Severe Acute Asthma in the Emergency Department:

CTS Symposium.

Brian H. Rowe, MD, MSc, CCFP(EM)Canada Research Chair in Emergency Airway Diseases

Associate Dean (Clinical Reseaerch), FoMD

Professor, Department of Emergency Medicine

University of Alberta

Conflicts

• Support for the studies reported in this talk:– CIHR (ON);– Physician's Services Inc. (PSI) Foundation (ON);– Medical Services Inc. (MSI) Foundation (AB);– University of Alberta Hospital Foundation (AB) – Canadian Assoc. of Emergency Physicians (CAEP);– Emergency Health Services - RAC (ON);– Department of Emergency Medicine, U of Alberta;– Drugs supplied: AZ, GSK;– Partial study funding: GSK.

• The presenter is not a paid employee or consultant for any sponsor except the University of Alberta.

Outline

• Epidemiology of acute/ED asthma.• Severity assessment.• Predictors of admission and relapse.• CTS-CAEP asthma guidelines.

– In-ED management;– After-ED management.

• Summary.

Pathophysiology - Asthma

• Definition: relapsing chronic disease characterized by symptoms of dyspnea.

• Pathophysiology: – Primary: Airway inflammation (heterogeneity);

– Secondary: broncho-constriction (most symptoms);

– Long-term: may produce inflammatory scarring and fixed obstruction.

• Summary: treatment addresses primary inflammation and secondary bronchospasm.

ED Asthma

• Asthma exacerbations are common ED presentations.

• Exacerbations result in significant:– Costs to the health care system;– Impairments in quality of life for patients;– Lost time from work, school or activities.

• Potential for serious sequelae:– Hospitalizations and complications; – Rarely - death.

Asthma – how it should be treated…

Asthma – how it is treated…

ED Asthma Visits in Alberta

• ACCS methods:– Data on 104 EDs in Alberta;– All ED encounters;– Trained and supervised medical records

nosologists code each chart.

• Validity of ED diagnosis of asthma:– Comparison of respiratory presentations by

multiple ED physicians: asthma > COPD > LRI >>> URI reliability.

Rowe BH, et al. Chest. 2009

A person visits an Alberta ED every 16 minutes with asthma

• Over 6 yrs, 200,000 visits

• 93,150 people

• Adults – 105,813 visits

• Children– 94,187 visits

• 1.8% to 2.4% of all ED visits

• 2.1 visits/person, 63% only one visit

Age specific ED visit rates/1000

24.8 per 1000(22.9 to 26.6)

2.6 times higher rates

Age group and gender directly standardized rates (DSRs) per 1000

In 2004/5, Welfare group (<65yr) had

19.2 per 1000(17.9 to 20.5)

12.4 per 1000(11.7 to 13.1)

9.5 per 1000(9.3 to 9.7)

Summary

• ED asthma in Alberta is declining but still common:– Confirmation: Teresa To/ICES data.

• Admission rates remain stable.• Children present more frequently than adults.• There is considerable room for improvement in

acute asthma care in Canada!– Confirmation: Diane Lougheed et al.

Severity assessment (CAEP/CTS)

Mild Moderate Severe PEFR > 60% predicted

> 300 L/min 40-60% predicted

200-300 L/min Unable

< 40% predicted <200 L/min

FEV-1 > 60% predicted > 2.1 L

40-60% predicted 1.6-2.1 L

Unable <40% predicted

<1.6 L SaO2

- -

< 90%

Hx Increased -agonists

Exertional dyspnea + cough

Partial relief from -agon -agonist q 4 hours dyspnea, cough @ rest

No relief -agonists -agonist > q 2 hours

agitated

Physical -

-

Diaphoretic Tachycardic

ED (simple) Approach

A d m it to ho sp ita l1 0%

P a tie n t un cha ng ed , se ve re o r d e te r io ra te s.

? R x

O n IC SM od era te -se ve re

e xacerb a tion

? R x

N o t on IC SM od era te -se ve re

e xacerb a tion

? R x

V ery m i lde xacerb a tion

P E FR 7 0-8 0%@ p resen ta tion

D isch arg e h om e9 0%

P atie n t im prov esM e ets D /C c ri te r ia

A cu te A s thm a P rese n ta tion to the E DR x in E D a n d re -a sse ss

90% of visits resulted in discharges from EDs in 2004/2005

Discharged 179,585

Discharged from program of clinic

757

Left against medical advice 902

Admitted to CCU or OR 511

Admitted to other area 16,930

Admitted to another facility

1,205

Expired in ambulatory care service

21

Expired on arrival to ambulatory care service

5

Left without being seen 84

Rowe BH, et al. Chest. 2009

Westfall, J. M. et al. JAMA 2007;297:403-406

Translational model

Finding the evidence

2011

Especially productive EM group: Cochrane Airways Group.

Cochrane in-ED asthma treatments:

• Beneficial effect confirmed:– MDI + spacers vs nebulization (Cates);– Early systemic corticosteroids (Rowe); – Inhaled CS (Edmonds);– Anticholinergics (Plotnick);– Early systemic magnesium sulfate (Rowe).

• Beneficial effect lacking:– Antibiotics (Graham);– Heliox (Rodrigo);– Aminophylline (Belda).

• Insufficient evidence: NIV.

Hodder R, et al. Can Med Assoc J. 2010

CTS-CAEP Asthma Guideline

• Inhaled SABA:– Recommends salbutamol.

• Inhaled SAAC:– Recommends IB to reduce admission.

• Systemic corticosteroids:– Recommends SCS to reduce admission.

• Adjunctive care:– IV MgSO4, ICS, IM epinephrine, NIV?

Hodder R, et al. Can Med Assoc J. 2010

Nebulizers vs MDI + Spacers?

• Evidence:– Cochrane Review (high quality);– Wide search updated 2009;– Search identified 27 trials (2295 children and

614 adults) from ED and community settings. – Variable spacer devices (doesn't seem to make

a difference) and doses (higher doses don’t seem to be more efficacious).

– Outcomes sub-grouped into peds and adults.

Nebulizers vs MDI + Spacers?

Cates CA, et al. CL 2010. Outcome: admissions.

Nebulizers vs MDI + Spacers?

Cates CA, et al. CL 2010. Outcome: LOS in ED.

Nebulizers vs MDI + Spacers?

Cates CA, CL 2010. Outcome: Rise in pulse rate (% baseline).

Canadian data

• Survey of the use of nebulizers and spacers in Canadian Pediatric EDs (83% response).

• Overall, 21% of emergency physicians used MDI and spacer.

• The largest perceived barriers amongst non-users included safety and costs, and the lack of a physician champion for change.

• Gradient from East (more use) to West (less use) in Canada.

Osmond M, et al. Acad Emerg Med 2007; 14:1106–1113.

Summary

• Patients with life threatening asthma exacerbations were excluded from the studies, so the results cannot be assumed to apply to this group.

• Analysis of the data regarding lung function tests in many papers was complicated by a lack of standardized reporting.

• MDI + spacer conclusion: – Children - superiority proven; – Adults – no differences vs. equivalence.

CTS-CAEP Asthma Guideline

• Inhaled SABA:– Recommends salbutamol.

• Inhaled SAAC:– Recommends IB to reduce admission.

• Systemic corticosteroids:– Recommends SCS to reduce admission.

• Adjunctive care:– IV MgSO4, ICS, IM epinephrine, NIV?

Hodder R, et al. Can Med Assoc J. 2010

Anticholinergics (ipratropium bromide)

• During the ED stay– P: 2189 patients, > 18 years of age;– D: 7 high quality RCTs;– I: single/multiple IB compared to placebo;– O: 26% reduction to hospital (RR = 0.74; 95%

CI: 0.60 to 0.89, with a NNT of 9);

– O: increase in early FEV1: modest with single (ES = 0.34); large with multiple (ES = 0.78).

• Summary: use often and early.

IB + SABA in the ED

CTS-CAEP Asthma Guideline

• Inhaled SABA:– Recommends salbutamol.

• Inhaled SAAC:– Recommends IB to reduce admission.

• Systemic corticosteroids:– Recommends SCS to reduce admission.

• Adjunctive care:– IV MgSO4, ICS, IM epinephrine, NIV?

Hodder R, et al. Can Med Assoc J. 2010

Systemic Corticosteroids

• During the ED stay– Mainstay of ED asthma

treatment.

• CAEP AIR study:– 96% SABA (3);– 85% SAAC (3);– 78% of ED patients

received SCS.

• What’s the evidence?

Rowe BH, et al. Acad Emerg Med 2008; 15:709–717

Rowe BH, et al. Cochrane Library, Version 1. 2007

Systemic CS to prevent admission

• During the ED stay– P: 863 patients (435 corticosteroids; 428

placebo);– D: 12 variable quality RCTs;– I: systemic CS compared to “SOC”;– O: reduction in admissions (RR = 0.75; 95%

CI: 0.64, 0.85; NNT = 8);– O: earlier treatment, earlier effects observed.

• Summary: use often and early.

Rowe BH, et al. Cochrane Library, Version 1. 2007

SCS - admissions

CTS-CAEP Asthma Guideline

• Inhaled SABA:– Recommends salbutamol.

• Inhaled SAAC:– Recommends IB to reduce admission.

• Systemic corticosteroids:– Recommends SCS reduces admission.

• Adjunctive care:– IV MgSO4, ICS, IM epinephrine, NIV?

Hodder R, et al. Can Med Assoc J. 2010

Rowe BH, et al. Cochrane Library, Version 1. 2007

In-ED use of MgSO4 (admissions)

In-ED use of ICS (admissions)

Treatment after discharge

Preventing relapses

Alberta data - Relapse to ED

~6.4% individuals had a repeat ED visit at 7 days.

Alberta Data - next MD visit

~35% had at least one (non-ED) follow-up visit within 7 days for any reason; time to first F/U = 19 days (95% CI: 18 to 21).

Follow-up

• Relapse occurs following discharge and other evidence suggests treatment plays a role.

• Guidelines recommend follow-up for reassessment and educational reinforcement.

• Follow-up after ED remains less than ideal and so ED MDs need to ensure patients are covered during the sub-acute phase.

Cochrane post-ED asthma treatments:

• Beneficial effect confirmed:– Early PO corticosteroids (Rowe);

– Inhaled CS (Edmonds);

– Non-pharmacological approaches:• Action plans and regular follow-up (multiple).

• Beneficial effect lacking:– Antibiotics (Graham);

– Non-pharmacological approaches;

– Nutritional supplementation.

• Insufficient evidence: LABA, LKTs.

Hodder R, et al. Can Med Assoc J. 2010

CTS-CAEP Asthma Guidelines

• Systemic corticosteroids:– Recommends SCS to reduce relapse.

• Inhaled corticosteroids:– Recommends ICS to reduce relapse.

• Adjunctive care:– Close follow-up, asthma education, smoking

cessation, immunizations, AAP.

Hodder R, et al. Can Med Assoc J. 2010

Cochrane Review• Following the ED stay:

– D: Randomized controlled trials (7; quality RCTs);

– P: acute asthma discharged (374 pts, all ages);– I: “SCS” (oral/IM) for 7-10 days;– C: vs “standard care”;– O: reduction in relapse (RR: 0.39; NNT: 5);– O: reduction in use of beta-agonists (2/day).

Systemic CS: preventing relapses

Summary

• Unless contra-indicated, systemic corticosteroids should be prescribed for acute asthma at discharge.

• IM corticosteroids as effective as oral agents (advantage: compliance; disadvantage: injection pain/bruising).

• Tapering corticosteroids, not generally felt to be necessary (several trials to support this).

CTS-CAEP Asthma Guidelines

• Systemic corticosteroids (SCS):– Recommends SCS to reduce relapse.

• Inhaled corticosteroids:– Recommends ICS to reduce relapse.

• Adjunctive care:– Close follow-up, asthma education, smoking

cessation, immunizations, AAP.

Hodder R, et al. Can Med Assoc J. 2010

Flow chart – CS + ICS vs CS alone

Emergency DepartmentTreatment

SABA 2 puffs QID + Prednisone 50 mg OD

SABA 2 puffs QID + Prednisone 50 mg OD

R

Visit: 1 Telephone Clinic Visit

Week: 0 10-14 days 4 weeks

Placebo Turbuhaler/day X 4 weeks

Emergency Department discharge

Budesonide 1600ug/day X 4 weeks

Rowe BH, et al. JAMA 1999

ICS

No ICS

0 7 14 21Time to Relapse (days)

Number at RiskICS

No ICS89 80 77 7791 77 74 68

0

10

20

30

40

50

60

70

80

90

100

% R

ela

pse

Fre

eRelapse

Rowe BH, et al. JAMA 1999

ICS

• Following the ED visit:– D: 10 high quality RCTs; – P: patients discharged from ED, all ages;– I: ICS for 7-21 days;– C: +/- oral prednisone + -agonists;– O: relapse to additional care;– Comparisons:

• Primary: ICS + CS vs CS;

• Secondary: ICS vs CS.

ICS + CS vs CS Evidence

Edmonds ML, et al. Cochrane Library 2007

CTS-CAEP Asthma Guidelines

• Systemic corticosteroids:– Recommends SCS to reduce relapse.

• Inhaled corticosteroids:– Recommends ICS to reduce relapse.

• Adjunctive care:– LABA?, close follow-up, asthma education,

smoking cessation, immunizations, AAP.

Hodder R, et al. Can Med Assoc J. 2010

Flow chart - ICS vs ICS/LABA

Emergency DepartmentTreatment

SABA 2 puffs QID + Prednisone 50 mg OD

SABA 2 puffs QID + Prednisone 50 mg OD

R

Visit: 1 Telephone Telephone

Week: 0 10-14 days 4 weeks

Fluticasone 1000ug/Salmeterol per day X 4 weeks

Emergency Department discharge

Fluticasone 1000ug/day X 4 weeks

Rowe BH, et al Acad Emerg Med 2007; 14:833-40.

ADVAIR

FLOVENT

0 7 14 21Time to Relapse (days)

Number at RiskADVAIR

FLOVENT69 61 56 5468 59 55 53

0

10

20

30

40

50

60

70

80

90

100

% R

ela

pse

Fre

eRelapse

Rowe BH, et al Acad Emerg Med 2007; 14:833-40.

05

10

15

20

25

30

% R

ela

pse

N= 37 34 31 34

No ICS ICS

ADVAIRFLOVENT

Relapse by Prior ICS Use

Rowe BH, et al. Acad Emerg Med 2008 (ePub Aug)

Relapse predictors - AIR Sub-Study

• Design: Prospective cohort.• Patients: Consecutive patients with acute asthma

enrolled in ED by trained research nurses at following informed consent.

• Setting: 20 ED sites across Canada (2004-2005)• Assessment: Pre-ED, in-ED and post ED

(discretion of the treating MD) care documented.• Outcome assessment: 2-week telephone contact.• Primary outcome: relapse.

Rowe BH, et al. Acad Emerg Med 2008; 15:709–717

Multi-variate LR relapse model

Summary

• ED visits are common, vary by region and treatment varies.

• In –ED: – SABA/SAAC; SCS; IV MgSO4, ICS and ? NIV.

• Post-discharge:– SCS, ICS +/- LABA

• Follow-ups:– Delays common and methods of “connecting” under

studied.

• Delivery of non-drug treatments important.

Thanks for the invitation!

Questions….?

Mild exacerbation Severe exacerbation

Confirm Diagnosis

Acute Asthma Management – Adults

In-ED management

Fast-acting beta-agonist and ipratropium bromide

Treat complications

Systemic corticosteroid (SCS)

NIV

IV MgSO4, inhaled corticosteroids

Adjust therapy based on history/response

Pre-ED management minimal Pre-ED ICS adherence

Control environment, education, referral(s)

Acute Asthma Management – Adults

Post-ED management

Fast-acting bronchodilator

Written Discharge Plan

Inhaled corticosteroid (ICS)

?

Add a LABA

Systemic corticosteroid (SCS)

Adjust therapy based on severity

/response