◆ Control dynamic hyperinflation during mechanical ventilation by using low minute ventilation, low tidal volume, and high inspiratory flow to achieve a plateau pressure ≤25 cmH2O.
◆ Accept high peak inspiratory pressure that results from high inspiratory flow so long as plateau pressure is safe.
◆ Recognize lactic acidosis from salbutamol.
◆ Avoid myopathy by avoiding or minimizing neuromuscular blockade.
◆ Reduce the ventilator rate if a pneumothorax is suspected to protect the second lung.
Airflow limitation occurs in asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis, bronchiectasis, bronchiolitis obliterans, and a component of airflow limitation can accompany a number of other less common conditions.
Both acute severe asthma and exacerbations of chronic airflow limitation can be life-threatening emergencies, requiring urgent medical treatment and ventilatory support. If these are not available or instigated in a timely way, cardiorespiratory arrest can occur, resulting in death or hypoxic cerebral injury. Even after instigation of invasive ventilatory support the risk is not over, as both medical therapy and the ventilator technique also have significant risk of morbidity and mortality. Understanding the mechanism of these problems is key to avoiding them.
Pathophysiology and causes of airflow limitation
The pathogenesis of asthma has both genetic and environmental factors. There is an increase in worldwide prevalence . Reduced exposure to childhood infections as a result of antibiotics and a more hygienic lifestyle are believed to lead to increased IgE-dependent airway inflammation and bronchial hyperreactivity (the ‘hygiene hypothesis’) with local allergen exposure determining the specific antibody responses . Triggers of acute asthma can be non-specific (cold air, exercise, pollutants), specific allergens (house mite, pollen, animal danders), modifiers of airway control (aspirin, β-blockers), or stress or emotion. No precipitant can be identified in over 30% of exacerbations.
Two patterns of acute severe asthma have been identified . Usual acute severe asthma is the more common group (80–90%), with progression of symptoms over many hours or days, often with a background of poor control and recurrent presentations. This group is predominantly female, triggered by upper respiratory infections and responds slowly to treatment. Pathology is dominated by mucous inspissation and chronic bronchial wall inflammation with eosinophilia . ‘Hyperacute’, ‘fulminating’, ‘asphyxic’, or ‘sudden onset’ severe asthma is where the interval between onset of symptoms and intubation is less than 3 hours [3,4,5]. This presentation is less common (approximately 10–20% of life-threatening presentations) and tends to occur in younger male patients with relatively normal lung function, but high bronchial reactivity. Massive respiratory allergen exposure, cold air or exercise and psychosocial stress are the most frequent triggers . This group characteristically has neutrophilic inflammation, typically responds quickly to bronchodilators and is thought to be mainly due to bronchial smooth muscle contraction.
COPD also has both host and environmental factors. Environmental factors include tobacco smoke, air pollution, indoor fumes (e.g. from solid biomass fuel) and poor socio-economic status. The biggest single factor in over 95% of patients with COPD is tobacco smoking. Marijuana smoking may cause premature and quite advanced bullous emphysema due to extremely hot and toxic inhaled smoke held at peak inspiration for prolonged periods of time . 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) . Only approximately 15% of smokers develop COPD.
In both asthma and COPD, reduced expiratory airflow is primarily due to increased small airway resistance usually due to varying combinations of mucosal oedema and hypertrophy, secretions, bronchospasm, airway tortuosity, and airflow turbulence. In COPD, the loss of lung parenchyma and its elastic tissues (the emphysema component) further reduces expiratory airflow by a decrease in elastic support of the small airways and reduced lung elastic recoil. Reduction of lung elastic recoil pressure is due both to loss of lung elastin and loss of alveolar surface tension from alveolar wall destruction.
Common problems associated with treatment
The majority of critically-ill patients who require mechanical ventilation do not have airflow limitation; their lungs return to functional residual capacity or passive relaxation volume at the end of tidal expiration (Fig. 110.1) where the recoil pressures of the lungs (to collapse) and chest wall (to expand) are balanced.
This is not the case in a patient with any significant airflow limitation. Slower expiratory flow results in incomplete exhalation of the inspired tidal volume (VT) in the expiratory time available and part of the inspired volume is trapped by the arrival of each new breath after commencement of mechanical ventilation (‘gas trapping’, Fig. 110.1). The lungs undergo dynamic hyperinflation . The expiratory time to complete exhalation in severe airflow limitation may be 30–90 sec . Gas trapping does not continue indefinitely, but increases lung volume over 6–12 breaths until an equilibrium point is reached where the inspired VT (which could not be completely expired at lower lung volumes) is able to be expired in the same expiratory time . This equilibrium point is enabled by two factors—the increase in lung elastic recoil pressure and in small airway calibre, both of which normally occur as lung volume increases. The three primary determinants of this equilibrium point are the volume going in (VT), the time for it to come out (determined both by respiratory rate and inspiratory flow or the I:E ratio) and, of course, the severity of airflow limitation.
In moderate airflow limitation with spontaneous breathing this process is adaptive; it allows the desired minute ventilation to be achieved at a higher lung volume, albeit with increased work of breathing and loss of inspiratory reserve. When airflow limitation becomes severe during spontaneous breathing, dynamic hyperinflation will continue to total lung capacity (Fig. 110.2). Hypercapnia occurs in the absence of fatigue as a result of the physical limits on inspiration and expiration, where the maximum achievable minute ventilation is less than that required for normocapnia. Of course, at this lung volume, the inspiratory muscles length is very short and has little mechanical advantage over the already maximally-inflated chest wall and so muscle fatigue can rapidly occur with worsening hypercapnia.
Once mechanical ventilation is commenced, ventilation is easily increased, resulting in more dynamic hyperinflation to above total lung capacity (Fig. 110.2) where hypotension and risk of pneumothorax will readily occur .
The passive relaxation volume of the lung, i.e. the functional residual capacity (FRC) after prolonged expiration (30–90 sec in a paralysed patient), is elevated in moderate to severe airflow obstruction by airway closure that occurs throughout expiration. In severe asthma requiring mechanical ventilation FRC is 50% above normal  and only 1.4 L below total lung capacity (Fig. 110.2). A period of 30–90 sec apnoea during mechanical ventilation will allow the lungs to exhale all dynamically-trapped gas and return to this FRC (Fig. 110.2) with release of circulatory compromise . Restoration of ventilation will return the lungs to their previous hyperinflation within 6–10 breaths (Fig. 110.2). It has been shown that ventilation to end-inspiratory lung volumes above total lung capacity (TLC) greatly increases the risk of hypotension and pneumothorax, while ventilation that keeps the plateau pressure (Pplat) ≤25 cmH2O reduces that risk .
The biggest single ventilator variable affecting the trapped gas volume (Fig. 110.3) is the minute ventilation (VE, Fig. 110.3) . A large VT slightly increases trapped gas levels at each level of VE, but greatly increases the end-inspiratory lung volume with risk of pneumothorax. The changes in central venous and oesophageal pressures, and the reductions in mean arterial pressure most directly relate to the end-expiratory lung volume  (Fig. 110.4). The only ventilator pattern that places all patients below the safety line equivalent to TLC is a low VT and a low VE (Fig. 110.3).
In patients requiring mechanical ventilation for severe asthma, the minute ventilation required to normalize PaCO2 and pH can require a high level of VE. If these levels of VE are used, the result is excessive dynamic hyperinflation in most patients, significant risk of hypotension and pneumothorax, and increase in asthma ventilation mortality [9,12]. Safe ventilation should result in an end-inspiratory lung volume (Vei) ≤20 mL/kg (1.4 L) and a Pplat of less than 25 mLH2O. This usually requires a VE of ≤115 mL/kg/min (≤8 L/min), which will result in most patients being initially hypercapnic.
During volume controlled ventilation, the use of a high inspiratory flow (Vi) in the presence of airflow limitation will result in a high peak inspiratory pressure (PIP), but a lower Pplat. When the Vi is turned down there is a very gratifying reduction in PIP at every level of minute ventilation, but hidden beneath this falling airway pressure is an increasing Pplat (Fig. 110.5) that may convert a patient from a safe to an unsafe level of dynamic hyperinflation [8,12].
A safe level of dynamic hyperinflation (Pplat 25 cmH2O) with a high PIP may not need change, accepting that high PIP is necessary in severe asthma to allow inspiration of a safe tidal volume over a short time inspiratory time. A high PIP in the presence of otherwise safe ventilation has never been shown to cause harm in severe airway obstruction.
Treatment-induced lactic acidosis
Both intravenous salbutamol and continuously nebulized salbutamol can, and often do, cause lactic acidosis [13,14]. Over the course of 1–2 hours, particularly after a bolus dose of intravenous salbutamol, the lactate level may rise as high as 12 mmol/L . The benefits of nebulized salbutamol in acute severe airway obstruction are beyond question . Intravenous salbutamol has never been shown to have additional benefit above maximal doses of nebulized salbutamol [13,17], but has the theoretical advantage of reaching airways that are completely occluded and, hence, inaccessible to nebulized salbutamol.
It is commonly used in acute severe asthma refractory to initial treatment in some countries. Thus, intravenous salbutamol may improve airflow limitation, but may concurrently increase dyspnoea, distress, and fatigue by the production of lactic acid. This resolves rapidly with infusion reduction or cessation. With continued infusions, the lactic acidosis is usually resolved within 24 hours. This phenomenon is shared with other intravenous beta-agonists. The mechanism is not clear, but is probably a direct effect on intracellular metabolism.
Necrotizing myopathy after prolonged ventilation
It has now been widely reported [15,18,19] that patients with severe asthma who receive prolonged neuromuscular blockade or even effective paralysis by heavy sedation  can suffer from an acute necrotizing myopathy. This characterized by generalized weakness and hyporeflexia, which can range from mild weakness (not delaying ICU discharge) to profound weakness requiring prolonged mechanical ventilation, rehabilitation, and significant disability at 12 months. Sensation is intact. Electromyography shows a myopathic pattern, sometimes with false features of neuropathy. Serum creatine kinase (CK) levels are always abnormal and levels may range from mild elevation to greater than 10,000 IU. Levels do not correlate well with weakness as a muscular person may have a large, but transient CK rise with minimal weakness and an elderly person with poor muscle mass might have small elevations for an extended time period with severe weakness. Muscle biopsy shows three characteristic features:
◆ Non-uniform muscle wasting with pale staining.
◆ Nuclear crowding, but lack of inflammatory infiltrate.
◆ Vacuolation (Fig. 110.6).
Myopathy severity has been shown to correlate with dose of neuromuscular blocking agents received .
Ventilation-induced circulatory collapse
A small subset of patients have such severe asthma that the usual safe ventilation results in extreme dynamic hyperinflation with acute circulatory collapse and apparent electromechanical dissociation within a short time of commencing mechanical ventilation. If this phenomenon is not recognized early it can lead to prolonged, futile standard resuscitation, eventually leading to asystole, and brain damage or death. A period of apnoea or much reduced minute ventilation will usually result in circulatory improvement. Additional fluid resuscitation and inotropes may also be required.
Pneumothoraces in severe airflow limitation are most commonly caused by excessive dynamic hyperinflation, central venous cannulation, or intercostal insertion of an intravenous cannula for a suspected pneumothorax. They are almost always under tension during mechanical ventilation because the airways themselves expand during inspiration, and collapse during expiration resulting in a valve-like effect and airway closure prevents the lung from collapsing and sealing the air leak. Such a pneumothorax will significantly reduce ventilation to that lung and increase ventilation to the second lung greatly increasing the risk of bilateral tension pneumothoraces. While either an urgent chest X-ray (if mild hypotension) or an intercostal catheter insertion (if severe hypotension) is required promptly, the first action should be a reduction in ventilation to prevent a pneumothorax in the second lung.
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