1. BY MELISSA JAKUBOWSKI PULMONARY DISEASE TREATMENT CONCERNING COPD

2. AGENDA Introduce the journal article Review of preliminary background Discuss the details of the study Evaluation of the study Discuss how the implications of the study translate into practice Questions

3. JOURNAL ARTICLE Efficacy of corticosteroid therapy in patients with an acute exacerbation of chronic obstructive pulmonary disease receiving ventilatory support

4. THIS STUDY ASSESSED: The effect of systemic corticosteroids on ICU patients who were mechanically ventilated (invasive or noninvasive) due to COPD exacerbations

5. IMPORTANCE Previous randomized trials assessing the effect of systemic corticosteroid therapy on COPD exacerbations have excluded patients with respiratory failure who required mechanical ventilation or ICU admission Critically ill patients in the ICU are more prone to develop complications potentially associated with corticosteroid therapy

6. HOSPITAL TREATMENT FOR COPD Bronchodilators Antibiotics Oxygen Corticosteroids

7. COPD AND CORTICOSTEROID THERAPY COPD: airways damaged interfering with the exchange of oxygen and carbon dioxide in the lungs Function: reduce lung and bronchial tube inflammation related to tissue damage and improve respiratory function

8. SHORT-TERM SIDE EFFECTS Increased appetite Fluid retention Weight gain Increased blood pressure Hyperglycemia

9. SYSTEMIC STEROIDS, CORTICOSTEROIDS Prednisone Prednisolone Methylprednisolone Betamethasone Beclamethasone Dexamethasone Flurocortisone Hydrocortisone Triamcinolone

10. SCREENING FOR SUBJECTS Screening: 354 patients from 8 hospitals in 4 countries from July 2005 – July 2009 Criteria: hospitalization because of exacerbation of COPD requiring ventilatory support in the ICU Controls: diagnosis of “exacerbation of COPD” was explicitly defined; patients with conditions that would alter integrity of study were excluded

11. ETHICS Approved by the ethics committee at each hospital Written informed consent obtained from patients or their surrogates

12. STUDY POPULATION 354 patients screened for eligibility 46 Patients with conventional mechanical ventilation 37 Patients with noninvasive mechanical ventilation 271 (76%) patients excluded 165 Steroid treatment 42 Pneumonia 23 Refused consent 34 Other

13. BASELINE CHARACTERISTICS CharacteristicPlacebo Group (n=40) Corticosteroid Group (n=43) P Value Age (year)67.669.10.52 Men (%)34320.23 SAPS II36.3 0.99 Comorbid condition (%) DM2235 0.07 Reason for acute exacerbation of COPD (%) 0.72 Initial ventilatory support (%) 0.60 Blood gases0.72 Blood glucose (mg/dL) 158.7193.30.02

14. STUDY DESIGN Within 24 hours after ICU admission, patients randomly assigned to either corticosteroid group or placebo group 46 Patients with conventional mechanical ventilation 25 Patients assigned to receive corticosteroids 21 Patients assigned to receive placebo 19 Patients assigned to receive placebo 18 Patients assigned to receive corticosteroids 37 Patients with noninvasive mechanical ventilation

15. LENGTH OF ADMINISTRATION: 10 DAYS Treatment Group Methylprednisolone Placebo Group Normal saline solution

16. ADMINISTRATION REGIMEN Days 1-3 0.5 mg/kg every 6 hours Day 4-6 0.5 mg/kg every 12 hours Days 7-10 0.5 mg/kg per day

17. OUTCOME MEASURES Duration of mechanical ventilation, d Length of ICU stay, d Length of hospital stay, d In-ICU mortality, % Failure of NIMV, % Reintubation within 48 hours of planned extubation and received CMV either initially or after failure of NIMV, %

18. FREQUENCY OF ADVERSE EVENTS Superinfection Gastrointestinal bleeding Arterial hypertension Hyperglycemia Ventilator-associated pneumonia Delirium ICU-acquired paresis

19. OTHER DAILY MEASUREMENTS ABG analysis C-reactive protein Maximal blood glucose level Daily dose of insulin PEEP (positive end-expiratory pressure): only in patients who were intubated

20. RESULTS: OUTCOME MEASURES OutcomePlacebo GroupCorticosteroid Group P Value Duration of mechanical ventilation, d 430.04 Length of ICU stay, d 760.09 Length of hospital stay, d 15130.30 In-ICU mortality, % 10120.81 Failure of NIMV, % 3700.004 Reintubation within 48h, % 19140.71

21. REDUCTION IN DURATION OF MECHANICAL VENTILATION

22. REDUCTION IN THE INCIDENCE OF NIV FAILURE

23. FREQUENCY OF ADVERSE EVENTS EventPlacebo GroupCorticosteroid Group P Value Superinfection650.65 GI bleeding220.60 Arterial HTN420.42 Hyperglycemia10200.04 Vent-associated pneumonia 340.77 Delirium310.35 ICU-acquired paresis 00…

24. PROS VS. CONS Pros Modest reduction in the duration of mechanical ventilation Increased success of NIMV Trend towards shorter ICU stay Cons Hyperglycemia

25. EVALUATION OF THE STUDY : PROS 1 st study to confirm the benefits of systemic corticosteroid therapy for ICU patients receiving MV for COPD exacerbation Validates its usage in clinical practice today Double-blinded experiment Source of funding

26. PROS (CONTINUED) Funded by University of Vall d’Hebron Hospital, Laboratory of Experimental Cardiology (LEC) LEC mission statement: “to contribute to lessen the impact of cardiovascular diseases on survival capacity and quality of life of the general population by elucidating the mechanisms of disease and proposing new treatments”

27. EVALUATION OF THE STUDY: CONS Results will not have an impact on current clinical treatment practice guidelines Sample size was small (83) Length of study (5 years) Does not mention the effect of the drug on eating behavior

28. RESOURCE Alia I, de la Cal MA, Esteban A, et al. Efficacy of corticosteroid therapy in patients with an acute exacerbation of chronic obstructive pulmonary disease receiving ventilatory support. Arch Intern Med. 2011;171(21):1939- 1946. Accessed April 13, 2012.

29. ADDITIONAL THOUGHTS What about corticosteroid long- term side-effects? Optimal dose and length of treatment? How do the findings translate into practice?

30. QUESTIONS