Key words: arousal index; obstructive sleep apnea; quality of life; short arousal; sleepiness driving

Transcription

1 Obstuctive Slee Anea Syndome, Sleeiness, and Quality of Life* Mata A. Gon alves, MD; Teesa Paiva, MD; Elizabeth Ramos, MS; and Chistian Guilleminault, MD, BiolD Objective: To evaluate the addition of shot aousals of > 3 s on indexes of slee-disodeed beathing (SDB) and subjective sleeiness in atients with obstuctive slee anea (OSA), and to evaluate the quality of life and eoted difficulty diving with aousal index and indexes of SDB. Method: Data was collected fom a geneal clinical evaluation, and evaluations using the Ewoth sleeiness scale (ESS), the slee disodes questionnaie, the Beck deession inventoy (BDI), the Medical Outcomes Study 36-item shot fom health suvey (SF-36), a questionnaie on diving difficulties and accidents, and olysomnogahy. Results: A total of 135 male subjects (mean [ SD] age, yeas; mean body mass index [BMI], kg/m 2 ; mean anea-hyonea index [AHI], events e hou) wee studied. Of these subjects, 70.4% acknowledged having diven while sleey. ESS scoes coelated significantly with the aousal index and AHI, and negatively with the lowest ateial oxygen satuation. The hysical functioning, geneal health, and ole hysical subscales of the SF-36 coelated with the aousal index. No significant coelation was seen in multile egession analyses afte adjusting fo age and BMI, using eots of sleeiness while diving as the deendent vaiable. Conclusion: Seveal subjective comlaints and subscales of the SF-36 coelated significantly with a fequency of SDB-elated aousal of > 3 s. Patients eceived that an oganic health oblem had been imaiing thei quality of life moe than an emotional oblem, desite elevated scoes on the BDI. Howeve, if sleeiness while diving was common in OSA atients, it was not significant. Many clinical and olysomnogahic vaiables may be consideed as ossible indeendent vaiables in the egession analysis. Othe unelated factos have a geate imact. To elate sleeiness while diving only to the usually studied vaiables in OSA atients is an ovesimlification. (CHEST 2004; 125: ) Key wods: aousal index; obstuctive slee anea; quality of life; shot aousal; sleeiness diving Abbeviations: AHI anea-hyonea index; BDI Beck deession inventoy; BMI body mass index; CPAP continuous ositive aiway essue; ESS Ewoth sleeiness scale; OSA obstuctive slee anea; REM aid eye movement; Sao 2 ateial oxygen satuation; SDB slee-disodeed beathing; SF-36 Medical Outcomes Study 36-item shot fom health suvey; SWS slow-wave slee In the 1980s, the noctunal slee of obstuctive slee anea (OSA) atients was scoed using intenational citeia of Rechtschaffen and Kales. 1 Often, no significant elationshi was found between (1) the anea-hyonea index (AHI), the time sent awake duing the night, and the daytime ateial oxygen satuation (Sao 2 ), and (2) comlaints of tiedness, fatigue, and sleeiness. 2 4 *Fom the Instituto do Sono, Chonobiologia, e Telemedecina Poto (D. Gon alves), Poto, Potugal; the Instituto do Sono, Chonobiologia, e Telemedecina Lisbon (D. Paiva), Lisbon, Potugal; the Deatment of Eidemiology (Ms. Ramos), Univesity Medical School, Poto, Potugal; and Stanfod Univesity Slee Disodes Clinic (D. Guilleminault), Stanfod, CA. This wok was at of a thesis by D. Gon alves fulfilling the equiements fo a Mastes degee in Mental Health fom the Slee Reseach Cente of the National Heat, Lung, and Blood Institute of the National Institutes of Health. In 1992, the Ameican Slee Disodes Association defined shot aousal as an aousal with a duation of 3 to 15 s. 5 Using a osective, standadized otocol, we investigated whethe the adjunction of shot aousals to the scoing of slee distubance in OSA atients yielded a stonge elationshi between (1) the AHI and subjective sleeiness mea- D. Guilleminault was the eciient of an academic awad fom the Slee Reseach Cente, the National Heat, Lung, and Blood Institute, the National Institutes of Health. Manuscit eceived July 2, 2003; evision acceted Decembe 23, Reoduction of this aticle is ohibited without witten emission fom the Ameican College of Chest Physicians ( emissions@chestnet.og). Coesondence to: Chistian Guilleminault, MD, BiolD, Stanfod Univesity Slee Disodes Clinic, 401 Quay Rd, Suite 3301, Stanfod, CA 94305; cguil@stanfod.edu CHEST / 125 / 6/ JUNE,

2 sued by the Ewoth sleeiness scale (ESS) 6 and (2) the AHI and the numbe of aousals e hou of slee (ie, the aousal index). We also evaluated the elationshis among eoted sleeiness, quality of life evaluated using the Medical Outcomes Study 36-item shot fom health suvey (SF-36), 7 the esence of deessive mood, 8 and the eoted difficulties of diving befoe teatment with nasal continuous ositive aiway essue (CPAP). Subjects Potocol Duing a 12-month eiod, male subjects between 20 and 65 yeas of age, who had been efeed fo snoing, fatigue, and/o daytime sleeiness, undewent a standadized osective otocol that included a geneal clinical evaluation, and evaluations by a slee secialist and sychiatist. Subjects who had exeienced chonic sychiatic disodes, alcoholism, dug abuse, intake of sychotoic medications (including hynotic and stimulant agents), unstable medical egimens, cicadian hythm disodes, and othe slee disodes leading to slee disution wee excluded fom the study. All othe atients, including those with a stable medical egimen (eg, hyetension medication intake) fo 6 months, wee included in the study. The otocol was esticted to men to avoid the influence of the menstual cycle. Tools All of the subjects wee inteviewed by slee disode secialists and sychiatists. They comleted the ESS 6 (which is an eight-item, 4-oint scale evaluating sleeiness in daily situations), the slee disodes questionnaie (which is a validated 180- question questionnaie using a 5-oint Liket scale to evaluate slee and its disodes), 9 the Beck deession inventoy (BDI), 8 a quality-of-life questionnaie (the SF-36), 7 and a questionnaie about the esence of sleeiness while diving and having an automobile accident due to sleeiness. The questions that addessed diving wee as follows: Have you fallen aslee at the wheel any time duing the last 2 yeas? Have you had any diving accident while sleey duing the last 2 yeas? Do you believe that this accident was elated to being sleey at the wheel? Polysomnogahy Fo the uose of the study, each subject esonding to the inclusion citeia undewent a noctunal olysomnogam with a minimum of 8 h in bed. The following vaiables wee systematically monitoed using a comuteized slee system (EMBLA; Flaga; Reykjavik, Iceland): EEG (leads C3/A2, C4/A1, O1/A2, and O2/A1); electooculogam; chin and leg electomyogam; ECG (modified V2 lead); and body osition. Resiation was monitoed using oal and nasal themistos, uncalibated thoacic and abdominal inductive esiatoy lethysmogahy, ulse oximety, and neck micohone. Data Analysis Anea and hyonea wee subdivided into cental, mixed, and obstuctive tyes. They wee scoed following the Ameican Academy of Slee Medicine ecommendations. 10 Slee was scoed following the Intenational and Ameican Slee Disodes Association citeia. 4 An aousal index (ie, the numbe of aousals e hou of slee) was calculated, and it included all aousals of 3 s in duation. Each scoed aousal was examined, and a distinction was made between beathing-elated aousals and non beathing-elated aousals. Statistical Analysis Descitive statistics using mean SD wee used. If nomally distibuted, continuous vaiables wee analyzed by Student t test. Nonaametic analysis (ie, Kuskal-Wallis test) was efomed on vaiables without nomal distibution. 2 tests wee efomed on ecentages with the Yates coection facto. If a comaison was efomed with a numbe infeio to five subjects e cell, the Fishe exact test was alied. The Seaman coelation coefficient was calculated in the investigations of quality of life. Multile egession analyses wee efomed afte the identification of significant vaiables by simle linea egession and with aoiate adjustments. Subjects Results The study included 135 male subjects. The mean ( SD) age was yeas, the mean body mass index (BMI) was kg/m 2, the mean AHI was events e h, the mean BDI was , 60 subjects (44.4%) eoted symtoms of esohageal eflux, 62 subjects (45.9%) eoted moe than one nightly eisode of noctuia, and 25 atients (18.5%) eceived antihyetensive medication. All subjects had a dives license and dove at least weekly. Twenty-five subjects (18.5%) eoted automobile accidents due to sleeiness, and 95 subjects (70.4%) acknowledged having diven while sleey. Noctunal slee vaiables and daytime scales of sleeiness ae esented in Table 1. Othe vaiables, including esiatoy vaiables duing slee, ae esented in Table 2. Anea-Hyonea Index, Slee, and Sleeiness The AHI and the lowest Sao 2 wee selected as olysomnogahic vaiables indicative of slee- Table 1 Noctunal Slee and Daytime Sleeiness Vaiables Vaiables Mean SD Total slee time, min REM slee, % SWS, % REM latency, min AHI Aousal index ESS Somnolence diving, No. 91 (67.4%) Accident due to somnolence, No. 25 (18.5%) 2092 Clinical Investigations

3 Table 2 Subscale Scoes of the SF-36 and Clinical Data Fom the Studied Subjects Vaiables Mean SD SF-36 subscales Physical functioning Role hysical Bodily ain Geneal health Vitality Social function Role emotional Mental health Age, y BDI ESS BMI, kg/m AHI, events/h Lowest Sao 2,% disodeed beathing (SDB). These two vaiables ae not indeendent of a coelation facto ( 0.665; ), but they wee each consideed indeendently, as thei imact on slee EEG may not be the same. The aousal index esented hee included all aousals 3 s in duation. As calculated fo the total gou, a mean of 7 3% of these aousals wee not elated to a beathing event. The elationshi between the AHI and the aousal index is esented in Figue 1. As can be seen, the coelation was highly significant, with a stee sloe ( 0.783; 0.001). It was also vey significant when the lowest Sao 2 and aousal index wee studied ( 0.502; ). When subjective measues of sleeiness wee consideed, the ESS scoes coelated significantly with the aousal index, as shown in Figue 2 ( 0.303; 0.001). ESS scoes coelated with AHI ( 0.338; ) and coelated negatively with the lowest Sao 2 ( 0.379; ). The two othe vaiables (ie, a eot of exeiencing sleeiness at the wheel and having had a diving accident while sleey) wee also significantly coelated with the AHI ( fo both vaiables). An investigation of slee stages showed that the degee of slee disution coelated with the selected indexes of SDB and the amounts of slow-wave slee (SWS) and aid eye movement (REM) slee. The ecentage of SWS coelated negatively with the aousal index ( 0.572; ) and with the AHI ( 0.458; ). Similaly, the ecentage of REM slee coelated negatively with the aousal index ( 0.317; ) and with the AHI ( 0.354; ). The disution of REM slee was so imotant in some subjects that the timing of REM slee also was distubed. Fou subjects had an REM slee latency (ie, slee-onset REM slee eiod) of 15 min without any signs o symtoms of nacolesy syndome. These fou subjects had a mean age of Figue 1. Coelation between AHI and aousal index. The AHI is exessed as the numbe of events e hou of slee, and the aousal index is exessed as the numbe of aousals of 3s e hou of slee ( 0.783; 0.001). Figue 2. Coelation between ESS and aousal index. Aousal index is exessed as in Figue 1 ( 0.303; 0.001). The egession line is significant but is not as stee as those fo othe vaiables. This diffeence may be elated to the limitations of the ESS. 11,12 CHEST / 125 / 6/ JUNE,

4 yeas, a mean BMI of kg/ m 2, a mean AHI of , a mean lowest Sao 2 of %, and mean ESS of Howeve, these esults, including the measuement of BMI, wee not significantly diffeent fom those fo the total gou (by Fishe exact test). They wee situated in the lowe quatile, howeve, fo both AHI and lowest Sao 2. Oveall, REM slee latency was significantly coelated with the aousal index ( 0.246; 0.004). Imact of Quality-of-Life Scoe The mean SF-36 subscale scoes and mean BDI values ae esented in Table 2. The oveall SF-36 scoe had no ositive coelation with AHI ( 0.58; 0,533). Each subscale of the SF-36 was studied, and coelation coefficients wee calculated. The following fou diffeent vaiables wee consideed: the AHI; the mean Sao 2 ; the lowest Sao 2 ; and the aousal index. They ae esented in Table 3. The only significant coelations with the AHI wee with the hysical functioning and geneal health subscales of the SF-36. Thee was no coelation with the mean Sao 2, and only one coelation with the mean lowest Sao 2 (the bodily ain subscale). The significant coelations between the aousal index and the SF-36 subscales wee the hysical functioning subscale with the AHI and the ole hysical subscale. None of the coefficients, even if statistically significant, wee vey high, and all wee indicative of the ecetion of an oganic disode. Relationshi Between Subjective Sleeiness and Clinical Vaiables We conside high scoes on the ESS and eots of sleeiness while diving as indicatos of subjective daytime sleeiness. These vaiables wee studied as deendent vaiables. We conside the following vaiables to be clinically elevant: aousal index; AHI; lowest Sao 2 ; total slee time; age; ofessional activity; and BMI. A linea egession with aoiate adjustment was efomed to identify the vaiables needed fo a multile egession analysis (ie, age, BMI, and AHI), with ESS as the deendent vaiable. Afte adjusting fo age, AHI, and BMI, age ( 0.001) and AHI ( 0.005) wee the significant vaiables. The model exlained 41% of the vaiance ( 0.41; F statistic 11.7; vaiance with age: 0.02; 0.07; and vaiance with AHI: 0.01; 0.006). When we conside the eot of diving accidents as the deendent vaiable, none of the indeendent vaiables laced in the egession is significant. Fo examle, the AHI has a value of With a eot Table 3 Coelation Coefficients Between SF-36 Subscales and Resiatoy Vaiables* PF RP BP GH V SF RE MH Vaiables AHI Aousal index Sao 2 Mean Lowest *PF hysical functioning; RP ole hysical; BP bodily ain; GH geneal health; V vitality; SF social functioning; RE ole emotional; MH mental health Clinical Investigations

5 of sleeiness while diving as the deendent vaiable, only AHI was initially significantly coelated ( 0.04), but the model exlained only 3% of the vaiance ( 0.03). When we adjust fo BMI and age, this significant elation disaeas. Thus, none of the studied vaiables ae significant with esect to self-eoted sleeiness while diving and/o having diving accidents. Comments Contovesies exist about the elationshi between OSA and daytime sleeiness. 2 4 Thee ae also contovesies about the elationshi between olysomnogahic indexes of OSA and disutions in EEG duing slee. The latte contovesy is of long standing, as studies 2 in the 1980s showed no significant elationshi between AHI and EEG changes duing slee, aticulaly those that indicate aousals. In theoy, daytime consequences (ie, sleeiness and fatigue) ae elated to noctunal slee disution. One ossibility fo the absence of coelation between OSA and EEG may elate to the scoing of slee, aticulaly the absence of tabulating shot aousals. Ou study indicates that the scoing of shot (ie, 3 s) EEG aousals leads to a stonge coelation than those eviously ublished. To assue scoing consistency in the scoing of shot EEG aousals, one individual scoed all of the obtained ecods. Also, the inclusion/exclusion citeia wee designed to limit the isk of confounding conditions that could be esonsible fo shot EEG aousals. Much effot was made to closely follow the otocol. The total numbe of aousals was taken into consideation, but most (mean, 93%) wee elated to abnomal beathing duing slee in this gou of clea OSA atients. The esults show that a coelation between the aousal index and OSA is shown when AHI and lowest Sao 2 ae selected as the indexes of SDB. Othe slee indexes, including the ecentage of SWS, the ecentage of REM, o REM slee latency, also coelate well with AHI and lowest Sao 2, as did the indicatos of subjective sleeiness. These findings ae not too suising, and confim that significant coelations can be obtained between subjective comlaints and olygahic findings. Often, a delay in the aeaance of REM slee is seen in OSAS atients, but, as aleady obseved, 3 slee onset REM slee eiods can be seen in some atients. The fou subjects in which these occued wee in the ue quatile fo the numbe of aousals. At the end of the osective study, teatment with nasal CPAP comletely eliminated these eiods of slee onset REM slee. If thee ae significant coelations between noctunal slee distubances and the fequency of SDBelated aousals, one may ague, howeve, that, even if stengthened with a tabulation of shot aousals, the olysomnogahic measues did not coelate stongly with the subjective measuements of sleeiness. The ESS, fo examle, exlains only 9% of the vaiance in subjective sleeiness. A stong debate exists on the elationshi between data fom one night of olysomnogahy and scales looking at a much longe time eiod One ossibility is that othe EEG makes of slee disution have to be integated. Tezano et al 14 have emhasized that cyclical altenating attens should be systematically studied in atients with slee disodes. Cyclical altenating attens encomass not only the shot EEG aousals descibed in 1992, but take into account the instability to slee as elated to abnomal beathing. Bette analyses of EEG changes, including the ecently oosed detection of esiatoy cycle-elated EEG changes in SDB by Chevin et al, 15 also may ovide futhe useful infomation. Coelations between quality-of-life measuements and the olysomnogahic vaiables wee shown, and the aousal index was one of the vaiables. The ole hysical and hysical functioning subscales of the SF-36 coelated with the aousal index, the geneal health and hysical functioning subscales coelated with the AHI, and lowest Sao 2 coelated with the bodily ain subscale. The abnomal scoes obtained with the subscales geneal health, hysical functioning, ole hysical, and bodily ain indicate that the atients eceived that an oganic health oblem had been imaiing thei quality of life moe than an emotional oblem, desite elevated scoes on the BDI. The contovesy about the existence of OSA atients with AHIs of 30 events e hou of slee without subjective sleeiness could not be esolved with this study, since the enty citeia included comlaints of daytime fatigue o sleeiness, as confimed by ESS scoes. 16 Desite the imovement in coelations between seveal olysomnogahic vaiables and subjective eots, the comlex issue of sleeiness while diving in atients with OSAS was incomletely esolved. A lage numbe of subjects (91 subjects; 67%) eoted the esence of sleeiness while diving. The AHI was initially the only significant vaiable in the egession analysis that exloed the ole of seveal indeendent vaiables in the exlanation of the diving oblem, and when we adjusted the model fo age and BMI, it became nonsignificant. Clealy, othe factos not consideed in the study, and not diectly associated with the olysomnogahic vaiables tabulated hee, had a much geate imact on this eot. As mentioned above, one ossibility is CHEST / 125 / 6/ JUNE,

6 that othe EEG makes of slee disution have to be integated. 14,15 Indeendently of the intoduction of these new citeia and to bette define the seveity of the slee imaiment elated to the beathing disode, one should be citical in the isk attibution to only one vaiable (SDB hee) when consideing the comlex behavio of diving. Linking the obstuctive slee aneic events and thei associated olygahic changes to sleeiness while diving, which is a common tendency with these atients, may be an ovegenealization 17 even if diving accidents may be eoted moe often in OSAS atients. 18,19 Seveal studies of slee deivation and slee estiction have shown that thee ae imotant individual diffeences in diving imaiment due to slee distubance. Also, the esence of daytime fatigue o sleeiness may lead to behavioal adjustments to avoid it. Finally, the seveity of sleeiness while diving may be unmasked only in secific conditions, such as long diving, diving at secific times of the day, o adjunction of anothe facto (eg, slee estiction o the need fo geate attention to diving). The OSAS may lead to slee estiction elated to difficulties on the job, the need to efom fo longe eiods of time due to seconday tiedness, slowe efomance duing the day, and the seconday eduction of total slee time. Ou finding is of a cautionay natue. The teatment of OSA may eliminate one facto involved in sleeiness while diving but may not comletely eliminate the oblem. This should lead to a systematic eassessment of the diving difficulties afte seveal months of teatment to avoid an unjustified sense of secuity with the escition and aoiate use of nasal CPAP. Finally, anothe cautionay note. Ou study was efomed in men, and the age ange (39 to 67 yeas) is well-suited to the majoity of OSAS atients, but ou study ovides no infomation on women and does not conside eldely subjects. ACKNOWLEDGMENT: We thank Stehen Books, MD, fo his editing of the manuscit. Refeences 1 Rechtschaffen A, Kales A, eds. A manual of standadized teminology, techniques and scoing systems fo slee stages of human subjects. Los Angeles, CA: Bain Infomation Sevice/Bain Reseach Institute, Univesity of Califonia Los Angeles, Roth T, Hatse KM, Zoich F, et al. Multile nas and evaluation of daytime sleeiness in atients with ue aiway slee anea. Slee 1980; 3: Guilleminault C, Patinen M, Quea-Salva MA, et al. Deteminants of daytime sleeiness in obstuctive slee anea. Chest 1988; 94: Patinen M, Guilleminault C. Daytime sleeiness and vascula mobidity at seven-yea follow-u in obstuctive slee anea atients. Chest 1990; 97: Ameican Slee Disodes Association. EEG aousals scoing ules and examles: a eliminay eot fom the Slee Disodes Atlas Task Foce of the Ameican Slee Disodes Association. Slee 1992; 15: Johns MW. A new method fo measuing sleeiness: the Ewoth sleeiness scale. Slee 1991; 14: Wae JE, Snow KK, Kosinski M, et al. SF-36 health suvey manual and inteetation guide. Boston, MA: The Health Institute, New England Medical Cente, Beebe D, Fine E, Holmbeck GN. Low-end secificity of fou deession measues: findings and suggestions fo the eseach use of deession tests. J Pes Assess 1996; 67: Miles L. Slee questionnaie and assessment of wakefulness. In: Guilleminault C, ed. Sleeing and waking disodes: indications and techniques. Menlo Pak, CA: Addison Wesley, 1982; Ameican Academy of Slee Medicine. Slee-elated beathing disodes in adults: ecommendations fo syndome definition and measuement techniques in clinical eseach; the eot of an Ameican Academy of Slee Medicine Task Foce. Slee 1999; 22: Chevin RD, Kaeme HC, Guilleminault C. Coelates of slee latency on the multile slee latency test in a clinical oulation. Electoencehalog Clin Neuohysiol 1995; 95: Chevin RD, Aldich MS, Pickett R, et al. Comaison of the esults of the Ewoth Sleeiness Scale and the Multile Slee Latency Test. J Psychosom Res 1997; 42: Johns MW. Slee oensity vaies with behaviou and the situation in which it is measued: the concet of somnificity. J Slee Res 2002; 11: Tezano MG, Paino L, Shieiei A, et al. Atlas, ules and ecoding techniques fo the scoing of cyclic altenating atten (CAP) in human slee. Slee Med 2001; 2: Chevin RD, Buns JW, Subotic NS, et al. Method fo detection of esiatoy cycle-elated EEG changes in slee disodeed beathing. Slee 2004; 27: Babe F, Mayoalas LR, Duan J, et al. Teatment with continuous ositive aiway essue is not effective in atients with slee anea but no daytime sleeiness. Ann Inten Med 2001; 134: Babe F, Peicas J, Munoz A, et al. Automobile accidents in atients with slee anea syndome: an eidemiologic and mechanistic study. Am J Resi Cit Cae Med 1998; 158: Geoge CF, Nickeson PW, Hanly PJ, et al. Slee anoea atients have moe automobile accidents [lette]. Lancet 1987; 2: Wu H, Yan-Go F. Self eoted automobiles accidents involving atients with obstuctive slee anea. Neuology 1996; 46: Clinical Investigations