wake patterns

Inter-individual differences in the phase of the endogenous circadian rhythms have been established. Individuals with early circadian phase are called morning types; those with late circadian phase are evening types. The Horne and Östberg Morningness-Eveningness Questionnaire (MEQ) is the most frequently used to assess individual chronotype. The distribution of MEQ scores is likely to be biased by several fact, ors, such as gender, age, genetic background, latitude, and social habits. The objective of the present study was to determine the effect of different social synchronizers on the sleep/wake cycle of persons with different chronotypes. Volunteers were selected from a total of 1232 UFPR undergraduate students who completed the MEQ. Thirty-two subjects completed the study, including 8 morning types, 8 evening types and 16 intermediate types. Sleep schedules were recorded by actigraphy for 1 week on two occasions: during the school term and during vacation. Sleep onset and offset times, sleep duration, and mid-sleep time for each chronotype group were compared by the Mann-Whitney U-test separately for school term and vacation. School term and vacation data were compared by the Wilcoxon matched-pair test. Morning types showed earlier sleep times and longer sleep duration compared with evening types (23:00 ± 44 and 508.9 ± 50.27 vs 01:08 ± 61.95 and 456.44 ± 59.08, for the weekdays during vacation). During vacation, the subjects showed later sleep times, except for the morning types, who did not exhibit differences for sleep onset times. The results support the idea that social schedules have an impact on the expression of circadian rhythmicity but this impact depends on the individual chronotype.

Effect of melatonin administration on subjective sleep quality in chronic obstructive pulmonary disease

Disturbed sleep is common in chronic obstructive pulmonary disease (COPD). Conventional hypnotics worsen nocturnal hypoxemia and, in severe cases, can lead to respiratory failure. Exogenous melatonin has somnogenic properties in normal subjects and can improve sleep in several clinical conditions. This randomized, double-blind, placebo-controlled study was carried out to determine the effects of melatonin on sleep in COPD. Thirty consecutive patients with moderate to very severe COPD were initially recruited for the study. None of the participants had a history of disease exacerbation 4 weeks prior to the study, obstructive sleep apnea, mental disorders, current use of oral steroids, methylxanthines or hypnotic-sedative medication, nocturnal oxygen therapy, and shift work. Patients received 3 mg melatonin (N = 12) or placebo (N = 13), orally in a single dose, 1 h before bedtime for 21 consecutive days. Sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI) and daytime sleepiness was measured by the Epworth Sleepiness Scale. Pulmonary function and functional exercise level were assessed by spirometry and the 6-min walk test, respectively. Twenty-five patients completed the study protocol and were included in the final analysis. Melatonin treatment significantly improved global PSQI scores (P = 0.012), particularly sleep latency (P = 0.008) and sleep duration (P = 0.046). No differences in daytime sleepiness, lung function and functional exercise level were observed. We conclude that melatonin can improve sleep in COPD. Further long-term studies involving larger number of patients are needed before melatonin can be safely recommended for the management of sleep disturbances in these patients.