Acute severe asthma exacerbations in children younger than 12 years

Objectives
! PRESENT: Key recommendations for diagnosis & management of acute severe
asthma in children.
! EMPHASIS ON: Confirming diagnosis of asthma, to avoid both under- and over-
treatment.

GINA Global Strategy for Asthma
Management and Prevention 2020

What’s Asthma?
GINA 2020 © Global Initiative for Asthma
Asthma is a Chronic Inflammatory Airway Disease Characterized by:
— Airway Obstruction: Reversible either spontaneously or with treatment and occurs
predominantly in small-to-medium-sized airways.
— Airway Inflammation: Involves many different cells, including neutrophils, mast cells,
eosinophils and T lymphocytes.
— Airway Hyperresponsiveness: to a variety of stimuli (viral infections, cold air, exercise,
emotions, as well as environmental allergens and pollutants).

What’s Asthma?
Asthma is a Chronic Inflammatory Airway Disease Characterized by:
— Recurrent Episodes of Coughing, Wheezing, Shortness of Breath and Chest tightness,
particularly at night or early morning, and when the airways are exposed to various risk
factors.
— Airway Remodeling: Responsible for the irreversible airway obstruction.

Lazaar AL and Panettieri RA, Am J Med, 2003;115:652-659

Lazaar AL and Panettieri RA, Am J Med, 2003;115:652-659
Potential Influences:
— Increase in the irreversible component of airway obstruction
— Accelerated decline in pulmonary function
— Persistence of airway hyperresponsiveness
— Promote severe bronchospasm through:
! Loss of airway distensibility
! Increased contractile response
! Loss of elastic recoil

The Interplay and Interaction Between Airway Inflammation &
The Clinical Symptoms and Pathophysiology of Asthma

The Interplay and Interaction Between Airway Inflammation &
The Clinical Symptoms and Pathophysiology of Asthma
Asthma Symptoms
(Bronchoconstriction)
Persistent Airflow
Obstruction
Asthma Exacerbations
(Hyperreactivity)

• Making the diagnosis of asthma is based on identifying both:
! A Characteristic Pattern of Respiratory Symptoms: wheezing, shortness of breath,
chest tightness or cough, and
! Variable Expiratory Airflow Limitation.
• The pattern of symptoms is important, as respiratory symptoms may be due to acute or
chronic conditions other than asthma.

• The following features Increase Probability that respiratory symptoms are
due to asthma:
! More than one symptom (wheezing, shortness of breath, cough, chest tightness).
! Symptoms often worse at night or in early morning.
! Symptoms vary over time and in intensity.
! Symptoms are triggered by viral infections, exercise, allergen exposure, changes
in weather, laughter, or irritants.

• The following features Decrease Probability that respiratory symptoms are
due to asthma:
! Isolated cough with no other respiratory symptoms
! Chronic production of sputum
! Shortness of breath associated with dizziness, light-headedness or peripheral
tingling (paresthesia)
! Chest pain
! Exercise-induced dyspnea with stridor.

— Asthma causes symptoms: wheezing, chest tightness, shortness of breath and coughing
that vary over time in their occurrence, frequency and intensity.
— Symptoms are associated with variable expiratory airflow, due to
! Bronchoconstriction (airway narrowing)
! Airway wall thickening
! Increased mucus

SYMPTOM PATTERN
(May change over time)

• Confirm presence of Airflow Limitation:
! Document that FEV1/FVC is reduced.
! FEV1/ FVC ratio is normally > 0.75 – 0.80 in healthy adults, and > 0.90 in children.

• Confirm variation in Lung Function is greater than in healthy individuals:
! The greater the variation, the greater probability that the diagnosis is asthma.
! Excessive bronchodilator reversibility (children: increase >12% predicted).
! Significant increase in FEV1 or PEF after 4 weeks of controller treatment.

Asthma
(before BD)
Asthma
(after BD)
Normal
Volume
Time (seconds)
FEV1
1 2 3 4 5 6
Flow
Normal
Asthma
(after BD)
Asthma
(before BD)
FEV1

GINA Global Strategy for Asthma
Management and Prevention 2020

CHILDHOOD ASTHMA
— Asthma is the most common chronic disease of childhood,
— Its prevalence is increasing, affecting 5-10% of children worldwide,
— Resulting in ~ 500,000 hospitalizations annually.
— Unfortunately, childhood asthma can't be cured, and symptoms may continue into
adulthood.
— But with the right treatment, the child can keep symptoms under control and prevent
damage to growing lungs.

Status Asthmaticus
— Status asthmaticus is an acute severe exacerbation of asthma that does not improve with
standard therapy in the emergency department and may progress to respiratory failure
without prompt and aggressive intervention.
— The pathologic hallmarks of asthma are airway inflammation, excessive mucus production,
mucus plugging, and airway bronchospasm, all of which may lead to severe airflow
obstruction.
— Airflow obstruction produces varying degrees of respiratory insufficiency and can progress
to respiratory failure.

Status Asthmaticus
— Children with acute severe asthma who fail to improve with initial treatment in the
emergency department should be admitted to the pediatric ICU (PICU).

Risk Factors for developing Acute Severe Asthma
— History of increased use of home bronchodilator treatment without improvement.
— History of previous ICU admissions, with or without intubation.
— Asthma exacerbation despite recent or current use of corticosteroids.
— Frequent ED visits and/or hospitalization (implies poor control).
— Less than 10% improvement in PEFR from baseline despite treatment.
— History of syncope or seizures during acute exacerbation.

— Oxygen saturation below 92% despite supplemental oxygen.
— Asthma exacerbations precipitated by food.
— Use of more than 2 beta-agonist metered-dose inhaler (MDI) canisters per month.
— Insufficient controller therapy or poor adherence to controller therapy
— History of severe asthma exacerbation without wheezing (i.e., silent chest): Such
patients are unable to generate enough airflow to wheeze due to either severe airway
obstruction or be fatigued. This is an ominous sign of impending respiratory failure.

Silent Chest = Danger

Clinical Presentation
— Typically, patients present a few days after the onset of a viral respiratory illness, following
exposure to a potent allergen or irritant, or after exercise in a cold environment.
— Patients with status asthmaticus have severe dyspnea that has developed over hours to
days.
— Patients are usually tachypneic upon examination and, in the early stages of status
asthmaticus, may have significant wheezing. Initially, wheezing is heard only during
expiration, but wheezing later occurs during expiration and inspiration.

— The chest is hyperexpanded, and accessory muscles, particularly the sternocleidomastoid,
scalene, and intercostal muscles, are used. Later, as bronchoconstriction worsens, the
wheezing may disappear, which may indicate severe airflow obstruction.
— In patients with severe asthma, a difference of greater than 25 mm Hg in systolic blood
pressure between inspiration and expiration usually indicates severe airway obstruction.
— An inability to speak more than one or two words at a time may also be observed in the
later stages of an acute asthma episode.

— Ventilation/perfusion mismatch results in decreased oxygen saturation and hypoxia.
— Vital signs may show tachycardia and hypertension.
— The patient’s level of consciousness may progress from lethargy to agitation, air hunger,
and even syncope and seizures.
— If untreated, prolonged airway obstruction and marked increase in the work of breathing
may eventually lead to bradycardia, hypoventilation, and even cardiorespiratory arrest.

— Some patients prefer to remain seated and leaning forward, rather than assuming a
supine position (Tripod position).
— Intercostal and subcostal retractions and the use of abdominal muscles may be
observed. in patients with status asthmaticus.
— An abnormally prolonged expiratory phase with audible wheezing can be observed.
— Patients with moderate to severe asthma are often unable to speak in full sentences.
— Dehydration can occur more frequently in children.

— With worsening hypoxemia, hypercarbia, marked air trapping, and hyperinflation may be
observed.
— As hypoxemia progresses, lethargy progresses to agitation caused by air hunger and
hypercarbia develops.
— Both hypoxemia and hypercarbia can lead to seizures and coma and are late signs of
respiratory compromise.

— In moderate to severe status asthmaticus, abdominal muscle use can cause symptoms of
abdominal pain.
— Pulsus paradoxus (a decrease in systolic blood pressure during inspiration) results from
a decrease in cardiac stroke volume with inspiration.
— Pulsus paradoxus of > 20 mm Hg correlates well with the presence of severe airways
obstruction (i.e., FEV1 < 60% predicted).

Lab Studies
— The selection of laboratory studies depends on historical data and patient condition.
— Tests that should be performed in patients with status asthmaticus include the following:
! Complete blood cell (CBC) count
! Arterial blood gas (ABG) analysis
! Serum electrolyte levels
! Serum glucose levels

Lab Studies
— The selection of laboratory studies depends on historical data and patient condition.
— Tests that should be performed in patients with status asthmaticus include the following:
! Pulmonary Function Testing: PEF & Spirometry
! Pulse oximetry
! Chest radiography

Indications for PICU admission include the following:
— Altered sensorium.
— Use of continuous inhaled beta-agonist therapy.
— Exhaustion.
— Markedly decreased air entry.
— Rising PCO2 despite treatment.

Indications for PICU admission include the following:
— Presence of high-risk factors for a severe attack.
— Failure to improve despite adequate therapy.

PreintubationTherapies
— Much of the morbidity associated with the treatment of severe asthma is related to the
complications of mechanical ventilation (MV) in patients with severe airflow obstruction.
— As a result, the goal of initial treatment of patients with life-threatening status asthmaticus
is to improve their ability to ventilate without resorting to intubation and MV.
— The medical therapies should be undertaken swiftly and aggressively with the goal of
reversing the bronchospasm before respiratory failure necessitates invasive ventilation.

— Close monitoring of gas exchange, cardiovascular status, and mental status are crucial to
assessing response to therapy and determining the appropriate interventions.

The primary Preintubation Therapies (Initial Therapy) include:
— Supplemental oxygen,
— Fluid Replacement: Rehydration,
— Inhaled Beta-2 Agonists: Continuous or intermittent,
— Inhaled Anticholinergics: Intermittent,
— Systemic Corticosteroids.
— Systemic magnesium sulfate.

Adjunctive Therapies include:
— Intravenous Terbutaline: Continuous infusion
— Intravenous Aminophylline
— Endotracheal Intubation
— Mechanical ventilation (MV).

Supplemental Humidified Oxygen
— Monitoring the patient’s oxygen saturation (PaO2) via pulse oximetry is essential during
the initial treatment of status asthmaticus.
— ABG values are usually used to assess hypercapnia during the patient's initial
assessment.
— Supplemental humidified oxygen must be administered for any patient hospitalized with
acute severe asthma, especially at night and with increasing SABA administration.

Supplemental Humidified Oxygen
— Oxygen helps to correct V/Q mismatch and can be provided via nasal cannula or face
masks.
— The goal of supplemental O2 therapy is an O2 saturation above 90%
— Tracheal intubation and mechanical ventilation are indicated for respiratory failure.

Fluid Replacement
— Hydration status monitoring is especially important in infants and young children,
whose increased respiratory rate (insensible water losses) and decreased oral intake
put them at higher risk for dehydration.
— Special attention to the patient's electrolyte status is important.
! Hypokalemia may result from either corticosteroid use or beta-agonist use.
! Correcting hypokalemia may help to wean an intubated patient with asthma from
mechanical ventilation.

Inhaled Short-Acting Beta-2 Agonists (SABAs)
— Inhaled β2-agonist agents, typically Albuterol (Salbutamol, Ventolin), remain the 1st line
therapy in asthma to reverse acute bronchoconstriction.
— The frequency of β2-agonist administration varies according to severity of symptoms
and occurrence of adverse side effects.
— Handheld Nebulized Salbutamol may be administered either continuously at a dose of
5 - 15 mg/hr, or intermittently (every 20 min - 1 hr at a dose of 0.15 mg/kg per
nebulization (minimum 2.5 mg; maximum 5 mg) or 0.3-0.5 mL of a 0.5% formulation
mixed with 2.5 mL of normal saline.

Inhaled Short-Acting Beta-2 Agonists (SABA)
— Salbutamol can be used via an MDI with a chamber. The dose is 4 puffs, repeated at
15- to 30-minute intervals as needed. Most patients respond within 1 hour of treatment.
— The nebulized, inhaled route of administration is generally the most effective route of
delivery for β2-agonists.
— β2-agonists are generally most effective in the early asthma reaction phase. However,
patients who present with status asthmaticus despite frequent use of β2-agonists at
home may have tachyphylaxis and may exhibit resistance to these agents.

Inhaled Anticholinergics
— Anticholinergic agents act via inhibition of cyclic GMP–mediated bronchoconstriction.
— They may also decrease mucus production and improve mucociliary clearance.
— Ipratropium bromide (Atrovent): is the recommended anticholinergic agent of choice as
add-on therapy to β2-agonists.

Inhaled Anticholinergics
— The recommended dose of nebulized ipratropium bromide is 250 µg per dose every 6
hours for 24 hours for children who weigh < 20 kg or ≤ 6 years of age; 500 µg per dose
every 6 hours for 24 hours for children who weigh > 20 kg or ≥ 6 years of age, mixed
with salbutamol/NS solution.
— The dose may be repeated every 20 minute for the first hour and thereafter every 4 - 6
hours.

Systemic Corticosteroids
— Immediate administration of systemic corticosteroids is critical to early management of
life-threatening status asthmaticus:
! Decrease the intense airway inflammation and swelling.
! Decrease mucus production, improve oxygenation and reduce β2-agonist requirements.
! Potentiate the effects of β2-agonist agents by increasing β2-receptor expression.

Systemic Corticosteroids
— The anti-inflammatory effect of corticosteroids is generally observed at least 4-6 hr after
administration.
— Corticosteroids may be administered intravenously or orally.
— Methylprednisolone IV is generally prescribed for the critical care setting: A loading dose of
2 mg/kg, then 0.5 - 1 mg/kg/dose every 6 hr, with a maximum dose of 60 mg/day.
— Prednisone can be given orally at a dose of 1-2 mg/kg daily.

— Adjunctive therapies may be helpful when the standard combination of oxygen
and intermittent or continuous Salbutamol, intermittent inhaled ipratropium
bromide and systemic corticosteroids are insufficient in relieving significant
respiratory distress in severe acute asthma.

— Magnesium can relax smooth muscle and hence cause bronchodilatation by competing
with calcium at calcium-mediated smooth muscle binding sites.
— Intravenous magnesium sulphate may be effective in children with severe acute asthma.
— The recent GINA-guidelines suggest that IV magnesium sulphate may be considered in
acute moderate and severe asthma with incomplete response to initial treatment during
the first 1-2 hours.

— The recommended dose in children range from 25-75 mg/kg infused over 20 minutes, with
a maximum dose of 2.5 g.
— IV magnesium sulphate is not included in recent guidelines for children < 5 yr of age.
— Adverse effects may include facial warmth, flushing, tingling, nausea, and hypotension.

— Some patients with refractory status asthmaticus may respond to intravenous administration of β2-agonists.
— Intravenous terbutaline has been shown to improve pulmonary function and gas exchange in children with status
asthmaticus.
— Reported doses for IV terbutaline Infusion in children: 10 µg /kg IV loading dose administered over 10 minutes,
followed by an infusion of 0.1 to 10 µg /kg/minute).
— The infusion can be increased in 0.1 to 1 µg /kg/minute increments every 30 minutes, depending upon the
patient's degree of respiratory distress, heart rate, perfusion, and quality of aeration, to a maximum dose of 5 to
10 µg /kg/minute
— The dose administered should be titrated to effect and adverse cardiac effects (tachycardia, arrhythmias, ECG
changes).

— Intravenous aminophylline is reserved for children with severe status asthmaticus,
impending respiratory failure and not responding to IV terbutaline.
— The recommended Loading Dose: 6 mg/kg, followed by infusion of 0.5 - 1 mg/kg/hr that
is titrated based upon serum levels.
— Therapeutic serum theophylline levels range between 10 and 20 µg /mL. We suggest
target levels of 12 to 15 µg /mL, particularly upon initiation of therapy.

— we reserve aminophylline as an option for the child with severe status asthmaticus and
impending respiratory failure who has not responded to terbutaline.
— 6 mg/kg intravenous loading dose, followed by infusion of 0.5 to 1 mg/kg/hour that is titrated
based upon levels). The recommended starting dose of the infusion (after the loading dose)
varies by age for patients:
— • 6 weeks to 6 months – 0.5 mg/kg/hour • 6 to 12 months – 0.6 to 0.7 mg/kg/hour • 1 to 9 years –
1 mg/kg/hour 9 to 16 years – 0.8 mg/kg/hour
— Therapeutic levels range between 10 and 20 µg /mL. We suggest target levels of 12 to
15 µg /mL, particularly upon initiation of therapy.

Q. 1
— When a patient is diagnosed with acute severe asthma, which of the following is TRUE:
A. IV aminophylline is recommended as a first line drug in acute asthma management in children.
B. IV magnesium sulphate can be used in young children during acute severe asthma attacks.
C. Ipratropium bromide has a mild additional bronchodilating effect when added to β2-agonists that
may only be significant in severe asthma.
D. Immediate administration of IV Methylprednisolone is critical to early management of life-threatening
asthma.

Q. 2
— Severe asthma is a subset of difficult-to-treat asthma that remains uncontrolled
despite:
A. Increasing dosage of medicine
B. Hospitalizing following serious exacerbation
C. Treating contributory factors such as inhaler technique and adherence
D. Ignoring underlying environmental allergens

Q. 3
— PICU admission for child with acute severe asthma is indicated in the following situations
EXCEPT:
A. Increasing dosage of medicine.
B. When the PEF or FEV1 after treatment is greater than 50% of the predicted value but
less than 70% of the predicted value.
C. Treating contributory factors such as inhaler technique and adherence.
D. Ignoring underlying environmental allergens.

Q. 3
— PICU admission for child with acute severe asthma is indicated in the following situations
EXCEPT:
B. When the PEF or FEV1 after treatment is greater than 50% of the predicted value but less
than 70% of the predicted value.

Q. 3
— Hospitalization in an PICU for child with acute severe asthma is indicated in the
following situations EXCEPT:
B. When the PEF or FEV1 after treatment is greater than 50% of the predicted value but less
than 70% of the predicted value.

Q. 5
— In childhood asthma:
A. Over 90% of patients show exercise-induced bronchoconstriction
B. Hypercapnia is the first physiological disturbance in status asthmaticus
C. Infants are unresponsive to bronchodilators
D. Spontaneous cure occurs before adolescence
E. Cough may be the only symptom

Q. 6
— Bronchoconstriction is a recognized side effect of:
A. Captopril
B. Atenolol
C. Ibuprofen
D. Paracetamol
E. Salbutamol

Q. 7
— Adverse effects of frequently administered β2-agonist therapy in acute severe asthma
include all the following EXCEPT :
A. Tremor
B. Irritability
C. Tachycardia
D. Hypokalemia
E. Mouth dryness

Q. 8
— In emergency department, the patient may be discharged to home if there is symptomatic
improvement. Of the following, the MOST likely discharge medication used is:
A. Inhaled β-agonist only
B. Oral corticosteroid only
C. inhaled corticosteroid only
D. inhaled β-agonist plus oral corticosteroid
E. oral β-agonist plus inhaled corticosteroid

Acute severe asthma exacerbations in children younger than 12 years

Acute severe asthma exacerbations in children younger than 12 years

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