Acute Asthma Acute Asthma Exacerbation: Exacerbation:

Management in the EDManagement in the EDPatrick PLAISANCE, M.D., PhD.Patrick PLAISANCE, M.D., PhD.

Associate ProfessorAssociate Professor

Department of Anesthesia, MGH, MUHC.Department of Anesthesia, MGH, MUHC.

NIH DefinitionNIH Definition Chronic inflammatory changes in the Chronic inflammatory changes in the

bronchial submucosabronchial submucosa

Increased responsiveness of the airwaysIncreased responsiveness of the airways

Reversible expiratory airway obstructionReversible expiratory airway obstruction

Ventilatory :Ventilatory : dynamic resistances dynamic resistances

residual volumeresidual volume

AtelectasesAtelectases

V/P mismatchingV/P mismatching

Airways dynamic collapseAirways dynamic collapse

Hemodynamic :Hemodynamic : Paradoxical pulse > 18 mmHgParadoxical pulse > 18 mmHg

Ventilatory and Ventilatory and Hemodynamic Hemodynamic ConsequencesConsequences

Triggering FactorsTriggering Factors• Infection:

– Bacterial sinusitis– Tracheo-bronchial infection– Viral infection of the airways

• Medications:– Beta blockers (collyrium), aspirine, NSAI, antibiotics

• Others:– Gastro-oesophageal reflux– Psycho-sociological factors – Stress– Exercise – Stop of chronic treatment

Bad Prognosis FactorsBad Prognosis Factors

• Previous severe exacerbations

• Hospitalization within the last year

• Psycho-sociological factors

• Previous intubations

• Stop of corticosteroid treatment

• Low patient’s compliance

Importance of an Early Treatment

Inhalation versus IV Infusion in Mild Exacerbations

Inhalation versus IV Infusion in Severe Exacerbations

Efficacy of the Inhaled Efficacy of the Inhaled RouteRoute

- nebulizer- nebulizer- gas flow- gas flow- driving gas- driving gas

Advantages of the Inhaled Advantages of the Inhaled RouteRoute

• Direct respiratory tropism• Short onset of action• Low doses• Less side-effects

• Simultaneous O2 delivery

• Humidification of the airways

Intermittent versus Intermittent versus Continuous NebulizationContinuous Nebulization

• Small benefit from continuous nebulization– Gibbs et al. Acad Emerg Med, 2000

• Beneficial effect on severe exacerbations• No increased side-effects

– Moler et al. Am J Respir Crit Care Med, 1995

• Reduction of staff time– Fink et al. Respir Care 2000

Guidelines on Nebulizer Guidelines on Nebulizer TherapyTherapy

(British Thoracic Society, (British Thoracic Society, ThoraxThorax 1997) 1997)

• Driving gas (SpO2 > 90%):

– Air + simultaneous O2 (nasal prong)

– O2

• Fill volume of 4 mL (if residual volume > 1 mL)

• Flow rate 6-8 L/min• Nebulization time < 10 min

Meter-Dose InhalersMeter-Dose Inhalerswith Holding Chamberswith Holding Chambers

• As effective as nebulizers (Cates et al. Cochrane Database Syst Rev, 2000)– Similar hospital admission rate– Similar improvement in PEFR and FEV1– Children:

HR more important duration of the treatment in the ED

• Progressive administration of the medication

• Interesting for children < 3 years

22+ Mechanism of Action+ Mechanism of Action

muco-ciliary clearence

vascular permeability

• Inhibition of transmitter release from mast cells

22 Agonists Agonists

• Selective (Terbutaline, Salbutamol)– First line therapy– Short onset of action (2-5 min)– Long duration of action (3-6 h)– Different routes of administration

• Non selective (epinephrine)– Vasoconstricting agent– Short duration of action– Side effects

AnticholinergicsAnticholinergicsMechanism of ActionMechanism of Action

• Ach competitive inhibitors

• muscarinic receptors antagonists

• Bronchodilators

• Inhibitors of the bronchoconstriction induced by irritant agents

Anticholinergics + Anticholinergics + 22 AgonistsAgonistsChildrenChildren

• Schuh S et al. Pediatr 1995:– N = 120– 5-17 y.o. FEV1, PEFR, hospitalization stay:

•Salbutamol < salbutamol + 1 ipratropium < Salbutamol + 3 ipratropium

•More interesting in severe exacerbations

Anticholinergics + Anticholinergics + 22 + +Meta-analyses ChildrenMeta-analyses Children

• Plotnick LH et al. Cochrane Database Syst Rev 2000– N = 836 children– Spirometric improvement Hospital admission rates

Anticholinergics + Anticholinergics + 22 AgonistsAgonists

Meta-analyses AdultsMeta-analyses Adults• Rodrigo et al. Am J Med 1999

– n = 1483– Randomized studies, double-blind, controlled– Results:

• Pulmonary function improvement Hospital admission

• Stoodley et al. Ann Emerg Med 1999– N = 1377– Slight clinical improvement– No side-effects

Anticholinergics and Anticholinergics and 22+ in Adults+ in Adults

Groups Groups PEFR (L/min) PEFR (L/min) PEFR (L/min) PEFR (L/min) PEFR (L/min) PEFR (L/min) HospitalHospital

T12hT12h T36h T36h T60h stay (d) T60h stay (d)______________________________________________________________________________________________________________S + IB 12hS + IB 12h 68 68 62 62 56 56 5,4* 5,4*

S + IB 36hS + IB 36h 81 81 73 73 47 47 4,1 4,1

S + IB 60hS + IB 60h 100100 69 69 42 42 4 4

* p < 0,01* p < 0,01

Brophy C et al. Brophy C et al. ThoraxThorax 1998 1998

CorticosteroidsCorticosteroids hospital admission if administered within the 1st hour

• Equal benefit of orally and IV administration– Rowe et al. Cochrane Database Syst Rev, 2000

• Dose ranging from 30-400 mg methylprednisolone :– Manser et al. Cochrane Database Syst Rev, 2000

• Inhaled vs systemic corticosteroids: (Edmonds et al. Cochrane Database Syst Rev. 2003) PEFR and FEV1 as compared with placebo

– as effective as systemic corticosteroids ?

– Combination better than systemic route alone ?

MethylxanthinesMethylxanthines

• No benefit from adding methylxanthines

to 2+

• More adverse effects– Parameswaran et al. Cochrane Database Syst Rev

2000

MgSOMgSO44

• Inhalation:– Improvement in clinical score (Fischl), PEFR, PP– Nannini LJJr. Am J Med 2000– Mangat HS Eur Respir J 1998

PEFR

• IV:– Boonyavorakul C. Respiratology 2000

• Hospital admission = NS; score = NS

– Rowe BH. Ann Emerg Med 2000 admission rate in severe asthma exacerbations

Helium PropertiesHelium Properties

• Inert gas, colourless, odourlessInert gas, colourless, odourless

• Density lower than air and ODensity lower than air and O22

• No diffusion through cellular membranes No diffusion through cellular membranes

• No chemical and physiological actionNo chemical and physiological action

• Action due to its physical propertiesAction due to its physical properties

No bronchodilator and anti-inflammatory actionNo bronchodilator and anti-inflammatory action

Barach et al. Ann Int Med 1935Barach et al. Ann Int Med 1935

• The use of Helium in the Treatment of The use of Helium in the Treatment of Asthma and Obstructive Lesions in the Asthma and Obstructive Lesions in the Larynx and Trachea Larynx and Trachea

StudiesStudies

• Small trials or case reports with poor methodology

• Evaluation criteria varying from one study to another

• Different treatment duration

Importance of Flow RateImportance of Flow Rate

. Continuous nebulization. Continuous nebulization

. P1 = 3,5 bars. P1 = 3,5 bars

Gas flowGas flow Q = 8 L/min Q = 12.7 L/min Q = 8 L/min Q = 8 L/min Q = 12.7 L/min Q = 8 L/min He/OHe/O22 He/ O He/ O22 O O22

__________________________________________________________________________________________________________________________P2 (bars)P2 (bars) 0.64 0.64 1.411.41 1.451.45

MMAD (mm)MMAD (mm) 5.365.36 3.183.18 3.603.60

Nebulized massNebulized massafter 10 ’ (g)after 10 ’ (g) 2.252.25 3.353.35 2,.852,.85

Nebulized massNebulized massafter 15 ’ (g)after 15 ’ (g) 3.353.35 4.084.08 3.693.69

Nebulized massNebulized massafter 20 ’ (g)after 20 ’ (g) 3.833.83 4.464.46 4.064.06

PEFR

100120

150

250

190

290

192

330

0

50

100

150

200

250

300

350

T0 T20 T40 T60

O2He-O2

*

**

*p < 0,01*p < 0,01

L/min

O2 HeO2 p

Transfer to ICU (%) 62,89% 52% nsMean duration of stay in ICU 4,1 ± 5,4 2,1± 2,6 nsPatient still in ICU at Day 4 19 8 0,02Intubation rate 7,37% 1% 0,03

Within the last 3 monthsASUR2001

30 %

38 %

23 %

8 %

0%

5%

10%

15%

20%

25%

30%

no(n = 1237)

General Practitioner (n =1555)

Pneumologist (n = 962)

Both(n =333)

Patients having a peak flow at home : 16 % (n = 652)

Salmeron et al. Asthma severity and adequacy of management in accident and emergency departments in France : a prospective study. The Lancet ; 2001 ; 358 : 629 – 35.

4 087 asthma exacerbations

Severity Upon ArrivalASUR2001

Mild to moderate exacerbation

(PEFR > 50%)

Salmeron S, et al. Asthma severity and adequacy of management in accident and emergency departments in France : a prospective study. The Lancet ; 2001 ; 358 : 629 – 35.

26 %(n = 975) 49 %

(n = 1834)

25 %(n = 963)

Fatal asthma

(PEFR < 30%) Severe exacerbation

(30 % PEFR 50 %)

• age• gender• recent corticosteroid treatment per os• hospitalization within the last year

The severity of exacerbation is independent of :

Treatment in the EDASUR2001

Salmeron S, et al. Asthma severity and adequacy of management in accident and emergency departments in France : a prospective study. The Lancet ; 2001 ; 358 : 629 – 35.

95 % (n = 924)

0

10 %

20 %

30 %

40 %

50 %

60 %

70 %

80 %

90 %

93 % (n = 1708) 89 %

(n = 860)

51 %(n = 494)

50 %(n = 913) 45 %

(n = 434)

68 %(n = 666) 61 %

(n = 1117)49 %

(n = 468)

Inhaled 2 agonists

Inhaledanticholinergiques

Systemic corticosteroids

Mild to moderate exacerbation

Fatal asthma

Severe exacerbation

• inhaled 2 agonists : 92 % (n = 3492)• inhaled anticholinergics : 49 % (n = 1841)• systemic corticosteroids : 60 % (n = 2251)

Pre-Determined Management Pre-Determined Management PlanPlan

• McFadden et al. McFadden et al. Am J MedAm J Med 1995 1995– Length of stay in the ERLength of stay in the ER

– Admission ratesAdmission rates

– Re-admissionRe-admission

– Cost savingsCost savings

Initial MonitoringInitial Monitoring

• Pulse oxymetryPulse oxymetry

• PEFR (best of three)PEFR (best of three)

• Pulse, BPPulse, BP

• RRRR

• Clinical judgement:Clinical judgement:– CyanosisCyanosis

– Use of accessory musclesUse of accessory muscles

– StridorStridor

– diaphoresisdiaphoresis

• Blood gassesBlood gasses

Initial Treatment in ChildrenInitial Treatment in Children

Inhaled Treatment Inhaled Treatment Associated Associated

TreatmentTreatment

every 20’ within the 1st hourevery 20’ within the 1st hour

. O. O22 6-8 L/min (SpO 6-8 L/min (SpO22 95%) 95%) . Salbutamol or . Salbutamol or

TerbutalineTerbutaline

. Salbutamol 0.5%: 0.03 mL/kg or 7-10 . Salbutamol 0.5%: 0.03 mL/kg or 7-10 g/kg SCg/kg SC

Terbutaline 5 mg + IB 0.25 mgTerbutaline 5 mg + IB 0.25 mg . HSHC 5 mg/kg or . HSHC 5 mg/kg or

methyl-methyl-

. Or 0.2-0.3 puffs/kg with MDI . Or 0.2-0.3 puffs/kg with MDI prednisolone 2 mg/kg prednisolone 2 mg/kg

IVDIVD

+ HC+ HC

Initial Treatment in AdultsInitial Treatment in Adults

Inhaled Treatment Inhaled Treatment Associated Treatment Associated Treatment

every 20 min within the 1st hourevery 20 min within the 1st hour

. O. O22 6-8 L/min (SpO 6-8 L/min (SpO22 90%) 90%) . Salbutamol or . Salbutamol or

TerbutalineTerbutaline

. Salbutamol 2.5 mg (or 7.5 mg (0.5 mg) or . Salbutamol 2.5 mg (or 7.5 mg (0.5 mg) or

epinephrine epinephrine

continuously) + IB 0.5 mg continuously) + IB 0.5 mg 0.25 mg SC 0.25 mg SC

. or 2-3 puffs with MDI + HC . HSHC 200-400 mg or. or 2-3 puffs with MDI + HC . HSHC 200-400 mg or

. or epinephrine 2 mg + 3 mL NS methyl-prednisolone 1 . or epinephrine 2 mg + 3 mL NS methyl-prednisolone 1

mg/kg mg/kg IV IV

Inhospital TreatmentInhospital Treatment

Initial treatmentInitial treatment

Improvement (PEFR: 50-70%)Improvement (PEFR: 50-70%)No improvement (PEFR < 50%)No improvement (PEFR < 50%)

Good responseGood responseresponse>1hresponse>1hExamination nlExamination nlPEFR > 70%PEFR > 70%

Incomplete ResponseIncomplete Response. Moderate signs. Moderate signs. PEFR: 50-70%. PEFR: 50-70%

No improvementNo improvement. Severe signs. Severe signs. PEFR < 30%. PEFR < 30%. PaCO. PaCO22 > 45 mmHg > 45 mmHg. PaO. PaO22 < 60 mmHg < 60 mmHg

DischargeDischarge

Admission Admission ICUICU

22+: 1/h for 1-3 h+: 1/h for 1-3 h 22+ + IB: 3/h pdt 1-3 h+ + IB: 3/h pdt 1-3 h22 IV IV

PEFR > 70%PEFR > 70%Examination nlExamination nl12h with no tt12h with no tt

No improvement No improvement within 6-12hwithin 6-12h

AntibioticsAntibiotics

• Graham et al. Cochrane Database Syst Rev. 2001– No benefit when comparing antibiotics to placebo

• Indications: GOLD-guideline (Pauwels et al. Respir Care 2001)– Worsening dyspnea and cough– Increased sputum volume and purulence– Infiltrates on the chest X-ray

NIVNIV

• VS-PEP (Shivaran U et al. Resp 1987) residual volume respiratory work– Risks:

• Overdistension of zones with low resistance• Pulmonary hyperinflation

ConclusionConclusion

• Importance of an early treatment Importance of an early treatment

• Importance of nebulizationImportance of nebulization

• Combination Combination 22 agonists/Ipratropium Bromide agonists/Ipratropium Bromide

• Combination of different routesCombination of different routes

• PEFR monitoringPEFR monitoring

• Interest of MgSOInterest of MgSO44 and Helium ? and Helium ?