睡眠醫學-難兄(肺) 難弟(心)

今天振華如期回來覆診，現在他日間亦不再嗜睡(Daytime Sleepiness)，連續正氣壓機(Continuous Positive Airway Pressure, CPAP) 的所有數據也十分理想。但他忽然追問我為何上次診症時再三叮噣他要好好處理血壓高和糖尿病?究竟阻塞性睡眠窒息症(obstructive sleep apnea, OSA )與前者有沒有關係? 毫無疑問振華在覆診前已上網查找過相關資料，想找我核實一下吧!

 阻塞性睡眠窒息症已經被確認是引起高血壓的一個因素(1,2)，而且患上高血壓的風險與睡眠窒息症的嚴重程度有強烈關係(3)。醫學界認為是由於睡眠窒息症在晚間引起交感神經過度活躍(excessive sympathetic activation)(4)及過多醛固酮(aldosterone)分泌有關(5)。睡眠窒息症更常見於那些耐藥高血壓 (resistant hypertension) 患者中(6,7)。而使用連續正氣壓機(CPAP) 正好減少交感神經過度活躍，從而降低血壓(8)，但病人必須每晚佩帶CPAP起碼五小時以上才有此效用(9)。一般來說在越嚴重的睡眠窒息症病人身上，CPAP越有效降低血壓(10)，而且效果亦與每晚佩帶CPAP時間成正比(11)。雖然大部份文獻匯報CPAP只能降低血壓2至3 mmHg，但相反，若果中止患上高血壓及睡眠窒息症的病人使用CPAP，那麼他們的血壓卻可以反彈5至9 mm Hg(12)。

 

振華好奇追問: 「冠心病，心律不正及心臟衰歇又和睡眠窒息症有沒有關係呢？」他果然做了不少功課! 有不少心臟衰歇的病人患有睡眠窒息症(13)，而睡眠窒息症所引起過度活躍的交感神經，會加劇病人左心室功能失調(14)。另外中樞神經性(central)及阻塞性(obstructive)睡眠窒息症同樣常見於心臟衰歇的病人，有效治療睡眠窒息症可減少此類病人的心血管病的風險(15)。心房顫震(Atrial fibrillation) 亦常見於阻塞性睡眠窒息症病人(16)，更可能引發病人突然死亡(17)，多項研究亦發現冠心病和睡眠窒息症有一定關係(18-20)。 

心血管疾病當然亦包括腦中風(stroke)，美國心臟學會(American Heart Association) 亦倡議要留心中風病人有沒有睡眠窒息症(21)，一個龐大(25,760位病人)的薈萃分析(meta-analysis)指出阻塞性睡眠窒息症病人會有更高(約常人兩倍)的腦中風危險(22)，而且這批中風病人更容易再中風(23)及死亡(24) 。至於使用CPAP能否改善病人中風後的康復及死亡率就未有定論(25,26)。 

振華忍無可忍再問我:「究竟阻塞性睡眠窒息症和糖尿病有沒有關係?」答䅁是可能有關(27-29)。我心想:「大哥同你傾了這麼久，今日門診又睇唔夠數!」

 

參考文獻:

1.    Association between severe obstructive sleep apnea and incident arterial hypertension in the older people population. Sleep Med 2013; 14: 838–842.

2.    Association between treated and untreated obstructive sleep apnea and risk of hypertension. JAMA 2012; 307: 2169–2176.

3.    Prospective study of the association between sleep-disordered breathing and hypertension. N Engl J Med 2000; 342: 1378–1384.

4.    Hypertension and obstructive sleep apnoea syndrome: current perspectives. J Hum Hypertens 2009; 23: 431–443

5.    Plasma aldosterone is related to severity of obstructive sleep apnea in subjects with resistant hypertension. Chest 2007; 131: 453–459

6.    Obstructive sleep apnea: the most common secondary cause of hypertension associated with resistant hypertension. Hypertension 2011; 58: 811–817.

7.    Prevalence and associated factors of obstructive sleep apnea in patients with resistant hypertension. Am J Hypertens 2014; 27: 1069–1078.

8.    Sympathetic-nerve activity during sleep in normal subjects. N Engl J Med 1993; 328: 303–307.

9.    The impact of continuous positive airway pressure on blood pressure in patients with obstructive sleep apnea syndrome: evidence from a meta-analysis of placebo-controlled randomized trials. Arch Intern Med 2007; 167: 757–764.

10.  Continuous positive airway pressure treatment in sleep apnea patients with resistant hypertension: a randomized, controlled trial. J Hypertens 2010; 28: 2161–2168.

11.  Effect of continuous positive airway pressure on the incidence of hypertension and cardiovascular events in nonsleepy patients with obstructive sleep apnea: a randomized controlled trial. JAMA 2012; 307: 2161–2168.

12.  Effect of CPAP withdrawal on BP in OSA. Chest 2016;150(6): 1202-10

13.  Influence of obstructive sleep apnea on mortality in patients with heart failure. J Am Coll Cardiol 2007; 49: 1625–1631

14.  The progression from hypertension to congestive heart failure. JAMA 1996; 275: 1557–1562.

15.  Heart failure and sleep disordered breathing. Curr Opin Cardiol 2016;31:224-228

16.  Obstructive sleep apnea, obesity, and the risk of incident atrial fibrillation. J Am Coll Cardiol 2007; 49: 565–571.

17.  Day-night pattern of sudden death in obstructive sleep apnea. N Engl J Med 2005; 352: 1206–1214.

18.  Sleep apnea is a stronger predictor for coronary heart disease than traditional risk factors. Sleep Breath 2012; 16: 695–701.

19.  Prospective study of obstructive sleep apnea and incident coronary heart disease and heart failure: the sleep heart health study. Circulation 2010; 122: 352–360.

20.  Increased incidence of coronary artery disease in sleep apnoea: a long-term follow-up. Eur Respir J 2006; 28: 596–602.

21.  Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/ American Stroke Association. Stroke 2014;45:2160-236

22.  Obstructive sleep apnea and risk of cardiovascular disease and all-cause mortality: a meta-analysis of prospective cohort studies. Int J Cardiol 2013;169:207-14.

23.  Sleep disorderd breathing and recurrence of cerebrovascular events, case-fatality, and functional outcome in patients with ischemic stroke or transient ischemic attack. J Physiol Pharmacol 2008;59(suppl 6):615-21.

24.  Early treatment of obstructive apnoea and stroke outcome: a randomised controlled trial. Eur Respir J 2011;37:1128-36.

25.  Increased incidence of non-fatal cardiovascular events in stroke patients with sleep apnoea: effects of CPAP treatment. Eur Respir J 2012;39: 906-12.

26.  Early treatment of obstructive apnoea and stroke outcome: a randomised controlled trial. Eur Respir J 2011;37:1128-36.

27.  Nocturnal intermittent hypoxia and the development of type 2 diabetes: the Circulatory Risk in Communities Study (CIRCS). Diabetologia 2010; 53: 481–488

28.  Insulin resistance and adipose-derived hormones in young men with untreated obstructive sleep apnea. Sleep Breath 2013; 17: 403–409..

29.  Sleep disordered  breathing, glucose intolerance, and insulin resistance: the Sleep Heart Health Study. Am J Epidemiol 2004; 160: 521–530.

**為保障個人私隱及達到教育效果，因此文中案例可能由真實及/或虛構病例改編而成***

 

                                        下期預告

                    老撾之旅

接受慈善團體邀請到老撾，參加這國家週年內科醫學會議(14^th Lao Internal Medicine Conference, 9-10 Feb 2017, ICTC,  Vientiane Lao PDR) ，並主講慢性阻塞性肺病 (Diagnosis & Management of COPD)。亦有機會參觀了當地醫院，院舍由蘇聯建造於八十年代。 

瞓得唔好! 點算呀?--撐住氣道、撐住度氣

一如所料睡眠測試顯示振華患上了嚴重的睡眠窒息症(OSA),他的AHI(呼吸暫停次數/Apnea-Hypopnea Index)達到一小時60多次，而他的血含氧量在睡眠時可以下跌至50%!其實他亦早知不妙，所以事前亦上網查找了不少資料。振華清楚知道連續正氣壓機(Continuous Positive Airway Pressure, CPAP) 是治療睡眠窒息症的重要方案(1)。CPAP的原理其實十分簡單-它運用加壓了的空氣撐住氣道，以致病人睡眠時呼吸道不再收窄、甚至會封閉起來(2)。但這種治療方法是治標不治本-病人使用CPAP，他的睡眠窒息症就會受到控制，但不是根治睡眠窒息症。使用CPAP亦可能引致使用者口鼻乾涸、鼻塞、面部皮膚被面罩壓傷…(3)

因此振華請教我可否單靠減肥來處理他嚴重的睡眠窒息症?每一個肥胖的睡眠窒息症病人都要減肥(1)，通過各種生活節制及改變的確可以大幅減肥及改善睡眠窒息症(4)，但可惜這種方案能否長期有效(超過五年)則存疑(5)。另外只有小撮病人能單靠減肥達致AHI少於(6,7)，究竟這種方法對中等及嚴重的睡眠窒息症是否有效更加是另一重大疑問。對二百多磅的振華來說，單靠減肥肯定不足夠，最重要是用減肥來處理睡眠窒息症是不可能即時生效，這剛剛是CPAP的好處-即用即生效!

但振華提出他經常到各地出差，帶著CPAP機過海關可能會遇上麻煩，他聽說一些特別牙膠(Mandibular Advancement Splint/MAS) 也可治療睡眠窒息症的，這個發明創作是利用醫學原理，是將下頷向前伸展定位在適當位置上，不讓舌根等軟組織擠壓到呼吸通道。這樣一來，咽喉部呼吸通道撐開，增加通氣空間，讓呼吸通暢，睡眠呼吸中止症的發生自然會減少。無疑MAS能改善AHI及日間嗜睡程度(EDS)(8)。但大部份專家都認為MAS只可應用在輕度或最多是中度睡眠窒息症而矣(9,10)。因此我們通常只會使用MAS於那些因副作用不能使用CPAP機或那些極其抗拒CPAP 的病人(1)。

這時振華顯得不耐煩:「那不如動手術一了百了吧!」可惜事情那有這麼簡單，唯有當病人的睡眠窒息症是由那些可動手術改善的結構(surgically correctable abnormality) 形成，醫生才會考慮外科手術方案:functional rhinoplasty, septoplasty, turbinoplasty, palatal surgery and orthognathic surgery…(11)。每一個病人都可能需要不同的手術方案，另外那主治團隊的專長亦影響最後的選擇。

既然振華現在還是三心兩意，我建議他先用CPAP-那是個可逆轉的(reversible) 方案。日後他仍大可選擇MAS 或手術。雖然定壓(fixed) 或自動(auto) 連續正氣壓機同樣有效，但他身為上市公司主席，不如用較昂貴的自動機(Auto-titrating CPAP)吧! 他苦笑說CPAP機的開支是否可以扣稅的? 果然是老闆! 最後請三叮噣振華要好好處理他的糖尿病和血壓，因為睡眠窒息症與心血管病是息息相關的。

參考文獻:

1.    Management of obstructive sleep apnea in adults: a clinical practice guideline from the American college of physicians> Ann Intern Med 2013;159:471-483。

2.    Continuous positive airway pressure for obstructive sleep apnea in adults. Cochrane Database Syst Rev 2006;(3):CD001106

3.    Treatment of obstructive sleep apnea in primary care. Am Fam Physician 2004;69(3):561-8

4.    Weight loss from life style interventions and severity of sleep apnoea: a systemic review and meta-analysis. Sleep Medicine 2014;15:1173-83

5.    Sustained improvement in mild obstructive sleep apnea after a diet and physical activity based life style intervention: postinterventional follow up. Am J Clin Nutr 2010;92(4):688

6.    Longer term effects of very low energy diet on obstructive sleep apnoea in cohort derived from randomized controlled trial: prospective observational follow up study. BMJ 2011:342

7.    Lifestyle intervention with weight reduction. First line treatment in mild obstructive sleep apnea. Am J Respir Crit Care med2009;179(4):320-7

8.    Mandibular advancement splint [MAS] therapy for obstructive sleep apnea-an overview and quality assessment of systemic reviews. Sleep Breath 2015;19:1101-8

9.    American academy of sleep medicine. Practice parameters for the treatment of snoring and obstructive sleep apnea with oral appliances: an update for 2005.sleep 2006;29:240-243

10.  Scottish intercollegiate guidelines network. Management of obstructive sleep apnoea/hypopnea in adults: a national clinical guideline. http://www.sign.ac.uk/pdf/sign73.pdf

11.  Surgical management of obstructive sleep apnea. Plast Reconstr 2016;137:1263-72 

 **為保障個人私隱及達到教育效果，因此文中案例可能由真實及/或虛構病例改編而成***