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Educational Objectives:
After evaluating this article participants will be able to:
-Discuss the current, evidence-based treatment recommendations for patients with acute exacerbations of COPD (AECOPD)
-Incorporate corticosteroids into clinical practice, based on evidence-based standards
-Rationally prescribe antibiotics, based on their benefits and limitations
-Employ non-invasive positive pressure ventilation in appropriate cases

 
The Setup:
You are working in a busy ED when a 58-year-old male presents with worsening dyspnea over a few days, with increasing cough and purulent sputum production. He is well known to your ED as a lifelong smoker with moderate to severe COPD with increasing exacerbations. Your clinical assessment reveals a patient with moderate respiratory distress, audible wheezing and oxygen saturation of 90% (room air), but who is otherwise speaking normally and mentating well with normal vital signs. You initiate short-acting bronchodilators (beta-agonists, anticholinergics), while pondering your other treatment options…

Your Choices:
You have determined that your patient is having a AECOPD. Based on his past history of stable, moderate COPD and recent worsening symptoms, he will need to be admitted. In addition to bronchodilator therapy, you consider the following questions:
(1) Does this patient need steroids? If so, in what form and by what route?
(2) Does this patient need antibiotics (Abx)? If so, which one(s)?
(3) Can this patient use non-invasive positive pressure ventilation (NIPPV), or should we just intubate him if he deteriorates?

The Evidence:
Quon, BS, Gan, WQ, Sin, DD. Chest 2008; 133: 756-766. Contemporary Management of Acute Exacerbations of COPD: A Systematic Review and Metaanalysis.


Study Design: This article was a systematic review and meta-analysis of all relevant randomized trials aimed at treatment interventions for AECOPD. The authors examined all trials relevant to the use of steroids, antibiotics and NIPPV for AECOPD.

Population: Adult patients (age 50+ years in reported studies), with AECOPD. Patients met the Global Initiative for Chronic Obstructive Lung Disease (GOLD) definition of COPD: a change in baseline dyspnea, cough, and/or sputum beyond day-to-day variation that might mandate medication change. Mixed patient settings.

Interventions: Systemic corticosteroids (IV, PO dosing; 6 studies methylprednisolone, 2 each prednisone or hydrocortisone), antibiotics (in and out patient settings; beta-lactams 43%, tetracyclines 29%), NIPPV

Comparator: Standard therapy (placebo for corticosteroid (CS) trials and Abx trials; doxapram for NIPPV trials)

Outcomes: Risk of treatment failures, hospital length-of-stay (LOS), intubation rates, in-hospital mortality. Treatment failure defined as either clinical deterioration, study withdrawal due to unsatisfactory clinical improvement, or relapse of exacerbation symptoms during follow-up period.

Appraisal of Evidence: This meta-analysis was comprehensive in its search strategy and rating of quality of evidence. There was no significant heterogeneity amongst the trials examining steroids and NIPPV in treating AECOPD, but there was among the antibiotics trials (based on difference between inpatient vs. outpatient treatment settings). Heterogeneity is defined as study-to-study variability beyond that expected by chance alone suggesting that the design may be measuring different populations, interventions, or outcomes and ought not be combined into a meta-analysis.
 
The Results: The results of the meta-analysis are summarized in the table.

click on chart to view pdf
alt

Subgroups
•Trend to increased benefit of NIPPV to avoid intubation with lower initial pH values.
•No significant benefits for Abx on short-term lung FEV measures, blood gases or hospital LOS.
•No significant differences noted between Abx classes studied.

How do I apply this information to my patients?

1) Systemic corticosteroids reduce treatment failures by 46% in combined in- and out-patient AECOPD exacerbations, and there is no difference in efficacy between parenteral or orally administered corticosteroids.

2) Antibiotics reduced treatment failure by 46% and improved survival in hospitalized patients. There were no benefits noted in outpatients (2 studies). These results must be interpreted with caution in light of significant heterogeneity amongst compared Abx trials. Only 3 studies examining Abx benefits on AECOPD outcomes have been conducted since 1987, likely reflecting the accepted practice of using Abx for AECOPD.

3) Antibiotics and NIPPV were both found to reduce in-hospital mortality, with moret robust trials in the NIPPV groups. It is hypothesized that the Abx benefits were most realized in those patients with nosocomial infections and intubated patients at risk of venilator-associated pneumonia.

4) NIPPV significantly reduced intubation and hospital LOS, as well as in-hospital mortality. Greater benefits to reduce intubation were noted with lower initial pH measures (reflecting more severe respiratory acidosis). This finding is in keeping with GOLD recommendations to apply NIPPV to AECOPD patients with pH <7.35.
While there may be other indications for the use of NIPPV for AECOPD, they extend beyond the conclusions supported by this article.

Case Resolution:
Based on your assessment of this patient having a severe AECOPD presentation needing admission, you decide to treat this patient with systemic steroids, antibiotics (based on local practices), and NIPPV. The patient steadily improves in the ED, and is transferred to an inpatient ward…

Commentary:
In a disease with increasing incidence and high burden of hospitalization (avg. cost $660/day), admission to ICU (25%) and in-hospital mortality (10%), it is important to identify those interventions that will reduce important patient and system outcomes (treatment failure, hospital LOS, intubation rates, mortality). This study identifies interventions that will reduce a number of these negative outcomes in hospitalized patients.

Although systemic steroids and antibiotics seem to still be the standard of care, it is not as clear from this study which patients can benefit from various interventions in the ambulatory setting,

Suneel Upadhye, MD, MSc, is an Assistant Clinical Professor/Undergraduate Coordinator, Division of Emergency Medicine, McMaster University



     

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