human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: 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 
    Output:
    
agent
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: 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 
    Output:
    