Systemic corticosteroids in the treatment of acute exacerbations of copd

1,407 views

Published on

0 Comments
5 Likes
Statistics
Notes
  • Be the first to comment

No Downloads
Views
Total views
1,407
On SlideShare
0
From Embeds
0
Number of Embeds
3
Actions
Shares
0
Downloads
0
Comments
0
Likes
5
Embeds 0
No embeds

No notes for slide

Systemic corticosteroids in the treatment of acute exacerbations of copd

  1. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 11.  2013/08/08 - 2013/08/14  Coffee grounding vomiting, abdominal distension, fatigue and anorexia  Admission due to UGI bleeding   Pantoprazole, Metoclopramide 11
  12. 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. 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. 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. 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. 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. 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. 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. 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. 20 What is the optimal steroid regimen ?  : , systemic vs. nebulized  Duration  To taper or not to taper
  21. 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. 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. 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. 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. 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. 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. 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. 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. 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. 30 Characteristics comparison JAMA 2010 Jun 16;303(23):2359
  31. 31. 31 Setting and treatment JAMA 2010 Jun 16;303(23):2359
  32. 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. 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. 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. 35 What is the optimal steroid regimen ?  Route and dose: • High topical antiinflammatory activity • Low level of systemic activity
  36. 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. 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. 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. 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. 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. 41 What is the optimal steroid regimen ?  Route and dose   To taper or not to taper
  42. 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. 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. 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. 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. 46 What is the optimal steroid regimen ?  Route and dose  Duration 
  47. 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. 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. 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. 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. 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. 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. 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. 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. 55

×