睡眠醫學二十四之除CPAP以外

最近再次與偉民(假名)茶聚時，自不然問候他睡眠窒息症(Obstructive Sleep Apnea, OSA)的情況，他卻滿腹牢騷地投訴連續正氣壓機(CPAP)的各種不是。雖然CPAP能改善他睡眠窒息症的病徵，但卻是個治標不治本的方案，要”成世人”晚晚都用CPAP超過四小時! 大多數病人真的很難有如此恆心。我也明白偉民的感受。大部份研究亦發現病人對CPAP 的遵從性[Adherence] 不高，新型的面罩及CPAP 機也無助改善這個現象[1]。身形龐大的偉民好奇地問我:「減肥是否可根治睡眠窒息症?」從各種關於減肥的研究[包括改變飲食習慣及減肥手術] 結果來說，減肥的確有助改善睡眠窒息症的病情，但卻甚少能根治睡眠窒息症 [2,3]，而且不能及不應在極短時間內大幅度減肥，否則更加危害健康。

而特制的牙膠[ ORAL APPLIANCE,OA] 有助將下顎[Mandible]及或脷拉前，從而防止病人在睡眠時上氣道崩塌[upper airway collapse]。而OA治療睡眠窒息症的效能在乎儀器能將下顎拉前多少[4-6] ，但OA亦有一定的副作用: 分泌過多口水、口腔或牙肉不適、牙關及其肌肉拉緊[7]，雖然這些副作用大多是輕微和短暫，但已令某些人放棄OA的治療[8]，長期使用OA亦會令病人面相有所改變[9]。醫生一般只會對患上輕度睡眠窒息症的病人使用OA， OA醫治睡眠窒息症的效能確實較CPAP次優，病人使用OA後可能每小時仍有15至20次的窒息[10] 。但由於病人對CPAP的遵從率[adherence] 偏低，最後OA 的整體的治療效果亦能達至與CPAP相若[11-14]，而且同樣能降低血壓[15-16] 。當然如果病人增肥了，OA的醫療效率自然會下降[17]。

近年本港相當流行一種口腔運動[oropharyngeal exercise/myofunctional therapy]，它是源於語言治療[consisting of isometric and isotonic exercises involving the tongue , soft palate and lateral pharyngeal wall][18]，初步研究發現此等口腔運動對睡眠窒息症有一定裨益[19-20]，但病人要有持之以恆，勤於練習才能發揮功效，情況與使用CPAP治療睡眠窒息症相似-靠恆心!

這時我從口袋中取出兩片特殊鼻貼名為Nasal EPAP，這個小玩意是分別貼在病人兩個鼻孔，當病人吸氣時，外邊的空氣在沒有任何阻擋的情況下被吸入鼻孔內；呼氣時活門卻關上，鼻孔內空氣只能從兩個小孔呼出，氣管壓力因而增加，將受堵塞的呼吸道打開打開。[These valves operate by utilizing the patient’s own breathing to create a positive end-expiratory pressure with minimal inspiratory resistance. This high end-expiratory pressure leads to upper airway dilation with subsequent tracheal traction and increased lung volumes during exhalation, thereby making the upper airway more resistant to narrowing/closure during ensuing inspiration] [21-22] 。本港威爾斯醫院亦發表過關於這個儀器的小型研究[23]，發現nasal EPAP 對睡眠窒息症有一定的舒緩作用，若病人不考慮CPAP的話，nasal EPAP 是其中一種另類選擇。較大型的醫學回顧[systemic review] 亦發現病人使用nasal EPAP 後可減少一半窒息次數[24]，奈何暫時不知 nasal EPAP對那類病人最有效[25]。由於病人要每天更換 Nasal EPAP ，所以長期使用nasal EPAP的費用實在不輕，因而亦會影響它的流行性。

美國藥物管理局[USA Food and Drug Administration, FDA]最近批淮了一個類似心臟起搏器的儀器[UPPER AIRWAY STIMULATION, UAS]，作醫治睡眠窒息症之用，其原理是當病人入睡了，UAS會刺激病人特定的神經線[HYPOGLOSSAL nerve] 令病人的脷及軟齶[soft plate] 移動，從而擴闊了氣道 [retrolingular and retropalatal airways][26] 。

總括來說，在各種另類治療睡眠窒息症方案之中，唯有牙膠 [Oral Appliance] 擁有豐富的醫學實證，但CPAP 仍是醫治阻塞性睡眠窒息症的第一線有效策略。

參考文獻:

1.Trends in CPAP adherence over twenty years of data collection: a flattened curve. J. Otolaryngol. Head Neck Surg. 2016; 45: 43.

2. The impact of bariatric surgery on obstructive sleep apnea: a systematic review. Obes. Surg. 2013; 23: 414–23

3.Weight loss from lifestyle interventions and severity of sleep apnoea: a systematic review and meta-analysis. Sleep Med. 2014; 15: 1173–83.

4.Mandibular advancement for obstructive sleep apnea: dose effect on apnea, long-term use and tolerance. Respiration 2008; 76: 386–92.

5.Mandibular advancement titration for obstructive sleep apnea: optimization of the procedure by combining clinical and oximetric parameters. Chest 2004; 125: 1761–7.

6. An evaluation of a titration strategy for prescription of oral appliances for obstructive sleep apnea. Chest 2008; 133: 1135–41.

7. Oral appliances for snoring and obstructive sleep apnea: a review. Sleep 2006; 29: 244–62.

8.Effects of mandibular posture on obstructive sleep apnea severity and the temporomandibular joint in patients fitted with an oral appliance. Sleep 2002; 25: 507–13.

9. Predictors of long-term orthodontic side effects from mandibular advancement devices in patients with snoring and obstructive sleep apnea. Am. J. Orthod. Dentofacial Orthop. 2006; 129: 214–21.

10. Cardiovascular mortality in obstructive sleep apnoea treated with continuous positive airway pressure or oral appliance: an observational study. Respirology 2013; 18: 1184–90.

11. Efficacy of positive airway pressure and oral appliance in mild to moderate obstructive sleep apnea. Am. J. Respir. Crit. Care Med. 2004; 170: 656–64.

12. The effects of 1-year treatment with a herbst mandibular advancement splint on obstructive sleep apnea, oxidative stress, and endothelial function. Chest 2007; 131: 740–9.

13. Mandibular advancement device and CPAP upon cardiovascular parameters in OSA. Sleep Breath. 2014; 18: 749–59.

14. Microvascular endothelial function in obstructive sleep apnea: impact of continuous positive airway pressure and mandibular advancement. Sleep Med. 2009; 10: 746–52.

15. Health outcomes of continuous positive airway pressure versus oral appliance Treatment for obstructive sleep apnea: a randomized controlled trial. Am. J. Respir. Crit. Care Med. 2013; 187: 879–87.

16. CPAP vs mandibular advancement devices and blood pressure in patients with obstructive sleep apnea: a systematic review and meta-analysis. JAMA 2015; 314: 2280–93.

17. Mandibular advancement devices in 630 men and women with obstructive sleep apnea and snoring: tolerability and predictors of treatment success. Chest 2004; 125: 1270–8.

18. Effects of oropharyngeal exercises on patients with moderate obstructive sleep apnea syndrome. Am. J. Respir. Crit. Care Med. 2009; 179: 962–6.

19. Myofunctional therapy to treat obstructive sleep apnea: a systematic review and meta-analysis. Sleep 2015; 38: 669–75.

20. Effect of speech therapy as adjunct treatment to continuous positive airway pressure on the quality of life of patients with obstructive sleep apnea. Sleep Med. 2013; 14: 628–35.

21. Changes in lung volume and upper airway using MRI during application of nasal expiratory positive airway pressure in patients with sleep disordered breathing. J. Appl. Physiol. (1985) 2011; 111: 1400–9.

22 Lung volume and continuous positive airway pressure requirements in obstructive sleep apnea. Am. J. Respir. Crit. Care Med. 2005; 172: 114–7.

23. Role of nasal positive end expiratory pressure valve as an alternative treatment of obstructive sleep apnea in Chinese patients. Respirology 2015 doi:10.1111/resp. 12703

24. Nasal expiratory positive airway pressure devices (Provent) for OSA: a systematic review and meta-analysis. Sleep Disord. 2015; 2015: 734798.

25. Predictors of response to a nasal expiratory resistor device and its potential mechanisms of action for treatment of obstructive sleep apnea. J. Clin. Sleep Med. 2011; 7: 13–22.

26. Effect of upper-airway stimulation for obstructive sleep apnoea on airway dimensions. Eur. Respir. J. 2015; 45: 129–38.

                      走出安舒區

在過去的復活節，舉家搬離住了二十多年的社區，搬到現在工作機構的附近，以便夜間需要工作時更加方便。以前一直住在新界地區，空氣清新，環境十分零靜，家居甚為寬敞。新居卻位於市中心，幸好是座落於一條較安靜的橫街，但人聲及車聲仍然少不了。居所是一座已有四十多年歷史的獨立式大廈，業主也沿用原裝的鐵窗，這下子真的可以一嘗鐵窗風味了! 房子始於是有四十多年樓齡，設計和設備都是已過時的，新居亦比舊的細少了二三百呎，因此家人難免有各種埋怨。年紀老邁的母親也要重新適應這個社區，但回想這次搬家，完全是家人為我著想，減少舟車勞頓，在全新工作綱位上能更容易適應吧! 心裡甚是感激家人。

這個社區對我來說有點陌生，但又不是完全不認識? 三十年前我初入行時就在這社區的一間小型公立醫院工作了一年，但往後我就不大經常重臨這社區了。最近一次在午膳後，我不知為何就走回到這個公立醫院-我事業的起步點，一切事和人當然已經面目全非了，但我仍能找到昔日的宿舍和工作的病房，一時難免百般滋味在心頭，畢竟一轉眼已三十年過去，感嘆又回到這社區，而且是另一種身份-私人執業。看過一幅畫: 機會、奇蹟、人生另一高峰總在你的安舒區之外。以我這個臨近退休才轉工的大叔來說，要克服心理關口，離開安舒區一點也不容易。在新綱位半年多了，我開始適應了某些人、事物和處事方法，人的EQ也提昇了不少。最後連居住了二十載的社區也離開了，這次是切切底底走出我以往的安舒區-工作和生活的地域及模式來個徹底的轉變。明天是如何我不知道、也不能完全掌握。人生本來就是場冒險之旅，你不肯走出原本的安舒區，就不能發掘更多可能性! 話雖是老生常談，但對我來說卻是真實無比的。

睡眠醫學二十三之失眠加睡眠窒息症

很久沒有跟振華(假名)茶聚了，他突然電聯我，但第一句話竟然是:「唉!瞓得又死、唔瞓得重死!」我自然追問他此話何解。振華告訴我他公司最近重組分折再上市，工作壓力超巨大，所以近來他開始患上了失眠。本來他已經有睡眠窒息症需要配帶連續正氣壓機(CPAP)，現在又得了失眠--當然瞓唔著就無睡眠窒息症、但失眠就更痛苦了!

我隨即安慰振華，這兩種睡眠問題其實都是十分普遍的，學者在1973年第一次匯報這兩者並存的案例[1]。在睡眠窒息病患者中同樣出現失眠病徵的有6%至84%[2-6]，相反在那些尋求治理失眠者當中，有7至69%同時出現睡眠窒息病徵[7-11]。有理由相信這些文獻極可能低估了兩者並存的案例，原因可能是不同研究採用不同的失眠定意、不同類型的失眠又有不同睡眠窒息的病發率[2,4] 。至於失眠的發病率是否與睡眠窒息症的病情有關，不同的研究又得出相反的結論[12,13]。

患有並存病症[OSA -INSOMNIA comorbid conditions] 的人與患上單一疾病的分別如下:那些主要為睡眠窒息病徵求診的多為女性[14,15]、易有腿不寧症[restless legs syndromes][6.13]。而那些主要為失眠求診的多為男性[11,16]、肥胖及年長[7,11]、出現更多睡眠窒息病徵[17,18]。患有並存病症 [OSA -INSOMNIA comorbid conditions]的病人會更容易患上抑鬱及其他精神問題[19], 心臟病[20]，甚至不能工作[21]，但這些現象究竟是因還是果卻不得而知。

當睡眠窒息症與失眠同時發生在同一病人身上，失眠問題會影響睡眠窒息症的治療效果[22-25]: 減少病人長期依時使用連續正壓機[CPAP]。但睡眠窒息症是否會影響失眠的治療結果就不得而知[26,27]。雖然醫學界已經掌握如何治療單獨失眠及睡眠窒息症，但怎樣去醫治並存病症就並不簡單，舉例說某些安眠藥{Benzodiazepines}會加劇睡眠窒息病徵 [28,29] ，另一方面並存病患者使用連續正壓機[CPAP] 又能否改善並存的失眠呢就不得而知? 由於現在還未有完整的指引，唯有採用各種方法同時醫治失眠及睡眠窒息症吧!

說到這裡振華已呼呼入睡了! 喂未帶呼吸機[CPAP] 呀!

參考文獻:

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2. Insomnia in untreated sleep apnea patients compared to controls. J Sleep Res. 2012; 21(2):131–8.

3. Prevalence of new-onset insomnia in patients with obstructive sleep apnoea syndrome treated with nocturnal ventilatory support. Rev Port Pneumol. 2012; 18(1):15–21.

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5. Relationships between insomnia and sleep-disordered breathing. Chest. 2003; 123(1): 310–1.

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7. Polysomnography reveals unexpectedly high rates of organic sleep disorders in patients with prediagnosed primary insomnia. Sleep Breath. 2012; 16(4): 1097–103.

8. Sleep apnea in elderly adults with chronic insomnia. J Am Geriatr Soc. 2012; 60(12):2366–8.

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10. Prevalence and prediction of primary sleep disorders in a clinical trial of depressed patients with insomnia. J Clin Sleep Med. 2009; 5(5):454–8.

11. Frequency and predictors of obstructive sleep apnea among individuals with major depressive disorder and insomnia. J Psychosom Res. 2009; 67(2):135–41.

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13. Insomnia complaints in patients evaluated for obstructive sleep apnea. Sleep Breath. 2005; 9(3):104–10

14. Gender and ethnic differences in prevalence of self-reported insomnia among patients with obstructive sleep apnea. Sleep Breath. 2011; 15(4): 711–5.

15. Differences between men and women in the clinical presentation of patients diagnosed with obstructive sleep apnea syndrome. Sleep. 2005; 28(3):309– 14.

16. Occult sleep apnea in a recruited sample of older adults with insomnia. J Consult Clin Psychol. 1999; 67(3):405–10

17. Consequences of comorbid insomnia symptoms and sleep-related breathing disorder in elderly subjects. Arch Intern Med. 2006; 166

18. Sleep apnea in elderly adults with chronic insomnia. J Am Geriatr Soc. 2012; 60(12):2366–8.

19. Frequency of insomnia report in patients with obstructive sleep apnoea hypopnea syndrome (OSAHS). Sleep Med. 2004; 5(5):449–56.

20. Sleep apnea-plus: prevalence, risk factors, and association with cardiovascular diseases using United States population-level data. Sleep Med. 2012; 13(6):637–44

21. The joint contribution of insomnia and obstructive sleep apnoea on sickness absence. J Sleep Res. 2013; 22(2):223–30

22. Clinical co-morbidities in obstructive sleep apnea syndrome treated with mandibular repositioning appliance. Respir Med. 2006; 100(6):988– 95.

23. Sleep maintenance insomnia complaints predict poor CPAP adherence: a clinical case series. Sleep Med. 2010; 11(8):772–6

24. Insomnia symptoms influence CPAP compliance. Sleep Breath. 2013; 17(1):99–104.

25. Determinants of continuous positive airway pressure adherence in a sleep clinic cohort of South Florida Hispanic veterans. Sleep Breath. 2013; 17(1): 351–63.

26. Is the treatment of insomnia impared when OSA is also present? Sleep. 2011; 34(Abstract Supplement):508.

27. Insomnia related to sleep apnoea: effect of long-term auto-adjusting positive airway pressure treatment. Eur Respir J. 2013; 41(3):593–600

28. Triazolam in patients with obstructive sleep apnea. Am J Respir Crit Care Med. 1995; 151(2 Pt 1):450–4.

29. Effect of flurazepam on sleep-disordered breathing and nocturnal oxygen desaturation in asymptomatic subjects. Am J Med. 1982; 73(2):239–43.