An explanation of the effect of the disorder on driving. Advice not to drive when the indiv idual is sleepy or advice that driving must cease if excessive sleepiness is present. This may have implications on work which may have to cease prior to treatment. Explanation of th erapy available. If possible, have a family member, partner or a friend present for informa tion and to hear advice. Keep clear documentation. Recommend provision of written advice to the patient. \200 \200 Noti \201 cation to DVLA In the UK it is the doctor \200\231s responsibility to advise the patient to notify the DVLA on diagnosis of a sleep disorder that may affect the ability to drive. It is the responsibility of the patient who holds a license to notify the DVLA by t elephone or letter. The DVLA will then send forms both to the patient and doctor requesting information about diagnosis, treatment and satisfactory control of symptoms. The written c onsent of the patient is usually forwarded by the DVLA with the form. The doc- tor should e nsure this is obtained before providing any information. The DVLA considers the information provided and will then continue or revoke the driving license. It is advis- able to follow -up drivers to ensure adequate control of symptoms and compliance with therapy. Further reading American Academy of Sleep Medicine (2005). The International Classi \201 c ation of Sleep Disorders 2nd edn. Diagnostic and Coding Manual, Westchester: USA. Driver and Vehicle Licensing Agency drivers medical group (2008) Guide to current medical s tandards of \201 tness to drive. www. dvla.gov.uk George CF. Reduction of motor vehicle collisions following treat- ment of sleep apnea with nasal CPAP. Thorax 2001; 56: 508 \200\223512. George CF, Findley LJ, Hack MA. Across countr y viewpoints on sleepiness during driving. Am J Resp Crit Care Med 2002; 165(6): 74 746 \200\223749. National Institute of Clinical Excellence Technology Appraisal (2008). Sleep Apnoea- Contin uous Positive Airway Pressure (CPAP) TA139. www.nice.org.uk/guidelines/TA/ published Insurance The patient should be advised to notify the insurers of the diagnosis of a sleep disorder. Dif \201 cult situations If a symptomatic patient with a sleep disorder continues to drive against medical advice it is important to involve other people in discussions including ge neral practitioners, nurses, family and friends. G VAN RENSBURG & J CATTERALL 370 15.3 The overlap syndrome Introductions The overlap syndrome was \201 rst used to describe the coex- istence of OSA S and COPD. Patients are prone to severe hypoxemia during sleep, especially rapid eye movem ent (REM) sleep, in addition to the hypoxaemic episodes from obstructive sleep apnoea. This is due to worsening of alve- olar hypoventilation during sleep. The most marked falls in n octurnal arterial oxygen saturation occur in COPD patients who are hypoxic and hypercapnic when awake. In recent years, the term has come to be used more widely and to include obesit y-related hypoventilation. Obesity is not only associated with obstructive sleep apnoea but it is an increasingly common cause of hypoventilation. Daytime hypoxia and hypercapnia are increased in patients with a BMI >40. Most authors now regard the overlap syndrome as any combination of two or more of these three conditions (Fig. 15.3.1). The syndrome is being d iagnosed with increas- ing frequency, and as obesity levels continue to rise, it is set to become more prevalent in the future. resistive load in contributing to alveolar hypoventilation is illustrated by the ability of CPAP alone to reverse hyper- capnia and hypoxia in some patients with the overlap syndrome . However, in other patients CPAP alone is insuf \201 cient to restore ventilation to adeq uate levels. In these patients, the other factors which contribute to non-apnoeic hypoventi - lation are presumably of more importance. These factors include decreased functional resi dual capacity, reduced ventilatory response to hypercapnia and hypoxia, decreased chest com pliance in morbid obesity and generalized airway resistance in COPD. The reduced ventilator y drive is of particular interest for there is evidence that it is not \201 xed. Some pat ients who do not respond well to CPAP at \201 rst can be established on CPAP after a peri od of non-invasive ventilation. The short- term ventilatory support improves arterial gas t ensions and results in the ventilatory drive being re-set. After this, relatively normal ox ygen and carbon dioxide levels can be maintained with CPAP alone. Clinical aproach General The overlap syndrome should be suspected when COPD or morbid obesi ty is associated with sleep disruption and daytime sleepiness, especially if there is dayti me hypoxia and hypercapnia. It should also be considered when patients already receiving CP AP treatment for OSAS have persistent symptoms of sleep disruption or carbon dioxide retent ion (especially if they are morbidly obese and/or have COPD). History: key points \200 \200 \200 \200 Obesity hypo- ventilation OSA COPD Daytime sleepiness and/or poor sleep quality. Known COPD or signi \201 cant smoking histor y. Morning headaches due to hypercapnia in a few patients. Inadequate or incomplete respons e to CPAP (in patients already on CPAP for OSA). Fig. 15.3.1 The overlap syndrome. Pathogenesis and implications for treatment In pure obstructive sleep apnoea, the arterial oxygen satu- ration usually returns to baseline after each episode of hypoxaemia, and the a rterial blood gas tensions when awake are usually normal. In contrast, in the overlap syn- drome, the arterial oxygen saturation usually remains low between episodes of obstructive s leep apnoea, and these patients are usually hypoxaemic and hypercapnic when awake. Alveolar ventilation is reduced. Ventilation falls normally during non-REM sleep and drops further during periods of REM sleep. In healthy individuals, the resulting falls in arterial oxygen tension cause little change in arterial oxygen saturation because they lie on the flat par t of the oxyhaemoglobin dissociation curve. However, patients with severe COPD or obesity h ypoventi- lation syndrome often have marked falls in arterial oxygen saturation during REM sleep. This is partly because they lie on a steeper part of the oxyhaemoglobin dissociation curve and partly because they hypoventilate more than healthy individuals, both when awake and during sleep. When obstructive sleep apnoea coexists with severe COPD or obesity-relat ed hypoventilation the level of ven- tilation tends to fall further because of the episodes of upper airway obstruction. The importance of this extra Examination: key points \200 Morbid obesity \200\223 usually BMI >40 unless COPD also present. Physical signs of pulmon ary hypertension and right ven- tricular failure. Investigations Overnight oximetry \200 The baseline arterial oxygen saturation during sleep is usually lower and less stable than in pure obstructive sleep apnoea. In a typical study, gradual falls in arterial oxygen satu ra- tion caused by hypoventilation are combined with more rapid ( \200\230saw-tooth \200 \231) \202 uctuations caused by obstructive sleep apnoea. However, note that, at low SaO2 , sharp falls in arterial oxygen saturation can also result from hypoventilation alone, bec ause of the shape of the oxyhaemoglobin dissociation curve. Arterial blood gas measurements Daytime hypercapnia is common. Measure arterial blood gas t ensions if the daytime oxygen saturation is low and/or symptoms of hypercapnia are present. CHAPTER 15.3 The overlap syndrome 371 Transcutaneous CO2 This is a useful adjunct if available. It can be used to help titrate th e level of ventilation. After an unsuccessful trial of nasal CPAP, he was established on non-invasive ventilation. Overnight oxygenation improved markedly (Fig. 15.3.2b) and his symptoms resolved. He remain s on long-term non-invasive ventilation. AUTHOR \200\231S TIP Polysomnography adds little in most cases. Assessment is usually based on skilled interpretation of the history and overnight oximetry, followed by trials of tre atment. Treatment CPAP \200 CPAP alone or with oxygen supplementation improves symptoms and daytime arterial gas tensio ns in many patients. However, others continue to have symptoms and signi \201 - cant desat uration during REM sleep, with ongoing hyper- capnia despite the abolition of obstructive a pnoeas and hypopnoeas with CPAP. These patients should be con- sidered for non-invasive ven tilation. (a) Non-invasive ventilation (NIV) \200 NIV has been shown to be effective in treating OSA patients with hypercapnia. A short perio d of NIV can reset the central respiratory drive, enabling patients to continue with CPAP t hereafter. (b) Fig. 15.3.2 Overnight arterial oxygen saturation (a) before treatment and (b) during treatm ent with non-invasive ventilation using an inspiratory pressure of 16 cmH2O and an expirato ry pressure of 6 cmH2O without supplemental oxygen. Each line represents one hour and shows a continuous recording of the arterial oxygen saturation between 70 and 100%. Supplemental oxygen \200 Although oxygen therapy alone is safe in most patients with uncomplicated COPD, it can lead to dangerous hypercapnia in the overlap syndrome. However, oxygen therapy can be used in c ombination with NIV, and some- times with CPAP, if hypoxaemia persists due to COPD. Further reading Flenley DC. Disordered Breathing during sleep: discussion paper. Example case A 50-year-old man with a 40 pack-year smoking history complained of tiredness, poor sleep quality, loud snoring and morning headaches. On clinical examination, he was mo rbidly obese with a BMI of 42kg/m2 and had pedal oedema. The FEV1 was 1.1 litres and the FV C 2.5 litres. The arterial oxygen saturation was 93% breathing air, PaO2 6.5kPa, PaCO2 7.1k Pa and pH 7.41 Overnight oximetry (Fig. 15.3.2a) showed a low baseline saturation during th e night, gradual falls in arterial oxy- gen saturation due to hypoventilation and superimpo sed rapid falls in oxygen saturation due to obstructive sleep apnoea and hypoventilation. J Royal Soc Med 1985; 78: 1031 \200\2231033. Mohsenin V. Sleep in Chronic obstructive Pulmonary Disease. Sem Resp Crit Care Med 2005; 26(1): 109 \200\223116. Laaban J, Chailleux E. Daytime Hypercapnia in Adult patients with Obstructive Sleep Apnoea Syndrome in France, before Initiating nocturnal nasal Continuous Positive Airway Pressure T herapy. Chest 2005; 127(3): 710 \200\223715. Piper AJ, Sullivan CE. Effects of Short-term NIPPV in the Treatment of Patients with Severe Obstructive Sleep apnoea and Hypercapnia. Chest 1994; 105: 434 \200\223440. Resta O, Foscino-Barbaro MP, Bon \201 tto P, et al. Prevalence and mechanisms of diurnal h ypercapnia in a sample of morbidly obese subjects with obstructive sleep apnoea. Resp Med 2 000; 94: 240 \200\223246. Resta O, Foschino-Barbaro MP, Brindicci C, et al. Hypercapnia in overlap syndrome: possible determinant factors. Sleep Breath 2002; 6(1): 11 \200\22317. S PATEL & A WHITTLE 372 15.4 Non-invasive ventilatory support in the acute setting Overview CPAP and non-invasive positive pressure ventilation (NIPPV or NIV) are the commone st forms of non-invasive ventilatory support. In the acute setting, CPAP is used as an adju nct in the management of pure hypoxic respiratory failure (type I), whereas NIV uses bi-lev el pressure ventila- tion to treat alveolar hypoventilation presenting as decom- pensated h ypercapnic respiratory failure (type II). Despite their different indications, the two form s of ventilatory support share many practical aspects. History Think about clues to disproportionate respiratory failure: \200 \200 Smoking history (undiagnosed COPD?). No smoking history (is this acute asthma, requiring ur gent ITU referral rather than NIV?). Drug history (sedative or opiate overdose possible?). Somnolence and snoring (OSA or overlap syndromes). Morning headaches, fatigue (nocturnal hy poventilation). Old polio (physical disability not always obvious). Old TB (thoracoplasty o r other collapse therapy?). Trauma or surgery affecting thoracic compliance, dia- phragmati c movement or brainstem ventilatory control. \200 \200 \200 \200 \200 Indications in the acute setting CPAP Improves hypoxia in non-acidotic respiratory failure: \200 Examination \200 Pneumonia and pneumonitis, as an interim measure before invasive ventilation or as ceiling of treatment. Acute cardiogenic pulmonary oedema. Severe obstructive sleep apnoea (OSA). Don \200\231t ignore the obvious: chest wall distortion or obe- sity may be longstanding bu t decompensate acutely. Signs of cor pulmonale suggest chronic hypoxia. Signs of pneumothor ax or pleural effusion suggest alter- native treatable causes. Reduced respiratory rate and conscious level are key indicators of CO2 narcosis. \200 \200 NIV Treats hypercapnic respiratory failure with acidosis, including: \200 \200 Acute exacerbations of COPD. Decompensated chronic hypoventilation due to chest wall deform ity, obesity hypoventilation ( OSA), neuro- muscular disease. Rare conditions: congenital or acquired abnormalities of ventilatory control, metabolic disorders. Acute cardiogenic p ulmonary oedema. Investigation Arterial blood gas measurements (ABGs) are essential to establish the pattern of respiratory failure. Simpli \201 ed: \200 PaO2 <8.0kPa and normal/low PaCO2 despite high FiO2: type I respiratory failure, think abou t CPAP and ITU. High PaO2 and high PaCO2: FiO2: too high in a hypoven- tilating patient, so give controlled FiO2: and recheck. PaO2 <8.0kPa and high CO2 with pH <7.35 despite con- tr olled FiO2: suggests the need for NIV. NIV will also improve oxygenation and may be better toler- ated than CPAP, so can be used i n type I respiratory failure. Contra-indications \200 \200 \200 \200 CXR is essential to exclude a pneumothorax and to investi- gate possible pneumonia or effus ion. Look for CXR clues: hyperexpansion, old TB, elevated hemidiaphragm, scoliosis. Investi gation of persistent respiratory failure includes over- night oximetry (look for REM-relate d desaturation seen in hypoventilation, or saw-tooth desaturation of OSA), early morning AB Gs or overnight capnography for CO2 retention. Commencing treatment \200 Facial trauma or burns. Untreated pneumothorax. Vomiting or risk of aspiration. Fixed upper airway obstruction. Caution is required in patients with decreased conscious level and unprotected airway, or e xcessive secretions. Mechanisms of action CPAP \200 \200 \200 \200 Decide and document the ceiling of treatment in case NIV is unsuccessful: patients suitable for ITU, particularly those with type I failure, should be discussed early to anticipate t he need for escalation and invasive ventilation. Patients unsuitable for escalation due to advanced dis- ease, frailty or co-morbidity may still bene \201 t from a trial period of C PAP or NIV. CPAP or NIV should be implemented by staff trained and familiar with the equipm ent and with mask \201 tting. A \200\230full-face mask \200\231 covering nose and mouth is most com- monly used in the acute setting. Nasal masks or pillows are preferred by some patients but need more co- operation to avoid mouth breathing. Helmets are used less but ma y overcome intractable leakage problems. Allow the patient to hold the mask onto their face for familiarization. The ease with which the mask can be removed should be demonstrated. Recruits underventilated or collapsed lung units. Increases FiO2 (due to mask ef \201 cien cy). Splints the upper airway. Of \202 oads inspiratory muscles to reduce work of breathin g. NIV \200 Expiratory positive airway pressure (EPAP) overcomes elevated intrinsic positive end-expira tory pressure (PEEP), so delaying airway collapse in expiration. EPAP recruits underventila ted or collapsed lung units. Inspiratory positive airway pressure (IPAP) assists inspi- rat ion and reduces the work of breathing against increased lung and chest wall compliance. The combined effect of EPAP and IPAP is to increase tidal volume and alveolar ventilation. \200 Clinical evaluation A full clinical evaluation is required in all acute patients; the follo wing are pointers that may help in the context of respiratory failure, and is not an exhaus tive list. CPAP Two types of equipment can deliver CPAP: \200 Fixed pressure \200\230PEEP valve \200\231 on an airtight mask, with air/oxy- gen fed into the mask ( \202 ow rates of 40 \200\22360 l/min required). CHAPTER 15.4 Non-invasive ventilatory support in the acute setting 373 This reliably delivers high FiO2, and is the type usually used in emergency departments or ITU. An adjustable pressure-driven CPAP unit (or NIV unit with IPAP and EPAP settings equal ). Most NIV units can deliver high FiO2; CPAP units may require O2 to be entrained and cann ot guarantee FiO2 >50%. prolonged period of NIV to treat the effects of long-term hypercapnia on central ventilator y control. Once stabilized, some can be converted to domiciliary CPAP for the longer term. Think about hypoventilation in obese patients labeled as having \200\230heart failure \200 \231 despite well preserved car- diac function on echo: check ABGs. All obese patients with respiratory failure should be investigated with overnight oximetry. Weight loss is curativ e. Initial pressure settings of 5 cmH2O are suitable to familiar- ize the patient to the circu it. Increase the pressure over 30 minutes. Aim for 10 \200\22312.5 cmH2O for pneumonia or p ul- monary oedema; higher pressures may be required to treat severe OSA in obese patients. Neuromusculoskeletal disease Respiratory failure in acute neuromuscular disease (e.g. Guill ain \200\223Barr syndrome, myasthenic crisis) should be managed in a high-dependency sett ing with immediate access to invasive ventilation; NIV may provide a holding measure. Patie nts with chronic neuromusculoskeletal dis- ease (e.g. muscular dystrophy, post-polio syndro me, kypho- scoliosis) may decompensate and present acutely: NIV is often effective, and the se patients are likely to require long-term domiciliary nocturnal NIV. Patients with chest wall deformity may require higher pressures. NIV \200 \200\230Spontaneous/timed \200\231 mode on a pressure-support venti- lator is usually used , with breaths triggered by the patient \200\231s respiratory effort and a back-up rate of 8 \200\22312 breaths/min- ute if no effort is detected. The back-up rate must be below the patient \200\231s own respiratory rate; a patient with a very low rate is unlikely to be su itable for NIV. Start with IPAP/EPAP 10/4 cmH2O aiming to titrate up over 30 minutes, e.g. to IPAP 16 \200\22318 and EPAP 5 \200\2236, according to the patient \200\231s response. Th e maximum prac- tical IPAP is normally 20 cmH2O. EPAP must overcome intrinsic PEEP (high in obstructive lung disease) or upper airway obstruction in OSA: up to 10 cmH2O is sometimes needed. Use controlled oxygen at the lowest rate required to achieve target SaO2; aim to im prove oxygenation by optimal pressure support rather than high FiO2. A target of 85 \200 \22390% is often suf \201 cient in COPD. Monitor respiratory rate, SaO2 and conscious leve l as well as haemodynamics; observe patient comfort and synchonisation with the ventilator. Check ABGs after 1 hour, and again when a steady state is reached or if the patient \200 \231s condition changes. Reduced conscious level due to CO2 narcosis is a rela- tive contra indication to NIV, but is acceptable if NIV is the ceiling of treatment. Doxapram has occas ionally been used to improve respiratory drive to assist NIV. Acute cardiogenic pulmonary oedema CPAP and NIV are effective in cardiogenic pulmonary oede ma and reduce the need for intubation. Their effects appear to be equivalent, and neither t herapy increases the incidence of acute myocardial infarction. CPAP is usually cheaper and more rapidly available in the emergency department. Other considerations After the acute phase, breaks for food, drink and social interaction a re usually feasible. Weaning is achieved by steadily increasing the length of breaks from v entilation. Patients requiring prolonged NIV may be more comforta- ble with a nasal mask, a fter stabilization on a full-face mask. In severely unwell patients nutrition must be addre ssed early, by NG feeding if necessary. Thromboprophylaxis should be considered: most NIV p atients will bene \201 t. Pitfalls and tips \200 Skin breakdown can be disastrous. It may be due to poor or tight mask \201 tting with ina dequate monitoring. Allow periods off ventilation; vary the mask type and position; protect the skin with a dressing. Think about the breathing circuit: we have seen exhala- tion por ts blocked, removed or fouled with secretions. Humidi \201 cation can aid tolerance of CPA P/NIV, but don \200\231t drown the patient: keep the reservoir below the level of the patie nt \200\231s head. Increase pressures cautiously in patients with severe emphysema or bulla e: there is a risk of pneumothorax. Air swallowing is a problem. An NG tube can reduce subs equent gastric dilatation and prevent diaphragmatic splinting; rarely a \202 atus tube is necessary. Speci \201 c clinical presentations COPD NIV is of proven bene \201 t in acute exacerbati on of COPD with decompensated hypercapnic respiratory failure (pH <7.35). Poor response to NIV is often due to excessive FiO2 with inadequate pressure support. Pneumonia CPAP can imp rove oxygenation in patients with pneumo- nia providing secretions can be controlled adequa tely. Hypercapnia and acidosis suggest co-existing COPD or a tiring patient and require an escalation in therapy. Immunocompromised patients Immunocompromised patients have an extremely poor prognosis when intubated for respiratory failure. Early NIV has been shown to reduce the need for intubat ion and to improve mortality in this group. Further reading British Thoracic Society Standards of Care Committee Non-inva- sive ventila tion in acute respiratory failure. Thorax. 2002; 57(3):192 \200\223211. Perez de Llano LA, Golpe R, et al. Short-term and long-term effects of nasal intermittent p ositive pressure ventilation in patients with obesity-hypoventilation syndrome. Chest 2005; 128(2): 587 \200\223594. Peter JV, Moran JL, et al. Effect of non-invasive positive pressu re ventilation (NIPPV) on mortality in patients with acute cardiogenic pulmonary oedema: a meta-analysis. Lancet 2006; 367(9517): 1155 \200\2231163. Obesity Respiratory failure in obesity may be due to severe OSA, which responds to CPAP, or to obesity hypoventilation syn- drome. The latter group hypoventilate despite treatment of upper airway obstruction, and so require NIV. These patients can present with acute-on-chr onic respiratory fail- ure: ask about the duration of symptoms of hypoventilation or cor pu lmonale. They may require higher NIV pressures to overcome poor thoracic compliance, and ma y require a Ram FS, Picot J, Lightowler J, et al. Non-invasive positive pressure ventilation for treatm ent of respiratory failure due to exacerba- tions of chronic obstructive pulmonary disease. Rev Cochrane Database Syst 2004; 3: CD004104. A SIMMONDS 374 15.5 Nocturnal hypoventilation A reduction in overall ventilation is a natural accompani- ment of sleep and in normal indi viduals arterial oxygen saturation falls by a few per cent and PCO2 level rises by around 0 .5kPa. These physiological changes are most marked during REM sleep. Nocturnal hypoventilat ion becomes clinically signi \201 cant in conditions where either the respiratory muscle p ump is compromised or ventilatory drive is reduced (see Table 15.5.1), and may contribute t o the development and progres- sion of daytime (diurnal) respiratory failure in these group s. It should not be forgotten that common conditions over- lap. While there is no evidence tha t the prevalence of obstructive sleep apnoea (OSA) is increased in COPD, the coexistence of COPD and OSA is likely to produce noc- turnal hypoxaemia disproportionate to daytime SaO2 and will not be adequately addressed by long-term oxygen therapy (LTOT). Sleep studies in C OPD patients are there- fore indicated in COPD patients with witnessed apnoeas, crescendo d ecrescendo snoring, disproportionate hypox- aemia in relation to spirometry or daytime somn olence. In LTOT recipients sleep studies are advisable in those with marked daytime hyperca pnia or symptoms of CO2 retention (e.g. morning headache, nocturnal confusion, frequent hyp er- capnic exacerbations), and also in those in whom features of right heart failure and po lycythaemia persist while on LTOT (assuming compliance with LTOT has been con \201 rmed). Table 15.5.1 Reduced ventilatory pump: neuromuscular disease Muscular dystrophies Myopathies Neuromuscular and chest wall patients Routine evaluation of patients with neuromuscular dis ease and chest wall disorders includes assessment of symptoms and pulmonary function. Patie nts with isolated chest wall defects, e.g. idiopathic scoliosis and a vital capacity of >50 % predicted are unlikely to develop ventilatory insuf \201 ciency long term, so respirator y clinic follow-up is unnecessary. However individuals with progressive conditions, e.g. Du chenne muscular dystrophy or motor neuron disease, should be seen regularly and a sleep stu dy is indicated in those with symptoms of nocturnal hypoventilation, dysp- noea and FVC <60 %. Special attention should be played to high-risk groups, e.g. motor neuron disease and a particular catch in congenital disorders is that profound hypoventila- tion can be seen in those with severe chest wall restriction, e.g. chest \200\230en cuirasse \200\231 or rigid spine syndrome, despite a relatively preserved vital capacity. In a series of young patien ts with congenital myopathies, spinal muscular atrophy and muscular dystrophies, Ragette et al. found that a FVC capacity of <60% had a 91% sensitiv- ity and 89% speci \201 city for predicting the onset of sleep disordered breathing. Continuous hypoventilation was seen in REM and non-REM sleep once VC was less than 40% predicted and a VC of <25% predicted had a 92% sen- sitivity and 93% speci \201 city for predicting daytime ventila- tory failure. T he authors also measured maximum inspiratory mouth pressures, but these were less accurate at predicting respiratory insuf \201 ciency and did not add to VC measurements. Cough peak \202 ow measurement is use- ful to predict cough ef \201 cacy. In most neuromuscular co ndi- tons inspiratory and expiratory muscles are similarly affected. Discrepancies occur su ch as in isolated diaphragm paralysis due to phrenic nerve injury and in some spinal muscul ar atrophy patients in whom expiratory muscle weakness may outstrip inspiratory muscle weak ness. In motor neuron disease patients a sleep study is indicated if there is orthopnoea, r apid progression of symptoms, or VC <60%. There is no point in a sleep study if daytime PCO 2 is elevated. PCO2 values will be inevitably higher at night and time is wasted as the app ropriate action is to institute NIV if this is in accordance with the patient \200\231s wis hes. Theoretically, multichannel studies to differentiate obstructive apnoeas and hypopnoea s from hypoventilation may be helpful, but in practice bi-level ventilators are com- monly used and can be titrated to deal with all respiratory events regardless of etiology. Spinal muscular atrophy High spinal cord injury Motor neuron disease (amyotrophic lateral sclerosis) High ventilatory load COPD Cystic \201 brosis Bronchiectasis Morbid obesity Scoliosis/chest wall disorder Thoracoplasty Reduced ventilatory drive Congenital central hypoventilation syndromes Acquired central hypoventilation syndromes Sedative and analgesic drugs Prader \200\223Willi syndrome Etiology A combination of factors of factors underlies the reduction in alveolar ventlation . With the onset of sleep, ventilation falls due to a reduction in cortical ventilatory dri ve associ- ated with wakefulness, upper airway resistance increases as tone in pharyngeal m uscles falls and the ability to compen- sate for this increased resistance is diminished. B oth hyper- cpanic and hypoxic ventilatory drive are also reduced. Particularly during REM s leep there is hypotonia of the intercostal and accessory muscles with a switch to a dia- ph ragmatic pattern of breathing. REM sleep is therefore a challenging time for individuals wi th diaphragm weakness. In the supine position functional residual capacity will fall and ve ntlilation perfusion matching deteriorates especially in COPD patients. Nocturnal hypoxaemi a alters pulmo- nary haemodynamics \200\223 COPD patients who desaturate at night have sig ni \201 cantly higher pulmonary artery pressure and red cell mass than non-desaturators. F urther adverse consequences include dysrhythmias, nocturnal ischaemia, sleep fragmentation and possible neurocognitive effects. Predicting nocturnal hypoventilation COPD The extent on nocturnal desaturation in COPD pati ents is usually correlated with daytime SaO2 and CO2 levels. CHAPTER 15.5 Nocturnal hypoventilation 375 Diagnosis of nocturnal hypoventilation The characteristic features of nocturnal hypoventila tion can often be detected from an oximetry trace. Whereas recurrent saw tooth dips are see n in OSA, in nocturnal hypovention several longer periods if desaturation are seen coincidi ng with the periodicity of REM sleep. (As a corollary, mild hypoventilation may therefore b e missed if the patients sleep poorly and no REM sleep occur.) Strictly speaking, alveolar hyopoventilation should be de \201 ned by a rise in PCO2 and therefore endtidal of trans- cutaneous CO2 monitoring is helpful. Intermittent arterial blood gas measurements or an art erial line overnight is not conducive to sleep. Some centers rely on early morning blood ga s measure- ments, but these may be misleading, depending on the rela- tionship between the patient waking and measurement being made. nocturnal hypoventilation, 70% of the control group had developed daytime respiratory failu re, recurrent chest infections or marked symptoms within a year and 90% experienced these p roblems with 2 years. This would suggest that once nocturnal hypoventilation occurs, consid eration should be given to initiating NIV in the next year. Progression can be more indolen t in chest wall patients, and in these symptoms need to be marked or the trade off between nuisance value of NIV and symptom relief is not in the patients favor, and compliance likel y to be poor. COPD: LTOT is gold standard treatment in COPD patients who ful \201 l standa rd criteria. As indicated above a subgroup of patients may not tolerate LTOT due to hyperca pnia, and in these and those with recurrent hypercapnic exacerba- tions domiciliary NIV may have a role. Tuggey et al. showed that NIV may be cost effective in the selective group of patients who are regularly admitted with acute exacerba- tions and tolerate NIV well. Rand omized controlled trials are not conclusive on this point however, mostly as they have look ed at mortality as an end point and have been underpowered. NIV may also be helpful in othe r patients groups, e.g. in those with bronchiectasis or cystic \201 brosis and marked sym ptoms of nocturnal hypoventilation or as a bridge to transplantation. Central sleep apnoea Central sleep apnoea in adults is de \201 ned by the presence of epis odes of apnoea lasting for >10 seconds during which respiratory effort is absent. Central a pnoeas may either occur as a result of a profound reduction in ventilatory drive, e.g. foll owing brain stem stroke or as a result of heightened respiratory drive as in heart failure patients. In practice, the term embraces periodic breathing and Cheyne \200\223Stokes respi ration (Fig. 15.5.2) in which a cre- scendo decrescendo pattern of breathing is intersperse d with central apnoeas. In the latter, pulmonary oedema stim- ulates lung receptors leading to hyperventilation. This drives down CO2 such that an apnoea occurs, and the apnoea is te rminated by an arousal associated with hyperpnoea which again reduces CO2 precipitously and the cycle continues. Fig. 15.5.1 Nocturnal hypoventilation: 3 cycles during REM sleep. Transcutanous CO2 (TcCO2) monitoring has been criti- cised in the past, but a variety of ma chines are now in regu- lar use and proving useful, providing the limitations of endtidal C O2 are borne in mind. Transcutaneous measure- ments will always reveal a trend, not breath by breath results, and values are approx 0.5kPa above arterial values. Careful attentions s hould however be paid to calibrating the device with test gas mixtures, skin preparation an d application of the CO2 electrode. A printout of actual data (Fig. 15.5.1) should always b e available rather than sum- mary statistics so that artifacts can be detected and dis- car ded from \201 nal analysis. In Europe polysomnography is rarely used to diagnose nocturna l hypoventilation or other respiratory sleep disorders or to titrate therapy, e.g. deter- m ine NIV settings. Occasionally it may be helpful when problem solving in dif \201 cult cas es, or when treatment is not working optimally. Treatment Asymptomatic mild hypoventilation in a chest wall or neu- romuscular patient does not require treatment, in a chest wall patient, yearly repeat sleep study would be reasona ble although 6-monthly studies preferable in DMD. In Duchenne muscular dystrophy a randomiz ed controlled trial showed no evidence that prophylactic non-invasive ventilation is indica ted. Around a decade ago, consensus conference recommen- dations were that NIV should be us ed once daytime PCO2 exceeds 6kPa. However, the rate of progression of noctur- nal hypovent ilation may be dif \201 cult to predict and as a result many individuals may develop preci pitous daytime ventila- tory failure usually due to a chest infection. In one trial in whic h patients with neuromuscular and chest wall disease were randomized to NIV or control grou p at the onset of Fig. 15.5.2 Cheyne \200\223Stokes ventilation. The two types of central apnoea can easily be differenti- ated by measuring PCO2 level. A f urther learning point is that in some patients with marked respiratory muscle dys- function and obstructive apnoeas, inspiratory muscle A SIMMONDS 376 weakness is insufficient to generate detectable effort (pseudocentral apnoea). Symptomatic nocturnal hypoventilation can be effectively treated with nocturnal NIV which i mproves survival and outcome in chest wall and neuromuscular disease and may help selected COPD patients with marked hyper- capnia or recurrent hypercapnic exacerbations. Sleep disordered breathing in chronic heart failure (CHF) In severe CHF the prevalence of sleep disordered breath- ing (SDB) is at least 10 times gre ater than in the general population, and is associated with an increased risk of mor- talit y. In mild to moderate CHF, it has recently been shown that the prevalence of SDB remains h igh at approximately 50% and about half of these patients have predominantly central sleep apnoea. While treatment of obstructive sleep apnoea in CHF with CPAP is clearly evidence-ba sed, CPAP had not been shown to be beneficial in heart failure patients with central sleep apnoea. In these patients, pre- senting symptoms differ from OSA patients \200\223 sleepin ess is not a major feature, and treatment remains controversial. Oxygen therapy may be help ful but recent work suggests that stabilizing the respiratory pattern by a device that cap- tures ventilation and smoothes the respiratory disturbance may be effective (Autoset CS, R esMed Inc.). This is being tested in a current European randomized controlled trial. Further reading American Thoracic Society Consensus Statement. Respiratory care of the pati ent with Duchenne muscular dystrophy. American Journal of Respir Crit Care Med 2004; 170: 4 56 \200\223465. Consensus Conference. Clinical Indications for Noninvasive Positive Pressure Ventilation in Chronic Respiratory Failure due to Restrictive Lung Disease, COPD, and nocturnal hypoventi lation \200\223 a Consensus conference report. Chest 1999; 116: 521 \200\223534. Mellies U, Ragette R, Schwake C, et al. Long-term noninvasive ventilation in children and a dolescents with neuromuscular disorders. Eur Respir J 2003; 22: 631 \200\223636. Ragette R, Mellies U, Schwake C, et al. Patterns and predictors of sleep disordered breathi ng in primary myopathies. Thorax 2002; 57: 724 \200\223728. Raphael J-C, Chevret S, Chastang C, et al. Randomized trial of preventive nasal ventilation in Duchenne muscular dystrophy. Lancet 1994; 343: 1600 \200\2231604. Takasaki Y, Orr D, Popkin J, et al. Effect of nasal continuous positive airway pressure on sleep apnea in congestive heart failure. Am Rev Respir Dis 1989; 140: 1578 \200\2231584. Key recommendations \200 There should be a high suspicion of nocturnal hypoven- tilation in patients with conditions reducing ventilatory capacity and drive and disorders increasing ventilatory load \200 \223 ask about symptoms of nocturnal hypoventilation, e.g. morning headaches, poor sleep qu ality, waking breathless, vivid dreams. Nocturnal hypoventilation can be diagnosed by over- night oximtry and PCO2 measured continuously with transcutaneous or endtidal CO2 probes. C entral sleep apnoea is caused by either severely reduced ventilatory drive or in conditions that destabi- lise respiratory pattern as a result of enhanced ventila- tory drive, e.g. h eart failure, breathing at high altitude. Teschler H, Dohring J, Wang YM, et al. Adaptive pressure support servo-ventilation: a novel treatment for Cheyne-Stokes respira- tion in heart failure and central sleep apnea. Am J R esp Crit Care Med 2001; 164: 614 \200\223619. Tuggey JM, Plant PK, Elliott MW. Domiciliary non-invasive ventila- tion for recurrent acido tic exacerbations of COPD: an economic analysis. Thorax 2003; 58: 867 \200\223871. Ward SA, Chatwin M, Heather S, et al. Randomized controlled trial of non-invasive ventilati on (NIV) for nocturnal hypoventilation in neuromuscular and chest wall disease patients wit h daytime normocapnia. Thorax 2005; 60: 1019 \200\2231024. This page intentionally left blank J PEPPERELL 378 15.6 Cheyne \200\223Stokes respiration associated with left ventricular failure Investigations Con \201 rm LVF with Echo and brain natriuretic peptide. Exclude type II re spiratory failure with ABG sampling. Cheyne \200\223Stokes respiration (CSR) is characterized by the cyclical pattern of smooth crescendo decrescendo periods of hyperventilation with accompanying periods of central apno ea. It is variably called central sleep apnoea and peri- odic breathing. CSR is a respirato ry complication of chronic left ventricular failure (LVF). CSR is important clinically beca use it can cause symptoms, worsens heart failure and is amenable to treatment. Overnight pulse oximetry Approximately half of patients with NYHA class III and IV will hav e an apnoea hypoxia index (AHI) of between 0 \200\22310 per hour on multi channel sleep stu dy. Oximetry is a simple screening tool looking for repetitive desaturations. Compared to O SA, CSR tends to have a longer time period, lower amplitude desaturations through the apnoe a and a slower rise in saturation at end apnoea (Fig. 15.6.1).