ACUTE EXACERBATION OF COPD

DR.IRAPPA MADABHAVI

DEFINITION OF AE-COPD
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 disease
GOLD, 2006 (Rabe et al. 2007)

FREQUENCY OF EXACERBATION

Exacerbation rates according to baseline lung function. Vestbo J,

Epidemiology of AECOPD, AECOPD Lung Biology in Health and Disease, vol183, 2004

The Study to Understand Prognosis and Preferences for Outcomes and Rates of Treatment (SUPPORT)
In-hospital mortality rate of 11% in patients with acute hypercapnic respiratory failure. The 180-day mortality rate was 33% and the 2-yr mortality rate was 49%
Am J Respir Crit Care Med 1996; 154: 959 967.

Triggers of COPD exacerbation

Wedzicha JA et al Lancet 2007

AETIOLOGY OF EXACERBATION
Infectious agents, including bacteria, viruses and atypical pathogens are currently implicated in up to 80% of acute exacerbation.
Sethi S. Infectious etiology of acute exacerbations of chronic bronchitis. Chest 2000; 117:380S385Stions

Bacteria likely playing a role in 50% of exacerbations

Sethi S. New developments in the pathogenesis of acute exacerbations of chronic obstructive pulmonary disease. Curr Opin Infect Dis 2004; 17(2):113 119.

BACTERIAL ETIOLOGY
The three predominant bacterial species isolated are 60% cases Nontypeable Haemophilus influenzae, Moraxella catarrhalis Streptococcus pneumoniae. . 10% - Atypical Chlamydia Other less frequently isolated potential pathogens include Pseudomonas aeruginosa gram-negative enterobacteria Staphylococcus aureus Haemophilus parainfluenzae Nseir S et al, Respiration 2008 Haemophilus hemolyticus

Eller J et al Chest, 1998

ROLE OF VIRAL INFECTION

Respirology (2010) 15, 536542

VIRAL INFECTION AND AE-COPD

More severe as reflected by Longer length of hospitalization Decrease in FEV1, FEV1%, FEV1/FVC% and diffusion capacity Trend towards greater hypoxaemia. Longer median symptom recovery time than did non-viral exacerbations (13 and 6 days respectively).

AIR POLUTION and AECOPD

Hospital admissions for AECOPD were increased with increased environmental pollution.
London: Thorax (50) 1995 p.1188 6 European cities: ERJ (10) 1997 p. 1064 Taiwan: J. Tox. Env. Health (70), 207 Brazil: Cod Saudi P (22) 2006 p. 2669 Hong Kong: Thorax, 2007

Secondary Causes of AECOPD and/or comorbidities

Pneumonia Left or Right heart failure Arrhythmias Pulmonary embolism Spontaneous pneumothorax Inappropriate oxygen therapy Drugs (hypnotics, diuretics, etc) Metabolic diseases Poor nutritional stage Other acute disease (GI Bleeding) End-Stage disease (fatigue resp. muscles)
[1st ERS Guidelines 1995]

 Prevalence of Pulmonary Embolism in acuter exacerbations of COPD: a systematic review and metaanalysis. Rizkallah J et al. Chest 2009;135(3):786-93.

Conclusions: One of four COPD patients who require hospitalization of an acute exacerbation may have PE. A diagnosis of PE should be considered in patients with exacerbation severe enough to warrant hospitalization, especially in those with an intermediate to-high pretest probability of PE.

IMPACT OF EXACERBATION

Increase economic burden

Increase systemic inflammation and comorbidity

Lancet 2007; 370: 78696

Corticosteroids in the Management of Acute Exacerbations

Faster improvement in the FEV1 by about 100 mL over the first 3 days of treatment Reduce treatment failure, relapse and length of hospital stay Induce side effects (such as hyperglycaemia) (SCCOPE TRIAL)
N Engl J Med 1999; 340:19411947

ANTIBIOTIC THERAPY
Anthonisen criteria of severity of exacerbation

Three levels of severity of exacerbation were defined: The most severe (type 1) comprised worsening dyspnea with increased sputum volume and purulence, Type 2 was only two of these symptoms Type 3 was any one of the symptoms with evidence of fever and/or an upper respiratory tract infection

Indications for hospitalisation of patients with a COPD exacerbation

Presence of high-risk co-morbid conditions, including pneumonia, cardiac arrhythmia, congestive heart failure, diabetes mellitus, renal or liver failure Inadequate response of symptoms to outpatient management Marked increase in dyspnoea Inability to eat or sleep due to symptoms Worsening hypoxaemia Worsening hypercapnia Changes in mental status Inability of the patient to care for her/himself Uncertain diagnosis Inadequate home care
ERS-ATS COPD Guidelines

INDICATION FOR ICU ADMISSION

Severe dyspnea that responds inadequately to initial therapy Changes in mental status Persistent or worsening hypoxaemia PaO2<40 mmHg, PaCo2 >60 mmHg, pH< 7.25 despite supplemental oxygen and NIV Need for invasive mechanical ventilation and vasopressor therapy

Etiology of primary AECOPD

Sethi et al. Chest 2000; 117: 380s-5s

Indication for Empiric Antibiotic Therapy in AECOPD

Severity of AECOPD judged by 3 Anthonisen criteria: Worsening of dyspnea Increased sputum volume Increased sputum purulence AB indicated/useful in 3/3 Type 1 or severe AE 2/3 Type 2 or moderate AE Type 1 or severe AE, and Type 2 or 1/3 Type 3 or mild AE moderate AE if sputum
is purulent

STRATIFICATION OF AE-COPD PATIENTS

GROUP GROUP-A DEFINITIONS MILD EXACERBATIONS, NO RISK FACTORS FOR POOR OUTCOME MICROORGANISMS Streptococcus pneumoniae H. influenzae Moraxella catarrhalis C.PNEUMONIAE VIRUSES GROUP-A PLUS RESISTANT ORGANISM, BETALACTAMASE PRODUCING PENICILLIN RESISTANT STREPTOCOCCI PNEUMONIAE,ENTEROBACT ERIACEAE

GROUP-B

MODERATE EXACERBATIONS, WITH RISK FACTORS FOR POOR OUTCOME

GROUP-C

SEVERE EXACERBATIONS, WITH RISK FACTORS FOR PSEUDOMONAS AERUGINOSA

GROUP-B PLUS PSEUDOMONAS AERUGINOSA

Presence of comorbid diseases, frequent exacerbations >3/year, severe COPD, Antimicrobial use within past 3 months

Antibiotic therapy in AE-COPD

GROUP-A Patients with only one cardinal symptoms should not receive antibiotics If indicated, then Beta-lactam, Tetracycline TMP-SMX Alternative: betalactam/beta lactamase inhibitor, advanced macrolides, 2 or 3rd generation cephalosporine GROUP-B beta-lactam/beta lactamase inhibitor, Alternative oral therapy fluoroquinolones-gemi, levo and gatifloxacin

Antibiotic therapy in AE-COPD

GROUP-C patients at risk for PS.aeruginosa Ciprofloxacin or levofloxacin at high doses Antibiotics therapy in patients of COPD could be given for 5-7 days

INDICATIONS FOR NIV IN AE-COPD

Moderate-to-severe respiratory distress with use of accessory muscle and abdominal paradox Moderate to severe acidosis (pH 7.35) and/ or hypercapnia (Paco2 > 45 mm Hg) Tachypnea (respiratory rate > 25/min)

Do not use this therapy if the patient Has

Respiratory arrest Is medically unstable (hypotensive shock, uncontrolled cardiac ischemia or arrhythmias) Cannot protect the airway (impaired cough or swallowing mechanism) Has excessive secretions Is agitated or uncooperative Has facial trauma, burns, or surgery, or anatomic abnormalities interfering with mask fit Has an Acute Physiology and Chronic Health Evaluation (APACHE) score > 29 RESPIR CARE 1997; 42:364369 EUR RESPIR J 2005; 25:348355; THORAX 2002; 57:192211.

INDICATION FOR INVASIVE MECHANICAL VENTILATION

NPPV failure (worsening of arterial blood gases and/or pH in 12 hr or lack of improvement in arterial blood gases and/or pH after 4 hr) Severe acidosis (pH < 7.25) and hypercapnia [PaCO2 >60 mm Hg] Life-threatening hypoxemia [PaO2/FiO2 < 200 mm Hg] Tachypnea >35 breathsmin Other complications include metabolic abnormalities, sepsis, pneumonia, pulmonary embolism, barotraumas, and massive pleural effusion.

OXYGEN THERAPY IN AE-COPD

The goal is to maintain SaO2 at >90%. Main delivery devices include nasal cannula and venturi mask. Alternative delivery devices include nonrebreather mask, reservoir cannula, nasal cannula or transtracheal catheter. ABG should be monitored for PaO2, PaCO2 and pH. Prevention of tissue hypoxia supercedes CO2 retention concerns. If CO2 retention occurs, monitor for acidaemia. If acidaemia occurs, consider mechanical ventilation.

 >3 exacerbations in the past 12 months Comorbidities (especially cardiac disease) Severe or very severe airflow obstruction at baseline (FEV1 50% predicted) Recent (within past 3 months) systemic antibiotic use Table 16.1

Risk factors for poor outcome and/or for antibiotic-resistant pathogens in AECB

 Hypoxia at exacerbation of COPD is primarily the consequence of ventilation-perfusion (V/Q) imbalance and may be life threatening, for example through cardiac arrhythmia. Oxygen should therefore be used to correct hypoxia in respiratory failure. This should be administered in a controlled manner, to prevent the hypercapnia which will occur in a minority of patients

 GOLD recommendations, antibiotics should be given to patients with exacerbations with the three major symptoms, to those with two symptoms provided increased sputum purulence is present, and to those who are critically ill and needing mechanical support. The oral route is preferred and is cheaper. Their administration should be based on the patterns of local bacterial resistance and their use should be maintained for a period of 310 days If an exacerbation responds poorly to empirical antibiotic treatment, the patient should be re-evaluated for complications with microbiological reassessment if necessary.

NON-PHARMACOLOGICAL TREATMENT

OXYGEN THERAPY
Administer controlled low inspired oxygen concentrations (either 24% or 28%) through high flow (Venturi) masks at flow rates of 24 l/min. This strategy increases PaO2 sufficiently to maintain optimal values above 60 mm Hg and to ensure adequate SaO2 levels (>90%) without risking detrimental carbon dioxide retention and acidosis. Low flow devices such as nasal prongs or cannulae are less accurate as they deliver a variable and higher inspired oxygen concentration which can result in suppression of respiratory drive, carbon dioxide narcosis, and eventually respiratory arrest, if the patient is not appropriately monitored

BRONCHODILATORS
Short acting inhaled b2 agonists and anticholinergic agents remain the main treatment modality for exacerbations as they reduce symptoms and improve airflow obstruction No significant differences in FEV1 between the use of hand held MDIs with a good inhaler technique (with or without a spacer device) and nebulizers

 The first step is an appropriate medical history which identifies one or more of the three cardinal symptoms: increased shortness of breath, increased sputum volume, and increased sputum purulence The second step is a physical examination to identify the principal respiratory signs (rapid and shallow breathing, use of accessory respiratory muscles, paradoxical chest wall motion, wheezing, attenuated or absent breath sounds, hyperresonance on percussion, purse lip breathing), cardiovascular signs (increased and/or abnormal pulse heart rate, right heart failure, peripheral oedema, haemodynamic instability), and general signs (altered mental status, central cyanosis)

 The third step involves the recognition of clinical conditions that are often associated with COPDfor example, pulmonary conditions (pneumonia, pneumothorax, pleural effusion, lung cancer, upper airway obstruction, rib fracture), cardiovascular conditions (pulmonary embolism, right/left heartfailure), and drug related causes (sedatives, narcotics)

 The fourth step includes several standard diagnostic procedures such as arterial blood gas analysis, chest radiography, routine blood tests, ECG, and Gram stain and culture when sputum is purulent. The use of pulse oximetry alone to measure arterial oxygen saturation (SaO2) is only recommended for mild exacerbations. Forced spirometry is of limited usefulness for the management of exacerbations but is mandatory during the recovery or follow up period to confirm the diagnosis of COPD or to monitor further slow improvement. Peak expiratory flow rate (PEFR), used as an alternative measurement of airflow limitation, correlates well with forced expiratory volume in 1 second (FEV1),although the clinical implications of this correlation remain unclear