- The patient presented with an acute exacerbation of COPD with respiratory acidosis and was treated with BiPAP, bronchodilators, antibiotics, and systemic corticosteroids. - Despite treatment, he developed hyperglycemia and hypertension which were managed by adjusting antihyperglycemic and antihypertensive medications. - He showed improvement in respiratory status and was discharged with a tapering course of prednisolone and other medications while continuing home BiPAP use.

1. Systemic in the Treatment of
of
1
臨床藥學與藥物科技研究所 陳秋縈
指導老師 李政宏醫師
2013. 10. 15

2. Age 79
Gender Male
HT/BW 168 cm/49.3 kg
BMI 17.5
2
Social History Smoking 4-5 PPD for
30+ years, quit at 2005
Family History Not contributory
Drug Allergy NKDA
Past medical history
• COPD with recurrent AE episode,
chronic CO2 retention
(baseline pCO2 ≈ 60 mmHg)
• CHF
• Old pulmonary TB
• Liver cirrhosis, HBV related, pugh A
• HTN
• Type 2 DM
• Gastric ulcer history (2012/11)
• CKD (Cr 1.7 mg/dL, eGFR 39)
Chief complaint
Conscious disturbance on 2013/08/01
Admission date 2013/08/01
Status A nursing home
resident
AE: Acute exacerbation

3. 3
2002 01/31 – 02/05 03/10 – 03/13
2005 06/24 – 07/09
2011 07/28 – 08/01 09/24 – 09/30 12/03 – 12/07
2012 07/26 – 07/31 10/05 – 10/12 11/13 – 11/16
2013 06/25 – 07/01
07/23
08/01 Emergency Department
• Some choking episode and whitish sputum recently
• SPO2 drop, dyspnea, drowsy conscious
Emergency Department
• Acute on CO2 retention, pneumonia
• 拒絕住院，Transfer to 台南市私立臨安老人養護中心
• Augmentin 875/125 mg/tab 1# BID x3 days

4. Physical Examination
 Conscious: E4V5M6
 Vital sign:
T/P/R=36.8/90/20 , BP= 135/66
 SpO2: 62% in room air
ABG: Respiratory acidosis
4
Room air After BiPAP used
pH 7.2 7.36
PaCO2 (mmHg) 111 75
PaO2 (mmHg) 210?? 61
HCO2 (mmol/L) 43.4 42.7
BE (mmol/L) 15.4 14.2
ABG: Arterial blood gas
Chest X ray
 Hyperinflation and increased
infiltrates over bilateral lung
without interval change

5. 5
檢驗項目 參考值 檢驗值
WBC(10^3/μL) 3.4-9.1 4.2
RBC(10^6/μL) 4.26-5.56 4.85
Hb(g/dL) 13.5-17 10.4
Hct(%) 39.1-48.9 36
MCV(fl) 82.6-97.4 74.2
MCH(pg) 28.5-34 21.5
MCHC(g/dL) 33.8-35.6 29
RDW(%) 11.9-14.3 19
Plt(10^3/μL) 138-353 77
Seg(%) 43-64 69.7
Eos(%) 0-1 0.9
Baso(%) 0-6 0.2
Mono(%) 3-9 7.7
Lymph(%) 27-47 21.5
檢驗項目 參考值 檢驗值
CREA(mg/dL) 0.7-1.5 1.73
eGFR 38
ALT(U/L) 0-54 38
NA(mmol/L) 135-148 140
K(mmol/L) 3.5-5 4.1
CRP(mg/L) 0-8 10.1
Impression:
• Acute exacerbation
of COPD with CO2 retention

6. Date Event Management
8/1 • COPD AE with acute CO2 retention • Gram stain and sputum culture
• BiPAP use and bronchodilator
Ipratropium/Salbutamol 1amp NEB q12h
• Corticosteroid
Methylprednisolone 20mg IVD q12h
• Empirical ABX
Unasyn 1500mg q12h
• Antihyperglycemic drugs
Sitagliptin 25mg qd
8/2 • Gram stain: GNB heavy
• Hyperglycemia
BS 161 209  305 349 mg/dL
• Hypertension
BP 173/85 mmHg
• Shift unasyn to piperacillin 4g IVD q8h
• Shift IV Methylprednisolone to
prednisolone 10mg bid
• Sitagliptin 50mg qd
• Amlodipine 5mg qd
Captopril 12.5mg tid
6
Admission
7/23 ED Sputum Culture
P. aeruginosa: Piperacillin S

7. Date Event Management
8/3 • Hyperglycemia
11am: 311 mg/dL
09pm: 315 mg/dL
• RI 8 IU SC STAT
8/4 • Still poor control of blood sugar
and blood pressure
• Shift amlodipine, captopril to
Nifedipine 20mg bid, Ramipril 10mg qd
• Repaglinide 0.5mg tid AC
8/5 • Afebrile, no respiratory distress,
bil clear breathing sound,
wheezing (-)
• CXR: no evidence of pneumonia
• 8/2 Sputum culture report
• Shift piperacillin to levofloxacin 500mg QD
• Taper steroid to prednisolone 5mg bid
7
8/2 Sputum culture report Pseudomonas aeruginosa Moderate
W.B.C.: >25 /LPF Piperacillin S Ciprofloxacin S
Epithelial cell: <5 /LPF Pip/Tazobactam S Imipenem S
Gentamicin S Ceftazidime S
Amikacin S Meropenem S
Levofloxacin S Cefepime S

8. Date Event Management
8/6 • Epigastric dullness, twice
vomiting after meal, hypoactive
bowel sound
• Metoclopramide 3.84mg tid AC
Famotidine 20mg bid
• Try home BiPAP use
8/7 • Discharge with home BiPAP use • Discharge medication x 5 days
Prednisolone 5mg BID
Levofloxacin 500mg QD AC
Ambroxol 30 TID
Sitagliptin 50mg QD
Nifedipine 20mg BID
Ramipril 10mg QD
Metoclopramide 3.84mg TID AC
Famotidine 20mg BID
8

9. 9
161
209
305
349
265
311
230
315
234
356
238
269
141
256 245
211
179
145 145 146
102
116
0
50
100
150
200
250
300
350
400
8/1 8/2 8/3 8/4 8/5 8/6 8/7
146
175
157
142
159
153
139
151
141 143
153 153
141
149 152
145
139
100
120
140
160
180
8/1 8/2 8/3 8/4 8/5 8/6 8/7
200
RI 8 IU SC STAT
Blood sugar (mg/dL)
Blood pressure (mmHg)
Sitagliptin 25mg qd 50mg qd
Repaglinide 0.5mg TID AC
Amlodipine 5mg qd
Captopril 12.5mg tid
Nifedipine 20 mg bid
Ramipril 10mg qd

10. 8/1 8/2 8/3 8/4 8/5 8/6 8/7
Ambroxol 30 mg tid
Ipratropium/salbutamol 1amp q12h q8h
Methylprednisolone
Prednisolone 10mg BID 5mg bid
Piperacillin 4g IVD q8h
Levofloxacin 500mg qd
Sitagliptin 25mg qd 50mg
RI 8IU st 8IU st
Repaglinide 0.5mg tid AC
Captopril 12.5mg bid AC
Amlodipine 5 mg QD
Nifedipine 20 mg BID
Ramipril 10mg QD
Metoclopramide 3.85mg tid AC
Famotidine 20mg bid
10
20mg IVD q12h
Admission
BS 349 mg/dL
BP 173/85 mmHg
Still poor control
of BS and BP
No dyspnea,
improving
Epigastric dullness,
vomiting
Discharge

11.  2013/08/08 - 2013/08/14
 Coffee grounding vomiting, abdominal distension, fatigue and
anorexia
 Admission due to UGI bleeding
  Pantoprazole, Metoclopramide
11

12.  Overview of AECOPD
 Epidemiology
 Treatment and Guideline recommendations
 Discussion
 What is the optimal steroid regimen ?
 Route and dose
 Duration
 To taper or not to taper
 Back to our patient
 Take home message
acute exacerbations of chronic obstructive pulmonary disease (AECOPD) 12

13. Definition
 An acute event characterized by a worsening of the patient’s
respiratory symptoms that is beyond normal day-to-day variations
and leads to a change in medication
Incidence/Prevalence
 Estimated 4%-10% prevalence of COPD worldwide
 Patients with COPD will experience 2–3 exacerbations/year
Causes:
 Respiratory tract infections (viral or bacterial)
 Air pollution
 Idiopathic (in about 33%)
131. Am J Respir Crit Care Med. 2013 Feb 15;187(4):347-65. 2. Am J Health Syst Pharm. 2010 Jul 1;67(13):1061-9
3. Chest 2003 May;123(5):1684

14. In-hospital mortality: 8–11%
 Mortality-related factors:
Older age, long-term use of oral corticosteroids, higher PaCO2, diabetes
 Hyperglycemia associated with higher mortality and longer hospital stay
Mortality after hospital discharge
 All-cause mortality up to 49% at 3 years after discharge
 40% at 1 year for patients requiring mechanical ventilation
141. Am J Respir Crit Care Med. 2013 Feb 15;187(4):347-65 2. Chest. 2003 Aug;124(2):459-67 3. Thorax 2006 Apr;61(4):284
Blood Glucose Mortality Median Length of Stay
< 108 mg/dL 12% 7 days
108-124 mg/dL 16% 9 days
126-160 mg/dL 21% 10 days
> 162 mg/dL 31% 12 days

15. Treatment goal
 To minimize the impact of the current exacerbation
 To prevent the development of subsequent exacerbations
Pharmacologic approach
 Short-acting bronchodilators
 Inhaled beta2-agonists with or without anticholinergics
 Antibiotics
 Increased Dyspnea, sputum volume, sputum purulence
 Require mechanical ventilation (invasive or noninvasive)
 Systemic corticosteroids
15Am J Respir Crit Care Med. 2013 Feb 15;187(4):347-65.

16. Title
Systemic corticosteroids for acute exacerbations of COPD
Cochrane Database Syst Rev 2009 Jan 21;(1):CD001288
Method
 Meta-analysis of 11 RCTs
 1,081 participants (81% male) with AECOPD
Results
Comparing vs.
 Treatment failure: OR 0.5 (95% CI 0.36-0.69), NNT 10
 Duration of hospitalization: mean difference -1.22 days (95% CI -
2.26 to -0.18 days)
 Improved FEV1, dyspnea, and blood gases at < 72 hours and at
end of treatment
 No significant difference in mortality
 Adverse drug event: OR 2.33 (95% CI 1.60-3.40), NNH 5
 Risk of hyperglycemia: OR 4.95 (95% CI 2.47-9.91), NNH 10
16

17. Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2013
• A dose of 30-40 mg prednisolone per day for 10–14 days is
recommended (Evidence D)
• Therapy with oral prednisolone is preferable
• Nebulized budesonide alone may be an alternative (although more
expensive) to oral corticosteroids in the treatment of exacerbations
American Thoracic Society/European Respiratory Society (ATS/ERS) 2004
• Oral prednisone 30–40 mg/day for 10 days
• If patient can not tolerate, give the equivalent dose i.v. for up 14 days
• Consider use inhaled corticosteroids by MDI or hand-held nebuliser
Am J Respir Crit Care Med. 2013 Feb 15;187(4):347-65.
Eur Respir J 2004;23:932–46.
17

18. Institute for Clinical Systems Improvement (ICSI) 2013
• Oral prednisone at 30-40 mg/day for 7-14 days
• Treatment beyond two weeks does not provide any additional benefit, but
does increase the likelihood of significant side effects such as hyperglycemia
• There is no need to discontinue inhaled steroids while the patient is taking oral
prednisone
Canadian Thoracic Society (CTS) 2008
• Oral or parenteral corticosteroids (dosages of 25-50 mg/day of prednisone
equivalent for 7-14 days)
National Institute for Health and Clinical Excellence (NICE) 2010
• Prednisolone 30 mg orally for 7-14 days
• Course of corticosteroid treatment should not be longer than 14 days as there
is no advantage in prolonged therapy
18
Institute for Clinical Systems Improvement (ICSI) http://www.icsi.org.
Can Respir J 2008;15(Suppl A):1A-8A.
BMJ 2010 Jun 25;340:c3134

19. 191. Am J Health Syst Pharm. 2010 Jul 1;67(13):1061-9. 2. Pharmacotherapy. 2006 Apr;26(4):522-32.
• Fewer treatment failures
• Reduce the risks of early relapse
• Shorter hospital length of stay
• Improve lung function (FEV1)
• Improve arterial hypoxemia
(PaO2)
• Hyperglycemia
• Fluid retention
• Elevated blood pressure
• Insomnia
• Mood swings/psychosis
• Gastrititis
• Imunosuppression/infection
• Fracture
Controversy about
optimal steroid regimen
Consensus of using systemic
corticosteroids
Adverse outcomes in medically
complex hospitalized patients

20. 20
What is the optimal steroid regimen ?
 : , systemic vs. nebulized
 Duration
 To taper or not to taper

21.  Pharmacokinetics
 Oral glucocorticoids are rapidly absorbed (peak serum levels
achieved at one hour after ingestion)
 Virtually complete bioavailability
 Oral therapy has several advantages over IV therapy
 Convenient to administration
 Cheaper
 No need for IV access (risk of infection, pain)
 Theoretically earlier hospital discharge
 There have been several studies of asthma exacerbations that
have shown a similar efficacy for IV and oral corticosteroid
21
Br J Clin Pharmacol. 1980;10(5):503-508.
Chest. 2007 Dec;132(6):1741-7. Epub 2007 Jul 23.
Am J Emerg Med. 1992;10:301-310.

22. 22SGRQ: St. George Respiratory Questionnaire
CCQ: Clinical COPD Questionnaire
Study design Randomized, double-dummy, placebo-controlled, non-inferiority study
Population
210 patients hospitalized for AECOPD
• Key inclusion: age >40 yr, smoking history, FEV1 <80%
• Key exclusion: very severe exacerbation, asthma, pneumonia
Treatment
regimen
• Oral vs. IV prednisolone 60 mg/day for 5 days,
followed by oral prednisolone 30 mg/day tapered with 5 mg/day to 0 mg
or a prior maintenance dose
• All patients received nebulized ipratropium, albuterol and amoxicillin/
clavulanate
Outcome
• Primary: treatment failure
• Secondary: changes from days 1 to 7 in FEV1, SGRQ scores, CCQ scores,
length of hospital stay
Follow-up 90 days

23. 23
*Values are given as the mean ± SD or No. (%), unless otherwise indicated.
†Parameters used in the minimization method to allocate patients to a treatment group by using a computer program.
Chest. 2007 Dec;132(6):1741-7. Epub 2007 Jul 23.
Demographic characteristics did not differ between the two groups at baseline
• Patients were not excluded if
they had used systemic
corticosteroids before study
enrollment
• Post-hoc subgroup analyses

24. 24
Chest. 2007 Dec;132(6):1741-7. Epub 2007 Jul 23.
after 2 weeks
within 2 weeks
Intention-to-treat analysis showed no significant difference between
the two groups in treatment failure rate

25.  A difference of ≤15% in treatment failure between groups would be
sufficient to accept non-inferiority
25Chest. 2007 Dec;132(6):1741-7. Epub 2007 Jul 23.
IV prednisolone
better
Oral prednisolone
better

26. Secondary Outcome IV Prednisolone Oral Prednisolone 95% CI
FEV 1 improved* (L) 0.10±0.23 0.12±0.19 -0.09 to 0.04
SGRQ total score improved* (points) 4.4±14.2 3.7±12.6 -3.3 to 4.7
CCQ total score improved* (points) 1.0±1.0 1.1±1.0 -0.4 to 0.19
Length of hospital stay (days) 11.9±8.6 11.2±6.7 -1.5 to 2.9
26Chest. 2007 Dec;132(6):1741-7. Epub 2007 Jul 23.
• Over 1 week, clinically relevant improvements were found in spirometry and
health-related quality of life
• Without significant differences between the two treatment groups
*changes from days 1 to 7

27.  Higher treatment failure rate (59%) than that seen in other trials
(37%)
 Whether the dose and duration of steroids were optimal ?
 Actively collected treatment failure data
 Prescription habits
 Did not exclude patients treated with systemic glucocorticoids in the 30
days prior to admission (77%)
Post-hoc subgroup analyses: did not influence the results
27Chest. 2007 Dec;132(6):1741-7. Epub 2007 Jul 23.
N Engl J Med. 1999;340(25):1941-1947.
Conclusion
• Oral prednisolone is not inferior to IV treatment in the first 90 days after
starting therapy
• Suggest that the oral route is preferable in the treatment of AECOPD

28. 28
JAMA 2010 Jun 16;303(23):2359
Title
Association of corticosteroid dose and route of administration with risk of
treatment failure in acute exacerbation of COPD
Study design Retrospective, pharmacoepidemiological cohort study
Method
• Patients admitted to the hospital (at 414 US centers) with AECOPD and
received corticosteroids during first 2 hospital days
• Patients admitted directly to ICU were excluded
• Followed for ≥ 30 days
Outcome
• Primary outcome: treatment failure
₋ In-hospital mortality
₋ Initiation of mechanical ventilation after second hospital day
₋ Readmission for COPD within 30 days
• Secondary outcome:
₋ Length of stay
₋ Hospital cost

29. 29JAMA 2010 Jun 16;303(23):2359
79,985 Eligible patients
Initial
treatment
Total dose in first 2 days, in
mg prednisone equivalents,
median (IQR)
IV steroids
N=73,765 (92%)
600 (350-781)
high-dose
Oral steroids
N=6,220 (8%)
60 (40-120)
low-dose

30. 30
Characteristics
comparison
JAMA 2010 Jun 16;303(23):2359

31. 31
Setting and
treatment
JAMA 2010 Jun 16;303(23):2359

32.  Adjust for
 Using propensity score
Probability of initial treatment with low-dose oral steroids
 Multivariable regression
 Propensity-matched cohort
 Possible residual biases due to
 Use a instrumental variable analysis
Whether increased rate of treatment with oral steroids was associated
with a change in the risk of treatment failure ?
32JAMA 2010 Jun 16;303(23):2359

33. Model
Treatment Failure
OR (95% CI)
Length of Stay
Ratio (95% CI)
Total Cost
Ratio (95% CI)
Unadjusted 0.91 (0.83-1.00) 0.92 (0.91-0.93) 0.92 (0.91-0.93)
Propensity score- and
covariate-adjusted
0.93 (0.84-1.02) 0.92 (0.91-0.94) 0.93 (0.91-0.94)
Matched sample adjusted for
unbalanced covariates
0.84 (0.75-0.95) 0.90 (0.88-0.91) 0.91 (0.89-0.93)
Group treatment for 10% increase
in hospital proportion oral
steroids, covariate adjusted
1.00 (0.97-1.03)
33
Conclusion
Initial treatment with low-dose oral steroids are not associated with worse
outcomes than high-dose IV corticosteroids for patients hospitalized with AECOPD

34. Current guidelines recommendation
 Oral steroids as first-line treatment for AECOPD
 Dosage: prednisolone 30-40 mg/day
Existing evidence
 No significant benefit to the use of high dose IV over low dose oral
corticosteroids
 Similar in efficacy
 Low-dose oral therapy is associated with shorter hospital stays and
lower total hospital cost
 Parenteral corticosteroids should be reserved for patients with poor
intestinal absorption or comorbid conditions that prevent safe oral
intake
34

35. 35
What is the optimal steroid regimen ?
 Route and dose:
• High topical antiinflammatory activity
• Low level of systemic activity

36. 36Bronchodilator: salbutamol 2.5 mg qid + ipratropium 0.5 mg qid
Eur Respir J. 2007 Apr;29(4):660-7.
Title The role of nebulised budesonide in the treatment of exacerbations of COPD.
Study design Randomized, single-blind, parallel-group study
Patients
• 121 patients hospitalized with AECOPD
• Key exclusion:
Level III exacerbation, pneumonia, systemic corticosteroids < 1 month
 not excluding asthma
• Mean age: 64.1± 8.9 yrs (female/male = 0.1)
• Mean FEV1 at admission: 37.2± 12.2%
Method
• Group 1: bronchodilator
• Group 2: bronchodilator + IV prednisolone 40 mg QD
• Group 3: bronchodilator + NEB budesonide 1.5 mg QID
• Patients were hospitalized for ≥ 10 days
Outcome
measure
• During 10-day hospitalization: spirometric parameters, ABG
• After discharge: exacerbation and rehospitalization rate within 1 month

37. 37Eur Respir J. 2007 Apr;29(4):660-7.
FEV1 PaO2
 Group 1 (Bronchodilator only)
 Group 2 (IV)
 Group 3 (NEB)
Group3 (NEB):
Significant improve FEV1 from
baseline at 24h
Group 2 (IV) & 3 (NEB):
Significant improve PaO2 from
baseline at 24h

38. 38Eur Respir J. 2007 Apr;29(4):660-7.
Blood glucose
 Group 1 (Bronchodilator only)
 Group 2 (IV)
 Group 3 (NEB)
Group 2 (IV):
Significant higher blood glucose
level than the other groups in 7-
and 10-day measurements
(P < 0.05)

39. Group 1 Group 2 Group 3
Patients, n 39 40 42
Patients discharged at day 10, % 54 50 45
Patients discharged after 15 days, % 10 10 7
Exacerbation rates within 1 month of discharge 14 8 9
Rehospitalization rates within 1 month of discharge 8 4 5
39Eur Respir J. 2007 Apr;29(4):660-7.
IV NEB
 Early and late discharge rates did not differ between the groups (P > 0.05)
 Lower reexacerbation and rehospitalization rates in the corticosteroid
groups, but not statistically significant
Conclusion
Nebulized budesonide might be an effective and well tolerated alternative to
systemic corticosteroids in AECOPD
Bronchodilator only

40. Current guidelines recommendation
 Nebulized budesonide might be an alternative to systemic corticosteroids
in AECOPD
Existing evidence
 Nebulized corticosteroids may be as effective as systemic
corticosteroids in AECOPD, except in very severe cases
 Exerted less systemic activity, as indicated by serial blood glucose
measurement
 Dosage used in studies: budesonide 4-8 mg/day
 Further larger studies are needed
 Different types of nebulized corticosteroid, dosage, long-term impact
on clinical outcomes
40Eur Respir J. 2007 Apr;29(4):660-7.
Am J Respir Crit Care Med. 2013 Feb 15;187(4):347-65.

41. 41
What is the optimal steroid regimen ?
 Route and dose

 To taper or not to taper

42. 42
REDUCE: Reduction in the Use of Corticosteroids in Exacerbated COPD
Title
Short-term vs. conventional glucocorticoid therapy in acute exacerbations of
COPD: the REDUCE randomized clinical trial.
JAMA. 2013 Jun 5;309(21):2223-31.
Study design Noninferiority RCT followed for 6 months
Population
• Enrolling 314 patients presenting to emergency department with AECOPD
₋ > 40 years old (mean age 70 years)
₋ Past or present smokers (≥20 pack-years)
₋ Exclusion: history of asthma, pneumonia, survival <6 months
Treatment
regimen
• Antibiotic for 7 days plus nebulized short-acting bronchodilator while
hospitalized
• ICS plus LABA plus tiotropium for 6 months
Methylprednisolone
40 mg IV
Prednisone
40 mg/day oral
Placebo
Prednisone
40 mg/day oral
Day 1 Day 2-5
Day 6-14
5 days
vs.
14 days

43. 43
JAMA. 2013 Jun 5;309(21):2223-31.
Most patients had severe
or very severe COPD
More women in the
conventional group
P=.02
14 days 5 days

44. Comparing prednisone for
 Re-exacerbation
 Intention-to-treat 35.9% vs. 36.8% (noninferiority met)
 Per-protocol 36.7% vs. 38.3% (noninferiority met)
 Median time to re-exacerbation: 43.5 days vs. 29 days (no p value reported)
 Mortality, need for mechanical ventilation, or adverse events: not significant
 Median hospital stay: 8 days vs. 9 days (p = 0.04)
 Mean cumulative prednisone dose: 379 mg vs. 793 mg (p < 0.001)
44Noninferiority criterion was < 15% difference in re-exacerbation rates between groups
JAMA. 2013 Jun 5;309(21):2223-31.
Conclusion
• 5-day glucocorticoid was noninferior to a 14-day course with respect to re-
exacerbation during 6 months of follow-up
• These findings support the use of a 5-day course

45.  The optimal duration of systemic glucocorticoid therapy often depends on
 Severity of the exacerbation
 Observed response to therapy
 Current guidelines recommendation: 10-14 days course
 Existing evidence
 Shorter course is as effective: 5 days vs. 14 days
 Did not study very critically ill population, in which the risk/benefit
tradeoff with steroids and response to steroids might be somewhat
different
 Further study is needed to determine whether some patients might do
better with the longer course
451. Am J Respir Crit Care Med. 2013 Feb 15;187(4):347-65. 2. Cochrane Database Syst Rev. 2011 Oct 5;(10):CD006897.
3. JAMA. 2013 Jun 5;309(21):2223-31.

46. 46
What is the optimal steroid regimen ?
 Route and dose
 Duration


47. The decision to taper is based on
 Risk of adrenal insufficiency ?
 Negative feedback and suppression of the hypothalamic–pituitary–
adrenal (HPA) axis
 Risk for disease relapse on withdrawal of corticosteroids
therapy ?
 In both clinical practice and clinical studies, steroid regimens often
include a taper.
 A study by found that 79% of hospital discharges for AECOPD
included a tapered corticosteroid regimen…
47Am J Health Syst Pharm. 2006;63:645-652.
Pharmacotherapy. 2006 Apr;26(4):522-32.

48.  Dose administered
 Physiological replacement dosage: prednisone 5–7.5 mg/day
 Potency and half-lives of corticosteroid agent
 Long-acting glucocorticoid accumulate with repeated dosing
eg. dexamethasone
 Timing of the dose
 Higher risk of nighttime administration
 Multiple daily dose > single daily dose > alternate-day therapy
 Duration of exposure
 Durations less than 3 weeks, regardless of dosage, is generally
considered safe and should not lead to adrenal suppression
481. Drugs. 1989 Nov;38(5):838-45. 2.Thorax. 1981;36:22-24. 3. Pharmacotherapy. 2006 Apr;26(4):522-32.

49.  Patients with asthma: abruptly stopping steroids does not
increase the risk of disease relapse
 AECOPD: There is no evidence to suggest that abrupt
discontinuation of steroids leads to clinical worsening of disease
49Int J Clin Pharmacol Ther. 2002 Jun;40(6):256-62.
Pharmacotherapy. 2006 Apr;26(4):522-32.
To taper or not to taper ?
• Tapering solely because of concerns about adrenal suppression is not
necessary if the duration of therapy is less than three weeks
• There is a lack of evidence advocating for or against the use of tapered
steroid regimens in AECOPD
• Clinical guidelines do not address the tapering of corticosteroids

50. 50
8/1 8/2 8/3 8/4 8/5 8/6 8/7 8/8
Admission
BS 349 mg/dL
BP 173/85 mmHg
Still poor control
of BS and BP
No dyspnea,
improving
Epigastric dullness,
vomiting
Discharge
Methylprednisolone 20mg IVD q12h
Prednisolone 10mg BID 5mg bid
Discharge medication
5mg bid x 5 days
UGI
bleeding
Past medical history
• COPD with recurrent AE episode: 3 times/year
• Gastric ulcer history (2012/11)
• HTN
• Type 2 DM …

51. 51
GOLD ATS/ERS ICSI NICE CTS
Route Oral Oral Oral Oral Oral or IV
Dose
Prednisolone
30-40 mg/day
Prednisone
30-40 mg/day
Prednisone
30-40 mg/day
Prednisolone
30 mg/day
Prednisone
25-50 mg/day
Duration 10-14 days 10 days 7-14 days 7-14 days 7-14 days
Other
Nebulized
alternative
IV, nebulized
alternative
No need to
discontinue
ICS

52. Study (n) Comparison Study Period Conclusion
Chest. 2007
(n=210)
Oral vs. IV prednisolone 60
mg/day for 5 days then tapper
90 days Oral is noninferior to IV
JAMA 2010
(n=79,985)
Low-dose oral steroids vs.
High-dose IV steroids
≥ 30 days
Similar efficacy
Shorter hospital stays
Lower total hospital cost
Eur respir J. 2007
(n=121)
NEB budesonide 1.5mg qid vs.
IV prednisolone 40mg qd
10 days
NEB as effective as systemic
corticosteroid
Higher blood glucose level in
IV group
JAMA. 2013
(n=314)
Oral prednisone 40 mg/day
5 days vs. 14 days
6 months 5 days noninferior to 14 days
Extrapolate these results to common practice is limited
• Patients with pneumonia
• Severe respiratory failure 52

53. 53
An issue as patients experience
more frequent exacerbations
Several adverse effects of
corticosteroid correlate with
cumulative dose
Psychosis, bone loss, muscle wasting,
metabolic changes…
Steroid exposure should be
minimized  shorter duration?
Potentially reducing costs and lowering
the risks of steroid-associated adverse
events
• Recurrent AE episode: 3 times/year
• Gastric ulcer history (2012/11)
• HTN
• Type 2 DM …

54. Corticosteroids are recommended for patients admitted with
AECOPD
 Oral administration is preferred over IV:
Prednisone 30-40 mg/day
 Similar in efficacy
 Lower cost and hospital length of stay
 A 5-day course of treatment is appropriate for most patients with
AECOPD
 Nebulized budesonide might be an effective and well tolerated
alternative to systemic corticosteroids
 There is no evidence that tapering is necessary
54

55. 55