Severe Asthma Management in the ED

• First steps:
  • Place on capnography
  • Continuous albuterol nebulizer
    • 10 mg/hr for 5-10kg
    • 15 mg/hr for 10-20kg
    • 20 mg/hr for >20kg 
    • Max dose 30 mg/kg
  • Consider a DuoNeb (ipratropium/albuterol)
    • 1.5 mg inhaled over the first hour of therapy
    • Followed by 0.5 mg may be nebulized Q4-6 hours. 
    • 2-3 doses are recommended
  • Get IV access
  • IV Steroids 
    • Methylprednisolone
    • Dexamethasone
  • IV Magnesium sulfate 
    • Dosing 25-75 mg/kg
    • Max dose 2g 
  • IVF
    • Lots of losses with tachypnea 
    • Want to pump up that preload incase things go south 
  • Call RT
• Briefly consider other diagnoses:
  • Heart Failure
  • Anaphylaxis
  • Aspiration
  • Tracheal stenosis
  • Inhaled foreign body
  • PE
  • Hyperventilation syndrome
  • Pneumothorax
  • Vocal cord dysfunction

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Therapy Options:

• Magnesium 
  • Multicenter retrospective cohort study analyzed clinical data from 7 EDs from 2012 to 2017. We described use of IV Mg in children aged 2-17 years treated for acute asthma and its effect on blood pressure
    • ~6,500 kids received IV Mg-–about 10.5% of the total visits 
    • Average time to administration was 154 minutes 
    • 11.1% of patients were able to be discharged home after administration
    • 6.8% became hypotensive
  • Intravenous and Nebulized Magnesium Sulfate for Treating Acute Asthma in Children: A Systematic Review and Meta-Analysis
    • PubMed, Cochrane Library, and EMBASE databases 
    • Ten randomized and quasi-randomized trials (6 IV, 4 nebulized) were identified.
    • IV Mg sulfate treatment is associated with significant improvement in pulmonary function (standardized mean difference, 1.94; 95% CI, 0.80-3.08; P = 0.0008) and hospital admission (RR, 0.55; 95% CI, 0.31-0.95; P = 0.03). 
    • Nebulized Mg sulfate treatment shows no significant effect on respiratory function or hospital admission 
  • High-Dose Magnesium Sulfate Infusion for Severe Asthma in the Emergency Department Efficacy Study
    • All patients of 6–16 years old who failed to improve after 2 hours of standard therapy for asthma.
    • Patients either received a high-dose prolonged infusion or a bolus infusion
    • 50 mg/kg over 1 hour (bolus) 
    • Prolonged magnesium sulfate infusion of 50 mg/kg/hr for 4 hours 
    • Asthma severity was assessed via asthma scores and peak expiratory flow rates at 0-2-6 hours. 
    • Primary outcome was discharge to home at 24 hours.
    • 38 total patients; 19 in each group
    • There was a significant difference in the patients discharged at 24 hours: 47% in high-dose prolonged magnesium sulfate infusion (9/19) versus 10% (2/21) in the bolus group 
  • IV magnesium sulfate in the treatment of acute severe asthma: a multicenter randomized controlled trial
    • Primary efficacy end point was FEV1 at 240 min, & the data analysis was intent to treat.
    • final FEV1 was 51.1% predicted in the magnesium-treated group and 53.9% predicted in the placebo-treated group (mean difference, - 2.9%, 95% CI, - 9.4 to 3.7; p = not significant). Overall, the use of magnesium sulfate did not improve hospital admission rates.
    • Administration of 2 g of IV magnesium sulfate improves pulmonary function when used as an adjunct to standard therapy in patients with very severe, acute asthma.
  • Magnesium sulphate in acute severe asthma in children (MAGNETIC): a randomised, placebo-controlled trial
    • Randomized placebo-controlled, multi-center, parallel trial in the UK
    • Enrolled kids (2–16 years) with severe acute asthma who did not respond to standard inhaled treatment 
    • nebulised albuterol and ipratropium bromide with either :
      • 2·5 mL of isotonic MgSO 4 
      • 2·5 mL of isotonic saline (placebo group) 
    • An asthma severity score was measured on three occasions at 20-min intervals. 
    • Nebulized isotonic MgSO did not show a clinically significant improvement in mean ASS in children with acute severe asthma. 
    • However, the greatest clinical response was seen in children with more severe attacks (SaO 2<92%) at presentation and those with preceding symptoms lasting less than 6 h.
• Ipratropium 
  • DuoNeb dosing:
    • 1.5 mg inhaled over the first hour of therapy
    • Followed by 0.5 mg may be nebulized Q4-6 hours. 
    • 2-3 doses are recommended
  • Efficacy and safety of ipratropium bromide/albuterol compared with albuterol in patients with moderate-to-severe asthma: a randomized controlled trial
    • Looked at differences with use of each as “as needed” controller medications
    • 226 patients, ≥18 years old, with inadequately controlled, moderate-to-severe asthma were randomized
    • Found significant improvement in the ipratropium bromide/albuterol group after 4 weeks
  • The Use of Ipratropium Bromide for the Management of Acute Asthma Exacerbation in Adults and Children: A Systematic Review
    • Dr. S. Aaron , M.Sc., M.D., F.R.C.P.C. &Shawn D. Aaron , M.Sc., M.D., F.R.C.P.C.
    • There is a modest statistical improvement in airflow obstruction when ipratropium is used as an adjunctive to beta2-agonists for the treatment of acute asthma exacerbation. In pediatric asthma exacerbation, use of ipratropium also appears to improve clinical outcomes
  • Randomized Trial of the Addition of Ipratropium Bromide to Albuterol and Corticosteroid Therapy in Children Hospitalized Because of an Acute Asthma Exacerbation Norma Goggin, MD, MRCP; Colin Macarthur, MB, ChB, PhD; Patricia C. Parkin, MD, FRCPC
    • The addition of 2 to 3 doses of inhaled ipratropium bromide to β2-agonist therapy in the emergency department treatment of children with severe asthma improves lung function and reduces the hospital admission rate. The role of ipratropium bromide in the treatment of children hospitalized following emergency department treatment has not been well studied
• Capnography
  • Normal range is 35 - 45 mmHg
  • Will be diminished in severe asthmatics as they are not moving air
  • In asthmatics the wave form changes from the typical box-shape we’re used to to more of a shark fin or wave shape
  • This up slope represents changes in Phase II 
    • Phase II: the expiratory upstroke, a sharp incline in which CO2 levels increase dramatically 
  • https://www.acepnow.com/article/how-to-use-end-tidal-capnography-to-monitor-asthmatic-patients/
    • Each portion of the lung is associated with its own ventilation-perfusion ratio (V:Q) that subsequently determines its respective PaCO2. 
    • During expiration in an asthma exacerbation, the areas of the lung with less bronchoconstriction have a lower PaCO2 and will preferentially be expired first. 
    • The regions of the lung with a greater degree of obstruction will have a higher PaCO2 and will have delayed emptying. 
    • The desynchronization of alveolar emptying causes changes within the capnogram waveform; the slope of Phase II decreases, the slope of Phase III increases as the more highly obstructed alveoli expire their retained CO2 in a delayed fashion, and these changes in the slope result in an increased α angle

• Recheck:
  • Next steps:
    • Continue continuous nebs
    • Subcutaneous terbutaline 
  • Systemic beta 2 agonist 
    • 10 mcg/kg IV loading dose over 10 minutes
    • 0.5 mcg/kg/min
    • Can increase dose q30 min to max dose of 10 mcg/kg/min
    • Can cause elevations in troponin
  • If there hasn’t been improving, consider IM epinephrine instead
    • Same as anaphylaxis dose 
    • 0.01 mg/kg of 1mg/ml (1:1000) IM for peds‐ Max dose 0.5 mg
    • 0.3-0.5 for adults 
• Aminophylline
  • Drug combination of theophylline and ethylenediamine
  • Used for reversible airway obstructions but also thigh cellulite cream….
  • Phosphodiesterase Inhibitor, Adenosine receptor antagonist, &  Histone deacetylase activator
  • Dosing:
    • 6 mg/kg loading dose
    • 0.5-1 mg/kg/hr
  • Recommended starting dose
    • 1-9 years: 1 mg/kg/hr
    • 10-16 years old: 0.8 mg/kg/hr 
  • Narrow therapeutic index and is associated with a wide range of adverse effects
  • Does an aminophylline injection in addition to bronchodilators for an asthma attack improve lung function and other outcomes or cause harm?
  • 2012 Cochrane Review - aminophylline is not significantly better than other bronchodilator drugs, and has more adverse effects. 
• Heliox
  • Lack of Benefit of Heliox During Mechanical Ventilation of Subjects With Severe Air-Flow Obstruction
    • Ann Allergy Asthma Immunol. 2014 
    • Respiratory Care, 2018
    • In mechanically ventilated subjects with severe air-flow obstruction, administration of heliox had no effect on indices of dynamic hyperinflation (plateau pressure and total PEEP) and resulted in only a small reduction in PaCO2
  • Heliox-driven β2-agonists nebulization for children and adults with acute asthma: a systematic review with meta-analysis
    • Eleven trials from 10 studies 
    • Heliox presented a statistically significant difference for mean percentage of change in peak expiratory flow (17.2%; 95% confidence interval 5.2-29.2, P = .005). 
    • Post hoc subgroup analysis showed that patients with severe and very severe asthma showed a significant improvement in peak expiratory flow compared with those with mild to moderate acute asthma. 
    • Heliox-driven nebulization also produced significant decreases in the risk of hospitalizations (odds ratio 0.49, 95% confidence interval 0.31-0.79, P = .003) 
    • Severity of exacerbations (pediatric studies; standard mean difference -0.74, 95%% confidence interval -1.45 to -0.03, P = .04)
  • Heliox for nonintubated acute asthma patients
    • Cochrane review 2016
    • Pooling of the eight trials showed no significant group differences 
    • There was significant heterogeneity among the studies. 
    • Heliox use did improve pulmonary function only in the subgroup of patients with the most severe baseline pulmonary function impairment; however, this conclusion is based on a small number of studies. 
    • There were no significant differences between groups when adults versus children or high versus low heliox dose 
    • At the end of treatment, participants treated with heliox showed no significant different risk of admission to hospital (RR 0.83, 95%CI 0.66-1.08, P = 0.17, I(2) = 0%)

• Noninvasive Ventilation
  • Decreases WOB -> larger tidal volumes
  • The MoA of NIV in status asthmaticus seems to be based on its bronchodilator effect, which induces alveolar recruitment.
  • PEEP through NIV helps overcome the patient’s intrinsic PEEP resulting in bronchodilation
    • Bronchodilation -> increased airflow -> re-expansion of areas previously collapsed with atelectasis -> improvement of V/Q mismatch -> decreased work of breathing
  • IPAP can help unload some of the work of accessory inspiratory muscles and increase tidal volumes 
    • May improve distribution of aerosolized meds into the deep portions of airway 
  • Goal is to use BiPAP to stave off intubation but if it doesn’t work change the patient’s course it still provides an excellent way to preoxygenate
  • Remember: : PEEP and FiO2 will help your oxygenation, while pressure support will help you ventilate.
  • Settings to Maximize Inspiratory Support
    • Inspiratory pressure start around 7-8 but can increase slowly up to 15
    • PEEP 3-5 cmH2O which is low, only enough to match patient's auto-PEEP
    • IPAP = EPAP or PEEP + Pressure Support
    • IPAP > 20-25 is enough pressure to over come the lower esophageal sphincter  gastric insufflation -> vomiting 
  • High inspiratory flow rate 
  • Low I:E ratio (eg 1:5) and prolonged expiratory phase
  • Once you’ve placed the patient on BiPAP and allowed them to chill out they should be pulling reasonably large TVs around 5cc/kg of ideal body weight
    • If the TV is low they may not be ventilating 
  • If the patient cannot tolerate BiPAP you can always put them on HFNC while they are getting continuous nebs to help reduce dead space 
  • Several studies have shown NIV can be safe and effective in pediatric patients with severe asthma
    • There is one study showing increased PICU admissions in moderate asthmatics who were treated with BiPAP
    • Small sample size
    • Could not distinguish if admissions were secondary to worsening condition (eg BiPAP led to air stacking) or because of treatment momentum (floors don’t take kids on BiPAP and may be nervous to take a kid who was even treated with BiPAP while in the ED) 
  • Noninvasive ventilation in status asthmaticus in children: levels of evidence 
    • Rev Bras Ter Intensiva. 2015 Oct-Dec; 27(4): 390–396. doi: 10.5935/0103-507X.20150065
    • Search, selection and analysis were conducted for all original articles on asthma and NIV in children (up to 18 years old) published until September 1, 2014 
    • Serval observational studies and two non-blinded randomized control trials 
    • The results suggest that noninvasive ventilation is applicable for the treatment of status asthmaticus in most pediatric patients unresponsive to standard treatment. However, the available evidence cannot be considered as conclusive, as further high-quality research is likely to have impacts on and change the estimates of effects.
  • Clinical Outcomes After Bilevel Positive Airway Pressure Treatment for Acute Asthma Exacerbations
    • Christopher Golden, BS, MS, OTD1; Meng Xu, MPH2; Cristina M. Estrada, MD3; et alDonald H. Arnold, MD, MPH3 JAMA Pediatr. 2015;169(2):186-188. doi:10.1001/jamapediatrics.2014.2767
    • 933 children and adolescents aged 5 to 17 years who were admitted to the Vanderbuilt pediatric emergency department with acute asthma exacerbations.
    • Primary predictor variable was BiPAP treatment (yes or no) among participants who did not have signs of respiratory failure.
    • Outcomes included hospital admission, admission to the pediatric intensive care unit (PICU), hospital length of stay, and time to spacing of albuterol inhalation to every 4 hours (hereinafter referred to as time to albuterol Q4h) (a metric of exacerbation resolution) based on severity scoring by respiratory therapists.
    • The results indicate that BiPAP treatment of children and adolescents with acute asthma exacerbations who have no signs of impending respiratory failure is associated with a greater likelihood of hospital and PICU admission and no apparent benefit in decreased length of stay or time to albuterol Q4h. 
    • The study is limited because it cannot resolve whether these findings are a consequence of clinical momentum after positive pressure ventilation or of increased air trapping and ventilation-perfusion mismatch, derangements that worsen an exacerbation
  • Bilevel Positive Airway Pressure ventilation efficiently improves respiratory distress in initial hours treating children with severe asthma exacerbation
    • Chun-Min Kang 1, En-Ting Wu 1, Ching-Chia Wang 1, Frank Lu 1, Bor-Luen Chiang 2, Ting-An Yen 3PMID: 31806384 DOI: 10.1016/j.jfma.2019.11.013
      
    • We included data of 46 admissions from 33 different patients (24 with BiPAP and 21 without BiPAP.) The BiPAP group had significantly higher initial RR as well as higher severity scores compared with the other group (p < 0.001). The RR improved significantly in the following time intervals in BiPAP group. There was no significant difference in HR between groups in any of the time intervals. The serum pCO2 levels decreased significantly after initiation of ventilation support in the BiPAP group, and SpO2 levels improved significantly for both groups.
• Agitated Asthmatics 
  • Ketamine
    • Use dissociative dosing—generally frowned upon with use of NIV bc we’d like the patient to tell us if there is something wrong with the mask or be able to take it off if they start to vomit BUUUUUT you’re going to be in the room watching these patients closely until they turn the corner so it should be ok
    • Does not affect respiratory drive
    • Theoretical bronchodilation with large doses, however, has never directly been liked to improved outcomes in asthmatic patients 
  • Dexmedetomidine 
    • Usually start low and titrate up slowly…but may want to consider the reverse in these patients bc it can take awhile to work
    • Alpha 2 antagonists can relax smooth muscle --> directly improving the patient’s condition 
    • Can induce bradycardia 
  • Some thoughts? 
    • Consider Dex when the patient is doing okay but needs help relaxing
    • Consider Ketamine when the patient is severely agitated ripping off their mask that need to relax quickly or if preparing to intubate but want to try NIV as a last ditch effort to prevent having to go down that route
      • In that case you are using ketamine like you would of any other delayed sequence intubation and if it happens ot turn them around that’s great, if not you just provided some great pre-oxygenation 
  • Opioids
    • Can decrease respiratory drive... which is suboptimal
    • IF you don’t have any other option I’d stick to small doses of fentanyl bc it is quick on/quick off
  • Benzos 
    • Bad for the same reason as opioids so again avoid if possible 
    • You really shouldn’t be giving these meds if you have dex or ketamine available 

• Intubation
  • About 1/4 of kids intubated for asthma have complications (pneumothorax, impaired Preload, cardiovascular collapse) because of increased intrathoracic pressures.
    
  • If the patient that you just intubated for his/her asthma becomes unstable / hypotensive, the first thing you should do is disconnect the ventilator and allow the patient to exhale (likely that intrathoracic pressures have increased preventing venous return to the right heart). Consider pneumothorax after that.
  • Consider delayed sequence intubation with ketamine and BiPAP as we discussed
  • If you have to BVM the patient keep RR low (10-12)
  • Optimize pre-intubation hemodynamics
  • Pressure bag IVF or start pressures if need be
    • if you haven’t already started them on an epi drip to assist with bronchodilation this may be the time to do so
  • Use as large of a tube as you can to minimize airway resistance
  • Paralyze with a longer acting agent (aka roc over sux), allows you to take control over your respiratory mechanics 
  • Consider calling the ECMO team early for these patients 
  • If the patient becomes hypotensive after intubation consider S-H-I-T:
    • Stacking (hyperinflation)
    • Hypovolemia
    • Induction drugs
    • Tension pneumothorax
  • Ventilator Settings:
    • Respiratory rate of 12 breaths/minute
    • Inspiratory time (I-time) of 1 second
    • Inspiratory pressure of 40 cm, with a PEEP of 5 cm
    • TV of 6-8 cc per kg of IDEAL body weight 
    • You can start with an FiO2 of 100% per usual but should be able to titrate down quickly 
    • Allow for permissive hypercapnia BUT monitor pH closely 
  • Barotrauma will cause more problems than moderate hypercapnia will in an intubated patient
• Plateau Pressure
  • Check plateau pressure NOT peak pressure
  • Done by preforming an inspiratory pause on the vent 
  • >30 is bad 
  • Represents the pressure that is applied by the mechanical ventilator to the small airways and alveoli
  • High plateau pressures = higher risks of barotrauma
  • To reduce PP you can:
  • Decreasing the tidal volume
  • Decrease PEEP
  • Decrease flow 
  • Increasing the patient's sedation or paralyze the patient (on beneficial in the acute setting) ​