Pierre Goussard , RP Gie , S Kling
Tygerberg Children's Hospital,
Cape Town , South Africa
Acute severe asthma in children
• 2 year old boy from Delft
• Presents with tight chest and wheezing
• No previous episodes
• No TB contact
• No allergies
• No important previous medical history
• No clubbing
• Severely distress
• Trachea central
• Reduced ventilation bilaterally but right
more than left
• Berotec and Atrovent nebs
• Salbutamol IV
• Solumedrol IV
• Desaturated and intubated
• At this stage very little ventilation right
and hyperresonant on percussion
• Estimated prevalence in South Africa
– 10 – 15%
• Most asthmatics have mild to moderate
disease, with severe asthma thought to
affect less than 10% of asthmatics.
Levin M.S A Resp r J 2006;12(1) 14- 18.
Moore WC J Allergy Clin Immunol l 2006; 17: 487-494
• Acute attacks of asthma come on
• May occur in patients with well-controlled
asthma, but usually are an indication of
failure of the long-term management plan.
• Acute severe asthma is one of the most
common medical emergency situations in
“Defined as wheezing which does not
respond to initial treatment with inhaled
Mannix R, Bachur R: Status asthmaticus in children. Curr Opin
Pediatr 2007, 19:281-7.
Werner HA: Status asthmaticus in children. Chest 2001,
What define a severe acute attack?
• Disturbance in level of consciousness
• Inability to speak and/or feed
• Severely diminished or absent breath sounds
• Central cyanosis.
• Use of accessory muscles while breathing.
• Increased respiratory and cardiac rate
• Non-invasive objective measures, which aid in
the assessment of the patient with acute asthma
– peak expiratory flow rate (PEF)
– pulse oximetry
Who are at risk for fatal asthma
• Previous ICU admission for asthma, especially if
mechanical ventilation required
• Current or very recent treatment with prednisone
• Hospitalization or emergency department visit
for asthma in the past year
• Not currently using inhaled corticosteroids
• Excessive use of short-acting inhaled ß2 agonist
• Chronic severity with impaired lung functions
Robertson et al have found that in 51
paediatric deaths from asthma in Australia
only in 39% where was a potentially
preventable cause of death
Robertson CF et al .Ped Pulmomology 2002;13:95- 100
• Marked changes in lung volume and pleural pressures
impact on the function of both left and right ventricles.
• Spontaneously breathing children with severe asthma
have negative intrapleural pressures
• Mean pleural pressure becomes more negative with
increasing severity of the attack.
• Negative intrapleural pressure causes increased left
ventricular afterload and favors transcapillary filtration of
edema fluid into airspaces resulting in a high risk for
• Right ventricular afterload is increased secondary to
hypoxic pulmonary vasoconstriction, acidosis, and
increased lung volume.
• This actually inappropriate term describes an
exaggeration of the normal inspiratory drop in
arterial pressure (normally < 5 mm Hg, but < 10
mm Hg in pulses paradoxus).
• Pulsus paradoxus is the result of a marked
inspiratory decrease in left sided cardiac output,
caused by decreased left atrial return from
increased capacitance of the pulmonary
vascular bed, and increased left ventricular
afterload from negative pleural pressures.
• Extent of wheeze does not necessarily reflect the
extent of bronchopulmonary obstruction, since
some degree of airflow is required to produce a
• Decreasing wheeze and breath sounds and a
"quiet chest“ in a child with increasing respiratory
efforts may signal imminent respiratory failure.
• Conversely, increasing wheeze in a child with
severe asthma may indicate improvement.
McFadden ER Jr, Kiser R, DeGroot W: Acute bronchial asthma:
relations between clinical and physiologic manifestations. N
Engl J Med 1973, 288:221-5.
Is it asthma
• Other conditions present with airway
– Small airways obstruction
– Large airway obstruction
• Hypoxemia and the increased work of breathing
may result in anaerobic muscle work and
accumulation of lactate.
• During an asthma attack, metabolic acidosis
may initially be compensated for by
hyperventilation and a respiratory alkalosis
• But as respiratory failure develops, increasing
arterial CO2 will result in a respiratory acidosis
and a further decrease in arterial pH
• Increasing levels of CO2 is a ominous sign
• Hypocarbia → Nomal PCO2 = trouble
Chest X-ray in severe asthma
• Relevant in search for underlining
– Air leakages
• Ventilated patients
Basic treatment of acute asthma
• Repeated doses of short acting B2 agonist
– driven by oxygen
– repeated doses every 15 – 30 min
• Systemic corticosteroids
– The earlier they are administered the better
• Oxygen must be considered as a drug in a
situation of acute asthma
– reducing hypoxic pulmonary vasoconstriction
– ventilation-perfusion mismatch
• Recent guidelines recommend that
oxygen saturation in children should be
kept above 95%
Global Strategy for Asthma Management and Prevention
2008 (update) [http://www.ginasthma.org]
• Inhaled bronchodilators
– B2 agonists
• Additional treatment
– IV theophylline
– IV b2-agonists
– IV magnesium sulphate
Inhaled B2 agonists
• There is evidence suggesting that continuous
administration of nebulised β2-agonists may
have a better and prolonged bronchodilatory
effect compared to intermittent therapy
• A sustained stimulation of β2-receptors is
accomplished, and a possible rebound
bronchoconstriction reported during intermittent
therapy is prevented
• An often used rule of thumb is that β2-agonist
should be administered until development of
significant side effects, a strategy requiring close
Carroll W, Lenney W: Drug therapy in the management of
acute asthma. Arch Dis Child Educ Pract Ed 2007, 92(3):ep82-ep86
• Nebulizes Salbuterol, 2.5 mg (diluted to 4
mL), in uncomplicated asthma, double the
concentration in severe cases
• Undiluted drug for severe status
Werner HA. Chest 2001 ; 119:1913-1929
Nebulized vs MDI B2 agonist
• A meta-analysis performed in 491 children
under 5 years of age with acute
• Patients who received b-agonists by MDI
and valved holding chamber showed a
significant decrease in the admission rate
compared with those receiving nebulizer
treatments [odds ratio (OR), 0.42;95% CI,
Castro-Rodriguez JA et al. J Pediatr 2004; 145:172–177.
• Patient may use an empty MDI during an acute
• Even with adequate supervision, correct MDI
technique, and a full MDI device, hospitalized
children may benefit from nebulized b-agonists
over MDI forms.
• The potential for suboptimal MDI technique may
increase with increasing severity of
• The nebulized route allows continuous
• The combination of nebulised IB with a nebulised ß2
agonist has been shown to result in greater
bronchodilatation than a ß2 agonist alone.
• The most severely affected patients benefit the most,
and IB should be considered in combination with inhaled
ß2 agonists :
– More severe forms of asthma
– Early in the acute attack,
– If there is an incomplete response to inhaled ß2 agonists on their
• May be repeated every 20 min for the first hour and
every four hours thereafter
Plotnick LH et al. Cochrane library issue 3 2001
• Both the a-agonist and b-agonist effects of adrenaline
might be beneficial, with the a-effect decreasing oedema
and the b-effect responsible for bronchodilation
• In infants and young children with acute asthma and
mucosal oedema and secretion may dominate the
• Inhaled β2-agonists may be less efficient.
• Nebulised adrenaline has a rapid but short acting effect on
mucosal oedema and may be of value as initial treatment
also in severely obstructed older children, before
administration of inhaled β2-agonists.
Carlsen KH, Carlsen KCL: Pharmaceutical treatment strategies
for childhood asthma. Curr Opin Allergy Clin Immunol 2008,
• The use of IV salbutamol (15 mcg/kg as a once-off
dose) in the early management of acute severe
asthma in children has been shown to reduce the
duration of the exacerbation and hasten the
discharge from hospital of the children.
• In the intensive care unit IV salbutamol by
continuous infusion is effective and probably safer
• Side effect
– Cardiovascular in nature
Browne GJ et al. Lancet 1997;349:301-305
• The positive effect from theophylline infusion on acute
asthma is well documented, as are the potential for side
effects and severe or even fatal complications
• May be used in cases of near fatal or life threatening
asthma in the intensive care unit.
• Inhaled drugs may have limited effect in children with
nearly complete airway obstruction and have practical
limitations in ventilated patients.
• A reasonable starting point is a 6-mg/kg
aminophylline load followed by a 1-mg/kg/h
`Cochrane concluded that in children with
severe asthma , the addition of IV
aminophylline to b2 agonists and steroids
improves lung functions within 6 hours`
Cochrane Database Syst Rev 2005;
• Steroid tablets or liquid are effective as injected steroids.
– Effect after 3-4 hours
• But patient must be able to swallow and not vomit
• Usual dose of oral prednisone or prednisolone is
• Hydrocortisone of 4 mg/kg or methylprednisolone 0.5 -
1.0 mg/kg every 4-6 hour are alternatives to oral
steroids, but may be reserved for children unable to
receive oral administration due to severity or low age
• A prolonged course of treatment may be particularly
necessary if the exacerbation is the result of
longstanding untreated bronchial inflammation.
BTS guidelines 2005
• Higher steroid doses do not appear to offer a
therapeutic advantage, and because the risk of
myopathy is significant, especially in the ventilated
• The concomitant use of systemic corticosteroids and
paralytic agents should be avoided if at all possible.
• There is some suggestion that for patients with
severe symptoms i.v. corticosteroid therapy might
have an early effect (within 1–6 h) by reversing b2-
receptor down regulation seen in chronic b2-agonist
Ellul-Micallef R, Fenech FF. Effect of intravenous prednisolone in
asthmatics with diminished adrenergic responsiveness. Lancet
1975; 2: 1269–71.
• Adrenaline 0.01 ml/kg of a 1:1000 solu-
tion administered subcutaneously may be
used in patients who are moribund on
presentation to the ED, or where in- haled
therapy is not available.
• Magnesium cause smooth muscle relaxation secondary to inhibition
of calcium uptake.
• A single dose of IV magnesium sulphate has been shown to be safe
and effective in those patients with acute severe asthma who have
had a poor response to initial therapy.
• The response to magnesium appears to be best in patients who
present with very severe illness.
• The recent GINA-guidelines suggest that iv magnesium may be
considered in acute moderate and severe asthma with incomplete
response to initial treatment during the first 1-2 hours
• The dose is 25 - 50 mg/kg/dose (maximum 2 g) by slow IV infusion.
Ciarallo L et al. J Pediatr 1996;129809-814
Global Strategy for Asthma Management and Prevention
2008 (update) [http://www.ginasthma.org]
• One double-blind placebo-controlled study reported a
significant increase in peak expiratory flow, FEV1, and
forced vital capacity in children who had asthma and
were treated with a single 40-mg/kg dose of
magnesium sulfate (MgSO4) infused over 20 minutes,
along with steroids and inhaled bronchodilators,
compared with control subjects who received saline
• These patients were significantly more likely to be
discharged home from the presenting ED than control
subjects (0 of 14 patients; P = .002).
Ciarallo L, Brousseau D, Reinert S. Higher-dose intravenous magnesium
therapy for children with moderate to severeacute asthma. Arch Pediatr
Adolesc Med. Oct 2000;154(10):979-83.
Is there a role for ICS during acute
• Emerging data suggest that high doses of ICS
may be as effective as systemic corticosteroids
in the treatment of acute asthma exacerbations
• During more severe exacerbations, there is little
published evidence regarding corticosteroid
dosage and duration.
Volovitz B. Respir Med 2007; 101:685–695.
• It is inadvisable to overhydrate patients
with acute asthma, and the recommended
IV fluid volume in children should not
exceed 50 ml/kg/24 hours.
– Pulmonary oedema
Clinical phenotypes :risk of PICU
• Obesity may be an important confounder in
children with asthma
• Genetic variations in the population may also be
important in influencing response to therapy for
acute asthma .
• Recently, Carroll et al identified a population of
children admitted to the ICU with severe asthma
who were slow-responders to b-agonist therapy
Carroll CL et al.Pediatr Crit are 2006; 7:527–531.
Carroll CL et al.Pediatr Pulmonol 2008; 43:627–633
– 80:20 mixture of helium-oxygen is most effective, and heliox
loses most of its clinical utility when the FiO2 is greater than
40%, reducing the percentage of helium to less than 60%
• Leukotriene antagonists
– montelukast intravenousl
– administered in the ED to patients presenting with acute
asthma resulted in improved FEV1 within20 min of
– Patients treated with montelukast tended to receive less b-
agonists and have fewer treatment failures than patients
Camargo CA Jr, Smithline HA, Malice MP, Green SA, Reiss TF.
A randomized controlled trial of intravenous montelukast in
acute asthma. Am. J. Respir. Crit. Care Med. 2003; 167: 528– 33.
• Intubation and positive pressure ventilation of an
asthmatic child may:
– increase bronchoconstriction,
– Increase the risk of airway leakage
– has disadvantageous effects on circulation and cardiac
• < 1% of asthmatic children admitted to a children’s
hospital and 5 to 10% of asthmatic patients admitted to
pediatric intensive care require intubation.
Dworkin G et al. Mechanical ventilation for status asthmaticus in
children. J Pediatr 1989; 114:545–549
Pirie J et al.Changes in treatment and outcomes of children receiving
care in the ICUs for severe acute asthma. Pediatr Emerg Care 1998;
When to intubate
• Absolute indications for intubation:
– include severe hypoxia
– cardiopulmonary arrest
– severe deterioration of the mental status of the child.
• Relative indications:
– are progress of respiratory failure
– increasing CO2 despite adequate utilisation of all
available treatment measure
– Global initiative for asthma suggests PC02 > 45 mmHg
is an indication for ICU admission
Decision should not only depend on blood gas , but
should be made on clinical grounds
• Before intubation, the child should be properly preoxygenated.
• Atropine may be indicated together with a sedative and a rapid
• Ketamine (1-2 mg/kg i.v) is often recommended due to its
• Neuromuscular blockade
• Cuffed ET
• Complications post intubation:
– cardiac arrest
– pneumothorax and hypoxia may develop
• Hypotension may be caused by hyperinflation with decreased
veneous return to the heart, aggravated by the vasodilatory effects
of medications used during intubation.
• Hypotension may be prevented by a fluid bolus given prior to
> 50% OF THE COMPLICATIONS IN
ASTHMATIC PATIENTS BEING
VENTILATED OCCUR DURING OR
IMMEDIATELY AFTER INTUBATION
Zimmerman JL et al. Crit Care Med 1993;21:1727-1730
• Positive pressure ventilation is complicated by severe airway
obstruction and air trapping, which results in hyperinflated
lungs that may resist further inflation and has a high risk of
• Asthma is a disease increased airway resistance, resulting in
prolongation of the time constant (the time needed for lung
units to fill and empty). Slow ventilator rates are needed.
• In the face of high peak airway pressures, the principle of
mechanical ventilation of status asthmaticus is controlled
hypoventilation, tolerating higher levels of PCO2 in order to
minimize tidal volume and peak inspiratory pressures.
• Permissive hypercapnia can be tolerated as long as the patient
remains adequately oxygenated.
• A longer I:E ratio, often greater than 1:3-4, helps allow time for
optimal exhalation, facilitating ventilation and avoiding
excessive further air-trapping (auto-PEEP).
• The use PEEP is controversial. A patient with status
asthmaticus in respiratory failure on mechanical
ventilation usually has a significant amount of air
trapping that results in intrinsic PEEP, which may be
worsened by maintaining PEEP during exhalation.
• However, some patients may benefit by the addition of
PEEP, perhaps by maintaining airway patency during
• In a patient who remains refractory to the initial
ventilatory settings with no or very low PEEP, cautiously
increasing the PEEP may prove beneficial
• Rate – slow
– Well below what is normal for age
• IT – 0.75s- 1.5s
• PiP – Normally very high
– Due to high inspiratory flow
– PIP does not represent alveolar pressures
– Not good indicator of the risk of barotrauma
– Inspiratory plateau pressure better
– Try keep < 40 cmH20
• PEEP - ?
– Not morphine because of histamine release
– Ph >7.10 but need to oxygenate in less than
FiO2 < 0.6
• Halothane and isoflurane have been
successfully administered in children
receiving mechanical ventilation with life-
• Difficult and lots of complications
– Halothane- cardiac problems
– Increase intrapulmonary shunt
42% experienced a complication. Complication rate 15 times more in
the ventilated patients
Carrol CL et al. Pediatric Pulmonology 2007;42:914-919
Bronchoscopy and BAL
• Mucous plugging may be a reason why a small
number of children does not improve despite
• Asthmatic children with massive bronchial cast
or plastic bronchitis have been described
• Children being ventilated and whose condition is
deteriorating despite maximal therapy , severe
mucous plugging must be considered
• Bronchoscopy in this setting may be very
– Case reports
Duval ELIMet al. Ped Pulmonol 2000;30:350-353
Hebbar KB et al.Critical Care 2009;13:R29
Acute severe asthma
2.B2 agonist plus IB
ICU admission for
IV salbutamol or IV aminophyllin
Intubation plus ventilation
Add Ketamine infusion
Use muscle relaxant
Duration of treatment + 1 hour
allowed before next step