TREATMENT OF COPD EXACERBATIONS

1. TREATMENT OF COPD EXACERBATIONS Prof.Dr.Hakan GÜNEN İnönü Üniversitesi Tıp Fakültesi Göğüs Hastalıkları Ana Bilim Dalı MALATYA

2. Objective • To learn about the treatment of exacerbations of chronic obstructive pulmonary disease (COPD) (outpatients, hospital, intensive care unit)

3. Overview of Presentation • Introduction • Definition of COPD exacerbation • Epidemiology of COPD exacerbation • Patient evaluation • Treatment at home • Treatment at hospital and intensive care unit • Other treatments • Discharge criteria and follow-up

4. Introduction • COPD is the 4th leading cause of death worldwide • It is the 3rd. leading cause of death in Turkey. • Mortality in COPD is significant. • Mortality during exacerbations is approximately 5-10% • Cost of treatment in COPD is high (8500 USD per year) • Cost of treatment in COPD exacerbations is much higher (5400 USD per exacerbation)

5. Definitions of Exacerbations of COPD • Previous definitions: a)Antonisen’s definition (1987): This definition is based upon the hypothesis that exacerbations are are caused by bacterial infections. “defined as worsening of at least one of the cardinal COPD symptoms, dyspnea, ,increased sputum volume or sputum purulence; Type 1, Type 2, Type 3”

6. Definitions of Exacerbations of COPD • ACCP Working Group definition (2000) “a sustained worsening of the patient’s condition, from the stable state and beyond normal day-to-day variations, that is acute in onset and necessitates a change in regular medication in a patient with underlying COPD”

7. Definitions of Exacerbations of COPD • c)Definition of ATS-ERS (2004): “an exacerbation of COPD is an event in the natural course of the disease characterised by a change in the patient’s baseline dyspnoea, cough and/or sputum beyond day-to-day variability sufficient to warrant a change in management”

8. Definitions of Exacerbations of COPD d) Definition of GOLD: GOLD avoided making a specific definition until 2006. Their definition resembels ATS-ERS definition. Definition of GOLD 2007; “An exacerbation of COPD is defined as an event in the natural course of the disease characterized by a change in the patientes baseline dyspnea, cough, and/or sputum that is beyond normal day-to-day variations, is acute in onset, and may warrant a change in regular medication in a patient with underlying COPD.”

9. Definitions of Exacerbations of COPD • Conclusion: • There is no consensus regarding the definition. • Even investigators set study specific their own definitions (ISOLDE – “worsening of COPD symptoms which necessitates oral steroid and/or antibiotic utilization”). • Conflicts (acute exacerbation, attack, acute attack etc.)

10. Causes of COPD Exacerbations • Bacterial and viral infections are assumed to be responsible from 70-80% of the exacerbations -Primary causes: Infections, inhalation of environmental irritants, cold air, uncompliance with the treatment -Sekondary causes: Pneumoniae, pulmonary emboli, pneumothorax, cardiac failures

11. Causes of COPD Exacerbations

12. Causes of COPD Exacerbations • Bacterial causes: S. Pneumoniae, H. İnfluenza, M. Catarrhalis, (less frequently, Mycoplasma P. , Chylamidia P., P. aeuroginosa). • Viral causes: Rhinoviruses, RSV, (less frequently Influenza A-B, Parainfluenza, Coronavirus, Adenovirus).

13. Epidemiology of COPD Exacerbations • Until recently, attack rates were not evaluated and analyzed as a primary result in the studies. There are few studies addressing this issue. • However, attack rates have been utilized in comparing the different primary results in COPD studies.

14. Epidemiology of COPD Exacerbations • So far it is not possible to give a certain figure on exacerbation rates in COPD patients. • Patient statements, hospitalization rates, medical records, PEF values, complicated device utlizations, drug dozimeters, phone calls, home visits etc. • Studies bare many pitfalls, perfect method could not be reached yet.

15. Epidemiology of COPD Exacerbations • Exacerbation rates from major COPD studies; TORCH: 1 exacerbation/year MISTRAL: 1,5 exacerbation/year GLAXO world data: 1exacerbation/year ISOLDE: 1,5 exacerbation/year

16. Epidemiology of COPD Exacerbations • What is the reality?? • Haughney et al.; 4.6 exacerbation/year (ERJ 2005) • PERCEIVE study; 5.1 exacerbation/year • Conclusions: According to the results of all studies 1) COPD patients do not report at least half of their exacerbations when asked. 2) One of every 2 exacerbation ends with hospitalization (8 times more exacerbation and hospitalization rates than asthma)

17. Epidemiology of COPD Exacerbations • FEV1; Most significant factor on COPD exacerbation rates (Burge et al. ERJ 2003)

18. Determining Severity of Exacerbation • There is no consensus in determining the severity of an exacerbation. • However, it is important in determining how to treat and where to treat the patient -home, hospital, intensive care unit -non-invasive, invasive mechanical ventilation -bronchodilator dosages -corticosteroid durations -antibiotic choice -additional treatments (diuretics, cardiac support destek)

19. Determining Severity of Exacerbation • Anthonisen’s (1987) classification • The classification based upon symptom severity and symptom duration with spirometric alterations (Seemungal ve ark. AJRCCM 2000)

20. Determining Severity of Exacerbation • Classification based upon the increased need for bronchodilators and antibiotic use, corticosteroid administration and hospitalization (Burge et al. ERJ 2003)

21. Determining Severity of Exacerbation • GOLD’s recommendations are quite subjective “Assessment of the severity of an exacerbation is based on the patientes medical history before the exacerbation, preexisting comorbidities, symptoms, physical examination, arterial blood gas measurements, and other laboratory tests. Specific information is required on the frequency and severity of attacks of breathlessness and cough, sputum volume and color, and limitation of daily activities. When available, prior arterial blood gas measurements are extremely useful for comparison with those made during the acute episode, as an acute change in these tests is more important than their absolute values“.

22. Determining Severity of Exacerbation • GOLD’s recommendations for assessment of COPD exacerbations: medical history and signs of severity

23. Determining Severity of Exacerbation • GOLD’s other recommendations; - Spirometry and PEF measurements - Arterial blood gas analysis (PaO2<60 mmHg, PaCO2>50 mmHg, pH<7.35) - Chest films and ECG - Blood tests (leucocyte, hemoglobin, electrolytes, blood glucose) - Sputum Gram staining and culture antibiogram

24. Determining Severity of Exacerbation • Home or hospital? There is no strict criteria about which patients should be treated at home. However there are some criteria which patients should not be treated at home Respiratory rate higher than 25/min Pulse rate higher than110/min PaO2 less than 60 mm Hg Abnormal chest radiograph Serious concomitant disease Altered mental state Living alone

25. At Home Treatment Plan • ABC plan -Antibiotic -Bronkodilators -Corticosteroid

26. At Home Treatment Plan • GOLD’s recommendation

27. Antibiotics • Although there is no consensus, antibiotics are recommended when there is an increase in one of the cardinal COPD symptoms in addition to increased sputum purulence in patients who will be treated outpatients settings (GOLD 2007).

28. Antibiotics • Oral route should be preferred Treatment duration 3-10 days

29. Bronchodilators

30. Bronchodilators; how and how much?? - If the patient can use, inhalers or spacers should be preferred. There is no additional efficacy administrating the drugs by nebulizers except indicated. - Short acting Beta-2 mimetics should be preferred. Initial doses can be given more frequently. The total dose should not exceed 12 times a day by inhaled or nebulized routes. - Side effects??

31. Bronchodilators • Maximum dose of anticholinergics should not exceed 6 times a day (inhaled or nebulized). • Even at the initial period, it should not be given more frequently than 2 hrs. • Intermittent combination with Beta-2 agonists is justified • Side effects?? • Theophyllin??

32. Corticosteroids - If the expected result from frequent initial bronchodilator treatment can not be obtained specifically in patients with FEV1<%50; 7-10 days perdnisolone 30-40 mgr/gün (GOLD 2007) - Oral route should be preferred - It is assumed to shorten the recovery period and accelarates the normalization of FEV1 and PaO2 ?? - SIDE EFFECTS??? - High dose nebulized budesonide may be an alternative (GOLD 2007 ref.419)

33. Hospital Treatment of COPD Exacerbations • Mortality in hospitalized patients is higher than the mortality in patients treated at home (1-2% versus 10%) • Mortality is much higher in patients treated at intensive care unit than the patients treated at ward (3% versus 27 %) (GOLD 2007, 316. ref.)

34. Hospitalization Criteria in COPD Exacerbations • Marked increase in intensity of symptoms, such as sudden development of resting dyspnea • Severe underlying COPD • Onset of new physical signs (e.g., cyanosis, peripheral edema) • Failure of exacerbation to respond to initial medical management • Significant comorbidities • Frequent exacerbations • Newly occurring arrhythmias • Diagnostic uncertainty • Older age • Insufficient home support

35. Treatment Algorhytm • Assess severity of symptoms, blood gases, chest X-ray • Administer controlled oxygen therapy and repeat arterial blood gas measurement after 30-60 minutes • Bronchodilators: – Increase doses and/or frequency – Combine 2-agonists and anticholinergics – Use spacers or air-driven nebulizers – Consider adding intravenous mehylxanthines, if needed • Add oral or intravenous glucocorticosteroids • Consider antibiotics (oral or occasionally intravenous) when signs of bacterial infection • Consider noninvasive mechanical ventilation • At all times: – Monitor fluid balance and nutrition – Consider subcutaneous heparin – Identify and treat associated conditions (e.g., heart failure, arrhythmias) – Closely monitor condition of the patient

36. In the Ward or Intensive Care Unit? • Severe dyspnea that responds inadequately to initial emergency therapy • Changes in mental status (confusion, lethargy, coma) • Persistent or worsening hypoxemia (PaO2<40 mmHg), and/or severe/worsening hypercapnia (PaCO2>60 mmHg), and/or severe/worsening respiratory acidosis (pH<7.25) despite supplemental oxygen and noninvasive ventilation • Need for invasive mechanical ventilation • Hemodynamic instability — need for vasopressors These patients should be transferred to the intensive care unit

37. Oxygen Treatment • Oxygen treatment should be given in a controlled manner (PaO2>60 mm Hg or Saturation >90) • CO2 retention and development of acidosis should be monitored • Arterial blood gas analysis should be repeated every 30-60 minutes. After the stability, pulse oximetry could be applied. • The route of oxygen delivery depends upon patient comfort or physician’s experience

38. Bronchodilator Treatment • Inhaled or nebulized short acting Beta-2 agonists should be preferred • In cases with limited response, combination with anticholinergics can be tried • Same principles for bronchodilator treatment at home are applicable (the routes and dosages) • Theophylline infusion can be tried in cases with unresolving symptoms (efficacy?, side effects?, narrow therapeutic range?, close monitorization?).

39. Corticosteroid Treatment • It should be initiated to every hospitalized patient without any contraindication • It shortens the hospitalization period, and accelarates the recovery of hypoxemia and FEV1 • 30-40 mg prednizolone/day, 7-15 days • Oral or intravenous • Side effects??? • Alternative: high dose nebulized budesonide? (GOLD 2007)

40. Antibiotic treatment; to whom, when and which antibiotic • Worsening of 3 cardinal COPD symptoms • Worsening of at least 1 cardinal COPD symptom in addition to increased sputum purulence • In conditions where invasive or non-invasive mechanical ventilation indicated Hospitalized patients are Grup B and C any more

41. Antibiotic Treatment • Group B: In addition to Group A; beta lactamase producing penicillinase resistant S.pneumoniae and Enterobacteriacea (K. Pneumoniae, E. coli, Proteus, Enterobacter vs.). No risk for P. aeruginosa. • Group C: In adition to Group B, there is risk for P. aeruginosa

42. Antibiotic Treatment • While the severity of exacerbation is increasing, infecting microorganism profile shifts from S.pneumoniae to Gram (-) enteric bacilli and P.aeruginosa

43. Antibiotic Treatment Shifting Microorganisms

44. Antibiotic Algorhytm

45. Antibiotic Treatment • Oral or intravenous. • 3-10 days

46. Additional Therapeutic Options • Respiratory stimulants; Not recommenden in general termsç. Only doxapram may be tried in cases where noninvasive ventilation is indicared but can not be available 2. Ventilatory support: Noninvasive and invasive mechanical ventilation

47. Noninvasive Mechanical Ventilation • It helps in avoiding ICU admissions and intubation. • Its indications have increased for the last 10 years. • Indicated in 40% of hospitalized patients with COPD exacerbations. • Success rate 70-80%

48. Indications of Noninvasive Mechanical Ventilation • Moderate to severe dyspnea with use of accessory muscles and paradoxical abdominal motion • Moderate to severe acidosis (pH less than 7.35 ) and/ or hypercapnia (PaCO2 > 45 mm Hg) • Respiratory frequency > 25 breaths per minute

49. Contraindications of Noninvasive Mechanical Ventilation • Respiratory arrest • Cardiovascular instability (hypotension, arrhythmias, myocardial infarction) • Change in mental status; uncooperative patient • High aspiration risk • Viscous or copious secretions • Recent facial or gastroesophageal surgery • Craniofacial trauma • Fixed nasopharyngeal abnormalities • Burns • Extreme obesity.

50. How to Apply Noninvasive Mechanical Ventilation • CPAP mode is not recommended in COPD patients except in cases where BIPAP is not available • BIPAP mode is recommended to be adjusted from low pressures to high pressures • Initial pressures approximately İ:8 mm Hg, E:4 cm H2O • Arterial blood gas analyses and SpO2 will help in titrating the pressures