COPD: A Management Plan for Acute Exacerbations of This Chronic Illness George L. Higgins III, M.D., F.A.C.E.P. Professor of Emergency Medicine Maine Medical Center Tufts University School of Medicine

Case Study: HPI A 70 year old man in transported to your small, rural ED by EMS personnel with a chief complaint of shortness of breath. He has several chronic illnesses, including COPD, CAD with stable angina, and symptomatic peripheral vascular disease.

Case Study: HPI He has become increasingly SOB over the past three days, and has noted a moderate increase in sputum production. He denies fever/chills, chest pain, and hemoptysis. Today, his SOB has dramatically worsened.

Case Study: Focused PMH Over the past year he has presented to your ED twice for COPD exacerbations: admitted once and more recently discharged from the ED with a course of antibiotics. He has never required mechanical ventilation.

Case Study: Social History He’s a widower and lives alone, but enjoys woodworking. He has smoked two packs of cigarettes a day for nearly fifty years and continues to do so. He drinks 2-3 beers daily.

Case Study: COPD Medications Long-acting inhaled anticholenergic (tiotropium) Long-acting inhaled beta-agonist (salmeterol) Inhaled corticosteroid (fluticasone) He insists he’s compliant

Case Study: Pertinent PE Findings BP 160/90, RR 30, P 110, T 37.5 O2 saturation 82% on mask O2 Obviously fatigued Chachetic in appearance Sitting upright Acutely dyspneic Diaphoretic Using accessory muscles of respiration Decreased breath sounds bilaterally

His Chest X-Ray

Another COPD Chest X-Ray

Beware! Large Alveolar Blebs Can Mimic Pneumothorax

Case Study: Additional Information With significant effort, he hands you an index card provided to him by his physician, documenting his recent baseline lung function: FEV1 60% of predicted FEV1/FVC 25% of predicted. He also tells you he never wants to be kept alive on a breathing machine.

This Patient Allows Us to Explore Practical and Pertinent Issues The GOLD classification of COPD The GOLD classification of COPD Risk factors for COPD exacerbations Risk factors for COPD exacerbations Risk factors for ED discharge relapse Risk factors for ED discharge relapse Admission criteria Admission criteria Effective and ineffective therapies Effective and ineffective therapies Indications for the initiation of antibiotics Indications for the initiation of antibiotics Targets for oxygen therapy Targets for oxygen therapy Options for ventilatory support Options for ventilatory support

COPD Defined “Chronic obstructive pulmonary disease (COPD) is a preventable and treatable disease state characterized by airflow limitation that is not fully reversible. The airflow limitation is usually progressive and is associated with an abnormal inflammatory response of the lungs to noxious particles or gases, primarily caused by cigarette smoking. Although COPD affects the lungs, it also produces significant systemic consequences.” Eur Respir J 2004; 23: 932 – 946

Socio-economic Impact of COPD In the United States…. In the United States… million emergency department visits 1.5+ million emergency department visits Nearly 800,000 hospitalizations Nearly 800,000 hospitalizations Over 120,000 deaths Over 120,000 deaths Healthcare costs exceed $32 billion annually Healthcare costs exceed $32 billion annually $14 billion lost annually due to work absence $14 billion lost annually due to work absence 6-month mortality rate = 33%, 12-month = 43% 6-month mortality rate = 33%, 12-month = 43%

COPD Mortality Increasing JAMA. 2005;294:

Percent Change in Age-Adjusted Death Rates, U.S., Proportion of 1965 Rate –59% –64% –35% +163% –7% Coronary Heart Disease Coronary Heart Disease Stroke Other CVD COPD All Other Causes All Other Causes Source: NHLBI/NIH/DHHS

COPD Mortality: Perverse Gender Equality MMWR 2005

20 Risk Factors for COPD Nutrition Infections Socio-economic status Aging Populations

Oxidative Stress and Inflammation Barnes, PJ. Chronic obstructive pulmonary disease. NEJM 2000.

Interesting Trivia In non-smokers with normal lungs, the natural aging process from age 25 to age 75 results in… In non-smokers with normal lungs, the natural aging process from age 25 to age 75 results in… 20% reduction in vital capacity 20% reduction in vital capacity 25% decrease in FEV1 (30ml/year) 25% decrease in FEV1 (30ml/year) Elastin fiber degradation with less elastic recoil Elastin fiber degradation with less elastic recoil In some smokers, the FEV1 can decrease by 150ml/year! In some smokers, the FEV1 can decrease by 150ml/year!

Interesting Trivia A single, average cigar, as compared to a single, average cigarette, has… A single, average cigar, as compared to a single, average cigarette, has… 20 times the amount of tobacco 20 times the amount of tobacco 7 times the tar 7 times the tar 11 times the carbon monoxide 11 times the carbon monoxide 4 times the nicotine 4 times the nicotine Cigar smoke is more alkaline, which facilitates absorption through the oral vasculature Cigar smoke is more alkaline, which facilitates absorption through the oral vasculature

Impact of Smoking on FEV1 BMJ 1977; 1: 1645 –

GOLD Classification of COPD (Global initiative for chronic Obstructive Lung Disease) Stage I: Mild FEV 1 /FVC < 0.70 FEV 1 > 80% predicted Stage II: Moderate FEV 1 /FVC < % > FEV 1 < 80% predicted Stage III: Severe FEV 1 /FVC < % > FEV 1 < 50% predicted Stage IV: Very Severe FEV 1 /FVC < 0.70 FEV 1 < 30% predicted or FEV 1 < 50% predicted plus chronic respiratory failure

Causes of Death in COPD NEJM 356:

27 Relieve symptoms Prevent disease progression Improve exercise tolerance Improve health status Prevent and treat complications Prevent and treat exacerbations Reduce mortality Goals of COPD Management

IV: Very Severe IV: Very Severe III: Severe III: Severe II: Moderate II: Moderate I: Mild I: Mild Therapy at Each Stage of COPD  FEV 1 /FVC < 70  FEV 1 > 80%  FEV 1 /FVC < 70%  50% > FEV 1 FEV 1 < 80%  FEV 1 /FVC < 70%  30% > FEV 1 FEV 1 < 50% FEV 1 /FVC < 70% FEV 1 /FVC < 70%  FEV 1 < 30% or FEV 1 < 50% plus Chronic Respiratory Failure Add Regular Treatment with One or More Long-acting Bronchodilators When Needed Add Rehabilitation Add Inhaled Glucocorticoids for Repeated Exacerbations Active Reduction of Risk Factors Influenza and Pneumonia Vaccination Add Short-acting Bronchodilator When Needed Add Long Term Oxygen for Respiratory Failure Consider Surgical Treatments End of life Discussions

Estimated Direct Costs of COPD Care The Obvious Goal: Prevent Acute Exacerbations

Risk Factors for a COPD Exasperation Advanced age Advanced age Chronic mucous hypersecretion with productive cough Chronic mucous hypersecretion with productive cough Longer duration of COPD Longer duration of COPD Antibiotic therapy within the past year Antibiotic therapy within the past year Hospitalization within the past year Hospitalization within the past year Co-morbidities Co-morbidities e.g. CAD, CHF, DM e.g. CAD, CHF, DM

Mortality from a COPD Exacerbation with Hypercapnia 10% in-hospital mortality 10% in-hospital mortality 20% 60-day mortality 20% 60-day mortality 30% 180-day mortality 30% 180-day mortality 40% 1-year mortality 40% 1-year mortality 50% 2-year mortality 50% 2-year mortality

Challenging Differential Diagnosis COPD ASTHMA Onset in mid-life Symptoms slowly progressive Long smoking history Dyspnea during exercise Largely irreversible airflow limitation Onset early in life Symptoms vary from day to day Symptoms at night/early morning Allergy, rhinitis, and/or eczema Family history of asthma Largely reversible airflow limitation

Challenging Differential Diagnosis COPD ASTHMA Hypoxia and hypercarbia common CarboxyHb common Polycythemia common Purulent sputum typical Compensated metabolic acidosis common Hypoxia and hypercarbia uncommon (except in extremis) CarboxyHb normal Polycythemia rare Purulent sputum uncommon Compensated metabolic acidosis rare

A Therapeutic Management Plan for Acute Exacerbations

The List of Therapeutic Options is Short but Sweet Oxygen Oxygen Bronchodilators Bronchodilators Beta-agonists Beta-agonists Anticholenergics Anticholenergics Systemic glucocorticoids Systemic glucocorticoids Antibiotics Antibiotics Non-invasive mechanical ventilation Non-invasive mechanical ventilation Conventional mechanical ventilation Conventional mechanical ventilation

Oxygen Therapy Hypoxia is a defining feature of acute exacerbations of COPD Hypoxia is a defining feature of acute exacerbations of COPD Supplemental oxygen is essential Supplemental oxygen is essential Target PaO mm Hg Target PaO mm Hg Target O2 saturation 90% Target O2 saturation 90% If hypoxia cannot be corrected, think of other causes (e.g. pulmonary embolus, pneumonia) If hypoxia cannot be corrected, think of other causes (e.g. pulmonary embolus, pneumonia) Permissive hypercapnia is acceptable Permissive hypercapnia is acceptable Ventilatory support may be required Ventilatory support may be required

Home Oxygen Therapy Benefits of long-term oxygen in COPD Benefits of long-term oxygen in COPD Improved tolerance of exercise and other ambulatory activities Improved tolerance of exercise and other ambulatory activities Decreased pulmonary hypertension Decreased pulmonary hypertension Improved neuropsychiatric function Improved neuropsychiatric function Decreased erythrocytosis and polycythemia Decreased erythrocytosis and polycythemia Reduced morbidity and mortality Reduced morbidity and mortality

Bronchodilators: Beta-agonists Sort-acting: albuterol, levalbuterol Sort-acting: albuterol, levalbuterol Rapid bronchodilation Rapid bronchodilation Rescue medication Rescue medication Long-acting: salmeterol, formoterol, arformoterol Long-acting: salmeterol, formoterol, arformoterol Improve dyspnea Improve dyspnea Increase FEV1 Increase FEV1 No role in acute exacerbations No role in acute exacerbations Adverse effects Adverse effects Palpitations, tremor, tachycardia, hypokalemia, worsening V/Q mismatch Palpitations, tremor, tachycardia, hypokalemia, worsening V/Q mismatch

Bronchodilators: Beta-agonists Albuterol is the “Go To” agent at this time Albuterol is the “Go To” agent at this time Nebulized dose: 2.5-5mg every 1-2 hours Nebulized dose: 2.5-5mg every 1-2 hours MDI with spacer: 180mcg (2 puffs) every 1-2 hours MDI with spacer: 180mcg (2 puffs) every 1-2 hours The breathing mechanics in the acutely dyspneic patient make this route less effective The breathing mechanics in the acutely dyspneic patient make this route less effective Continuous nebulization has not been proven to add bennefit in COPD Continuous nebulization has not been proven to add bennefit in COPD Subcutaneous or intravenous beta-agonist administration is rarely required Subcutaneous or intravenous beta-agonist administration is rarely required

Bronchodilator Therapy: Anticholinergics Anticholinergics (ipratropium, tiotropium) are effective bronchodilators in COPD Anticholinergics (ipratropium, tiotropium) are effective bronchodilators in COPD Vagal cholinergic tone often is the only reversible cause of airway obstruction in COPD Vagal cholinergic tone often is the only reversible cause of airway obstruction in COPD Block the muscarinic receptors on airway smooth muscle causing relaxation of the muscle and decreased bronchoconstriction Block the muscarinic receptors on airway smooth muscle causing relaxation of the muscle and decreased bronchoconstriction May also reduce airway mucus secretions and improve secretion clearance May also reduce airway mucus secretions and improve secretion clearance

Bronchodilator Therapy: Anticholinergics Ipratropium is the “Go To” agent at this time Ipratropium is the “Go To” agent at this time Nebulized dose: 500mcg every 2-4 hours Nebulized dose: 500mcg every 2-4 hours MDI with spacer: 36mcg (2 puffs) every 2-4 hours MDI with spacer: 36mcg (2 puffs) every 2-4 hours The breathing mechanics in the acutely dyspneic patient make this route less effective The breathing mechanics in the acutely dyspneic patient make this route less effective There is no role for the long-acting anticholinergic agents (e.g. tiotropium) in acute phase management There is no role for the long-acting anticholinergic agents (e.g. tiotropium) in acute phase management

Systemic Corticosteroids Corticosteroids in acute exacerbations… Corticosteroids in acute exacerbations… Reduce the 30-day and 90-day treatment failure rates Reduce the 30-day and 90-day treatment failure rates Shorten hospital length of stay Shorten hospital length of stay Improve lung function Improve lung function N Engl J Med 1999; 340(25): Typical agents and doses include… Typical agents and doses include… Methylprednisolone mg IV BID to QID Methylprednisolone mg IV BID to QID Prednisone 60mg PO in the less severely ill patient Prednisone 60mg PO in the less severely ill patient Inhaled corticosteroids have not been shown to benefit patients in the acute phase of care Inhaled corticosteroids have not been shown to benefit patients in the acute phase of care

Non-invasive Positive Pressure Ventilation Have a low threshold for instituting NPPV Have a low threshold for instituting NPPV Benefits of NPPV include… Benefits of NPPV include… Fewer intubations Fewer intubations Decreased mortality Decreased mortality Shortened ICU length of stay Shortened ICU length of stay Move to conventional mechanical ventilation if… Move to conventional mechanical ventilation if… Patient fails an NPPV trial Patient fails an NPPV trial Patient benefits but will not tolerate NPPV Patient benefits but will not tolerate NPPV Patient has contraindications to NPPV Patient has contraindications to NPPV

Contraindications to NPPV Immediate intubation required Immediate intubation required Hemodynamic instability Hemodynamic instability Encephalopathy or inability to cooperate Encephalopathy or inability to cooperate Facial deformity, surgery or trauma Facial deformity, surgery or trauma Upper airway obstruction Upper airway obstruction Inability to protect airway or clear secretions Inability to protect airway or clear secretions High risk for aspiration High risk for aspiration

Etiology of COPD Exacerbations

Indications for Antibiotics in COPD Exacerbations The general recommendation is to provide antibiotic therapy if the COPD patient presents with at least two of the following: The general recommendation is to provide antibiotic therapy if the COPD patient presents with at least two of the following: Increased dyspnea Increased dyspnea Increased sputum production Increased sputum production Increased purulence of sputum Increased purulence of sputum Nearly 100% of the patients I manage will meet these criteria Nearly 100% of the patients I manage will meet these criteria

Antibiotics Selection depends on severity of illness Selection depends on severity of illness Out-patient Out-patient Admission Admission Obtain sputum culture to evaluate for resistant organisms Obtain sputum culture to evaluate for resistant organisms Antibiotics in COPD exacerbations appear to… Antibiotics in COPD exacerbations appear to… Reduce the risk of short-term mortality by 77% Reduce the risk of short-term mortality by 77% Decrease the risk of treatment failure by 53% Decrease the risk of treatment failure by 53%

Antibiotics Proven choices Proven choices Amoxicillin mg TID Amoxicillin mg TID Doxycycline 100mg BID Doxycycline 100mg BID Azithromycin 500mg, then 250mg QD for 4 doses Azithromycin 500mg, then 250mg QD for 4 doses Trimethoprim-Sulfa 1 DS tablet BID Trimethoprim-Sulfa 1 DS tablet BID Duration days Duration days For more severely ill patients, treat like hospital acquired pneumonia For more severely ill patients, treat like hospital acquired pneumonia E.g. levofloxacin or ceftriaxone E.g. levofloxacin or ceftriaxone

Traditional Therapies No Longer Recommended for Acute Exacerbations of COPD Mucokinetic/mucolytic agents Mucokinetic/mucolytic agents Lack of efficacy, can worsen bronchospasm Lack of efficacy, can worsen bronchospasm Mechanical chest physiotherapy Mechanical chest physiotherapy Lack of efficacy, can worsen bronchospasm Lack of efficacy, can worsen bronchospasm Methylxanthines (e.g. aminophyline) Methylxanthines (e.g. aminophyline) Low efficacy, high incidence of side effects Low efficacy, high incidence of side effects Newer phosphodiasterases are emerging Newer phosphodiasterases are emerging

Admit the Patient with… Co-morbid conditions: Pneumonia, cardiac arrhythmia, congestive heart failure, diabetes mellitus, renal or liver failure Inadequate response of symptoms to outpatient management Marked increase in dyspnea Inability to eat or sleep due to symptoms Worsening hypoxemia, hypercapnia Changes in mental status Inability of the patient to care for her/himself Lack of home support Uncertain diagnosis Risk factors for failing an ED discharge Eur Respir J 2004; 23: 932 – 946

Risk Factors for a Failed ED Discharge Greater number of ED neb treatments Greater number of ED neb treatments Home oxygen therapy Home oxygen therapy An ED visit within the past week An ED visit within the past week A prior unexpected relapse after an ED visit A prior unexpected relapse after an ED visit Discharge from ED with steroids and/or antibiotics Discharge from ED with steroids and/or antibiotics

Summary Thoughts COPD is a chronic inflammatory disease that impacts other systems COPD is a chronic inflammatory disease that impacts other systems cardiac, skeletal, metabolic, nutritional cardiac, skeletal, metabolic, nutritional COPD is a growing problem causing major morbidity and mortality in the US and worldwide COPD is a growing problem causing major morbidity and mortality in the US and worldwide Smoking cessation programs and treatments are essential Smoking cessation programs and treatments are essential Treatment of stable COPD should progress in a deliberate, evidence-based, stepwise fashion Treatment of stable COPD should progress in a deliberate, evidence-based, stepwise fashion

Summary Thoughts Spirometry is essential for diagnosis and ongoing management Spirometry is essential for diagnosis and ongoing management Prevention of exacerbations is a primary goal Prevention of exacerbations is a primary goal A rational and easily applied management plan is effective in the treatment of acute COPD exacerbations A rational and easily applied management plan is effective in the treatment of acute COPD exacerbations

Summary of Treatment Recommendations in the ED Administer a combination of a short-acting anti-cholinergic agent and a short-acting beta-agonist Administer a combination of a short-acting anti-cholinergic agent and a short-acting beta-agonist E.g. albuterol neb 2.5mg by every 1-2 hrs plus ipratropium neb 500mcg every 2-4 hrs E.g. albuterol neb 2.5mg by every 1-2 hrs plus ipratropium neb 500mcg every 2-4 hrs Administer systemic corticosteroids Administer systemic corticosteroids E.g. methylprednisolone 125mg IV E.g. methylprednisolone 125mg IV Prednisone 60mg PO (for less severely ill) Prednisone 60mg PO (for less severely ill)

Summary of Treatment Recommendations in the ED Initiate antibiotic therapy Initiate antibiotic therapy E.g. amoxicillin, doxycycline or trimethoprim- sulfamethoxazole for out-patient therapy and less ill patients E.g. amoxicillin, doxycycline or trimethoprim- sulfamethoxazole for out-patient therapy and less ill patients E.g. levofloxacin or ceftriaxone for more severely ill patients E.g. levofloxacin or ceftriaxone for more severely ill patients Initiate oxygen therapy with targets of… Initiate oxygen therapy with targets of… PaO2 of 60-65mmHg PaO2 of 60-65mmHg Hemoglobin saturation of 90% Hemoglobin saturation of 90%

Summary of Treatment Recommendations in the ED If ventilatory support is required… If ventilatory support is required… Provide a trial of non-invasive positive pressure ventilation if possible Provide a trial of non-invasive positive pressure ventilation if possible Conventional mechanical ventilation should be initiated if the patient fails a NPPV trial Conventional mechanical ventilation should be initiated if the patient fails a NPPV trial Have a low threshold for admission Have a low threshold for admission These are very sick people! These are very sick people!

Thanks for Your Kind Attention