Treatment of Acute Asthma in Adults

The following should be noted:

Oxygen

Oxygen should be administered to any patient with oxygen saturations below 94% and where pulse oximetry is not immediately available. The oxygen should be titrated to maintain saturations between 94 and 98%. Nebulisers should be driven by oxygen (at least 6l/min.) since there is a risk of desaturation if air-driven systems are used.

β2 agonists

Metered dose β2 agonist inhalers with spacers (4 puffs of salbutamol then 2puffs every 2 minutes up to a maximum of 10 puffs) should be used in patients with moderate exacerbations.
Nebulisers may provide superior drug delivery for patients with severe exacerbations and allow concurrent oxygen administration. Repeat doses of 5mg salbutamol nebulisers can be used when the initial response is inadequate. This is sometimes termed “back to back nebulisers”. In practice a nebuliser takes 15-30 minutes to fully administer the drug. Administering more than 10mg of salbutamol per hour is unlikely to improve effectiveness but may increase side effects, which include tremor and tachycardia. Special delivery systems can deliver “continuous” nebulisers at 10mg per hour but are not usually available in the ED.
Meta-analyses have not demonstrated superiority of intravenous over nebulised salbutamol in acute asthma. However, intravenous β2 agonists may be beneficial when nebulisers cannot deliver the drug effectively (patient pulling mask off/poor air entry). Nebulised adrenaline has not shown superiority to salbutamol and is a less selective β agonist.

Learning bite

An Inhaler with a spacer is the preferred delivery system for patients with moderate severity asthma.

Ipratropium Bromide

Anticholinergic nebulisers may not be beneficial for mild exacerbations of asthma and the British asthma guidelines only advocate their use (Ipratropium Bromide 500 micrograms nebuliser) in cases which are severe, life-threatening, or poorly responsive to β2 agonist therapy.
Side effects are uncommon but include dry mouth, dry eyes, blurred vision, tachycardia, flushing, confusion and urinary retention. Ipratropium bromide is long acting and should not be given more frequently than 4 hourly. If it is given more frequently, the risk of side-effects is increased, particularly in the elderly.

Learning bite

If Ipratropium Bromide has been given by nebuliser in the ambulance it should not be repeated in the first 4 hours in the ED.

Steroids

Early steroid administration in acute severe asthmatic exacerbations is associated with a reduced need for hospital admission [8]. They should be given acutely to patients with the following features:

• Life-threatening asthma
• PEFR <75% best or predicted after initial salbutamol treatment (5 mg nebuliser or spacer as appropriate)
• Any indicator of severe asthma after initial appropriate salbutamol therapy

Taking two 25 mg tablets or soluble prednisolone is preferable to eight or ten 5 mg tablets for patients who are at risk of hypoxia when the oxygen mask is removed. Intravenous hydrocortisone (100 mg qds) does not work faster than oral steroids but can be used for patients who are too breathless to swallow or who are vomiting.
A course of steroids should be prescribed for adults whose PEFR was initially <50% best or predicted that have improved sufficiently with treatment to be considered suitable for discharge. Steroids can be stopped abruptly after 5 days as long as the patient continues inhaled steroids. Longer courses are indicated if the patient remains symptomatic or is on long term steroid maintenance therapy.
In 2008, a small randomised trial [9] reported that adults attending an Israeli ED had significantly higher rates of discharge from the ED at 2 hours when inhaled steroids were administered acutely. Use of inhaled steroids, either alone or in conjunction with intravenous steroids, was associated with improved lung function at 2 hours compared to use of intravenous steroids alone. Pulmonary vasoconstriction has been postulated as a possible explanation for inhaled steroid effect in such a short timeframe. It is unclear whether this outcome will be replicated in larger trials but the British guidelines advise that inhaled steroids be started, or continued, as soon as possible after an acute attack.

Early steroid administration in acute severe asthmatic exacerbations is associated with a reduced need for hospital admission.

Magnesium Sulphate

BTS guidelines state that a systematic review of 25 RCTs (13 including adults) involving 2,907 patients with asthma showed that nebulised magnesium sulphate when used in addition to nebulised β2 agonist (with or without nebulised ipratropium) provided no benefit in terms of lung function or need for hospital admission. Subgroup analysis of the most severe patients was not possible due to heterogeneity in studies and the use of multiple different end-points. Some smaller studies noted modest improvements in lung function with nebulised magnesium in the most severe subgroup (presenting FEV1 50% at presentation and the study failed to show improvement in either rate of hospital admission or breathlessness as judged by a visual analogue score. A single dose of intravenous magnesium sulphate is safe and may improve lung function and reduce intubation rates in patients with acute severe asthma. Intravenous magnesium sulphate may also reduce hospital admissions in adults with acute asthma who have had little or no response to standard treatment. However, the heterogeneous nature of the studies included in this review and lack of information on the severity of the asthma attack or when intravenous magnesium was given in relation to standard treatment limit the conclusions that can be drawn. The safety and efficacy of repeated intravenous (IV) doses of magnesium sulphate have not been assessed. Repeated doses could cause hypermagnesaemia with muscle weakness and respiratory fatigue.

Consider giving a single dose of intravenous magnesium sulphate to patients with acute severe asthma (PEF <50% best or predicted) who have not had a good initial response to inhaled bronchodilator therapy.

Magnesium sulphate 1.2-2g IV infusion over 20 minutes should only be used following consultation with senior medical staff.

The most common dose is magnesium sulphate 2g in 100mls of 0.9% sodium chloride over 20 minutes.  This dose mirrors that used in the 3MG study, which did not show any benefit in terms of hospital admission or VAS of breathlessness at 2 hours post administration.

Intravenous aminophylline

Aminophylline is of unproven benefit in life-threatening asthma and, unlike magnesium, is pro-arrhythmic. The British asthma guidelines state that it should only be administered for life threatening asthma on the recommendation of senior medical staff.

If the patient is on maintenance oral therapy a baseline theophylline/ aminophylline level should be taken before a maintenance infusion of intravenous aminophylline infusion is started. If the patient is not on maintenance therapy, a loading dose infusion should be given first.

Loading dose
Intravenous aminophylline 5 mg/kg over 20 minutes

Maintenance dose
Intravenous aminophylline infusion of 0.5–0.7 mg/kg/hr

Intravenous fluid
There is no evidence to suggest that routine intravenous fluid improves outcome in acute asthma. There is a role for fluid when patients are dehydrated or have electrolyte imbalance (hypokalaemia).

Antibiotics
The British asthma guideline discourages routine antibiotic prescription in acute asthma. Infective triggers are most commonly viral.

Leukotriene antagonists
Research is ongoing but there is no current evidence to support the use of leukotriene antagonists in acute asthma.

Heliox (helium/oxygen)

Inhaling heliox has theoretical benefits since its low density reduces the work of breathing and should improve bronchodilator delivery. However, its use is impractical and existing studies have failed to demonstrate convincing improvements in pulmonary function. Its use not recommended outside of clinical trials.

Nebulised furosemide

A theoretical bronchodilator of research interest. To date, nebulised furosemide has not been shown to be significantly better than nebulised β2 agonists.