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:
–
–
–
–
–
–
–
–
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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.
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
Rowe BH, et al. Chest. 2009
Age specific ED visit rates/1000
In 2004/5, Welfare
group (<65yr) had
2.6 times higher rates
Age group and gender directly standardized rates (DSRs) per 1000
24.8 per 1000
(22.9 to 26.6)
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
FEV-1
> 60% predicted
> 2.1 L
40-60% predicted
1.6-2.1 L
Unable
< 40% predicted
<200 L/min
Unable
<40% predicted
<1.6 L
-
-
SaO2
Hx
Increased Partial relief from -agon
agonists
-agonist q 4 hours
Exertional dyspnea
dyspnea, cough @ rest
+ cough
Physical
-
-
< 90%
No relief -agonists
-agonist > q 2 hours
agitated
Diaphoretic
Tachycardic
ED (simple) Approach
Acute Asthma Presentation to the ED
Rx in ED and re-assess
Patient unchanged, severe or
deteriorates.
Patient improves
Meets D/C criteria
Admit to hospital
10%
Discharge home
90%
On ICS
Moderate-severe
exacerbation
Not on ICS
Moderate-severe
exacerbation
Very mild
exacerbation
PEFR 70-80%
@ presentation
? Rx
? Rx
? Rx
90%
Discharged
of visits resulted in discharges
from EDs in 2004/2005
179,585
Discharged from program
of clinic
757
Left against medical advice
902
Admitted to CCU or OR
511
Admitted to other area
Admitted to another
facility
Expired in ambulatory care
service
16,930
1,205
21
Expired on arrival to
ambulatory care service
5
Left without being seen
84
Rowe BH, et al. Chest. 2009
Translational model
Westfall, J. M. et al. JAMA 2007;297:403-406
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 nonusers 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
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
Rowe BH, et al. Cochrane Library, Version 1. 2007
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
In-ED use of MgSO4 (admissions)
Rowe BH, et al. Cochrane Library, Version 1. 2007
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
Study
CS
n/N
Plac ebo
n/N
R R (fix ed)
95% C I
W eight
R elaps e R ate
R R 95% C I
7-10 day follow -up
Feil 1983
5/49
10/53
33.03
0.54
[0.20, 1.47]
Lee 1993a
0/19
1/16
5.57
0.28
[0.01, 6.51]
Lee 1993b
1/17
1/16
3.54
0.95
[0.06, 13.82]
McNamara 1993
2/30
8/26
29.47
0.22
[0.05, 0.93]
S hapiro 1983
0/11
0/15
Chapman 1991
3/48
8/45
Not E stimable
28.39
Sub-Total
11/174 28/171
Tes t for ov erall effec t: z =2.86 (P=0.004)
100.00
0.35
[0.10, 1.24]
0.39 [0.21, 0.74]
21 day follow -up
Chapman 1991
10/48
20/45
100
Sub-Total
10/48 10/48
Tes t for ov erall effec t: z =2.32 (P=0.02)
0.01
0.10
1
C ortic os teroids
100.00
10
100
Plac ebo
0.48
[0.25, 0.89]
0.47 [0.25, 0.89]
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 Department discharge

Budesonide 1600ug/day X 4 weeks
Emergency
Department
Treatment
SABA 2 puffs QID + Prednisone 50 mg OD
R
Placebo Turbuhaler/day X 4 weeks
SABA 2 puffs QID + Prednisone 50 mg OD
Visit:
Week:
1
0
Telephone
10-14 days
Rowe BH, et al. JAMA 1999
Clinic Visit
4 weeks
Relapse
100
ICS
90
% Relapse Free
80
70
No ICS
60
50
40
30
20
10
0
0
Number at Risk
ICS 89
No ICS 91
7
14
Time to Relapse (days)
21
80
77
77
68
Rowe BH, et al. JAMA 1999
77
74
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
Study
IC S+C S C S
n/N
n/N
R R (fix ed)
95% C I
W eight
R elaps e R ate
R R 95% C I
20-24 day follow -up
B renner 2000
4/51
4/53
Camargo 2000
30/310
37/307
Rowe 1999
12/94
23/94
6.12
58
35.88
Total
46/455 64/454
Tes t for ov erall effec t: z =1.84 (P=0.07)
0.01
0.10
1
IC S+Oral C S
100.00
10
100
Oral C S
Edmonds ML, et al. Cochrane Library 2007
1.04
[0.27, 3.94]
0.8
[0.51, 1.27]
0.52
[0.28, 0.99]
0.72 [0.50, 0.1.02]
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 Department discharge

Fluticasone 1000ug/day X 4 weeks
Emergency
Department
Treatment
SABA 2 puffs QID + Prednisone 50 mg OD
R
Fluticasone 1000ug/Salmeterol per day X 4 weeks
SABA 2 puffs QID + Prednisone 50 mg OD
Visit:
Week:
1
0
Telephone
10-14 days
Rowe BH, et al Acad Emerg Med 2007; 14:833-40.
Telephone
4 weeks
Relapse
100
ADVAIR
90
F LO VENT
% Relapse Free
80
70
60
50
40
30
20
10
0
0
Number at Risk
ADVAIR 69
FLOVENT 68
7
14
Time to Relapse (days)
21
61
59
54
53
56
55
30
Relapse by Prior ICS Use
15
10
5
0
% Relapse
20
25
AD VAIR
FLOVEN T
N=
37
No ICS
34
31
34
ICS
Rowe BH, et al Acad Emerg Med 2007; 14:833-40.
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 (ePub Aug)
Multi-variate LR relapse model
Rowe BH, et al. Acad Emerg Med 2008; 15:709–717
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….?
Acute Asthma Management – Adults
In-ED management
NIV
IV MgSO4,
inhaled corticosteroids
Systemic corticosteroid (SCS)
Fast-acting beta-agonist and ipratropium bromide
Treat complications
Confirm Diagnosis
Mild exacerbation
Severe exacerbation
Acute Asthma Management – Adults
Post-ED management
?
Add a LABA
Inhaled corticosteroid (ICS)
Systemic corticosteroid (SCS)
Fast-acting bronchodilator
Written Discharge Plan
Control environment, education, referral(s)
Pre-ED management minimal
Pre-ED ICS adherence