Acute respiratory failure in chronic obstructive pulmonary disease

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Chapter 26 Acute respiratory failure in chronic obstructive pulmonary disease

Matthew T. Naughton, David V. Tuxen

The terms ‘chronic obstructive pulmonary or airways disease’ (COPD or COAD) are applied to patients with chronic bronchitis and/or emphysema. COPD affects 5% of the adult population, is the fifth most common cause of death worldwide and is the only major cause of death that is increasing in prevalence.1 Despite this, when an acute deterioration occurs, most precipitating factors are reversible and the outcome is usually good.2 This justifies aggressive management in the majority of patients.

AETIOLOGY

The causes of COPD can be divided into environmental and host factors. Environmental factors include tobacco smoke, air pollution, indoor fumes (e.g. indoor cooking with solid biomass fuel) and poor socioeconomic status. The biggest single factor in over 95% of patients with COPD is tobacco smoking (Figure 26.1). However, only approximately 15% of smokers develop COPD. Marijuana smoking may cause premature and quite advanced bullous emphysema compared with tobacco smokers due to extremely hot and toxic inhaled smoke held at peak inspiration for prolonged periods of time.3 Host factors are the balance between circulating proteases and antiproteases (e.g. alpha-1 antitrypsin deficiency) and the intake of antioxidant vitamins (A, C, E).4

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Figure 26.1 Decline in lung function with age in different smoking categories. FEV1, forced expiratory volume in 1 second; COPD, chronic obstructive pulmonary disease.

PATHOPHYSIOLOGY

Reduced expiratory airflow in COPD is due to both increased airway resistance and reduced lung elastic recoil. Airway resistance is increased by mucosal oedema and hypertrophy, secretions, bronchospasm, airway tortuosity and airflow turbulence and loss of lung parenchymal elastic tissues that normally support the small airways. Loss of lung elastic recoil pressure is due both to loss of lung elastin and loss of alveolar surface tension from alveolar wall destruction.

Reduced lung elastic recoil decreases expiratory airflow by reducing the alveolar pressure driving expiratory airflow and by reducing the intraluminal airway pressure, which normally distends small airways during expiration. Forced expiration increases alveolar driving pressure but also causes dynamic airway compression resulting in no improvement or sometimes reduction in expiratory airflow. These factors are present in varying proportions, depending on the degree of chronic bronchitis and emphysema and the individual patient.

Airflow limitation results in prolonged expiration, pulmonary hyperinflation, inspiratory muscle disadvantage, increased work of breathing and the sensation of dyspnoea. All these factors are worsened during an exacerbation of COPD.

Pulmonary hyperinflation has both static and dynamic components. The static component remains at the end of an expiratory period long enough for all expiratory airflow to cease (30–120 s), enabling the lungs and chest wall to reach their static functional residual capacity (FRC). This component of hyperinflation is due to loss of parenchymal elastic recoil, chest wall adaptation5 and airway closure that occurs throughout expiration. Dynamic pulmonary hyperinflation is the further increase in hyperinflation due to slow expiratory airflow not allowing completion of expiration before the arrival of the next breath. The extent of dynamic hyperinflation depends on the severity of airflow obstruction, the amount inspired (tidal volume) and the expiratory time.6 Thus, the degree of hyperinflation may vary in a patient with changes in minute ventilation due to changes in CO2 production (depending on exercise, diet or the metabolic response to illness) or dead space, as well as with changes in airflow obstruction during an exacerbation.

Chest wall hyperinflation leads to suboptimal muscle length–tension relationships and mechanical disadvantage, thereby predisposing patients to respiratory muscle fatigue, as the work of breathing increases, particularly if associated with myopathic situations (steroids, electrolyte disturbances). Minor reductions in lung function due to infection, mild cardiac failure or atelectasis increase the work of breathing, due to both increases in respiratory impedance and increases in dead space. With acute changes in workload, rapid decompensation with ventilatory failure and acute hypercapnia may occur.

Central respiratory drive may also be impaired, or poorly responsive to physiological triggers – hypoxaemia or hypercapnia – and lead to chronic hypercapnia. This may occur in the setting of sleep (i.e. obstructive sleep apnoea), obesity or drugs (sedatives, antiepileptics, alcohol).

Hypoxia and vascular wall changes lead to pulmonary vasoconstriction, pulmonary hypertension, cor pulmonale, V/Q mismatching and the development of shunts.

CHRONIC BRONCHITIS OR EMPHYSEMA?

The value of labelling patients as chronic bronchitis or emphysema is uncertain as the two disease processes usually coexist and the principles of management are similar. Five pathophysiologic processes may be present to varying degrees in each patient with COPD: (1) inflammatory airway narrowing (bronchiolitis); (2) loss of connective tissues tethering airways; (3) loss of alveoli and capillaries; (4) hyperinflation; and (5) increased pulmonary vascular resistance. Early/mild COPD tends to be dominated by bronchiolitis with a minimal component of emphysema (Figure 26.2), whereas when COPD becomes severe, the reverse is true. However, recognition that COPD is dominated by one of these patterns is helpful with regard to clinical pattern and prognosis.

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Figure 26.2 Proportional contributions of bronchiolitis and emphysema at different levels of severity of lung disease.

CLINICAL FEATURES OF ACUTE RESPIRATORY FAILURE IN COPD

Acute respiratory failure (ARF) in COPD can present with two distinct clinical patterns7 (Table 26.1).

Table 26.1 Clinical differences between normocapnic and hypercapnic chronic obstructive pulmonary disease

Normocapnic (PaCO2 35–45 mmHg) Hypercapnic (PaCO2 > 45 mmHg)
Emphysema > chronic bronchitis Chronic bronchitis > emphysema
Thin Obese
Pursed-lip breathing Central nervous system depression: consider the role of oxygen therapy
Accessory muscle use Alcohol, sedatives, analgesics
Hyperinflated Sleep-related hypoventilation
Right heart failure late Right heart failure early

PRECIPITANTS OF ACUTE RESPIRATORY FAILURE

In approximately 50% of patients, there is an infective cause, in 25% heart failure and in the remaining 25% retained secretions, air pollution, coexistent medical problems (e.g. pulmonary embolus, medication compliance or side-effects) or no cause can be identified8 (Table 26.2).

Table 26.2 Precipitants of acute respiratory failure in chronic obstructive pulmonary disease

Infective (including aspiration)
Left ventricular failure (systolic and diastolic failure)
Sputum retention (postoperative, traumatic)
Pulmonary embolism
Pneumothoraces and bullae
Uncontrolled oxygen
Sedation
Medication – non-compliance or side-effects
Nutritional (K, PO4, Mg deficiency, CHO excess)
Sleep apnoea

The most common bacterial isolates are Streptococcus pneumoniae and Haemophilus influenzae in 80% of exacerbations.9S. viridans,10Moraxella (previously Branhamella) catarrhalis,11Mycoplasma pneumoniae12 and Pseudomonas aeruginosa may also be found. Viruses can be isolated in 20–30% of exacerbations13 and include rhinovirus, influenza and parainfluenza viruses, coronaviruses and occasionally adenovirus, and respiratory syncytial virus. Whether these organisms are pathogens or colonisers is often unclear.

PNEUMONIA

Pneumonia has been estimated to account for 20% of presentations requiring mechanical ventilation.13 It is most commonly caused by S. pneumoniae and H. influenzae but Mycoplasma, Legionella, enteric Gram-negatives and viruses are occasional causes.

LEFT VENTRICULAR FAILURE

Left ventricular (LV) systolic failure may result from coexisting ischaemic heart disease, fluid overload, tachyarrhythmias or biventricular failure secondary to cor pulmonale. LV diastolic failure occurs commonly and is precipitated by hypoxaemia, tachycardia,14 pericardial constraint due to intrinsic positive end-expiratory pressure (PEEPi) or right ventricular (RV) dilation. Increased work of breathing related to COPD will also increase by up to 10-fold the amount of blood flow to the respiratory pump muscles,15 thereby causing an increased demand upon the overall cardiac output. In patients with borderline cardiac status, this may precipitate heart failure. The components of right and LV failure can be accurately distinguished by Doppler echocardiography. Pulmonary congestion can be difficult to diagnose because of the abnormal breath sounds and chest X-ray appearance which are commonly present in COPD. In a recent publication, 51% of patients with acute exacerbation of COPD had echocardiographic evidence of left heart failure (systolic 11%, diastolic 32%, systolic and diastolic 7%).16

UNCONTROLLED OXYGEN ADMINISTRATION

This may precipitate acute hypercapnia in patients with more severe COPD, due to: (1) shunting blood to low-V/Q lung units and increasing dead space; (2) loss of hypoxic drive; (3) dissociation of CO2 from Hb molecule (Haldane effect); and (4) anxiolysis and reduction in tachypnoea.

DIAGNOSIS AND ASSESSMENT

DIAGNOSIS

The clinical examination findings of COPD depend upon severity.

In mild stable disease (e.g. forced expiratory volume in 1 second (FEV1) 50–70% predicted normal), an expiratory wheeze on forced expiration and mild exertional dyspnoea may be the only symptoms.

In moderate-severity COPD (e.g. FEV1 30–50% predicted normal), modest to severe exertional dyspnoea is associated with clinical signs of hyperinflation (ptosed upper border of liver beyond the level of nipple and loss of cardiac percussion) and signs of increased work of breathing (use of accessory muscles and tracheal tug).

In severe stable COPD (e.g. FEV1 < 30% predicted normal), marked accessory muscle use is associated with tachypnoea at rest, pursed-lip breathing, hypoxaemia and signs of pulmonary hypertension (RV heave, loud and palpable pulmonary second sound and elevated a-wave in jugular venous pressure (JVP)) and cor pulmonale (elevated JVP, hepatomegaly, ankle swelling).

In severe unstable COPD, there is marked tachypnoea at rest, hypoxaemia and tachycardia, and, in some, signs of hypercapnia (dilated cutaneous veins, blurred vision, headaches, obtunded mentation, confusion).

Clinical examination may also identify associated medical conditions that might have precipitated the exacerbation such as crackles and bronchial breathing due to infection, crackles and cardiomegaly related to heart failure or mediastinal shift related to a pneumothorax.

Basic investigations such as spirometry are very useful in confirming a clinical diagnosis and determining severity of disease. The severity of COPD may be best judged by the reduction in FEV1 compared with predicted values. Vital capacity (VC) is initially normal and decreases later in the course of the disease, but to a lesser degree than the FEV1.

An FEV1/VC ratio < 70% with an FEV1 of 50–80% predicted normal without a bronchodilator response usually indicates mild COPD. A significant bronchodilator response, which implies asthma, is regarded as a 12% or greater increase and 200 ml increase in either FEV1 or VC. An FEV1 30–50% predicted normal indicates moderately severe COPD and FEV1 < 30% predicted normal indicates severe COPD.

Although the diagnosis may be based on spirometry alone, further lung function testing may be useful to characterise the disease. Flow–volume curves demonstrate reduced expiratory flow rates at various lung volumes and show the characteristic concave expiratory flow pattern. Lung volumes measured by either helium dilution or plethysmography show elevated total lung capacity, FRC and residual volume. Characteristically, the residual volume/total lung capacity ratio is > 40% in COPD and represents intrathoracic gas trapping. The total lung carbon monoxide (TLCO) uptake is a measurement of alveolar surface area and its reduction approximates the amount of emphysema present (usually < 80% predicted normal).

A chest X-ray will commonly show hyperinflated lung fields, as suggested by 10 ribs visible posteriorly, six ribs visible anteriorly or large airspace anterior to heart (> 1/3 of the length of the sternum), flattened diaphragms (best seen on lateral chest X-ray) and a paucity of lung markings. Pulmonary hypertension is manifest by enlarged proximal and attenuated distal vascular markings and by RV and atrial enlargement. Lung bullae may be evident.

A high-resolution computed tomographic (CT) scan of the chest (1–2-mm slices) can demonstrate characteristic appearance and regional distribution of emphysema. It can also assess for coexistent bronchiectasis, LV failure17 and pulmonary fibrosis. Such scans are less sensitive than standard chest CT scans (1-cm slice) for detecting pulmonary lesions (e.g. neoplasms). Nuclear ventilation perfusion scans can also provide a characteristic appearance of COPD.

An electrocardiogram (ECG) is commonly normal but may show features of right atrial or RV hypertrophy and RV strain, including P pulmonale, right-axis deviation, dominant R-waves in V1–2, right bundle-branch block, ST depression and T-wave flattening or inversion in V1–3. These changes may be chronic or may develop acutely if there is significant increase in pulmonary vascular resistance during the illness. The ECG may also show coexistent ischaemic heart disease, tachycardia and atrial fibrillation. Occasionally, continuous ECG monitoring is required to identify transient arrhythmias, which may also precipitate acute deterioration. Plasma brain natriuretic peptide (BNP) levels may also assist in the diagnosis of heart failure (elevated BNP) from pulmonary causes (low BNP) in patients under 70 years free of renal impairment.

DIFFERENTIAL DIAGNOSIS

The history of chronic asthma is one of long-term dyspnoea, wheeze and cough, usually at night or upon exercise, beginning in childhood with clear-cut precipitating agents (e.g. weather, dust, pets, drugs) and a favourable response to either steroids or inhaled β2-agonists. Late-onset asthma (> 40 years of age) is not uncommon and is often associated with recurrent gastro-oesophageal reflux. In both forms of asthma, TLCO is normal. There is usually a bronchodilator response in the FEV1 if the patient has unstable asthma. In patients in whom asthma is considered but lung function tests are normal, the FEV1 response to an inhalational challenge (e.g. methacholine or hypertonic saline) may assist in discriminating asthma from other causes of dyspnoea.

Bronchiolitis obliterans is a condition which presents as a fixed airflow obstruction following a viral illness, inhalation of toxic fumes, following bone marrow or heart/lung transplantation, or related to drugs (e.g. penicillamine). It generally begins as a cough some weeks after insult and insidious onset of dyspnoea. There is a broad spectrum of radiological appearances from normal to reticulonodular to diffuse nodular. Lung tissue via bronchoscopy or by thoracoscopy is required for diagnosis. Histologically, there is a characteristic chronic bronchiolar inflammation appearance, and if granulation tissue extends into the alveoli, it is referred to as bronchiolitis obliterans or organising pneumonia. Removal of the offending agent and instigation of steroids are generally associated with a favourable prognosis.

Bronchiectasis is often associated with fixed mild to moderate airflow obstruction. A chronic productive cough (daily for 2 consecutive years) is characteristic. Clinical features such as clubbing, localised pulmonary crackles and a characteristic appearance on high-resolution CT, with dilated or plugged small airways at least twice the size of accompanying blood vessel, assist in the diagnosis.

Chronic heart failure (CHF) may be a differential diagnosis of COPD, or simply coexist, as both disorders are common in smokers.14,16 Orthopnoea and paroxysmal nocturnal dyspnoea are features which correlate with heart failure severity. A past history of myocardial ischaemia or atrial fibrillation should alert one to the possibility of heart failure. An echocardiogram and high-resolution CT (looking for shift in interstitial oedema with changes in posture from supine to prone)17 are sensitive markers of CHF.

DIAGNOSIS OF RESPIRATORY FAILURE

An exacerbation of COPD is usually clinically obvious. However, it is important to diagnose the extent of deterioration. The following may be useful.

BLOOD GASES

Blood gases are mandatory to assess hypoxia, hypercapnia and acid–base status. Chronic hypercapnia may be recognised by a bicarbonate level > 30 mmol/l and a base excess > 4 mmol/l indicating renal compensation. However, other causes of a high serum bicarbonate need to be excluded (e.g. diuretic therapy, high-dose steroids or high-volume gastric fluid loss) or chronic hypercapnia may be incorrectly assumed and the severity of COPD overestimated. Renal compensation for chronic hypercapnia will increase the serum bicarbonate by approximately 4 mmol/l for each 10 mmHg (1.33 kPa) of chronic PaCO2 rise above 40 mmHg (5.3 kPa), in order to return pH to the low-normal range. Irrespective of the COPD patient’s usual PaCO2 level, an acute increase in PaCO2 leads to a decreased arterial pH. This indicates that compensatory mechanisms are exhausted and there is an increased risk of respiratory collapse.

NON-VENTILATORY MANAGEMENT

OXYGEN THERAPY

Oxygen given by low-flow intranasal cannulae or 24–35% Venturi mask should be titrated to achieve a saturation (SpO2) of 90 ± 2% as these levels will avoid significant increases in PaCO2 in the majority of COPD patients with ARF. Increases in PaCO2 are most common in patients with initial PaCO2 > 50 mmHg and pH < 7.35.18 If the rise in PaCO2 is excessive (> 10 mmHg or 1.33 kPa), then FiO2 should be reduced, titrating SpO2 to 2–3% below the previous value, and arterial blood gases should be repeated. If no PaCO2 rise occurs with oxygen therapy, then a higher SpO2 may be targeted with repeat blood gases.

Inadequate reversal of hypoxia (e.g. SpO2 < 85%) is suggestive of an additional problem such as pneumonia, pulmonary oedema or embolus, or a pneumothorax. Investigation of this should commence and a higher O2 delivery system should be used (see Chapter 24). Although high levels of O2 should be avoided, reversal of hypoxia is important and O2 should not be withheld in the presence of hypercapnia, or withdrawn if it worsens.

BRONCHODILATORS

Bronchodilators are routinely given in all acute exacerbations of COPD because a small reversible component of airflow obstruction is common, and bronchodilators improve mucociliary clearance of secretions.19 However, a large meta-analysis of 22 large randomised controlled long-term trials of ambulatory COPD patients involving either anticholinergics and/or β2 agonists (short- and long-acting) over 3–60 months indicates that anticholinergics are more favourable than placebo in terms of acute exacerbations, hospitalisations and respiratory deaths.20 There were no favourable advantages with β2-agonists compared with placebo for acute exacerbations or hospitalisations, and placebo was better than β2-agonists in terms of respiratory death.20

ANTICHOLINERGIC AGENTS

Anticholinergic agents, such as ipratropium bromide, have been shown to have a similar or greater bronchodilator action than β-agonists in COPD,1,21,22 and also to have fewer side-effects and no tachyphylaxis. Anticholinergic agents should be used routinely in COPD with ARF and many now believe them to be the agent of first choice.1 An ipratropium bromide nebule of 0.5 mg in 2 ml should be nebulised initially 2-hourly, then every 4–6 hours. Long-term use of ipratropium bromide has been shown to reduce the incidence of exacerbations23 and is therefore recommended for chronic use in ambulatory COPD. Long-acting anticholinergics (e.g. tiotropium) offer potential of once-daily dosing.

NEBULISED β2-AGONISTS

Nebulised β-agonists are also effective bronchodilators in COPD,21,22 although they may cause tachycardia, tremor, mild reductions in potassium and PaCO2 (due to pulmonary vasodilatation) and tachyphylaxis. Nebulised β-agonists (e.g. salbutamol, terbutaline or fenoterol) given 2–4-hourly should be used routinely in combination with ipratropium. This combination has been shown to be more effective than either agent alone.1 Parenteral sympathomimetic agents are rarely indicated and not recommended for routine use. In stable patients, long-term use of β-agonists may improve symptoms of dyspnoea, particularly in the subgroup of COPD with an objective bronchodilator response. Long-acting β-agonists may also have a beneficial effect on symptoms, quality of life and exercise capacity in COPD.24

AMINOPHYLLINE

Aminophylline is a weak bronchodilator in COPD. It improves diaphragm contractility,25 stimulates respiratory drive,26 improves mucociliary transport27 and right heart function,28 is anti-inflammatory29 and is a weak diuretic. Some studies have shown no benefit and significant side-effects,30 whereas others have shown small benefit31 instable COPD. Theophylline has a number of additional effects that may also be of benefit in COPD, although the clinical importance of these is not yet established. For an exacerbation, aminophylline (loading dose 5–6 mg/kg IV over 30 min, followed by an infusion of 0.5 mg/kg per h) is commonly also given, despite doubt about its overall benefit. Serum theophylline levels must be monitored regularly to reduce risk of toxicity. The low therapeutic range should be targeted (55–85 mmol/l) for the best ratio of effect to side-effect.32 The high therapeutic range (85–110 mmol/l) has little additional benefit and a significant increase in side-effects,32 but is thought necessary for diaphragm contractility and respiratory stimulation effects. There is some evidence in favour of theophylline use in the long-term management33 of COPD but, due to its narrow therapeutic window, it should be used with caution.

STEROIDS

In acute exacerbations of COPD, short-term steroids have been shown to improve airflow obstruction,34 including those patients requiring mechanical ventilation for COPD.35 Doses similar to those for acute asthma should be used. Methylprednisolone 0.5 mg/kg, given 6-hourly for 72 h, was used in the study by Albert et al.,34 demonstrating benefit in patients with an exacerbation of COPD. Current American Thoracic Society guidelines recommend the equivalent to oral prednisolone at 0.5 mg/kg body weight for up to 10 days, then ceasing; however, this will depend upon the response to treatment, and their premorbid use.1 Steroids should be avoided if the deterioration is clearly due to bacterial pneumonia without bronchospasm.

Longer-term oral steroids in COPD are associated with a substantial increased risk of side-effects (osteoporosis, diabetes, peptic ulcer, myopathy, systemic hypertension, fluid retention, weight gain), which are likely to impair quality of life and precipitate readmission and are therefore not recommended.1 A small group of patients (15%) may demonstrate a significant bronchodilator response; coexistent asthma is likely in these patients and longer-term high-dose (oral or inhaled) steroids may be necessary. In the majority of patients, long-term inhaled steroids do not improve lung function or survival; however, they do improve quality of life and reduce admissions and are therefore recommended as long-term treatment at low to medium dose.1

ANTIBIOTICS

Antibiotics have an accepted role in the treatment of infection-induced exacerbations of COPD. Amoxicillin is a suitable first-line agent against Haemophilus influenzae and Streptococcus pneumoniae for outpatient exacerbations.36 Serious exacerbations requiring hospital admission require newer agents such as ciprofloxacin or a third-generation cephalosporin.37 Antibiotics for pneumonia are discussed elsewhere in this volume.

SECRETION CLEARANCE TECHNIQUES

Clearance of lower respiratory secretions is of crucial importance.

CHEST PHYSIOTHERAPY

Chest physiotherapy should be initiated and regularly repeated as both a curative and preventive measure. Encouragement of coughing and deep breathing are the two most important factors. ‘Bubble positive expiratory pressure (PEP)’ is an inexpensive method of assisting sputum clearance in patients with retained secretions or those having difficulty expectorating.

NEBULISED MUCOLYTIC AGENTS

Nebulised mucolytic agents, such as acetylcysteine, continue to be proposed, although their benefit has never been established in acute exacerbations of COPD.38 Oral mucolytics have been shown to reduce cough frequency and severity in stable COPD.39

OROPHARYNGEAL/NASOPHARYNGEAL SUCTIONING

Oropharyngeal/nasopharyngeal suctioning can be performed with or without a nasopharyngeal airway. It is desirable but uncommon for the suctioning catheter to enter the trachea; the technique is useful in clearing pharyngeal secretions, stimulating coughing and clearing lower respiratory secretions coughed only as far as the hypopharynx in patients with suppressed conscious states.

FIBREOPTIC BRONCHOSCOPY

Fibreoptic bronchoscopy is occasionally used in COPD with ARF. Although effective in clearing sputum, it is labour-intensive and may be poorly tolerated by a patient with marginal respiratory function. Indications are lobar consolidation, where sputum plug obstruction is suspected, for bronchoalveolar lavage to diagnose pneumonia or to assist difficult secretion clearance.

OTHER MEASURES

Other adjunctive measures are applicable to some patients.

HYDRATION, DIURETICS, DIGOXIN AND VASODILATORS

COPD patients are sensitive to changes in fluid status and intravenous hydration should be undertaken with care and minimised. Diuretics and digoxin are of benefit if LV failure is present. Even if evidence of LV failure is minimal, a trial of diuresis is worthwhile in patients refractory to usual treatment. Digoxin has been shown to improve LV function in patients with cor pulmonale.40

Diuretics will reduce fluid overload in cor pulmonale; however, care should be taken with severe pulmonary hypertension where a decrease in RV filling pressure may result in a low-output state. Digoxin is of no established benefit to RV function in cor pulmonale, where the primary problem is increased afterload.41 Pulmonary hypertension is commonly present in severe COPD and is associated with a poor prognosis. In stable COPD pulmonary vasodilators may have acutely beneficial effects42 but have not yet been shown to improve outcome.43 In ARF, pulmonary hypertension invariably increases and may precipitate acute cor pulmonale. Although not clinically proven, pulmonary vasodilators have a rational basis in this setting. Numerous agents have been or are undergoing trials to reduce pulmonary hypertension in COPD. These agents include calcium channel blockers (e.g. nifedipine), endothelin receptor antagonists (e.g. bosentan), phosphodiesterase inhibitors (e.g. sildenafil) and prostacycline analogues (e.g. epoprostenil, iloprost and trepostinil).42 Side-effects include systemic hypotension, tachycardia, worsening of hypoxia and failure to improve haemodynamics. A trial of vasodilators appears reasonable if cor pulmonale is present with ARF, provided that response to therapy is carefully monitored. The diagnosis and response to treatment of pulmonary hypertension may require a right heart catheter.

ANTICOAGULANTS

Subcutaneous heparin (e.g. 5000 units b.d.) is recommended as a prophylactic measure against venous thromboembolism. There is no evidence for warfarinisation in COPD patients with pulmonary hypertension.

ELECTROLYTE CORRECTION

Electrolyte correction is important. Hypophosphataemia is common and may cause respiratory muscle weakness.44 Hypomagnesaemia,45 hypocalcaemia46 and hypokalaemia may also be present and may impair respiratory muscle function. Hyponatraemia may occur with inappropriate antidiuretic hormone release or with excess use of diuretics and inappropriate intravenous fluids.

HYPOTHYROIDISM

Hypothyroidism is an important condition to be recognised, particularly in the hypercapnic patient group.

INTERCOSTAL DRAINAGE

Intercostal drainage is indicated for pneumothorax and pleural effusions of sufficient volume to compromise respiratory function. Formal intercostal catheter insertion may be required but mandates hospital admission and is associated with infection and discomfort. Simple aspiration of pneumothoraces has been shown to result in few complications, a reduced admission rate and reduced hospital stay.

RESPIRATORY STIMULANTS

Many drugs have been shown to increase respiratory drive and lower PaCO2. These include acetazolamide, medroxyprogesterone, naloxone, doxapram and almitrine. Use of such agents presupposes that the limiting factor is reduced respiratory drive, whereas the majority of ARF is limited by a reduced capacity to deal with an increased load to breathing. Side-effects include increased dyspnoea and fatigue, impaired sleeping, with almitrine, and increased pulmonary hypertension. Respiratory stimulants have not been shown to improve either short-term or long-term outcome. As a result respiratory stimulants are not recommended or used in ARF. Narcotic- or benzodiazepine-induced respiratory depression is best managed with the appropriate antagonist – naloxone or flumazenil.

NUTRITION

Nutrition is important, as patients with severe COPD are often undernourished and suffer a deterioration in nutritional status when hospitalised. This poor nutritional state is associated with decreased respiratory muscle mass and strength, increased risk of fatigue, ARF and death. Enteral feeding is preferred, but parenteral nutrition should be considered if enteral feeding is not tolerated. Excessive carbohydrate calories should be avoided as this increases CO2 production (by ∼15%) and may worsen respiratory failure. Low-carbohydrate/high-fat combinations are preferred in ARF during spontaneous ventilation.

NON-INVASIVE VENTILATION (NIV)

NIV is a technique in which ventilatory support is provided via a nasal or facial mask without endotracheal intubation. There have been several randomised controlled trials of NIV in COPD patients with acute hypercapnic respiratory failure which have demonstrated improved respiratory physiology, reduced mortality (up to 12 months), reduced iatrogenic complications, reduced need for intubation and mechanical ventilation and reduced length of stay in hospital.47–50 All studies have shown good tolerance of the technique (∼80% of patients), with few side-effects, improvements in both oxygenation and PaCO2 compared with medically treated control patients.51,52

The goal of this technique is: (1) to unload respiratory muscles and augment ventilation and oxygenation, reduce CO2 and correct acidosis until the underlying problem can be reversed; (2) when applied intermittently, to offset the adverse effects of sleep or position-induced adverse changes to ventilation, increased upper airway resistance and lung volume.

Indications for NIV are a deterioration of COPD with: (1) acute dyspnoea; (2) respiratory rate > 28 breaths/min; (3) PaCO2 > 45 mmHg with a pH < 7.35, despite optimal medical treatment and not related to excessive supplemental oxygen. Although these indications are for mild exacerbations, most randomised studies have used these as entry guidelines.47–50 Initial guidelines recommended NIV use to be limited to patients with pH in the range 7.25–7.35; however, recent evidence suggests that NIV is useful even in those patients with lower pH values (to as low as 7.0) and associated more severe hypercapnia (as high as 140 mmHg).53 Included in the indications are recently extubated patients in whom NIV has been shown to reduce reintubation rates significantly.54 Recently NIV has been advocated for use in patients with hypoxic respiratory failure,55 but success is significantly less in the setting of hypoxaemia and either normocapnia or hypocapnia.56 NIV may also have a role in some patients where mechanical ventilation is considered inappropriate.

Side-effects of NIV have included discomfort, intolerance, skin necrosis, gastric distension and aspiration. Pressure support has been reported as better tolerated than assist/control.51

INVASIVE MECHANICAL VENTILATION

OUTCOME OF ARF AND THE DECISION TO VENTILATE INVASIVELY

When respiratory failure progresses or fails to resolve despite aggressive conservative management, including NIV, mechanical ventilatory support may be necessary. The decision to ventilate requires careful consideration in some patients who may have near-end-stage lung disease and whose quality of life may not justify aggressive treatment. This decision requires consideration of the outcome of ARF.

Patients with COPD have a reduced life expectancy compared with an age-matched general population group and this life expectancy decreases in proportion with severity of COPD as assessed by FEV1 (Figure 26.3).

image

Figure 26.3 Survival curves for various patient groups with chronic obstructive pulmonary disease (COPD). Note: these are approximations only, based on other studies13,57 with different patient numbers, criteria and study periods. FEV1, forced expiratory volume in 1 second; ARF, acute respiratory failure.

An episode of ARF further decreases survival (see Figure 26.3). ARF precipitated only by bronchitis has a better outcome,2 whereas ARF due to more serious causes, such as pneumonia, LV failure and pulmonary embolus, has a worse outcome57 and studies including all such outcomes have lower survival rates (see Figure 26.3).

If ARF requires invasive mechanical ventilation, survival decreases further still (see Figure 26.3). Although the majority of patients do not require mechanical ventilation, the short-term survival in this more severe subset is still good, with a hospital survival rate in some series as high as 80%,58 but 2- and 3-year survival is significantly lower (see Figure 26.3).59,60 The severity of ARF and the severity of underlying COPD based on FEV1, lifestyle score and dyspnoea score are also predictors of outcome.13,57 Lifestyle13 and dyspnoea61 categories may be the most useful factors in the decision to withhold mechanical ventilation. Lifestyle categories 3 (house-bound and at least partly dependent) and 4 (bed- or chair-bound) indicate both a poor outcome (see Figure 26.3)13 and quality of life that may not justify aggressive treatment.

Thus invasive mechanical ventilation may be withheld in end-stage lung disease, when low survival, poor quality of life or permanent ventilator dependence are likely. This decision should be based on the following criteria. In general, patients must fulfil all the following criteria for invasive mechanical ventilation to be withheld:

• known severe COPD, which has been assessed and failed to respond to adequate therapy
• severe limitation of lifestyle by dyspnoea with a poor prior quality of life
• no identifiable reversible factors (e.g. pneumonia, sputum retention, LV failure)

If end-stage lung disease is suspected but there is insufficient information, then a trial of aggressive therapy, including invasive mechanical ventilation, should be undertaken and subsequently withdrawn if unsuccessful. Despite this, most patients with COPD who present with ARF do not have end-stage disease and, although their immediate problems may be life-threatening, their short-term outcome is sufficiently good to justify full active treatment.

INDICATIONS FOR INVASIVE MECHANICAL SUPPORT

• The clinical appearance of fatigue and impending respiratory collapse despite non-invasive ventilatory support
• Deteriorating conscious state due to fatigue or hypercapnia or both
• Hypoxia refractory to high levels of inspired O2
• Deterioration due to failure of secretion clearance
• Respiratory arrest

MECHANICAL VENTILATION TECHNIQUE

The goals of mechanical ventilation in COPD are to support ventilation while reversible components improve, to allow respiratory muscle to rest and recover whilst preventing wasting from total inactivity and to minimise dynamic hyperinflation. This is usually best accomplished with low-level ventilatory support. Patients requiring low-level support may be commenced on 8–15 cmH2O pressure support, with 3–8 cmH2O PEEP. Patients who are completely exhausted, postarrest, comatose or not tolerating pressure support alone, should be commenced or transferred to synchronised intermittent mandatory ventilation mode.

Excessive dynamic hyperinflation must be avoided by using a low minute ventilation – 115/ml per kg is a guideline6 – and allowing adequate time for expiration. This should be achieved by the use of a small tidal volume (8 ml/kg) and a ventilator rate < 14 breaths/min.6,62 Dynamic hyperinflation can be assessed clinically, by visualising the expiratory flow–time curve, and by measuring plateau airway pressure (Pplat) or PEEPi. Pplat should be measured by applying an end-inspiratory pause of 0.5 s. This should only be applied following a single breath as it shortens expiratory time and, if it is applied to a series of breaths, it increases dynamic hyperinflation, resulting in an increased Pplat level and increased risk to the patient. If Pplat is > 25 cmH2O, there is likely to be dynamic hyperinflation, and the ventilator rate should be reduced. However, Pplat may be high without dynamic hyperinflation if chest wall compliance is low. Intrinsic PEEP measured as a prolonged end-expiratory pause more directly assesses dynamic hyperinflation. Provided PEEPi is accurately measured, it is a useful tool to follow dynamic hyperinflation. In severe airflow limitation it may be necessary to accept low levels of PEEPi, but as PEEPi rises above 8–10 cmH2O, further prolongation of expiratory time must be considered. Although still controversial, the use of a high inspiratory flow rate is recommended,6,63 as it results in a shorter inspiratory time and hence a longer expiratory time for a given ventilatory rate. It has been shown to reduce dynamic hyperinflation and alveolar pressure6 further and to improve gas exchange.63

If dynamic hyperinflation is excessive and causing circulatory compromise or risk of barotrauma, then minute ventilation should be decreased, hypercapnic acidosis accepted and spontaneous ventilation, which will only increase dynamic hyperinflation, should be discouraged by sedation. Muscle relaxants should be avoided unless essential. When dynamic hyperinflation is critical during controlled mechanical ventilation, PEEPi increases pulmonary hyperinflation and should not be applied.64

If dynamic hyperinflation is not excessive then spontaneous ventilation should be encouraged to promote ongoing respiratory muscle activity and to minimise wasting. Flow-by, pressure support and low-level CPAP may all reduce the work of spontaneous breathing and promote a better ventilatory pattern. CPAP approximately equal to the level of PEEPi is most commonly recommended.65 Care must be taken with all of these supports as each can increase dynamic hyperinflation by a different mechanism, leading to circulatory compromise or risk of barotrauma. Flow-by increases resistance through the expiratory valve, pressure support increases tidal volume and may increase inspiratory time and CPAP increases FRC.

WEANING FROM INVASIVE MECHANICAL VENTILATION

Weaning a patient with severe COPD from ventilatory support can be difficult and prolonged. Numerous criteria have been proposed to assess the capacity of the patient to wean;66 however, the predictive value of any of these individual criteria is limited. The simple criterion of patient respiration rate/tidal volume < 100 breaths/min per litre had the best predictive value for weaning success, but the advantage of this overly simple clinical assessment during weaning is uncertain.66 Weaning or withdrawal of ventilation is further discussed elsewhere in this volume.

TRACHEOSTOMY

In a small group of patients who have failed extubation despite NIV or who have required long-term ventilatory support, tracheostomy may be beneficial. After 10 days of endotracheal intubation, the risk of trauma and sepsis increases.

A tracheostomy allows long-term ventilatory support, sputum clearance, protection of the upper airway from oral secretions and, off mechanical ventilation, reduced dead space and upper-airway resistance. Compared with naso/orotracheal intubation, tracheostomy is much less intrusive and therefore less sedation is required. Also, it allows direct access to the large airways for the purpose of suctioning and bronchoscopy. However, patients are unable to generate sufficient upper-airway seal to cough, and as such may have ongoing atelectasis until tracheostomy removal and the development of an effective cough. Usually a nasoenteric feeding tube is required. Consider percutaneous endoscopic gastrostomy (PEG) tube feeding if long-term tracheostomy is being considered to avoid nasal trauma and infection and to reduce oesophagitis. Minimal occlusion tracheostomy cuff pressures (usually < 20 cmH2O) should be checked 8-hourly. Use of double-lumen tracheostomies with adequate humidification is recommended to allow for inner-tube cleaning and the avoidance of occlusion due to dried secretions.

Consider removing the tracheostomy when:

1 there is an absence of upper-airway obstruction (e.g. no granulation tissue or tracheal stenosis)
2 suctioning is becoming less frequent (< 2–4-hourly)
3 the patient is cooperative and has a good capacity to cough, for example, good respiratory muscle strength
4 the patient is able to protect the upper airway from aspiration
5 the patient is less dependent on invasive ventilatory support (e.g. not continuous) and non-invasive ventilatory support is available
6 there is a decreasing oxygenation requirement (e.g. FiO2 < 40%)

FAILED WEANING

A small group of patients with end-stage lung disease will be unable to wean successfully from ventilator support despite optimisation of all reversible factors. A number of options now exist for such patients:

• long-term institutional or home ventilatory support
• withdrawal of support. Permanent institutional mechanical ventilation for a patient with low general health status represents a poor quality of life and withdrawal of support may be a preferable alternative

POST INTENSIVE UNIT CARE

REHABILITATION

Rehabilitation should be considered for all patients with COPD, particularly those following ARF. There are numerous randomised controlled trials showing improvements in exercise physiology, lung function, quality of life and reduced hospitalisation rates.67,68 Such programmes include extensive education and aerobic upper and lower-limb and respiratory muscle exercise, usually three times per week over a 6-week period. Patients are recommended to continue with exercises regularly and independently thereafter.

VACCINATION

Vaccination should be considered in all patients with COPD when stable. Annual influenza and 5-yearly pneumococcal vaccination is recommended.1

LUNG VOLUME REDUCTION SURGERY

Lung volume reduction surgery is a palliative surgical procedure for patients aged < 75 years, with advanced disabling emphysema. Poorly perfused and poorly ventilated areas of one or both lungs, thought to compress relatively preserved areas of well-functioning lung tissue, are excised by either midline sternotomy or endoscopically, with video assistance.69 Such areas in the lung, usually apically placed, are determined by V/Q scans and high-resolution CT scans. Suitable patients must have undergone a pulmonary rehabilitation programme, be on optimal medical treatment and have disabling dyspnoea and anatomically suitable (apical bullous) emphysema. Patients with profoundly severe emphysema (e.g. FEV1 or TLCO < 20% predicted) are unlikely to benefit.69 Group mean data suggest that the mean FEV1 increases from 0.5 to 0.91 litres, and the mean 6-min walk distance increases from 205 to 290 metres, both associated with significant improvement in quality of life. The peak improvements in physiology occur at 1–2 years and thereafter decline to presurgical levels. Improvements in survival are yet to be determined.69

LUNG TRANSPLANTATION

Lung transplantation is another palliative surgical procedure for patients with advanced disabling COPD who are aged < 65 years, are not ventilator-dependent, are on less than 10 mg prednisolone/day and are free of significant coexistent disease. It may be used following lung volume reduction surgery. The current 1-, 2- and 5-year international survival figures are 75, 66 and 50% respectively.70 Common complications are systemic hypertension, bronchiolitis obliterans, acute rejection, viral infection with cytomegalovirus and neoplasms.66 Its widespread application in COPD is in doubt because of the very limited supply of donor lungs.71

PROGNOSIS

Patients with sufficiently severe COPD to warrant hospital admission incur an inpatient mortality of 7%, and 90-day mortality of 15% in the UK.72 Predictors of mortality were performance status, age and admission urea, albumin, pH and SpO2 plus the presence of respiratory physicians involved in the care.72 Although in-hospital mortality for hypercapnic COPD patients may reach 62%,73 in an Australian report, in-hospital mortality for hypercapnic COPD patients treated with NIV was 11% and all deaths were with palliative intent, which followed time to allow for patient and family discussions. In Hong Kong, acute hypercapnic COPD patients have a 12-month readmission rate of 80% and a 49% 1-year mortality.74 The body mass index, airflow obstruction, dyspnoea and exercise capacity (BODE) index75 is a 10-point scale made up from the following four variables: (1) body mass index; (2) airflow obstruction; (3) severity of dyspnoea; and (4) exercise capacity, and has been found to be very useful in predicting survival in ambulatory patients with COPD (Table 26.3).

Table 26.3 The body mass index, airflow obstruction, dyspnoea and exercise capacity (BODE) index (maximum is 10)

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