Acute Severe Asthma and Status Asthmaticus

Asthma is a common disease and its frequency sometimes detracts from its potential seriousness. Severe asthma in children is the third most common cause of hospital admission and the most common cause of paediatric ICU admission.^1,2 In adult asthmatics, only 5-10% have severe disease but these individuals carry a substantial proportion of the cost (both in terms of morbidity and economic) and run the highest risk of acute severe exacerbations and death.³

Status asthmaticus is severe asthma that does not respond well to immediate care and is a life-threatening medical emergency.
Ensuing respiratory failure results in hypoxia, carbon dioxide retention and acidosis. The exact mechanism underlying the development of an acute severe asthma attacks remains elusive but there appear to be two phenotypes:^4,5

• Gradual onset - in about 80%, severe attacks develop over more than 48 hours. These are associated with eosinophilic infiltration and slow response to therapy.
• Sudden onset - often in association with significant allergen exposure. Patients tend to be older and to present between midnight and 8 am. These type of attacks are associated with neutrophilic inflammation and a swifter response to therapy.

In deaths from asthma there is often a failure of either the patient and their family or carers or the health care team or indeed both to appreciate the full severity of the situation. Patients frequently have adverse psychosocial factors that interact with the ability to judge or manage their disease or have a diminished perception of their dyspnoea that leads to late presentation. Medical care continues to fail sometimes to treat acute severe asthma aggressively enough or to comply with national guidelines.⁶

According to Asthma UK:⁷

• There were 77,000 UK hospital admissions for asthma in 2005, 40% of which were children.
• There were approximately 1,300 deaths from asthma in 2005 in the UK. Twenty seven deaths were in patients under 14 years old.
• An estimated 75% of admissions for asthma are avoidable and as many as 90% of the deaths from asthma are thought preventable.
• Most deaths occurred before admission to hospital.

Risk factors

Risk factors for asthma related death include:⁶

• A background disease pattern of chronic severe asthma
  

  Severe asthma: Previous near-fatal asthma Previous admission for asthma, especially in last year 3 or more classes of asthma medication Heavy or increasing use of beta2-agonists Frequent emergency contacts for asthma care especially in the last year 'Brittle' asthma

• Inadequately treated disease +/- inadequately medical monitoring
• Inappropriate beta-blocker prescription or heavy sedation
• Non-steroidal anti-inflammatory sensitivity
• Use of a long acting beta₂-agonist such as salmeterol, especially if not using a steroid inhaler⁸
• Personal or passive smoking
• Adverse behavioural/psychosocial factors:
  • Non-compliance
  • Frequent DNAs
  • Self discharge
  • Psychiatric illness (psychosis, depression, deliberate self harm)
  • Denial of illness
  • Alcohol or street drug use
  • Obesity
  • Learning difficulties
  • Employment problems
  • Income problems
  • Social isolation
  • Childhood abuse
  • Severe domestic, marital or legal stressors
• Seasonal variation (in the UK, peak of deaths in under 44 years in July-August and December-January in older patients)

Environmental conditions - air pollution (ozone, sulphur dioxide, nitrogen dioxide and particulates) and pollen levels are thought to influence the rate of hospital admissions.⁹
Pregnancy will exacerbate asthma control in about a third of affected women. Treat the asthma - medication should be continued/stepped up where necessary; it is a lesser risk to the fetus than uncontrolled asthma or severe exacerbations.

Symptoms

• Shortness of breath may developed over hours or days but is usually progressive rather than sudden.
• A history of poor control is common.
• Often there has been a recent increase in use of reliever inhalers with decreasing response.
• Possible respiratory tract infection or exposure to an allergen or trigger.

Signs

• The patient will usually appear pink. Cyanosis is a serious sign.
• Respiratory rate is raised.
• Tachycardia is usual and may be increased by use of beta₂-agonists.
• Accessory muscles of respiration are employed (best assessed by palpation of the neck muscles) and the chest appears hyper-inflated.
• In normal breathing the ratio of the duration of inspiration to expiration is about 1:2 but as asthma becomes more severe the expiratory phase becomes relatively more prolonged.
• There are usually expiratory rhonchi in asthma but they may be inspiratory also in severe asthma.
  

  Pitfalls: A very tight chest may not wheeze at all due to poor air entry. Beware the silent chest. Patients with severe or life-threatening asthma may not appear distressed. The presence of any relevant abnormality should alert the doctor. Where signs/symptoms cross categories of severity, always assign the most severe category.

• Pulsus paradoxus is no longer recommended as a reliable indicator of the severity of an asthma attack.

Status asthmaticus must be distinguished from other causes of acute breathlessness including:

• Wheezing in children can be caused by a variety of infective conditions including RSV-causing bronchiolitis, epiglottis and croup
• Foreign body inhalation and other causes of stridor (vascular ring, tracheomalacia etc.)
• Primary pulmonary hypertension
• Pneumothorax with or without asthma
• Inhalation injury
• Cardiac failure ('cardiac asthma')

Initial assessment

• Take a very quick history and brief examination (conscious level, colour, pulse, BP, respiratory rate, listen to chest etc.).
• Supplement with objective bedside investigations if available:
  • Peak Expiratory Flow Rate (PEF) - this can be useful as an objective measurement and should be attempted with adults and children over 5 years, but can be unreliable due to distress or poor cooperation. PEF should be compared to a personal best PEF done when within the previous 2 years and when clinically well controlled.
  • Pulse Oximetry - a good quick measure of oxygenation.

Use these to assess severity:⁶

Immediate treatment

• Consider need for immediate transfer to hospital - arrange 999 ambulance.
• Give high flow oxygen (>60%) if available. Aim for oxygen saturations of at least 92%.
• Outside hospital, high dose beta₂-agonists may be given via large spacer devices (4-10 puffs inhaled individually) or nebulisers once available (this should be oxygen driven where available). Repeat every 10-20 minutes.
• If life-threatening asthma or severe asthma with poor response to above, give nebulised ipratropium. This can be mixed with nebulised salbutamol (i.e. combined with step above) in adults and children > 2 years. Repeat every 4-6 hours.
• Corticosteroids reduce mortality and should be given as early in the acute attack as possible. Give oral steroids (10 mg if <2, 20 mg if aged 2-5, 30-40 mg in older children and 40-50 mg in adults). If moribund or oral route not available give hydrocortisone 100 mg iv.

Referral

Criteria for admission:

• Any feature of life threatening or near-fatal attack.
• Any feature of severe attack persisting after initial treatment.
• Patients with PEF>75% best or predicted one hour after initial treatment but where:
  • Significant symptoms
  • Concerns about compliance
  • Socially isolated/lives alone
  • Psychological problems
  • Physical disability or learning difficulties
  • Previous near-fatal or brittle asthma
  • Exacerbation despite adequate dose of oral steroid tablets prior to presentation
  • Presentation at night
  • Pregnancy

Where admitting:

• Arrange a 999 ambulance if any feature of life threatening or worsening acute severe asthma.
• Stay with the patient until the ambulance arrives. Maintaining calm in the patient and their family is very important - patients with acute asthma are often highly anxious and getting a small child to accept treatment via a noisy nebuliser or face-mask based device may be challenging.
• Continue treating (high dose short-acting beta₂-agonist via oxygen driven nebuliser) and regularly reassessing patient (at least every 15 minutes) until transfer to hospital achieved.
• Send written assessment and referral details with patient.

Further hospital based management

Monitoring and investigations

• Continue regular monitoring - PEF following nebulised or inhaled beta₂-agonists, continuous oxygen saturation monitoring, pulse, respiratory rate.
• Blood tests - FBC, serum potassium and glucose, serum theophylline (where aminophylline is used for more than 24 hours).
• Arterial blood gases should be checked where life-threatening features. The 4 stages of blood gas progression in status asthmaticus are as follows:
  • The 1st stage is characterised by hyperventilation with a normal pO₂ and low pCO₂
  • The 2nd stage has hyperventilation but hypoxemia so that both pO₂ and pCO₂ are low
  • The 3rd stage gives a "false-normal" pCO₂ as ventilation has decreased. This is extremely serious and indicates respiratory muscle fatigue with the need for admission to the ICU and, probably, intubation with mechanical ventilation
  • The 4th stage has a low pO₂ and a high pCO₂ as respiratory muscles fail.
  Repeat blood gases within 2 hours of starting treatment when:
  • The initial pO₂ is <8 kPa unless SaO2 is >92%.
  • The initial pCO₂ is normal or raised.
  • The patient's condition deteriorates.
  • The 3rd and 4th stages require admission to ICU.
• Consider the need for CXR - routine use is not recommended but it may be used to exclude consolidation or pneumothorax and is needed prior to mechanical ventilation.

Treatment

• High flow oxygen via mask to maintain oxygen saturations >92%.
• Nebulised high dose beta₂-agonists - move from intermittent repeated doses (every 15-30 minutes) to continuous nebulisation where the attack remains severe or there is poor initial response. Intravenous beta₂-agonists should be reserved for those where inhaled therapy cannot be used reliably.
• Nebulised ipratropium - add to beta₂-agonist treatment where acute severe or life threatening features.
• Steroid therapy - continue oral prednisolone therapy for 3 days (children) or 5 days (adults), until a good recovery has been achieved. Intravenous hydrocortisone should be reserved for patients unable to take oral medication.
• IV fluids where dehydrated and correction of hypokalaemia (caused/exacerbated by beta₂-agonist and steroid regimes).
• Bolus IV magnesium sulphate - in those over 5 years with poorly responsive acute severe or life threatening asthma, after consultation with senior staff.
• IV aminophylline - only used in patients with near-fatal or life threatening asthma with poor response to initial treatment after consultation with senior staff. Side effects e.g. arrhythmias and vomiting increase with its use.
• Antibiotics are not indicated routinely.
• Heliox (helium/oxygen mixture) is not currently recommended.
• Where patients are failing to respond to treatment, they require transfer to ICU or HDU conditions.
• Those with worsening hypoxia, hypercapnia, drowsiness or unconsciousness and those experiencing a respiratory arrest require intubation. This is technically difficult and and should be undertaken by an anaesthetist or ICU consultant.
• The use of non invasive positive pressure ventilation (NIPPV) in status asthmaticus remains controversial.¹⁰

Complications of status asthmaticus include:

• Aspiration pneumonia
• Pneumomediastinum
• Pneumothorax
• Rhabdomyolysis
• Respiratory failure and arrest
• Cardiac arrest
• Hypoxic-ischaemic brain injury
• Death

In one study of children admitted to PICU, there was a 22% complication rate, increased by intubation.² The risk of death is increased where there is delay in getting treatment, particularly time to starting steroids, comorbidities such as congestive heart failure or COPD and in smokers. Mortality is highest in the very young and very old.

• All patients with asthma, but especially those with poorly controlled disease should have access to education about their condition, regular review and an asthma action plan.
• In addition to an asthma register, an "at risk" asthma register may help.¹¹ If "at-risk" patients fail to attend for appointments this should be followed up actively.¹²
• Those who are difficult to control need referral to specialist services.
• Be especially vigilant about those with psycho-social adverse factors too.
• Beta₂-agonist therapy used in isolation is only appropriate for those with the mildest variant of asthma.
• Receptionists, ambulance control and those who are first point of contact by patients must appreciate that an asthmatic having difficulty breathing needs to be seen as an emergency.
• Hospital admission should be an opportunity to review the patient's care plan.
• Anyone who has required admission should be followed up by a respiratory physician for at least a year.
• Patients who have had near-fatal asthma or brittle asthma should remain under specialist care indefinitely.