key: cord-022050-h24f0fpd authors: Naughton, Matthew T.; Tuxen, David V. title: Acute Exacerbations of Chronic Obstructive Pulmonary Disease and Asthma date: 2009-05-15 journal: Clinical Critical Care Medicine DOI: 10.1016/b978-0-323-02844-8.50029-9 sha: doc_id: 22050 cord_uid: h24f0fpd nan Chronic obstructive pulmonary disease (COPD) and asthma are conditions characterized by fixed and variable airflow obstruction, respectively. Increased use of inhaled steroids and exacerbation management plans have resulted in decreased hospital and intensive care admission rates for asthma. The same is not true for COPD. Although both can have common overlapping clinical presentations (Table 24 .1) and are responsible for significant morbidity and mortality, with a demand on intensive care services, their etiology and management differ. COPD is a condition in which permanent airflow obstruction occurs, associated with alveolar destruction (emphysema) and inflammation of the airway walls (chronic bronchitis). Asthma is defined by variable airflow obstruction that is reversible, completely or partially, spontaneously or with treatment, and is associated with airway inflammation and increased airway responsiveness to a variety of stimuli. Worldwide, it has been estimated that 1.1 billion people have COPD, a prevalence expected to increase to 1.6 billion people by 2025. In the United Kingdom, 20% of men and 10% of women older than age 45 years report a chronic cough with sputum, with 4% of men and 2% of women meeting diagnostic criteria for COPD. In the United States, COPD is estimated to occur in up to 19% of the adult community and result in 16 million physician visits and 500,000 hospital admissions per year. COPD is the fourth most common cause of death worldwide, accounting for 5% of all deaths-an age-adjusted rate that has risen from 1965 to 1995, in comparison with those for cardiovascular disease and stroke, both of which have declined. The mortality of COPD patients admitted to the hospital is 15%, exceeding that for myocardial infarction. Risk factors for mortality in COPD are low body mass index, degree of airflow obstruction as measured by FEV 1 , exercise limitation, and degree of dyspnea. Survival can also be predicted by the PaCO 2 ( Fig. 24 .1). Asthma is estimated to occur in 20% of children and 8% of adults, with 5% to 10% of these having poorly controlled disease. Life-threatening episodes occur in 0.5% of patients. In the United States, asthma is responsible for 1.8 million emergency department visits per year, with 1 in 4 requiring overnight admission. New Zealand, Australia, and the United Kingdom have the greatest prevalence rates. Chapter 24 Matthew T. Naughton and David V. Tuxen • Hypercapnic chronic obstructive pulmonary disease (COPD) patients should be treated with noninvasive ventilation and supplemental oxygen sufficient to overcome hypoxemia but avoid hyperoxia. • Intravenous or oral steroids in COPD should be limited to 3 to 10 days in most cases. • In acute severe asthma, there is no proof that the intravenous administration of short-acting b-agonists has an advantage over adequate nebulized administration. • In severe asthma, dynamic pulmonary hyperinflation due to mechanical ventilation can result in hypotension, pnemothoraces, and, in very severe asthma, circulatory collapse with pulseless electrical activity (i.e., electromechanical dissociation). This can be acutely relieved with a 60-second apnea test and thereafter prevented by a slow respiratory rate and a long expiratory time with permissive hypercapnia. • Following acute severe exacerbations of COPD and asthma, precipitating factors should be sought and avoided or treated. Patient-orientated action plans should be instituted to avoid further acute deterioration. Ninety-five percent of patients with COPD have tobacco smoking as a risk factor. Other environmental factors include exposure to secondary tobacco smoke, air pollution, indoor fumes (e.g., indoor cooking with solid biomass fuel), and poor socioeconomic status. Host factors are also important but, with the exception of a 1 -antitrypsin deficiency, are poorly understood. Although there is a clear familial prevalence of asthma, and several genes have been implicated, no single gene defined could allow for meaningful genetic planning. A number of other risk factors have been proposed, including (1) inadequate exposure to allergens due to excessive antibiotic use, (2) excessively clean dust-free environment (i.e., the hygiene hypothesis), (3) excessive exposure to common allergic (e.g., house dust mite, pollen, and animal dander) or nonallergic triggers (e.g., cold air, exercise, and atmospheric pollutants), and (4) exposure to medications that modulate airway control (e.g., aspirin and beta blockers). The increasing prevalence of asthma during the past 50 years has been attributed to increasing environmental exposures. Exposure to infections such as respiratory syncytial virus and parainfluenza (in children) and Chlamydia (in adults) has been implicated as a risk factor. Stress and socioeconomic status have also been implicated. In 30% of patients, no precipitant can be identified. Reduction in expiratory airflow occurs because of increased airway resistance and reduced lung elastic recoil. Airway resistance increases in the 4th-to 12th-generation airways as a result of mucosal inflammation, basement membrane thickening, edema, mucosal hypertrophy, secretions, and bronchospasm. Loss of lung elastic recoil is due to destruction of lung elastin and reduction in alveolar surface tension. Reduced elastic recoil decreases expiratory airflow by reducing the alveolar pressure driving expiratory airflow. Forced expiration increases alveolar driving pressure but also causes dynamic airway compression, resulting in no improvement, or sometimes a reduction, in expiratory airflow. The importance of this factor is a function of the degree of emphysema in each individual patient. Hypoxia and vascular wall changes lead to pulmonary vasoconstriction, pulmonary hypertension, cor pulmonale, and ventilation-to-perfusion heterogeneity. Most commonly, smoking-related COPD results in apical, rather than basal, disease ( Fig. 24. 2), whereas a 1 antitrypsin deficiency usually causes basal emphysema. Central respiratory drive may also be poorly responsive to the physiological trigger of hypercapnic acidosis, contributing to chronic hypercapnia. This may occur in the setting of sleep (i.e., obstructive sleep apnea), obesity, drugs (sedatives, antiepileptics, and alcohol), or metabolic disturbance (metabolic alkalosis). Postmortem studies indicate that small airway narrowing occurs as a result of bronchial wall edema, inflammatory cell infiltrates, smooth muscle hypertrophy and hyperplasia, collagen deposition beneath the basement membrane thickening, and intraluminal secretions of eosinophilic inflammatory cells. Eosinophils infiltrate the nerve bundles and release major basic protein, which antagonizes the inhibitory M 2 muscarinic receptor present on parasympathetic nerve endings. The nocturnal (or circadian) exacerbation commonly seen in asthma is due to a combination of factors, including exposure to cool dry air, inhalation of excessive allergens related to bedding, and circadian changes in airway diameter and cortisol. In COPD and asthma, pulmonary hyperinflation has both static and dynamic components. The static component is the increase in functional residual capacity (FRC) that exists at the end of an exhalation that is long enough for all expiratory airflow to cease (i.e., 30-120 sec). This component of hyperinflation is primarily due to airway closure that occurs throughout exhalation. Dynamic hyperinflation is the further increase in hyperinflation that occurs because of failure to complete exhalation before beginning the inhalation associated with the next breath. The extent of dynamic hyperinflation depends on the severity of airflow obstruction, the amount inspired (i.e., the tidal volume), and the expiratory time. Thus, the degree of hyperinflation may vary with changes in tidal volume and/or respira- tory rate that occur in response to changes in CO 2 production (as a function of exercise, diet, fever, or the metabolic response to illness) or changes in dead space, as well as with changes in airflow obstruction that occur during an exacerbation. Chest wall hyperinflation puts the inspiratory respiratory muscles at a mechanical disadvantage, increases the work of breathing, and predisposes patients to developing respiratory muscle fatigue. Chronic use of corticosteroids, electrolyte disturbances, and/or other medications may also contribute to this problem. In COPD, minor reductions in lung function due to infection, cardiac failure, or atelectasis increase the work of breathing by increasing airway resistance, lung stiffness, and/or dead space. This may result in rapid decompensation with ventilatory failure, acute hypercapnia, and respiratory acidosis as the tidal volume falls as a result of the increased volume of trapped gas and diminished respiratory muscle strength. during exhalation, use their accessory respiratory muscles for inhalation, are hyperinflated, and may develop right heart failure but only late in their course. In contrast, patients with a PaCO 2 greater than 45 mm Hg are generally more obese, have depression of their hypoxic and/or hypercarbic ventilatory drives (which can be worsened by excessive oxygen, alcohol, sedatives, or analgesics), have sleep-related hypoventilation, and are more likely to develop right heart failure early. Approximately 50% of patients with an acute exacerbation of COPD will be hypercapnic, a portion of them as a result of excessive oxygen administration. Acute exacerbations of COPD seem to result from respiratory infections (~50%) or cardiac failure (~25%). The remaining 25% may have retained secretions, air pollution, coexistent medical problems (e.g., pulmonary embolus, gastroesophageal reflux, and medication compliance or side effects) or no cause can be identified (Box 24.1). The most common bacterial isolates are Streptococcus pneumoniae, Hemophilus influenzae, Streptococcus viridans, and Moraxella catarrhalis. Mycobacterium pneumonia and Pseudomonas aeruginosa may also be found. Viruses have been isolated in 20% to 30% of exacerbations. These include rhinovirus, influenza and parainfluenza viruses, corona viruses, and, occasionally, adenovirus and respiratory syncitial virus have been isolated in 20% to 30% of exacerbations. Whether these organisms are pathogens or colonizers is often unclear. Pneumonia may account for 20% of those presentations requiring mechanical ventilation. Left ventricular systolic failure may result from coexisting ischemic heart disease, fluid overload, or tachyarrhythmias. Diastolic dysfunction may occur secondary to right ventricular dilation. Many of these patients have high levels of intrinsic positive end-expiratory pressure (PEEP) (or auto-PEEP), particularly during acute exacerbations, and this may decrease cardiac output by decreasing venous return. The increased work of breathing related to COPD will also contribute to heart failure because blood flow distributed to the respiratory muscles may increase by up to 10-fold. In the absence of roentgenographic evidence of pulmonary edema, left ventricular failure may be difficult to diagnose. Uncontrolled oxygen administration may precipitate acute hypercapnia in patients with acute COPD exacerbations as a result of relaxing hypoxic vasoconstriction, thereby allowing increased perfusion to regions with reduced alveolar ventilation. Although a reduction in hypercarbic drive was previously thought to account for this problem, the contribution of abnormal drive is limited. An accurate and detailed history is needed to distinguish asthma from other causes of dyspnea. Classically, asthmatic patients will have wheeze, cough, and/or dyspnea occurring with exercise, at night, or with exposure to specific triggers. When asthma is mild, there is typically a prompt resolution following inhalation of short-acting b-agonists (SABAs). The assessment of asthma severity (Table 24 .2) and triage is crucial. Most commonly, patients with severe asthma have a history of previous hospitalizations for asthma (some that may be near fatal), low socioeconomic status, female gender, obesity, nighttime symptoms, FEV 1 less than 60% with optimal treatment, continual symptoms, reduced quality of life, use of oral or systemic steroids in the past 12 months, use of more than canister of SABA per month, elevated residual volume-tototal lung capacity (RV:TLC) ratio on pulmonary function testing, and a peak expiratory flow rate variability of more than 30% (i.e., variability-(bestworst)/best reading). A typical pattern is the progression over hours to days, occurring in the setting of a history of recurrent presentations. This form is associated with greater airway inflammation and generally responds poorly, or incompletely, to initial bronchodilator therapy but responds to steroid and bronchodilators over a few hours or days. Less commonly, patients can present with hyperacute exacerbations, with the interval between the onset of symptoms and respiratory failure of less than 3 hours. This form of asthma occurs in younger patients, more commonly male, with intervening normal lung function but with highly sensitive bronchial reactivity to triggers, which is attributed to marked bronchial smooth muscle contraction. This form of asthma responds to SABA treatment within minutes to hours. Physical examination should include assessment of speech (ability to speak in sentences, phrases, or words), oxygen saturation, heart rate, pulsus paradox, use of accessory muscles, chest auscultation, conscious state, and response to immediate inhaled bronchodilators. Pulse higher than 120 beats/min, respiratory rate higher than 30/min, and pulsus paradox more than 15 mm Hg indicate severe asthma. Auscultatory findings of a silent chest may indicate extremely severe bronchospasm or the presence of pneumothorax. The diagnosis of COPD is usually established prior to patient presentation, with respiratory failure based on history, clinical examination, and investigations. Patients with COPD usually have a history of smoking more than 20 pack-years. In some settings, exposure to indoor solid fuel heating or cooking or a family history of a 1 -antitrypsin deficiency may be causative or contributing factors. They may have a history of chronic cough and sputum production and describe exertional dyspnea and wheeze. In patients with mild, stable disease, an expiratory wheeze on forced expiration and mild exertional dyspnea may be the only findings. In patients with moderate disease, modest to severe exertional dyspnea is associated with clinical signs of hyperinflation and increased work of breathing. In severe but stable disease, marked accessory muscle use is seen in association with tachypnea at rest, pursed lip breathing, hypoxemia, and signs of pulmonary hypertension [right ventricular heave, loud and palpable pulmonary second sound, and elevated "a" wave in jugular venous pressure (JVP)] and cor pulmonale (elevated JVP, hepatomegaly, and ankle swelling). In severe unstable COPD, there is marked tachypnea at rest, hypoxemia and tachycardia, and, in some cases, signs of hypercapnia (dilated cutaneous veins, blurred vision, headaches, obtunded mentation, and confusion). Clinical examination may also identify associated medical conditions precipitating the exacerbation, such as pulmonary crepitations and bronchial breathing with pneumonia, crepitations and cardiomegaly related to heart failure, or mediastinal shift related to a pneumothorax. The severity of COPD is best judged by assessing pulmonary function [i.e., peak expiratory flow rate (PEFR)] or FEV 1 . The vital capacity (VC) is initially normal and decreases later in the course of the disease but to a lesser degree than the FEV 1 . An FEV 1 :VC ratio less than 70% with an FEV 1 50% to 80% of predicted without a bronchodilator response usually indicates mild COPD. A significant bronchodilator response (i.e., >12% or >200 mL increase in either FEV 1 or VC) implies a diagnosis of asthma. An FEV 1 30% to 50% predicted indicates moderately severe COPD, and an FEV 1 less than 30% predicted indicates severe disease. Although the diagnosis may be based on spirometry alone, further lung function testing may be useful to characterize sever-ity. Flow volume curves demonstrate reduced expiratory flow rates and show the characteristic "concave" expiratory flow pattern. Lung volumes measured either by helium dilution or by plethysmography show elevated TLC, FRC, and RV. The RV:TLC ratio is characteristically more than 40%, representing intrathoracic gas trapping. The diffusion capacity, a measurement of alveolar surface area, is usually less than 80% predicted and is reduced in proportion to the extent of emphysema. Chest x-rays will commonly show hyperinflated lung fields as suggested by flattened diaphragms (best seen on lateral CXR), evidence of emphysematous bullae, and/or a paucity of lung markings. Pulmonary hypertension may be suggested by the presence of enlarged proximal pulmonary arteries, attenuated distal vascular markings, and right ventricular enlargement. High-resolution computed tomography (CT) scans show emphysema and can also confirm coexistent bronciectasis. Such scans are less sensitive than standard chest CT scans (1-cm slice) for detecting pulmonary lesions (e.g., neoplasms) ( Fig. 24 .3). Nuclear ventilation-perfusion scans show diffuse, well-matched, nonsegmental ventilation-perfusion abnormalities, with the degree of severity matching what is seen clinically. Arterial blood gases are mandatory to assess the degree of hypoxia and hypercapnia and to determine the acid-base status. A serum bicarbonate level more than 30 mEq/liter indicates either renal compensation for a chronic respiratory acidosis or a primary metabolic alkalosis (e.g., diuretic therapy, high-dose steroids, or high-volume gastric fluid loss). Renal compensation for chronic hypercapnia will increase the serum bicarbonate by approximately 4 mEq/liter for each 10 mm Hg of chronic PaCO 2 rise above 40 mm Hg in order to return pH to the low normal range. The electrocardiogram (ECG) is commonly normal but may show features of right atrial or right ventricular hypertrophy and strain, including P pulmonale, right axis deviation, dominant R waves in V1-V2, right bundle branch block, and ST depression and T wave flattening or inversion in V1-V3. These changes may be chronic or may develop acutely if there is a marked increase in pulmonary vascular resistance during the illness. The ECG may also show coexistent ischemic heart disease, tachycardia, and atrial fibrillation. Occasionally, continuous ECG monitoring is required to identify transient arrhythmias, which may also precipitate an acute deterioration. As with COPD, the diagnosis of asthma is usually apparent from history and examination. Tests of airflow obstruction are needed to assess severity. A PEFR of less than 100 L/min or an FEV 1 of less than 1 liter indicates a life-threatening asthma situation. These should be repeated to assess response to treatment. In mild to moderate asthma, arterial blood gases show a respiratory alkalosis as ventilation generally increases. In severe asthma, hypoxemia is present and can be easily corrected with supplemental oxygen with normal pH and PaCO 2 . In fulminant disease, hypercapnic respiratory acidosis develops with more severe hypoxemia. The respiratory acidosis may be compounded by lactic acidosis if intravenous SABAs (salbutamol, epinephrine, or isoprenaline) are used. Occasionally, continuously nebulized salbutamol can produce lactic acidosis. The chest x-ray rarely shows consolidation but should be obtained regardless, seeking evidence of pneumothorax or Chapter 24 pneumomediastinum (Fig. 24.4) . Importantly, a chest x-ray will also assist in excluding other differential diagnoses, such as left ventricular failure and possibly inhaled foreign bodies. If pulmonary infiltrates are found, the possibility of allergic bronchopulmonary aspergillosis should be considered. Serum IgE and eosinophil levels can be obtained in the acute setting. If either is elevated, the diagnosis of "extrinsic" asthma is established and even more attention should be paid to seeking out a specific allergen. Other causes of "asthma" should always be considered (e.g., inhaled foreign body, aspiration, left ventricular failure, pulmonary embolus, and pneumothorax). A new asthma exacerbation in an already hospitalized patient is more likely to be due to these causes than due to the asthma. Oxygen given by low-flow intranasal cannulae (1-4 L/min) or 24% to 35% by Venturi mask should be initiated with the goal of achieving an arterial saturation (SaCO 2 ) of 90 ± 2% because this will limit O 2 -induced increases in PaCO 2 (which occur most commonly in patients with initial PaCO 2 >50 mm Hg and pH <7.35). If the rise in PaCO 2 is excessive (>10 mm Hg), consider reducing the FIO 2 to a SaO 2 of 87% or 88% versus increasing the level of noninvasive positive pressure ventilatory support. Although high levels of O 2 should be avoided (SaO 2 >95%), reversal of hypoxia is important and O 2 should not be withheld in the presence of hypercapnia nor withdrawn if it worsens. Inadequate improvement of hypoxia with oxygen suggests that an additional problem is present (e.g., pneumonia, pulmonary edema, pulmonary embolus, or pneumothorax) and the diagnostic investigation should be broadened. While this is occurring, however, additional O 2 should be administered to alleviate the hypoxemia. Bronchodilators are routinely given in all exacerbations of COPD because a small reversible component of airflow obstruction is common, and bronchodilators may also improve mucociliary clearance of secretions. Anticholinergic agents have a similar or greater bronchodilator action than b-agonists in COPD, and they also have fewer side effects and are not associated with the development of tachyphylaxis. Anticholinergic agents should be used routinely in COPD with acute respiratory failure, and many now believe them to be the agent of first choice. Ipratropium bromide, 0.5 mg in 2 mL, should be given either as a metered-dose inhaler (preferentially) or nebulized initially every 2 hours and then every 4 to 6 hours. Chronic use of a long-acting anticholinergic (i.e., tiotropium) reduces the incidence of exacerbations, but this agent should not be used in the intensive care setting. Nebulized b-agonists are also effective bronchodilators in COPD, although they may cause tachycardia, tremor, mild reductions in potassium and PaO 2 (due to pulmonary vasodilatation), and tachyphylaxis. SABAs (e.g., salbutamol, terbutaline, or fenoterol) should be given by metered-dose inhaler or nebulizer every 2 to 4 hours in combination with ipratropium. The combination is more effective than either agent alone. Con- tinuous inhalation is not recommended because this has been shown to increase side effects without augmenting the response to treatment. Parenteral administration is also not recommended. In stable patients, long-term use of b-agonists may improve symptoms of dyspnea, particularly in the subgroup of COPD with an objective bronchodilator response. Long-acting b-agonists (LABAs) may also have a beneficial effect on symptoms, quality of life, and exercise capacity. Aminophylline is a weak bronchodilator in COPD. Although studies suggest that it improves diaphragm contractility, stimulates respiratory drive, improves mucociliary transport and right heart function, is anti-inflammatory, and is a weak diuretic, other studies have shown no or small benefits and frequent side effects when given to patients with acute COPD exacerbations. Accordingly, the literature does not support including this medication in the treatment of acute exacerbations. Short-term systemic corticosteroids improve the rate of airflow limitation in patients with acute COPD exacerbations. Current American Thoracic Society guidelines and Cochrane Reviews recommend a maximum dose equivalent to oral prednisolone at 0.5 mg/kg body weight for 3 to 10 days. Steroids should be avoided if the deterioration is clearly due to bacterial pneumonia without bronchospasm. Long-term oral steroids in COPD are associated with a number of serious side effects (e.g., osteoporosis, diabetes, peptic ulcer, myopathy, systemic hypertension, fluid retention, and weight gain) that are likely to impair quality of life and precipitate readmission. Accordingly, long-term use should be avoided whenever possible. A small group of patients (no more than 15% of the COPD population) may have a more than 50% improvement in their FEV 1 following 2 or 3 weeks of systemic corticosteroids. In these patients, the dose should be tapered to the lowest possible that maintains this improvement, and alternate-day dosing and/or a trial of chronic inhaled steroids can be considered. In the majority of patients, long-term inhaled steroids do not improve lung function or survival (although a trial designed and supported by the pharmaceutical industry suggests they may improve quality of life and reduce hospital admissions). Antibiotics have an accepted role in the treatment of infectioninduced exacerbations of COPD. Amoxicillin is a suitable firstline agent against H. influenzae, S. pneumoniae, and M. catarrahalis. If a chest x-ray suggests a component of pneumonia, then community-acquired pneumonia guidelines should be followed and treatment should include a tetracycline, macrolide, or fluoroquinolone. Treatment of associated medical conditions, such as fluid overload (diuretics), left heart failure (digoxin and vasodilators), pneumothorax (intercostal drainage), pulmonary embolus (anticoagulation), and electrolyte correction, should be undertaken as appropriate. Respiratory stimulants (e.g., acetazolamide, medroxyprogesterone, naloxone, doxapram, and almitrine) have no role because attempts to increase minute ventilation will increase dynamic hyperinflation and reduce muscle effectiveness and thereby increase work of breathing and fatigue. Narcotic-or benzodiazepine-induced respiratory depression is best managed with the appropriate antagonistnaloxone or flumazenil, respectively. Excessive carbohydrate calories should be avoided because this increases CO 2 production and may worsen respiratory failure. Noninvasive ventilation (NIV), a technique in which ventilatory support is provided via a nasal, facial, total face, or oral mask (Fig. 24.5) , should be considered in hypercapnic patients. Several randomized controlled trials have demonstrated improved respiratory physiology, reduced mortality, reduced iatrogenic complications, reduced need for intubation and mechanical ventilation, and reduced length of stay in hospital (Table 24 .3 and Fig. 24.6) . All studies have shown good tolerance of the technique (~80% of patients) with few side effects and improvements in both oxygenation and PaCO 2 compared with medically treated control patients. NIV unloads the inspiratory respiratory muscles, thereby reducing the work of breathing and the attendant CO 2 production. This immediately improves respiratory acidosis, even if alveolar ventilation is unchanged. Indications for NIV to treat acute exacerbations of COPD are acute dyspnea, respiratory rate higher than 28 beats/min, or PaCO 2 higher than 45 mm Hg with a pH less than 7.35 despite optimal medical treatment. Although these indications include mild to moderate exacerbations, most randomized studies have used these as entry guidelines (Table 24. 3). COPD patients liberated from invasive ventilatory support may also benefit from NIV, although studies have questioned the utility of its use in this setting. Side effects of NIV include discomfort, intolerance, skin necrosis (Fig. 24.7) , gastric distention, barotrauma, and aspiration. Choice of mask is extremely important. Face masks are generally preferred in the emergency setting, but if their use is complicated by air leaks, claustrophobia, discomfort, or nasal skin damage, then a larger face (head hood) may be better tolerated or more effective. Nasal masks are more suited to long-term support and usually not recommended for an acute exacerbation. Invasive ventilatory support may be required if respiratory failure progresses despite the previously discussed measures or if the patient is drowsy, uncooperative, or in extremis. 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. Obviously, this problem is markedly attenuated if primary care or outpatient specialty physicians appropriately address end-of-life issues with these patients prior to the acute exacerbation. The goals of invasive ventilatory support in COPD are to allow respiratory muscles to rest and recover without causing them to atrophy from total inactivity and to minimize dynamic hyperinflation. A variety of approaches can be used, but pressure-support ventilation is frequently employed in milder exacerbations. Since auto-PEEP exists in virtually every patient during an acute exacerbation, however, continuous positive airway pressure (CPAP) should always be applied. The level of CPAP should be adjusted and readjusted empirically, observing the work of breathing associated with inspiration (or by observing the esophageal pressure trace if this is being monitored). It cannot be adjusted on the basis of the airway pressure trace. Pressure support should be titrated to achieve an adequate tidal volume (250-400 mL), adequate spontaneous rate (<30 breaths/min), and patient comfort without excessive minute ventilation (<115 mL/kg/min) or excessive correction of hypercapnia. More severely affected patients need continuous ventilation or synchronized intermittent ventilation; dynamic hyperinflation should be avoided by using a low minute ventilation (115/mL/kg is a guide). This should be achieved by the use of a small tidal volume (8 mL/kg) and a ventilator rate less than 14 breaths/min. Plateau airway pressure (Pplat) should be measured by applying an end-inspiratory pause of 0.5 second following a single breath. This maneuver shortens expiratory time, and if it is applied to a series of breaths it will increase dynamic hyperinflation, increase the Pplat level, and increase the risk of volutrauma. If Pplat exceeds 25 cm H 2 O, the ventilator rate should be reduced. If a higher minute ventilation is required for excessive hypercapnic acidosis, the degree of dynamic hyperinflation and its effects should be assessed using Pplat. Use of a high inspiratory flow rate is recommended because it results in a shorter inspiratory time and hence a longer expiratory time for a given ven- Figure 24 .6. A series of arterial blood gases taken from a 51-yearold man with severe smoking-related COPD (FEV 1 , 500 mL) over 84 hr who demonstrates acute hyperoxic-induced hypercapnia upon a background of chronic compensated hypercapnia. A reduction in inspired oxygen concentration and noninvasive ventilation prevented intubation and mechanical ventilation. Despite presenting with severe hypercapnic acidosis and altered conscious state, the patient was suitable for discharge 3 days later. tilatory rate, which in turn reduces dynamic hyperinflation and alveolar pressure and improves gas exchange. If dynamic hyperinflation is excessive (with attendant circulatory compromise and/or a risk of barotraumas), minute ventilation should be decreased, accepting the resulting hypercapnic acidosis. Muscle relaxants should be avoided unless essential. Normally, however, spontaneous ventilation should be encouraged to promote ongoing respiratory muscle activity and minimize wasting. Flow-by, pressure support, and low-level CPAP may all reduce the work of spontaneous breathing and promote a better ventilatory pattern. Care must be taken with all these supports because 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 functional residual capacity. Patients who have been invasively ventilated for 7 to 10 days and have failed a trial of extubation with noninvasive ventilatory support may benefit from the insertion of a tracheotomy tube. This may be done via dilational (Seldinger) or surgical techniques. Generally, the former is more convenient, can be done in the ICU, and heals more quickly upon removal. The advantages of a tracheostomy are that dead space is reduced; the endotracheal tube can be removed from the mouth or nose, thus reducing local irritation and sedation; and it facilitates suctioning. The disadvantages include nosocomial infection, local trauma, reduced capacity to cough effectively, and loss of natural humidification. Protection of the airway from secretions that accumulate above the tracheostomy is not 100% even with the tracheostomy cuff inflated. Appropriate reduction in time on ventilatory support with an awake cooperative patient, allowing for periods of some respiratory work to maintain muscle strength, is crucial before eventual cessation of ventilatory support and removal of tracheostomy. Usually, tracheostomies can be safely removed if suctioning occurs less frequently than every 2 hours and patients are capable of independent ventilation and coughing (i.e., adequate muscle strength and drive) and have no anatomic abnormality that would preclude natural ventilation. Response to treatment within the first 2 hours is an important predictor of outcome. The patient should be allowed to sit upright and be given humidified oxygen at flow rates that keep the oxygen saturation higher than 90%. The development of oxygen-induced hypercapnia may indicate either underlying COPD with chronic hypercapnia or deteriorating progressive severe asthma. SABAs (salbutamol, albuterol, tertbutaline, and isoprenaline) are the cornerstone of acute asthma management. Salbutamol has b 2 selective bronchodilator properties with minimal b 1mediated cardiac toxicity and is thus the first choice b-agonist. LABAs such as salmeterol or eformoterol should not be used in acute asthma management. The mode of bronchodilator delivery is an important consideration. Multidose inhalers with spacer devices have the greatest penetration of drug into the lungs (~30%), are inexpensive, and should be used in patients with mild to moderate severity who are cooperative. In severe asthma or in uncooperative patients, nebulizers should be used; however, only approximately 10% of the drug reaches the lungs. Nebulizers require 8 to 15 liters per minute gas flow to operate, and this can be achieved with an electric air pump or with pressurized oxygen or air. Nebulized particle size ranges from 1 to 3 mm. Intravenous delivery of b-agonist has no advantage over the inhaled route. In severe asthma, a standard approach is to initiate nebulized 5 mg salbutamol with 8 L/min oxygen every 30 minutes in severe cases and every 2 to 4 hours in mild to moderate asthma. The volume of salbutamol should be made up to 2 to 4 mL with saline or short-acting anticholinergics. Side effects of the b 2 -agonists include tachycardia, arrhythmias, hypertension, hypotension, tremor, hypokalemia, worsening of ventilation-perfusion matching, and hyperglycemia. Lactic acidosis (up to 10-12 mmol/liter) is a common, doserelated consequence of intravenous SABA, appearing in as many as 70% of patients approximately 2 to 4 hours after initiation of treatment. When stable, SABAs should be replaced with LABAs in combination with inhaled steroid cover. LABAs should not be used as single treatments in asthma because there have been reported events of increased mortality, particularly in African Americans. Anticholinergics should be used as an adjunct treatment to a SABA rather than a single first-line treatment. Again, metered dose inhalers are preferable, but the medication can also be administered via nebulizer (usual dosages are 250-500 mg every 4-6 hr). Blurred vision may occur due to local effects on the eye. Anticholinergic preservative-induced bronchospasm has been reported and should be considered in patients with persistent wheeze. Systemic corticosteroids reduce hospitalization rates, mortality, and length of hospital stay in patients with asthma. Their mode of action is to primarily decrease the inflammatory response and the associated bronchospasm and mucus secretion, with an onset of action 6 to 12 hours after administration. Hydrocortisone (2-4 mg/kg) or methylprednisolone (0.5-1 mg/kg) is given intravenously, or prednisone or prednisolone (0.5-1.0 mg/kg) is given orally every 6 hours. These high doses are usually continued for 1 to 3 days or until clear clinical improvement is observed, after which they are tapered and replaced with inhaled steroids. Side effects of steroids include hyperglycemia, hypokalemia, hypertension, acute psychosis, myopathy, and gastritis. Longer term steroids are associated with additional problems, such as osteoporosis, cataracts, diabetes, oral thrush, and other secondary infections. Aminophylline has bronchodilatory and a variety of other antiinflammatory properties due to its ability to inhibit phosphodiesterase. The role of theophylline in acute asthma is not clear due to conflicting results from clinical trials and its narrow Chapter 24 therapeutic window, and its side effects include vomiting, tachyarrhythmias, headaches, restlessness, and convulsions. It is a fourth-line agent following SABAs, anticholinergics, and steroids. A usual dosage regime is a loading dose of 3 mg/kg and infusion rate of 0.5 mg/kg. Serum levels need to be monitored. Several alternative treatments have been proposed, such as methotrexate, intravenous g-globulin, cyclosporine, colchicines, troleandomycoin, lignocaine, and magnesium sulfate, with either no or marginal effect. Helium gas mixture has been used, as has the sedative ketamine, with similar marginal degrees of success. Noninvasive ventilatory support has been used infrequently for several years in acute asthma, and only in recent years have reports confirmed its safety and efficacy. In addition to expiratory airway pressure countering the effects of auto-PEEP, inspiratory positive airway pressure may counter the increased inspiratory resistance. Potential complications with noninvasive ventilation are patient-ventilator asynchrony, gas trapping (pulmonary or gastric), and decreased cardiac output from decreased venous return. Careful monitoring, similar to that of an intubated patient, is required. This should be considered in patients with severe and lifethreatening asthma (Table 24 .2) who have failed medical treatments as listed previously. As in COPD, the consequence of delayed expiratory airflow in asthma is that the inspired tidal volume cannot be completely exhaled to functional residual capacity and a proportion of each breath is trapped, impairing the arrival of each new breath. As lung volume increases, expiratory airflow also increases as a result of increasing small airway caliber and increasing elastic recoil pressure. This enables the lungs to inflate to an equilibrium point at which all the tidal volume is able to be exhaled during the expiratory time available. In mild airflow obstruction, this process is adaptive because it enables required minute ventilation to be achieved at a higher lung volume with only moderate loss of inspiratory muscle power. When airflow obstruction is severe, however, the equilibrium point may encroach on total lung capacity. The hyperinflation is the result of both airflow limitation and the increased minute ventilation required to provide a normal PaCO 2 . Complaints of needing ventilatory help, clinical appearance of exhaustion, deteriorating respiratory status, or reduced conscious state are more important indicators of the need for intubation than any specific PaCO 2 . The first 24 hours after intubation is the period of highest risk for ventilation-induced dynamic hyperinflation because airflow obstruction is often at its worst, CO 2 production and dead space are the highest, and hence the minute ventilation requirement is highest. At this time, patient respiratory distress and clinician desire to reduce hypercapnic acidosis can easily lead to a level of ventilation that results in excessive dynamic hyperinflation with risk of hypotension, pneumothoraces, and, uncommonly, circulatory collapse. As in COPD, initial minute ventilation should be restricted to 115 mL/kg/min (8 liters/min for a 70-kg lean weight patient) or less, tidal volume 8 mL/kg (560 mL for a 70-kg lean weight patient) or less, and respiratory rate 14 breaths/min or less. This should be delivered with a short inspiratory time (VI ≥ 80 liters/min or Ti ≤ 0.5 sec) to allow a long expiratory time (Te ≤ 3.5 sec) to minimize dynamic hyperinflation. Either pressure or volume control mode can be used to achieve this. Volume control mode is more established, results in more reliable volume delivery, and is preferred by these authors. PEEP can be used to counter intrinsic PEEP, but the possibility of increasing lung volume further (as will occur if external PEEP exceeds intrinsic PEEP) must be kept in mind. External PEEP will only be necessary if the patient continues to have spontaneous ventilation and is unable to trigger the ventilation. Generally, these patients receive heavy sedation to suppress their normal response to hypercarbia when their bronchospasm is so severe that sufficient alveolar ventilation cannot be accomplished. Although some patients may require one or two bolus doses of neuromuscular blocking agents, these agents should be avoided if possible because of the concern for profound, long-term myopathy thought to occur more frequently in patients receiving the combination of neuromuscular blocking agents and corticosteroids. Once initial ventilation is established, dynamic hyperinflation should be assessed by measuring Pplat and auto-PEEP and observing the response of central venous pressure and blood pressure to a transient period of reduced respiratory rate or ventilator disconnection. If Pplat is more than 25 cm H 2 O or circulatory improvement occurs, respiratory rate should be reduced and ventilation reassessed. If Pplat is low (e.g., <20-22 cm H 2 O) and hypercapnia is present, respiratory rate may be increased. Once asthma has improved, sedation may be reduced and spontaneous ventilation in CPAP mode with pressure support can occur. CPAP 5 to 10 cm H 2 O can be introduced to match auto-PEEP and reduce work of breathing. Hypotension can occur as a result of sedation, ventilationinduced dynamic hyperinflation, pneumothorax, hypovolemia, or arrhythmias. Pplat is commonly higher than 25 cm H 2 O, but an equally important assessment for hypotension is the response of the blood pressure and central venous pressure to 60 sec of ventilator disconnection ("apnea test"). Circulatory arrest with apparent electromechanical dissociation is a recognized complication of severe asthma. It occurs usually within 10 minutes of intubation and can result in severe cerebral ischemic injury and death if not recognized and managed appropriately. Most patients can tolerate mechanical ventilation with 115 mL/kg/min ventilation; however, a small number of patients with unusually severe asthma can develop life-threatening levels of dynamic hyperinflation despite this restriction in minute ventilation. In these patients, a 60-to 90second apnea test should be undertaken and ventilation resumed at the respiratory rate of 2 to 6 breaths/min. A common pitfall is the insertion of intravenous cannulae into the chest in the belief that this circulatory collapse is due to tension pneumothoraces. These procedures usually result in the complication they are seeking to relieve, and it is often difficult to know if a pneumothorax was initially present. Apnea testing should precede intercostal cannulae, and, if possible, incision with blunt insertion technique should be used. Pathophysiology of severe asthma. NHBLI workshop The nature of small-airway obstruction in chronic obstructive pulmonary disease Treatment of oxygen induced hypercapnia (correspondence) Glucocorticoid for acute severe asthma in hospitalized patients Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. NHLBI/WHO Global Initiative for Chronic Obstructive Lung Disease (GOLD) workshop summary Early use of noninvasive ventilation for acute exacerbations of chronic obstructive pulmonary disease on general respiratory wards: A multicentre randomised controlled trial Non-invasive positive pressure ventilation for treatment of respiratory failure due to exacerbations of chronic obstructive pulmonary disease. Cochrane Database Systematic Rev FDA safety alert Sleep and sleep disordered breathing in adults with predominantly mild obstructive airway disease A pilot prospective randomized placebo controlled trial of bilevel positive airway pressure in acute asthmatic attacks Chapter 24 Uncontrolled oxygen administration in COPD Inadequate use of noninvasive ventilation in COPD Excessive minute ventilation during mechanical ventilation Circulatory collapse soon after intubation in patients with very severe asthma Early intercostal cannula insertion during circulatory collapse Development of myopathy due to prolonged muscle relaxation and steroids High-resolution CT scans not contiguous and thus may miss pulmonary lesions Inadequate post-ICU follow-up to recognize and treat precipitating factors Etiology of acute exacerbation of COPD and asthma Dosage and duration of corticosteroids in acute COPD and asthma Role of noninvasive ventilation and acute exacerbations of asthma Role of intravenous short-acting b-agonists Development of hyperoxic hypercapnia in COPD Circulatory failure and pneumothoraces with mechanical ventilation Myopathy Lactic acidosis Micro-macroaspiration of enteral feeds during sleep/supine position Acute necrotizing myopathy is characterized by muscle weakness and histological evidence of myonecrosis, muscle cell vacuolization, and type II muscle atrophy. Myopathy ranges in severity from mild limb weakness to functional quadraparesis. Diagnosis is made by elevated creatine kinase levels and electromyography. Muscle biopsy is usually not required. There are no specific treatments and recovery is usually complete, but in severely affected patients significant weakness may still be present at 12 months. Boxes 24.2, 24.3, and 24.4 list the pitfalls, complications, and controversies.