Management of acute exacerbation of COPD in hospitalized patients

Management of acute exacerbation of COPD in hospitalized patients

Prof. Nasser Behbehani 1st Kuwait North America update in

Internal Medicine4th medical scientific conference

Mubarak Alkabeer hospital

question On a beautiful Friday afternoon like

today I’d rather be A) outside with the family having fun B) sitting here listening to Naser Behbehani

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) don’t know

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 )

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

4th question Almost all patients admitted with AECOPD

receive nebulized steroid ( budesonide ) on top of IV or oral steroids

A) yes B) No

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

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

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

Course in hospital

Echo was done CT chest was done no spirometry done ( daily notes say

bilateral expiratory wheeze) treatment on discharge

On discharge

Total steroid dose1) 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 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

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.

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 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

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.

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 > 5 mm Hg (risk ratio, 2.10 [CI, 1.23 to

3.58].


Management issues


treatment Oxygen therapy Pharmacological intervention

Bronchodilators Steroids Antibiotics methylxanthines

Assisted ventilation Non invasive invasive

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 .

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.

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

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%

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

A Randomized Controlled Trial To Assess the Optimal Dose and Effect of Nebulized Albuterol in Acute Exacerbations of COPDS 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

The patients were followed until discharge and prior to discharge again a dose response curve after MDI was constructed


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


Dose response curve to MDI

Patient on 2.5 mg by nebN = 40

Dose response curve to MDI

Patient on 5 mg by nebN = 46

On admission

On discharge On discharge

On admission

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.

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

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

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

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.

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.

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

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.

Time to re-exacerbation

Intention to treat analysis

Per protocol analysis


Survival curve

Death Death or exacerbation


FEV1

Steroid dose for exacerbation Conclusion

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

Systemic steroid

Inhaled steroid

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. 2012;9:CD007498.

Use of antibiotics in AECOPD

Frequency of pathogens

Atypical organisms e.g Chlamydia, Mycoplasma. legionella are rare in AECOPD

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 <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

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

Inadequate response of symptoms to outpatient managementMarked increase in dyspneaInability to eat or sleep due to symptomsWorsening hypoxemiaWorsening hypercapniaChanges in mental statusInability to care for oneself (ie, lack of home support)Uncertain diagnosisHigh risk comorbidities including pneumonia, cardiac arrhythmia, heart failure, diabetes mellitus, renal failure, or liver failure

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 changeThe 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 hoursThe patient rapidly becomes unconscious, cough becomes ineffective, and the PaCO2 rises at a rate of 30 mmHg or more per hourThe 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 >74 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

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, PaCO2≥45 mmHg (6 kPa), and urea >8 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]

Documents

Management of acute exacerbation of COPD in hospitalized patients