paediatric acute severe asthma paediatric life threatening asthma

1. paediatric acute severe asthmapaediatric life threatening asthma evidence consensus experience opinion “what I do” Julie McEniery

2. paediatric acute severe asthmapaediatric life threatening asthma life threatening asthma success useful vs harmful evidence

3. oxygen • provide to all children with severe acute asthma even those with normal oxygenation • pulse oximetry useful but does not predict courselevel 111-2 Boychuk, R.B., Yamamoto L.G., DeMesa C.J., & Kiyabu, K.M. (2006) Correlation of initial emergency department pulse oximetry values in asthma severity classes (steps) with the risk of hospitalization. American Journal of Emergency Medicine, 24(1), 48–52. Keahey, L., Bulloch, B., Becker, A.B., Pollack, C.V., Clark, S., & Camargo, C.A. (2002). Initial oxygen saturation as a predictor of admission in children presenting to the emergency department with acute asthma. Annals of Emergency Medicine,40 (3), 300–7.

4. oxygen • occasionally refractory hypoxia • VQ mismatch ? collapse/consolidation LRTI • peak insp flow entrains air around mask • maybe salbutamol effect – discuss later • variable distress usually severe • give more oxygen! • continuous nebs 8 L/m – add O2 tubing from separate flowmeter • high flow nasal cannulae 2 L/kg/min FiO2 1.0 • high concentration mask, given salbutamol iv instead • mask PEEP – hand held, NIV

5. salbutamol inhaled • level 1 efficacy • mdi 10 puffs as effective as neb but not better level 11 efficacy • 2-agonists enhance action glucocorticoids • nebuliser therapy should be wall oxygen driven Cates CJ, Crilly JA, Rowe BH. Holding chambers (spacers) versus nebulisers for beta-agonist treatment of acute asthma. Cochrane Database Syst Rev 2006; 2:CD000052. Deerjanwong, J., Manuyakorn, W., Prapphal, N., Harnruthakorn, C., Sritippayawan, S., & Samransamruajkit, R. (2005). Randomised controlled trial of salbutamol aerosol therapy via metered dose inhaler-spacer versus jet nebulizer in young children with wheezing. Pediatric Pulmonology, 39, 466-72.. Delgado, A., Chou, K. J., Silver, E.J., & Crain, E.F. (2003). Nebulizers vs metered-dose inhalers with spacers for bronchodilator therapy to treat wheezing in children aged 2 to 24 months in a pediatric emergency department. Archives of Pediatric & Adolescent Medicine,157, 76-80.

6. salbutamol inhaled • **mdi use interrupts oxygen • be aware of adverse effects with frequent or continuous nebs (not only seen with infusion) • don’t depend on continuous nebs

7. ipratropium bromide • level 1 efficacy for initial management 3 doses • inhibits cGMP mediated bronchoconstriction • not absorbed into blood, minimal adverse effects • consider repeating 4-6 hourly • why not, little harm? Plotnick, L.H., & Ducharme, F.M. (2000). Combined inhaled anticholinergics and beta2-agonists for initial treatment of acute asthma in children. Cochrane Database of Systematic Reviews, 3, Art. No.: 000060.. Rodrigo, G.J., & Castro-Rodrigues, J.A. (2005). Anticholinergics in the treatment of children and adults with acute asthma: A systematic review with meta-analysis. Thorax, 60 (9), 740-6.

8. systemic glucocorticoids • level 1 & 11 efficacy Edmonds, M.L., Camargo, C.A., Pollack, C.V., & Rowe, B.H. (2003). Early use of inhaled corticosteroids in the emergency department treatment of acute asthma. Cochrane Database of Systematic Reviews, 3, Art. No.: CD002308. Rowe, B.H., Edmonds, M.L., Spooner, C.H., Diner, B., & Camargo, C.A. (2004). Corticosteroid therapy for acute asthma. Respiratory Medicine, 98 (4), 275–84.

9. glucocorticoids in acute severe asthma • this takes hours and hours and hours and hours Barnes PJ & Aldock IM. (2003) How Do Corticosteroids Work in Asthma? Ann Intern Med, 139;359-370.

10. systemic glucocorticoids • level 1 & 11 efficacy • iv early if not improving • methylprednisolone iv 2mg/kg initially then1mg/kg q6h first day • hydrocortisone 8-10mg/kg initially then4-5mg/kg q6h first day • hypersensitivity to methylprednisolone sodium succinate reported • the other therapies just fill in time for corticosteroids to kick in Edmonds, M.L., Camargo, C.A., Pollack, C.V., & Rowe, B.H. (2003). Early use of inhaled corticosteroids in the emergency department treatment of acute asthma. Cochrane Database of Systematic Reviews, 3, Art. No.: CD002308. Rowe, B.H., Edmonds, M.L., Spooner, C.H., Diner, B., & Camargo, C.A. (2004). Corticosteroid therapy for acute asthma. Respiratory Medicine, 98 (4), 275–84.

11. magnesium sulphate • level 1 efficacy • mechanism not clearly defined - includes smooth muscle relaxation, inhibition mast cell degranulation, inhibition acetylcholine • salbutamol causes fall in ser Mg • MgSO4 25-100mg/kg (max 2g) iv infusion over 20min • monitor for hypotension, toxicity rare • preference use before iv salbutamol Cheuk, D.K., Chau, T.C., & Lee, S.L. (2005). A meta-analysis on intravenous magnesium sulphate for treating acute asthma. Archives of Disease in Childhood,90 (1), 74–7.Rowe, B.H., Bretzlaff, J.A., Bourdon, C., Bota, G.W., & Camargo, C.A. (2000). Intravenous magnesium sulfate treatment for acute asthma in the emergency department: A systematic review of the literature. Annals of Emergency Medicine,36 (3), 181–90.

12. salbutamol intravenous • level 11 – ongoing debate • load 15mcg/kg less controversial than continuing infusion • continuous infusion dose range 1-10 mcg/kg/min • increased recognition adverse effects Bohn D. Metabolic acidosis in severe asthma: Is it the disease or is it the doctor? Pediatr Crit Care Med 2007;8(6):582. Tobin A. Intravenous Salbutamol : Too Much of a Good Thing ? Critical Care and Resuscitation 2005;7:119-27.

13. salbutamol adverse effects • glucose & insulin ↑ BSLliver muscle ß2glycogenolysis, hyperinsulinaemia • potassium ↓ K+Na/K-ATPase intracellular shift • lactate ↑ lactic acidosisanaerobic glycolysis in muscle, increased vent demand

14. salbutamol adverse effects • glucose & insulin ↑ BSLliver muscle ß2glycogenolysis, hyperinsulinaemia • potassium ↓ K+Na/K-ATPase intracellular shift • lactate ↑ lactic acidosisanaerobic glycolysis in muscle, increased vent demand • cardiovascular ↓ BP ↑ HRvasodilation skeletal muscle beds + reflex tachycardia, vasodilation pulmonary bed uncouples VQ matchtachycardia cardiac ß1, direct inotrope, prolongs QTc interval, cardiac ß2 exacerbated by low K+low Mg • increases minute ventilation (does not x BBB) • metabolic rate ↑ oxygen consumption ↑ CO2 production • tolerance (reduced ß receptor sensitivity)

15. salbutamol intravenous • level 11 – ongoing debate • load 15mcg/kg less controversial than continuing infusion • continuous infusion dose range 1-10 mcg/kg/min • increased recognition adverse effects • measure ABG / VBG and lactate, taper dose if lactic acidosis present Bohn D. Metabolic acidosis in severe asthma: Is it the disease or is it the doctor? Pediatr Crit Care Med 2007;8(6):582. Tobin A. Intravenous Salbutamol : Too Much of a Good Thing ? Critical Care and Resuscitation 2005;7:119-27.

16. theophylline • Level 1 • mechanism complex • phosphodiesterase inhibition (smooth muscle relaxant) requires high plasma concentration • also effective at low concentration anti-inflammatory action via HDAC (switches genes off), potentiate steroid effect • also stimulate endogenous catecholamine, central respiratory stimulant, augment diaphragm contractility etc • rolewhen salbutamol ineffective or side effects marked Mitra A et al. 2005 Intravenous aminophylline for accute severe asthma in children over two years receiving inhaled bronchodilators. Cochtrane Database of Systematic Reviews

17. iv fluids • maybe dry • severe asthma impairs cardiac filling / function • may benefit from bolus 10ml/kg 0.9%normal saline • use isotonic fluids, watch glucose, avoid overhydration • I use 2/3 maintenance

18. non-invasive positive pressure ventilation nippv • limited data • challenging in paediatrics • unloads fatigued muscles, reduces dynamic hyperinflation, reduces dead space ventilation Ram, F.S., Wellington, S., Rowe, B.H, & Wedzicha, J.A. (2005). Non-invasive positive pressure ventilation for treatment of respiratory failure due to severe acute exacerbations of asthma. Cochrane Database of Systematic Reviews, 1, Art. No.: CD004360. Thill PJ, McGuire JK, Baden HP, et al. Noninvasive positive-pressure ventilation in children with lower airway obstruction. Pediatr Crit Care 2004; 5:337–342. Carroll CL, Schramm CM. Noninvasive positive pressure ventilation for the treatment of status asthmaticus in children. Ann Allergy Asthma Immunol 2006; 96:454–459. Beers SL, Abramo TJ, Bracken A, Wiebe RA. Bilevel positive airway pressure in the treatment of status asthmaticus in pediatrics. Am J Emerg Med 2007; 25:6–9. Teague WG. Noninvasive ventilation in the pediatric intensive care unit for children with acute respiratory failure. Pediatr Pulmonol 2003; 35:418–426.

19. non-invasive positive pressure ventilation nippv • high flow nasal cannulae 2 L/kg/min FiO2 1.0 and wean • in desperation.. • CPAP via hand held anaesthesia T-piece and face mask • ventilator eg Respironics V60 • exhausted child doesn’t usually need sedation • only needed for a few hours

20. slow responder phenotype / genotype • emerging data • obesity • polymorphisms of ß2 receptor (homozygosity for glycine instead of arginine at amino acid position 16 assoc with improved response to ß2 agonist Rx) Carroll CL, Stoltz P, Raykov N, et al. Childhood overweight increases hospital admission rates for asthma. Pediatrics 2007; 120:734–740. Carroll CL, Bhandari A, Zucker AR, Schramm CM. Childhood obesity increases duration of therapy during severe asthma exacerbations. Pediatr Crit Care 2006; 7:527–531. Carroll CL, Schramm CM, Zucker AR. Slow responders to IV b2-adrenergic receptor agonist therapy: defining a novel phenotype in pediatric asthma. Pediatr Pulmonol 2008; 43:627–633. Carroll CL, Stoltz P, Schramm CM, Zucker AR. b2-adrenergic receptor polymorphisms affect response to treatment in near fatal asthma exacerbations in children. Chest 2008. doi: 10.1378/chest.08-2041.

21. maybe it isn’t asthma? • not. . .bronchiolitis <1 year, family has URTI • grey zone older infant younger toddler • maybe asthma >2 year, repeated events, sounds wheezy, responds to asthma treatment • infection • respiratory distress due to metabolic acidosis and hyperventilation • foreign body

22. “she’s starting to look tired” “eveyone’s tired – it’s past bedtime” “he’s starting to look tired”

23. tired or decompensating?

24. decompensation • catecholamine xs • pale, tachycardic, anxious • working hard • blood gas may help  • “getting tired” • moribund • unconscious • brief phase • CO2 usually high

25. summary • oxygen • salbutamol nebuliser with oxygen • corticosteroids systemic oral or iv decent dose • ipratropium nebuliser with oxygen • magnesium sulphate iv load safe and helpful • salbutamol iv initial load useful • salbutamol infusion be aware of plateau of effect, lactic acidosis, hyperglycaemia • aminophylline may be used in life threatening asthma • non invasive bilevel ventilatory support • don’t treat the wheeze, treat the physiology

26. acknowledgements • RCH PICU “acute severe asthma guidelines”recently revised by Tavey Dorofaeff • RCH Emergency Department“initial management and triage of acute severe asthma” • QH Children’s Health Services draft document“children and infants with asthma – acute management”author Greater Brisbane metropolitan procedures and work instructions working group • the children’s hospital at westmead“acute asthma: management, education and dischan\rge practice guideline”