treatment of asthma exacerbations in the pediatric emergency department

Treatment of Asthma Exacerbations in the Pediatric Emergency

DepartmentFive Important Questions

June 27th, 2014Justin Davis, MD

Objectives1. What is an asthma exacerbation?

2. How can one determine the severity?

3. What is “status asthmaticus”?

4. What is the role of various primary treatments?

5. What is the role of adjunctive/secondary treatments?

1. What is an asthma exacerbation?

Variety of triggers

Airway hyper-responsiveness and inflammationMucous plugging, V/Q mismatch

Decrease in expiratory airflow

Combination of symptoms – dyspnea, wheezing, chest tightness

Acute or subacute

Can occur in someone with good control.

Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma; National Heart, Lung and Blood Institute, National Asthma Education and Prevention Program; 2007 U.S. Department of Health and Human Services

1. What is an asthma exacerbation?

Increasing prevalence of asthma (9.6% in 2009).

Mortality lower in children.

Hospitalization rate may be leveling off or declining.

ICU care still increasing.

Koninckx, M, Buysse C., Hoog M. Management of status asthmaticus in children. Paediatric Respiratory Reviews 14 (2013) 78-85

2. Assessment & SeverityRespiratory Rate

Generally increasedNot necessarily an indicator of severity

WheezesTypically expiratory If also inspiratory more severe If absent imminent respiratory failure

Or inadequate exam

2. Assessment & SeverityPeak expiratory flow

(PEF) or Forced Expiratory Volume (FEV1)Difficult if < 5-6 year

old, in the ED setting, severe exacerbations

Mild: >70% predicted (or personal best)

Severe: <40% predicted

2. Assessment & SeverityWork of breathing

Scalene and SCM – forceful inhalation

Abdominals, internal intercostals – forceful expiration

Indicates moderate to severe exacerbation

May not be present in patients with imminent respiratory arrest

2. Assessment & SeverityPulse Oximetry

Transient hypoxia relatively common after treatments.

Initial borderline to mild hypoxia an indicator of moderate to severe exacerbation.

Hypoxia after one hour of treatment correlates with increased risk of hospital admission

PCO2

Blood gas analysis rarely need for treatment of pediatric asthma exacerbations


2. Assessment & Severity Pulsus Paradoxus

Inspiration negative chest pressure lower pulse pressure

Expiration positive chest pressure higher pulse pressure

< 10 mm Hg normal 10-25 mm Hg moderate 25-40 mm Hg severe Loss of pulsus paradoxus respiratory failure

Just like sudden loss of work of breathing in someone who is still not moving air


2. Assessment & SeverityRed Flags

Alteration in mental status Not necessarily completely unconscious

Bradycardia

Severity scores – why use them?Reliably + rapidly identify severity level Identify changes in clinical statusResearch purposesProtocols, pathways

2. Assessment & Severity – Asthma ScoresItems in Score Validity Measures Reliability Measures

Asthma Severity Score (ASS) (3)

Wheeze (0-3), Heart rate (0-3), Accessory Muscle Use (0-

3)

1. Physician severity judgment, 2. Oxygen saturation, 3. PEFR

1. Interobserver reliability

Preschool Respiratory Assessment Measure

(PRAM) (4)

Wheeze (0-3), Air entry (0-3), Scalene contractions (0-2), Suprasternal retractions (0-2), oxygen saturation (0-2)

1. Resistance to forced oscillation (RFO), 2. Clinician

and parent severity judgment, 3. Change in score

correlation with change in RFO

1. interobserver reliability, 2. internal consistency

Pulmonary Index (PI) (5)

Wheeze (0-3), Repsiratory Rate (0-3),

Inspiratory/Expiratory ratio (0-3), Accessory Muscle Use

(0-3)

1. Spirometry, 2. ED Disposition, 3. Change in

score with treatment during ED course

Pulmonary Score (PS) (16)Wheeze (0-3), Respiratory

rate (0-3), Sternocleidomastoid use (0-

3)

1. PEFR, 2. Change in score with treatment during ED

course

Pediatric Asthma Severity Score (2)

Wheezing, Prolonged Expiration, Work of

Breathing

1. PEFR, 2. Oxygen Saturation, 3.

Responsiveness to treatment, 4. Hospital

admission

1. interobserver reliability good to excellent

3. What is status asthmaticus?Asthma Exacerbation

Severe, Life-threatening

Unresponsive to usual therapy

Some definitions include more factors.


3. What is status asthmaticus?Fatal and near-fatal asthma2

Type 1(80%) – slow onset, progressive airway obstruction, already using bronchodilators extensively, more inflammation + mucous plugging

Type 2 – sudden onset, more bronchoconstriction; higher incidence of AMS, respiratory arrest, acidemia; rapid deterioration but rapid recovery with treatment

Koninckx, M, Buysse C., Hoog M. Management of status asthmaticus in children. Paediatric Respiratory Reviews 14 (2013) 78-85

3. What is status asthmaticus?Risk factors for asthma-related death?

History: ICU, Intubation, 2 hospitalizations or 3 ED visits in past year, any hospitalization in last month, > 2 canisters/month, lack of written asthma action plan

Social- inner city, low socioeconomic status, substance use

Comorbidities – cardiac disease, psychiatric disease, other chronic lung diseases

4. Primary Treatments

Bronchodilation – inhaled beta agonists

Anti-inflammatory – systemic corticosteroids

Oxygen

Rehydration prn

Wilkinson, M, Bullock B, Garcia-Filian P, Keahey L. Efficacy of Racemic Albuterol versus Levalbuterol used as a Continuous Nebulization for the Treatment of Acute Asthma Exacerbations: A Randomized, Double-Blind, Clinical Trial

4. Primary Treatments – Albuterol versus Levalbuterol?

Wilkinson 201199 children, ED visits for moderate/severe

exacerbation7.5 mg albuterol versus 3.75 mg levalbuterol

Further treatments given with same medStandard care; Double-blinded

After one hour, spirometry and asthma scores showed greater improvement in albuterol group.No differences in side effects, HR, RR, SaO2No difference in admission rate

Wilkinson, M, Bullock B, Garcia-Filian P, Keahey L. Efficacy of Racemic Albuterol versus Levalbuterol used as a Continuous Nebulization for the Treatment of Acute Asthma Exacerbations: A Randomized, Double-Blind, Clinical Trial

4. Primary Treatments – Delivery Methods?

Breathing Machine/Nebulizer/JetAdvantage: coordination not required, effective

with tidal breathing, ability to give high doses (continuous nebulizer), ability to give supplemental O2

Disadvantage: treatment time, sanitation, device preparation

Metered Dose InhalerAdvantage: treatment time, sanitation, preparationDisadvantage: coordination, ability to give high

doses in life threatening asthma

4. Primary Treatments – Nebs vs MDI?

Cates et al. 2013Review of RCTs comparing MDI/spacer versus

nebulization in ED (39 trials, 1897 children, 729 adults)

For children, mean length of ED stay was shorter with MDI/spacer

Spirometry, risk of admission not differentLower pulse and risk of tremor with MDIMany of the studies excluded severe

exacerbations, critically ill patients.

Cates CJ, Welsh EJ, Rowe BH. Holding chambers (spacers) versus nebulisers for beta-agonist treatment of acute asthma. Cochrane Database of Systematic Reviews 2013, Issue 9. Art. No.: CD000052. DOI: 10.1002/14651858.CD000052.pub3.

4. Primary Treatments – Neb vs. MDI?

Duarte 2002196 children presenting with mild to moderate

exacerbations were randomized to either receive ED treatment with a home-made non-valved spacer or a nebulizer. Improvement in peak expiratory flow was the same in both groups.

Duarte M, Camargos P. Efficacy and safety of a homemade non-valved spacer for bronchodilator therapy in acute asthma. Acta Paediatrica 2002;91:909–13


Sannier 200779 children presenting with mild to moderate

exacerbations were randomized to receive ED treatment with MDI and spacer or a nebulizer. Hospitalization rate, asthma scores, peak flows, SaO2, respiratory rates and other side effects were the same.

Sannier N, Timsit S, Cojocaru B, Leis A, Wille C, Garel D,et al.Metered-dose inhaler with spacer versus nebulization for severe and potentially severe acute asthma treatment in the pediatric emergency department. [French]. Revue Francaise d Allergologie et d Immunologie Clinique 2007; Vol. 47, issue 2:64–71.


Batra 1997Children presenting to the ED with an asthma

exacerbation (any severity) were randomized to MDI versus nebulizer.

No difference in outcomes between the two groupsClinical assessments at 20, 40 and 60 minutesHospital admission rate

Batra V, Sethi G, Sachdev H. Comparative efficacy of jet nebuliser and metered dose inhaler with spacer device in the treatment of acute asthma. Indian Pediatrics 1997;34:497–503


Breath Actuated NebulizerThere are different types, but Aeroeclipse® seems

to be most well studies in pediatric EDHigher percentage of respiratory range partciles.Works best with mouthpiece, mask can be used as

well.No studies comparing with MDI.Can be manually activated.

Early non-randomized study showed favorable results but had several limitations.1

1. Titus MO, Eady M, King L, Bowman M. Effectiveness of a Breath-Actuated Nebulizer Device on Asthma Care in the Pediatric Emergency Department. Clin Pediatr 2012 51: 1150-1154


Breath Actuated Nebulizer (BAN), Sabato 2011 149 children presenting to the ED with mild to severe asthma

exacerbations were randomized to use either the Aeroeclipse® breath-actuated nebulizer or standard nebulizer.

BAN group had greater improvement in symptom score and respiratory rate, lower hospital admission rate. No difference in adverse effects.

Older patients & those with more severe symptoms were more likely to have greater improvement with BAN.

There were patients as young as 6 months of age who were able to breath-actuate. A greater percentage of the BAN patients accepted their aerosol treatments.

Potential confounders: masks in the BAN group had better seal; BAN group likely received higher actual dose of albuterol.Sabato K, Ward P, Hawk W, et al. Randomized controlled trial of

a breath-actuated nebulizer in pediatric asthma patients in the emergency department. Respir Care. 2011;56:761-770.

4. Primary Treatments – continuous versus intermittent treatments

Per most recent NHLBI guidelines, either is acceptable.

Camargo et al. 2003 Review of randomized controlled trials evaluating continuous versus

intermittent inhaled beta-agonists in the emergency setting. Eight trials were included in the analysis. Continuous treatments were associated with greater improvement in

spirometry and reduced rates of hospital admissions.

Camargo CA, Spooner CH, Rowe BH. Continuous versus intermittent beta-agonists in the treatment of acute asthma. Cochrane Database Syst Rev. 2003; (4): CD001115

4. Primary Treatments – Atrovent Anticholinergic

Causes bronchodilation without inhibiting mucociliary clearance (unlike atropine)

May be helpful in the ED setting in terms of greater improvement in symptom scores and spirometry.1

Effect is additive to inhaled beta-agonists. Not really helpful on its own.

Kline-Krammes S, Patel NH, Robinson S. Childhood Asthma: A Guide for Pediatric Emergency Medicine Providers. Emerg Med Clin N Am 31

4. Primary Treatments – Steroids?

Start as early as possibleEffect starts in 1-3 hours, maximum effect at 4-8

hoursPO or IVCan avoid steroids for mild exacerbations with

complete response to initial beta agonist treatment

+/-5 day course of orapred or prednisone frequently givenTwo day course of dexamethasone likely just as

effective.1


1. Qureshi F, Zaritsky A, Poirier MP. Comparative efficacy of oral dexamethasone versus oral prednisone in acute pediatric asthma. J Pediatr 2001; 139(1):20–6.

4. Primary Treatments – Inhaled Steroids?

Edmonds et al. 2012aReview of studies comparing ICS added to usual

care for ED treatment of asthma exacerbations.ICS versus systemic steroidsICS + systemic steroids versus systemic steroids

aloneICS versus placebo (no systemic steroids)

Patients given ICS less likely to be admitted to hospital & had small improvements in spirometry compared with patients not given systemic steroids.

No significant improvement in pulmonary function, symptom scores or admission rates when given in addition to systemic steroids.

Emonds ML, Milan SJ, Camargo Jr CA, Pollack CV, Rowe BH. Early use of inhaled corticosteroids in the emergency department treatment of acute asthma. Cochrane Database of Systematic Reviews 2012, Issue 12. Art. No.: D002308


Singhi et al. 199960 children presenting to an urban pediatric ED

with a moderate exacerbation were randomized to receive either budesonide 400 mcg or placebo at half hour intervals for three doses.

Children in the intervention group showed greater improvements in RR, PEFR, and symptom scores.

Singhi SC, Banerjee S, Nanjundaswamy HM. Inhaled Budesonide in Acute Asthma. J. Paediatr. Child Health 1999; 35; 483-487


Scarfone et al. 1995111 children presenting to an urban pediatric ED

with a moderate exacerbation were randomized to receive oral prednisone or 1.5 mg/kg nebulized dexamethasone.

Dexamethasone group had improvement in:Discharge home within 2 hoursUnplanned return visits within 48 hours

Improvement more pronounced in those treated with mouthpiece versus face mask.

Scarfone RJ, Loiselle JM, Wiley JF, et al. Nebulized dexamethasone versus oral prednisone in the emergency treatment of asthmatic children. Ann Emerg Med 1995; 26:480–486


Macias 2003135 children presenting to an urban pediatric ED

with a moderate exacerbation were randomized to receive either inhaled triamcinolone (in ED and after discharge) or oral steroids.

Lower hospitalization and unscheduled return rate in inhaled steroid group.

No placebo control.

Macias CG, Felner EI, Gan V. Inhaled Corticosteroids May be Superior to Systemic Corticosteroids in Children with Moderate-to-Severe Acute Asthma. Pediatric Asthma, Allergy and Immunology 2003; 16(3): 121-128


Schuh 2000100 children presenting to the ED with a severe

asthma exacerbation (FEV1 less than 60% of predicted) were randomized to either receive 2 mg of inhaled fluticasone via MDI/spacer or 2mg/kg of prednisone.

FEV1 increased by twice as much in the oral steroid group after four hours. The hospitalization rate for children treated with fluticasone was three-fold higher.

Schuh S, Reisman J, Alshehri M, Dupuis A, Corey M, Arseneault R, Alothman G, Tennis O, Canny G. A comparison of inhaled fluticasone and oral prednisone for children with severe acute asthma. N Engl J Med 2000;343(10):689–94.


Upham 2011180 children presenting to the ED with a moderate

to severe asthma exacerbation were randomized to either receive 2 mg of inhaled budesonide or placebo along with usual care (including systemic steroids).

No change change in symptom scores at 2 hours. No difference in hospitalization rates.

Upham BD, Mollen CJ, Scarfone RJ, Seiden J, Chew A, Zorc JJ. Nebulized budesonide added to standard pediatric emergency department treatment of acute asthma: a randomized, double-blind trial. Acad Emerg Med 2011;18: 665–73.

4. Primary Treatments – Oxygen?

Guidelines recommend oxygen as needed to achief normal SaO2.

Supplemental O2 likely more important in children.

Oxygen has mild bronchodilatory effect.

Hyperoxia not necessary.

Rodrigo GJ, Rodriquez Verde M, Peregalli V, et al. Effects of short-term 28% and 100% oxygen on PaCO2 and peak expiratory flow rate in acute asthma: a randomized trial. Chest 2003;124(4):1312–7.

4. Primary Treatments – Fluids?

Patients with severe exacerbations are often dehydrated and have increased ongoing insensible losses.

PO rehydration preferable but not always possible.

Extensive variation in practice.


4. Primary Treatments – Not Indicated?

Mucolytics

Chest physical therapy


5. Secondary Treatments?

Magnesium Sulfate

Helium

IV Beta Agonists

IV Methylxanthines

IV LRTAs


5. Secondary Treatments – Magnesium Sulfate?

Calcium antagonism

Relaxation of smooth muscle

Anti-inflammatory

RisksHypotension

Can be given iv or inhaled.

5. Secondary Treatments – Nebulized Magnesium Sulfate?

Powel 2012Review of RCT comparing nebulized Magnesium

Sulfate versus standard care.16 trials (7 adult, 4 child, 3 both)No improvement in pulmonary function (3 studies)No advantage in terms of hospital admission

(4 studies)No serious adverse events

Powell C, Dwan K, Milan SJ, Beasley R, Hughes R, Knopp-Sihota JA, Rowe BH. Inhaled magnesium sulfate in the treatment of acute asthma. Cochrane Database of Systematic Reviews 2012, Issue 12. Art. No.: CD003898. DOI: 10.1002/14651858.CD003898.pub5.

5. Secondary Treatments – Nebulized Magnesium Sulfate?

MANETIC Clinical Trial Multi-center trial in the UK508 children presenting to 30 different emergency

departments with severe exacerbations were randomized to receive 2.5 ml (151 mg) of nebulized magnesium sulfate versus placebo in addition to standard care.

Children in MS group had sustained improvements in symptom scores. Larger effect noted in those with more severe symptoms. No differences in other outcomes; no difference in adverse events.

Powell C, Kolamunnage-Dona R, Lowe J, Boland A, Petrou S, Doull I, et al.MAGNEsium Trial In Children (MAGNETIC): a randomised, placebo controlled trial and economic evaluation of nebulised magnesium sulphate in acute severe asthma in children. Health Technol Assess 2013;17(45)

5. Secondary Treatments – IV Magnesium Sulfate?

Guidelines suggest usage in patients who have moderate to severe exacerbations not responsive to initial albuterol treatment.

Most common ED use Initial treatment of patients with severe or life-

threatening asthma.Subsequent use in patients who don’t improve

after first hour of therapy.


5. Secondary Treatments – IV Magnesium Sulfate?

Mohammed 2007

Systematic review of randomized and quasi-randomized trials of iv magnesium (15 studies, 5 pediatric)Adults – improvement in respiratory function, no

effect on hospital admissionChildren – improvement in respiratory function and

reduction in hospital admission

Mohammed S, goodacre S. Intravensou and nebulized Magnesium Sulphate for acute asthma: systematic review and meta-analysis. Emerg Med J 2007; 24: 823-830

5. Secondary Treatments – IV Magnesium Sulfate –Early Use?

Ciarallo 2000

Thirty children who presented to two emergency departments with moderate to severe exacerbations received either 40 mg/kg IV Magnesium versus Placebo.

Mg group had greater improvement in spirometry and were more likely to be discharged home (8/16 versus 0/14).

Children < 6 yo excluded.

Ciarallo L, Brousseau D, Reinert S. Higher-dose intravenous magnesium therapy for children with moderate to severe acute asthma. Arch Pediatr Adolesc Med 2000;154:979–83.Gurkon 1999

5. Secondary Treatments – IV Magnesium Sulfate –Early Use?

Torres 2012

143 children presenting to an ED in Argentina were randomized to receive Magnesium Sulfate versus standard care in the first hour of treatment.Not clear if blinded.

33% in the control group required mechanical ventilation compared with 5% in the intervention group.

Torres S, Sticco N, Bosch JJ, Iolster T, Siaba A, Rocca RM, Schnitzler E. Effectiveness of magnesium sulfate as initial treatment of acute severe asthma in children, conducted in a tertiary-level university hospital: a randomized, controlled trial. Arch Argent Pediatr 2012 Aug; 110(4): 291-6

5. Secondary Treatments – IV Magnesium Sulfate –Late Use?

Scarfone 2000

54 children who presented to the ED with a moderate to severe exacerbation were randomized to either receive magnesium sulfate (75 mg/kg) or placebo after an initial albuterol treatment and IV solumedrol.

The mean change in pulmonary index score over the following two hours was not different in both groups.

No difference in hospitalization rate.Scarfone RJ, Loiselle JM, Joffe MD, et al. A randomized trial of magnesium in the emergency department treatment of children with asthma. Ann Emerg Med2000;36:572–8

5. Secondary Treatments – Helium?

Colorless, odorless, less dense

Improved CO2 diffusion

Promotes laminar flow, higher flow rate even in turbulent flow conditions

If not using premixed tanks, care must be taken to avoid giving hypoxic gas mixture.

Higher thermal conduction

Gupta VK, Cheifetz IM. Heliox administration in the pediatric intensive care unit: an evidence-based review. Pediatr Crit Care Med 2005;6(2):204–11.

5. Secondary Treatments – Helium?

Guidelines say it “can be considered” for use in asthma exacerbations.

Potential usesAs a “rescue” treatment early in therapy until

conventional therapies have had maximal effectFor air delivery in intubated patients, especially

early in illnessFor delivery of aerosols

5. Secondary Treatments – Helium Rescue therapy?

Kudukis 1997Double-blind, RCT of 18 children with status

asthmaticus showed improvement in pulsus paradoxus, peak expiratory flow and dyspnea scores in patients treated with 15 minutes of 80:20 Heliox.

Carter 1996Double-blind, RCT of 11 children with status

asthmaticus showed small improvements in peak flows in patients treated with 70:30 heliox but no improvement in other outcomes. Patients had already been treated for at least six hours prior to enrollment.

Kudukis TM, Manthous CA, Schmidt GA, et al: Inhaled helium–oxygen revisited: effect of inhaled helium– oxygen during the treatment of status asthmaticus in children. J Pediatr 1997; 130:217–224

Carter ER, Webb CR, Moffitt DR: Evaluation of heliox in children hospitalized with acute severe asthma. A randomized crossover trial.Chest 1996; 109:1256–1261

5. Secondary Treatments – Helium in children intubated due to asthma?

Abd-Allah 2003Retrospective review of 28 intubated patients

using helium concentrations from 32 to 74%. With similar ventilator settings, PIP was

significantly decreased with heliox treatment. CO2 and pH also improved with heliox

treatment. .

Abd-Allah SA, Rogers MS, Terry M, et al: Helium–oxygen therapy for pediatric acute severe asthma requiring mechanical ventilation. Pediatr Crit Care Med 2003; 4:353–357

5. Secondary Treatments – Helium for delivery of aerosol treatments?

Results promising in adults.

Conflicting results in children.

Rivera 20006 41 children in the ED with moderate to severe

exacerbations were randomized to receive initial albuterol driven by heliox or usual care.

No difference between groups in symptom scores after 20 minutes, admission rate, or rate of intubation.

Rivera ML, Kim TY, Stewart GM, Minasyan L, Brown L. Albuterol nebulized in heliox in the initial ED treatment of pediatric asthma: a blinded, randomized controlled trial. Am J Emerg Med 2006;24(1):38–42.

5. Secondary Treatments – Helium for delivery of aerosol treatments?

Kim 2005 30 children in the ED with moderate to severe

exacerbations were randomized to receive, after an initial 5mg albuterol neb and oral steroids, continuous albuterol by heliox or oxygen. Blinded video assessments, provider and patient not

blinded. The mean change in pulmonary index over the subsequent

four hours was almost twice as much in the heliox group. More patients in the heliox group were discharged from the

hospital within 12 hours. No difference in rate of discharge from ED, PICU admission.

Kim IK, Phrampus E, Venkataraman S, Pitetti R, Saville A, Corcoran T, Gracely E, Funt N, Thompson A. Helium/oxygen-driven albuterol nebulization in the treatment of children with moderate to severe asthma exacerbations: a randomized, controlled trial. Pediatrics 2005;116(5):1127–33.

5. Secondary Treatments – iv beta agonists?

Selective agents – terbutaline, bedoradrine (IV)

Non-selective agents – epinephrine

Travers 2012Systematic review of RCTs of iv beta agonists for

asthma in the acute setting. Three pediatric studies identified.

Limited evidence from RCTs to support use of IV beta agonists.

Travers AH, Milan SJ, Jones AP, Camargo CA, Rowe BH. Addition of intravenous beta(2)-agonists to inhaled beta(2) agonists for acute asthma. Cochrane Database Syst Rev. 2012 Dec 12; 12: CD010179


Browne 1997Children presenting to the ED with a severe

asthma exacerbation who did not improve after an initial albuterol treatment were randomized to receive 15 mcg/kg iv salbutamol or saline placebo in addition to standard care.

OutcomesRecovery time (time until able to space treatments)

4 hours in intervention group versus 11.5 hours in control group

Time until discharge criteria met – 9.7 hours earlier in intervention group

Browne GJ, Penna AS, Phung X, Soo M. Randomised trial of intravenous salbutamol in early management of acute severe asthma in children. The Lancet. 1997; Vol. 349, 301-305


Bogie 2007 49 children with asthma between age 2-17 who

required ICU admission (but not intubation) were randomized to receive IV terbutaline versus placebo in addition to standard care.

Standard care included continuous albuterol up to 20 mg/hr, steroids, fluid bolus. Aminophylline given for non-responders (more given in intervention group). No patients received magnesium. Some patients in both groups received inhaled or subcutaneous terbutaline in ED prior to enrollment in the PICU.

Improvements noted in severity scores, duration of continuous nebs, and ICU stay were present but not statistically significant.

Browne GJ, Penna AS, Phung X, Soo M. Randomised trial of intravenous salbutamol in early management of acute severe asthma in children. The Lancet. 1997; Vol. 349, 301-305


Nowak 2010 and Matsuda 2012 Bedoradrine is a newer selective beta-2 agonist. A phase two clinical trial published in 2012 in Journal of

Asthma showed improvements in FEV1 versus placebo.1

A related poster presentation of a randomized, placebo-controlled study of the drug (added to standard of care) showed reduced hospitalization rates and improved FEV1.

2. Nowak R, Iwaki Y, Matsuda K, Johnson K. Reduced Hospital Admission and Improved Pulmonary Function following Intravenous MN-221 (Bedoradrine), a Novel Highly Selective Beta2-Adrenergic Receptor Agonist, Adjunctive to Standard of Care in Severe Acute Exacerbation of Asthma.

1. Matsuda K, Makhay M, Johnson K and Iwaki Y. Evaluation of Bedoradrine Sulfate (MN-221), a Novel, Highly Selective Beta2-Adrenergic Receptor Agonist for the Treatment of Asthma via Intravenous infusion. Journa of Asthma 2012; 49(10): 1071–1078

5. Secondary Treatments – Intravenous Leukotriene Receptor

Antagonists Evidence exists in adult literature that iv administrating

may be effective in acute severe asthma. Pediatric Studies appear to be lacking.

Camargo CA, Smithline HA, Malice MP, et al. A randomized controlled trial of intravenous montelukast in acute asthma. Am J Respir Crit Care Med 2003; 167(4):528–33.

5. Secondary Treatments – Methylxanthines

Not recommend by guidelines for routine treatment of acute asthma in children.

Recent systematic review of adult studies showed no evidence reduced hospitalization rate, improved severity scores, or other outcomes. Significant amount of vomiting and arrhythmias not uncommon.1

Meta-analysis in children from 2005 including 7 trials showed statistically significant (but maybe not clinically significant) improvement in spirometry when added to usual care but no improvement in other outcomes. Methylxanthines led to a three-fold increased risk of vomiting (but not arrythmias).2

1. Nair P, Milan SJ,Rowe BH. Addition of intravenous aminophylline to inhaled beta(2)-agonists in adults with acute asthma. Cohcrane Database Syst Review. 2012 Dec 12: 12 CD002742

2. Mitra A, Bassler, Goodman K, Lasserson TJ, Ducharme FM. Intravenous Aminophylline for acute severe asthma in children over two years receiving inhaled bronchodilators. Cochrane Database Syst Rev 2005 Apr 18; (2): CD 001276

5. Secondary Treatments – Ketamine Case studies and observational studies have shown

promising results.1

One RCT in children did not show improvement in outcomes.2

1. Jat KR, Chawla D. Ketamine for management of acute exacerbations of asthma in children. Cochrane Database of Systematic Reviews 2012, Issue 11. Art. No.: CD009293. DOI: 10.1002/14651858.CD009293.pub2.

2. Allen JY, Macias CG. The efficacy of ketamine in pediatric emergency department patients who present with acute severe asthma. Annals of Emergency Medicine 2005;46(1): 43–50.

treatment of asthma exacerbations in the pediatric emergency department

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life threatening asthma

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