Surfactant dysfunction in collapsed region Decreased thoracoabdominal compliance (passive a nd compressive atelectasis) Increased risk of infection Increased bacterial growth in colla psed region Development of respiratory failure Collapse Consolidation Effusion Marked Marked Minimal Absent Variable Absent Volume loss Compensatory hyperin \202 ation Tracheal shift \200 \200 Towards lesion Absent Away from lesion Away from lesion Not elevated The severity of the changes seen depends on the degree and rapidity of the developing colla pse. Towards lesion Absent Mediastinal shift Diaphragm position Unilateral elevation Not elevated Incidence Pulmonary collapse is not uncommon, the exact frequency depending on the cause. I n patients who have undergone open abdominal surgery the incidence of significant subsegmen tal collapse approaches 20 \200\22325%. Absent Present Absent Air bronchogram 253 CHAPTER 17.3 Pulmonary collapse and atelectasis Radiology Radiographic signs of collapse may be direct or indirect Direct \200 \200 \200 Speci \201 c management options Physiotherapy There is little evidence for the prophylacti c use of physio- therapy for the prevention of atelectasis. However, there is evidence for its ef \201 cacy in treatment. Including manual treatments (percussion, vibration and posi tive pressure assist devices) in conjunction with patient positioning. Displacement of intralobular \201 ssures Loss of aeration Vascular and bronchial crowding Indirect \200 \200 \200 \200 \200 Fibreoptic bronchoscopy Aside from its diagnostic use, bronchoscopy can be used for therape utic intervention, e.g. to remove a foreign body, or, more commonly, remove retained secret ions. It is commonly applied in the ICU, achieving similar results to physiotherapy. Case s eries demonstrate an improvement in PaO2, lung compliance and CXR \201 ndings. It can be con- sidered in lobar and segmental rather than subsegmental collapse, but may be less effe ctive in patients who demon- strate air bronchograms on the preceding chest \201 lm. Elevation of hemidiaphragm Mediastinal displacement Hilar displacement Compensatory hyperin \202 ation of remaining lung Crowding of ribs Lobar collapse is associated with well de \201 ned patterns on the chest radiograph. Howev er, CXR signs can be subtle and easily overlooked by the unwary clinician. Total lung colla pse results in complete opaci \201 cation of the effected hemithorax, with indicators of m arked volume loss on that side, mediastinal shift and hyperin \202 ation of the contralat- eral lung. Subsegmental (plate, discoid) atelectasis may appear as peripheral band-like de nsities perpendicular to the pleural surface. Mucolytics (N-acetylcysteine, DNase) Such therapies aim to reduce the viscosity of secretio ns, making them easier to clear and reducing mucus plugging. Although DNase has been shown to be effective in cystic \201 brosis, de \201 nitive evidence in other conditions is sc arce. Mechanical ventilation The following maneuvers can be considered in isolation or in concert to re-expand collapsed regions/prevent regional (dependent) lung collapse; \200 \200 Generic management Stabilize the patient \200 \200 \200 Oxygen, \200\230ABC \200\231 Assess the need for ventilatory support (invasive or non-inva sive i.e. respiratory rate, ABGs) Higher levels of PEEP/CPAP Recruitment maneuvers: transient application ofhigh levels of PE EP (30 \200\22340cm H2O) Positioning the patient with collapsed segments in non- (less) dep endent position, Identify causes and treat It is important to identify the likely causes of collapse as some are amenable to speci \201 c therapeutic interventions: Further reading Ashizawa K, Hayashi K, Aso N, et al. Lobar atelectasis: diagnostic Intrinsic airway obstruction: \200 \200 pitfalls on chest radiography. Br Radiol J 2001; 74: 89 \200\22397. bronchoscopy to remove the source of obstruction endobronchial stenting for a neoplastic le sion Hansell DM, Armstrong P, Lynch D, et al. Basic patterns of lung disease. In: Imaging of dis eases of the chest. Phillidelphia: Elsevier Mosby, 2005: 69 \200\223141. Removing external sources of compression: \200 \200 \200 Kreider M, Lipson D. Bronchoscopy for atelectasis in the ICU: a case report and review of t he literature, Chest 2003; 124: 344 \200\22350. Schindler MB. Treatment of atelectasis: whe re is the evidence? Drain pleural effusion Treat pneumothorax Drain large ascites Crit Care 2005; 9: 341 \200\2232. Re-expansion of collapsed lung: \200 \200 Stiller K. Physiotherapy in intensive care: towards an evidence- based practice. Chest 2000; 118; 1801 \200\22313. CPAP Mechanical ventilation with PEEP 254 A ZUREK Chronic obstructive pulmonary disease (COPD) De \201 nition COPD is characterized by slowly progressive airflow obstruction that is not fully reversible with treatment. Air \202 ow obstruction is de \201 ned as an FEV1 (forc ed expiratory volume in 1s) of <80% predicted and an FEV1/FVC (forced vital capacity) ratio of <0.7. Smoking is by far the most important cause of COPD. Others include air pollution, occupational dust (e.g. coal) and chemical (e.g. cadmium) exposure, and genetic causes ( 1-antitrypsin de \201 ciency). Severity de \201 ned on the basis of FEV1: Mild: Moderate: Severe: Lung transplantation: single or double lung if FEV1 is <25% predicted and/or cor pulmonale are present plus severe symptoms despite maximal medical therapy. Recipients must be non-sm okers, <65 years old. Lung volume reduction surgery: consider in patients with upper lobe-p redominant emphysema where symp- toms persist despite maximal medical therapy. Lung functio n parameters should be at least 20% predicted and PaCO2 <7.3kPa. Bullectomy for patients wi th signi \201 cant dyspnoea or complications due to a single large bulla. Acute exacerbations of COPD (AECOPD) A major cause of morbidity and mortality accounting fo r 1 in 8 of acute medical admissions. Typically patients present with increased dyspnoea, c ough or wheeze, chest tightness, sputum volume and/or purulence. FEV1 50 \200\22380% predicted FEV1 30 \200\22349% predicted FEV1 <30% predicted Differential diagnosis Asthma, bronchiectasis, cardiac failure, lung cancer, bron- chioliti s. These conditions may also co-exist with COPD. Investigations include CXR, pulse oximetry and measure- ment of acute bronchodilator reversibility plus (where indi- cated) full lung function testing, peak \202 ow diary, FBC, ABGs, ECG, echocardiogram, sputum culture, 1-antitrypsin level and thoracic CT scan. Causes Commonly infective (viral and bacterial), but others include air pollution (nitrogen and sulfur dioxide, ozone and particulates) and temperature changes. In some cases the cau se is unidenti \201 able. The most common bacterial patho- gens are Haemophilus in \202 u enzae, Streptococcus pneumoniae and Moraxella catarrhalis. Viral causes include rhinovirus, in \202 uenza, coronavirus and adenovirus. Management of stable COPD Most treatments for stable COPD aim at controlling symp- toms, pr eventing exacerbations and maintaining or improving exercise capacity and quality of life. Only long-term oxygen therapy (LTOT) in hypoxaemic patients has been shown to reduce mortal ity. Smoking cessation reduces the rate of decline of lung function while lung transplantat ion and lung volume reduction surgery can result in improved lung function. However, surger y is only appropriate and available for a small minority of COPD patients. Current manageme nt of stable COPD includes: \200 Differential diagnosis Pneumonia, pulmonary oedema, PE, pneumothorax, pleu- ral effusion, l ung cancer, UAO, recurrent aspiration. Investigations CXE, ECG, ABGs, FBC, U&Es, CRP plus blood cultures if pyrexial, and theophyl line level if the patient is on oral theophylline therapy. Assess severity Signs of a severe exacerbation include severe dyspnoea/ tachypnoea, use of accessory muscles and pursed lip breathing, acute confusion, new peripheral oedema, new cya nosis and respiratory acidosis on ABGs. Mortality rises sharply in patients with a pH of <7 .25. If none of the above is present, the patient may be suitable for home management of th eir exacerbation dependent upon other co-morbidities and social circumstances. Inhaled bronchodilators: short- and long-acting 2 ago- nists and anticholinergics. High d ose inhaled corticosteroids to prevent exacerba- tions in moderate and severe COPD. Oral mo di \201 ed release theophyllines. Oral mucolytics in patients with productive cough. Diure tics for oedema due to cor pulmonale. Oxygen: short burst for relief of acute dyspnoea. LTO T for patients with PaO2 <7.3kPa (or <8.0kPa plus poly- cythaemia or cor pulmonale). Ambula tory oxygen for patients who desaturate on exercise and in whom exercise capacity and/or sy mptoms improve when oxygen is administered. Pulmonary rehabilitation: multi-disciplinary pr ogram comprising physical training and disease education suitable for all patients in whom dyspnoea limits their activity. Smoking cessation: nicotine replacement therapy, bupro- pio n or varenicline combined with an appropriate support program. Pneumococcal and annual in \202 uenza vaccination. Dietetic advice for patients with abnormal BMI. Nocturnal NIV may b e of value in patients with chronic hypercapnic ventilatory failure with nocturnal hypovent i- lation and repeated admissions. \200 \200 \200 Controlled oxygen Aim to maintain adequate levels of oxygenation without precipitating wors ening hypercapnia and acidosis. Ideally SaO2 should be between 90 and 95%, although in some patients with chronic hypoxia a target of 85 \200\22390% is more appropriate. Oxygen shoul d be delivered via face masks that allow accurate determination of FiO2. SpO2 should be mon itored, and ABGs repeated regularly according to response to treatment. Hypoxaemia may reco ver slowly following AECOPD, after other symptoms have improved. This only requires treatme nt if the patient is symptomatic. For oxygen to be supplied to a patient \200\231s home, a Home Oxygen Order Form (HOOF) needs to be completed. In these circumstances, the respira- t ory team should be contacted so that assessment for LTOT can be arranged 6 weeks later. \200 \200 255 CHAPTER 17.4 Chronic obstructive pulmonary disease (COPD) Invasive ventilation Patients with good pre-exacerbation functional status and no clinicall y signi \201 cant co-morbidities should be consid- ered for invasive ventilation if they a re deteriorating despite maximal medical therapy including NIV. The mortality rate for this group ( 25%) compares favorably with that of patients requiring invasive ventilation for o ther causes of ARF. However, the prognosis deteriorates in patients requiring >72h of venti lation. NIV has been used to assist weaning patients from invasive ventilation. Nebulized bronchodilators Salbutamol 2 \200\2234 hourly plus as required, and ipratropium 6 hourly should be prescribed until the patient has recov- ered suf \201 ciently to use inh alers. Nebulizers should be driven with compressed air in patients with severe respira- tor y acidosis, with supplemental oxygen being delivered via nasal cannulae if required. Systemic steroids All patients should be prescribed oral prednisolone 30mg/ day for 1 \200 \2232 weeks. IV hydrocortisone should only be used in patients who are unable to take paren tal medication. There is no proven bene \201 t in continuing steroids beyond 14 days eithe r to promote further recovery or to prevent exacerbations, although a small minority of pat ients with advanced COPD require maintenance therapy. Respiratory stimulants Doxapram is now chei \202 y used when NIV is unavailable, contraind icated or not tolerated. It can be used along with NIV in patients who are particularly dro wsy and CO2 retaining. Physiotherapy There is a lack of good evidence for the bene \201 t of physio- therapy in A ECOPD. However, it is probably of value in patients with signi \201 cant sputum production , particularly when using a positive expiratory pressure mask to assist coughing. Antibiotic therapy Antibiotics should be reserved for patients with increased sputum purule nce unless there is other clinical evidence of infection (e.g. pyrexia, high CRP) or consol idation on CXR. In the absence of pneumonia, a single antibiotic given orally is appropriat e for all patients able to take parental medica- tion. Choice of antibiotic will be determi ned by local policy and is in \202 uenced by recent previous antibiotic therapy, pre- viou s sputum results and recent hospitalization. Palliative care Opioids (initially oramorph 2.5mg up to 4 hourly) should be given to patien ts with dyspnoea that is not responsive to other therapy. This treatment is also useful for cough. Opioids should not be reserved solely for patients who are in the terminal phase of their illness. Where anxiety is a major factor, benzodiazepines should also be administere d (e.g. lorazepam 0.5 \200\2231mg up to 8 hourly). The palliative care team should be invol ved. Intravenous aminophylline Consider only in patients with a severe exacerbation who are not responding adequately to nebulized bronchodila- tors, particularly those with predominant w heeze. A load- ing dose should not be given to patients who were on oral theophylline prior to admission. Aminophylline levels should be measured within 24h of starting treatment and daily thereafter. Prognosis Following admission with AECOPD, recovery takes 1 \200\2232 weeks, but in 25% of patients is more than a month, with some patients never regaining their previous func- tion al level. The 3 month mortality rate is 15%. One- fourth of patients are re-admitted withi n 3 months. For patients requiring either NIV or admission to ITU, the 1yr mortality is 50 %. Treatment of acute respiratory failure NIV has been shown to reduce mortality and hasten re cov- ery in AECOPD patients presenting with hypercapnic respiratory failure compared with s tandard medical care. It reduces the need for intubation and has a lower complica- tion rat e than treatment with invasive ventilation. It should be used in hypoxaemic patients with a pH of <7.35 and a PaCO2 of >6kPa in whom a trial of optimal medical man- agement as descri bed above has been ineffective. It is important to be aware of iatrogenic hypercapnic acido sis caused by the administration of high concentration oxygen. Such patients often improve once the FiO2 is lowered without the need for NIV. NIV should be delivered on a dedicated u nit with appropri- ate levels of monitoring and staff training/experience. This usually mea ns ITU/HDU or a high monitoring bay on an admission or respiratory ward. Prior to commencem ent of NIV, the ceiling of therapy should be agreed, in particular if invasive ventilation on ITU is to be commenced if the patient is deteriorating despite NIV. Patients with a pH o f <7.25 are at increased risk of treatment failure with NIV and, if appropriate, should be treated on ITU or consid- ered for invasive ventilation at the outset. Further reading Breen D, Churches T, Hawker F, et al. Acute respiratory failure secondary t o COPD treated in the intensive care unit: a long term follow up study. Thorax 2002; 57: 29 \200\22333. Burge PS, Calverley PMA, Jones PW, et al. Randomized, double- blind, placebo controlled stu dy of \202 uticasone propionate in patients with moderate to severe COPD: the ISOLDE tria l. BMJ 2000; 320: 1297 \200\223303. Chu CM, Chan VL, Lin AWN, et al. Readmission rates and life threatening events in COPD surv ivors treated with non-invasive ventilation for acute hypercapnic respiratory failure. Thor ax 2004; 59: 1020 \200\2235. National Institute of Health and Clinical Excellence, National clini- cal guideline on mana gement of COPD in adults in primary and secondary care. NICE guideline. Thorax 2004; 59 sup pl. 1: 1 \200\223232. Plant PK, Owen JL, Elliott MW. Early use of non-invasive ventilation for acute exacerbations of COPD on general respiratory wards: a multicentre randomized cont rolled trial. Lancet 2000; 355: 1931 \200\2235. 256 S FINNEY & M GRIFFITHS ARDS: diagnosis History and de \201 nition The adult respiratory distress syndrome was \201 rst describe d in a case series of only 12 patients from Colorado in 1967. The North American \200\223Eu ropean Consensus Conference (NAECC) proposed that the syndrome be de \201 ned as the acute onset of refractory hypoxaemia in association with bilateral pulmonary in \201 ltrates wi th no evidence of elevated left atrial pressure (Table 17.5.1). These de \201 nitions are now established, but inevitably they lack a pathognomic test, the X-ray criteria are subjec tive and the oxygenation criteria do not take account of the provision of ventilatory sup- port. The NAECC simultaneously changed the name to acute respiratory distress syndrome (ARD S) recognizing that, whilst the pathological appearances are super \201 cially similar to the respiratory distress syndrome of the new- born, the condition does occur in children an d is otherwise distinct The value of dividing the syndrome into ALI and ARDS is questionabl e as the outcome of patients present- ing in either category is similar. Table 17.5.2 Clinical risk factors for ARDS Direct lung injury Indirect lung injury Sepsis syndrome (40%) and shock Pneumonia (12%)* Aspiration of gastric contents (20%) Thoracic trauma/pulmonary contusion Inhalation injury (smoke, toxin, near drowning) Reperfusion injury (lung transplant, pleural effusion drainag e) Thoracic irradiation Fat embolism syndrome Multiple trauma Blood product transfusion (35%)** Acute pancreatitis Drug overdose/drug reaction Cardiopulmonary bypass Pregnancy related (eclampsia, amniotic \202 uid embolism) Tumor ly sis syndrome Head injury/raised intracranial pressure Table 17.5.1 NAECC de \201 nition of ALI and ARDS Figures in parentheses are the approximate percentage of patients with single risk factors that develop ARDS. *For patients with pneumonia admitted to an ICU. **For the transfusion o f 15 units of blood in 1 day. Exclusion of cardiogenic pulmonary oedema Timing Oxygenation CXR PAoP \211 18mm Hg if measured or no clinical evidence of left atrial hypertension Acute PaO2/FiO2 \211 300mm Hg Bilateral opacities consistent with pulmonary oedema ALI rather than from respiratory failure and, despite severe acute lung damage, chronic respira tory failure afflicts a small proportion of survivors. Chronic weakness and neuropsy- chiat ric problems that may be permanent are the greatest barrier to survivors returning to their normal lives. PaO2/FiO2 \211 200mm Hg ARDS Differential diagnoses The clinical criteria used to de \201 ne the syndrome are vague, e. g those used to exclude cardiogenic pulmonary oedema, which is the most important different ial. Numerous condi- tions may present as ARDS despite not sharing the charac- teristic pat hology (diffuse alveolar damage) and pathophysiology: \200 \200 PaO2/FiO2 = arterial partial pressure of oxygen/inspired oxygen fraction; PAoP = pulmonary artery occlusion pressure. Causes and risk factors The likelihood of developing ARDS depends on the type and number of predisposing conditions and on patient characteristics. For example, predisposing factors include alcoholism and emerging genetic polymorphisms, whilst diabetes mellitus is protecti ve. Although the causes of ALI/ ARDS may be divided into direct and indirect injuries (Tabl e 17.5.2), outcomes are similar if other variables are controlled for. acute neutrophilic in \202 ammation dysfunction of the alveolar-capillary membrane causing pulmonary oedema microvascular dysfunction causing ventilation \200\223perfusion mismatchi ng and hypoxaemia \201 broproliferation. Some of these less common conditions, such as acute eosi- nophilic pneumonia, acute interst itial pneumonitis, cryp- togenic organizing pneumonia, diffuse alveolar hemorrhage and bila teral pulmonary embolism, have speci \201 c treat- ments, emphasizing the importance of di agnosing the underlying cause of ARDS. Other conditions may be man- aged differently becaus e of their relatively poor prognosis, e.g. lymphangitis carcinomatosa. Epidemiology and incidence A recent survey in a de \201 ned region of the USA reported tha t the incidence and mortality of ALI/ARDS increases with age from 16 per 100 000 person-yea rs and 24% for teenag- ers, to 306 per 100 000 person-years and 60% for those >75 years. Th e majority of patients with ALI/ARDS have either been weaned from ventilatory support or ha ve died within the \201 rst 10 days; 10% of patients require support for >1 month. Morta lity rates from most observational studies vary between 35 and 60%, although this will vary depending on the age of the patient and the presence of non-pulmo- nary organ dysfunctions , particularly shock and hepatic failure. In specialist centers, survival rates have improv ed over the last 20 years. Most ARDS patients tend to die with Clinical features and investigations The primary aim of the initial clinical assessment is to iden- tify the underlying causes of ARDS and organ system fail- ures that require urgent support. Excluding cardiogenic pulmonary oedema is based on the patient \200\231s history, CXR and ECG in the \201 rst instance, although further information 257 CHAPTER 17.5 ARDS: diagnosis may be obtained from a pulmonary artery catheter and echocardiogram in selected cases. Thor acic CT demon- strates characteristic appearances in ARDS, with an indi- rect cause and evi dence of the initial insult when the cause of ARDS was pulmonary. Subsequent assessments sh ould focus on detecting the complications of ARDS and critical illness, most notably hospit al-acquired infection. Thoracic CT not uncommonly reveals pathology that is not evident on a plain chest \201 lm, e.g. pneumothorax, pleural effusion, pneumonia and lung abscess. Dakin J, Grif \201 ths M. The pulmonary physician in critical care 1: pul- monary investig ations for acute respiratory failure. Thorax 2002; 57: 79 \200\22385. Grif \201 ths MJD, Evans TW. Acute respiratory distress syndrome. In: Gibson GJ, Geddes DM , Costabel U, wt al., eds. Respiratory medicine, 3rd edn. London: Saunders, 2003: 736 \200 \22363. Montgomery AB, Stager MA, Carrico CJ, et al. Causes of mortality in patients with the adult respiratory distress syndrome. Am Rev Respir Dis 1985; 132: 485 \200\2239. Rubenfeld GD, Caldwell E, Peabody E, et al. Incidence and outcomes of acute lung injury. N Engl J Med 2005; 353: 1685 \200\22393. Rubenfeld GD, Herridge MS. Epidemiology and outcomes of acute Further reading Acute Respiratory Distress Syndrome Network. Ventilation with lower tidal v olumes as compared with traditional tidal volumes for acute lung injury and the acute respi ratory distress syndrome. N Engl J Med 2000; 342: 1301 \200\2238. lung injury. Chest 2007; 131: 554 \200\22362. Wheeler AP, Bernard GR. Acute lung injury and the acute respiratory distress syndrome: a cl inical review. Lancet 2007; 369: 1553 \200\22364. Bernard GR, Artigas A, Brigham KL, et al. The American \200\223European Consensus Conferenc e on ARDS. De \201 nitions, mechanisms, rele- vant outcomes, and clinical trial coordinati on. Am J Respir Crit Care Med 1994; 149: 818 \200\22324. 258 A BASTIN & M GRIFFITHS ARDS: general management Introduction Despite the large number of studies carried out investigat- ing novel therapie s for patients with ARDS, only the use of low tidal volume ventilation has been shown to im prove mortality. However, improvements in the survival of these patients in specialist cent ers have preceded the widespread adoption of protective ventilation and emphasize the impor tance of optimizing supportive care. Carrying out clinical trials in a highly heterogenous critically ill population of patients is fraught with pitfalls, which are exacerbated by th e loose criteria that de \201 ne the syndrome. hydrostatic pressure, because osmotic forces are less able to retain \202 uid in capillar ies. Whilst removing lung water improves respiratory function, dehydration of critically il l patients may precipitate multiple organ failure. A recent study compared the effects of l iberal and conservative \202 uid administration strategies in 1000 patients with ALI. Alt hough there was no effect on mortality, the conserva- tive strategy improved lung function and shortened the duration of mechanical ventilation without increasing non- pulmonary orga n failures. Corticosteroids Corticosteroids may modify the course of lung injury by reducing the activi ty of a variety of proin \202 ammatory and \201 brogenic mediators. However, their admin istration is not bene \201 cial early in the course of the syndrome. Several small studies suggested clinical bene \201 ts of extended moderate- to high-dose methylprednisolone whe n given to patients with ARDS at least 1 week after diagnosis. A recent rand- omized, blind ed trial involving 180 patients who had acute lung injury for at least 7 days demonstrated no effect on mortality of methylprednisolone vs placebo. However, methylprednisolone increa sed the number of ventilator- free and shock-free days, with an improvement in oxygena- tio n and compliance. Methylprednisolone did not increase the rate of infectious complications, but was associated with a higher rate of neuromuscular weakness. Unfortunately, these data have not ended the controversy over the role of corticosteroids in the treatment of ARDS. -Adrenergic agonists Besides other effects, agonists increase \202 uid clearance fro m the airspace of the lung. A continuous infusion of salb- utamol decreased an index of lun g water in patients with ARDS. Larger trials powered to determine the effect of salbutamol on survival in ARDS are planned. General supportive care In the absence of speci \201 c treatments for ARDS, the man- ageme nt involves aggressive treatment of the underlying causes, and prevention and treatment of the complications of ARDS and critical illness. Accordingly, prophylaxis against stress ulc eration, venous thrombosis and pressure ulcers should be administered as indicated. In esse nce, the objec- tive is to buy time and to optimize conditions for the lungs to recover. Infection Non-pulmonary sepsis and pneumonia are amongst the most common causes of ARDS. Co nversely, sepsis and VAP are common complications of ARDS. VAP is dif \201 cult to diagnos e in patients with ARDS because of the frequent co-existence of pulmonary in \201 ltrates and raised indices of in \202 ammation. The importance of preventative measures including oropharyngeal antiseptics and prompt aggressive antibiotic treatment cannot be overemphasiz ed. Nutrition All patients with respiratory failure should receive a high fat, low carbohydrate diet to reduce carbon dioxide pro- duction and thus ventilatory demand. Enteral nutrition removes the disadvantages of parenteral feeding, such as catheter-related infection and imp aired hypoxic pulmonary vasoconstriction. The advantages of enteral feeding include improve d gut barrier function (decreasing translocation of bacteria and their toxins) and a decrea sed incidence of stress ulceration. So-called \200\230immunonutrition \200\231 contains su pplements designed to in \202 uence speci \201 cally in \202 amma- tory responses and GI integrity. Small studies have demon- strated bene \201 ts in respiratory parameters and t he duration of mechanical ventilation, but not on mortality; multi-cen- tre studies will be required to determine the effects on mortality. Similarly, the role of tight glycaemic con trol in the management of ARDS is uncertain. Surfactant replacement De \201 ciency and dysfunction of surfactant contributes to the pat hogenesis of ARDS by encouraging alveolar collapse and compromising host defense. Despite t herapeutic success in neonates with respiratory distress syndrome, multiple trials of synth etic surfactant preparations in adults with ARDS have shown no survival bene \201 t. Possi ble expla- nations for this failure include inadequate surfactant delivery to diseased lung units, and poor biological activity of the synthetic preparations. Further reading Baudouin SV. Exogenous surfactant replacement in ARDS \200\224one Sedation and paralysis Protocols that include regular interruption of sedative infu- sions shorten the duration of mechanical ventilation and facilitate weaning. Neuromuscular juncti on blockers are commonly required to manage patients with ARDS. Their use, particularly whe n given simultaneously with corticos- teroids, is associated with critical illness neuromyo pathy, a major cause of morbidity in survivors. day, someday, or never? N Engl J Med 2004; 351: 853 \200\2235. Brun-Buisson C. Preventing ventilator associated pneumonia. BMJ 2007; 334: 861 \200\2232. Grif \201 ths MJD, Evans TW. Acute respiratory distress syndrome. In: Gibson GJ, Geddes DM , Costabel U, et al, eds. Respiratory medicine, 3rd edn. London: Saunders, 2003: 736 \200 \22363. Kress JP, Pohlman AS, O \200\231Connor MF, et al. Daily interruption of sedative infusions in critically ill patients undergoing mechanical ventilation. N Engl J Med 2000; 342: 1471 \200\2237. Fluid management Whilst pulmonary oedema in ARDS is not caused by \202 uid overload or hi gh left atrial pressure, the high permeability of the pulmonary microvasculature results in leakage of osmotically active molecules into the interstitial space. The formation of oede ma, therefore, depends directly on Milberg JA, Davis DR, Steinberg KP, et al. Improved survival of patients with acute respira tory distress syndrome (ARDS): 1983 \200\2231993. JAMA 1995; 273: 306 \200\2239. Perkins GD, McAuley DF, Thickett DR, et al. The beta-agonist lung injury trial (BALTI): a r andomized placebo-controlled clinical trial. Am J Respir Crit Care Med 2006; 173: 281 \200 \2237. 259 CHAPTER 17.6 ARDS: general management Wiedemann HP, Wheeler AP, Bernard GR, et al. Comparison of two \202 uid-management strate gies in acute lung injury. N Engl J Med 2006; 354: 2564 \200\22375. Singer P, Theilla M, Fisher H, et al. Bene \201 t of an enteral diet enriched with eicosap entaenoic acid and gamma-linolenic acid in ventilated patients with acute lung injury. Crit Care Med 2006; 34: 1033 \200\2238. Steinberg KP, Hudson LD, Goodman RB, et al. Ef \201 cacy and safety of corticosteroids for persistent acute respiratory distress syndrome. N Engl J Med 2006; 354: 1671 \200\22384. 260 J PARK & M GRIFFITHS ARDS: ventilatory management Introduction Despite the heterogenous nature of ARDS, the ARMA ARDS network study of 860 pa tients demonstrated the dramatic effect that ventilatory management has on survival in this syndrome. In essence, invasive mechanical ventilation is a necessary evil that is required in almost all cases, but which further damages the lung and contributes to multiple organ failure. theoretically cause less ventilator-associated lung injury: large studies are underway to d e \201 ne its role in adult ARDS. Perhaps the ultimate means of resting the injured lung i s to perform Extra Corporeal Oxygenation. This technique requires that the patient \200\231 s blood passes across a membrane to supplement gas exchange. Because of associated com- pli cations, this has traditionally been used as a salvage therapy, which is only of proven ben efit in children. However, newer devices such as the Novalung require a less invasive app roach and less anticoagulation, suggesting that this and similar devices may have an increa sing role in the future. Ventilator-associated lung injury Experiments carried out 30 \200\22340 years ago demonstra ted that high tidal volume and high pressure ventilation caused lung injury in healthy anim als, and that previously damaged lung was particularly susceptible to these effects. Simila r models implicated the effects of overdistension (volutrauma) as opposed to high airway pr essure (baro- trauma). and demonstrated the injurious effects of cyclic expansion and colla pse of lung units de \201 cient in surfactant activity (atelectotrauma). The \200\230biot rauma hypothesis \200\231 addresses the question of how the effect of injurious mechanical ventilation affects mortality, when only a small minority of patients succumb to respirator y failure. The hypothesis is supported by clinical studies demonstrating that injurious, as opposed to protective, mechanical ventilation was associated with the detection of increas ed concentrations of in \202 ammatory mediators in bronchoal- veolar lavage and plasma. Fr om these studies it can be inferred that injurious mechanical ventilation stimulates the pr oduction of in \202 ammatory mediators that overspill from the lung into the systemic circ ulation and contribute to multiple organ failure. Adjuncts to ventilatory support In many cases of ARDS, especially those with an indirect no n-pulmonary cause, there is a predominance of collapse and consolidation in dependent lung regions. Turning patients from supine to prone improves ventilation \200\223 perfusion matc hing and signi \201 cantly affects gas exchange in 2/3 cases of ARDS. Furthermore, the we ight of the mediastinum is removed from the left lower lobe, secre- tion clearance may be e nhanced and ventilator-associated lung injury may be mitigated. Large studies have failed t o demonstrate a bene \201 t in terms of survival or duration of mechanical ventilation wit h prone positioning, whilst the procedure is labor intensive and associated with tube displ acement and a higher incidence of pressure sores. Inhaled vasodilators, nebulized prostacyc lin or Nitric Oxide (NO) also improve oxygenation in 2/3 cases of lung injury, but have re peatedly failed to improve survival in multi-center clinical trials. Recommendations for instituting invasive mechanical ventilation in patients with ARDS It is not possible to describe ideal ventilator parameters for all patients with ARDS; mechanica l ventilation settings need to be individualized and changed with time to suit the patient \200\231s condition. This is best achieved with an empirical approach and patience; however , some guidelines may be applied: \200 Ventilation strategy It is now accepted that mechanical ventilation is inevitably damaging to the injured lung and it is neither necessary nor desirable to strive to achieve normal A BGs in patients with ARDS. The ARMA study demonstrated improved survival by selecting a tid al volume target of 6 as opposed to 12ml/ kg predicted body weight (PBW). However, it is no t known whether 6ml/kg is the optimal tidal volume and there does not appear to be a thresh old, or safe plateau pressure, below which there is no advantage in decreasing tidal volume . PEEP recruits collapsed lung, reduces intrapulmo- nary shunting and improves oxygenation, making it a central part of the mechanical ventilation strategy in ARDS, because large par ts of the lung are collapsed owing to de \201 - cient surfactant activity. PEEP also has d etrimental effects primarily by overdistending compliant alveoli or by decreas- ing venous return, RV function and oxygen delivery. In patients being ventilated with a target tidal v olume of 6ml/kg, there was no bene \201 t in using high (14mm Hg) against low (8mm Hg) PEE P in the ALVEOLI ARDS network study. Similarly, the application of high airway pressure for a limited period (recruitment maneuvers) confers short- term physiological bene \201 t on ly, but may be useful to rescue patients with life-threatening hypoxia. Tidal volume of 6ml/kg predicted body weight (PBW), calculated as follows: for men, PBW = 5 0.0 + 0.91 (height in cm \200\223 152.4); and for women, PBW = 45.5 + 0.91 (height in cm \200\223 152.4). If the plateau pressure is >30cm H2O, try to decrease tidal volume further if gas exchange targets can still be met. This may be unnecessary if there is an extrapulm onary cause of restriction, e.g. abdominal distension. Respiratory rate of 20/min, which wi ll tend to mitigate respiratory acidosis but ensure that expiration is com- pleted before t he subsequent inspiration starts in order to avoid breath stacking. Accept a pH >7.2 and do not worry about hypercapnia unless there is concurrent intracranial hypertension or other contraindications. Respiratory acidosis is generally well tolerated unless the rise in carb on dioxide tension is rapid. Oxygen saturation target of 88 \200\22392% to minimize oxygen toxicity. Set PEEP between 14 and 8mm Hg, start at a high level and decrease, until the com pliance or oxygenation deteriorates. Alternative modes of respiratory support There is very little evidence to favor one ventila tory mode over another in adult patients with ARDS. High frequency ventilation aims to mini mize tidal volume whilst maintaining recruitment through a high mean airway pressure. This mode improves oxygenation and should 261 CHAPTER 17.7 ARDS: ventilatory management Whilst muscle relaxants and full sedation may be required initially, these should be withdr awn or minimized as soon as possible to avoid neuromuscular sequelae. Refractory hypoxaemia may be improved by prone positioning, recruitment maneuvers and the adminis- tration of an inhaled vasodilator such as NO, although none of these interventions can be recommended fo r routine use. Ferguson ND, Villar J, et al. Understanding high-frequency oscillation: lessons from the an imal kingdom. Intensive Care Med 2007; 33: 1316 \200\2238. Gattinoni L, Caironi P, Cressoni M, et al. Lung recruitment in patients with the acute resp iratory distress syndrome. N Engl J Med 2006; 354: 1775 \200\22386. Guerin C, Gaillard S, Lemasson S, et al. 2004. Effects of systematic prone positioning in h ypoxemic acute respiratory failure: a rand- omized controlled trial. JAMA 292: 2379 \200 \22387. Hager DN, Krishnan JA, Hayden DL, et al. Tidal volume reduction in patients with acute lung injury when plateau pressures are not high. Am J Respir Crit Care Med 2005; 172: 1241 \200 \2235. Further reading Acute Respiratory Distress Syndrome Network. Ventilation with lower tidal v olumes as compared with traditional tidal volumes for acute lung injury and the acute respi ratory distress syndrome. N Engl J Med 2000; 342: 1301 \200\2238. Pinhu L, Whitehead T, Evans,T, et al. Ventilator-associated lung injury. Lancet 2003; 361: 332 \200\22340. Ranieri VM, Giunta F, Suter PM, et al. Mechanical ventilation as a mediator of multisystem organ failure in acute respiratory distress syndrome. JAMA 2000; 284: 43 \200\2234. Brower RG, Lanken PN, MacIntyre N, et al. Higher versus lower positive end-expiratory press ures in patients with the acute respiratory distress syndrome. N Engl J Med 2004; 351: 327 \200\22336. 262 S SINGH Asthma