Further reading Abramov Y, Elchalal U, Schenker JG. Pulmonary manifestations of severe ovar ian hyperstimulation syndrome: a multicenter study. Fertil Steril 1999; 71: 645 \200\223651 . Halla JT, Schronhenloher RE, Volanakis JE. Immune complexes and other laboratory features o f pleural effusions. Ann Intern Med 1980; 92: 748 \200\223752. Light RW. Pleural effusions after coronary artery bypass graft surgery. Curr Opin Pulm Med 2002; 8: 308 \200\223311. N MASKELL 352 14.9 Pleural infection Epidemiology Pleural effusions occur in up to 40% of patients with pneu- monia. Pleural inf ection affects patients of all ages but is more common in children and the elderly. Men are affected twice as often as women. Its incidence is higher in those with diabetes, alcoholi sm, substance abuse and chronic lung disease. Class 2 \200\223 typical parapneumonic: >10mm thick, glucose >40 mg/dl, pH > 7.2. \200 Class 3 \200\223 borderline complicated: pH 7.0-7.2 or LDH >1000 Gram stain negative. \200 Class 4 \200\223 simple complicated: pH < 7.0 or Gram stain positive. No loculation or frank pus. \200 Class 5 \200\223 complex complicated: 0 0 1 pH < 7.0 Gram stain positive. Loculations. \200 Class 6 \200\223 Simple empyema: 0 8 Frank pus, single locule or free \202 owing. \200 Class 7 \200\223 Complex empyema: Frank pus, multiple loculations. 0 6 y c n e u q e r F Differential diagnosis The commonest problem with the differential diagnosis is failure to make the correct positive diagnosis. Often the presentation is indolent (especially in the elderly) with weight loss and anorexia and little fever. Other possible causes for the effu sion include: \200 \200 \200 \200 0 4 0 2 0 18 \200\22324 25 \200\22334 35 \200\22344 45 \200\22354 55 \200\22364 65 \200\22374 75 \200\22384 85 \200\22394 Age group (years) Tuberculosis effusion. Malignancy. Rheumatoid pleural effusion. Pulmonary embolus with asso ciated effusion. Male Female Fig. 14.9.1 Empyema frequency. Etiology Associated conditions \200 The commonest causes of pleural infection are: \200 \200 \200 \200 \200 Lemierre \200\231s syndrome \200\223 acute oropharyngeal infection with Fusobacterium spec ies leading to septic throm- bophlebitis of the internal jugular vein, septic pulmonary emb oli and empyema. Secondary to a community-acquired pneumonia (70%). Secondary to a hospital-acquired pneumon ia (12%). Primary empyema (5%). Post operative (10%). Miscellaneous (bacteraemia, oesophage al rupture, IV drug abuse, abdominal infection/collection) (3%). Bacteriology This differs signi \201 cantly between pleural infection acquired in the comm unity and those acquire in the hospital setting. In view of this they require different emp irical antibiotics. In one large randomized trial throughout the UK the following bacteria were cultured: Pathophysiology This can be divided into three stages \200 The development of the initial effusion is due to increased permeability of the pleural membranes. Fluid moves into the space owing to lo cally increased capillary vascular permeability. The accumulating pleural \202 uid has a normal glucose level and pH. \200 Secondary bacterial invasion occurs and the high level of \201 brinolytic activity in the pleural space is suppressed and tissue plasminogen act ivator inhibitor 1 and 2 rise. This leads to \201 brin deposition over the visceral and p arietal pleura and loculations form. Bacterial metabolism lead to increased lactic acid pro duction and fall in pH. \200 Proliferation of fibroblasts and evolution of pleural scarri ng. An inelastic peel forms on both pleural surfaces with dense \201 broid septations. As solid \201 brous peel replaces the soft \201 brin lung function is impaired. The exudative phase Community acquired \200 \200 \200 \200 \200 \200 \200 \200 S. Milleri group (32%). Streptococcus pneumoniae (13%). Other Streptococci (7%). Staphyloco cci (11%). Anaerobes (16%). Enterobacteriaecea (7%). Proteus (3%). H. in \202 uenzae (3%). The \201 bropurulent phase Hospital acquired \200 MRSA (26%). \200 Staphylococci (18%). \200 Enterobacteriacea ( 16%). \200 Enterococci (13%). \200 Pseudomonas (5%). \200 Streptococci (10%). The organizing stage Classi \201 cation Light \200\231s classification of parapneumonic effusions and empyema \200 It should be noted that up to 40% of patients with pleural infection do not ever have a pos itive bacterial culture. This is partly due many having already started antibiotics before hospital presentation. Class 1 \200\223 non signi \201 cant: Small <10 mm thick. No thoracentesis required. CHAPTER 14.9 Pleural infection 353 Investigations Pleural \202 uid sampling Fluid should be sent to the laboratory for gluco se, LDH and protein measurements as well as standard cytological and microbiological invest igations. A sample of \202 uid (not frank pus) should also be placed in a heparinised syr inge and the pH measured CT \200 Useful in trying to distinguish a lung abscess from a pleu- ral collection. Also helpful in evaluating the drain position and any residual location in a patient not responding to med ical treatment where surgery is being contemplated. With a contrast CT, as with other exuda tive effusions, pleural enhancement is seen. Imaging The imaging features of parapneumonic effusion and empy- ema depend upon the state of evolution of the effusion and the underlying etiology. The imaging will also often have to be circumstance led, e.g. a ultrasound for ill unstable patients on ITU. Differentiating between a lung abscess and empyema on enhanced CT. The following rules are often useful in distinguishing a lung abscess for an empyema: Lung abscess \200 \200 \200 Chest radiology \200 Often round in shape. Vessels passing through or near. Indistinct boundary between lung par enchyma and collection. Thick and irregular wall, making contact with chest wall at acute a ngle. In general, a pleural effusion is demonstated often in association with consolidation. The effusion is commonly unilateral. If uncomplicated it behaves like a non-infected sterile ef fusion with a normal meniscus sign. If complicated it may be loculated. It will then have a lentiform, pleural based opacity. If the effusion is within a \201 ssure it may have the appearance of a \200\230pseudotumour \200\231. Empyema \200 \200 \200 \200 Lenticular in shape. No vessels closely associated. Compression of surrounding lung. Smooth margins creating obtuse angles, following contours of chest. Fig. 14.9.2 CXR of a loculated empyema. Ultrasound \200 Fig. 14.9.4 Loculated empyema on CT. The majority of parapneumonic effusions will be septated and may be hyperechoic. Whereas se ptations are readily visualized on ultrasound, pleural thickening is poorly visualized and CT is better. Treatment AUTHOR \200\231S TIP \200 A complicated parapneumonic effusion due to Proteus spp. does not result an acidic effusion . The pH of the pleural \202 uid should be measured (using an arterial blood gas machine and heparinised syringe) in all cases of suggested parapneumonic effusions. This should not be done with frank pus as it will damage the machine. A pH <7.2 is an indication that form al tube drainage will be required. Antibiotics As the microbiology is very different between community- acquired and hospital- acquired pleural infection they require different empirical antibiotic regimens at presenta tion. Possible empirical antibiotic regimens: \200 \200 Community acquired \200\223 co-amoxiclav and metronidazole. Hospital acquired \200\223 me ropenem and vancomycin. Fig. 14.9.3 Pleural ultrasound showing loculations. N MASKELL 354 The role of other \201 brinolytics are still being evaluated and the MIST 2 trial should be reporting shortly. Tube drainage The optimal size of chest tube to use in cases of pleural infection is still a subject of vigorous debate. However, patients entered into the large UK \200\223MIST 1 tr ial did just as well if a small-bore drain was inserted initially as a large-bore drain. Th ey also experienced signi \201 cantly less pain and discomfort. For this reason, the autho r would always start with a small chest tube (12 \200\22314F) and ensure that is was \202 ushed regularly (20ml normal saline 6hrly). Nutrition This is an important cornerstone of management and often overlooked until later i n the disease process. Early nutritional assessment and NG feeding if necessary is rec- omm ended. Surgery Unfortunately 20 \200\22330% of patients will fail medical manage- ment. If this oc curs then prompt referral to thoracic sur- gery is recommended. Options include: \200 \200 \200 Monitoring response to medical management The best markers of response to medical managemen t include: \200 \200 \200 Falling CRP. Settling of a spiking temperature. Clinical signs of resolution of sepsis. VATS. Open thoracotomy with decortication. Rib resection with open drainage. In the event that these indices are improving, the author would tend to avoid acting on wor rying chest radiology as this often lags signi \201 cantly behind the patient \200\231s im provement. When patients look as if they have avoided surgery by the narrowest of margins, prolonged oral antibiotics and close follow-up in out-patients with monitoring of the chest radiograph and CRP is advised. Further reading BTS guidelines on the management of pleural disease. Thorax 2003;58(Suppl II):ii1 \200\223ii59. Light RW, Lee YCG (eds). Textbook of Pleural Disease. London: Hodder Arnold, 2008. Fibrinolytics The MIST 1 trial showed no bene \201 t in giving intrapleural streptokinase to patients with pleural infection, in terms of reduced mortality or need for surgery. This page intentionally left blank G CARDILLO & D WALLER 356 14.10 Surgery for pleural diseases Spontaneous pneumothorax Primary spontaneous pneumothorax Indications: second episode; pers istent air leak (>3 \200\2234 days); failure to achieve re-expansion following drainage of a 1st episode, haemopneumothorax, 1st contralateral episode, bilateral pneumothorax. Profes sions at risk: scuba divers, pilots. Principles: closure of source of air leak; obtaining p leural adhesions. Approach: modern literature favors video assisted thora- coscopic surgery (VATS) which usually results in reduced hospitalization, postoperative analgesia and impro ved cos- mesis than thoracotomy with comparable success rate. Procedure: pleuropulmonary ad hesions must be divided to reveal blebs or bullae which should undergo stapled resec- tion. In the absence of visible bullae or blebs blind resec- tion of the apex reduces recurrence . Pleurodesis can be achieved by pleurectomy (either apical or total), pleural abrasion or talc poudrage. Complications: the risk of recurrence is 2 \200\2234%. Pleurectomy and pleur al abrasion carry a small risk of postoperative bleeding. The concern regarding the use of talc poudrage in young patients seems unjusti \201 ed. A long-term survey showed no oncolo gical risk associated with asbestos-free talc. Systemic talc granulomatosis is avoided by t he standard use of larger particles (<11% of particles <5 micron). The theoretical risks of adult respiratory distress syndrome and long-term respiratory dysfunction have not been se en in large series reported by Cardillo. Rare complications include: Horner \200\231s syndr ome and chronic wound pain. of expeditious removal of parietal and visceral debris with- out injuring the lung with a l ow morbidity and mortality rate. The early use of VATS debridement with directed, magni \201 ed identi \201 cation and lysis of pleural adhesions has been shown to have bene \201 ts over closed methods. VATS decortication achieving lung re-expansion in more chronic situations is also feasible but is operator dependent. Open decortication remains the stan dard of care. In those un \201 t for thoracotomy, rib resection and open drainage via a th o- racostomy is an option. Complications: conversion of VATS to thoracotomy must be accepte d at consent, the rate is operator dependent. AUTHOR \200\231S TIP Again, early referral for surgery in the \201 brinopurulent phase of the disease increases the success of VATS and redcues the need for open decortication. Ini tial drainage should be large-bore and image-guided. Pleural effusion Indications: undiagnosed, symptomatic or recurrent pleural effusion. Princ iples: to obtain a suf \201 ciently large pleural biopsy and to achieve pleural symphysis and in some cases re-expan- sion of the trapped lung. Approach/procedure: VATS via one or t wo 2cm incisions and the insufflation of a sclerosing agent. Among sclerosing agents, asbes tos-free talc has proved to be supe- rior to other commonly used agents with a success rate ranging from 81 \200\223100%. VATS. VATS pleurodesis has been shown to be more effective t han bed-side instillation of a talc slurry. In the \200\230trapped-lung syndrome \200\231 treatment options include: the insertion of a pleuroperitoneal shunt; insertion of a long-t erm silicone chest drainage tube or attempts to re-expand the lung. Re-expansion can be ach ieved by visceral decortication which can be performed by VATS. VATS can be effectively per formed on a sedated, spontaneously ventilating patient. Secondary spontaneous pneumothorax Indications: It is observed mostly in older people with doc- umented lung disease and because the risks of a second episode are high intervention i s recommended after the \201 rst episode. AUTHOR \200\231S TIP Early referral for surgery is essential if VATS is to be suc- cessful. Prolonged pleural drainage increase the risk of pleural sepsis and adhesions which increas e the need for thoracotomy. AUTHOR \200\231S TIPS \200 Thoracoscopy is indicated after the intial pleural aspi- ration. Repeated thoracocentesis c an be associated with pleural \202 uid contamination leading to loculation and subsequent empyema. Thoracoscopic talc poudrage represents the treatment of choice for recurrent pleu ral effusions. Talc slurry represents an alternative in patients not \201 t for surgery. Principles, approach, procedure: these are largely the same as for primary spontaneous pneu mothorax. Complications: the recurrence rate is higher than for pri- mary spontaneous pneum othorax. Pleural empyema Indications: persistent loculated pleural sepsis after tube drainage (intra pleural \201 brinolytic therapy, in our opinion, has very little role); chronic pleural t hickening causing symptomatic restrictive ventilatory de \201 cit. Principles: removal of purulent material (debridement); removal of in \202 ammatory cortex from visceral and pari etal pleural surfaces (decortication). Approach/procedure: the result of treatment must be independent from the surgical approach, either open (stan- dard thoracotomy or minithoracot omy) or VATS. The choice of approach should not compromise the principles Localized (solitary) \201 brous tumors of the pleura Localized (or solitary) \201 brous tumor of the pleura (LFTP) (also called subpleural \201 broma) is a rare, slow-growing n eo- plasm.It is thought to be nonmesothelial in origin, not to be associated with asbestos exposure and usually shows a good prognosis, in contrast to diffuse mesothelioma. The surgi cal treatment of choice is local removal by VATS with intraoperative assessment of free sur gical margins. If the parietal pleura show signs of tumor invasion, a chest wall resection is recommended. Pedunculated lesions can be safely treated with a wedge resection if origin ating from CHAPTER 14.10 Surgery for pleural diseases 357 the visceral pleura or with a local resection with extrapleu- ral dissection if originating from the parietal pleura, provided that the surgical margins are negative. Prospective randomized trials are ongoing in UK to evalu- ate the respective roles of EPP i n the MARS trial and VATS debulking in the MesoVATS trial. Complications: operative mortali ty from EPP or P/D is less then 5% in experienced centers. Signi \201 cant morbidity may o ccur in up to 50%. Mesothelioma Indications: symptom control, tumor debulking, or radical excision. Selection criteria: include: \201 tness for GA, \201 tness for pneu- monectomy and tumor stage. P reoperative staging should include CT and PET where possible. PET is useful for detecting o ccult distant disease but not for mediastinal nodes, nor is CT thus mediastinos- copy is ma ndatory to exclude extrapleural nodal metasta- ses where radical surgery is planned. Proced ures: VATS can be used to perform talc pleurodesis or parietal pleurectomy. VATS decorticat ion can also relieve entrapped lung. Extrapleural pneumonectomy (EPP) involves the en-bloc excision of the pleura, lung, pericardium and diaphragm. Radical pleurectomy/decortication (P/D) may achieve the same clearance but preserves the lung. The longest surgical survival has included adjuvant treat- ment with chemotherapy and radical radiotherapy. In node negat ive, completely resected epithelial mesothelioma 5-year survival is a goal of treatment. VA TS debulking sur- gery may prolong survival when compared to biopsy alone. AUTHOR \200\231S TIP Mesothelima should be suspected in all males born in the 1940s who pre sent with pleural effusion, thickening or pleuritic pain. Recruitment into clinical trials should encouraged. Further reading Baumann MH, Strange C, Heffner JE, et al. Management of sponta- neous pneum othorax. ACCP Delphi consensus statement. Chest 2001; 119: 590 \200\223602. Halstead JC, Lim E, Venkataswaran R, et al. Improved survival with VATS pleurectomy-decorti cation in advanced malignant mesothelioma. Eur J Surg Oncol 2005; 31: 314 \200\223320. Henry M, Arnold T, and Harvey J, et al. BTS guidelines for the man- agement of spontaneous pneumothorax. Thorax 2003; 58: 39 \200\22352. Wait MA, Sharma S, Hohn J, et al. A randomize d trial of empyema therapy. Chest 1997; 111: 1548 \200\2231551. Waller DA. Malignant Mesothelioma \200\223 British surgical strategies Lung Cancer 2004; 45S: S81S84. This page intentionally left blank 359 Chapter 15 Sleep Chapter contents 15.1 Obstructive sleep apnoea 360 15.2 Driving 368 15.3 The overlap syndrome 370 15.4 Non-i nvasive ventilatory support in the acute setting 372 15.5 Nocturnal hypoventilation 374 15. 6 Cheyne \200\223Stokes respiration associated with left ventricular failure 378 15.7 Other causes of sleepiness 380 M KOHLER & J STRADLING 360 15.1 Obstructive sleep apnoea De \201 nition Obstructive sleep apnoea/hypopnoea (OSAH) is the term for a sleep disorder characterized by dynamic upper airway obstruction during sleep. It is part of the spectrum of sleep-related breathing disorders, with trivial snoring at one end and repetitive comple te upper airway obstruction, causing apnoeas with oxygen desaturations and arousals, at the other. Apnoeas during sleep can be classi \201 ed as one of three commonly recognized typ es: obstructive, central and mixed. An obstructive apnoea is characterized by a respira- to ry effort during the apnoeic period, while a central apnoea shows neither air \202 ow nor respiratory effort. Mixed apnoeas begin with a central component followed by an obstructive component. Mixed apnoeas are not really a separate entity but sometimes occur in associati on with both primary obstructive and central aetiologies. a pragmatic distinction should be made between the sleep study \201 ndings of repetitive apnoeas, oxygen desaturations or arousals on their own, and such an abnormal sleep study pl us the presence of daytime symptoms (obstructive sleep apnoea syndrome, OSAS). This differe ntiation is particu- larly important in patients who are considered to have upper airway re sistance syndrome (UARS). It has been shown in clinical studies that certain individuals wi th UARS show upper airway narrowing leading to sleep fragmenta- tion and excessive daytime sleepiness in the absence of an increased number of apnoeas, hypopnoeas or dips in oxygen s aturation. The de \201 nition of OSAS/UARS, which implies clinically signi \201 cant symp toms and thus requiring consideration of treatment, can be summarized as follows: Upper airway narrowing during sleep, causing suf \201 cient sleep fragmentation to result in signi \201 cant symptoms, usually excessive daytime sleepiness. Normal breathing Obstructive hypopnoea Obstructive apnoea Central apnoea Pathophysiology Although full explanations for OSA still need to be de \201 ned, the princ ipal pathophysiologic mechanism of the disorder is dynamic narrowing of the upper airway as sociated with sleep. The upper airway is de \201 ned as the space between the nasal and or al ori \201 ces and the epiglottis (Fig. 15.1.2). In Ex Air flow Flow limitation Pleural pressure + \210\222 Rib cage excursion Abdomen excursion EMG diaphragm Fig. 15.1.1 Discrimination of apnoea types. Each panel represents one whole breath. Obstruc tive and central apnoea/ hypopnoea are differentiated by the presence or absence of respira tory effort as evidenced by oesophageal pressure, diaphragmatic EMG recordings or other ind irect measure of respiratory effort: asynchrony or paradoxical motion of rib cage and abdom en recorded by inductance plethysmography and changes in pulse transit time provide indirec t evidence of increased respiratory effort. During partial upper airway obstruction, the co ntour of the inspiratory \202 ow curve is typically \202 attened. (Adapted from Kohler M, Bloch KE 2003.) Nasopharynx Oropharynx Laryngopharynx Historically, an arbitrary de \201 nition of an apnoea was made as breathing cessation for longer than 10 seconds; and hypopnoea was a reduction in air \202 ow >50% from the previo us stable baseline, lasting >10 seconds, and in some centers, requiring association with a >3% decline in oxyhaemoglobin saturation. Because >5 apnoeas/hypopnoeas per hour of sleep w ere found to be uncommon in sleep studies of healthy young adults, the standard de \201 ni tion of OSA became >5 apnoeas per hour of sleep, or >35 per night. The number of apnoea/ hy popnoea events increases with age, and therefore many more events per hour of sleep can be normal in the elderly. Numerical sleep data, which are based on counts of events during a s leep study (e.g. apnoea \200\223hypopnoea index), are commonly used to de \201 ne OSAH, al though they are not very useful in de \201 ning overall disease severity and the necessity for treatment. This is partly because there is a poor correlation between symptoms and sle ep study \201 nd- ings, and partly due to night-to-night variation in these indi- ces. Be cause this definition lacks clinical usefulness, Fig. 15.1.2 Anatomy of the pharynx. Airway narrowing in patients with OSA can occur at multi- ple sites of the upper airway, bu t it happens most com- monly in the region of the pharynx, because of its anatomical and fu nctional characteristics. The pharynx consists of a complex muscular tube which serves two major purposes: breathing and swallowing. When the phar- ynx is being used to breathe, it i s held open by dilator mus- cles. During swallowing it collapses and thereby enables perist altic movements to propel food. The functional diver- sity of the pharynx is achieved by th e \202 oppy and collapsible muscular tube which also has the capacity of being held open rigidly by dilating muscles. During sleep, the dilator muscles show reduced activity, and c onsequently some pharyngeal narrowing occurs even in healthy individuals. CHAPTER 15.1 Obstructive sleep apnoea 361 The collapsibility of the pharynx can be de \201 ned by the critical collapsing pressure ( Pcrit) surrounding the oro- and nasopharynx, which has been shown to be abnormally high in patients with OSA. In theory, the upper airway resembles a Starling resistor (Fig. 15.1.3), consisting of a mainly rigid tube (nose), followed by a collapsible part (pharynx), and fo llowed by another rigid tube (laryngeal airway). During inspiration, \202 ow will persist as long as the nasal pressure is greater than the pressure in the collapsi- ble pharynx wh ich will be subatmospheric. In sleeping healthy individuals, air \202 ow continues because inspiratory nasal pressure is approximately 0 cmH2O and pharyngeal pressure, although suba tmospheric, remains above Pcrit (about \210\22210 cmH2O, subatmospheric). In contrast, it has been shown that the peripharyngeal Pcrit in patients with signi \201 cant OSA is often about, or even above, 0 cmH2O during sleep and therefore the pharynx easily collapses and air \202 ow ceases. Simple snorers are somewhere in between. techniques, have shown that patients with OSA have a smaller pharyngeal cross-sectional are a than control sub- jects (Fig. 15.1.4). It has not been possible to determine a cut-off si ze for the upper airway that differentiates a patient with OSA from a healthy individual. Fig. 15.1.4 MRI images of the upper airway in a healthy control (A) and a subject with OSA (B). Note the crowded airway, with more neck adiposity and a degree of retrognathia. (Adapt ed from Schwab RJ 1998.) In children with OSA, the pharynx can commonly be crowded by enlarged tonsils and adenoids; this cause is much less common in adults. Functional causes of OSA There is some evidence for a relationship between nasal obstructio n and OSA. Data from physiological studies sug- gest that upper airway narrowing and snorin g can be induced by greater subatmospheric pharyngeal pressures, caused by an increased nas al resistance, as would be pre- dicted from the Starling resistor model. The model also pre dicts that apnoeas would be self terminating as described earlier in this chapter. However, it is unlikely that the pharynx indeed behaves like a simple Starling resistor. This is pr obably due to surface adhesive forces between the opposed pharynx walls, which will tend to hold the pharynx closed once collapsed, and hysteresis effects. This theory is supported b y the observation that the pressure needed to reopen the collapsed pharynx exceeds its clos ing pressure. The patency of the pharynx is also in \202 uenced by motor output from the C NS to upper airway muscles, which can be differentiated into \201 ve striated muscles (m. palatoglos- sus, m. palatopharyngeus, m. levator palatine, m. tensor palatine, and m. uvul ae). In awake subjects, the m. pala- toglossus, palatopharyngeus and levator palatini show electromyographic activity during inspiration that keeps the upper airway open during the r espiratory cycle. Sleep is generally associated with decreased upper airway muscle activity and tone. In patients with OSA, genioglossus EMG activity is increased during wakefulness compared to healthy controls (probably re \202 ecting increased activity to defend the air way), with a greater proportional decrease at sleep onset. This disproportional reduction o f upper air- way muscle tone is associated with a higher tendency to upper airway collapse during sleep. An additional possible pathophysiological explanation for dysfunction of the upper airway in patients with OSA is that there may be a reduced protective re \202 ex mec hanism in the pharynx. In healthy subjects, receptors in the pharynx detect pressure falls and provoke an increase of pharyngeal dilator muscle tone which prevents collapse of the ph arynx. Repetitive airway narrowing during snoring, smoking and alcohol may injure the mucos a and nerves in the pharynx, interrupting this reflex and thereby facilitating the developm ent of OSA. Fig. 15.1.3 Upper airway resembling a Starling resistor. Subatmospheric Pcrit in healthy su bjects (left) compared to patients with OSA (right). When external pressure at any point al ong a collapsible tube (pharynx) is greater than the intraluminal pressure then collapse wi ll occur, but the consequent cessation of air \202 ow will return the intraluminal pressur e to atmospheric and may allow the airway to spring open again \200\223 this produces snor ing. However, if the external Pcrit pressure is greater than that at the nose, collapse occ urs at some location along the tube where the transmural pressure equals zero or above, pro ducing an apnoea, rather than just snoring. As a consequence, clinically significant upper airflow obstruction is determined by factors , such as anatomical abnormalities in the pharynx, or dysfunction of the pharyn- geal dilat or muscles, which both facilitate the narrowing or collapsibility of the pharynx. Thus, pos sible causes of obstructive sleep apnoea can be divided into two major groups: \200 \200 Anatomical causes. Functional causes. Anatomical causes of OSA The most common anatomical factor contributing to the pathogenesis of OSA is neck obesity which compromises upper airway patency by increased loading from th e adipose tissue surrounding the pharyngeal lumen, and therefore increases Pcrit. In variou s observational studies, neck circumference has been shown to correlate with the fre- quenc y of apnoeas better than any other index of obesity. Craniofacial abnormalities, like retro - and micrognathia, are also frequently observed in patients with OSA. These conditions are associated with crowding of the pharyngeal space, which decrease the resting cross-section al area of the upper airway. Studies, using radiological imaging M KOHLER & J STRADLING 362 \200 \200 Some pharmacologic agents (e.g. alcohol, opiates, benzodi- azepines) can promote OSA by inh ibition of CNS activity, re \202 ex muscle tone, and thus motor output to upper airway mus cles: this decreased muscle tone produces a higher propensity for the pharynx to collapse. Polycythaemia (in cases with daytime hypoxia). Neuropsychological impairment. Increased ane sthetic risk. It must be stressed that a direct causal relationship has not been established for most of these complications. As accidents and cardiovascular complications probably con- tribute mo st to the number of premature deaths in patients with OSAS, they will be discussed in detai l. Causes of OSA Anatomical \200 \200 Neck obesity. Retrognathia, micrognathia and maxillary underdevelop- ment. Pharyngeal encro achment (e.g. tonsillar and adenoid hypertrophy, acromegaly). Chronic nasal obstruction (e. g. polyps, turbinate hypertrophy, rhinitis), possibly plays a minor role in the pathogenesi s of OSA. Accidents The most immediate risk from OSAS relates to falling asleep at the wheel. The ris k of causing traf \201 c accidents is elevated 3- to 10-fold in patients with OSAS. Accide nts typically occur at night when driving alone on monotonous highways. As the vehicle usua lly crashes into an obstacle without the driver breaking, the consequences are particu- lar ly grave. Therefore, all patients with OSAS should be advised of the following (and recorde d in the medical notes!): \200 Functional \200 Alcohol. \200 Sedative drugs (e.g. opiates, benzodiazepines). \200 Sl eep deprivation. \200 Bulbar palsies. \200 Neurological degenerative disorders (e.g.mul tisystem atrophy). Myopathies (e.g. Duchenne muscular dystrophy). Hypothyroidism. Notify the DVLA at the time of diagnosis, or shortly after. They will send the patient a sh ort questionnaire. If they admit to excessive daytime sleepiness, their driving license is revoked until they are effectively treated and sleepiness has resolved. Do not drive while sleepy. Heavy goods or public service vehicle drivers should be advised to stop driving ent irely, until the sleepiness has resolved completely. In the case of class 2 license hold- e rs the success of the treatment must be veri \201 ed by a specialist clinic. \200 \200 Immediate consequences of OSAS Once signi \201 cant upper airway obstruction occurs there will be increased inspiratory effort to overcome it. At a speci \201 c level of pleural pr essure (usually about \210\22215 cmH2O in non-sleep deprived subjects, but down to \210 \22280 cmH2O in OSAS) patients tend to arouse from sleep. The recurrent arousals result in two major consequences: sleep fragmentation, which leads to excessive daytime sleepi- ness, and autonomic changes including elevation of arterial blood pressure. Treatment success is de \201 ned as a normal ESS (Epworth Sleepiness Score <10) and eviden ce of adequate nasal CPAP usage (minimum usage of at least 3 hours per night, every night, veri \201 ed by downloaded machine data). Cardiovascular complications Severe sleep apnoea syndrome (affecting about 1 \200\2232% of the male population) is associated with a high cardiovascu- lar risk. Over 10 years, 14% of this group are predicted (by Framingham-index) to experience a stroke and 23% a myocardial infarction \200\223 a 37% combined risk. There are several potential mechanisms of vascul ar dam- age operating in sleep apnoea. During each apnoea cycle there are stereotypic rises in blood pressure, usually >30mmHg, and not uncommonly >100mmHg. These rises will induce s hear stresses in blood vessel walls \200\223 forces that are thought to cause vascular wal l damage and initiation of atherosclerosis. Each apnoea is also associated with hypox- aemi a and re-oxygenation, which may be disadvantageous through repeated \200\230ischaemia re-p erfusion injury \200\231. Sleep apnoea patients show evidence of increased production of re active oxygen species, increased systemic catecholamine production, abnormal vascular react ivity, reduced baro- receptor sensitivity and possibly impaired insulin resistance. Further more, circulating vascular risk factors (e.g. choles- terol, CRP) have been shown to be ele vated in OSA. Thus many features of the sleep apnoea syndrome may poten- tially contribute to vascular damage. It is dif \201 cult to esti- mate the risk reduction that correcting t hese factors might produce, because it has not been accurately de \201 ned from long-term randomized, controlled clinical trials. Cor pulmonale can result from severe untreated OSAS which probably constituted the original \200\230Pickwickian syndrome \200\231. It occurs if a patient has daytime hypoxaemia, Fig. 15.1.5 Blood pressure swings in OSAS. Arterial tracing during sleep (3 mins, Finapre s device) showing instant return of large systemic BP surges, with each of three apnoea ter minations, following removal of affective CPAP in a man with obstructive sleep apnoea. Long-term consequences of OSAS OSAS may be associated with various complications, including the following: \200 \200 \200 \200 \200 \200 \200 Accidents. Arterial hypertension. Arrhythmias. Myocardial infarction and stroke. Cor pulmon ale. Ventilatory failure. Insulin resistance. CHAPTER 15.1 Obstructive sleep apnoea 363 The most common complaint of patients with OSAS is excessive daytime sleepiness. This \201 nding shows a consid- erable inter-subject variability and the de \201 nition of abno r- mality can be dif \201 cult. The most widely used score to assess daytime sleepiness is the Epworth sleepiness scale (ESS) which asks patients to rate their tendency to fall asle ep in eight different situations of varying stimulation. most often resulting from co-existing COPD. Chronic hypoxaemia results in pulmonary hyperte nsion and \202 uid retention, producing the picture of cor pulmonale. Epidemiology There are a large number of studies on the prevalence of OSAS in the general p opulation, but the frequency of this disorder is still open to debate, mainly because of co ntrover- sies concerning clinical diagnostic approaches and the lack of a uniform de \201 nition of OSA(S). As a consequence, the reported prevalence of OSA differs considerably bet ween the various population based studies with a range from as low as 0.3% to as high as 26 % in middle-aged people. Broadly it is believed that up to approximately 2 \200\2234% of th e popula- tion in Western countries suffer from clinically signi \201 cant OSAS. The highe st frequencies are found in countries with a high prevalence of obesity as there is evidenc e for a strong correlation between BMI and OSA. The prevalence of OSA has been reported to be >20% in a community sample of middle-aged men with a mean BMI of 30.5kg/m2. Ethnic origi n seems to in \202 uence the prevalence of OSA, since a higher proportion of individuals w ith African or Oriental origin seem to have OSA compared to whites and Asians. An inherited basis for OSA is suggested by reports of fam- ilies with multiple affected members and gen etic epidemio- logic studies; the genetic basis for upper airway narrowing during sleep has not been de \201 ned yet. However, risk of OSA among relatives of patients with the disor der is almost twice that among neighborhood control subjects. Potential pathogenetic explan ations for these \201 ndings are provided by familial studies which have demonstrated tha t craniofacial abnormalities, structural features of the upper airway, and the propensity t o develop obesity are at least partially inherited. There is a strong predominance of OSA i n men, 2 \200\2233 times more men are affected than pre-menopausal women. Why men are at hi gher risk for the development of OSA is still unclear, however, hormonal in \202 uences on breathing during sleep and fat distribution cannot fully explain this differ- ence. The pr evalence in females probably increases after menopause, shifting the male-to-female ratio t o 2:1, possi- bly because body fat is redistributed to the upper body. OSA occurs in all ag es, although the prevalence in children and the elderly has been investigated less thorough ly. Several large population-based studies suggest that the mean age of patients with OSAS at presentation lies between 40 and 50 years. The prevalence of OSA and OSAS seems to rise continually with age and to level off after the age of 65 years. Of note, healthy elderly i ndividu- als commonly have a higher frequency of apnoeas/ hypopnoeas, which makes the de \201 nition of a clinically sig- ni \201 cant cut-off level of apnoeas even more dif \201 cult. Epworth Sleepiness Scale How likely are you to doze off or fall asleep in the situations described in the box below, in contrast to feeling just tired? This refers to your usual way of life in recent times. Even if you haven \200\231t done som e of these things recently try to work out how they would have affected you. Use the following scale to choose the most appropriate number for each situation: 0 = would never doze 2 = Moderate chance of dozing 1 = Slight chance of dozing 3 = High chance of dozing Situation Chance of dozing Sitting and reading Watching TV Sitting, inactive in a public place (e.g. a theater or a meeting) As a passenger in a car for an hour without a break Lying down to rest in the afternoon when circumstances permit Sitting and talking to someone Sitting quietly after a lunch without alcohol In a car, while stopped for a few minutes in the traffic Fig. 15.1.6 Epworth sleepiness scale. An ESS score of \211 10 is generally regarded as abn ormally sleepy and requires further investigations to \201 nd the underlying cause. Of no te, there is no good correlation between ESS and the severity of OSA which might be explain ed by perception problems of patients with OSA regarding their sleepiness. Furthermore, the re are many other possible reasons for excessive daytime sleepiness which are discussed els ewhere in this book.