CAUSES 73 Diffuse alveolar hemorrhage not uncommon complication of leu- kaemia, and allogeneic or aut ologous HSCT; similar clinical presenta- tion to that of pneumonia; haemoptysis is rare; mu ltilobar CXR/CT in \201 ltrates; proposed diagnostic criteria include exclusion of infecti on, progressively bloodier returns from BAL of three different subseg- mental bronchi (alth ough limited sensitivity and speci \201 city), and \211 20% of alveolar macrophages haemo siderin- \201 lled (although may require several days to appear); reported mortality range s 30 \200\223100% \200\230Idiopathic pneumonia syndrome \200\231 following allogeneic or a utologous HSCT; breathlessness with hypoxia and multilobar CXR/CT in \201 ltrates; infecti on excluded with BAL and ideally a second later investigation (e.g. repeat BAL or lung biop sy); diffuse alveolar damage or interstitial pneumonitis on biopsy; mortality >70% Engraftm ent syndrome comprises fever, ARDS, and erythematosus rash during marrow recovery post-HSCT Chronic air \202 ow obstruction (bronchiolitis obliterans) following allo- geneic HSCT (f rom non-identical sibling or unrelated individual; occurs only extremely rarely following a utologous procedure); typically associ- ated with chronic graft-versus-host disease (GVHD); gradual onset dry cough, dyspnoea, wheeze, obstructive spirometry; CXR often normal; air-t rapping and bronchial dilatation on HRCT; TBB low sensitivity; may be complicated by Asperg illus infection; variable course Post-transplant lymphoproliferative disease most common fo llowing lung transplant (p 317); may also follow other solid organ or allogeneic HSC transp lant Pulmonary alveolar proteinosis (p 630) Pulmonary veno-occlusive disease Pulmonary meta static calci \201 cation may complicate chronic renal failure and rarely progress after tr ansplantation; usually asymptomatic, rarely causes restrictive ventilatory defect; CXR show s single or multiple nodules or patches of consolidation, may not appear calci \201 ed; CT typically diagnostic, although biopsy occasionally needed Right hemidiaphragm dysfunction is common after liver transplant, and usually not relevant clinically. \200 \200 Multiple disease processes About 30% of patients have two or more disease processes account ing for their respiratory involvement. Secondary infection with a different infectious agen t (commonly Aspergillus or Gram-negative bacteria such as Pseudomonas) may complicate eithe r a primary respiratory infection or a non-infectious process such as pulmo- nary embolism. Secondary infection is associated with a poor prognosis; consider particularly in patients who deteriorate after an initial response to treatment, and in patients who are neutropeni c. Pleural effusion Differential diagnosis in non-HIV immunocompro- mised patients includes cardiac failure and \202 uid overload, pulmonary embolism, drug-related, parapneumonic ( bacterial including Nocardia, fungal, e.g. PCP), or related to underlying disease (e.g. leu kaemic in \201 ltrates, lymphoma, chylothorax, myeloma). Pleural effusions are common afte r liver transplant: usually right-sided or bilateral transudates and resolve by third week; may require drainage if symptomatic. CHAPTER 12 Pulmonary disease (non-HIV) 74 Differential diagnosis of pulmonary complications based on time course after transplantatio n Solid organ transplantation First month post-transplant (recent surgery ITU) \200 Nosocomial bacterial infection (Gram-negative, S. aureus \200\224including MRSA, Legionella ) ARDS Pulmonary oedema Drug-induced Pulmonary embolism Pleural effusion (especially after liver transplant) Right hemidiaphragm dysfunction (after liver transplant). \200 \200 \200 \200 \200 Months 1 \200\2236 (maximal immunosuppression) \200 Opportunistic infection (CMV, PCP, Nocardia, Aspergillus, Scedosporium apiospermum) Drug-in duced Post-transplant lymphoproliferative disease. \200 Months >6 (reduction in immunosuppression, unless rejection) \200 Common community-acquired pathogens (Haemophilus in \202 uenzae, Streptococcus pneumoniae, Legionella, tuberculosis, non-tuberculous mycobacteria, PCP, endemic mycoses e.g. Histopla sma, viruses e.g. in \202 u- enza, para-in \202 uenza, adenovirus, RSV) Opportunistic pat hogens (see above) Post-transplant lymphoproliferative disease Pulmonary metastatic calci \201 cation. \200 \200 DIFFERENTIAL DIAGNOSIS OF PULMONARY COMPLICATIONS 75 Haematopoietic stem cell transplantation (HSCT) First month post-transplant (prolonged neut ropenia pre-engraftment) \200 Infection (bacteria, e.g. Pseudomonas aeruginosa, Escherich ia coli, Klebsiella pneumoniae, Haemophilus in \202 uenzae, Staphylococcus aureus, Legione lla species; fungi, e.g. Aspergillus; viruses e.g. herpes simplex, adenovirus) Pulmonary oe dema ARDS Transfusion-related acute lung injury Drug-induced Diffuse alveolar hemorrhage Id iopathic pneumonia syndrome. \200 \200 \200 \200 \200 Months 1-3 (impaired cellular immunity post-engraftment, related in part to immunosuppressi ve drugs and GVHD) \200 Opportunistic infection (Gram-negative bacteria, Nocardia, CMV, herpes simplex, PCP) Drug-i nduced Diffuse alveolar hemorrhage Idiopathic pneumonia syndrome Engraftment syndrome Post- transplant lymphoproliferative disease Pulmonary veno-occlusive disease. \200 \200 \200 \200 \200 Months >3 (poor lymphocyte function, particularly following allogeneic HSCT) \200 Infection (Gram-positive bacteria, CMV, herpes, varicella-zoster, tuberculosis, non-tubercu lous mycobacteria, PCP, Aspergillus, endemic mycoses, e.g. Histoplasma) Chronic air \202 o w obstruction (bronchiolitis obliterans, associated with GVHD) Post-transplant lymphoprolif erative disease Pulmonary veno-occlusive disease. \200 CHAPTER 12 Pulmonary disease (non-HIV) 76 Treatment Antimicrobials Depending on the clinical circumstances, antimicrobials may need t o be started prior to de \201 nitive investigations (see p 69), although blood cultures sh ould always precede antibiotic treatment. Choice of anti- microbial depends on the underlyi ng condition and local hospital policy. \200 In general, most neutropenic patients are treated with broad-spectrum antibiotics providing both Gram-positive and Gram-negative cover, e.g. piperacillin (4.5 g IV qds); antifungals are considered if slow response to treatment or subsequent deterioration. Consider vancomyc in if MRSA is a possibility Treatment for CMV and PCP is associated with signi \201 cant s ide-effects, and ideally should be based on a de \201 nitive diagnosis. In unwell patients who are strongly suspected to have PCP, treatment (p 478) can be started immediately, as B AL Pneumocystis jiroveci stains remain positive for up to 2 weeks Antituberculous treatment should only rarely be administered in the absence of a microbiological diagnosis. Diuretics Fluid overload and pulmonary oedema are common following renal and HSCT transplan tation, and typical clinical and radiological signs may be disguised; consider a trial of d iuretics. Steroids Despite a lack of randomized controlled trials, prednisolone (1 \200\223 2 mg/kg/day PO, or up to 2 g methylprednisolone IV daily) is often considered in the treatm ent of drug- or radiation-induced lung disease, engraftment syndrome, diffuse alveolar hemo rrhage, and idiopathic pneumonia syndrome following HSCT. Ideally exclude underlying infect ion prior to starting steroids. Prednisolone (40 \200\22380 mg daily PO) is recom- mended f or the treatment of PCP in patients with respiratory failure. Bronchiolitis obliterans foll owing allogeneic HSCT is usually treated with increased immunosuppression. Supportive treat ment Administer oxygen to maintain saturations >95%. Respiratory failure in immunocompromis ed patients is associated with a poor outcome: mortality following intubation and mechanica l ven- tilation ranges 60 \200\223100%. Early intermittent use of non-invasive ventilation in immunocompromised patients with pulmonary in \201 ltrates and hypoxia (de \201 ned as breathlessness, respiratory rate >30/min and PaO2/FiO2 ratio <200) has been shown to reduce the need for intubation and improve mortality. Before NIV is commenced, a decision regardi ng suitability for intubation and mechanical ventilation should be made. Surgery Surgical w edge resection or lobectomy may be considered in the treatment of invasive aspergillosis, e ither acutely for lesions adjacent to pulmonary vessels that are judged to have a signi \201 cant risk of massive haemoptysis, or at a later date for residual lesions at risk of r eactivation with further chemotherapy. TREATMENT 77 Further information Kotloff RM et al. Pulmonary complications of solid organ and hematopoie tic stem cell transplantation. AJRCCM 2004; 170: 22 \200\22348 Shorr AF et al. Pulmonary in \201 ltrates in the non-HIV-infected immunocompromised patien t. Chest 2004; 125: 260 \200\22371 Hilbert G et al. Non-invasive ventilation in immunosuppressed patients with pulmonary in \201 ltrates, fever, and acute respiratory failure. NEJM 2001; 344: 481 \200\2237 This page intentionally left blank 79 Chapter 13 Pulmonary disease in the immunocompromised (HIV) Clinical assessment 80 Further investigations and treatment 82 Causes of respiratory diseas e in HIV infection 83 CHAPTER 13 Pulmonary disease (HIV) 80 Clinical assessment Widespread use of highly active antiretroviral therapy (HAART) and anti - microbial prophylaxis in HIV has resulted in a longer survival, as well as changes in the nature of respiratory involvement. Respiratory disease remains common in the setting of HI V, and patients should be managed in consultation with an HIV specialist. Causes of respiratory disease in the HIV-infected patient are listed on p 83. Speci \201 c conditions are described separately (e.g. PCP p 476, TB p 487). Key steps in management ar e as follows. Clinical assessment \200 As with other causes of immunocompromise, clinical features of respiratory disease in HIV-i nfected patients are non-speci \201 c: breathless- ness, cough, fever, weight loss, and fa tigue are common, although chest symptoms are not always present Ask about treatment and co mpliance with HAART and PCP prophylaxis Source of HIV infection may be relevant: Kaposi \200\231s sarcoma occurs particularly in homosexual men, and in African men and women; tube r- culosis and bacterial pneumonia are more common in IV drug users Travel history may be u seful: infection with \200\230endemic mycoses \200\231 (e.g. histoplasmosis, blastomycosis , coccidioidomycosis) is well recognized in the USA, but rare in the UK Careful examination may provide clues to the respiratory condition. Pulmonary Kaposi \200\231s sarcoma is unus ual in the absence of disease else- where; palatal Kaposi \200\231s sarcoma in particular i s predictive of pulmonary involvement. Extrapulmonary mycobacterial disease is common, and may involve the liver, lymph nodes, pericardium, and meninges. \200 Investigations CXR \200 \200 CXR changes are relatively non-speci \201 c PCP classically appears as bilateral perihilar in \201 ltrates that progress to alveolar shadowing; more unusual patterns include small nodular in \201 ltrates or focal consolidation. CXR is normal in 10% of cases. Pneumothora x is suggestive of PCP Appearances of bacterial pneumonia are often atypical, e.g. diffuse bilateral in \201 ltrates mimicking PCP Pleural effusion or hilar/mediastinal lymphadenopa thy are unusual in PCP, and are more suggestive of mycobacterial infection or Kaposi \200 \231s sarcoma. CXR cavitation is unusual in tuberculosis occurring late in the course of HI V. CD4 count Useful in narrowing the differential diagnosis. Bacterial infection, including tu berculosis, occurs at any stage of disease, although infection is more severe at lower CD4 counts; PCP and atypical presentations of tuberculosis occur most commonly at CD4 <200 \227 106/L; non-tuberculous mycobacteria, Kaposi \200\231s sarcoma, and lymphoma occur late in the disease (CD4 <50 x 106/L). A recent increase in CD4 count (following the intro- duc tion of HAART) may suggest an immune reconstitution in \202 ammatory syndrome (IRIS, see o pposite). CLINICAL ASSESSMENT 81 Blood cultures should be taken prior to antimicrobial treatment. Bacteraemia is relatively common with bacterial pneumonia in HIV, particularly with S. pneumoniae infection. Bacterae mic tuberculosis may occur in advanced disease. Other blood tests Raised in \202 ammatory markers are a non-speci \201 c \201 nding. Sputum Induced sputum may assist the diagnosis of PCP and mycobacte- rial disease. Induced sputum has a sensitivity of about 60% for the diag- nosis of PCP. Tuberculosis is more like ly to be smear-negative in the setting of HIV, as cavitation in these patients is less comm on. Induced sputum should ideally be obtained in a negative-pressure room. Other cultures Consider sampling urine, stool, lymph node, or bone marrow in suspected myco bacterial disease, as extrapulmonary disease is common. CT chest is useful in looking for evidence of respiratory disease in patients with symptoms but a normal CXR, and may be helpful in directing invasive diagnostic procedures. CT is al so of bene \201 t in the diagnosis and staging of Kaposi \200\231s sarcoma and lymphoma. I mmune reconstitution in \202 ammatory syndrome (IRIS) [immune restoration disease (IRD) or paradoxical reaction] is a fairly poorly de \201 ned clinical syndrome resulting from res tored immunity to infectious or non- infectious antigens, following the introduction of HAA RT. The mechanism is uncertain, but probably includes partial recovery of the immune system or an exuberant host-antigen response with host genetic susceptibility. It is more likely in the context of current infection due to mycobacteria, herpes, varicella, and CMV. The cl inical features are variable and diverse, and depend on the underlying infectious or non-in fectious agent. A clini- cally silent infection may be \200\230unmasked \200\231 as the CD 4 count rises, and may be associated with an excessive in \202 ammatory response. The commonest clinical features are fever, lymphadenopathy, and wors- ening respiratory sym ptoms. New pulmonary in \201 ltrates and pleural effu- sions are common. TB-IRIS tends to develop within 2 months of the start of HAART, and CNS TB-IRIS is reported up to 10 months after HAART initiation. Corticosteroids seem to be effective although no RCT data exist. Various regimes are sugges ted, including methylprednisolone 40 mg bd and prednisolone 20 \200\22370 mg od for up to 7 weeks. Infectious agents must also be treated and, in the very unwell, this may mean empir ical treat- ment for PCP and TB, and high-dose steroids, whilst awaiting con \201 rmatory microbiology. CHAPTER 13 Pulmonary disease (HIV) 82 Further investigations and treatment Bronchoscopy and BAL \200 Bronchoscopy and BAL are safe and frequently diagnostic in this patient group, and should b e considered early in management, particularly in the presence of a diffuse CXR abnormality or following non-diagnostic induced sputum analysis. BAL should also be considered in pati ents with a localized CXR abnormality that has not responded to a trial of broad-spectrum a ntibiotics BAL \202 uid analysis: routine microscopy and culture for bacteria; additional stains and culture for fungi, mycobacteria, Nocardia; silver or immuno \202 uorescence st ain for Pneumocystis; cytology, including \202 ow cytometry for malignant cells; viral se rology. Consider additional tests such as Cryptococcus antigen detection or CMV PCR Both No cardia and Rhodococcus equi stain weakly acid-fast, and may be confused with mycobacteria K aposi \200\231s sarcoma appears as \200\230raised bruises \200\231 in the trachea or bronc hi on bronchoscopy; routine biopsy is not recommended, as diagnostic yield is low and signi \201 cant hemorrhage may occur. Lung biopsy If bronchoscopy and BAL are non-diagnostic, consider repeat bronchoscopy with T BB or surgical lung biopsy. TBB has a greater sensitivity than BAL, but potentially serious complications, such as pneu- mothorax or hemorrhage are signi \201 cantly more common. Treatment \200 Consider broad-spectrum antibiotics and empirical treatment for PCP (high-dose co-trimoxazo le, and steroids if the patient is in respiratory failure p 478). BAL Pneumocystis stains r emain positive for up to 2 weeks despite treatment, and so empirical treatment for PCP shou ld not be delayed if the patient is unwell and this diagnosis is suspected Further antimicr obial treatment can be directed at speci \201 c pathogens isolated from BAL or biopsy. CMV is commonly isolated from BAL \202 uid, but rarely, if ever, causes lung disease in the setting of HIV and the value of antiviral treatment in such cases is unknown Supportive the rapy with oxygen; consider NIV. ITU admission for invasive ventilation may be required. PCP is the commonest cause of respiratory failure requiring ITU admission in HIV-positive pati ents. Mortality from PCP requiring mechanical ventilation is about 60%, although it may be signi \201 cantly higher in patients with low CD4 counts Steroids may be effective in the treatment of non-speci \201 c interstitial pneumonitis and lymphocytic interstitial pneumo nitis. CAUSES OF RESPIRATORY DISEASE IN HIV INFECTION 83 Causes of respiratory disease in HIV infection (Commoner causes in bold) Infectious Bacteri a \200 \200 \200 \200 \200 \200 Streptococcus pneumoniae Haemophilus in \202 uenzae Staphylococcus aureus Gram-negative ba cteria, especially Pseudomonas Nocardia Rhodococcus equi. Mycobacteria \200 \200 \200 Mycobacterium tuberculosis Mycobacterium avium-intracellulare Mycobacterium kansasii. Viruses \200 \200 \200 \200 \200 In \202 uenza Para-in \202 uenza Respiratory syncytial virus Herpes simplex Adenovirus. Fungi \200 \200 \200 \200 Pneumocystis jiroveci Aspergillus spp. Cryptococcus neoformans Endemic mycoses. Parasites \200 Strongyloides stercoralis (hyperinfection syndrome \200\224rare). Non-infectious \200 \200 \200 \200 \200 \200 \200 \200 IRIS Kaposi \200\231s sarcoma Lymphoma Drug-induced lung disease Non-speci \201 c intersti tial pneumonitis Lymphocytic interstitial pneumonitis Cardiogenic pulmonary oedema Increase d risk of lung cancer. Commonest causes of pleural effusion in HIV infection are Kaposi \200\231s sarcoma, parapne umonic effusion, tuberculosis, PCP, and lymphoma. This page intentionally left blank 85 Chapter 14 Sleep and ventilation History 86 Examination and investigations 88 CHAPTER 14 Sleep and ventilation 86 History The problem Sleep apnoea and related problems are now a common reason for referral to many respiratory units. This is due to a much better recognition of the syndromes and th e increasing prevalence of obesity in the general population. Most respiratory units with s leep services are seeing patients primarily for possible obstructive sleep apnoea (OSA) and , therefore, most patients tend to be sleepy and referrals for insomnia are not usually enc ouraged. Patients arrive at a respiratory sleep unit for several different reasons. They are commonly: \200 Concerns that the patient may have sleep apnoea, with or without a full house of symptoms L oud snoring, with the patient or spouse seeking advice about noise reduction Referrals from the ENT department who may be considering offering surgery for snoring and wish to exclude OSA \201 rst Excessive daytime sleepiness, diagnosis unclear, might just be OSA, might b e narcolepsy, etc. Assessment pre bariatric surgery as prevalence of OSA very high Other no cturnal symptoms such as sleep walking, panic arousals, etc. \200 Thus in sleep out-patients the issues revolve around making the correct diagnosis of the ex cessive daytime sleepiness or nocturnal symptoms (and referring on if appropriate), offerin g simple advice for snoring, or putting the patient through the nasal continuous positive a irway pressure (CPAP) induction program. Some units perform a sleep study \201 rst on the basis of an appropriate referral letter as it is more ef \201 cient, others see the patient \201 rst and then book a sleep study if indicated. For the purposes of this account it is assumed that the patient is seen \201 rst. History A clear history of the exact presenting complaint is obviously necessary, concentrating on the following points when OSA is suspected (a full discussion is availabl e in the section on OSA, p 567). \200 Sleepiness: how severe, what does it interfere with, over how long has it been coming on, a nd does it reduce quality of life? The Epworth sleepiness scale is useful to assess this (s ee p 89). This is scored out of 24; 0 \200\2239 is considered normal and >9 excessively sle epy. It is only a guide and should be interpreted with the overall history Important to dif ferentiate sleepiness (tendency to nod off, due to inadequate sleep) from tiredness (feelin gs of exhaustion due to many causes, often without a tendency to nod off ) Snoring and apno eas. Best assessed from a witness: how loud, continuous, intermittent, and are there recogn ized \200\230stopping breathing \200\231 or choking episodes during sleep? Other OSA sympt oms, such as nocturia and restless sleep History of weight and neck size increases over the last 5 \200\22310 years (recent weight gains common) \200 HISTORY 87 History of nasal or other ENT surgery (previous palate surgery increases discomfort of CPAP ) Previous medical history (certain risk factors such as mandibular surgery, hypothyroidism , acromegaly, Down s, Prader \200\223Willi, etc.) Previous cardiovascular/cerebrovascular h istory and hypertension history (may in \202 uence decision to treat) Alcohol and smoking history Occupation and shift working Driving issues, such as sleepiness while driving and \200\230near misses \200\231 or actual sleep-related accidents Does the patient drive for a living and what kind of vehicle or license? \200 \200 If OSA seems unlikely, then other causes of sleepiness need to be consid- ered, concentrati ng on the commonest. Alternative diagnoses for excessive daytime sleepiness \200 \200 Depression, often missed Lifestyle issues \200\224alcohol, late night working, shift work, caffeine abuse, family circumstances, etc. Drugs \200\224some of the antihypertensives (e.g . B-blockers) and psycho- active drugs (e.g. antidepressants and anxiolytics) can provoke s leepiness Narcolepsy \200\224e.g. associated with cataplexy (sudden loss of muscle tone in response to excitement or anticipation), sleep paralysis (frightening paralysis on wakening for a few seconds or minutes), and proli \201 c vivid dreaming, often at sleep onset or d uring daytime naps Periodic limb movements during sleep (associated with restless legs duri ng the day, especially in renal failure) Post-severe head injury or cranial irradiation (hy pothalamic damage) Post-infectious (e.g. Epstein \200\223Barr virus) Idiopathic (sometimes hereditary) Certain neurological disorders such as myotonic dystrophy, Parkinson \200\231s, and previous stroke Simply being at the sleepier end of the normal spectrum The symptom ma y really be tiredness, such as in \200\230ME \200\231 or insomnia, when the ESS is usually low Blind insomnia/sleepiness \200\224circadian problem when 24-h cycle not linked with th e real world through blue light exposure and melatonin production. \200 \200 \200 \200 CHAPTER 14 Sleep and ventilation 88 Examination and investigations Examination of these patients is often relatively unhelpful. In OSA the main features to look for are: \200 Neck circumference (best measure of the obesity contribution to the cause of OSA, >17 in) a nd BMI Oropharynx, usually crowded with boggy mucosa, with perhaps large tonsils Teeth, cro wding suggests retrognathia/micrognathia (and mandibular advancement devices require sound teeth) Nasal patency (how easy will nasal CPAP be?). Also: \200 Assessment of respiratory function, signs of cor pulmonale, FEV1/VC ratio and SaO2 (COPD in creases likelihood of being in type II ventilatory failure, so-called \200\230overlap synd rome \200\231) Blood pressure (may in \202 uence decision to treat OSA) Evidence of endocr ine abnormalities: hypothyroidism, acromegaly, Cushing \200\231s, diabetes. \200 It may also be appropriate to look for: \200 \200 Evidence of a neuromuscular disorder, including a previous stroke Evidence of heart failure (central sleep apnoea, or Cheyne \200\223Stokes respiration, which can produce overnight o ximetry traces similar to those of OSA). Clinic tests to perform \200 Blood gas estimation if respiratory failure suspected (these OSA patients require more urge nt treatment) Thyroid function (hypothyroidism not always clinically obvious) plus other ho rmones if indicated Routine hematology and biochemistry (prevalence of type II dia- betes w ill be high in this overweight population) Some would recommend a fuller cardiovascular ris k assessment including cholesterol, fasting triglycerides, glucose, and folate since these patients are often in a high risk group (untreated 10-year car- diovascular event risk typi cally predicted to be about 35%). Other scenarios If it is known already from a prior sleep study that the patient has OSA, t hen the clinic appointment will revolve around a joint decision between the doctor and the patient as to whether a trial of treatment is indicated (usually nasal CPAP). This will dep end mainly on the severity of symptoms vs. the perceived inconvenience of the treatment. An abnormal sleep study is not a reason in its own right to prescribe CPAP. Weight loss is im portant, but rarely achievable, and other treatable causes of OSA must not be missed (e.g. hypothyroidism, tonsillar hyper- trophy) simply because nasal CPAP is available. EXAMINATION AND INVESTIGATIONS 89 If the patient has come via ENT and is being considered for pharyngeal surgery, then the re spiratory physician \200\231s role is to dissuade the patient from this route as the object ive success rate is poor and the hazards signi \201 - cant. The presence of signi \201 ca nt OSA is a contraindication to surgery. All other approaches to snoring, such as the use o f mandibular advancement devices, should be considered \201 rst, and pharyngeal surgery r egarded as the last resort of the totally desperate. EPWORTH SLEEPINESS SCALE Name: Hospital number Date: Your age (Yrs) Your sex (Male = M / Female = F) \200 How like ly are you to doze off or fall asleep in the situations described in the box below, in cont rast to feeling just tired? This refers to your usual way of life in recent times. Even if you haven \200\231t done some 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 situat ion:- \200 0 = Would never doze 1 = Slight chance of dozing 3 = High chance of dozing 2 = Moderate chance of dozing Situation Chance of dozing \235\221 Sitting and reading \235\221 Watching TV Sitting, inactive in a public place (e.g. a theater or a meeting) \235\221 \235\221 As a passenger in a car for an hour without a break Lying down to rest in the afternoon when circumstances permit \235\221 \235\221 Sitting and talking to someone \235\221 Sitting quietly after a lunch without alcohol \235\221 In a car, while stopped for a few minutes in the traf \201 c \235\221 Thank you for your cooperation Total score = Fig 14.1 Epworth Sleepiness Scale questionnaire. This page intentionally left blank 91 Chapter 15 Unexplained ventilatory failure Causes 92 Clinical assessment and management 96 CHAPTER 15 Unexplained ventilatory failure 92 Causes De \201 nition Ventilatory failure is conventionally divided into type I (hypoxia o nly, PaO2 <8 kPa) and type II (hypoxia and hypercapnia, PaCO2 >6 kPa): they are conceptuall y quite different. Type I is an increased alve- olar-to-arterial (A \200\223a) oxygen gradi ent (implying increased ventilation/per- fusion mismatch, V/Q), with adequate alveolar vent ilation to maintain a normal PaCO2. The number of causes is vast, including most of respira tory medicine, and requires the usual \200\230history, examination, and investigations \200\231. A more dif \201 cult, less common, clinical scenario is an unexplained rise in PaCO2 (>6 k Pa, type II), with no obvious cause following a standard assessment. This may occur in the out-patient, ward, A&E, or ICU setting. Pathophysiology A rise in PaCO2 can be due to V/Q m ismatch with inadequate compensatory hyperventilation, e.g. overwhelming asthma, when there will also be a large A \200\223a gradient indicating this increased V/Q mismatch. However, it can also be due to inadequate ventilatory drive, or primary ventilatory pump failure, w here the A \200\223a gradient will usually be normal. The list below contains mainly the ca uses that might not have been suspected from the initial assessment, but for completeness a lso includes more obvious causes. The conditions with asterisks are the ones most commonly discovered when the cause is not immediately obvious. Failure of drive Brainstem abnormality \200 \200 \200 Polio and post-polio syndrome* (exact mechanism unclear) Brainstem stroke (involvement of r espiratory centers bilaterally) Arnold \200\223Chiari malformation \200\224herniation of ce rebellum into foramen magnum compressing the brainstem Syringobulbia \200\224expansion of a \202 uid compartment in the middle of the spinal cord extending up into the medulla (can be associated with Arnold \200\223Chiari malformation) Surgical damage during operations f or Arnold \200\223Chiari and syringobulbia Encephalitis Brainstem tumor Congenital \200\224 usually presents soon after birth, can be later; abnormalities of neural crest development due to increased number of \200\230alanine repeats \200\231 in one of the homeobox genes ( PHOX2B) \200 \200 \200 Suppression \200 \200 Sedative drugs, including alcohol, opiates, etc.* Metabolic alkalosis (hypokalaemic alkalos is, diuretic-induced, prolonged vomiting) CAUSES 93 Pump failure Neurological (particularly if diaphragm involved) \200 Myopathies \200 Acid maltase de \201 ciency (Pompe \200\231s), diaphragm paralysis commonly occurs early o n* Duchenne muscular dystrophy Myotonic dystrophy Several other very rare primary or second ary myopathies, e.g. limb girdle, hypothyroid, drugs (hydroxychloroquine) \200 \200 Neuropathy \200 \200 Motor neuron disease (MND)* can affect diaphragm early on Bilateral diaphragm paralysis*, e .g. trauma, bilateral neuralgic amyotrophy (also known as \200\230brachial neuritis \200 \231, in \202 ammatory damage to nerves of lower brachial plexus \200\224cause unknown) Gu illain \200\223Barr Spinal muscular atrophy, autosomal recessive, spinal cord motor neuro ns High cord transection \200 Neuromuscular junction abnormalities \200 \200 \200 Myasthenia gravis* Lambert \200\223Eaton Myasthenic syndrome (LEMS) Anti-acetylcholine este rase poisoning (usually from organophos- phate insecticides) Mixed \200 Chest wall \200 \200 \200 Post- ITU ( \200\230critical care neuropathy \200\231), post muscle relaxant drugs* Obesity* Scoliosis* Post thoracoplasty (usually \200\230three stage \200\231, many ribs ca ved in starting from the top down \200\224done for tuberculosis prior to effective chemothe rapy) Flail chest Pneumothorax/large effusion Severe ankylosing spondilitis \200 \200 Airways obstruction/mixed \200 \200 Unrecognized COPD/severe asthma* Obstructive sleep apnoea and additional COPD/obesity/muscl e weakness*, sometimes called \200\230overlap syndrome \200\231. The ventilatory loading effects of obesity, COPD, and OSA can summate to produce ventilator y failure, when on their own they would not be regarded as of suf \201 cient severity. Est imating the contribution each is making to an individual \200\231s ventilatory failure can in \202 uence therapy, and expectations of success: e.g. if OSA dominant (>4% SaO2 dips/h >30) the ventilatory failure is likely to respond to CPAP; dominant COPD (FEV1 <25% predict ed) will need maximal lower airways dilator therapy (thresholds only for general guidance); but the likely poor response of the lower airways obstruction will mean that even limited additional weight reduction, and/or treatment of milder OSA, may be useful in the latter si tuation. CHAPTER 15 Unexplained ventilatory failure 94 Clinical presentation Slow onset In several of the above conditions, e.g. acid maltase de \201 ciency, MND, and scoliosis, the onset of ventilatory failure can be insidious and incl ude: \200 \200 \200 \200 \200 \200 General fatigue and/or hypersomnolence Headaches on awakening Morning confusion Morning cya nosis Ankle oedema ( \202 uid retention, cor pulmonale, from the hypoxia). Dyspnoea standi ng in the swimming pool (this usually indicates diaphragm paralysis, as pressure of water, even at 1 m depth, pushes unopposed diaphragm further up into the chest) Swallowing dif \201 culties (often MND), or other evidence of a more generalized proximal neuromuscular pr oblem. Rapid onset Sometimes the signi \201 cance of these symptoms is missed for a while and a r elatively trivial respiratory tract infection tips the balance and the patient goes into se vere ventilatory failure with coma. These individuals will end up ventilated on ICU and may be dif \201 cult to wean, or present again with ventilatory failure a few weeks after dis charge. Further information Resta O et al. Sleep-related breathing disorders, loud snoring and exce ssive daytime sleepiness in obese subjects. Int J Obes Relat Metab Disord 2001; 25: 669-75 This page intentionally left blank CHAPTER 15 Unexplained ventilatory failure 96 Clinical assessment and management History, examination, and investigations History Careful ly taken history, e.g. symptoms of subtle weakness prior to presentation, episode of should er pain (neuralgic amyotrophy), past history of polio, orthopnoea (diaphragm weakness), dru g history. Often this is not available as the patient may present unconscious. Examination Thorough examination, particularly neurological, e.g. fascicu- lation, diaphragm weakness ( inward drawing of abdomen on inspiration or snif \201 ng \200\224masked if on positive pre ssure ventilation), myotonia, as well as rarer signs seen in some of the conditions listed previously. Blood gasses taken breathing air (following >20 min off extra O2) \200 \200 \200 \200 Degree of CO2 retention Presence of a base excess indicating chronicity of CO2 retention Ca lculate A \200\223a gradient to detect any V/Q mismatch (p 792) In pure hypoventilation the re should be no signi \201 cant A \200\223a gradient (<2 kPa), unless there is associated basal atelectasis from poor lung expansion and/or obesity. Pulmonary function tests (p 827) \200 \200 \200 Presence of unexpected severe airways obstruction Reduced vital capacity (neurological or c hest wall) Further fall of VC (>20% de \201 nitely abnormal) on lying down \200\224 indica tive of diaphragm paralysis. A supine VC of <25% predicted is most predictive of this being the main cause of the raised PaCO2. Mouth pressures, sniff pressures, or trans-diaphragmat ic pressures; not much more helpful than lying and standing VC. Speci \201 c tests \200\224for some of the conditions listed above such as: \200 \200 \200 \200 EMG studies \200\223MND, myotonia MRI \200\223Gadolinium enhanced: Arnold \200\223Chiari, b rainstem lesion, syrinx CPK \200\223Some myopathies Sleep study \200\223E.g. (i) REM hypoxi a (early marker of ventilatory failure when supine VC usually has dropped below 60% predict ed normal), (ii) continuous nocturnal hypoventilation (when supine VC has dropped below 40% predicted), and (iii) obstructive sleep apnoea Blood \201 lm for abnormal lymphocyte cyt oplasmic vacuolation (mainly acid maltase de \201 ciency) Muscle biopsy \200\223acid malta se de \201 ciency (glycogen-containing vacuoles and low enzyme levels). Management of the underlying condition, if available, is paramount. Weak expiratory muscles and weak laryngeal adduction prevent effective coughing with an increased incidence of ser ious chest infections. Clearing retained secretions can be a major problem. Physiotherapist s can help teach patients and their carers sputum clearance techniques. Increasing the lung volume with positive pressure devices (e.g. the Bird device) and \200\230breath stacking \200\231 allows a higher expiratory \202 ow with improved clearance. Mechanical insuf \202 ator/exsuf \202 ator devices are available that both increase inspiratory volume and speed expiratory \202 ows. Their role is still being evaluated. CLINICAL ASSESSMENT AND MANAGEMENT 97 Lying down and sleeping with the whole bed tipped head up by about 20* greatly improves ven tilation in the presence of bilateral diaphragm paralysis. Just elevating the top half of t he bed, leaving the abdomen and legs horizontal, does not work. The abdominal contents have to descend into the pelvis to effectively \200\230of \202 oad \200\231 the diaphragm. Th is posture will also improve the ability to wean from assisted ventilation. In the situation of irreversibility, the decision will need to be taken as to whether non-invasive ventilation is appropriate (p 693). This page intentionally left blank Part 00 Part 2 Clinical conditions 16 Acute respiratory distress syndrome 17 Asbestos and the lung 18 Asthma 19 Bronchiectasis 20 Bronchiolitis 21 Chronic obstructive pulmonary disease (COPD) 22 Connective tissue dise ase and the lung 23 Cor pulmonale 24 Cystic \201 brosis 25 Eosinophilic lung disease 26 E xtreme environments: \202 ying, altitude, diving 27 Gastrointestinal disease and the lung 28 Hypersensitivity pneumonitis 29 Hyperventilation syndrome 30 Idiopathic interstitial pn eumonias 31 Lung cancer 32 Lung transplantation 101 107 121 149 159 165 185 201 205 227 235 243 249 255 259 279 317 33 Mediastinal abnormalities 34 Pediatric lung disorders pertinent 331 339 to adult patients 35 Pleural effusion 36 Pneumoconioses 37 Pneumothorax 38 Pulmonary hypert ension 39 Pulmonary thromboembolic disease 40 Respiratory infection: bacterial 41 Respirato ry infection: fungal 42 Respiratory infection: mycobacterial 43 Respiratory infection: para sitic 44 Respiratory infection: viral 45 Sarcoidosis 46 Sickle cell disease: pulmonary comp lications 47 Sleep apnoea and hypoventilation 48 Toxic agents 49 Unusual conditions (BOLD) 50 Upper airway diseases 51 Vasculitis and the lung 345 363 373 385 401 419 465 487 523 529 547 561 567 593 609 639 649 101 Chapter 16 Acute respiratory distress syndrome Pathophysiology and diagnosis 102 Management and complications 104 CHAPTER 16 Acute respiratory distress syndrome 102 Pathophysiology and diagnosis De \201 nition and epidemiology ARDS (previously shock lung) is not a single entity, but represents the severe end of a spectrum of acute lung injury d ue to many different insults. Essentially it is: \200 \200 \200 