Acute exacerbation of COPD-DIAGNOSIS AND MANAGEMENT.pptx

aecopd

1. ACUTE EXACERBATION OF COPD Diagnosis And Management Dr Dimple Makhija Senior Resident SGPGIMS

2. DEFINITION GOLD Acute worsening of respiratory symptoms that results in additional therapy

3. DEFINITION NICE GUIDELINES A worsening of the patient’s symptoms from their usual stable state which is beyond normal day-to-day variations, and is acute in onset

4. DEFINITION ERS/ATS guidelines Episodes of increasing respiratory symptoms, particularly dyspnea, cough and sputum production, and increased sputum purulence

5. Shortcomings of the definitions Relies exclusively on a patient’s subjective perception of increased respiratory symptoms which could be mimicked by other conditions such as pneumonia, cardiac events, or pulmonary embolism Does not relate the symptoms to measurable pathophysiological variables that could characterize the event itself Lacks a framework for timing of the event’s evolution Severity is established post event by the healthcare resource used to treat the event

6. DEFINITION In a patient with COPD, an exacerbation is an event characterized by dyspnea and/or cough and sputum that worsen over ≤14 d, which may be accompanied by tachypnea and/or tachycardia and is often associated with increased local and systemic inflammation caused by airway infection, pollution, or other insult to the airways.

7. Exacerbations are classified as: Mild -treated with short acting bronchodilators only(SABDs) Moderate -treated with SABDs plus antibiotics and/or oral corticosteroids Severe -patient requires hospitalization or visits the emergency room *Gold 2022

8. INPATIENT OR OUTPATIENT ?

9. Severity of exacerbations in Hospitalised Patients- GOLD 2022 Clinical scenario Respiratory rate Use of accessory respiratory muscles Change in mental status Supplemental oxygen given via Venturi mask (FiO2%) PCO2 pH No respiratory failure 20-30 No No 28-35 Normal Normal Acute respiratory failure (non-life threatening) >30 Yes No 35-40 40-60 Normal Acute respiratory failure (life-threatening) >30 Yes Yes >40 >60 <7.25

10. Pharmacological Treatment Bronchodilators- SABA with or without SAMA, are the initial bronchodilators for acute treatment of a COPD exacerbation(no high quality evidence). A Cochrane review published in 2010 concluded no difference in the degree of bronchodilation achieved with ipratropium bromide than that using a SABA. The combination of a beta2-agonist and ipratropium did not appear to increase the effect on FEV1 more than either used alone. Combination therapy with salbutamol and  ipratropium  is clearly superior to albuterol alone in stable COPD , but studies in acute exacerbations are limited. McCrory DC, Brown CD. Anti-cholinergic bronchodilators versus beta2-sympathomimetic agents for acute exacerbations of chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2002;2003(4):CD003900. doi : 10.1002/14651858.CD003900. PMID: 12519615; PMCID: PMC8753782 .

11. Narrative synthesis of 10 studies revealed no significant differences in most outcomes of interest relative to dose, delivery via inhaler or nebuliser , and type of β2-agonist used. Some evidence demonstrated significantly increased cardiac side effects with increased dosage of β2-agonist (45% versus 24%), P<0.05).

12. To compare the bronchodilator response to incremental doses of inhaled albuterol during and after recovery from an AECOPD, and to compare the effects of regular nebulized albuterol, 2.5 mg and 5 mg, on the speed of recovery. Significant improvement in Emax to inhaled albuterol as the COPD exacerbation resolved. No significant difference in outcomes including length of hospital stay or recovery of lung function between patients treated with regular 2.5 mg vs 5 mg of nebulized albuterol during an AECOPD.

13. METHOD OF DRUG DELIVERY- No significant differences in FEV1(primary outcome)between MDI with or without a spacer or nebulizers to deliver the agent

14. Use of LABA/LAMA Not specifically studied. GOLD guidelines advise their continuation during exacerbation. Start the medications as soon as possible prior to discharge

15. GLUCOCORTICOIDS Systemic Steroids- OPD setting/Ambulatory patients- As per the ERS guidelines - a short course (⩽14 days) of oral corticosteroids is suggested.(conditional recommendation, very low quality of evidence). GOLD- shorten recovery time improve lung function (FEV1), improve oxygenation, Reduce the risk of early relapse, treatment failure, and the length of hospitalization.

16. Patients requiring hospital admission- Administration of oral corticosteroids rather than intravenous corticosteroids if gastrointestinal access and function are intact is suggested (conditional recommendation, low quality of evidence).- ERS 2017 Therapy with oral prednisolone is equally effective to intravenous administration. Glucocorticoids may be less efficacious to treat acute COPD exacerbations in patients with lower levels of blood eosinophils Inhaled Glucocorticoids- High dose nebulized budesonide has been examined in few trials as alternative to systemic glucocorticoids but not in patients requiring ICU care.

17. Systemic corticosteroids should be administered to all patients experiencing AECOPD severe enough to seek emergent medical care. The lowest effective dose and shortest duration of therapy should be considered.

18. Trial Design Intervention Baseline patient characteristics Primary outcomes Secondary outcomes Davies et al R, DB, PC n=56 Oral prednisolone 30 mg once daily ×14 days versus placebo Mean age 67 years FEV1 =0.59 L Predicted FEV1 increased from 28.2% to 41.5% in the corticosteroid group (P,0.001) Hospital stays were shorter in the corticosteroid group Niewoehner et al (SCCOPE ) n=271 Oral glucocorticoid for 2 weeks versus 8 weeks versus placebo Mean age 67.6 years FEV1 =0.77 L Rate of treatment failure glucocorticoids versus placebo at 30 days (23% versus 33%, P=0.04) and 90 days (37% versus 48%, P=0.04) Systemic steroids (in both groups) associated with a shorter hospital stay (8.5 days versus 9.7 days for placebo, Aaron et al n=147 Oral prednisone 40 mg once daily versus placebo Mean age 69 years FEV1 =1 L Rate of relapse at 30 days was lower in the prednisone group versus placebo (27% versus 43%, Change in postbronchodilator FEV1 from day 1 to day 10 prednisone versus placebo (34% versus 15%,

19. IV VS ORAL CORTICOSTEROIDS This was a randomized, parallel-group study aiming to compare the effectiveness and safety of orally administered lower dose of steroids with  parenteral administration  of higher doses.

20. N= 40 These data show that  oral administration  of MP at a dose 32 mg/day for seven days significantly improves lung function, dyspnea scores and oxygenation in patients admitted to the hospital for COPD exacerbation and is as effective as and possibly safer than parenteral admininistration of higher doses . N=20 Oral methyl prednisolone 32mg/day for 7 days N= 20 IV MP at 1 mg/kg/day for four days and 0.5 mg/kg/day for three days

21. Duration of Corticosteroid Therapy GOLD- 30-40 MG/DAY x 5 DAYS ERS- THERAPY FOR 10-14 DAYS

22. Data in Support for a short course of steroids- SCCOPE trial- A double-blind, randomized trial of systemic glucocorticoids (given for two or eight weeks) or placebo in addition to other therapies No additional benefit in the longer course. Patients in the eight week group experienced more glucocorticoid-related side effects.

23. A randomized, noninferiority multicenter trial in 5 Swiss teaching hospitals, enrolling 314 patients presenting to the emergency department with acute COPD exacerbation, from March 2006 through February 2011. 5-day treatment with systemic glucocorticoids was noninferior to 14-day treatment with regard to reexacerbation within 6 months of follow-up 

24. RCT by Maltias et al on comparison of nebulized budesonide and oral prednisolone with placebo in the treatment of acute exacerbations of chronic obstructive pulmonary disease (AJRCCM – 2002). D ouble-blind, randomized, placebo-controlled trial in which the efficacy of nebulized budesonide, oral prednisolone, and placebo was compared in 199 patients with acute exacerbations of COPD requiring hospitalization (Patients received either 2 mg of budesonide every 6 h (n = 71), 30 mg of oral prednisolone every 12 h (n = 62), or placebo (n = 66). Both budesonide and prednisolone improved airflow in COPD patients with acute exacerbations when compared with placebo. Nebulized budesonide may be an alternative to oral prednisolone in the treatment of nonacidotic exacerbations of COPD but further studies should be done to evaluate its long-term impact on clinical outcomes after an initial episode of COPD exacerbation.

25. 9 studies which were included in this meta-analysis was conducted in subjects who were hospitalized and not critically ill. High-dose nebulized budesonide 4 – 8 mg/d was noninferior to systemic corticosteroids on the change in FEV1 between baseline and the last measured value and PaCO2 but of inferior efficacy for PaO2 change. Hyperglycemia was less frequent with high-dose nebulized budesonide.

26. A nationwide multicentre prospective trial (n=318) investigating eosinophil-guided corticosteroid treatment for AECOPD P atients were randomly assigned(1:1) to either eosinophil-guided therapy or standard therapy with systemic corticosteroids Patients received 80 mg of methylprednisolone on day 1, followed by either: (a) 37.5  mg of daily prednisolone for 4  days or (b) prednisolone only on the days when peripheral blood eosinophil count was≥  300 cell/microliter E osinophil-guided therapy was non-inferior compared with standard care for the number of days alive and out of hospital, and reduced the duration of systemic corticosteroid exposure, although we could not entirely exclude harm on some secondary outcome measures

27. In this study, exacerbations in outpatients with COPD were grouped in four independent clusters: bacterial-, viral-, eosinophilic predominant and “pauci-inflammatory,” associated with limited changes in the inflammatory profile. Low eosinophil counts at the presentation of the exacerbation, particularly if associated with elevated levels of CRP (a marker of possible concomitant infection), are associated with a poor prognosis of the exacerbation. Lower treatment failure rates in patients with high blood eosinophil levels receiving oral CS than in the standard care group. Vice versa, patients with low blood eosinophil levels experienced high failure rates when treated with OCS.

28. Antibiotics Antibiotics should be given to patients with exacerbations of COPD who have three cardinal symptoms: increase in dyspnea, sputum volume, and sputum purulence or require mechanical ventilation. ( Anthonisen et al) Shorten recovery time, reduce the risk of early relapse ,treatment failure and hospital duration.(Evidence B)- GOLD 2022 For ambulatory patients having a COPD exacerbation, administration of antibiotics is suggested (conditional recommendation, moderate quality of evidence). ERS- 2016

29. The choice of the antibiotic should be based on the local bacterial resistance pattern. Usually, initial empirical treatment is an aminopenicillin with clavulanic acid, macrolide, or tetracycline. In patients with frequent exacerbations, severe airflow limitation,and /or requiring mechanical ventilation, cultures from sputum or other materials from the lung should be performed

30. A Cochrane review (2018) , included 19 randomised studies that compared antibiotics versus placebo in a total of 2663 COPD patients with a wide range of flare-up severity. Antibiotics reduced treatment failures compared with placebo in outpatients with mild to moderate flare-ups and in patients admitted to an intensive care unit for very severe flare-ups with respiratory failure. However, antibiotics did not reduce treatment failures among hospitalised patients with severe flare-ups Use of antibiotics led to reduced mortality only in patients admitted to an intensive care unit Antibiotics did not reduce length of hospital stay for hospitalised patients. * Vollenweider DJ, Jarrett H, Steurer-Stey CA, Garcia- Aymerich J, Puhan MA. Antibiotics for exacerbations of chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2012;12:CD010257

31. Treatment of ambulatory exacerbations of mild-to moderate COPD with amoxicillin/clavulanate is more effective and significantly prolongs the time to the next exacerbation compared with placebo.

32. Randomised , controlled trial in 220 aecopd patients , comparing C-reactive protein (CRP)-guided antibiotic treatment ( (CRP ⩾50 mg·L−1 ) to patient reported symptoms in accordance with the GOLD strategy. Use of CRP as a biomarker to guide antibiotic treatment in severe acute exacerbations of COPD leads to a significant reduction in antibiotic treatment. In the present study, no differences in adverse events between both groups were found

33. CRP-guided prescribing of antibiotics for exacerbations of COPD in primary care clinics resulted in a lower percentage of patients who reported antibiotic use and who received antibiotic prescriptions from clinicians, with no evidence of harm

34. Prospective randomized controlled trial of 302 severe acute exacerbation of COPD with or without pneumonia admitted in ICU failed to demonstrate the ability of a PCT-guided strategy to safely reduce antibiotic exposure, Prompt initiation of antibiotherapy in this population improves 3-month survival regardless of the level of PCT

35. Of 509 papers identifed , 39 papers evaluating 61 biomarkers were eligible for inclusion. Moderate quality evidence was found for associations between serum C-reactive protein (CRP), serum procalcitonin (PCT), sputum interleukin (IL)-8 and sputum tumour necrosis factor alpha (TNF- α), and the presence of bacterial pathogens in the sputum of patients with AECOPD. Having bacterial pathogens was associated with a mean diference (higher) CRP and PCT of 29.44 mg/L and 0.76 ng/mL respectively

36. ADJUNCTS Appropriate fluid balance, Use of diuretics when clinically indicated, Anticoagulants, Treatment of comorbidities Nutritional aspects

37. RESPIRATORY SUPPORT CONTROLLED OXYGEN THERAPY- Supplemental oxygen should be titrated to improve the patient’s hypoxemia with a target saturation of 88-92% Blood gases should be checked frequently to ensure satisfactory oxygenation without carbon dioxide retention and/or worsening acidosis Augusti et al in 1999 (ERJ), compared nasal prong and venturi mask in terms of their potentiality to worsen respiratory acidosis and their capacity to maintain adequate (>90%) arterial oxygenation through time.

38. Both the VM and NPs are able to initially oxygenate arterial blood adequately without significantly worsening the pre-existing degree of respiratory acidosis but neither of them is able to guarantee an SaO2 of >90% through time in the majority of patients In AECOPD patients with respiratory failure it was suggested 1) arterial oxygen saturation is maximized at the beginning of treatment by increasing the inspiratory oxygen fraction 2) the Venturi mask is used whenever possible Carlos et al , assessed the impact of admission oxygen saturation level and baseline carbon dioxide on inpatient mortality in 2645 patients of COPD exacerbation (BMJ 2020) and observed inpatient mortality was lowest in those with oxygen saturations of 88%–92%. Even modest elevations in oxygen saturations above this range (93%–96%) were associated with an increased risk of death.

39. HIGH FLOW NASAL THERAPY Heated and humidified air-oxygen upto 60 L/min in adults. Decreases respiratory rate and effort, Decreased work of breathing, Improved gas exchange, Improves lung volume and dynamic compliance

40. VENTILATORY SUPPORT

41. NON INVASIVE MECHANICAL VENTILATION

42. Preferred initial mode of ventilation to treat acute respiratory failure in patients hospitalized for AECOPD It has been studied in RCTs ,showing a success rate of 80-85%. * R educes mortality and the intubation rate (ERS 2017) Decreases respiratory rate, work of breathing Improve oxygenation and acute respiratory acidosis Decreases complications such as ventilator associated pneumonia, and length of hospital stay . * Osadnik CR, Tee VS, Carson- Chahhoud KV, Picot J, Wedzicha JA, Smith BJ. Non-invasive ventilation for the management of acute hypercapnic respiratory failure due to exacerbation of chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2017

43. To evaluate the intubation and mortality risks of HFNC compared to non-invasive ventilation (NIV) and conventional oxygen therapy (COT) for AECOPD patients Seven RCTs and one observational study were included. No data were available for intubation or mortality risk for HFNC compared with COT Low-quality evidence indicates that HFNC does not increase intubation and mortality risks compared to NIV.

44. INVASIVE MECHANICAL VENTILATION

45. Hospital Discharge and Follow Up

46. 1-4 weeks Follow up- Review and understand treatment regimen Reassess Inhaler technique Reassess need for long term oxygen Consider patient eligibility to be enrolled in pulmonary rehabilitation Document symptoms – CAT or mMRC Determine status of comorbidties Reassess at 12-16 weeks in Follow up.

47. Practice changing Update There was a decrease in hospitalization rates with emergency department intravenous magnesium administration compared with placebo. S evere exacerbation that is not responding promptly to short-acting inhaled bronchodilators, IV administration of a single dose of  magnesium sulfate   is suggested (grade 2 C)

48. TREATMENTS WITHOUT DOCUMENTED BENEFIT Mucoactive Agents Methyl Xanthines - A Cochrane review published in 2008 determining the benefit of methylxanthines compared to placebo for COPD exacerbations. Conclusion- methylxanthines should not be used for COPD exacerbations. beneficial effects in lung function and clinical endpoints were inconsistent, whereas adverse effects were significantly increased. Nebulized Magnesium Chest Physiotherapy

49. © 2022 Global Initiative for Chronic Obstructive Lung Disease

50. THANK YOU