3. Bronchomotor Tone + Asthma

Changes in bronchial smooth muscle tone are mediated via the autonomic nervous system Parasympathetic: this is dominant in the control of airway smooth muscle tone. Vagal stimulation of muscarinic cholinergic receptors causes bronchoconstriction, mucus secretion and vasodilatation of bronchial vessels. Increases in bronchial smooth muscle tone are mediated via the second messenger cyclic GMP under parasympathetic control. Sympathetic: sympathetic efferent nerves may control vasomotor tone, but there is no direct sympathetic innervation of bronchial smooth muscle, despite the fact that β2-adrenoceptors are abundantly expressed on human airway smooth muscle and their stimulation leads to bronchodilatation. Smooth muscle fibre relaxation occurs via the production of cyclic AMP and the activation of myosin light chain kinase.

Drugs: β2-agonists such as salbutamol, terbutaline and adrenaline cause bronchodilatation by increasing cAMP formation. Phosphodiesterase (PDE) inhibitors such as theophyllines do not inhibit intracellular PDE at therapeutic doses, and their mechanisms of action remain speculative. Antimuscarinic drugs such as ipratropium antagonize cholinergic receptors. (This is non-specific antagonism of M1–M5 receptors.

Criteria for ventilatory support: in essence this is a clinical decision rather than one based on numerical criteria such as measurements of peak expiratory flow rate (PEFR) and arterial blood gases. These are particularly useful in quantifying the response to treatment but should not represent the main criteria for ventilation.

Clinical features: the patient with severe acute asthma is unable to talk in sentences and uses all the accessory muscles of ventilation. Their respiratory rate will be high (>25 min1), as will the heart rate (>100 min1). Oxygenation is usually maintained and the PaCO2 is low. A normal PaCO2 is ominous. The PEFR may be between 33% and 50% either of predicted or of the patient’s recent best effort. Pulsus paradoxus (in which the arterial pressure changes in response to the large intrathoracic pressure swings) is no longer regarded as a useful sign. Life-threatening asthma is characterized by exhaustion, failing respiratory effort, a silent chest and sometimes confusion. Patients may be bradycardic, hypotensive and mentally obtunded. PEFR is below 33% of predicted, SpO2 is less than 92% and the PaCO2 is elevated. At SpO2 above 92% patients are unlikely to be hypercapnic.

Treatment of bronchoconstriction: this consists of humidified oxygen at flow rates to maintain an oxygen saturation of 94% or greater, nebulized salbutamol 5.0 mg or terbutaline 2.5 mg, and ipratropium 0.5 mg (both via an oxygen-driven device). Nebulized adrenaline is not superior to salbutamol or terbutaline. A single dose of magnesium sulphate 1.2–2.0 g infused over 20 minutes may improve lung function in the acute short term, but the BTS is cautious about recommending its routine use, both because of the absence of robust evidence and because of concerns about toxicity. Hydrocortisone 100 mg or other corticosteroids will also have been given. The use of aminophylline is contentious; there is no firm evidence of additional benefit, although a 5 mg kg1 loading dose and infusion of around 0.5 mg kg1 h1 may improve symptoms in a subgroup of patients whose response to other therapies has been poor. The use of heliox (helium/oxygen mixtures in ratios of 80:20 or 70:30) is also not recommended, although the guideline acknowledges that in patients with severe obstruction there is the possibility of benefit. Similarly, it acknowledges that while ketamine is a potent bronchodilator, prospective trials are needed to confirm its value in the context of acute severe asthma. Critical care physicians are usually a bit less timorous, and ketamine is frequently administered to patients with refractory asthma (0.5–2.0 mg kg–1 hr–1). The value of intravenous leukotriene receptor antagonists also awaits further studies according to BTS/SIGN, and there is no parenteral preparation available in the British National Formulary. Nonetheless, their mechanism of action suggests that they might be of benefit. Volatile anaesthetics are also sometimes used in difficult cases in which other treatment options have been exhausted.

Treatment of respiratory failure: non-invasive ventilation has not yet established a place in management, and there is insufficient evidence to support the use of helium– oxygen mixtures. Patients will need general anaesthesia, administered cautiously because of the sudden loss of adrenergic stimulation. Traditional teaching has always held that these patients are dehydrated and need fluid resuscitation. The risk may have been exaggerated; there is some evidence, in children at least, that acute asthma attacks are accompanied by ADH release, and so hypovolaemia may be less of a danger. Ventilation can be problematic. Airways resistance is high, and lung compliance is reduced by over distension. High inflation pressures are almost inevitable and may lead to barotrauma. The distribution of ventilation in asthmatics is uneven, and high inflation pressures may be directed preferentially to relatively unobstructed bronchi. It is important to maximize expiration, if necessary by adjusting the ventilatory pattern, including the I:E ratio, so as to prevent further distension. It may be impossible to ensure minute ventilation that will clear CO2, and so permissive hypercapnia may be necessary. It may even be desirable, because hyperventilation to reduce PaCO2 can be associated with a substantial acute reduction in cardiac output.