Management of acute exacerbations of COPD

Pharm D student: Noha Alaa El Dine

Supervised by: Prof. Seham Hafez

Definition of Acute COPD Exacerbation

An exacerbation of chronic obstructive pulmonary disease (COPD) is an acute increase in symptoms beyond normal day-to-day variation.

This generally includes an acute increase in one or more of the following cardinal symptoms: Cough increases in frequency and severity Sputum production increases in volume and/or

changes character (more purulent) Dyspnea increases

Defined by: The Global Initiative for Chronic Obstructive Lung Disease (GOLD)

Definition of Acute COPD Exacerbation

Constitutional symptoms, an unchanged chest radiograph, a variable decrease in pulmonary function, and tachypnea are typical in acute exacerbations.

However, severe cases can lead to respiratory failure and death.

Defined by: The Global Initiative for Chronic Obstructive Lung Disease (GOLD)

Classification

Type III (mild) has one symptom plus at least one of the following:• Upper respiratory infection in the past 5 days• Fever without another apparent cause • Increased wheezing• Increased cough• Increase in respiratory rate or heart rate by 20% above baseline.

Type II (moderate) has two

Type I (severe) has all of the three symptoms

Based on health-care utilization, an exacerbation can be further classified as:

MildWhen the

patient has an increased

need for medication,

which he can manage in

his own normal

environment

Moderate When the patient has

an increased need for

medication and feels the need to seek additional medical

assistance

SevereWhen the

patient/caregiver recognizes obvious and/or

rapid deterioration in condition,

requiring hospitalizati

on

PRECIPITANTS  It is estimated that:

50 to 60 percent of

exacerbations are due to

respiratory infections

(mostly bacterial and

viral)

10 percent are due to

environmental pollution

30 percent are of unknown

etiology

Non compliance with medication use & physician orders:

•Smoking•Lack of a pulmonary rehabilitation program •Improper use of an inhaler•Poor adherence to a drug therapy program

RISK FACTORSAccording to observational studies, the risk of developing

an exacerbation of COPD correlates with: Advanced age Productive cough Duration of COPD Antibiotic therapy COPD-related hospitalization within the previous year Chronic mucous hypersecretion Theophylline therapy Having one or more comorbidities (eg, ischemic heart

disease, chronic heart failure, or diabetes mellitus). Gastroesophageal reflux disease (GERD) may be an

additional risk factor for COPD exacerbations. Additional studies are needed to confirm this observation.

TREATMENT GOALSSuccessful management of acute exacerbations of COPD in either the inpatient or outpatient setting requires attention to a number of key issues:

Identifying and ameliorating the cause of the acute exacerbation, if possible

Optimizing lung function by administering bronchodilators and other pharmacologic agents

Assuring adequate oxygenation and secretion clearance Averting the need for intubation, if possible Preventing complications of immobility, such as

thromboemboli and deconditioning Addressing nutritional needs

OXYGEN THERAPY

Supplemental oxygen is a critical component of acute therapy.

Arterial oxygen tension

(PaO2) of 60 to 70

mmHg

Oxyhemoglobin saturation of 90 to 94

percent

Target

PHARMACOLOGIC TREATMENT

The major components of managing an acute exacerbation of COPD:

Inhaled short-acting

bronchodilators (beta adrenergic

agonists and anticholinergic

agents)

Glucocorticoids

Antibiotics

Beta adrenergic agonists

Inhaled short-acting beta adrenergic agonists (eg, albuterol) are the mainstay of therapy for an acute exacerbation of COPD because of their rapid onset of action and efficacy in producing bronchodilation.

NebulizerMetered dose

inhaler (MDI) with a spacer device

Administration may be via

Many clinicians prefer nebulized therapy on the presumption of more reliable delivery of drug to the airway.

We favor nebulized therapy because we find that many patients have difficulty using proper MDI technique in this setting (during acute exacerbations).

Beta adrenergic agonists

Nebulizer

Metered dose inhaler (MDI) with a

spacer device

Vs

Equal efficac

y

Typical doses of albuterol for this indication are:

Beta adrenergic agonists

By Nebulizer:2.5 mg (diluted to a total of 3

mL) every one to four hours as

needed

By Metered dose inhaler (MDI) with a

spacer device:4 to 8 puffs (90 mcg per puff) every one to four hours as needed.

Beta adrenergic agonists

Increasing the dose of nebulized albuterol to 5 mg does not have a significant impact on spirometry or clinical outcomes. Similarly, continuously nebulized beta agonists have not been shown to confer an advantage.

Subcutaneous injection of short-acting beta adrenergic agonists is reserved for situations in which inhaled administration is not possible. Parenteral use of these agents results in greater inotropic and chronotropic effects, which may cause arrhythmias or myocardial ischemia in susceptible individuals.

Anticholinergic agents Inhaled short-acting anticholinergic agents

(eg, ipratropium bromide) are used with inhaled short-acting beta adrenergic agonists to treat exacerbations of COPD.

This is based on several studies that found that combination therapy produces synergistic bronchodilation in patients with a COPD exacerbation, an asthma exacerbation, or stable COPD. However, this finding has not been universal in patients having an exacerbation of COPD.

Typical doses of ipratropium for this indication are:

Anticholinergic agents

By Metered dose inhaler (MDI) with a

spacer device:2 puffs (18 mcg per puff) every four hours as needed.

By Nebulizer:500 mcg every four hours as

needed

Anticholinergic agents

The choice between the two might depend on potential undesirable side effects based on the comorbidity of the patient.

Beta adrenergic agonists

Choice

Anticholinergic agents have a safer and more tolerable side effect profile (tremors, dry mouth, and

urinary retention)

β2-agonists (tremors, headache,

nausea, vomiting,

palpitations, heart rate, and blood pressure

variations).This may be an important point to consider, when deciding

which bronchodilator agent to use during an acute exacerbation.

Glucocorticoids

Systemic glucocorticoid therapy improves:

Lung function Treatment success Reducing the length of hospital

stay

Glucocorticoids•Oral — Prednisone (40 to 60 mg orally, once daily) •High doses of systemic glucocorticoids increase the risk of side effects. Lower doses (eg, equivalent of 30 to 40 mg of Prednisone) may be equally effective and safe

The duration of systemic glucocorticoid therapy varies from patient to patient and exacerbation to exacerbation. As a rough guide,

most exacerbations should be treated with full dose therapy for 7

to 14 days

•After this time, many pulmonologists taper over about seven days as a trial to see if continued glucocorticoid therapy is required. •Tapering solely because of concerns about adrenal suppression is not necessary if the duration of therapy is less than three weeks (a duration too brief to cause adrenal atrophy).

Glucocorticoids The efficacy of inhaled glucocorticoids on the course of a COPD exacerbation has not been studied in randomized trials. Thus, they should not be used as a substitute for systemic glucocorticoid therapy.

Intravenous glucocorticoids should be given to patients who present with a severe exacerbation, who

•respond poorly to oral glucocorticoids,•who are vomiting, •or who may have impaired absorption due to decreased splanchnic perfusion (eg, patients in shock).

The optimal dose of systemic glucocorticoids for treating a COPD exacerbation is unknown. Frequently used regimens include:IV Methylprednisolone (60 to 125 mg, two to four times daily) Oral administration is used in most other patients.

Oral glucocorticoids are rapidly absorbed (peak serum levels achieved at one hour after ingestion) with virtually complete bioavailability and their efficacy is comparable to that with intravenous therapy.

Most Common Infectious Causes of COPD Exacerbations

Mild to moderate exacerbations Streptococcus pneumoniae

Haemophilus influenzae Moraxella catarrhalis Chlamydia pneumoniae Mycoplasma pneumoniae Viruses

Severe exacerbations Pseudomonas species Other gram-negative enteric bacilli

Antibiotics Commonly Used in Patients with COPD Exacerbations

Mild to moderate exacerbations* First-line antibiotics

Doxycycline (Vibramycin), 100 mg twice daily Trimethoprim-sulfamethoxazole (Septrin DS), one tablet twice daily

Amoxicillin-clavulanate potassium(Augmentin), one 500 mg/125 mg tablet three times daily or one 875 mg/125 mg tablet twice daily

Macrolides Clarithromycin (Klacid), 500 mg twice daily Azithromycin (Zithromax), 500 mg initially, then 250 mg daily

Fluoroquinolones Levofloxacin (Tavanic), 500 mg daily Gatifloxacin (Tequin), 400 mg daily Moxifloxacin (Avalox), 400 mg daily

*--For orally administered antibiotics, the usual duration of therapy is five to 10 days.

Antibiotics Commonly Used in Patients with COPD Exacerbations Moderate to severe exacerbations (Ý) Cephalosporins

Ceftriaxone (Rocephin), 1 to 2 g IV daily Cefotaxime (Claforan), 1 g IV every 8 to 12 hours Ceftazidime (Fortum), 1 to 2 g IV every 8 to 12 hours

Antipseudomonal penicillins Piperacillin-tazobactam (Tazocin), 3.375 g IV every

6 hours Ticarcillin-clavulanate potassium (Timentin), 3.1 g IV every 4 to 6 hours

Fluoroquinolones Levofloxacin(Tavanic), 500 mg IV daily Gatifloxacin(Tequin), 400 mg IV daily

Aminoglycoside Tobramycin (Tobracin), 1 mg per kg IV every 8 to 12 hours, or 5 mg per kg IV daily

Ý--Drugs are often used in combination for synergy; IV therapy is usually employed.

Mucoactive agents 

There is little evidence supporting the use of mucoactive agents (eg, N-acetylcysteine) in acute exacerbations of COPD.

Some mucoactive agents may worsen bronchospasm.

Methylxanthines

Aminophylline and theophylline are NOT recommended for the treatment of acute exacerbations of COPD.

In addition to lack of efficacy, methylxanthines caused significantly more nausea and vomiting than placebo and trended toward more frequent tremor, palpitations, and arrhythmias.

CHEST PHYSIOTHERAPY

Mechanical techniques to augment sputum clearance, such as:

Directed coughing, Chest physiotherapy with percussion and

vibration, Intermittent positive pressure breathing, and

postural drainage, have not been shown to be beneficial in COPD and

may provoke bronchoconstriction.

Their use in acute exacerbations of

COPD is not supported by clinical trials.

MECHANICAL VENTILATIONNoninvasive ventilation

Noninvasive positive pressure ventilation (NPPV) refers to mechanical ventilation delivered through a noninvasive interface, such as a face mask, nasal mask, or nasal prongs.

It improves numerous clinical outcomes and is the preferred method of ventilatory support in many patients with an acute exacerbation of COPD.

Invasive ventilationInvasive mechanical ventilation should be administered:

when patients fail NPPV,

do not tolerate NPPV, or

have contraindications to NPPV.

Management of acute COPD

Controlled O2 therapy

Nebulized bronchodilators

Steroids

Antibiotics

Physiotherapy to aid sputum expectoration

If no responseRepeat nebulizers & consider IV aminophylline

If no responseConsider NIPPV if RR >30 or pH<7.35

Consider intubation & ventillation if pH <7.26 & Pa CO2 is rising

Consider a respiratory stimulant (doxapram)[Only for patient who are not suitable for mechanical

ventillation]

PROGNOSIS

It is estimated that 14 % of patients admitted for an exacerbation of COPD will die within three months of admission.

Even if the acute exacerbation resolves, many patients never return to their baseline level of health.

PREVENTION of COPD exacerbation

Vaccination, pneumonia and annual flu vaccine (a flu shot can decrease serious illness and death by as much as 50% for patients with COPD).

Handwashing Balanced diet Sufficient amount of exercise/activity Adequate sleep Avoiding exposure to environmental irritants such as air

pollution (pay attention to air quality alerts) Extreme temperatures Cigarette smoke (including secondhand smoke) Avoid crowds, especially during cold and flu season Pulmonary rehabilitation Proper use of medications (including metered dose

inhaler technique)

References American Family Physician 2001: “COPD:

Management of Acute Exacerbations and Chronic Stable Disease”

Clinical Pharmacy & Therapeutics (fourth edition) Curr Opin Pulm Med 9(2):117-124, 2003. “Evidence-

Based Approach to Acute Exacerbations of COPD” D. Trendel RN, 2009: “Learn How to Manage and

Prevent COPD Exacerbations” Oxford handbook of clinical medicine (seventh

edition) Uptodate 2009