COPD Exacerbation

COPD ExacerbationUNM Best Practice MeetingJosh Young8/27/10

Why do we need to worry about this?Growing number of hospitalizations in the U.S.463,0020 in 1990726,000 in 200010% mortality in hospitalized patients~25% mortality in ICU admissions$32 billion in the U.S. in 2002 ($18 billion related to in-hospital care)2Best Practice Meeting - COPD Exacerbation

DefinitionThe Global Initiative for Chronic Obstructive Lung Disease (GOLD) defines an exacerbation as:an event in the natural course of the disease characterized by a change in the patients 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.Best Practice Meeting - COPD Exacerbation3

GoalsUnderstand the pathophysiology of exacerbationsLearn more about the current guidelines for treatment of COPD exacerbation and why?Discuss the current practices at UNM?Develop our own best practicesSmoking cessation4Best Practice Meeting - COPD Exacerbation

4Pathophysiology(Brief Overview)Characterized by 2 separate processesChronic Bronchitis:Excessive mucus production with airway obstruction mostly affecting the smaller airways with hyperplasia of mucus producing glands and damage to the endothelium that impairs the clearance of bacteria and mucus.Emphysema:Gradual destruction of alveolar septae and the pulmonary capillary bed5Best Practice Meeting - COPD Exacerbation

5Pathophysiology(Exacerbations)Exacerbations are heterogeneous in severity and presentationThey are usually contributed to bacterial or viral infection and pollutants such as tobacco smokeA significant amount (~30%) do not have a clear etiologySevere exacerbations are thought to be due to increased inflammation leading to worsening expiratory flow limitation and dynamic hyperinflation and increased air trappingThis increased air trapping causes your tidal breathing to shift closer to total lung capacity, where you have a less favorable relationship between volume and pressure 6Best Practice Meeting - COPD Exacerbation

GoalsUnderstand the pathophysiology of exacerbationsLearn more about the current guidelines for treatment of COPD exacerbation and why?Discuss the current practices at UNM?7Best Practice Meeting - COPD Exacerbation

Global Initiative for Chronic Obstructive Lung Disease (GOLD)Global organization initiated in 1998Goal to produce recommendations for management of COPD based on the best scientific information availableFirst guidelines were released in 2001 with a complete revision in 2006Last update in 2009 including articles up to June 30, 2009www.goldcopd.orgBest Practice Meeting - COPD Exacerbation8

Department of Veteran Affairs/ Department of DefenseVA/DoD clinical practice guideline for management of outpatient chronic obstructive pulmonary disease.Updated in 2007Focus mostly on outpatient management and target patients of VA/DoD systemBest Practice Meeting - COPD Exacerbation9

PreventionSmoking cessation is still the most effective intervention in reducing risk of developing COPD and decreasing its progressionRecommendations are to counsel smokers to quit at every opportunityApply affective counseling techniques Consider pharmacotherapy in situations where counseling isnt enoughInfluenza vaccines can reduce serious illness and death in COPD patients by 50%Pneumococcal vaccine is recommended in COPD patients over 65 years old and in patients with FEV1 < 40%Best Practice Meeting - COPD Exacerbation10

1. Pneumococcal shown to decrease incidence10EvaluationCareful history and physical examGeneral recommendations do not support spirometry upon acute evaluationPulse oximetryArterial blood gases Best Practice Meeting - COPD Exacerbation11

S/sx of severity:FEV1Duration of worsening or new sxsNumber of previous episodesComorbiditiesPresent treatment regimenUse of accessory muscles, paradoxical chest wall movements, central cyanosis, peripheral edema, hemodynamic instability, right heart CHF, mental status changesVA/DoD note that spirometry can be considered in patients able to perform the test and have baseline studies to compare to.Both agree in ABG important to evaluate severity with PaO2 < 60 mm Hg and/or SaO2 < 90% with or without PaCO2 > 50 mm Hg on RA indicates respiratory failureABG with acidosis pH < 7.36 plus PaCO2 > 45-60 mm Hg is an indication for mechanical ventilation11Evaluation and TriageChest X-rayECGCBC, BMPDifferential Diagnosis:Pulmonary embolism should be considered with any patient being hospitalized with a pretest probability of intermediate to highPneumonia, CHF, pneumothorax, pleural effusion, and cardiac arrhythmia

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ECG to evaluate right heart hypertrophy, arrhythmias, ischemiaLow SBP and inability to increase PaO2 > 60 mm Hg should suggest PE 12Prevalence of Pulmonary Embolism in Acute Exacerbations of COPD : A Systematic Review and Metaanalysis. Rizkallah et al. Chest. 2009.Clinical question: What is the prevalence of PE in acute exacerbations of COPD in patients who did and did not require hospitalization.Methods: Only cross-sectional or prospective studies that used CT scanning or pulmonary angiography for PE diagnosis were included.2,407 articles were identified, 5 met the inclusion criteria including 550 patientsOverall prevalence of PE was 19.9% (95% confidence interval [CI], 6.7 to 33.0%; p 0.014).Hospitalized patients 24.7% (95% CI, 17.9 to 31.4%; p 0.001)Best Practice Meeting - COPD Exacerbation13

Only 1 study calculated pretest probability use Geneva score and found prevalence of ~9%Note limitations of heterogeneity and small sample size13TriageHospitalization:Marked increase in intensity of symptoms (resting dyspnea)Severe underlying COPDOnset of new physical symptomsFailure of initial medical managementSignificant comorbiditiesFrequent exacerbationsNewly occurring arrhythmiasDiagnostic uncertaintyOlder ageInsufficient home supportBest Practice Meeting - COPD Exacerbation14

TriageMICU:Severe dyspnea that does not respond adequately to initial therapyChanges in mental statusPersistent or worsening hypoxemia (PaO2 < 40 mm Hg or hypercapnia PaCO2 > 60 mm Hg or pH < 7.25 despite O2 and NIVNeed for invasive mechanical ventilationNeed for vasopressorsBest Practice Meeting - COPD Exacerbation15

Oxygen TherapyBoth guidelines state that oxygen supplementation should be used to keep PaO2 > 60 mm Hg or SaO2 > 90%GOLD notes that CO2 retention can occur insidiously with little change in symptoms and recommend rechecking an ABG 30-60 minutes after oxygen therapy startedAppropriate to start before complete evaluationBest Practice Meeting - COPD Exacerbation16

1. No clear evidence to support this practice and there are no recommendations as what further treatment steps should be taken16Bronchodilators3 classes of medications:B2 agonists (albuterol)Anticholinergics (ipratropium)Methylxanthines (theophylline)Guidelines vary with respect to use and no studies appear to clearly demonstrate superiorityAgree that initiation of therapy can be started prior to full ED evaluationThere does not appear to be a difference in MDI or nebulizer therapy

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BronchodilatorsGOLD recommends stepwise approach to use by starting with short-acting B2-agonistIf no prompt response to treatment occurs, consider adding anticholinergicAll agree that methylxanthines should not be used routinely because of adverse effects and lack of efficacy Although, GOLD notes that they are considered second-line IV therapy

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Guidelines appear to be made without any significant evidenceMultiple studies show no improvement with addition of anticholinergicTheophylline side effects: nausea/vomiting, tremor, palpitations, and arrhythmias18GlucocorticosteroidsBoth guidelines agree that oral corticosteroids should be used for acute exacerbations30 40 mg of oral prednisolone dailyGOLD: 7-10 daysVA/DoD: up to 14 days

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EFFECT OF SYSTEMIC GLUCOCORTICOIDS ON EXACERBATIONS OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE. Niewoehner et al. N Engl J Med. 1999Double blind randomized trialClinical Question: Determine rates of treatment failure between systemic glucocorticoids and placebo. Secondary goal to determine the optimal duration of therapy.Methods: All patients admitted to participating VAs for COPD exacerbation who met inclusion criteria:Clinical diagnosis of COPD exacerbationAge > 50 years30 pack year smoking historyFEV1 of 1.5L or less or inability to complete testingBest Practice Meeting - COPD Exacerbation20

Treatment failure consists of:Death from any causeNeed for intubationReadmission for COPDIntensification of therapy20EFFECT OF SYSTEMIC GLUCOCORTICOIDS ON EXACERBATIONS OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE. Niewoehner et al. N Engl J Med. 1999Exclusion criteria included:Diagnosis of asthmaSystemic glucocorticoids in last 30 daysComorbidities making survival of 1 year unlikelyInability to give consentPatients hospitalized for at least 3 days and given IV Solu-Medrol followed by either 2 or 8 week taper starting at 60 mg of PrednisoneBest Practice Meeting - COPD Exacerbation21

21EFFECT OF SYSTEMIC GLUCOCORTICOIDS ON EXACERBATIONS OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE. Niewoehner et al. N Engl J Med. 1999Best Practice Meeting - COPD Exacerbation22

22EFFECT OF SYSTEMIC GLUCOCORTICOIDS ON EXACERBATIONS OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE. Niewoehner et al. N Engl J Med. 1999Best Practice Meeting - COPD Exacerbation23No significant difference in outcomes between 2 and 8 week coursesDid show complications with treatment arms including hyperglycemia and trend toward more hospitalizations for infection

23Oral corticosteroids in patients admitted to hospital withexacerbations of chronic obstructive pulmonary disease:a prospective randomised controlled trial. Davies et al. The Lancet. August 7, 1999Clinical question: Does oral prednisolone 30-40 mg modify rate of improvement of lung function or course of hospital stay?Design: RCT, double blind study of 60 ptsIncluded patients with COPD exacerbation, Age 40-80 years, 20 pack year history, FEV1 < 70%, and FEV1/FVC < 75% Best Practice Meeting - COPD Exacerbation24

Oral corticosteroids in patients admitted to hospital withexacerbations of chronic obstructive pulmonary disease:a prospective randomised controlled trial. Davies et al. The Lancet. August 7, 1999Excluded if personal or family history of asthma/atopy, uncontrolled LVF, clinical/radiological PNA, oral steroids in last month, or arterial pH < 7.26Patients randomized to prednisolone 30 mg for 14 days or placeboPatients followed to discharge with 6 week follow upBest Practice Meeting - COPD Exacerbation25

Oral corticosteroids in patients admitted to hospital withexacerbations of chronic obstructive pulmonary disease:a prospective randomised controlled trial. Davies et al. The Lancet. August 7, 1999Study showed FEV1 after bronchodilation increased more rapidly in the prednisolone group although no significant difference was found at 6 weeksHospital length of stay was decreased from 9 to 7 days in treatment groupBest Practice Meeting - COPD Exacerbation26

Oral or IV Prednisolone in theTreatment of COPD Exacerbations*A Randomized, Controlled, Double-blind Study. De Jong et al. Chest. 2007Randomized control trial comparing 60 mg of IV versus PO prednisoloneStudy results did not show any significant difference in short or long term outcomes.Best Practice Meeting - COPD Exacerbation27

AntibioticsAntibiotic therapy should be considered when patients have 2 of the 3 following symptoms:Increased dyspneaIncreased sputum volumeIncreased sputum purulenceAnd if the patient has a severe exacerbation requiring mechanical ventilationBest Practice Meeting - COPD Exacerbation28

AntibioticsCommon pathogens recovered from lower airways of patients with COPD exacerbation are S. pneumoniae, H. influenzae, and M. catarrhalisMost studies were done in chronic bronchitis and recommend 3-7 days of treatmentBest Practice Meeting - COPD Exacerbation29

AntibioticsType of antibiotic is divided by severity of exacerbation and risk factors for poor outcome:Comorbid conditionsSevere COPD> 3 exacerbations/yearAntimicrobial use in the last 3 monthsBest Practice Meeting - COPD Exacerbation30

AntibioticsMild with no risk factors:B-lactam, tetracycline, bactrimAlternative of augmentin, macrolide, 2-3 generation cephalosporinModerate with risk factors:B-lactam/B-lactamase inhibitor or fluoroquinoloneSevere with risk for P. aeruginosa:Fluoroquinolone or B-lactam with pseudomonas activityBest Practice Meeting - COPD Exacerbation31

Noninvasive Intermittent Ventilation (NIV)Improves respiratory acidosis, increases pH, reduces PaCO2Decreases need for endotrachial intubationReduces respiratory rate and dyspneaDecreases length of hospital stay and mortality

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Noninvasive Intermittent Ventilation (NIV)Indications:Moderate Severe dyspnea with use of accessory muscles and paradoxical abdominal motionModerate Severe acidosis pH < 7.35 and/or PaCO2 > 45 mm HgRespiratory rate > 25 breaths/minute

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Noninvasive Intermittent Ventilation (NIV)Relative contraindications:Respiratory arrestCardiovascular instabilityMental status changes preventing cooperabilityHigh aspiration riskThick/copious secretionsRecent facial or gasteroesophageal surgeryCraniofacial traumaFixed nasopharyngeal abnormalitiesBurnsExtreme obesity

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Noninvasive positive pressure ventilation to treat respiratory failure resulting from exacerbations of chronic obstructive pulmonary disease: Cochrane systematic review and metaanalysis. Lightowler et al. BMJ. January 25, 2003.Best Practice Meeting - COPD Exacerbation35

1. We defined treatment failure as the combination of mortality, need for intubation, and intolerance to the allocated treatment. Data from seven of the studies showed that NPPV resulted in a significantly lower risk of treatment failure (relative risk 0.51), compared with usual medical care, with a number needed to treat for NPPV to have a benefit of five (figure 2, table 1).2 3 1416 19 20 NPPV significantly reduced the risk of mortality (relative risk 0.41), with a number needed to treat of eight (figure 3, table 1). The risk of endotracheal intubation was more than halved with NPPV, and for every five patients treated with NPPV one patient would avoid intubation (figure 4, table 1). NPPV also reduced complications of treatment and length of stay in hospital (tables 1 and 2). NPPV significantly improved pH, PaCO2, and respiratory rate within one hour of initiation35Noninvasive Intermittent Ventilation (NIV)Best Practice Meeting - COPD Exacerbation36

Discharge and Follow UpDischarge criteria:Inhaled B2- agonist therapy is required no more that q4 hrsPatient, if previously ambulatory, is able to walk across the roomPatient is able to eat and sleepPatient has been clinically stable for 12-24 hrsABGs have been stable for 12-24 hrsPatient (Caregiver) understands correct use of medicationsFollow up and home care is arrangedPatient, family, and physician are confident patient can manage successfullyBest Practice Meeting - COPD Exacerbation37

Follow up itemsAbility to cope in usual environmentFEV1Inhaler techniqueUnderstanding of recommended treatment regimenNeed for long term oxygen therapy or nebulizer therapy38Best Practice Meeting - COPD Exacerbation

GoalsUnderstand the pathophysiology of exacerbationsLearn more about the current guidelines for treatment of COPD exacerbation and why?Discuss the current practices at UNM?39Best Practice Meeting - COPD Exacerbation

Do our current practices coincide with the current guidelines?40Best Practice Meeting - COPD ExacerbationResourcesBrochard L, Mancebo J, Wysocki M, Lofaso F, Conti G, Rauss A, et al. Noninvasive ventilation for acute exacerbations of chronic obstructive pulmonary disease. N Engl J Med 1995;333(13):817-22.

Davies L, Angus RM, Calverly PM. Oral corticosteroids of chronic obstructive pulmonary disease: a prospective randomised controlled trial. Lancet 1999;354(9177):456-60.

Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global Strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. Executive Summary, 2009.

Holguin F, Folch E, Redd SC, Mannino DM. Comorbidity and mortality in COPD-related hospitalizations in the United States, 1979 to 2001. Chest 2005;128(4):2005-11.

de Jong YP, Uil SM, Grotjohan HP, Postma DS, Kerstjens HA, van den Berg JW. Oral or IV prednisone in the treatment of COPD exacerbations: a randomized, controlled, double-blind study. Chest. 2007 Dec;132(6):1741-7. Epub 2007 Jul 23.

Lightowler JV, Wedzicha JA, Elliot MW, Ram FS. Non-invasive positive pressure ventilation to treat respiratory failure resulting from exacerbations of chronic obstructive pulmonary disease: Cochrane systematic review and meta-analysis. BMJ 2003;326(7382):185.

Maltais F, Ostinelli J, Bourbeau J, Tonnel AB, Jacquemet N, Haddon J, et al. Comparison of nebulized budesonide and oral prednisone with placebo in the treatment of acute exacerbations of chronic obstructive pulmonary disease: a randomized controlled trial. Am J Respir Crit Care Med 2002;165(5):698-703.

Niewoehner DE, Erbland ML, Deupree RH, Collins D, Gross NJ, Light RW, et al. Effect of systemic glucocorticoids on exacerbations of chronic obstructive pulmonary disease. Department of Veterans Affairs Cooperative Study Group. N Engl J Med 1999;340(25):1941-7.

Quon BS, Gan WQ, Sin DD. Contemporary Management of Acute Exacerbations of COPD: A Systematic Review and Metaanalysis. Chest. 2008:133;756-766.

Reilly JJ, Silverman EK, Shapiro SD. Ch. 254: Chronic Obstructive Pulmonary Disease. Harrisons Principals of Internal Medicine, 17th ed. (1635-1643). McGraw Hill, 2008.

Rizkallah J, Man SF, Sin DD. Prevalence of pulmonary embolism in acute exacerbations of COPD: a systematic review and metaanalysis. Chest. 2009 Mar;135(3):786-93. Epub 2008 Sep 23.

Stallberg B, Selroos O, Vogelmeier C, Andersson E, Ekstrom T, Larsson K. Budesonide/formoterol as effective as prednisone plus formoterol in acute exacerbations of COPD. A double-blind, randomised non-inferiority, parallel-group, multicentre study. Respir Res. 2009 Feb 19; 10:11.

Stoller, JK. Management of acute exacerbations of chronic obstructive pulmonary disease. Up to Date, www.uptodate.com. June 2010.

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