Management of acute exacerbation of COPD in
hospitalized patients
Prof. Nasser Behbehani
1st Kuwait North America update in
Internal Medicine
4th medical scientific conference
Mubarak Alkabeer hospital
question
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On a beautiful Friday afternoon like today I’d
rather be
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A) outside with the family having fun
B) sitting here listening to Naser Behbehani
1st question
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If a 70 year old man ex heavy smoker comes to your
hospital ED with dyspnea, cough , wheeze, his
saturation is 75%, he has bilateral wheeze.
What is the most likely initial form of oxygen that he will receive
 A) venturi mask at 24%
 B) nasal canulas
at 3-5 litres per minute
 C) re -breather mask
 D) simple oxygen mask
 E) don’t know
2nd question
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What is the most likely initial antibiotic that patients with
AECOPD and infection is suspected to be the trigger admitted to
your hospital will receive
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A) Amoxicillin-clavulinic acid
B) Ceftriaxone + Clarithromycin
C) 3rd generation cephalosporin alone
D) 2nd generation cephalosporin alone
E) a respiratory quinolone ( levofloxacin- Moxifloxacin )
3rd question
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the most likely steroid dose that patients admitted
with AECOPD will receive at our hospital
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A) Hydrocortisone 100 mg 3 or 4 time per day at least for
48 hrs. then switch to oral prednisone
B) Hydrocortisone 100 mg 3 or 4 time per day until almost
ready for discharge
C) prednisone 40 mg daily
D) Methylprednisolone 40-60 mg IV 3-4 time per day
E) higher doses
4th question
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Almost all patients admitted with AECOPD receive
nebulized steroid ( budesonide ) on top of IV or
oral steroids
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A) yes
B) No
Case presentation
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75 year old man ex smoker known to have ,
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COPD
Type II diabetes mellitus
hypertension
he presented to ED with 1 month history of
increasing dyspnea , no significant cough or
sputum
Frequent ED visits over last 1 month
Compliant with his medications
Case presentation
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Physical examination
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Heart rate 90/ min , Resp rate 26 , saturation
96% on room air, Temp 37.0
Marked bilateral wheeze
CXR
ABG
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Ph 7.51, PO2 26.9 Kpa, 3.13 Kpa , HCO3 18
mmole
Course in hospital
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Admitted 16th Feb to 7th March ( 3 weeks)
In hospital treatment
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Nebulized ( Salbutamole 0.5 ml + iparatropium
Bromide 1 ml ) every 4 hrs.
Nebulized Budesonide 500 mcg twice per day
Seretide ( Fluticasone + salmeterole) discuss
Tiotropium Bromide ( spiriva) once daily
Hydrocortizone 100 mg every 6 hrs. for then
overlapped with Prednisone 40 mg daily until
discharge
Ceftriaxone + clarithromycin for 10 days
Course in hospital
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Echo was done
CT chest was done
no spirometry done ( daily notes say bilateral
expiratory wheeze)
treatment on discharge
On discharge
Total steroid dose
1) Equivalent to 80 mg prednisone per day for 6 days
2) 40 mg daily for 15 days
3) After discharge 40 to 5 mg over 40 days
Final outcome
Larger dose does not mean
better
Acute exacerbation of COPD
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Definition according to WHO document
Significant increase in any of these symptoms
beyond day today variation
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Cough in severity or frequency
Sputum in volume or colour
dyspnea
Infection in Acute
exacerbation of COPD

Anthonisen NR et al. Antibiotic therapy in exacerbations of
chronic obstructive pulmonary disease. Ann Intern Med
1987;106:196–204.
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three groups
 Type 1 : increased breathlessness , sputum volume and
purulence
 type 2 : presence of two of these symptoms,
 and type 3: the presence of one of these symptoms in +
either recent URTI( 5 days), fever, increase wheezing or
cough , increased HR or Resp rate > 20 % baseline addition
to one of the following: an upper
Acute exacerbation of COPD
etiology
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CAUSES OF ACUTE EXACERBATIONS OF
COPD
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Respiratory infections 50-70% ( bacteria, viruses
atypical organisms)
10 % due to environmental pollution
30 % unknown etiology
heart failure
Pulmonary emboli
Pulmonary Embolism in Patients with Unexplained
Exacerbation of Chronic Obstructive Pulmonary Disease:
Prevalence and Risk Factors.
Tillie-Leblond et al , Ann Intern Med. 2006;144:390-396.
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Prospective cohort study in a single centre in France
211 consecutive patients admitted with unexplained
AECOPD not requiring (NIV)
All patients underwent CTPA, venous doppler US
within 48 hrs.
197 had were analyzed ( 14 patients were excluded)
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49 of 197 patients (25% [95% CI, 19% to 32%]) had PE
Most important risk factors
 previous thromboembolic disease (risk ratio, 2.43 [CI, 1.49
to 3.94],
 malignant disease (risk ratio, 1.82 [CI, 1.13 to 2.92])
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decrease in PCO2of > 5 mm Hg (risk ratio, 2.10 [CI, 1.23
to 3.58].
Acute exacerbation of COPD
Management issues
Acute exacerbation of COPD
treatment
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Oxygen therapy
Pharmacological intervention
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Bronchodilators
Steroids
Antibiotics
methylxanthines
Assisted ventilation
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Non invasive
invasive
Treatment : oxygen therapy
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Response to oxygen administration — 3 possible
outcomes
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The patient's clinical state and PaCO2 may improve or not
change
The patient may become drowsy but arousable in these
cases, the PaCO2 generally rises slowly by up to 20 mmHg
and then stabilizes after approximately 12 hours
The patient rapidly becomes unconscious, cough becomes
ineffective, and the PaCO2 rises at a rate of 30 mmHg or
more per hour
complete withdrawal of oxygen if hypercapnea
worsens is more dangerous .
Effects of the administration of O2 on ventilation and blood gases
in patients with chronic obstructive pulmonary disease during acute
respiratory failure.
Aubier M et al , Am Rev Respir Dis. 1980;122(5):747.
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Patients with severe COPD in ARF were given 100%
oxygen and the effect on ventilation, RR, TV, PaCO2
were measured
minute ventilation was reduced by 14% but returned
to within 93% of baseline within 12 minutes
PaCO2 increased by 23 mm Hg on average
This was due to several factors ( haldane effect ,
worsening V/Q mismatch)
BTS guideline for emergency oxygen use in
adult patients,
B R O’Driscoll Thorax 2008;63(Suppl VI):vi1–vi68
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Look for oxygen alert card that patient may have
People at risk for hypercapnea , initially one should
use venturi mask at 24%. ( nasal canula 1- liters
per minute)
urgent ABG should be done for such patient
Follow up ABG should be done within 30-45 minutes
after initiating oxygen therapy
Pre specified target oxygen saturation should be used
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For COPD or risk of hypercapnea 88-92%
Other conditions 94-98%
Bronchodilator therapy
solution contains in Mcg
 How much does 1 ml of salbutamole solution
(not nebules) contains in mg
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2.5 mg
5 mg
How much does 1 ml of ipratropium Bromide
contains in Mcg
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It comes in 2 concentration ( nebule)
250 mcg per 2.5 nebule
500 mcg per 2.5 ml nebule
A Randomized Controlled Trial To Assess the
Optimal Dose and Effect of Nebulized Albuterol in
Acute Exacerbations of COPD
S Nair et al CHEST 2005; 128:48–54
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86 patients presented to ED with AECOPD.
Patients randomized to either 2.5 mg or 5 mg
of Salbutamole every 4 hrs. after initially had
multiple doses of Salbutamole by MDI
The patients were followed until discharge
and prior to discharge again a dose response
curve after MDI was constructed
A Randomized Controlled Trial To Assess the
Optimal Dose and Effect of Nebulized Albuterol in
Acute Exacerbations of COPD
S Nair et al CHEST 2005; 128:48–54


86 patients presented to ED with AECOPD.
Patients randomized to either 2.5 mg or 5 mg
of Salbutamole every 4 hrs. after initially had
multiple doses of Salbutamole by MDI
A Randomized Controlled Trial To Assess the
Optimal Dose and Effect of Nebulized Albuterol in
Acute Exacerbations of COPD
S Nair et al CHEST 2005; 128:48–54
Patient on 2.5 mg by neb
N = 40
On discharge
Patient on 5 mg by neb
N = 46
On discharge
On admission
On admission
Dose response curve to MDI
Dose response curve to MDI
Recommendation for bronchodilators
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Either MDI wit spacer or nebulizer can be
used
Adding short acting anticholinergic was
shown to be beneficial in some studies.
More frequent doses ( every 20 minutes) for
three doses then hourly may be needed.
Steroid therapy

Effect of systemic glucocorticoids on exacerbations of
chronic obstructive pulmonary disease. Dennis
Niewoehner et al , N Engl J Med 1999;340:1941-7.

Short-term vs conventional glucocorticoid therapy in
acute exacerbations of chronic obstructive pulmonary
disease: the REDUCE randomized clinical trial.
Leuppi JD et al , JAMA. 2013 Jun;309(21):2223-31.
Effect of systemic glucocorticoids on exacerbations of
chronic obstructive pulmonary disease. Dennis Niewoehner
et al , N Engl J Med 1999;340:1941-7
RCT in 25 centres in the US.
271 patients admitted for AECOPD
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Steroid dose
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80 received steroid for 8 weeks
80 received steroids for 2 wks
111 received placebo
Solumedrole 125 mg IV q 6 hrs. for 3 days then oral
treatment 60 mg daily
Follow up for 6 months (180 days)
Primary outcome is treatment failure defined as
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Death, intubation, readmission for COPD, escalation of
therapy
Effect of systemic glucocorticoids on exacerbations of
chronic obstructive pulmonary disease. Dennis Niewoehner
et al , N Engl J Med 1999;340:1941-7
results
Effect of systemic glucocorticoids on exacerbations of
chronic obstructive pulmonary disease. Dennis Niewoehner
et al , N Engl J Med 1999;340:1941-7
results
Effect of systemic glucocorticoids on exacerbations of
chronic obstructive pulmonary disease.
Dennis Niewoehner et al , N Engl J Med 1999;340:1941-7
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Conclusion
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Steroid therapy does have moderate benefit in
AECOPD.
2 wks. therapy is similar to 8 wks.
There is significant hyperglycemia in the steroid
group.
A number of patients in the 8 wks. Group was
admitted for serious infection.
Short-term vs conventional glucocorticoid therapy in
acute exacerbations of chronic obstructive pulmonary
disease: the REDUCE randomized clinical trial.
Leuppi JD et al , JAMA. 2013 Jun;309(21):2223-31.
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REDUCE (Reduction in the Use of Corticosteroids in
Exacerbated COPD)
314 patients presenting to ED with AECOPD to 5
swiss teaching hospitals, (289, 92% admitted to
hospital.
Intervention
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outcome
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5 days of Prednisone 40 mg daily VS 14 days
Primary end point time to next exacerbation
Secondary outcomes (FEV1, Death )
Follow up for 6 months
Short-term vs conventional glucocorticoid therapy in acute
Intention tooftreat
exacerbations
chronic obstructive pulmonary
Per disease:
protocol The
analysis
analysis
REDUCE
randomized clinical trial.
Leuppi JD et al , JAMA. 2013 Jun;309(21):2223-31.
Time to re-exacerbation
Short-term vs conventional glucocorticoid therapy in acute
exacerbations of chronic obstructive pulmonary disease: The
Deathrandomized clinical trial.
Death or exacerbation
REDUCE
Leuppi JD et al , JAMA. 2013 Jun;309(21):2223-31.
Survival curve
Short-term vs conventional glucocorticoid therapy in acute
exacerbations of chronic obstructive pulmonary disease: The
REDUCE randomized clinical trial.
Leuppi JD et al , JAMA. 2013 Jun;309(21):2223-31.
FEV1
Steroid dose for exacerbation
Conclusion
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Systemic steroid
Oral treatment is as effective as IV.
If you use IV , restrict to 24 or 48 hrs.
5 days is adequate
NO need for tapering or overlap
Inhaled steroid
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There is no evidence for concomitant
addition of nebulized steroid during
exacerbation
Use of antibiotics
indication for starting antibiotics
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Increase sputum volume or purulence
Severe exacerbation ( requiring NIV)
Some advocate use it for all hospitalized patients
The indication for antibiotics in OPD exacerbation
without symptoms suggestive of infection is weak
Procalcitonin to initiate or discontinue antibiotics in
acute respiratory tract infections. Schuetz P, Cochrane
Database Syst Rev. 2012;9:CD007498.
Use of antibiotics in AECOPD
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Frequency of pathogens
Atypical organisms e.g Chlamydia, Mycoplasma.
legionella are rare in AECOPD
Choice of antibiotics
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Risk of pseudomonas infection
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recent hospitalization in the past 90 days.
frequent administration of antibiotics (≥4 courses
within the past year).
severe COPD (FEV1 <50 percent of predicted).
isolation of Pseudomonas aeruginosa during a
previous exacerbation,
colonization during a stable period, and systemic
glucocorticoid use
Choice of antibiotics in hospitalized
patients
Take home message
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AECOPD is different from pneumonia
Appropriate treatment
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Appropriate oxygen therapy from ED
Proper dose and frequency of bronchodilators
Steroid therapy for 5 days only without tapering
Most patients with hospitalized AECOPD needs
antibiotics ( single agent is adequate)
NIV for any patient with respiratory acidosis
Inadequate response of symptoms
to outpatient management
Marked increase in dyspnea
Inability to eat or sleep due to
symptoms
Worsening hypoxemia
Worsening hypercapnia
Changes in mental status
Inability to care for oneself (ie, lack
of home support)
Uncertain diagnosis
High risk comorbidities including
pneumonia, cardiac arrhythmia,
heart failure, diabetes mellitus,
A high FiO2 is not required to correct the
hypoxemia associated with most acute
exacerbations of COPD. Inability to
correct hypoxemia with a relatively low
FiO2 (eg, 4 L/min by nasal cannula or 35
percent by mask) should prompt
consideration of pulmonary emboli,
acute respiratory distress syndrome,
pulmonary edema, or severe pneumonia
as the cause of respiratory failure. (
Response to oxygen administration — There
are three possible outcomes when administering
uncontrolled oxygen therapy to a patient with
COPD and respiratory insufficiency [28]:
The patient's clinical state and PaCO2 may
improve or not change
The patient may become drowsy but can be
roused to cooperate with therapy; in these cases,
the PaCO2 generally rises slowly by up to 20
mmHg and then stabilizes after approximately 12
hours
The patient rapidly becomes unconscious, cough
becomes ineffective, and the PaCO2 rises at a
rate of 30 mmHg or more per hour
The risk for developing severe hypercapnia and
CO2 narcosis is greater in patients with a low
initial pH and/or PaO2 [28,29].
In a retrospective study of 95 patients with COPD
PROGNOSIS — Acute exacerbations of
COPD are associated with increased
mortality after hospital discharge.
It is estimated that 14 percent of patients
admitted for an exacerbation of COPD will
die within three months of admission
[47,48].
Among 1016 patients with an acute
exacerbation of COPD and a PaCO2 of 50
mmHg or more, the 6 and 12 month
mortality rates were 33 and 43 percent,
respectively [49].
In a study of 260 patients admitted with a
COPD exacerbation, the one year mortality
was 28 percent [50]. Independent risk
factors for mortality were age, male
gender, prior hospitalization for COPD,