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Therapeutic approach to bronchospasm and asthma 

Therapeutic approach to bronchospasm and asthma
Chapter:
Therapeutic approach to bronchospasm and asthma
Author(s):

Brett G. Sampson

and Andrew D. Bersten

DOI:
10.1093/med/9780199600830.003.0111
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date: 30 November 2020

Key points

  • Risk factors for life-threatening asthma include chronic severe asthma, taking ≥3 asthma medications, previous intensive care unit admissions, previous invasive ventilation, and psychosocial factors.

  • β‎2 agonists, anticholinergics, and corticosteroids are the mainstay of treatment.

  • A ventilation strategy of hypoventilation and permissive hypercapnoea minimizes barotrauma and dynamic hyperinflation.

  • Hypotension, cardiovascular collapse, and cardiac arrest may result from dynamic hyperinflation, tension pneumothorax, acute right heart failure, or arrhythmia.

  • Non-established therapies include leukotriene antagonists, non-invasive ventilation, and extracorporeal support.

Clinical assessment

A focused asthma history and examination enables grading of severity (Box 111.1). Risk factors for life-threatening asthma include chronic severe asthma, taking ≥3 asthma medications, previous intensive care unit (ICU) admissions, previous invasive ventilation, and psychosocial factors [1,2]. Chest examination should assess for pneumothorax, lung collapse, and hyperinflation. A ‘silent chest’ from maximally hyperinflated lungs may portend respiratory arrest. Alternative diagnoses, including left ventricular failure, inhaled foreign body, upper airway obstruction, and vocal cord dysfunction should be considered, especially if unresponsive to bronchodilator therapy.

* PEFR may not be possible in severe and life-threatening asthma, and may worsen bronchospasm.

** Absence of pulsus paradoxus does not exclude severe and life-threatening asthma.

Vocal cord dysfunction

Early recognition of vocal cord dysfunction (VCD), the inappropriate adduction of the vocal folds during respiration, may prevent β‎2 agonist toxicity and unnecessary intubation. VCD may mimic refractory asthma, affects 4–10% of asthma clinic patients, is more common in females, and a physical cause is identified in only 25% [3]‌. Diagnosis is by fibre optic observation of paradoxical vocal cord movement and possibly by computed tomography (CT) of the larynx [3].

β‎2 agonist toxicity

Adverse effects of β‎2 agonists range from tolerable side effects to serious toxicity. Side effects include tachycardia, arrhythmia, hypertension, hypotension, tremor, hypokalaemia, worsening of V/Q mismatch, and hyperglycaemia. β‎2 agonist toxicity may cause lactic acidosis with respiratory compensation, which can be mistakenly attributed to worsening or unresponsive asthma; often leading to further inappropriate β‎2 agonist administration [4]‌. β‎2 agonist toxicity is most often seen with intravenous (iv) infusions and continuous nebulization. ICU admission for closely supervised cessation, or reduction, of β‎2 agonist therapy allows safe resolution of the hyperlactataemia.

Chest radiograph

A chest radiograph is indicated in unresponsive severe asthma, when lower respiratory tract infection or barotrauma is suspected, after initiation of ventilation, and if the diagnosis is in doubt.

Pulse oximetry and arterial blood gas analysis

Pulse oximetry enables accurate titration of oxygen therapy. Hypoxaemia from V/Q mismatch and mucous plugging is common in severe asthma. Hypocapnoea and respiratory alkalosis from hyperventilation is seen initially in severe asthma. Normal PaCO2 or hypercapnoea usually represents more severe asthma, especially if the PaCO2 is rising on serial measurements. Arterial blood gas sampling is indicated to confirm hypoxaemia, and to measure PaCO2, pH, and lactate. Lactic acidosis and hypokalaemia from β‎2 agonist toxicity can be detected by arterial blood gas analysis.

Therapeutic management

Oxygen

Humidified oxygen should be applied to maintain SpO2 between 94 and 98% [2]‌. Hyperoxia from uncontrolled oxygen administration can worsen V/Q mismatch by releasing hypoxic vasoconstriction, leading to increasing hypercapnoea.

β‎2 agonists

Inhaled short-acting β‎2 agonists are the first line treatment. β‎2 agonist via metered dose inhalers (MDI) and spacer is more effective in cooperative patients than nebulization. Typically, four to eight puffs of salbutamol are administered 1–4-hourly [2,5]. Oxygen-driven nebulization is recommended in life-threatening asthma as delivery by MDI and spacer method is usually not possible. Nebulized salbutamol (5 mg every 15–30 minutes) is a common initial regimen, increasing the dosing interval to 1–4 hours according to response [2]‌. Continuous nebulization, e.g. salbutamol 5–10 mg/hour, may be more effective than intermittent administration [6]. Despite a lack of evidence, and a higher risk of toxicity, iv infusions of β‎2 agonist may be considered in life-threatening asthma unresponsive to continuous nebulization, e.g. salbutamol 5-20 micrograms/min. An iv bolus of 100–300 micrograms of salbutamol may be life-saving in the unintubated patient in extremis. While unresponsiveness to maximal β‎2 agonist therapy may suggest refractory asthma or a complication of asthma (Box 111.2), alternative diagnoses, and β‎2 agonist toxicity should always be considered.

Anticholinergics

Combining nebulized ipratropium bromide (500 micrograms 4–6-hourly) with nebulized β‎2 agonist produces significantly greater bronchodilation than β‎2 agonist alone [1,2,7]. An initial three doses 20 minutes apart might have additional benefit.

Corticosteroids

Prednisolone 50 mg daily (or 100 mg hydrocortisone 6-hourly if the oral route is not possible) should be commenced as early as possible and continued for at least 5 days [1,2]. Following recovery of the acute exacerbation, systemic steroids should be stopped or returned to maintenance dose, without tapering and inhaled steroids recommenced.

Magnesium sulfate

A single iv dose (1.2–2 g iv over 20 minutes) may be beneficial in severe and life-threatening asthma in patients who are unresponsive to maximal bronchodilator therapy [1,2,8]. However, evidence for the nebulized route is lacking [8]‌. While serious side effects from a single dose are uncommon, iv magnesium may cause respiratory muscle weakness, hypotension, flushing, sedation, areflexia, and arrhythmias, and therefore, repeat doses should be avoided.

Adrenaline

A slow iv bolus dose of 0.2–1 mg, over 3–5 minutes, followed by an infusion of 1–20 micrograms/min may be effective in selected patients. Subcutaneous and intramuscular adrenaline (0.3–0.5 mg) appears to be efficacious and safe in the prehospital environment for near fatal asthma that is unresponsive to β‎2 agonists.

While there is insufficient evidence for iv adrenaline in acute severe asthma, it may avert invasive ventilation when a patient is in extremis [9]‌.

Heliox

Helium/oxygen mixtures (e.g. Heliox 70:30) may decrease resistance to airflow, enhance delivery of nebulized bronchodilators, and improve pulmonary function in severe acute asthma [10]. However, the existing evidence does not support its use in asthma [1,10].

Anaesthetic agents

Ketamine infusion (0.5-2 mg/hr) has been reported to induce bronchodilation and avoid intubation in severe asthma [11], but there is insufficient evidence to recommend its use. The use of volatile anaesthetic agents (e.g. halothane) in ventilated patients has been described; hypotension, myocardial depression, and rebound bronchospasm, as well as the requirement for an anaesthetic machine with scavenging have limited their use.

Aminophylline

Aminophylline does not provide additional bronchodilation beyond that achieved by β‎2 agonist therapy in adults [1,12]. However, aminophylline is beneficial in children with unresponsive severe acute asthma [13]. Aminophylline has a narrow therapeutic index and unfavourable side effect profile (headache, nausea, vomiting, cardiac arrhythmias, and seizures).

Leukotriene antagonists

Leukotriene antagonists have shown early promise in the treatment of acute asthma [14,15], but their use is currently limited to clinical trials.

Ventilatory support

Dynamic hyperinflation and intrinsic PEEP

Dynamic hyperinflation is the progressive increase in lung volume occurring when severe airflow limitation prevents complete exhalation before onset of the next breath (commonly known as ‘gas trapping’) [16]. Functional residual capacity (FRC) progressively increases, shifting tidal ventilation into higher lung volumes, resulting in flattening of the diaphragm, mechanical disadvantage, and increased elastic load. Together with the underlying increase in resistive work, the minute ventilation required to maintain normocapnoea eventually becomes unachievable, resulting in hypercapnic respiratory failure.

Intrinsic positive end expiratory pressure (PEEPi) results from incomplete exhalation with progressively higher end-expiratory lung volumes and failure of alveolar pressure to return to zero at end expiration [16]. PEEPi measured as the airway pressure after an end-expiratory occlusion is the most common method used; however, this requires a relaxed patient and sufficient time for equilibration. Due to the heterogeneous distribution of inflammation and bronchospasm (and consequently dynamic hyperinflation and PEEPi), PEEPi should be considered an average value. Also, airway closure may prevent regional PEEPi from being measured underestimating gas trapping (Fig. 111.1) [16].

Fig. 111.1 Schematic representation of the heterogeneous distribution of airflow limitation and lung mechanics at end-inspiration and end-expiration in acute asthma. The figure represents the lung at both end-inspiration and end-expiration with associated airway time curves and relevant pressures during controlled mechanical ventilation in a relaxed patient. At end-inspiration a 0.5-second pause results in a fall from a peak airway pressure (Ppk) to the plateau airway pressure (Pplat) followed by a fall to the set PEEPe of 0 cmH2O. The difference between Ppk and Pplat is determined by the average inspiratory resistance and the inspiratory flow rate. As there is heterogeneous distribution of resistance, different lung units have different Ppk, but a constant Pplat. The average Ppk and Pplat is also shown in the major conducting airway. At end-expiration differences in resistance between lung units results in heterogeneous degrees of gas trapping and PEEPi. The result of an end-expiratory occlusion is shown in the airway pressure time relation with a rise in pressure to the average PEEPi (6 cmH2O) occurring over some seconds.

Fig. 111.1 Schematic representation of the heterogeneous distribution of airflow limitation and lung mechanics at end-inspiration and end-expiration in acute asthma. The figure represents the lung at both end-inspiration and end-expiration with associated airway time curves and relevant pressures during controlled mechanical ventilation in a relaxed patient. At end-inspiration a 0.5-second pause results in a fall from a peak airway pressure (Ppk) to the plateau airway pressure (Pplat) followed by a fall to the set PEEPe of 0 cmH2O. The difference between Ppk and Pplat is determined by the average inspiratory resistance and the inspiratory flow rate. As there is heterogeneous distribution of resistance, different lung units have different Ppk, but a constant Pplat. The average Ppk and Pplat is also shown in the major conducting airway. At end-expiration differences in resistance between lung units results in heterogeneous degrees of gas trapping and PEEPi. The result of an end-expiratory occlusion is shown in the airway pressure time relation with a rise in pressure to the average PEEPi (6 cmH2O) occurring over some seconds.

During spontaneous and supported ventilation, inspiratory effort must overcome PEEPi and reduce airway pressure below extrinsic PEEP (PEEPe), or below atmospheric pressure if no PEEPe is applied, before inspiratory flow can occur. This additional elastic load contributes to increased work of breathing and respiratory insufficiency. During supported or triggered ventilation a low level of PEEPe (typically 5 cmH2O), which is less than the PEEPi, can reduce inspiratory (threshold) work and allow easier triggering of the ventilator. During controlled ventilation, when there is no spontaneous respiratory effort, the traditional approach is to set PEEPe to zero to prevent further increases in lung volume. However, one study suggests that an empirical trial of PEEPe during controlled ventilation may paradoxically relieve over inflation [17].

Non-invasive ventilation

Although non-invasive ventilation (NIV) has potential benefits, there is insufficient evidence to support its use in asthma [18]. NIV applied PEEPe (5 cmH20) may reduce the inspiratory effort required to overcome PEEPi, shorten inspiratory time and improve minute ventilation; without worsening dynamic hyperinflation. Other possible benefits include reduced V/Q mismatch, improved response to bronchodilators, avoidance of mechanical ventilation, improved PEFR and FEV1, and shorter ICU and hospital stay. However, NIV has potential serious complications including gastric insufflation, aspiration, hypotension, and pneumothorax. A trial of NIV may be warranted in cooperative patients with severe asthma, but must not delay intubation and invasive ventilation. Non-invasive positive pressure ventilation (NPPV) is the most studied mode of NIV in asthma, with inspiratory positive airway pressures (IPAP) of 12–15 cmH2O and an expiratory positive airway pressure (EPAP) of 5 cmH2O [18].

Invasive ventilation

The decision to intubate should be made by an experienced clinician after a period of observation, taking into consideration the rapidity of asthma onset, response to treatment and projected clinical course. It may be safe to withhold intubation in hypercapnic hyperacute asthma responding to treatment, but may be necessary in normocapnic chronic severe asthma with exhaustion. Absolute indications for intubation include respiratory and cardiac arrest, severe hypoxaemia, severe exhaustion, and rapidly deteriorating conscious state [19].

Induction with ketamine may provide additional bronchodilation [19]. Intubation-induced bronchospasm may be attenuated by maximal pre-induction β‎2 agonist therapy; intravenous lidocaine has not been shown to be effective [19]. Once endotracheal tube placement is confirmed, slow hand ventilation (4–10 breaths/min) will maximize expiratory time until connection to the ventilator. A ventilation strategy that provides adequate oxygenation, while avoiding dynamic hyperinflation is required. This mandates a prolonged expiratory time with accompanying relative hypoventilation and permissive hypercapnoea. Prolonged expiratory time may be safely achieved with volume control ventilation at an initial tidal volume of 5–7 mL/kg and respiratory rate of 6–12/min. CO2 clearance may be improved by incrementally increasing tidal volume and reducing respiratory rate (preserving constant minute ventilation) to reduce the anatomical dead space ventilation fraction. PEEPe is usually set at zero to prevent further increases in lung volume and dynamic hyperinflation. Inspiratory flow rates should be initially set at 30–60 L/min. Although higher inspiratory flow rates (70–100 L/min) may reduce inspiratory time, resultant high peak airway pressures may expose over distended, well-ventilated lung units to barotrauma (Fig. 111.1). A constant inspiratory flow pattern offers the advantage of a simple estimate of inspiratory resistance when an inspiratory pause is used and prevents dissipation of visco-elastic forces aiding expiratory flow. However, the peak airway pressure will be higher than if a descending ramp inspiratory flow pattern is used. Adjustments of tidal volume, respiratory rate and inspiratory flow should be made to maintain a Pplat < 25 cmH2O. Acidaemia from permissive hypercapnoea is usually well tolerated. Sodium bicarbonate administration may be of benefit if the pH is below 7.15, although it can worsen intracellular acidosis. Deep sedation and intermittent neuromuscular blockade are usually required in the early ventilation period to avoid asynchrony.

Withdrawal of ventilation

Withdrawal of ventilation may be attempted once airflow limitation has improved, suggested by a decreasing Pplat and PEEPi. Sedation is reduced, respiratory rate increased and pressure support ventilation commenced once spontaneous respiratory effort returns. PEEPe (3-7 cmH20) may be cautiously introduced to assist triggering and reduce work of breathing.

Complications of ventilation

Hypotension, cardiovascular collapse, and cardiac arrest may result from dynamic hyperinflation, tension pneumothorax, acute right heart failure, or arrhythmia (Box 111.3). Cardiac arrest with pulseless electrical activity can occur from severe dynamic hyperinflation alone or from tension pneumothorax. Return of circulation after disconnection from the ventilator (for up to 60 seconds), the apnoea test, is both diagnostic and therapeutic for dynamic hyperinflation. Tension pneumothorax is difficult to diagnose and confirmation by chest radiograph should occur unless the patient is in cardiac arrest. Management is with chest drain insertion by blunt dissection; needle thoracentesis should be avoided to prevent iatrogenic pneumothorax. Complications such as myopathy and ventilator-associated pneumonia may prolong ventilator dependence.

Acute necrotizing myopathy associated with deep sedation, corticosteroids, and prolonged neuromuscular blockade may prolong ventilation weaning and slow overall recovery. Neuromuscular blockade should be used sparingly and systemic corticosteroid ceased as soon as possible to reduce the risk of myopathy. Mucous plugging and lung collapse may require bronchoscopic airway toilet.

Extracorporeal support

Extracorporeal support has been described in life-threatening asthma; registry data demonstrated an 83.3% survival to hospital discharge, compared with 50.8% in non-asthmatics [20].

References

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