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萬惡肥為首-肥胖肺換氣不足綜合症

今天遇到一位特別的病人，他常常引起他人的注目，不要誤會他是什麼韓式俊男美女，相反他倒像個日本相撲手-差不多兩個振華的身形! 我喜歡叫他肥師傅，不知是否與他做中式點心師傅有關，所以有如此龐大身形。許多年前他是因急性二型呼吸衰歇(acute type II respiratory failure) 入院，當時大家都以為他患有非常嚴重的阻塞性睡眠窒息症(OSA)，但因OSA引起呼吸衰歇的情況是絕無僅有的。所以我的團隊相信他實在是患上肥胖肺換氣不足綜合症(Obesity Hypoventilation Syndrome, OHS)。

事後亦証明我們的臨床診斷是正確-有30-70% OHS病人會因急性二型呼吸衰歇(acute type II respiratory failure) 入院(1)。當時大家對處理OHS的經驗甚少，所以借用了處理慢阻肺病急性發作(AECOPD)的方案，使用了高低正氣壓呼吸機(Bi- Level Positive airway pressure, Bilevel Therapy) 來改善肥師傅的呼吸衰歇情況，誤打誤撞下病人的病情穩定下來(2) ，不過相比慢阻肺病病人，肥師傅的反應較遲緩，其實這正是OHS 病人典型的表現(3) 。稍後肥師傅亦可以轉用連續正氣壓機(Continuous Positive Airway Pressure, CPAP) 出院。

大家對肥人患上阻塞性睡眠窒息症不會感到陌生，但什麼是肥胖肺換氣不足綜合症(Obesity Hypoventilation Syndrome, OHS)? 傳統上是指那些: 日間血含二氧化碳(PaCO2 >45mm Hg) ；BMI(BODY MASS INDEX) >30kg/m² ；又沒有其他明顯病因引起的慢性肺泡換氣不足(chronic alveolar hypoventilation) 的症候(4)。其病理十分複雜: 中央肥胖引致橫隔膜活動受制、肺容量減少、用作呼吸的肌肉功能失調…(5,6)。一般來說病人越肥血中含二氧化碳量越高(7)。另外阻塞性睡眠窒息症亦常見於OHS的病人(8)。內分泌失調(Leptin and insulin like growth factor-1)也可能扮演一定角色(9,10) 。

OHS 會帶來病人心血管和身陳代謝的改變(11)，OHS病人會比OSA病人更常有肺動脈高壓(pulmonary hypertension)(12)，因而傷害健康及日常活動量(13)。一旦OHS病人需要入院接受治療，他們的病情大多嚴重，甚至要住院多時或入住深切治療部(14)，前景(prognosis)亦不太樂觀(15) 。所以肥師傅上次是死裹逃生。要診斷OHS同樣要經睡眠測試(PSG)及量度病人睡眠時的血含二氧化碳量(16)。

第一線治療OHS的方案是利用正氣壓呼吸機(Positive Airway Pressure, PAP) 來逆轉其病理，連續正氣壓機(CPAP) 大多數已經能改善50-80% OHS病人的病情(17)，但自動連續正氣壓機(auto-titrating CPAP)卻不適用於OHS。若果CPAP 不能令病人的含氧量高於90%，那麼就應轉用高低正氣壓呼吸機(Bi-Level Positive airway pressure, Bilevel Therapy)(18)。幸好有部份病人在病情穩定後可以轉回用較經濟的CPAP(19)，肥師傅的情況就是個好例子。不過有10-20%的OHS病人不肯接受正氣壓呼吸機治療(PAP)，亦有另外10-20% 病人使用PAP的情況不理想(20,21)。單獨使用氧氣治療不單無助醫治OHS，甚至可能加重病人血中二氧化碳量(22,23)，但若果病人使用PAP後，血含氧量仍不達標，那麼這時就要加上氧氣治療(17,19)，不過仍然要小心觀察病人的血中二氧化碳量(20,24) 會否隨之上升。

 成功減肥當然可以大大改善OHS(25)的病情，但手術比其他方案更能保持”瘦身” 效果(26)。藥物治療對OHS是起不了大作用的(27,28)。但我嚇然發現肥師傅這些年來從未成功減過肥。他笑笑口說:「下次先至講呢樣! 減肥是終身事業、不用急的。」

 參考文獻:

1.    Obesity-hypoventilation syndrome: increased risk of death over sleep apnea syndrome. PLoS One. 2015;10(2):e0117808.

2.    Noninvasive ventilationin acute hypercapnic respiratory failure caused by obesity hypoventilation syndrome and chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2012;186(12):1279-1285.

3.    Determinants of noninvasive ventilation success or failure in morbidly obese patients in acute respiratory failure. PLoS One. 2014;9(5):e97563.

4.    Obesity hypoventilation syndrome: Does the current definition need revisiting? Thorax. 2014;69(1):83-84.

5.    Obesity hypoventilation syndrome–the big and the breathless. Sleep Med Rev. 2011;15(2):79-89.

6.    Observational study of the effect of obesity on lung volumes. Thorax. 2014;69(8): 752-759.

7.    Obesity-associated hypoventilation in hospitalized patients: prevalence, effects, and outcome. Am J Med. 2004;116(1):1-7.

8.    Hypercapnia and ventilatory periodicity in obstructive sleep apnea syndrome. Am J Respir Crit Care Med. 2002;166(8): 1112-1115

9.    Pleiotropic role of IGF-I in obesity hypoventilation syndrome. Growth Horm IGF Res. 2010;20(2):127-133.

10.  Association of serum leptin with hypoventilation in human obesity. Thorax. 2002;57(1):75-76.

11.  Morbidity prior to a diagnosis of sleep-disordered breathing: a controlled national study. J Clin Sleep Med. 2013;9(2):103-108

12.  The obesity hypoventilation syndrome revisited: a prospective study of 34 consecutive cases. Chest. 2001;120(2):369-376.

13.  Pulmonary hypertension in obesity-hypoventilation syndrome. Respir Med. 2013;107(12): 2061-2070.

14.  Obesity-associated hypoventilation in hospitalized patients: prevalence, effects, and outcome. Am J Med. 2004;116(1):1-7.

15.  Comorbidities and mortality in hypercapnic obese under domiciliary noninvasive ventilation. PLoS One. 2013;8(1):e52006

16.  Volume targeted versus pressure support non-invasive ventilation in patients with super obesity and chronic respiratory failure: a randomised controlled trial. Thorax. 2012;67(8):727-734.

17.  Impact of adherence with positive airway pressure therapy on hypercapnia in obstructive sleep apnea. J Clin Sleep Med. 2006;2(1):57-62.

18.  Continuous positive airway pressure in clinically stable patients with mild-to-moderate obesity hypoventilation syndrome and obstructive sleep apnoea. Respirology. 2013;18(7):1135-1142.

19.  Randomised trial of CPAP vs bilevel support in the treatment of obesity hypoventilation syndrome without severe nocturnal desaturation. Thorax. 2008;63(5):395-401.

20.  Long-term outcome of noninvasive positive pressure ventilation for obesity hypoventilation syndrome. Chest. 2010;138(1):84-90.

21.  Short-term and long-term effects of nasal intermittent positive pressure ventilation in patients with obesity-hypoventilation syndrome. Chest. 2005; 128(2):587-594.

22.  Moderate concentrations of supplemental oxygen worsen hypercapnia in obesity hypoventilation syndrome: a randomised crossover study. Thorax. 2014;69(4):346-353.

23.  The effect of supplemental oxygen on hypercapnia in subjects with obesity-associated hypoventilation: a randomized, crossover, clinical study. Chest. 2011;139(5):1018-1024.

24.  Mortality and prognostic factors in patients with obesity-hypoventilation syndrome undergoing noninvasive ventilation. J Intern Med. 2007;261(4):375-383.

25.  Current concepts in the pathogenesis of the obesity-hypoventilation syndrome. Mechanical and circulatory factors. Am J Med. 1974;57(3):402-420.

26.  Swedish Obese Subjects Study. Effects of bariatric surgery on mortality in Swedish obese subjects. N Engl J Med. 2007;357(8):741-752.

27.  Short-term medroxyprogesterone acetate in postmenopausal women with sleep disordered breathing: a placebo-controlled, randomized, double blind, parallel-group study. Menopause. 2014;21(4):361-368.

28.  Hypercapnic respiratory failure in obesity-hypoventilation syndrome: CO2 response and acetazolamide treatment effects. Respir Care. 2010;55(11):1442-1448.

**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

 

         睡眠醫學-嗚下、嗚下揸車好危險!

有機會與振華(假名)再茶聚時，自不然問候他的阻塞性睡眠窒息症(Obstructive Sleep Apnea, OSA)情況，振華經使用連續正氣壓機(Continuous Positive Airway Pressure, CPAP)後，日間嗜睡的情度大幅改善，他回想上一次在高速公路上架駛時睡著了真是驚險萬分!其實患有阻塞性睡眠窒息症的司機比其他司機有多2至10倍的撞車風險(1,2)。由於振華經常返回內地各處做生意，因此需要乘搭各類型長途車，他間中也會發現長途車司機架駛時打瞌睡，情況令乘客提心吊膽!

 振華一派嚴肅地問我患有阻塞性睡眠窒息症的司機是否適合”揸車”? 我們首先要分開私家車司機和商業車司機來討論。醫學界暫時未能訂立任何指標來判斷一個司機是否適合”揸車”，振華自作聰明說:「簡單用呼吸暫停次數/Apnoea-Hyponea Index ,AHI 就可以吧!」不同醫學團體的確曾經提議不同的AHI劃線(由AHI 20至40不等)來禁止司機”揸車”。可惜一個司機會否撞車與他的AHI度數沒有強烈關係(3)。相反司機是否曾經因架駛時入睡引致撞車的歷史更有預測性(4-5)，了解病人的嗜睡情度(用愛普渥斯嗜睡度量表/The Epworth Sleepiness Scale來評估)可能有幫助(6)，但使用其他複雜的測試(eg, multiple sleep latency test or maintenance of wakefulness test[7]) 就未必更有效用。

患有阻塞性睡眠窒息症的司機接受了CPAP治療後，若果他再沒有日間嗜睡的問題及架駛時入睡，那麼我們相信他可以安全架駛，不過這些有OSA的司機必需堅持有七成日子每晚使用四小時CPAP以上(8)，至於那些使用Oral Appliance, OA 的司機又如何? 有權威人仕相信唯有那些使用OA後能達至AHI少於10才適合”揸車”， 不過這些OSA司機同樣必需堅持有七成日子每晚使用OA四小時以上(9)。

在歐美國家，無論是立法機關或醫學界，對於商(職)業車司機的要求是更高的(10,11)。可是一個本地調查(有1016個巴士司機參與)(12)發現24%的司機曾經在架駛時打瞌睡。其中211個巴士司機接受了睡眠測試，原來竟然有17.5%的司機患上了睡眠窒息症(AHI>15/h)! 與之前另外一個小型研究(只有216個巴士司機參與)的結果接近(13) ，可惜香港在這方面沒有嚴格的規管。其實要時常安全架駛，真是每一位司機(有無OSA)的必然責任!

 

參考文獻:

1.    Cost-effectiveness of continuous positive airway pressure (CPAP) for moderate to severe obstructive sleep apnea hypopnea. Arch Intern Med 2006;166:977-84.

2.    Systematic review of motor vehicle crash risk in persons with sleep apnea. J Clin Sleep Med 2009;5:573-81

3.    Risk and severity of motor vehicle crashes in patients with obstructive sleep apnoea/ hypopnoea. Thorax 2008;63:536-41

4.    Factors associated with serious traffic crashes: A prospective study in southwest France; CESIR Group. Arch Intern Med 2012;172:1039-41.

5.    Sleepiness, near-misses and driving accidents among a representative population of French drivers. J Sleep Res 2010;19:578-84.

6.    New method for measuring daytime sleepiness: The Epworth Sleepiness Scale. Sleep 1991;14:540-5.

7.    Can the MSLT be a useful tool to assess motor vehicle crash risk in sleepy drivers? Sleep 2010;33:729-30.

8.    An Official American Thoracic Society Statement: Continuous positive airway pressure adherence tracking systems: The optimal monitorings strategies and outcome measures in adults. Am J Respir Crit Care Med 2013;188:613-20. 22.

9.    Obstructive sleep apnea and driving: A Canadian Thoracic Society and Canadian Sleep Society position paper. Can Respir J 2014;21(2):114-123.

10.  Statement from the joint task force of the American college of chest physicians, the American college of occupational and environmental medicine, and the national sleep foundation: sleep apnea and commercial motor vehicle operators. Chest 2006;130:902-5

11.  New rules on driver licensing for patients with OSA: EU directive 2014/85/EU. Eur Respir J 2016;47:39-41

12.  Sleep disordered breathing and continuous positive airway pressure compliance in a group of commercial bus drivers in Hong Kong. Respirology 2006;11(6):723-30

13.  Prevalence of snoring and sleep disordered breathing in a group of commercial bus drivers in Hong Kong. Internal Medicine Journal 2002;32(4):149-57

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