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COPD Exacerbations: Significance, Assessment, and Current Management

Presentation by Dr David Pierson, faculty of Pulmonary Medicine Update Course, Egypt. Knowledge resources at Scribe : www.scribeofegypt.com

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COPD Exacerbations: Significance, Assessment, and Current Management

  1. 1. David J Pierson MD Professor of Medicine University of Washington Seattle, WA, USA December, 2008 COPD Exacerbations: Significance, Assessment, and Current Management
  2. 2. COPD Exacerbations <ul><li>What is an exacerbation, and why are they important? </li></ul><ul><li>Diagnosis and assessment of severity </li></ul><ul><li>When and how to use bronchodilators, corticosteroids, and antibiotics </li></ul><ul><li>Oxygen therapy in the acute setting </li></ul><ul><li>When to use noninvasive ventilation </li></ul>
  3. 3. What Is an Exacerbation, and Why Are They Important? <ul><li>Definition: a sustained worsening of the patient’s symptoms from his or her usual stable state that is beyond normal day-to-day variation and acute in onset </li></ul><ul><ul><li>Onset usually over 1 to 3 days </li></ul></ul><ul><ul><li>Term should not be used for other acute processes occurring in a COPD patient </li></ul></ul>
  4. 4. <ul><li>750,000 hospitalizations annually in US </li></ul><ul><li> Mannino DM, Respir Care 2003;48(12):1185-91 </li></ul><ul><li>Account for ~ 70% of direct medical costs for COPD Sullivan SD et al, Chest 2000;117(suppl):S5-S9 </li></ul><ul><li>Acute mortality 10-15% www.goldcopd.com </li></ul><ul><li>Subsequent mortality as high as 40% in first year and 70% at 5 years </li></ul><ul><li>http://thorax.bmjjournals.com/content/vol59/suppl_1/ </li></ul>What Is an Exacerbation, and Why Are They Important?
  5. 5. Importance of Exacerbations: Lessons from the East London COPD Study* <ul><li>More common than previously thought (2.5-3.0 per year); half not brought to MD’s attention </li></ul><ul><li>Recovery takes longer than previously thought (PEF not back to baseline at 1 mo in 25%) </li></ul><ul><li>Faster FEV 1 decline with frequent exacerbations </li></ul><ul><li>Worse QOL with more frequent exacerbations </li></ul><ul><li>Early Rx hastens recovery and improves QOL </li></ul>* Wedzicha JA. Chest 2002;121(5 Suppl):136S-141S Wedzicha JA et al. Respir Care. 2003;48(12):1204-13
  6. 6. Survival after ICU Admission for COPD Exacerbation* *Rivera-Fernandez R et al, Crit Care Med 2006;34(Sep):(e-pub) <ul><li>742 pts with COPD admitted to 86 ICUs in Spain in 1992-1995 </li></ul><ul><li>508 admitted because of COPD exacerbations </li></ul><ul><li>75% required mechanical ventilation </li></ul><ul><li>Mortality: In ICU: 23% </li></ul><ul><ul><li>In hospital: 32% </li></ul></ul><ul><ul><li>After 6 years: 82% </li></ul></ul>
  7. 7. According to Pre-Admission Quality of Life According to Patient Age Survival after ICU Admission for COPD Exacerbation* *Rivera-Fernandez R et al, Crit Care Med 2006;34(Sep):(e-pub)
  8. 8. Managing COPD Exacerbations: Performance of 360 US Hospitals vs ACP-ACCP Guidelines* *Lindenaur PK et al, Ann Intern Med 2006;144(12):894-903 ( ~ 70,000 Patients; 2001)
  9. 9. Diagnosis and Assessment of Severity <ul><li>Does this patient have COPD? </li></ul><ul><li>Is it a COPD exacerbation or something else? </li></ul><ul><li>When to get arterial blood gases, chest X-rays, and other studies </li></ul><ul><li>When to admit the patient to the hospital </li></ul><ul><li>Indications for admission to the ICU </li></ul>
  10. 10. Does This Patient Have COPD? <ul><li>Only 15% of all smokers have COPD (35-45% in high-risk groups) </li></ul><ul><li>To be certain of the diagnosis requires spirometry </li></ul><ul><ul><li>GOLD definition: chronic respiratory symptoms, plus incompletely reversible airflow obstruction (FEV 1 /FVC < 70%) www.goldcopd.com </li></ul></ul><ul><li>There are other common causes of dyspnea and cough in middle-aged and elderly smokers </li></ul>
  11. 11. *Damarla M et al, Respir Care 2006 (Oct);51(10):1120-4. Use of Appropriate Diagnostic Confirmation in COPD vs CHF* <ul><li>6-month review of patients admitted to Caritas St Elizabeth’s Medical Center (Boston) with primary or secondary diagnosis of either COPD or CHF </li></ul><ul><li>How many patients had had spirometry or cardiac echo, respectively, to confirm the clinical diagnosis? </li></ul><ul><li>COPD: 553 patients; CHF: 789 patients </li></ul>
  12. 12. *Damarla M et al, Respir Care 2006 (Oct);51(10):1120-4. Use of Appropriate Diagnostic Confirmation in COPD vs CHF (in previous 8 years)*
  13. 13. *Damarla M et al, Respir Care 2006 (Oct);51(10):1120-4. Use of Appropriate Diagnostic Confirmation in COPD vs CHF* <ul><li>A large proportion of patients hospitalized with COPD (presumably patients with severe disease) have never had the diagnosis confirmed with spirometry </li></ul><ul><li>Patients diagnosed with COPD are much less likely to have had the appropriate confirmatory test than patients diagnosed with CHF </li></ul><ul><li>This is true even for patients with both conditions </li></ul>
  14. 14. Is It a COPD Exacerbation or Something Else? <ul><li>Pneumonia </li></ul><ul><li>Pneumothorax </li></ul><ul><li>Pulmonary embolism </li></ul><ul><li>Congestive heart failure/ pulmonary edema </li></ul><ul><li>Recurrent aspiration </li></ul><ul><li>Lung Cancer </li></ul><ul><li>Pleural effusion </li></ul>
  15. 15. Indications for Laboratory Evaluation (ABGs, CXR, CBC) in Patients with COPD Exacerbation <ul><li>Recent hospitalization, treatment for exacerbation, or other acute respiratory problem </li></ul><ul><li>Known very severe COPD (GOLD Stage IV * ) </li></ul><ul><li>Patient on continuous oxygen at home </li></ul><ul><li>Respiratory symptoms that are new for this patient </li></ul>*www.goldcopd.com
  16. 16. Indications for Laboratory Evaluation (ABGs, CXR, CBC) in Patients with COPD Exacerbation <ul><li>Marked, sustained increase in patient’s usual degree of dyspnea </li></ul><ul><li>Inability to speak in complete sentences </li></ul><ul><li>Pleuritic chest pain </li></ul><ul><li>Onset of respiratory distress sudden rather than over several hours or days </li></ul><ul><li>Hemoptysis </li></ul>
  17. 17. Indications for Laboratory Evaluation (ABGs, CXR, CBC) in Patients with COPD Exacerbation <ul><li>Altered mental status (new confusion; somnolence or obtundation) </li></ul><ul><li>Sustained tachypnea (RR > 30 breaths/min) </li></ul><ul><li>Sustained tachycardia (HR >100 beats/min) </li></ul><ul><li>Oximetry saturation < 90% on room air or patient’s usual supplemental oxygen </li></ul><ul><li>Fever (T > 38.3 C) </li></ul>
  18. 18. Indications for Laboratory Evaluation (ABGs, CXR, CBC) in Patients with COPD Exacerbation <ul><li>Hypotension (systolic BP < 100 mm Hg or 20% lower than patient’s usual) </li></ul><ul><li>Arrhythmias (new for this patient, or worse, or different pattern) </li></ul><ul><li>New or markedly worsened edema </li></ul><ul><li>Sustained use of accessory muscles of respiration at rest </li></ul><ul><li>Paradoxical chest/abdominal wall motion </li></ul>
  19. 19. <ul><li>Persistence of symptoms and signs listed previously despite initial treatment </li></ul><ul><li>Respiratory acidosis (eg, pH < 7.35) uncorrected with initial treatment </li></ul><ul><li>Presence of a complicating acute respiratory process (eg, pneumonia, pneumothorax) </li></ul><ul><li>Diagnostic uncertainty </li></ul><ul><li>Presence of significant comorbidities </li></ul>Indications for Hospital Admission in Patients with COPD Exacerbation
  20. 20. <ul><li>Severe impairment of activities of daily living </li></ul><ul><li>Significant recent decline in overall condition </li></ul><ul><li>Inability to eat or sleep because of ongoing respiratory symptoms </li></ul><ul><li>Older age </li></ul><ul><li>Need for therapy that cannot be provided in the home </li></ul><ul><li>Insufficient home support </li></ul>Indications for Hospital Admission in Patients with COPD Exacerbation
  21. 21. <ul><li>Need for NPPV, especially in initial hours of management </li></ul><ul><li>Need for invasive ventilatory support </li></ul><ul><li>Persistence of severe dyspnea, tachypnea, or tachycardia despite initial therapy </li></ul>Which Patients Should Be Admitted to the ICU?
  22. 22. <ul><li>Persistence of confusion, somnolence, or obtundation </li></ul><ul><ul><li>Inability to deliver necessary therapy </li></ul></ul><ul><ul><li>Higher likelihood of deterioration </li></ul></ul><ul><li>Persistence of severe hypoxemia (eg, need for > 40% O 2 ) </li></ul><ul><li>Persistence (or worsening) of respiratory acidosis (eg, elevated PCO 2 with pH < 7.30) </li></ul>Which Patients Should Be Admitted to the ICU?
  23. 23. Respiratory Arrest <ul><li>An All-Too-Common Scenario: </li></ul><ul><li>COPD Pt with exacerbation </li></ul><ul><li>Admitted to floor & worked up </li></ul><ul><li>Standard therapy begun </li></ul><ul><li>OK when last checked, but then… </li></ul>
  24. 24. Sudden Development vs Sudden Discovery Tachypnea Characteristic EMG Changes Paradoxical Respiration Respiratory Alternans CO 2 Retention Bradypnea Respiratory Arrest
  25. 25. COPD Exacerbations <ul><li>What is an exacerbation, and why are they important? </li></ul><ul><li>Diagnosis and assessment of severity </li></ul><ul><li>When and how to use bronchodilators, corticosteroids, and antibiotics </li></ul><ul><li>Oxygen therapy in the acute setting </li></ul><ul><li>When to use noninvasive ventilation </li></ul>
  26. 26. Bronchodilator Therapy in COPD Exacerbations <ul><li>Most studies have been done in: </li></ul><ul><ul><li>Acute asthma, not COPD </li></ul></ul><ul><ul><li>ED, with short-term outcomes </li></ul></ul><ul><li>Inhaled (vs parenteral) beta-agonists give equivalent benefit with fewer adverse effects </li></ul><ul><li>MDI + spacer is equivalent to nebulizer: </li></ul><ul><ul><li>In stable COPD </li></ul></ul><ul><ul><li>In stable & acute asthma, in children and adults </li></ul></ul><ul><ul><li>In intubated patients </li></ul></ul>
  27. 27. *McCrory DC et al, Cochrane Reviews 2003(1):CD003900 Ipratropium vs Beta-Agonist in COPD Exacerbations : Meta-Analysis of RCTs*
  28. 28. *McCrory DC et al, Cochrane Reviews 2003(1):CD003900 Beta-Agonist +/- Ipratropium in COPD Exacerbations : Meta-Analysis of RCTs*
  29. 29. *McCrory DC et al, Cochrane Reviews 2003(1):CD003900 Beta-Agonist +/- Ipratropium in COPD Exacerbations : Meta-Analysis of RCTs*
  30. 30. Beta-Agonist Administration with MDI+Spacer vs Nebulizer in Adults with Acute Asthma: Improvement in FEV 1 * *Cates CJ et al, Cochrane Reviews 2006(2):CD000052
  31. 31. Beta-Agonist Administration with MDI+Spacer vs Nebulizer in Adults with Acute Asthma: Hospital Admission* *Cates CJ et al, Cochrane Reviews 2006(2):CD000052
  32. 32. *McCrory DC et al, Cochrane Reviews 2003(1):CD003900 Ipratropium vs Beta-Agonist and Their Combination in COPD Exacerbations* <ul><li>Meta-analysis of RCTs examining FEV 1 short-term and at 24h, PaO 2 , and side-effects of: </li></ul><ul><ul><li>β -agonist vs ipratropium </li></ul></ul><ul><ul><li>β -agonist with and without ipratropium </li></ul></ul><ul><li>No differences in any measure examined </li></ul>
  33. 33. Bronchodilators in COPD Exacerbations: Current GOLD Recommendation* <ul><li>Short-acting inhaled β 2 -agonists are the primary therapy. </li></ul><ul><li>Short-acting inhaled anticholinergics are recommended if poor response. </li></ul><ul><li>Methylxanthines (theophylline) are optional. </li></ul><ul><li>There is no current role for long-acting β 2 -agonists, with or without inhaled corticosteroids. </li></ul>*www.goldcopd.com
  34. 34. Corticosteroids In COPD Exacerbations
  35. 35. *Albert RK, Martin TR, Lewis SW. Ann Intern Med 1980;92:753-758 Systemic Corticosteroids in COPD Exacerbations: The Albert Study* <ul><li>44 pts admitted to Seattle VA with exacerbations </li></ul><ul><li>FEV 1 < 60% pred or FEV 1 /FVC < 60% </li></ul><ul><li>PaO 2 < 65 on RA or PaCO 2 > 50 & pH < 7.35 </li></ul><ul><li>Exclusions: asthma, infiltrate, recent steroids </li></ul><ul><li>Methylprednisolone 0.5 mg/kg IVq6h vs placebo </li></ul><ul><li>All pts got aminophylline, isoproterenol, ABX </li></ul><ul><li>Duration: 72 hrs </li></ul><ul><li>Outcomes: pre/post BD FEV 1 , ABGs, glucose </li></ul>
  36. 36. *Albert RK, Martin TR, Lewis SW. Ann Intern Med 1980;92:753-758 Systemic Corticosteroids in COPD Exacerbations: The Albert Study* <ul><li>Greater improvement in both pre- and post-BD FEV 1 in steroid group (p < 0.001) </li></ul><ul><li>More patients with increases in FEV 1 of 40% or more in steroid group (p < 0.01) </li></ul><ul><li>2 pts died, 1 psychosis, 1 UGI bleed (all in steroid group); 1 UGI bleed in placebo group </li></ul><ul><li>Conclusion: IV methylprednisolone improves airflow more than placebo in COPD exacerbations. </li></ul>
  37. 37. Systemic Corticosteroids in COPD Exacerbations: The Thompson Study* *Thompson WH et al, AJRCCM 1996 Aug;154(2 Pt 1):407-12 <ul><li>27 Boise VA outpatients with exacerbations </li></ul><ul><li>FEV 1 < 60% pred or post-BD FEV 1 /FVC < 65% </li></ul><ul><li>Acute resp Sx for > 24h prompting hospital visit </li></ul><ul><li>Exclusions: asthma, other lung disease, CHF, recent steroid Rx, T > 38.5, pH < 7.35 </li></ul><ul><li>Prednisone 60 mg qd x 3d, then 40 mg qd x 3d, then 20 mg qd x 3d (vs vitamin B6 x 9d) </li></ul><ul><li>Usual meds, ABX only if infection on gram stain </li></ul><ul><li>Outcomes: spirometry; dyspnea (VAS), ABGs, Rx failure (hospitalization or prednisone) </li></ul>
  38. 38. Systemic Corticosteroids in COPD Exacerbations: The Thompson Study* *Thompson WH et al, AJRCCM 1996 Aug;154(2 Pt 1):407-12 <ul><li>More rapid improvement in oxygenation </li></ul><ul><ul><li>PaO 2 : 1.12 mm Hg/d vs -0.03 mm Hg/day; p = 0.002 </li></ul></ul><ul><ul><li>P(A-a)O 2 : 1.16 mm Hg/d vs -0.03 mm Hg/d; p = 0.04 </li></ul></ul><ul><li>More rapid improvement in airflow </li></ul><ul><ul><li>FEV 1 : 50 mL/d vs 0 mL/d, p = 0.006 </li></ul></ul><ul><ul><li>PEF: 0.15 L/s/d vs 0.04 L/s/d, p = 0.009 </li></ul></ul><ul><li>Fewer treatment failures (p = 0.002) </li></ul><ul><li>Trend toward more rapid improvement in dyspnea scores </li></ul>
  39. 39. *Wood-Baker RR et al, Cochrane Reviews 2005(1):CD001288 Systemic Corticosteroids in COPD Exacerbations: Meta-Analysis of RCTs* <ul><li>10 good-quality studies (951 pts) as of 2005 </li></ul><ul><li>Effects of Steroids (vs placebo, other Rx same): </li></ul><ul><ul><li>Fewer treatment failures within 30 days (Odds ratio = 0.48; Number needed to treat = 9) </li></ul></ul><ul><ul><li>More rapid FEV 1 improvement (WMD 140 mL @ 72 h) </li></ul></ul><ul><ul><li>Significant improvement in dyspnea and ABGs </li></ul></ul><ul><ul><li>No difference in mortality </li></ul></ul><ul><ul><li>Increased likelihood of adverse drug effect (OR 2.29; NNH = 6); hyperglycemia most likely (OR 5.48) </li></ul></ul>
  40. 40. *Wood-Baker RR et al, Cochrane Reviews 2005(1):CD001288 Management of COPD Exacerbation: Effect of Steroids on Early FEV 1 *
  41. 41. *Wood-Baker RR et al, Cochrane Reviews 2005(1):CD001288 Management of COPD Exacerbation: Effect of Steroids on Treatment Failure*
  42. 42. Wood-Baker RR et al, Cochrane Reviews 2005(1):CD001288
  43. 43. Wood-Baker RR et al, Cochrane Reviews 2005(1):CD001288
  44. 44. Corticosteroids in COPD Exacerbations: Current GOLD Recommendation* <ul><li>Recommended for hospitalized patients, and for home management if baseline FEV 1 < 50% predicted </li></ul><ul><li>Prednisone 30-40 mg/d for 7-10 days is effective; no benefit but  side effects with longer courses </li></ul><ul><li>Possible advantages of higher doses and/or parenteral administration unknown </li></ul>*www.goldcopd.com
  45. 45. Antibiotics In COPD Exacerbations
  46. 46. *Anthonisen NR et al, Ann Intern Med 1987;106:196-204 Antibiotics in COPD Exacerbations: The Anthonisen Study* <ul><li>362 exacerbations in 173 patients over 3.5-yrs </li></ul><ul><li>Randomized, double-blind, crossover trial </li></ul><ul><li>Rx with antibiotics (182 episodes) or placebo (180 episodes), plus usual therapy </li></ul><ul><li>Exacerbation severity: </li></ul><ul><ul><li>Type 1: Increased dyspnea, increased sputum </li></ul></ul><ul><ul><li>volume, and increased sputum purulence </li></ul></ul><ul><ul><li>Type 2: Any 2 of the above </li></ul></ul><ul><ul><li>Type 3: Any 1 of the above </li></ul></ul>
  47. 47. *Anthonisen NR et al, Ann Intern Med 1987;106:196-204 Antibiotics in COPD Exacerbations: The Anthonisen Study* <ul><li>362 exacerbations in 173 COPD patients over 3.5-yr period </li></ul><ul><li>Randomized, double-blind, crossover trial </li></ul><ul><li>Rx with antibiotics (182 episodes) or placebo (180 episodes), plus usual therapy </li></ul><ul><li>Successful Rx (as defined): 68% vs 55% </li></ul><ul><li>Rx failure with deterioration: 10% vs 19% </li></ul><ul><li>No difference in adverse effects </li></ul>
  48. 48. Efficacy of Antibiotics According to Exacerbation Severity* *Anthonisen NR et al, Ann Intern Med 1987;106:196-204
  49. 49. *Anthonisen NR et al, Ann Intern Med 1987;106:196-204 Treatment Failure with Deterioration According to Exacerbation Severity*
  50. 50. *Ram FSF et al, Cochrane Reviews 2006(2):CD004403 Antibiotics in COPD Exacerbations: Meta-Analysis of RCTs*
  51. 51. Antibiotics vs Placebo in Managing COPD Exacerbations: Mortality in Best-Designed RCTs* *Ram FSF et al, Cochrane Reviews 2006(2):CD004403
  52. 52. RCTs of Antibiotics in COPD Exacerbations: Hospitalized Patients vs Outpatients* *Ram FSF et al, Cochrane Reviews 2006(2):CD004403
  53. 53. *Ram FSF et al, Cochrane Reviews 2006(2):CD004403 Antibiotics vs Placebo in COPD Exacerbations: Short-Term Mortality*
  54. 54. *Ram FSF et al, Cochrane Reviews 2006(2):CD004403 Antibiotics vs Placebo in COPD Exacerbations: Treatment Failure*
  55. 55. Antibiotics in COPD Exacerbations: Current GOLD Recommendation* <ul><li>Anthonisen Type 1 exacerbation (  dyspnea,  sputum volume,  sputum purulence)—and also Type 2 (?) </li></ul><ul><li>Severe exacerbation requiring NPPV </li></ul><ul><li>Should cover most likely organisms </li></ul><ul><ul><li>S. pneumoniae </li></ul></ul><ul><ul><li>H. influenzae </li></ul></ul><ul><ul><li>M. catarrhalis </li></ul></ul>*www.goldcopd.com
  56. 56. COPD Exacerbations <ul><li>What is an exacerbation, and why are they important? </li></ul><ul><li>Diagnosis and assessment of severity </li></ul><ul><li>When and how to use bronchodilators, corticosteroids, and antibiotics </li></ul><ul><li>Oxygen therapy in the acute setting </li></ul><ul><li>When to use noninvasive ventilation </li></ul>
  57. 57. <ul><li>What is the physiologic mechanism? </li></ul><ul><li>Which patients are most at risk? </li></ul><ul><li>How big a problem is it? </li></ul><ul><li>What should we do about it? </li></ul>CO 2 Retention and Oxygen Therapy In COPD
  58. 58. RCT of High vs Low PaO 2 Targets in Managing COPD Exacerbations* <ul><li>34 pts with COPD exacerbations (RA PO 2 <50, PCO 2 >50) admitted to ICU </li></ul><ul><li>Randomized for O 2 titration to PO 2 50-70 or >70 mm Hg </li></ul><ul><li>2 pts in low-O 2 group required MV; 1 died </li></ul><ul><li>No pts in high-O 2 group had bad outcome </li></ul><ul><li>No statistically significant differences </li></ul><ul><li>Conclude that traditional teaching to avoid over-oxygenation may be wrong </li></ul>*Gomersall CD et al, Crit Care Med 2002;30(1):113-6
  59. 59. RCT of High vs Low PaO 2 Targets in Managing COPD Exacerbations* <ul><li>Several study design problems </li></ul><ul><li>Under-powered </li></ul><ul><li>Other differences in pt management (use of doxapram, etc) </li></ul><ul><li>Only RCT on this published to date </li></ul>*Gomersall CD et al, Crit Care Med 2002;30(1):113-6
  60. 60. Does Injudicious Oxygen Administration Cause Respiratory Acidosis?* <ul><li>1-yr prevalence study of COPD exacerbations </li></ul><ul><li>983 admissions to 3 hospitals in Leeds </li></ul><ul><li>918 (95%) had ABG on admission </li></ul><ul><li>47% were hypercapnic and 20% were acidemic (pH < 7.35) </li></ul><ul><li>Pts with highest initial PO 2 tended to be more acidemic </li></ul>*Plant PK et al, Thorax 2000;55:550-4
  61. 61. Patients with Higher Initial PaO 2 Tended to Have More Severe Acidemia* (Assumption is that they received too much O 2 initially) *Plant PK et al, Thorax 2000;55:550-4 < 55 55-75 75-100 > 100 Initial PaO 2 (mm Hg)
  62. 62. <ul><li>22 COPD pts hospitalized with exacerbations </li></ul><ul><li>Mean FEV 1 0.75 L (30% pred) </li></ul><ul><li>Studied within 72 h of admission </li></ul><ul><li>ABGs, Cardiac output, and V/Q distributions (MIGET) determined on RA and after 20 min breathing 100% O 2 </li></ul>* CO 2 Retention with O 2 Therapy in COPD Exacerbations: What Causes It?* *Robinson TD et al, AJRCCM 2000;161:1524-9
  63. 63. <ul><li>10 pts had < 3 mm Hg rise (non-retainers) </li></ul><ul><li>12 pts had > 3 mm Hg PCO 2 rise (retainers) </li></ul><ul><li>Minute ventilation fell in retainers (from 9.0 to 7.2 L/min) but not in nonretainers </li></ul><ul><li>V distribution in relation to Q became more deranged while breathing 100% O 2 in the retainers than in the non-retainers </li></ul><ul><li>Retainers had higher Bohr deadspace on O 2 </li></ul>CO 2 Retention with O 2 Therapy in COPD Exacerbations: What Causes It?* *Robinson TD et al, AJRCCM 2000;161:1524-9
  64. 64. <ul><li>22 COPD pts hospitalized with exacerbations </li></ul><ul><li>Mean FEV 1 0.75 L (30% pred) </li></ul><ul><li>Studied within 72 h of admission </li></ul><ul><li>ABGs on RA and after 20 min on 100% O 2 </li></ul><ul><li>10 pts had < 3 mm Hg rise (non-retainers) </li></ul><ul><li>12 pts had > 3 mm Hg PCO 2 rise (retainers) </li></ul><ul><ul><li>PO 2 : 54 on RA, 371 on 100% O 2 </li></ul></ul><ul><ul><li>PCO 2 : 56 on RA, 65 on 100%O 2 </li></ul></ul>*Robinson TD et al, AJRCCM 2000;161:1524-9 CO 2 Retention with O 2 Therapy in COPD Exacerbations: How Big a Problem?*
  65. 65. <ul><li>24 consecutive pts in ED with exacerbation </li></ul><ul><li>Median age 71; FEV 1 37% pred (26-49%) </li></ul><ul><li>Mean presenting PO 2 46, PCO 2 56 </li></ul><ul><li>Given O 2 by 24-40% Venturi mask to keep SpO 2 90-91% </li></ul><ul><li>ABGs repeated in 2 hr & regularly thereafter </li></ul>*Moloney ED et al, Lancet 2001;357:526-8 Clinically Important CO 2 Retention with Controlled Oxygen Therapy: How Often Does It Happen?*
  66. 66. <ul><li>Arterial PCO 2 rose more than 7.5 mm Hg in only 3 of 24 pts </li></ul><ul><li>Arterial pH fell below 7.25 in only 1 pt </li></ul><ul><li>No pt developed CO 2 narcosis or required assisted ventilation </li></ul><ul><li>Further PCO 2 rise did not occur after initial 2 hr </li></ul><ul><li>Pts with higher initial PCO 2 tended to have greater PCO 2 rises in with O 2 therapy </li></ul>*Moloney ED et al, Lancet 2001;357:526-8 Clinically Important CO 2 Retention with Controlled Oxygen Therapy: How Often Does It Happen?*
  67. 67. *Moloney ED et al, Lancet 2001;357:526-8 45 55 65 75 mm Hg 30 15 0 15 30 Changes in PCO 2 with Oxygen Therapy When SpO 2 is kept at 90-91%* PCO 2 Change vs Initial PCO 2 PCO 2 Change vs Initial pH
  68. 68. <ul><li>Depression of hypoxic ventilatory drive </li></ul><ul><li>Increased mismatching of ventilation and perfusion </li></ul><ul><li>Haldane effect </li></ul><ul><ul><li>Saturation of hemoglobin with oxygen reduces CO 2 -carrying capacity of blood </li></ul></ul>CO 2 Retention and Oxygen Therapy In COPD: Physiologic Mechanisms
  69. 69. <ul><li>There are probably several mechanisms. </li></ul><ul><li>It is only a threat when patients are acutely ill. </li></ul><ul><li>It happens in only a minority of patients. </li></ul><ul><li>It can be avoided by keeping SpO 2 90-92%. </li></ul><ul><li>Hypoxemia should not be allowed to persist because of fear of CO 2 narcosis and acidosis. </li></ul><ul><li>The goal is to get SpO 2 to 90% (PO 2 60 mm Hg) in all patients. </li></ul>CO 2 Retention and Oxygen Therapy In COPD: The Bottom Line
  70. 70. <ul><li>Pulse oximetry alone is not enough, in any potentially severe exacerbation </li></ul><ul><li>Presence and severity of acute-on-chronic respiratory acidosis is important, both prognostically and therapeutically </li></ul><ul><li>Must use ABGs in initial assessment, and also in initial monitoring of O 2 therapy (eg, at 30 ’ ) </li></ul><ul><li>Oximetry is valuable for subsequent monitoring once initial response to O 2 is determined </li></ul>COPD Exacerbations: Assessment of Oxygenation and Acid-Base Status
  71. 71. How Should Oxygen Be Delivered in Managing COPD Exacerbations? Nasal Venturi Cannula Mask Known, constant No (but this Yes (but delivered O 2 may not be not really) concentration? important) Likely to stay Yes No on patient? No need to remove Less well tolerated; for talking, eating, Must come off for aerosol Rx, etc talking, eating, meds Overall effectiveness ++ +
  72. 72. COPD Exacerbations <ul><li>What is an exacerbation, and why are they important? </li></ul><ul><li>Diagnosis and assessment of severity </li></ul><ul><li>When and how to use bronchodilators, corticosteroids, and antibiotics </li></ul><ul><li>Oxygen therapy in the acute setting </li></ul><ul><li>When to use noninvasive ventilation </li></ul>
  73. 73. *Brochard L et al, NEJM 1995;333(13):817-822 NPPV vs Usual Medical Care in Managing COPD Exacerbations * <ul><li>85 patients (out of 275 screened) admitted to 5 ICUs with COPD exacerbation </li></ul><ul><li>RR > 30, PO 2 < 45, pH < 7.35 (needed 2) </li></ul><ul><li>Exclusions: specific respiratory process, comorbidity, need for immediate intubation, unsuitability for NPPV, DNI </li></ul><ul><li>Randomized to NPPV vs usual Rx </li></ul><ul><li>PSV 20 (no PEEP) via special face mask </li></ul><ul><li>Standardized (strict) criteria for intubation </li></ul>
  74. 74. *Brochard L et al, NEJM 1995;333(13):817-822 NPPV in COPD Exacerbations : Patient Characteristics & Changes in the 1 st Hour*
  75. 75. *Brochard L et al, NEJM 1995;333(13):817-822 NPPV in COPD Exacerbations : Need for Intubation and Other Outcomes*
  76. 76. *Brochard L et al, NEJM 1995;333(13):817-822 NPPV in COPD Exacerbations : Timing of Need for Intubation*
  77. 77. *Brochard L et al, NEJM 1995;333(13):817-822 NPPV in COPD Exacerbations : Initial Effect on PCO 2 and PO 2 *
  78. 78. *Brochard L et al, NEJM 1995;333(13):817-822 NPPV in COPD Exacerbations : Effect on Length of Hospital Stay*
  79. 79. *Ram FSF et al, Cochrane Reviews 2004(3):CD004104 NPPV in COPD Exacerbations : Meta-Analysis of Randomized Trials* <ul><li>14 good-quality studies (758 pts) as of 2003 </li></ul><ul><li>Effects of NPPV (vs usual medical care): </li></ul><ul><ul><li>Decreases mortality (Relative risk = 0.52; Number needed to treat = 10) </li></ul></ul><ul><ul><li>Decreases need for intubation (RR 0.41; NNT = 4) </li></ul></ul><ul><ul><li>Reduces treatment failure (RR 0.48; NNT = 5) </li></ul></ul><ul><ul><li>Improves pH, PCO 2 , and respiratory rate </li></ul></ul><ul><ul><li>Decreases Rx-associated complications (RR 0.38) </li></ul></ul><ul><ul><li>Shortens hospital stay (WMD -3.24 days) </li></ul></ul>
  80. 80. *Ram FSF et al, Cochrane Reviews 2004(3):CD004104 NPPV in COPD Exacerbations : Effect on Treatment Failure*
  81. 81. *Ram FSF et al, Cochrane Reviews 2004(3):CD004104 NPPV in COPD Exacerbations : Effect on Mortality*
  82. 82. *Ram FSF et al, Cochrane Reviews 2004(3):CD004104 Effect of NPPV on Need for Intubation*
  83. 83. *Ram FSF et al, Cochrane Reviews 2004(3):CD004104 NPPV in COPD Exacerbations : Effect on Length of Hospital Stay*
  84. 84. Adverse Effects of NPPV <ul><li>Inability to ventilate (mask leaks) </li></ul><ul><li>Inability to tolerate mask (claustrophobia) </li></ul><ul><li>Eye irritation </li></ul><ul><li>Dryness of upper airway; rhinitis </li></ul><ul><li>Facial reddening, pain, or ulceration </li></ul><ul><li>Gastric distension (aerophagia) </li></ul>
  85. 85. *Ram FSF et al, Cochrane Reviews 2004(3):CD004104 NPPV in COPD Exacerbations : Meta-Analysis of Randomized Trials* <ul><li>14 good-quality studies (758 pts) as of 2003 </li></ul><ul><li>Effects of NPPV (vs usual medical care): </li></ul><ul><ul><li>Decreases mortality (Relative risk = 0.52; Number needed to treat = 10) </li></ul></ul><ul><ul><li>Decreases need for intubation (RR 0.41; NNT = 4 ) </li></ul></ul><ul><ul><li>Reduces treatment failure (RR 0.48; NNT = 5 ) </li></ul></ul><ul><ul><li>Improves pH, PCO 2 , and respiratory rate </li></ul></ul><ul><ul><li>Decreases Rx-associated complications ( RR 0.38 ) </li></ul></ul><ul><ul><li>Shortens hospital stay ( WMD -3.24 days ) </li></ul></ul>
  86. 86. Trends in NPPV Use, Nosocomial Infections, and ICU Mortality, 1994-2001* <ul><li>text </li></ul>*All patients admitted with COPD exacerbation and cardiac pulmonary edema. Girou E et al, JAMA 2003;290:2985-91
  87. 87. NPPV in Acute Respiratory Failure: Patient Selection <ul><li>Acute ventilatory failure (  PCO 2 ,  pH) </li></ul><ul><li>Hypoxemia easily correctable (eg, with 50% oxygen or less) </li></ul><ul><li>Respiratory distress (eg, tachypnea, accessory muscle use) </li></ul>
  88. 88. NPPV in Acute Respiratory Failure: Patient Selection <ul><li>Expected need for ventilatory support not more than 2-3 days </li></ul><ul><li>Secretions moderate in quantity; patient able to clear them spontaneously </li></ul><ul><li>Patient hemodynamically stable (no hypotension or serious arrhythmias) </li></ul>
  89. 89. NPPV in Acute Respiratory Failure: Patient Selection <ul><li>Intact bulbar function; ability to protect lower airway </li></ul><ul><li>Patient alert and cooperative </li></ul><ul><li>Availability of experienced staff and appropriate ICU setting </li></ul>
  90. 90. *Confalonieri M et al, Eur Respir J 2005;25:348-55 Predicting NPPV Failure in COPD Exacerbations* <ul><li>Risk stratification assessed in 1,033 consecutive patients (797 successes) in 2 ICUs, 6 special RICUs, and 5 general wards in Italy </li></ul><ul><li>> 70% likelihood of failure at time of admission: </li></ul><ul><ul><li>Glasgow Coma Scale score < 11 </li></ul></ul><ul><ul><li>APACHE II > 28 </li></ul></ul><ul><ul><li>Respiratory rate > 30 </li></ul></ul><ul><ul><li>Initial pH < 7.25 </li></ul></ul><ul><li>> 90% likelihood of failure after 2 hours of NPPV: </li></ul><ul><ul><li>Arterial pH < 7.25 </li></ul></ul>
  91. 91. *Confalonieri M et al, Eur Respir J 2005;25:348-55 Prospective Validation Cohort Original 1033 Patients Solid = On admission Dashed = After 2 hrs Predicting NPPV Failure in COPD Exacerbations* <ul><li>Results used to construct a risk failure chart </li></ul><ul><li>Chart validated prospectively on another series of 145 consecutive patients </li></ul>
  92. 92. *Confalonieri M et al, Eur Respir J 2005;25:348-55 Predicting NPPV Failure in COPD Exacerbations: Risk of Failure at Time of Presentation*
  93. 93. *Confalonieri M et al, Eur Respir J 2005;25:348-55 Predicting NPPV Failure in COPD Exacerbations: Risk of Failure after 2 Hours*
  94. 94. *Confalonieri M et al, Eur Respir J 2005;25:348-55 Predicting NPPV Failure in COPD Exacerbations*
  95. 95. COPD Exacerbation: Exclusion Criteria for NPPV <ul><li>Respiratory arrest </li></ul><ul><li>Cardiovascular instability </li></ul><ul><li>Impaired mental status </li></ul><ul><li>Uncooperative patient </li></ul><ul><li>High aspiration risk </li></ul>NHLBI/WHO Workshop Report, www.goldcopd.com
  96. 96. <ul><li>Viscous or copious secretions </li></ul><ul><li>Recent facial or gastroesophageal surgery </li></ul><ul><li>Craniofacial trauma; fixed nasopharyngeal abnormalities </li></ul><ul><li>Extreme obesity </li></ul>COPD Exacerbation: Exclusion Criteria for NPPV NHLBI/WHO Workshop Report, www.goldcopd.com
  97. 97. COPD Exacerbations <ul><li>What is an exacerbation, and why are they important? </li></ul><ul><li>Diagnosis and assessment of severity </li></ul><ul><li>When and how to use bronchodilators, corticosteroids, and antibiotics </li></ul><ul><li>Oxygen therapy in the acute setting </li></ul><ul><li>When to use noninvasive ventilation </li></ul>
  98. 98. <ul><li>Respiratory arrest </li></ul><ul><li>Somnolence; impaired mental status </li></ul><ul><li>Failure of noninvasive ventilation </li></ul><ul><li>Severe dyspnea with use of accessory muscles and paradoxical abdominal motion </li></ul><ul><li>Sustained respiratory rate > 35 breaths/min </li></ul>COPD Exacerbation: Indications for Intubation NHLBI/WHO Workshop Report, www.goldcopd.com
  99. 99. <ul><li>Life-threatening hypoxemia (PaO 2 < 40 or PaO 2 /FIO 2 < 200) </li></ul><ul><li>Severe acidosis (pH < 7.25) and hypercapnia (PaCO 2 > 60) </li></ul><ul><li>Cardiovascular complications (hypotension, shock, heart failure) </li></ul><ul><li>Other complications (metabolic abnormalities, sepsis, pneumonia, pulmonary embolism, barotrauma, massive pleural effusion) </li></ul>COPD Exacerbation: Indications for Intubation NHLBI/WHO Workshop Report, www.goldcopd.com

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