Management of acute exacerbation of COPD in hospitalized patients

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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

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question

• On a beautiful Friday afternoon like today Id
  rather be
• A) outside with the family having fun
• B) sitting here listening to Naser Behbehani

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1st question

• 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) dont know

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2nd question

• 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
• A) Amoxicillin-clavulinic acid
• B) Ceftriaxone Clarithromycin
• C) 3rd generation cephalosporin alone
• D) 2nd generation cephalosporin alone
• E) a respiratory quinolone ( levofloxacin-
  Moxifloxacin )

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3rd question

• the most likely steroid dose that patients
  admitted with AECOPD will receive at our
  hospital
• 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

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4th question

• Almost all patients admitted with AECOPD receive
  nebulized steroid ( budesonide ) on top of IV
  or oral steroids
• A) yes
• B) No

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Case presentation

• 75 year old man ex smoker known to have ,
• 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

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Case presentation

• Physical examination
• Heart rate 90/ min , Resp rate 26 , saturation
  96 on room air, Temp 37.0
• Marked bilateral wheeze
• CXR
• ABG
• Ph 7.51, PO2 26.9 Kpa, 3.13 Kpa , HCO3 18
  mmole

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Course in hospital

• Admitted 16th Feb to 7th March ( 3 weeks)
• In hospital treatment
• 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

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Course in hospital

• Echo was done
• CT chest was done
• no spirometry done ( daily notes say bilateral
  expiratory wheeze)
• treatment on discharge

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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
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Final outcome
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Larger dose does not mean better
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Acute exacerbation of COPD

• Definition according to WHO document
• Significant increase in any of these symptoms
  beyond day today variation
• Cough in severity or frequency
• Sputum in volume or colour
• dyspnea

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Infection in Acute exacerbation of COPD

• Anthonisen NR et al. Antibiotic therapy in
  exacerbations of chronic obstructive pulmonary
  disease. Ann Intern Med 1987106196204.
• 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 gt
  20 baseline addition to one of the following
  an upper

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Acute exacerbation of COPD etiology

• CAUSES OF ACUTE EXACERBATIONS OF COPD
• Respiratory infections 50-70 ( bacteria, viruses
  atypical organisms)
• 10 due to environmental pollution
• 30 unknown etiology
• heart failure
• Pulmonary emboli

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Pulmonary Embolism in Patients with Unexplained
Exacerbation of Chronic Obstructive Pulmonary
Disease Prevalence and Risk Factors.
Tillie-Leblond et al , Ann Intern Med.
2006144390-396.

• 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)
• 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)
• decrease in PCO2 of gt 5 mm Hg (risk ratio,
  2.10 CI, 1.23 to 3.58.

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Acute exacerbation of COPD

• Management issues

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Acute exacerbation of COPD treatment

• Oxygen therapy
• Pharmacological intervention
• Bronchodilators
• Steroids
• Antibiotics
• methylxanthines
• Assisted ventilation
• Non invasive
• invasive

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Treatment oxygen therapy

• Response to oxygen administration  3 possible
  outcomes
• 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 .

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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. 1980122(5)747.

• 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)

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BTS guideline for emergency oxygen use in adult
patients, B R ODriscoll Thorax 200863(Suppl
VI)vi1vi68

• 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
• For COPD or risk of hypercapnea 88-92
• Other conditions 94-98

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Bronchodilator therapy

• solution contains in Mcg
• How much does 1 ml of salbutamole solution (not
  nebules) contains in mg
• 2.5 mg
• 5 mg
• How much does 1 ml of ipratropium Bromide
  contains in Mcg
• It comes in 2 concentration ( nebule)
• 250 mcg per 2.5 nebule
• 500 mcg per 2.5 ml nebule

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A Randomized Controlled Trial To Assess the
Optimal Dose and Effect of Nebulized Albuterol in
Acute Exacerbations of COPDS Nair et al CHEST
2005 1284854

• 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

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A Randomized Controlled Trial To Assess the
Optimal Dose and Effect of Nebulized Albuterol in
Acute Exacerbations of COPDS Nair et al CHEST
2005 1284854

• 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

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A Randomized Controlled Trial To Assess the
Optimal Dose and Effect of Nebulized Albuterol in
Acute Exacerbations of COPDS Nair et al CHEST
2005 1284854
On discharge
On discharge
On admission
On admission
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Recommendation for bronchodilators

• 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.

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Steroid therapy

• Effect of systemic glucocorticoids on
  exacerbations of chronic obstructive pulmonary
  disease. Dennis Niewoehner et al , N Engl J Med
  19993401941-7.
• 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 Jun309(21)2223-31.

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Effect of systemic glucocorticoids on
exacerbations of chronic obstructive pulmonary
disease. Dennis Niewoehner et al , N Engl J Med
19993401941-7

• RCT in 25 centres in the US.
• 271 patients admitted for AECOPD
• 80 received steroid for 8 weeks
• 80 received steroids for 2 wks
• 111 received placebo
• Steroid dose
• 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
• Death, intubation, readmission for COPD,
  escalation of therapy

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Effect of systemic glucocorticoids on
exacerbations of chronic obstructive pulmonary
disease. Dennis Niewoehner et al , N Engl J Med
19993401941-7 results

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Effect of systemic glucocorticoids on
exacerbations of chronic obstructive pulmonary
disease. Dennis Niewoehner et al , N Engl J Med
19993401941-7 results

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Effect of systemic glucocorticoids on
exacerbations of chronic obstructive pulmonary
disease. Dennis Niewoehner et al , N Engl J Med
19993401941-7

• Conclusion
• 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.

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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
Jun309(21)2223-31.

• 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
• 5 days of Prednisone 40 mg daily VS 14 days
• outcome
• Primary end point time to next exacerbation
• Secondary outcomes (FEV1, Death )
• Follow up for 6 months

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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
Jun309(21)2223-31.
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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
Jun309(21)2223-31.
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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
Jun309(21)2223-31.
FEV1
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Steroid dose for exacerbation Conclusion
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
• There is no evidence for concomitant addition
  of nebulized steroid during exacerbation

Inhaled steroid
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Use of antibioticsindication for starting
antibiotics

• 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. 20129CD007498.

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Use of antibiotics in AECOPD

• Frequency of pathogens

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Choice of antibiotics

• Risk of pseudomonas infection
• recent hospitalization in the past 90 days.
• frequent administration of antibiotics (4
  courses within the past year).
• severe COPD (FEV1 lt50 percent of predicted).
• isolation of Pseudomonas aeruginosa during a
  previous exacerbation,
• colonization during a stable period, and systemic
  glucocorticoid use

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Choice of antibiotics in hospitalized patients
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Take home message

• AECOPD is different from pneumonia
• Appropriate treatment
• 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

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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,
renal failure, or liver failure
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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. (
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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 and hypercapnia who
presented with acute respiratory distress, oxygen
therapy targeting a PaO2 gt74 mmHg was associated
with increased length of stay, increased need for
noninvasive mechanical ventilation, and increased
rate of admission to an ICU 30. A causal
relationship cannot be concluded, however, due to
the study's observational design. Effect of
withdrawing oxygen  The major danger facing
patients who develop hypercapnia during treatment
with oxygen is that the abrupt removal of
supplemental oxygen may cause the PaO2 to fall to
a level 
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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,
PaCO245 mmHg (6 kPa), and urea
gt8 mmol/L. Patients hospitalized for a COPD
exacerbation who have a Pseudomonas aeruginosa in
their sputum have an increased risk of mortality
at three years than those without (59 versus 35
percent, HR 2.33, 95 CI 1.29-3.86), independent
of age, comorbidity, or COPD severity 51
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