Annual World CRITER Conference
Acute Severe COPD Management:
Is there anything more than NIV?
Brian H. Rowe, MD, MSc, CCFP(EM), FCCP
Tier I CRC in Evidence-based Emergency Medicine
Professor and Research Director
Department of Emergency Medicine
University of Alberta
Definition
• AECOPD:
– A sustained worsening of dyspnea, cough or
sputum production, for at least 2 days;
– Leading to an increase in the maintenance
medications and/or supplementation with
additional medications.
• Exacerbations are more common as severity
of COPD worsens.
• Recovery always incomplete, so prevention
is the key.
Diagnosis
• Confirm diagnosis with history, physical
and objective lung function measurements.
• Differential (other co-morbidities/causes):
–
–
–
–
–
–
HF: CXR, BNP/NT-proBNP;
PE: PTP (Wells’), D-dimer, advanced imaging;
CAP: CXR, advanced imaging;
ACS: ECG, biomarkers, provocative testing;
Pneumothorax: CXR, U/S, advanced imaging;
Others
Differentiating COPD from Asthma
Spirometry-2
FEV1/FVC > 0.7
FEV1/FVC < 0.7
O‘Donnell DE, et al. CRJ 2008;15:1A-8A
Question 1: Bronchodilator choices
• Not as clear cut as asthma.
• Both salbutamol and IB are effective.
• Synergy:
– Not demonstrated to date.
• Side effects:
– More pronounced with salbutamol.
• Delivery:
– MDI + spacer vs nebs.
Question 2: Efficacy of corticosteroids in
exacerbations of COPD?
All evidence
• Systemic corticosteroids vs placebo:
– Cochrane Review: high quality;
– Involving 11 trials and >1080 adult patients;
• Outcomes:
– Fewer treatment failures within 30 days (OR =
0.50; 95% CI: 0.36 to 0.69) – NNT = 10.
– LOS (Hosp): -1.2 days (95% CI: -2.3 to -0.2);
• Caveat:
–  S/Es (OR = 2.3; 95% CI: 1.6 to 3.4).
Walters JAE, et al. CDSR. 2009; 1:CD001288.
Outcome: treatment failure
Walters JAE, et al. CDSR. 2009; 1:CD001288.
Outcome: Mortality
Walters JAE, et al. CDSR. 2009; 1:CD001288.
Following discharge?
• Canadian study involving Pulmonary and
Emergency Medicine with low RofB:
– Concealed allocation;
– RCT;
– Multiple levels of blinding.
• AECOPD patients:
– Not on corticosteroids prior to presentation;
– Treated by ED physicians and improved to the
point where discharge was considered safe.
Aaron S, et al NEJM 2003; 348:2618-24.
Corticosteroids after discharge
Emergency Department discharge

Prednisone 40 mg po OD X 10 days
Emergency
Department
Treatment
Combivent® 2 puffs QID + antibiotics
R
Placebo prednisone
Combivent® 2 puffs QID + antibiotics
Visit:
Week:
1
0
PC1
10-14 days
Aaron S, et al NEJM 2003; 348:2618-24.
2
4 weeks
Prednisone for Out-Patient Acute
Exacerbation of COPD
Summary
• Systemic corticosteroids are effective in the
early treatment of acute severe COPD to
reduce failures and ↓ LOS.
• Systemic corticosteroids are effective in the
out-patient treatment of COPD to prevent
relapse (NNT: 7).
• S/E’s are impressive, so selection must be
appropriate.
• Duration: 5 = 10 days (new evidence).
Walters JAE, et al. CDSR. 2012: CD006897.
Question 3: Efficacy or antibiotics in
exacerbations of COPD?
Who needs them and which ones do you use?
Infectious etiology
• AECOPD can be associated with both viral
and bacterial infections.
• Bacteria growth related to severity:
– Mild:
• Usually associated with S. pneumonia.
– Severely ↓ FEV1/frequent exacerbations:
• Often associated with H. influenzae / M. catarrhalis.
– Frequent Abx/recent hospitalization/culture +ve:
• May be associated with P. aurigenosa.
Effectiveness of Antibiotics
in COPD
% Success
Placebo
Antibiotic
80
70
60
50
40
30
20
10
0
Type 1
Type 2
Type 3
Anthonisen NR, et al. Ann Intern Med 1987; 106:196-204.
All evidence
• Systemic antibiotics vs placebo (Type II/I):
– SR: high quality;
– Involving 11 trials and >900 adult patients;
• Outcomes:
– Lower mortality (RR = 0.23; 95% CI: 0.1 to
0.5) – NNT = 10.
– Fewer treatment failures (RR = 0.47; 95% CI:
0.4 to 0.6) – NNT = 3.
• NB: not influenced by the antibiotic choice.
Ram F, et al Cochrane Database Syst Rev. 2006; 2:CD004403
Proposed Therapies for AECOPD According
to Patient Subsets
Simple, uncomplicated
AECOPD
Complicated
AECOPD
Complicated AECOPD
at risk for P aeruginosa
 Any age
 >64 years
 < 4 exacerbations/yr
 >4 exacerbations/yr
 No comorbid illness
 Serious comorbid illness  Need for chronic
corticosteroid therapy
 FEV1 <50%
and frequent (>4/yr)
courses of antimicrobials
 FEV1 >50%
 Patients with chronic
bronchial sepsis
 FEV1 <35%
Macrolide (azithromycin, clarithromycin)
or new cephalosporin
(cefpodoxime,
cefuroxime, cefdinir),
doxycycline
Newer respiratory
fluoroquinolone or
amoxicillin/clavulanate
Fluoroquinolone
with antipseudomonal
activity (eg, ciprofloxacin)
FEV1 = Forced expiratory volume in 1 second. O’Donnell et al. Can Respir J. 2003;10(Suppl A):11A.
Canadian Guidelines
O'Donnell D, et al. CRJ 2007; 14:5B-32B
Question 4: Efficacy of NIV in
exacerbations of COPD?
Who needs it?
NIV
The evidence
•
•
•
•
•
Design: 10 RCTs (> 750 patients).
Population: Acute severe COPD.
Interventions: NIV + standard care.
Control: standard care.
Outcomes:
– Death, intubation, LOS
• High quality methods for SRs
Ram FSF, et al. CDSR. 2004, Issue 3.
NIV – treatment failures
Ram FSF, et al. CDSR. 2004, Issue 3.
NIV – Mortality outcome
Ram FSF, et al. CDSR. 2004, Issue 3.
NIV – Intubation outcome
Ram FSF, et al. CDSR. 2004, Issue 3.
Utilization data (others exist)
Chandra D, et al. Am J Respir Crit Care Med. 2012; 185:152–159.
Other issues
• Misuse is a concern in the ED.
• Tran et al poster at ICEM 2012:
– 912 eligible AECOPD patients in Calgary
receiving systemic CSs (severe);
– 67.4% had BG determination;
– 19.2% met criteria for respiratory failure and
treatment with NIV;
– Only 59.3% of these received treatment;
however, 44% of those who received NIV did
not meet criteria.
Question 5: In those who receive
antibiotics, what other issues should we be
considering?
Most recent antibiotics?
Percent resistant (or non-susceptible)
Effect of Prior Antibiotic on
S pneumoniae Resistance
35
No (or no known)
antibiotic use
Any prior antibiotic
30
Prior use same class
40
25
20
15
10
5
0
Penicillin
Cefotaxime
Erythromycin
Tmp/Smx
Quinolones
Vanderkooi OG, CID 2005;40: 1288-97
Question 6: In those who receive
antibiotics, what other issues should we be
considering?
Duration of treatment?
5 = 10 days
Evidence Summary
• Systematic review (21 studies; 10,698 pts).
• A short course of antibiotics (5 days) seems to be
just as effective in achieving clinical and
bacteriological cure rates as a longer course (7-10
days).
• Given the side effects of antibiotics and the elderly
nature of COPD patients, it seems reasonable to
reduce the duration of antibiotics in this patient
population.
Short (< 5 days) vs long (>7 days)
Moussaoui RE, et al. Thorax 2008; 63: 415-422
Real data (others exist)
Tsai et al. Acad Emerg Med. 2008; 15: 1275
Question 7: In patients with AECOPD, is
there evidence to assist in admission
decisions?
Canadian data.
Admission
• CAEP-RC (Academ Emerg Med; 2009)
– Of 501 study pts across 20 Canadian sites, 247 (49%;
95% CI: 45 to 54) admitted;
– Admission was associated with:
• ≥ 2 COPD admissions in the past two years (OR=2.10; 95% CI:
1.24 to 3.56);
• Receiving oral CS for COPD (OR=1.72; 95% CI: 1.08 to 2.74);
• CTAS 1-2 score (OR=2.04; 95% CI: 1.33 to 3.12);
• Receiving adjunct ED treatments (OR=3.95; 95% CI: 2.45 to
6.35).
• Use of EDs for usual COPD care was associated with a reduced
risk of admission (OR=0.43; 95% CI: 0.28 to 0.66).
Other considerations
• Gaps exist in what is known and what
patients need/are receiving:
– Follow-up: after ED visits;
– Medications:
• Appropriate chronic pharmacological management;
• Spacer devices.
– Counselling: smoking cessation;
– Immunization: influenza and pneumococcal;
– Prevention: Action plans and education.
Follow-up
• Evidence suggests that the majority of
patients with COPD have primary care
providers (PCP).
• Delays in follow-up may decrease the
chance to prevent the next deterioration:
– AB: median follow-up occurred at 13 days and
only 40% in the first 7 days following D/C.
• Needed: evidence of effective interventions
after discharge to enhance follow-up.
Prevention strategies
• Pulmonary rehabilitation better than most
pharmacological interventions.
• Problem:
– Limited availability;
– Rarely prescribed (<25% in recent study).
• Consider educational strategies for COPD:
– COPD education;
– Smoking cessation;
– Referral to specialist.
Future directions
• Decision rules for COPD
– Ottawa decision rule.
• Implementation of guidelines.
• Personalized/metabolomic medicine:
– Diagnostics (e.g., PCT, CRP, others);
– Treatments.
• New drug classes (biologics):
– Anti-ILx monoclonal antibodies and other
immune modulators.
Summary
• Systemic corticosteroids reduce failures:
– Consider in most admitted patients;
– Consider 5 days at discharge for Anthonisen type I and II
cases.
• Antibiotics improve outcomes:
– AECOPD classified as simple and complex;
– Ask about recent antibiotic use and sensitivity;
– Treat for 5 days, unless otherwise indicated.
• NIV:
– Consider in patents with extreme symptoms prior to
“IN2B8N”.
• Admissions:
– Predictable.
Annual World CRITER Conference
Thanks for Listening!
Questions?