**4. Treatment of COPD exacerbations**

All moderate and severe exacerbations must be evaluated in the hospital and in all severe exacerbations; arterial blood gas analysis must be performed. The patient must be evaluated immediately in terms of respiratory failure and oxygen therapy must be initiated if needed. Life threatening exacerbations should be followed up in the ICU. Respiratory failure with hypercapnia and respiratory acidosis is related with high mortality both at the time of admission and also during the 12 months follow up. While carbon dioxide retention is possible in moderate and severe exacerbations under oxygen therapy, arterial blood gas analysis must be performed every 30-60 minutes in order to detect the PaCO2 and pH levels.

The inhaled oxygen concentration must be titrated to achieve a SaO2> 90% or a PaO2> 60 mmHg. High-flow oxygen devices deliver oxygen more effectively than nasal canulas but nasal canulas may be tolerated better. If adequate oxygenation cannot be achieved by high flow masks or if the acidosis begins worsening (pH<7.35 and/or PaCO2> 50mmHg), noninvasive ventilation (NIV) is indicated. Success rates of NIV in COPD exacerbations are reported as 80-85% (Mehta&Hill 2001). The effect of NIV must be evaluated at the end of first and second hour by an arterial blood gas analysis. If there is worsening in the arterial blood gas result or if the patients cannot tolerate NIV, has worsening hypoxemia or has severe comorbidities such as myocardial infarction, hemodynamic instability, severe arrhythmias or sepsis, intubation and invasive mechanical ventilation must be initiated immediately.

Short acting inhaled β-2 agonists are the first line preferred drugs for COPD exacerbations. The dosage and frequency of these drugs must be increased. Another option is to add an inhaler short acting anticholinergic drug or increase the dosage if the patient is already taking the drug. Nevertheless, the effectiveness of this combination still remains controversial. If there is a long acting bronchodilator the patient is not using, it can also be added to the therapy even though there is no clinical evidence showing the benefit of these drugs during an exacerbation. In severe exacerbations if the patient cannot inhale effectively, nebulised forms must be used. The role of theophylline in COPD exacerbations is controversial. If there is not enough response to short acting inhaled β-2 agonists, it can be used as a second choice drug. Serum levels must be obtained and patients must be followed carefully because of its cardiovascular side effects.


\*Hospitalization in the last one month, frequent antibiotic use in the last one year, exacerbation causing severe respiratory failure, isolation of *P. Aeruginosa* in the sputum culture during stable state or prior exacerbations.

Table 3. Antibiotherapy options in infectious exacerbations of COPD

294 Chronic Obstructive Pulmonary Disease – Current Concepts and Practice

4. Pulmonary (pneumonia), or non-pulmonary (cardiac disease, diabetes mellitus)

All moderate and severe exacerbations must be evaluated in the hospital and in all severe exacerbations; arterial blood gas analysis must be performed. The patient must be evaluated immediately in terms of respiratory failure and oxygen therapy must be initiated if needed. Life threatening exacerbations should be followed up in the ICU. Respiratory failure with hypercapnia and respiratory acidosis is related with high mortality both at the time of admission and also during the 12 months follow up. While carbon dioxide retention is possible in moderate and severe exacerbations under oxygen therapy, arterial blood gas analysis must be performed every 30-60 minutes in order to

The inhaled oxygen concentration must be titrated to achieve a SaO2> 90% or a PaO2> 60 mmHg. High-flow oxygen devices deliver oxygen more effectively than nasal canulas but nasal canulas may be tolerated better. If adequate oxygenation cannot be achieved by high flow masks or if the acidosis begins worsening (pH<7.35 and/or PaCO2> 50mmHg), noninvasive ventilation (NIV) is indicated. Success rates of NIV in COPD exacerbations are reported as 80-85% (Mehta&Hill 2001). The effect of NIV must be evaluated at the end of first and second hour by an arterial blood gas analysis. If there is worsening in the arterial blood gas result or if the patients cannot tolerate NIV, has worsening hypoxemia or has severe comorbidities such as myocardial infarction, hemodynamic instability, severe arrhythmias or sepsis, intubation and invasive mechanical ventilation must be initiated

Short acting inhaled β-2 agonists are the first line preferred drugs for COPD exacerbations. The dosage and frequency of these drugs must be increased. Another option is to add an inhaler short acting anticholinergic drug or increase the dosage if the patient is already taking the drug. Nevertheless, the effectiveness of this combination still remains controversial. If there is a long acting bronchodilator the patient is not using, it can also be added to the therapy even though there is no clinical evidence showing the benefit of these drugs during an exacerbation. In severe exacerbations if the patient cannot inhale effectively, nebulised forms must be used. The role of theophylline in COPD exacerbations is controversial. If there is not enough response to short acting inhaled β-2 agonists, it can be used as a second choice drug. Serum levels must be obtained and patients must be followed

3. No response to initial drug therapy.

9. Detoriation in the arterial blood gas analysis results (pH< 7.35 or PaO2< 60mmHg or SaO2< 90%)

comorbidities with high risk. 5. Having exacerbations often. 6. Newly diagnosed arrhythmias.

7. Diagnostic uncertainty.

10. Insufficient home support

detect the PaCO2 and pH levels.

carefully because of its cardiovascular side effects.

immediately.

**4. Treatment of COPD exacerbations** 

8. Advanced age.

Management of Acute Exacerbations 297

patients. There are also some data showing that long term oxygen therapy reduces the risk of hospitalization and shortens hospital stays in severely ill COPD patients. Long-acting inhaled bronchodilators and inhaled corticosteroids to improve symptoms and reduce the risk of exacerbations in patients with stable COPD are reviewed elsewhere with promising

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Seemungal, T. A., et al. (2000). "Time course and recovery of exacerbations in patients with

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Adding systemic (oral or intravenous) glucocorticosteroids to other therapies in the hospital management of exacerbations of COPD is recommended (Niewoehner et al. 1999). Systemic use of corticosteroids may lead to fast recovery and improvement in hypoxemia and lung functions in COPD exacerbations. The recommended dosage of prednisolon is 30-40 mg/day for 7-10 days if the patient has an initial FEV1 value below 50%. Prolonged treatment does not have a positive affect, besides it may increase the risk of side effects (e.g. muscle atrophy, hyperglycemia).

Bronchoscopic studies showed that the amount of bacteria is increased nearly in 50% of COPD patients during an exacerbation when compared to the stable state(Sethi 2004). The decision to use antibiotics and the choice of antibiotic should be guided by the patient's symptoms (e.g., presence of purulent sputum), recent antibiotic use, and local microbial resistance patterns. Prophylactic or continuous use of antibiotics does not improve outcome in patients with COPD (Rabe, Hurd et al. 2007).

Even though the most common bacteria responsible for the exacerbations are H.influenzae, S. pneumoniae and M. Catarrhalis; some enteric Gram (-) bacteria and Pseudomonas aeruginosa are also isolated in most of the patiens with hypoxemia, severe airway obstruction, malnutrition, frequent hospitalization and antibiotic use history and comorbidity(Incalzi et al. 2006). There are some studies suggesting that atypical bacteria can also be an etiologic reason for an exacerbation but antibiotherapy targeting these bacteria showed no positive affect on clinical outcomes(Diederen et al. 2007; Tasbakan et al. 2007). Viruses can also be responsible in 15-40% of all exacerbations. Most of these are present with a bacterial infection.

Antibiotherapy reduces the mortality rates and treatment failure especially in severe exacerbations of COPD(Puhan et al. 2007). Antibiotics also decrease the relapse rates of exacerbationsin outpatients(Adams et al. 2000). Therefore, antibiotherapy is strongly indicated expecially if the patient has purulant sputum and increase in dyspnea. Treatment options according to clinical status is summarized in Table 3.
