Routes of Steroid Administration for COPD Exacerbation

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USE OF STEROIDS IN PATIENTS
WITH COPD EXACERBATION
Richard C. Walls
Patient Case: JS


64 yo female who presented with increasing shortness of
breath, wheezing, and hypoxia that did not adequately
respond to oxygen supplementation and intensified
bronchodilator therapy.
PMH and Home Medications

Atrial Fibrilation






Duloxetine 30 mg daily
Lorazepam 1 mg BID prn
Quetiapine 150 mg qhs
COPD

Ipratropium 2.5 mL q6h prn
Hypothyroidism

Aspirin 81 mg daily
Digoxin 0.25 mg daily
Diltiazem 240 mg daily


Metformin 500 mg BID
Hyperlipidemia


Levothyroxine 25 µg daily
Type II Diabetes

Depression/Anxiety



Simvastatin 20 mg qhs
Inpatient Medications



Albuterol 2.5 mg prn
Azithromycin 500 mg po
Methylprednisolone 60 mg IV
Why Steroids?

Niewoehner et al. (1999)1
 271
patients: 3 Treatment Groups
 Placebo
(n=111)
 3 days of methylprednisolone 125 mg q6h IV followed by


Oral prednisone tapered over 2 weeks (n=80)
Oral prednisone tapered over 8 weeks (n=80)
 Primary
outcome: death, intubation, readmission, or
intensification of COPD therapy
Why Steroids?
Percentage of Patients With a Primary Outcome Event1
Placebo
2 Weeks Steroids
8 Weeks Steroids
30 days
33% (3% death)
24% (0%)
22% (2%)
90 days
48% (4%)
38% (2%)
36% (2%)
6 months
54% (4%)
49% (2%)
52% (4%)

Fewer events with steroids after 30 & 90 days





No effect on mortality
No effect on all-cause mortality
No difference between duration of steroid treatment
Placebo length of stay 1.2 days longer than steroid
More adverse events with steroids

Hyperglycemia the most common significant adverse event
Why Steroids?

Davies et al. (1999)2




14 days of 30 mg prednisone po (n=29) daily or placebo (n=27)
Greater increase FEV1 with prednisone (92% vs. 85% at day 5 of
treatment)
Placebo length of stay 2 days longer than steroid
GOLD guidelines3



Recommend 30-40 mg prednisolone daily for 10-14 days in patients
with COPD exacerbation
Recently updated (2013) to include all patients with COPD
exacerbations
Recommendation graded Evidence Category D indicating a panel
consensus judgment
Controversies



Is oral administration as effective as IV?
Is there a role for inhaled steroids in the treatment
of COPD exacerbations?
Does the evidence support 30-40 mg prednisone
daily for 10-14 days as an ideal regimen?
Oral vs. IV Steroids

de Jong et al. (2007)4



5 days of 60 mg prednisolone daily either IV (n=107) or po (n=103)
Evaluated treatment failure: death, ICU admission, readmission to ICU due to
COPD, or intensification of therapy within 90 days of treatment
Oral (56.3%) non-inferior to IV (61.7%)




Overall treatment failure higher than 2 week regimen in Niewoehner trial (38%)1
First three days of Niewoehner trial featured steroid doses 2.6 times higher5
No data reported on adverse events
Ceviker, Sayiner (2013)6





7 days of 32 mg methylprednisolone po daily (n=20)
4 days 1 mg/kg/day methylprednisolone IV then 3 days of 0.5 mg/kg/day (n=20)
Both groups showed improvement in FEV1 (49.1% oral vs. 40.0% IV)
Less incidence of hyperglycemia in oral (22.2% vs. 55%)
Did not compare equipotent steroid doses
Systemic vs. Inhaled Steroids

Gunen et al. (2009)7
 Reviewed
trials comparing nebulized budesonide to
systemic steroids
 No difference in efficacy, fewer adverse events
(especially hyperglycemia) with budesonide
 Only reviewed 7 trials
 Small
trials (Averaged 88 patients)
 Short trials (Longest was 16 days)
 3 of the trials were for asthma exacerbation
Implications for JS

Literature Summary
Suggest usefulness in COPD exacerbation
 No clearly ideal dose, duration, or route of administration
 Suggests dose-response/dose-toxicity relationship


Pertinent Patient Specific Factors
Type II Diabetes: Risk of hyperglycemia with high doses
 Exacerbation possibly secondary to infection: Do we really
want to expose JS to another route of infection?
 JS is currently tolerating oral medications
 Exacerbation is not so severe that it is immediately life
threatening

Implications for JS

Given the patient’s clinical picture that puts her at
risk for corticosteroid and IV access related
complications, IV therapy at this point is likely
inappropriate, and initiating a course of 30 mg oral
prednisone daily would be more appropriate.
References
1.
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6.
7.
Niewoehner DE, Erbland ML, Deupree RH, Collins D, Gross NJ, Light RW, et al. Effect of systemic
glucocorticoids on exacerbations of chronic obstructive pulmonary disease. Department of Veterans
Affairs Cooperative Study Group. N Engl J Med 1999 Jun 24;340(25):1941-1947.
Davies L, Angus RM, Calverley PM. Oral corticosteroids in patients admitted to hospital with
exacerbations of chronic obstructive pulmonary disease: a prospective randomised controlled trial. Lancet
1999 Aug 7;354(9177):456-460.
Global Initiative for Chronic Obstructive Lung Disease. Global Strategy for the Diagnosis, Management,
and Prevention of Chronic Obstructive Pulmonary Disease. NHLBI/WHO workshop report. Bethesda, MD:
National Heart, Lung, and Blood Institute; April 2001. Updated February
2013, http://www.goldcopd.com/ .
de Jong YP, Uil SM, Grotjohan HP, Postma DS, Kerstjens HA, van den Berg JW. Oral or IV prednisolone in
the treatment of COPD exacerbations: a randomized, controlled, double-blind study. Chest 2007
Dec;132(6):1741-1747.
National Adrenal Diseases Foundation. Corticosteriod Comparison Chart.
http://www.nadf.us/tools/adrenalhormone.pdf
Ceviker Y, Sayiner A. Comparison of two systemic steroid regimens for the treatment of COPD
exacerbations. Pulm Pharmacol Ther 2013 Mar 18.
Gunen H, Mirici A, Meral M, Akgun M. Steroids in acute exacerbations of chronic obstructive pulmonary
disease: are nebulized and systemic forms comparable? Curr Opin Pulm Med 2009 Mar;15(2):133-137.
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