Time course of changes in breathing pattern in morphine‐ and oxycodone‐induced respiratory depression Effect of zopiclone on sleep, night-time ventilation, and daytime vigilance in upper airway resistance syndrome. Effects of oral narcotics on sleep-disordered breathing in healthy adults. Recurrent Hypoxemia in Children Is Associated with Increased Analgesic Sensitivity to Opiates A safety trial of sodium oxybate in patients with obstructive sleep apnea: Acute effects on sleep-disordered breathing. Effects of suvorexant, an orexin receptor antagonist, on breathing during sleep in patients with chronic obstructive pulmonary disease. Eszopiclone increases the respiratory arousal threshold and lowers the apnoea/hypopnoea index in obstructive sleep apnoea patients with a low arousal threshold. Effect of zolpidem on the efficacy of continuous positive airway pressure as treatment for obstructive sleep apnea. Experimental Pain and Opioid Analgesia in Volunteers at High Risk for Obstructive Sleep Apnea Triazolam in patients with obstructive sleep apnea. The occurrence of sleep-disordered breathing among middle-aged adults. Nitrazepam in patients with sleep apnoea: a double-blind placebo-controlled study. Increased prevalence of sleep-disordered breathing in adults. Zolpidem-polysomnographic study of the effect of a new hypnotic drug in sleep apnea syndrome High leg motor activity in sleep apnea hypopnea patients: efficacy of clonazepam combined with nasal CPAP on polysomnographic variables. Respiratory and Sleep Effects of Remifentanil in Volunteers with Moderate Obstructive Sleep Apnea A pilot study evaluating acute use of eszopiclone in patients with mild to moderate obstructive sleep apnea syndrome. The effects of a single mild dose of morphine on chemoreflexes and breathing in obstructive sleep apnea Safety of ramelteon in individuals with mild to moderate obstructive sleep apnea A systematic review of the effects of sedatives and anesthetics in patients with obstructive sleep apnea The effect of temazepam on respiration in elderly insomniacs with mild sleep apnea. Clonidine Premedication in Patients with Sleep Apnea Syndrome: A Randomized, Double-Blind, Placebo-Controlled Study Day-night variation of acute myocardial infarction in obstructive sleep apnea. Sleep apnea impairs the arousal response to airway occlusion. Effectiveness of ramelteon for insomnia symptoms in older adults with obstructive sleep apnea: a randomized placebo-controlled pilot study. Effects of continuous positive airway pressure therapy withdrawal in patients with obstructive sleep apnea: a randomized controlled trial. An oral hypnotic medication does not improve continuous positive airway pressure compliance in men with obstructive sleep apnea. The effect of diazepam on genioglossal muscle activity in normal human subjects. Impact of zaleplon on continuous positive airway pressure therapy compliance. Effect of flurazepam on sleep-disordered breathing and nocturnal oxygen desaturation in asymptomatic subjects. Characteristics of opioid prescriptions in 2009.
The time course of changes in breathing pattern in opioid‐induced respiratory depression was characterised for two opioids . Intravenous morphine ( 0.039 mg.kg−1 bolus + 0.215 mg.kg−1.h−1 infusion ) and oxycodone ( 0.05 mg.kg−1 bolus + 0.275 mg.kg−1.h−1 infusion ) were administered to six healthy male volunteers for 2 h in a r and om , double‐blind and cross‐over fashion . Monitoring included pulse oximetry  and noninvasive respiratory‐inductive plethysmography  for the measurement of breathing pattern . The total amounts of drugs given were 35.1 ( 0.0 ) mg [ mean ( SD ) ] morphine and 41.3 ( 8.0 ) mg oxycodone . Four of the six oxycodone infusions had to be stopped at 99 ( 14 ) min because of respiratory depression as judged by pulse oximetry . No morphine infusions were stopped . The first changes in breathing pattern were a decrease in respiratory rate and an increase in the contribution of the rib cage to tidal volume , while the compensatory increase in tidal volume became evident later . A decrease in minute ventilation and inspiratory duty cycle were also found We have assessed the effects of zopiclone ( 7.5 mg ) , a new cyclopyrrolone hypnotic drug , on ventilation , sleep parameters , and daytime vigilance in snorers with upper airway resistance syndrome ( UARS ) . Using a r and omized double-blind design , eight male patients with UARS took either oral zopiclone or a placebo each evening for seven consecutive days and then crossed over to the other drug after a 7 day placebo period .  Polysomnography followed by a multiple sleep latency test ( MSLT ) was performed during the last night of each treatment period . Zopiclone produced significant improvements in the sleep efficiency index ( total sleep time/time in bed ) ( placebo 84+/-15 % versus zopiclone 91+/-7 % ) and average MSLT ( placebo 10.3+/-3.7 min versus zopiclone 14.9+/-2.8 min ) , as well as nonsignificant improvements in sleep onset latency and total sleep time . It had no effect on sleep architecture or on the arousal index ( placebo 17+/-8 arousals x h(-1 ) versus zopiclone 17+/-4 arousals x h[-1 ] ) . Furthermore , none of the respiratory parameters were significantly affected by zopiclone . In conclusion , zopiclone has no adverse effects on sleep architecture , respiratory parameters during sleep , and daytime sleepiness in patients with UARS Alcohol and benzodiazepines may increase sleep-disordered breathing by decreasing activity of pharyngeal dilating muscles , favoring the development of obstructive apneas and hypopneas . Narcotics cause greater depression of wakeful respiration than the previously mentioned drugs ; however , the influence of narcotics on the upper airway and breathing during sleep has not been studied . We , therefore , examined , in 12 healthy adults , the effects of oral hydromorphone hydrochloride ( 2 and 4 mg ) on breathing during sleep and on a variety of awake respiratory variables ( minute ventilation , gas exchange , and chemoresponsiveness ) . In addition , awake pharyngeal inspiratory airflow resistance was determined before and after narcotic administration to assess the drug 's influence on patency of the upper airway . Following both doses , minute ventilation decreased , and carbon dioxide pressure increased . The 4-mg dose of hydromorphone hydrochloride also produced a significant decrement in the hypoxic ventilatory response , whereas hypercapnic responsiveness and pharyngeal resistance did not change following either dose of the drug . Despite the respiratory depression during wakefulness described previously , no significant change was observed in any measure of sleep-disordered breathing after either dose of narcotic . We conclude that in healthy individuals without suspected sleep apnea , oral hydromorphone in st and ard dosages does not significantly increase sleep-disordered breathing . This result may be due to a lack of selective depression of upper-airway muscular function by the doses of narcotic used Background : Postsurgical administration of opiates in patients with obstructive sleep apnea ( OSA ) has recently been linked to an increased risk for respiratory complications . The authors have attributed this association to an effect of recurrent oxygen desaturation accompanying OSA on endogenous opioid mechanisms that , in turn , alter responsiveness to subsequent administration of exogenous opiates . In a retrospective study , the authors have shown that oxygen desaturation and young age in children with OSA are correlated with a reduced opiate requirement for postoperative analgesia . Methods : The current study was design ed to test that conclusion prospect ively in 22 children with OSA scheduled to undergo adenotonsillectomy .  The children were stratified to those having displayed < 85 % or ≥ 85 % oxygen saturation nadir during sleep preoperatively . Using a blinded design , the children were given morphine postoperatively to achieve an identical behavioral pain score . Results : As compared with children in the ≥ 85 % group , the < 85 % oxygen saturation nadir group required one half the total analgesic morphine dose postoperatively , indicating heightened analgesic sensitivity  to morphine after recurrent hypoxemia . Conclusions : Previous recurrent hypoxemia in OSA is associated with increased analgesic sensitivity to subsequent morphine administration . Therefore , opiate dosing in children with OSA must take into account a history of recurrent hypoxemia OBJECTIVE Sodium oxybate ( SXB ) is an approved drug for the treatment of excessive daytime sleepiness ( EDS ) and cataplexy in narcolepsy . Obstructive sleep apnea syndrome ( OSAS ) is a condition that frequently co-occurs with narcolepsy . Given the known central nervous system ( CNS ) depressant effects of SXB , this study aim ed to examine its effects on sleep-disordered breathing ( SDB ) and sleep architecture in patients with OSAS . METHODS Sixty patients with a history of mild to moderate OSAS ( apnea-hypopnea index [AHI]>or=10 and < or=40 , mean oxygen saturation [ SaO(2 ) ] > or=75 % ) received one of four treatments of the following : ( 1 ) 9 g SXB , ( 2 ) 9 g SXB/modafinil 200 mg , ( 3 ) zolpidem 10 mg , and ( 4 ) placebo ( PBO ) in a r and omized , crossover design on four consecutive nights followed by overnight polysomnography . RESULTS Forty-two patients ( 70 % ) completed the study . The mean change from baseline in AHI and mean SaO(2 ) was not significantly different among groups following treatment . Central apneas in patients treated with SXB increased , and clinical ly significant oxygen desaturations were seen in three patients with SXB treatment . The most common treatment related adverse events were headache and nausea . CONCLUSION These results suggest that nighttime administration of 9 g SXB in patients with mild to moderate OSAS does not negatively impact SDB , as measured by mean change from baseline in AHI and SaO(2 ) , but might increase central apneas and cause oxygen desaturation in some individuals and should be used with caution OBJECTIVES There is a general concern that hypnotic medications in patients with respiratory disorders have the potential to decrease respiratory effort and blunt the arousal response to hypoxemia which may lead to sleep breathing disorders . We investigated whether suvorexant , an orexin receptor antagonist approved for treatment of insomnia at a maximum daily dose of 20 mg in the US , causes sleep breathing disorders in patients with chronic obstructive pulmonary disease ( COPD ) . DESIGN This was a r and omized , double-blind , placebo-controlled , 2-period , cross-over , study performed in 9 sleep laboratories/ clinical research units in the United States . The participants were 25 COPD patients aged 39 - 72 y with mild-to-moderate airflow limitation based on GOLD spirometry criteria . In each period , patients received suvorexant ( 40 mg in < 65 y-olds ; 30 mg in ≥65 y-olds ) or placebo for four consecutive nights . Respiratory function during sleep was measured by oxygen saturation using pulse oximetry ( SpO2 , primary endpoint ) and Apnea Hypopnea Index ( AHI , secondary endpoint ) . The study was powered to rule out a difference between treatments of -2 percentage points in SpO2 on Day 4 . RESULTS There was no treatment effect following single and multiple doses of suvorexant  on mean SpO2 during total sleep time ( Day 1 : suvorexant = 93.14 % , placebo = 93.24 % , difference = -0.10 [ 90 % CI : -0.50 , 0.31 ] ; Day 4 : suvorexant = 93.38 % , placebo = 92.99 % , difference = 0.39 [ 90 % CI : -0.12 , 0.91 ] ) . There was no clinical ly meaningful increase in mean AHI  by suvorexant compared with placebo on Day 1 ( difference = 0.72 [ 90 % CI : -0.60 , 2.04 ] ) or Day 4 ( difference = 2.05 [ 90 % CI : 0.33 , 3.77 ] ) . CONCLUSIONS These data do not suggest an overt respiratory depressant effect with 30 - 40 mg daily doses of suvorexant , up to twice the maximum recommended dose for treating insomnia in the US , in patients with mild-to-moderate COPD . Trial registration Clinical trials.gov identifier : NCT01293006 Recent insights into sleep apnoea pathogenesis reveal that a low respiratory arousal threshold ( awaken easily ) is important for many patients . As most patients experience stable breathing periods mediated by upper-airway dilator muscle activation via accumulation of respiratory stimuli , premature awakening may prevent respiratory stimuli build up as well as the result ing stabilization of sleep and breathing . The aim of the present physiological study was to determine the effects of a non-benzodiazepine sedative , eszopiclone , on the arousal threshold and the AHI ( apnoea/hypopnoea index ) in obstructive sleep apnoea patients . We hypothesized that eszopiclone would increase the arousal threshold and lower the AHI in patients with a low arousal threshold ( 0 to -15 cm H(2)O ) . Following a baseline overnight polysomnogram with an epiglottic pressure catheter to quantify the arousal threshold , 17 obstructive sleep apnoea patients , without major hypoxaemia [ nadir SaO(2 ) ( arterial blood oxygen saturation ) > 70 % ] , returned on two additional nights and received 3 mg of eszopiclone or placebo immediately prior to each study . Compared with placebo , eszopiclone significantly increased the arousal threshold [ -14.0 ( -19.9 to -10.9 ) compared with -18.0 ( -22.2 to -15.1 ) cm H(2)O ; P<0.01 ] , and sleep duration , improved sleep quality and lowered the AHI without respiratory event prolongation or worsening hypoxaemia . Among the eight patients identified as having a low arousal threshold , reductions in the AHI occurred invariably and were most pronounced ( 25±6 compared with 14±4 events/h of sleep ; P<0.01 ) . In conclusion , eszopiclone  increases the arousal threshold and lowers the AHI in obstructive sleep apnoea patients that do not have marked overnight hypoxaemia . The greatest reductions in the AHI occurred in those with a low arousal threshold . The results of this single night physiological study suggest that certain sedatives may be of therapeutic benefit for a definable subgroup of patients . However , additional treatment strategies are probably required to achieve elimination of apnoea STUDY OBJECTIVE Assess the effect of the hypnotic zolpidem on the efficacy of  nasal continuous positive airway pressure for treatment of Obstructive Sleep Apnea .  DESIGN R and omized double blind placebo controlled , cross-over study . SETTING Veterans Administration Medical Center . PATIENTS 16 patients with severe obstructive sleep apnea ( apnea+ hypopnea index > 30/hr ) , on CPAP therapy for at least 6 months . INTERVENTION Three sleep studies were performed over three consecutive weeks . On night one the pressure level required to prevent apnea , hypopnea , and snoring was determined . On the second and third study nights , either placebo ( P ) or 10 mg of zolpidem ( Z ) was given ( r and om order ) and subjects slept on the CPAP level determined on the first night . MEASUREMENTS Sleep architecture , apnea + hypopnea index , arterial oxygen saturation . RESULTS The sleep architecture was similar on the placebo and zolpidem nights except for a decrease in the sleep latency ( P : 23.5 + /- 4.7 ; Z : 13.1 + /- 3.3 minutes , P < 0.02 ) and a small decrease in the arousal index ( P < 0.03 ) on zolpidem nights . The was no significant difference between placebo and zolpidem nights in the apnea + hypopnea index ( P : 4.8 + /- 1.4 versus Z : 2.7 + /- 0.47 events/hour ) , oxygen desaturation index ( 1.46 + /- 0.53 versus 0.81 + /- 0.29 desaturations/hour ) , or the lowest SaO2 ( 91.4 + /- 0.6 versus 91.0 + /- 0.7 % ) . CONCLUSIONS Acute administration of zolpidem 10 mg does not impair the efficacy of an effective level of CPAP in patients with severe obstructive sleep apnea Background Obstructive sleep apnea ( OSA ) is characterized by recurrent nocturnal hypoxia and sleep disruption . Sleep fragmentation caused hyperalgesia in volunteers , while nocturnal hypoxemia enhanced morphine analgesic potency in children with OSA . This evidence directly relates to surgical OSA patients who are at risk for airway compromise due to postoperative use of opioids . Using accepted experimental pain models , we characterized pain processing and opioid analgesia in male volunteers recruited based on their risk for OSA . Methods After approval from the Intitutional Review Board and informed consent , we assessed heat and cold pain thresholds and tolerances in volunteers after overnight polysomnography ( PSG ) .  Three pro-inflammatory and 3 hypoxia markers were determined in the serum . Pain tests were performed at baseline , placebo , and two effect site concentrations of remifentanil ( 1 and 2 µg/ml ) , an μ-opioid agonist . Linear mixed effects regression models were employed to evaluate the association of 3 PSG descriptors [ wake after sleep onset , number of sleep stage shifts , and lowest oxyhemoglobin saturation ( SaO2 ) during sleep ] and all serum markers with pain thresholds and tolerances at baseline , as well as their changes under remifentanil . Results Forty-three volunteers ( 12 normal and 31 with a PSG-based diagnosis of OSA ) were included in the analysis . The lower nadir SaO2 and higher insulin growth factor binding protein-1 ( IGFBP-1 ) were associated with higher analgesic sensitivity to remifentanil ( SaO2 , P = 0.0440 ; IGFBP-1 , P = 0.0013 ) . Other pro-inflammatory mediators like interleukin-1β and tumor necrosis factor-α ( TNF-α ) were associated with an enhanced sensitivity to the opioid analgesic effect ( IL-1β , P = 0.0218 ; TNF-α , P = 0.0276 ) . Conclusions Nocturnal hypoxemia in subjects at high risk for OSA was associated with an increased potency of opioid analgesia . A serum hypoxia marker ( IGFBP-1 ) was associated with hypoalgesia and increased potency to opioid analgesia ; other pro-inflammatory mediators also predicted an enhanced opioid potency . Trial Registration : Clinical Trials.gov NCT00672737 The purpose of this study was to assess the effect of triazolam ( 0.25 mg ) on apnea duration and the arousal response to airway occlusion during sleep in patients with severe obstructive sleep apnea ( OSA ) . Twelve male subjects with a mean ( + /- SD ) age of 46.6 + /- 14.1 yr and body weight of 260.8 + /- 55.9 lb were studied on two nights separated by a non study night . They ingested triazolam ( 0.25 mg ) or placebo 0.5 h before bedtime in a r and omized double-blind crossover manner . In non-rapid-eye-movement ( NREM ) sleep , the mean ( + /- SEM ) duration of apnea/hypopnea was slightly increased ( 26.8 + /- 1.7 versus 23.8 + /- 1.2 s , p < 0.02 ) and the mean nadir in arterial oxygen saturation lower ( 80.1 + /- 1.9 versus 84.2 + /- 1.4 % , p < 0.001 ) on triazolam nights . In NREM sleep , the deflections in esophageal pressure prior to apnea termination were higher on triazolam nights ( 53.3 + /- 5.4 versus 44.5 + /- 4.8 cm H2O , p < 0.001 ) . However , the rate of increase in inspiratory effort ( esophageal pressure deflections ) during obstructive events was not decreased by triazolam . We conclude that triazolam increases the arousal threshold to airway occlusion , but that this results in only modest prolongation of event duration and increased desaturation at a dose of 0.25 mg in a group of large sleep apnea patients BACKGROUND Limited data have suggested that sleep-disordered breathing , a condition of repeated episodes of apnea and hypopnea during sleep , is prevalent among adults . Data from the Wisconsin Sleep Cohort Study , a longitudinal study of the natural history of cardiopulmonary disorders of sleep , were used to estimate the prevalence of undiagnosed sleep-disordered breathing among adults and address its importance to the public health . METHODS A r and om sample of 602 employed men and women 30 to 60 years old were studied by overnight polysomnography to determine the frequency of episodes of apnea and hypopnea per hour of sleep ( the apnea-hypopnea score ) . We measured the age- and sex-specific prevalence of sleep-disordered breathing in this group using three cutoff points for the apnea-hypopnea score ( > or = 5 , > or = 10 , and > or = 15 ) ; we used logistic regression to investigate risk factors . RESULTS The estimated prevalence of sleep-disordered breathing , defined as an apnea-hypopnea score of 5 or higher , was 9 percent for women and 24 percent for men . We estimated that 2 percent of women and 4 percent of men in the middle-aged work force meet the minimal diagnostic criteria for the sleep apnea syndrome ( an apnea-hypopnea score of 5 or higher and daytime hypersomnolence ) . Male sex and obesity were strongly associated with the presence of sleep-disordered breathing . Habitual snorers , both men and women , tended to have a higher prevalence of apnea-hypopnea scores of 15 or higher . CONCLUSIONS The prevalence of undiagnosed sleep-disordered breathing is high among men and is much higher than previously suspected among women . Undiagnosed sleep-disordered breathing is associated with daytime hypersomnolence We wanted to assess whether benzodiazepines worsen sleep apnoea , since their use in such patients has been controversial . Fourteen male patients with mild to moderate obstructive sleep apnoea were investigated in a placebo-controlled , double-blind study evaluating the influence of nitrazepam ( NIT ) on apnoea frequency and severity . Each patient was given oral nitrazepam 5 or 10 mg , or corresponding placebo , in a r and omized order on three separate nights . Wash-out time was one week . A complete sleep study was undertaken at each study night . Eleven patients completed the study . Although there were individuals with marked variability in apnoea index between the three study nights , there was no significant change in apnoea index or minimum arterial oxygen saturation with any of the two nitrazepam dosages studied . Only 3 out of 11 patients had a higher apnoea index after both nitrazepam doses compared to placebo , and in these patients the increase in sleep-disordered breathing was of marginal clinical significance . Nitrazepam caused a modest increase in total sleep time and a decrease in rapid eye movement ( REM ) sleep . These results demonstrate that nitrazepam does not worsen sleep apnoea in patients with mild to moderate sleep apnoea . The previously reported sleep apnoea promoting effects of benzodiazepines may be restricted to a small subgroup of patients with sleep-disordered breathing Sleep-disordered breathing is a common disorder with a range of harmful sequelae . Obesity is a strong causal factor for sleep-disordered breathing , and because of the ongoing obesity epidemic , previous estimates of sleep-disordered breathing prevalence require updating . We estimated the prevalence of sleep-disordered breathing in the United States for the periods of 1988 - 1994 and 2007 - 2010 using data from the Wisconsin Sleep Cohort Study , an ongoing community-based study that was established in 1988 with participants r and omly selected from an employed population of Wisconsin adults . A total of 1,520 participants who were 30 - 70 years of age had baseline polysomnography studies to assess the presence of sleep-disordered breathing . Participants were invited for repeat studies at 4-year intervals . The prevalence of sleep-disordered breathing was modeled as a function of age , sex , and body mass index , and estimates were extrapolated to US body mass index distributions estimated using data from the National Health and Nutrition Examination Survey . The current prevalence estimates of moderate to severe sleep-disordered breathing ( apnea-hypopnea index , measured as events/hour , ≥15 ) are 10 % ( 95 % confidence interval ( CI ) : 7 , 12 ) among 30 - 49-year-old men ; 17 % ( 95 % CI : 15 , 21 ) among 50 - 70-year-old men ; 3 % ( 95 % CI : 2 , 4 ) among 30 - 49-year-old women ; and 9 % ( 95 % CI : 7 , 11 ) among 50 - 70 year-old women . These estimated prevalence rates represent substantial increases over the last 2 decades ( relative increases of between 14 % and 55 % depending on the subgroup ) Clinical studies have shown that zolpidem , an original imidazopyridine derivative , induces and maintains sleep and does not have daytime side-effects . Polysomnography has revealed that this drug has several interesting qualities that benzodiazepines do not possess : stages 3 - 4 increase , stage 2 is unchanged or slightly reduced and no abnormal changes are detected on the EEG tracing . Like benzodiazepines , zolpidem slightly reduces REM sleep . The Multiple Sleep Latency Test confirmed that the drug does not cause daytime drowsiness . All the hypnotic drugs studied up to now worsen heavy snoring and obstructive sleep apnea syndrome . A controlled double blind cross-over trial assessed the effects of a single dose of zolpidem 20 mg on nocturnal breathing in patients with mild forms of sleep apnea syndrome .  The results indicate that , at this dose , the drug does not overcome the existing contraindications to the use of hypnotics in this syndrome The association of sleep apnea hypopnea syndrome ( SAHS ) with high leg activity in the same patient is a dilemma for the physician , as clonazepam , used to treat periodic leg movement syndrome ( PLMS ) can aggravate apneas , while nasal continuous positive airway pressure ( nCPAP ) can exacerbate PLMS . The present study aim ed to compare nCPAP alone ( n ) , nCPAP combined with clonazepam ( n+c ) and clonazepam alone ( c ) in patients with mild to moderate SAHS associated with high leg activity . Fourteen patients with an apnea hypopnea index ( AHI ) between 10 and 50 h(-1 ) and a leg movement index with regard to time in bed [ LMI ( TIB ) ] > 15 h(-1 ) on baseline polysomnography ( b ) were recorded on three consecutive nights with n , n+c and c , respectively . Leg movements were detected , using actigraphy , and were subsequently categorized into periodic , apnea- or hypopnea-related and nonperiodic movements ( defined as neither periodic nor related to a respiratory event ) . The three treatments were successful in improving breathing [ AHI b 26.1 ( 3.2 ) n 11.8 ( 2.4 ) n+c 5.0 ( 0.7 ) c 14.9 ( 1.8 ) h(-1 ) ] , leg activity [ LMI ( TIB ) b 391 ( 4.8 ) n 22.5 ( 4.4 ) n+c 23.9 ( 3.9 ) c 22.6 ( 3.7 ) h(-1 ) ] and sleep fragmentation [ stage shift index b 373 ( 2.6 ) n 28.6 ( 1.6 ) n+c 25.6 ( 1.8 ) c 26.6 ( 1.6 ) h(-1 ) ] . All types of movements were reduced , the effect being significant for respiratory events related and nonperiodic movements . Combination therapy was more effective than nCPAP alone in reducing the AHI and in improving sleep efficiency . We conclude that in patients with mild to moderate SASH associated with high leg activity , nCPAP  improves nocturnal breathing and clonazepam reduces leg activity . More unexpectedly nCPAP is beneficial on leg activity and clonazepam on breathing , probably through a decrease in sleep fragmentation . The best results are obtained with combination therapy Background : There is concern that opioid-based analgesia will worsen  sleep-related respiratory insufficiency in patients with obstructive sleep apnea ( OSA ) , result ing in serious morbidity or mortality . However , there are no studies that directly address the merit of this concern . Consequently , the authors design ed this study as the first prospect i ve , double-blind , placebo-controlled investigation of opioid pharmacology in patients with documented OSA . Methods : Patients ( n = 19 ) with moderate OSA documented by polysomnography ( sleep study ) were r and omized to undergo an additional sleep study while receiving either a saline infusion or a remifentanil infusion ( 0.075 & mgr;g • kg–1 · h–1 ) . Sleep stages , apneas , hypopneas , and arterial hemoglobin oxygen saturation were continually recorded during saline or remifentanil infusion , and were compared with values obtained during the patients ’ earlier sleep study . Results : Saline infusion had no effect on sleep or respiratory variables . In contrast , remifentanil increased Stage 1 sleep , markedly decreased rapid eye movement sleep , increased arousals from sleep , and decreased sleep efficiency . Remifentanil actually decreased the number of obstructive apneas , but markedly increased the number of central apneas . Arterial hemoglobin oxygen saturation was also significantly lower in OSA patients receiving remifentanil . Conclusions : The decrease in obstructive apneas likely result ed from the marked decrease in rapid eye movement sleep caused by remifentanil . Despite fewer obstructions , OSA was worse during remifentanil infusion because of a marked increase in the number of central apneas . These data suggest that caution is warranted when administering opioids to subjects with moderate OSA , but that the primary risk may be central apnea , not obstructive apnea OBJECTIVE To evaluate the effects of eszopiclone on measures of respiration and sleep using polysomnography in patients with mild to moderate obstructive sleep apnea syndrome ( OSAS ) . METHODS This double-blind , r and omized crossover study included patients ( 35 - 64 years ) with mild-to-moderate OSAS [ apnea and hypopnea index ( AHI ) range 10 and 40 ] . Patients received either eszopiclone 3 mg or placebo for two consecutive nights , with a 5 - 7 day washout between treatments . Continuous positive airway pressure ( CPAP ) was not allowed on nights in the sleep laboratory . RESULTS The primary endpoint , mean total AHI , was not significantly different from placebo ( 16.5 with placebo and 16.7 with eszopiclone ; 90 % confidence interval ( CI ) -1.7 , 1.9 ) . No significant differences in total arousals , respiratory arousals , duration of apnea and hypopnea episodes , or oxygen saturation were noted . Significant differences in spontaneous arousals ( 13.6 versus 11.4 for placebo and eszopiclone , respectively ; 90 % CI -3.7 , -0.7 ) , sleep efficiency ( 85.1 % and 88.4 % ; p=0.0075 ) , wake time after sleep onset ( 61.8 and 48.1 min ; p=0.0125 ) , and wake time during sleep ( 55.9 and 43.2 min ; p=0.013 ) were noted after eszopiclone treatment . Eszopiclone was well tolerated . CONCLUSIONS In this pilot study , eszopiclone did not worsen AHI , and it improved sleep maintenance and efficiency . Further study is warranted to determine whether eszopiclone could improve CPAP compliance or next-day function in patients with OSAS The effect of morphine on breathing and ventilatory chemoreflexes in obstructive sleep apnea ( OSA ) is unknown . It has been assumed that acute morphine use may induce deeper respiratory depression in OSA but this has not been investigated . We evaluated awake ventilatory chemoreflexes and overnight polysomnography  on 10 mild-moderate OSA patients before and after giving 30 mg oral controlled-release morphine . Morphine plasma concentrations were analysed . We found a 30-fold range of  morphine plasma concentrations with the fixed dose of morphine , and a higher plasma morphine concentration was associated with a higher CO(2 ) recruitment threshold ( VRT ) ( r=0.86 , p=0.006 ) and an improvement in sleep time with Sp(O(2 ) ) ( T90 ) ( r=-0.87 , p=0.005 ) compared to the baseline . The improvement in T90 also significantly correlated with the increase of VRT ( r=-0.79 , r=0.02 ) . In conclusion , in mild-to-moderate OSA patients , a single common dose of oral morphine may paradoxically improve OSA through modulating chemoreflexes . There is a large inter-individual variability in the responses , which may relate to individual morphine metabolism Ramelteon is a selective MT1/MT2-receptor agonist indicated for insomnia treatment . Because it has no depressant effects on the nervous system , it is not expected to affect the control of breathing . The potential effects of ramelteon on apneic and hypopneic events and arterial oxygen saturation ( SaO2 ) in individuals with obstructive sleep apnea were assessed . In this double-blind , r and omized , crossover study , 26 adults with mild to moderate obstructive sleep apnea received ramelteon 16 mg and placebo for one night each , with a 5- to 12-day washout period between treatments . Treatments were administered 30 min before habitual bedtime . Respiratory effort was monitored using respiratory inductance plethysmography ,  SaO2 was measured by pulse oximetry , and  sleep onset and duration were measured by polysomnography and post-sleep question naire . Post-sleep question naire also measured next-day residual effects . The primary measure was apnea – hypopnea index . Apnea – hypopnea index was similar in ramelteon and placebo groups ( 11.4 vs 11.1 , respectively ; CI = −2.1 , 2.6 , P = 0.812 ) . Ramelteon had no effect on the number of central , obstructive , or mixed apnea episodes . No significant differences were observed in SaO2 for the entire night between ramelteon and placebo ( 95.1 vs 94.7 % ; P = 0.070 ) . Ramelteon did not meaningfully affect sleep when evaluated by polysomnography and post-sleep question naire . Compared with placebo , ramelteon had no significant effect on next-day residual effects . Adverse events were reported by three subjects in the ramelteon  group : headache ( n = 2 ) and urinary tract infection ( n = 1 ) . No adverse events were reported with placebo . Ramelteon was well-tolerated and , as expected , did not worsen sleep apnea when administered to subjects with mild to moderate obstructive sleep apnea The objective of this review is to determine the effects of perioperative sedatives and anesthetics in surgical patients with obstructive sleep apnea ( OSA ) on respiratory events , medication requirements , hemodynamics , pain , emergence , and hospital stay . We search ed The Cochrane CENTRAL Register of Controlled Trials , Medline , Embase , and Cochrane Data base of Systematic Review s from 1950 to June 2010 for relevant articles . All prospect i ve and retrospective studies were eligible for inclusion if the effects of perioperative administration of sedation and anesthetics on medication requirements , pain , emergence , hemodynamics , respiratory events , and length of hospital stay in OSA patients were reported . The search strategy yielded 18 studies of 1467 patients . Of these , 456 patients were documented as having OSA . Few adverse respiratory effects were reported . Eight out of 700 ( 1.14 % ) patients undergoing middle ear surgery with midazolam and fentanyl had impaired upper airway patency and were retrospectively diagnosed as having OSA by polysomnography . Also , intraoperative snoring causing uvular edema in the postoperative period was described in an OSA patient undergoing upper limb surgery when propofol was administered with midazolam and fentanyl for sedation . A decrease in oxygen saturation in the postoperative period was described with propofol and isoflurane in 21 OSA patients undergoing uvulo-palato-pharyngoplasty and tonsillectomy surgery ( P<0.05 ) . Perioperative alpha 2 agonists were shown to decrease the use of anesthetics ( P<0.05 ) , analgesics ( P=0.008 ) and anti-hypertensives ( P<0.001 ) in OSA patients . Contradictory reports regarding emergence occurred with intraoperative dexmedetomidine . Intraoperative opioids decreased the analgesic consumption ( P=0.03 ) and pain scores ( P<0.05 ) in the postoperative period . There was limited data on the length of hospital stay . There were few adverse effects reported when patients with known OSA underwent elective surgery with the currently available sedatives and anesthetics . Adverse events were reported with midazolam . However , the quality and number of patients in the studies were limited . There is a need for further trials with large numbers and uniform reporting of outcomes This study evaluated the respiratory effect of temazepam in elderly subjects ( mean age 65 + /- 3.8 years ) , with mild sleep apnea . The 15 subjects of this report were enrolled in a larger r and omized trial comparing pharmacological and behavioral treatments for insomnia . Seven subjects received temazepam 15 - 30 mg/day either alone or in combination with behavior therapy , and eight subjects received placebo or behavior therapy . The mean baseline respiratory disturbance index ( RDI ) was 9.2 + /- 2.8 for the nondrug and 8.8 + /- 5.3 for the temazepam group . There were no significant time , group or interaction effects . There was no increase in the RDI in elderly subjects with mild respiratory apnea receiving 15 - 30 mg of temazepam Patients with sleep apnea often present with cardiac diseases and breathing difficulties , with a high risk of postoperative respiratory depression . We conducted a r and omized , double-blind , prospect i ve study in 30 adult patients with obstructive sleep apnea , undergoing elective ear-nose-throat surgery . The patients were r and omly assigned to receive placebo or clonidine ( 2 & mgr;g/kg oral ) the night before and the next morning 2 h before surgery . Spo2 , heart rate , mean arterial blood pressure , snoring , and oronasal airflow were monitored for 36 h. A st and ard anesthesia was used consisting of propofol and remifentanil . Anesthetic drug consumption , postoperative analgesics , and pain score were recorded . In the clonidine group , mean arterial blood pressures were significantly lower during induction , operation , and emergence from anesthesia . Both propofol dose required for induction ( 190 ± 32.2 mg ) and anesthesia ( 6.3 ± 1.3 mg · kg−1 · h−1 ) during surgery were significantly reduced in the clonidine group compared with the placebo group ( induction 218 ± 32.4 , anesthesia 7.70 ± 1.5 ; P < 0.05 ) . Piritramide consumption ( 7.4 ± 5.1 versus 14.2 ± 8.5 mg ; P < 0.05 ) and analgesia scores were significantly reduced in the clonidine group . Apnea and desaturation index were not different between the groups , whereas the minimal postoperative oxygen saturation on the day of surgery was significantly lower in the placebo than in the clonidine group ( 76.7 % ± 8.0 % versus 82.4 % ± 5.8 % ; P < 0.05 ) . We conclude that oral clonidine premedication stabilizes hemodynamic variables during induction , maintenance , and emergence from anesthesia and reduces the amount of intraoperative anesthetics and postoperative opioids without deterioration of ventilation OBJECTIVES This study sought to evaluate the day-night variation of acute myocardial infa rct ion ( MI ) in patients with obstructive sleep apnea ( OSA ) . BACKGROUND Obstructive sleep apnea has a high prevalence and is characterized by acute nocturnal hemodynamic and neurohormonal abnormalities that may increase the risk of MI during the night . METHODS We prospect ively studied 92 patients with MI for which the time of onset of chest pain was clearly identified . The presence of OSA was determined by overnight polysomnography .  RESULTS For patients with and without OSA , we compared the frequency of MI during different intervals of the day based on the onset time of chest pain . The groups had similar prevalence of comorbidities . Myocardial infa rct ion occurred between 12 am and 6 am in 32 % of OSA patients and 7 % of non-OSA patients ( p = 0.01 ) . The odds of having OSA  in those patients whose MI occurred between 12 am and 6 am was 6-fold higher than in the remaining 18 h of the day ( 95 % confidence interval : 1.3 to 27.3 , p = 0.01 ) . Of all patients having an MI between 12 am and 6 am , 91 % had OSA . CONCLUSIONS The diurnal variation in the onset of MI in OSA patients is strikingly different from the diurnal variation in non-OSA patients . Patients with nocturnal onset of MI have a high likelihood of having OSA . These findings suggest that OSA may be a trigger for MI . Patients having nocturnal onset of MI should be evaluated for OSA , and future research should address the effects of OSA therapy for prevention of nocturnal cardiac events We hypothesized that the increased arousal threshold to upper airway occlusion exhibited by patients with obstructive sleep apnea ( OSA ) is in part secondary to the disease process itself . To test this hypothesis , we studied the effects of withdrawal of three nights of nasal continuous positive airway pressure ( CPAP ) treatment on arousal in six male patients with severe OSA who were using nasal CPAP on a long-term basis . During the control week , patients slept with nasal CPAP at home and on the first of 2 nights in the sleep laboratory ( night C1 , CPAP ; night C2 , no CPAP ) . During the apnea week , patients slept without nasal CPAP for 2 nights at home and 2 nights in the sleep laboratory ( AP1 , AP2 ) . The control and apnea weeks were consecutive and in r and om order . The mean ( + /-SEM ) apnea+hypopnea index was 76.9 + /- 7.1 on AP1 vs 3.1 + /- 1.0 events per hour on C1 ( p<0.05 ) . Thus , the laboratory night ( and presumably the 2 nights at home ) preceding AP2 had dramatic increases in apnea compared with the nights preceding C2 . The apnea duration during nonrapid eye movement sleep on nights following apnea was greater ( AP2 : 28.7 + /- 1.5 vs C2 : 25.5 + /- 1 . 7 s ; p<0/05 ) and the arousal threshold as reflected by the maximum esophageal pressure deflection preceding arousal was higher ( DPmax ) ( AP2 : 55.1 + /- 5.7 vs C2 : 45.3 + /- 6.4 cm H2O ; p<0.005 ) . We conclude that prior sleep apnea increases the arousal threshold to upper airway occlusion on subsequent nights and prolongs the apneic events STUDY OBJECTIVES To evaluate the effectiveness of ramelteon , a melatonin receptor agonist , for the treatment of insomnia in older adults starting auto-titrating positive airway pressure ( APAP ) therapy for sleep apnea . METHODS A parallel group , r and omized , double-blind , placebo-controlled pilot effectiveness clinical trial . The study enrolled 21 research study participants who were ≥ 60 years old and had obstructive sleep apnea , defined by an apnea-hypopnea index ( AHI ) ≥ 5 events/h , with complaints of insomnia . The primary outcome measure was change in sleep onset latency determined from polysomnography at 4 weeks . Research study participants , all of whom were starting on APAP , were r and omized to ramelteon 8 mg ( n = 8) or placebo ( n = 13 ) . RESULTS Ramelteon treatment was associated with a statistically significant difference in sleep onset latency ( SOL ) as measured by polysomnography of 28.5 min ( ± 16.2 min ) compared to placebo ( 95 % C.I. 8.5 min to 48.6 min , effect size 1.35 , p = 0.008 ) . This was due to a 10.7 ( ± 17.0 ) min SOL reduction in the ramelteon arm and a 17.8 ( ± 23.5 ) min SOL increase in the placebo arm . No change was noted in subjective sleep onset latency ( -1.3 min , ± 19.3 min , 95 % C.I. : -21.4 min to 18.7 min ) . No statistically significant changes were noted in the AHI , sleep efficiency ( polysomnography and self-report ) , APAP adherence , Pittsburgh Sleep Quality Index global score , or Epworth Sleepiness Scale score when comparing ramelteon vs. placebo . Four adverse events occurred in the ramelteon arm and 2 in the placebo arm ; none were considered to be related to treatment . CONCLUSIONS Ramelteon was effective in improving objective , but not subjective , sleep onset latency even in older adults who were starting APAP therapy for sleep apnea . Further research is warranted in examining the role of ramelteon in the care of older adults with insomnia symptoms and sleep apnea RATIONALE To establish a new approach to investigate the physiological effects of obstructive sleep apnea ( OSA ) , and to evaluate novel treatments , during a period of continuous positive airway pressure ( CPAP ) withdrawal . OBJECTIVES To determine the effects of CPAP withdrawal . METHODS Forty-one patients with OSA and receiving CPAP were r and omized to either CPAP withdrawal ( subtherapeutic CPAP ) , or continued CPAP , for 2 weeks . Polysomnography , sleepiness , psychomotor performance , endothelial function , blood pressure ( BP ) , heart rate ( HR ) , urinary catecholamines , blood markers of systemic inflammation , and metabolism were assessed . MEASUREMENTS AND MAIN RESULTS CPAP withdrawal led to a recurrence of OSA within a few days and a return of subjective sleepiness , but was not associated with significant deterioration of psychomotor performance within 2 weeks . Endothelial function , assessed by flow-mediated dilatation , decreased significantly in the CPAP withdrawal group compared with therapeutic CPAP ( mean difference in change , -3.2 % ; 95 % confidence interval [ CI ] , -4.5 , -1.9 % ; P < 0.001 ) . Compared with continuing CPAP , 2 weeks of CPAP withdrawal was associated with a significant increase in morning systolic BP ( mean difference in change , + 8.5 mm Hg ; 95 % CI , + 1.7 , + 15.3 mm Hg ; P = 0.016 ) , morning diastolic BP ( mean difference in change , + 6.9 mm Hg ; 95 % CI , + 1.9 , + 11.9 mm Hg ; P = 0.008 ) , and morning HR ( mean difference in change , + 6.3 bpm , 95 % CI , + 0.4 , + 12.2 bpm ; P = 0.035 ) . CPAP withdrawal was associated with an increase in urinary catecholamines but did not lead to an increase in markers of systemic inflammation , insulin resistance , or blood lipids . CONCLUSIONS CPAP withdrawal usually leads to a rapid recurrence of OSA , a return of subjective sleepiness , and is associated with impaired endothelial function , increased urinary catecholamines , blood pressure , and heart rate . Thus the proposed study model appears to be suitable to evaluate physiological and therapeutic effects in OSA . Clinical trial registered with www.controlled-trials.com ( IS RCT N93153804 ) BACKGROUND Compliance with continuous positive airway pressure ( CPAP ) treatment for obstructive sleep apnea ( OSA ) is highly variable . Recent studies suggest that the initial experience with CPAP may determine long-term success . We hypothesized that administration of a hypnotic medication to new CPAP users would facilitate acclimation and increase usage . METHODS Seventy-two male OSA patients referred for CPAP treatment were r and omized to also receive an oral hypnotic agent ( zolpidem ) , placebo pill , or neither ( st and ard care ) for the first 14 days of CPAP treatment . CPAP usage ( effective mask pressure [ hours per day ] ) was recorded by an internal data chip . Patient symptoms were assessed with the Epworth sleepiness scale ( ESS ) and functional outcomes of sleep question naire ( FOSQ ) . Treatment groups were matched for age , body mass index , and baseline ESS and FOSQ scores . Despite r and omization , the st and ard care group had a higher apnea/hypopnea index than either the zolpidem or placebo pill groups ( 54.75 + /- 28.02 vs 32.61 + /- 25.12 vs 38.09 + /- 25.65 , p = 0.012 ) [ mean + /- SD ] . Compared to placebo pill and st and ard care groups , the zolpidem group did not show greater CPAP usage in terms of total days used ( zolpidem , 20.58 + /- 7.40 days ; placebo pill , 17.83 + /- 9.33 days ; st and ard care , 22.92 + /- 6.95 days ; p = 0.198 ) or average time used per night ( 4.43 + /- 1.16 h vs 4.23 + /- 2.14 h vs 4.94 + /- 1.44 h , p = 0.361 ) . All groups showed significant symptom improvements on both the ESS ( p < 0.001 ) and FOSQ ( p < 0.05 ) . CONCLUSION Administration of an oral hypnotic agent did not improve initial CPAP compliance in men with OSA We examined the effect of diazepam on the respiratory electromyographic ( EMG ) activity of the genioglossal muscle using a double-blind , placebo-controlled , r and omized protocol . Control measurements of minute ventilation , tidal volume , frequency , end-tidal CO2 , and peak integrated inspiratory genioglossal EMG activity were made in 10 normal awake male subjects during quiet breathing and CO2 rebreathing . Subjects then received either 10 mg of diazepam orally or a placebo , and all respiratory measurements were repeated after 45 min . Each subject was studied on 2 separate days , receiving each treatment on a different day . The placebo had no effect on any of the measured variables . After diazepam , we observed an increase in end-tidal CO2 rebreathing , diazepam was associated with a reduction in minute ventilation , tidal volume , and frequency . When compared at equal end-tidal CO2 levels , genioglossal EMG activity and tidal volume were significantly reduced after diazepam . However , only older subjects demonstrated a reduction in EMG activity when compared at equal tidal volumes during CO2 rebreathing . We conclude that diazepam selectively decreases genioglossal EMG activity during CO2 rebreathing only in older subjects STUDY OBJECTIVE To determine whether pretreatment with zaleplon immediately before CPAP titration improves 1-month CPAP adherence in subjects newly diagnosed with OSA . METHODS Prospect i ve , r and omized , double-blinded , placebo-controlled trial of a single dose of zaleplon 10 mg or matching placebo at the start of CPAP titration during laboratory-based , split-night polysomnography ( PSG ) . Baseline sleep symptoms were assessed with the Functional Outcomes of Sleep Question naire ( FOSQ ) and Epworth Sleepiness Scale ( ESS ) . CPAP usage and change in symptom question naire responses were assessed at 1-month follow-up . RESULTS One hundred thirty-four newly diagnosed OSA patients undergoing their initial split-night PSG ( 49.8 ± 11.3 years old with an apnea-hypopnea index of 16.5 ( 7 , 32 ) [ median ( interquartile range ) ] were r and omized to zaleplon ( n = 73 ) or placebo ( n = 63 ) . Complete follow-up data were available in 83 subjects ( 44 zaleplon group ;  39  placebo group ) . CPAP was used for 6.5 ( 5 , 7 ) h/day with zaleplon versus 6.5 ( 5 , 8) h/ day with placebo ( p = 0.64 ) . Improvements in FOSQ and ESS scores did not differ between the two groups . CONCLUSION A single dose of zaleplon at the start of a split-night CPAP titration does not result in superior CPAP adherence or improvement in symptoms at 1-month compared to placebo . Our data show that zaleplon is safe and is associated with shorter sleep latency during CPAP titration , but it does not translate into improved short-term CPAP adherence We assessed the effect of 30 mg of oral flurazepam on  sleep-disordered breathing and nocturnal oxygen desaturation  by performing a double-blind , placebo-controlled , r and omized study . Asymptomatic subjects , 17 men and three women ( mean age 49 years , mean weight 79 kg ) , were monitored for two consecutive nights .  Flurazepam was given to 10 subjects on night 1 and to 10 subjects on night 2 . Placebo was ingested on the other nights . Polysomnographic determinations included chest wall movement by impedance pneumography , nasal and oral airflow by thermistor probes , and continuous oxygen saturation by ear oximetry .  Flurazepam was associated with significant increases in the number of sleep events ( p = 0.01 ) , episodes of apnea ( p less than 0.01 ) , and total duration of apnea ( p less than 0.01 ) . The number of episodes of hypopnea of desaturation did not significantly increase , although the degree of desaturation increased after flurazepam ingestion ( p = 0.04 ) . Total sleep time significantly increased ( p = 0.04 ) , but could not account for the increased number of events . Sleep stage distribution was minimally altered by ingestion of flurazepam we chose the latter ; indeed network meta- analysis has been shown to potentially give more reliable results because of the integration of additional information . Although studies included in our review were from different sources , they were all r and omized controlled trials and hence contrasts between treatment groups within each study should be comparable . In addition , we focused only on CP/CPPS categories IIIA and IIIB to reduce heterogeneity due to disease severity and focused on outcomes measured using National Institutes of Health Chronic Prostatitis Symptom Index scales to reduce heterogeneity due to measurement error . Nevertheless , we explored potential discrepancies in treatment effects between direct and network meta- analysis results using the st and ardized normal method ( z ) . Directions of treatment effect for the 2 methods were identical for all 12 comparisons ; moreover , the magnitude of the effects between the 2 methods were similar except for -blocker vs placebo , where z was large and reached statistical significance ( 2.9380 , P=.003 ) . We believe that this is an example of increased precision of treatment effects due to the network method “ borrowing ” information from indirect comparisons . Third , Jackson et al disagree that study data should be exp and ed using a Stata comm and so that it could be included in the meta- analysis , question ing how we could know the distribution of data . We only used this comm and for the treatment responsiveness outcome , which is a dichotomous outcome and does not need any assumption about distribution , normal or otherwise . We believe that using all available data , rather than omitting studies , is an advantage and will lead to more valid estimates
BACKGROUND Obstructive sleep apnoea ( OSA ) is a common sleep disorder characterised by partial or complete upper airway occlusion during sleep , leading to intermittent cessation ( apnoea ) or reduction ( hypopnoea ) of airflow and dips in arterial oxygen saturation during sleep .
Many patients with recognised and unrecognised OSA receive hypnotics , sedatives and opiates/opioids to treat conditions including pain , anxiety and difficulty sleeping .
Concerns have been expressed that administration of these drugs to people with co-existing OSA may worsen OSA .
OBJECTIVES To investigate whether administration of sedative and hypnotic drugs exacerbates the severity of OSA ( as measured by the apnoea-hypopnoea index ( AHI ) or the 4 % oxygen desaturation index ( ODI ) ) in people with known OSA .