Davoud Eskandari

Impaired vigilance and increased accident rate in public transport operators is associated with sleep disorders

OBJECTIVES Sleep disturbances can impair alertness and neurocognitive performance and increase the risk of falling asleep at the wheel. We investigated the prevalence of sleep disorders among public transport operators (PTOs) and assessed the interventional effects on hypersomnolence and neurocognitive function in those diagnosed with obstructive sleep apnea (OSA). METHODS Overnight polygraphy and questionnaire data from 101 volunteers (72 males, median age 48 range [22-64] years, 87 PTOs) employed at the Gothenburg Public Transportation Company were assessed. Treatment was offered in cases with newly detected OSA. Daytime sleep episodes and neurocognitive function were assessed before and after intervention. RESULTS At baseline, symptoms of daytime hypersomnolence, insomnia, restless legs syndrome as well as objectively assessed OSA (apnea hypopnea index (AHI, determined by polygraphic recording)=17[5-46]n/h) were highly present in 26, 24, 10 and 22%, respectively. A history of work related traffic accident was more prevalent in patients with OSA (59%) compared to those without (37%, p<0.08). In the intervention group (n=12) OSA treatment reduced AHI by -23 [-81 to -5]n/h (p=0.002), determined by polysomnography. Reduction of OSA was associated with a significant reduction of subjective sleepiness and blood pressure. Measures of daytime sleep propensity (microsleep episodes from 9 [0-20.5] to 0 [0-12.5], p<0.01) and missed responses during performance tests were greatly reduced, indices of sustained attention improved. CONCLUSIONS PTOs had a high prevalence of sleep disorders, particularly OSA, which demonstrated a higher prevalence of work related accidents. Elimination of OSA led to significant subjective and objective improvements in daytime function. Our findings argue for greater awareness of sleep disorders and associated impacts on daytime function in public transport drivers.

Zonisamide reduces obstructive sleep apnoea: a randomised placebo-controlled study

Carbonic anhydrase inhibition reduces apnoeic events in sleep disordered breathing. Zonisamide inhibits carbonic anhydrase, and induces weight loss in obese patients. This study explored the relative influence of these two properties, which may both alleviate obstructive sleep apnoea (OSA). Continuous positive airway pressure (CPAP) was used as a standard care comparator. 47 patients with moderate-to-severe OSA and a body mass index of 27–35 kg·m−2 were randomised to receive either zonisamide, placebo or CPAP for 4 weeks. The open extension phase (20 weeks) compared CPAP and zonisamide. Polysomnography, biochemistry and symptoms were evaluated. At 4 weeks, zonisamide reduced apnoea/hypopnoea index (AHI) by a mean±sd 33±39% and oxygen desaturation index by 28±31% (p=0.02 and 0.014, respectively; placebo adjusted). The mean compliance adjusted reduction of AHI after zonisamide and CPAP was 13 and 61%, respectively, (p=0.001) at 24 weeks. Body weight was marginally changed at 4 weeks, but reduced after zonisamide and increased after CPAP at 24 weeks (-2.7±3.0 kg versus 2.3±2.0 kg, p<0.001). Zonisamide decreased bicarbonate at 4 and 24 weeks. Side-effects were more common after zonisamide. Zonisamide reduced OSA independent of body weight potentially by mechanisms related to carbonic anhydrase inhibition. The effect was less pronounced than that obtained by CPAP. The carbonic anhydrase inhibitor zonisamide reduces sleep apnoea, but the effect is inferior to CPAP treatment http://ow.ly/tnmQ1

Attention deficits detected in cognitive tests differentiate between sleep apnea patients with or without a motor vehicle accident

OBJECTIVES Obstructive sleep apnea (OSA) is associated with an increased motor vehicle accident (MVA) risk. Conventional measures of OSA severity do not predict individual risk. Cognitive function tests have failed to incorporate outcomes in risk prediction. We aimed to identify markers of cognitive function for MVA risk prediction in OSA. METHODS OSA patients [n = 114, 75% male, median age 51 (43-61) years, body mass index (BMI) 30 (27-33) kg/m2, apnea-hypopnea index 25 (6-49) n/h, and Epworth Sleepiness (ESS) score 11 (8-16)] were recruited from a sleep laboratory. Two cognitive function tests, the Attention Network Test (ANT) and a modified Oxford Sleep Resistance Test (OSLER) test (GOSLING), were assessed. RESULTS OSA patients with (n = 11) or without (n = 103) a MVA record in the Swedish traffic accident registry were identified. In patients with a MVA, 64% were commercial drivers. In patients with a MVA history, more lapses [42 (5-121) vs. 5 (1-25), P = 0.02] and fewer responses [238 (158-272) vs. 271 (256-277), P = 0.03] to stimuli in the ANT were found. In the GOSLING, the number of lapses was higher (29 (10-97) vs. 7 (2-19), P = 0.01) and the reaction time was longer [462 (393-551) vs. 407 (361-449) ms, P = 0.05]. OSA severity and ESS score poorly predicted MVAs (P > 0.2). CONCLUSIONS We have demonstrated that deficit in sustained attention, assessed by daytime neurocognitive function tests, was associated with MVA risk in OSA patients. We were unable to detect an association between MVA history and severity of OSA or the ESS score. The findings provide a rationale for further development of objective MVA risk assessment tools in OSA.

Increased Carbonic Anhydrase Activity is Associated with Sleep Apnea Severity and Related Hypoxemia

STUDY OBJECTIVES The catalytic function of the enzyme carbonic anhydrase (CA) plays a fundamental role in carbon dioxide (CO2), proton (H(+)), and bicarbonate (HCO3(-)) homeostasis. Hypoxia and tissue acidosis have been proposed to increase physiological CA activity in various compartments of the body. We hypothesized that CA activity in blood is upregulated in patients with obstructive sleep apnea (OSA). DESIGN Cross-sectional analysis of a sleep clinic cohort. SETTINGS Sleep laboratory at a university hospital. PARTICIPANTS Seventy referred patients with suspected OSA (48 males, age 54 ± 13 y, apnea-hypopnea index (AHI) median [interquartile range] 21 [8-41] n/h). INTERVENTIONS N/A. MEASUREMENTS AND RESULTS In-laboratory cardiorespiratory polygraphy was used to assess OSA. CA activity was determined by an in vitro assay that quantifies the pH change reflecting the conversion of CO2 and H2O to HCO3(-) and H(+). CA activity was positively associated with AHI and 4% oxygen desaturation index (ODI4) (Spearman correlation r = 0.44 and 0.47, both P < 0.001). The associations (CA activity versus logAHI and CA versus logODI4) were independent of sex, age, body mass index, presleep oxygen saturation, nocturnal oxygen saturation, hypertension status, and use of diuretic medication in two generalized linear models (P = 0.007 and 0.011, respectively). Sitting diastolic blood pressure was associated with CA activity after adjustment of sex, age, body mass index, mean oxygen saturation, and AHI (P = 0.046). CONCLUSIONS Carbonic anhydrase (CA) activity increased with apnea-hypopnea index and related nocturnal hypoxemia measures in patients with obstructive sleep apnea (OSA). Altered CA activity may constitute a component that modulates respiratory control and hemodynamic regulation in patients with OSA.

Association between short total sleep time and hypertension: the Skara Sleep Cohort.

Objectives: Apnea hypopnea index (AHI) is used to study the association between obstructive sleep apnea (OSA) and hypertension, but the independent contributions of total sleep time (TST) and apnea/hypopnea event count to hypertension have not been previously investigated. We studied the relationship between polysomnographically assessed TST and hypertension in a sex-balanced community-dwelling cohort of hypertensive patients and normotensive controls (Skara Sleep Cohort). Methods: Participants (n = 344, men 173, age 61.2 ± 6.5 years, BMI 28.6 ± 4.8 kg/m2, mean ± SD) underwent ambulatory home polysomnography. Hypertension was defined according to contemporary Swedish national guidelines. A multivariate logistic regression model was used to predict hypertension status from TST and apnea/hypopnea count (total events/night) adjusting for sex, age and BMI. Results: OSA was highly prevalent in this population (AHI 26 ± 24 events/h). Hypertensive patients had shorter TST than normotensive patients (353 ± 81 vs. 389 ± 65 min, P < 0.001), whereas total apnea/hypopnea count did not differ (167 ± 138 vs. 146 ± 148 events/night, P = 0.2). Multivariate logistic regression analysis revealed that short TST was associated with hypertension status [odds ratio 2.0; 95% confidence interval (95% CI) 1.2–3.3; P = 0.0015]. The significant association between apnea/hypopnea count and hypertension status was nonlinear (odds ratio 2.6; 95% CI 1.2–5.8; P = 0.04). The type of antihypertensive treatment was not found to significantly influence TST. Conclusion: Short sleep time assessed by polysomnography was associated with hypertension in this community-dwelling population. Short sleep and presence of sleep apnea appear to independently link to hypertension.

Acetazolamide Reduces Blood Pressure and Sleep-Disordered Breathing in Patients With Hypertension and Obstructive Sleep Apnea: A Randomized Controlled Trial

STUDY OBJECTIVES The carbonic anhydrase inhibitor acetazolamide (AZT) modulates blood pressure at high altitude and reduces sleep-disordered breathing in patients with obstructive sleep apnea (OSA). We aimed to investigate the treatment effect of AZT and in combination with continuous positive airway pressure (CPAP) on blood pressure in patients with hypertension and OSA. METHODS In a prospective, randomized, three-way crossover study, 13 male patients with hypertension and moderate to severe OSA (age 64 ± 7 years, body mass index 29 ± 4 kg/m2, and mean apnea-hypopnea index 37 ± 23 events/h) received AZT, CPAP, or AZT plus CPAP for 2-week periods. Antihypertensive medication was washed out. Office and 24-hour blood pressure, arterial stiffness, polygraphic sleep study data, and blood chemistry were compared. RESULTS AZT alone and AZT plus CPAP, but not CPAP alone, reduced office mean arterial pressure compared to baseline (-7 [95% CI -11 to -4], -7 [95% CI -11 to -4] and -1 [95% CI -5 to 4] mmHg, respectively; repeated- measures analysis of variance (RM-ANOVA; P = .015). Aortic systolic pressure and augmentation index, assessed by radial artery oscillatory tonometry, were unaffected by CPAP but decreased after AZT and AZT plus CPAP (RM-ANOVA P = .030 and .031, respectively). The apnea-hypopnea index was significantly reduced in all three treatment arms, most prominently by AZT plus CPAP (RM-ANOVA P = .003). The reduction of venous bicarbonate concentration following AZT was correlated with the change of apnea-hypopnea index (r = 0.66, P = .013). CONCLUSIONS AZT reduced blood pressure, vascular stiffness, and sleep-disordered breathing in patients with OSA and comorbid hypertension. Carbonic anhydrase inhibition may constitute a potential target for drug therapy in patients with sleep apnea and comorbid hypertension. CLINICAL TRIAL REGISTRATION Registry: ClinicalTrials.gov; Identifier: NCT02220803; Title: A Short Term Open, Randomized Cross-over Trial Exploring the Effect of Carbonic Anhydrase Inhibition by Acetazolamide on Sleep Apnea Associated Hypertension and Vascular Dysfunction; URL: https://clinicaltrials.gov/ct2/show/NCT02220803 and Registry: EU Clinical Trials Register; EudraCT Number: 2013-004866-33; Title: A short term open, randomized cross over trial exploring the effect of carbonic anhydrase inhibition by acetazolamide on sleep apnea associated hypertension; URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=2013-004866-33.