**3.1 Acute respiratory failure/Exacerbation of COPD**

Based upon the overwhelming evidence that NPPV reduces the need for intubation, reduces mortality and complications rates, and shortens the length of stay in both the intensive care unit (ICU) and hospital (Kramer et al. 1995; Brochard et al. 1995; Celikel et al. 1998; Martin et al. 2000; Carlucci et al. 2001; Mehta & Hill 2001) , NPPV should be considered as a standard of care in acute respiratory failure (ARF) due to COPD exacerbations (Keenan et al. 2011). Brochard et al. were the first to show that pressure-support ventilation administered via face mask significantly reduced the need for intubation, duration of mechanical ventilation, and ICU stay in patients with COPD exacerbations (Brochard et al. 1990). The patients with relatively mild COPD exacerbations are not likely to benefit from NPPV, which suggests that NPPV should be applied to selected patients who have moderate-to-severe COPD exacerbations. Though, patients with milder exacerbations appear to demonstrate a more rapid improvement in their level of dyspnea with NPPV treatment, the addition of NPPV to standard therapy for patients with milder exacerbations of COPD is not well tolerated (Keenan, Powers, & McCormack 2005). NPPV should be the first option for ventilatory

and consensus processes used to reach the recommendations presented here are the American College of Chest Physicians [ACCP] consensus report on clinical indications for NPPV in CRF due to restrictive lung disease, COPD and nocturnal hypoventilation published in 1999, the British Thoracic Society guidelines published in 2002, the Indian Society of Critical Care Medicine guidelines published in 2006, the guidelines from 12 German Medical Societies published in 2008 and the most recent guideline published in 2011 from Canadian Critical Care Trials Group/Canadian Critical Care Society Noninvasive

Severe COPD places the respiratory muscles at a mechanical disadvantage (Rochester, Braun, & Arora 1979). During COPD exacerbation, this situation becomes catastrophic. Exacerbations of COPD increase the respiratory load in these patients, exceeding their ability to adequately ventilate through a variety of mechanisms, including increasing hyperinflation with decreased diaphragmatic excursion and strength, increasing intrinsic positive end-expiratory pressure (PEEP), changes in respiratory patterns and increased respiratory frequency leading to ineffective or inadequate tidal volume generation. NPPV effectively unloads the respiratory muscles by increasing tidal volume, decreasing the respiratory rate, and decreasing the diaphragmatic work of breathing, which translates into an improvement in oxygenation, a reduction in hypercapnia, and an improvement in dyspnea. NPPV treatment counterbalances auto-PEEP, assists inspiration, reduces transdiaphragmatic pressure, lowers respiratory rate, rests the accessory muscles, increases functional residual capacity, decreases respiratory load and work of breathing and leads to favorable changes in the ventilation/perfusion ratio as well as the respiratory center and the sensivity of chemoreceptors (Mansfield & Naughton 1999; de Miguel et al. 2002). Expiration positive airway pressure (EPAP) counterbalances intrinsic PEEP. Inspiration positive airway pressure (IPAP) is capable of increasing tidal volume and subsequently decreasing the

Based upon the overwhelming evidence that NPPV reduces the need for intubation, reduces mortality and complications rates, and shortens the length of stay in both the intensive care unit (ICU) and hospital (Kramer et al. 1995; Brochard et al. 1995; Celikel et al. 1998; Martin et al. 2000; Carlucci et al. 2001; Mehta & Hill 2001) , NPPV should be considered as a standard of care in acute respiratory failure (ARF) due to COPD exacerbations (Keenan et al. 2011). Brochard et al. were the first to show that pressure-support ventilation administered via face mask significantly reduced the need for intubation, duration of mechanical ventilation, and ICU stay in patients with COPD exacerbations (Brochard et al. 1990). The patients with relatively mild COPD exacerbations are not likely to benefit from NPPV, which suggests that NPPV should be applied to selected patients who have moderate-to-severe COPD exacerbations. Though, patients with milder exacerbations appear to demonstrate a more rapid improvement in their level of dyspnea with NPPV treatment, the addition of NPPV to standard therapy for patients with milder exacerbations of COPD is not well tolerated (Keenan, Powers, & McCormack 2005). NPPV should be the first option for ventilatory

**2. Physiologic mechanism of NPPV effect in patients with COPD** 

Ventilation Guidelines Group.

elevated levels of PC02.

**3. Indications of NPPV in patients with COPD 3.1 Acute respiratory failure/Exacerbation of COPD**  support in patients with either a severe exacerbation of COPD or cardiogenic pulmonary edema(Keenan et al. 2011). Furthermore, consensus groups of experts advocate the routine use of NPPV for selected patients with COPD exacerbations (British Thoracic Society Standards of Care Committee 2002). High quality studies have shown that NPPV is an effective treatment for moderate to severe COPD exacerbation (Kramer et al. 1995; Celikel et al. 1998; Martin et al. 2000). In patients with mild to moderate ARF, characterized by pH levels between 7.25 and 7.35, the rate of NPPV failure was ranging from 15% to 20% (Elliott 2002; Lightowler et al. 2003). In more severely ill patients (pH<7.25), the rate of NPPV failure was inversely related to the severity of respiratory acidosis, rising up to 52%-62% (Conti et al. 2002; Squadrone et al. 2004). In patients with ''mild'' exacerbations, not complicated by respiratory acidosis, the use of NPPV was investigated in few studies, including patients in large majority with pH>7.35, which failed to demonstrate a better effectiveness of NPPV than standard medical therapy in preventing the occurrence of ARF (Bardi et al. 2000; Keenan, Powers, & McCormack 2005). Guidelines recommend the use of NPPV in addition to usual care in patients who have a severe exacerbation of COPD (pH<7.35 and relative hypercarbia) (grade 1A recommendation) (Keenan et al. 2011). Based on that evidence, the authors of the meta-analyses and the participants in the consensus groups recommended that NPPV should be used early in the course of a COPD exacerbation, in addition to the standard medical care (Lightowler et al. 2003; Keenan et al. 2003; British Thoracic Society Standards of Care Committee 2002) . NPPV is not appropriate for all COPD patients with ARF and the selection of candidates is important. Most of the indications and contraindications for NPPV in ARF are listed in Table 1 (Brochard et al. 1995). There are no absolute contraindications to NPPV although a number have been suggested (Ambrosino et al. 1995; Soo Hoo, Santiago, & Williams 1994). In part, these contraindications have been determined by the fact that they were exclusion criteria for the controlled trials. It is therefore accurate to state that NPPV is not proven in these circumstances rather than stating that it is contraindicated.

#### **3.2 Severe community-acquired pneumonia in patients with COPD**

The presence of pneumonia has been associated with poor outcome in patients treated with NPPV (Ambrosino et al. 1995). However COPD exacerbation is still an appropriate indication for NPPV even when complicated by community-acquired pneumonia (Confalonieri et al. 1999). In one randomized trial with patients suffering severe communityacquired pneumonia, NPPV reduced the need for intubation, and reduced mortality among the COPD subgroup of patients 2 months after hospital discharge (Confalonieri et al. 1999). But it is not clear whether NPPV should be used for severe community-acquired pneumonia in non-COPD patients.

#### **3.3 Adjunct to early liberation**

Patients with COPD can be considered for a trial of early extubation to NPPV in centres with extensive experience in the use of NPPV (Keenan et al. 2011). Guidelines suggest that NPPV be used to facilitate early liberation from mechanical ventilation in patients who have COPD, but only in centres that have expertise in this therapy (Grade 2B recommendation) (Keenan et al. 2011). Recent randomized controlled trials (RCTs) suggested benefit from NPPV after extubation in patients who had high risk of deterioration (Ferrer et al. 2006; Ferrer et al. 2009; Nava et al. 2005; Luo, Cheng, & Zhou 2001). The results of the RCTs of

Noninvasive Positive-Pressure Ventilation Therapy in Patients with COPD 337

It has been shown that NPPV in post-lung-resection patients with acute respiratory failure results in significantly less need for intubation, shorter ICU stay, and lower mortality rate than conventionally treated controls (Auriant et al. 2001) . The use of NPPV in selected postoperative patients (especially COPD patients) could maintain improved gas exchange

In the studies of patients in whom endotracheal intubation was contraindicated or postponed, COPD subgroup were supported with NPPV and weaned more successfully than the pneumonia or cancer subgroup of patients (Benhamou et al. 1992; Meduri et al. 1994). Thus, NPPV is indicated in do-not-intubate patients with acutely reversible processes that are known to respond well, including COPD exacerbations. However, if NPPV is to be used in a do-not-intubate patient, the patient and/or the family should be informed that NPPV is being used as a form of life support that may be uncomfortable and can be

The term ''overlap syndrome'' was introduced by Flenly to describe the association of obstructive sleep apnea syndrome (OSAS) and COPD (Flenley 1985). Even by chance alone, a patient with one of the disorders has a greater than 10% probability of also having the other disorder. Thus, when seeing a patient with either OSAS or COPD, it is reasonable to screen for the lower and longer nocturnal oxyhemoglobin desaturations, which produces more severe pulmonary hemodynamic complications (Chaouat et al. 1995; Bednarek et al. 2005). Concomitant COPD in patients with severe OSAS so called critical care syndrome is frequently associated with diurnal hypercapnia and acute ventilatory failure (Fletcher et al. 1991). There is an increase in the morbidity and mortality and risk of developing pulmonary hypertension and hypercapnic respiratory failure in patients with overlap syndrome than patients with OSAS alone and patients with usual COPD (Chaouat et al. 1995; Chaouat et al. 1999). NPPV with or without supplemental oxygen is now the treatment of choice for the

Improvement in daytime hypercapnia and gas exchange has been reported in overlap syndrome with continuous positive airway pressure (CPAP) treatment (Owens & Malhotra. 2010). Mild bronchodilatory effect due to amelioration of chronic irritation and responsiveness of the upper airway and reduction of the chronic airway has also been suggested as the possible mechanisms for the benefits of CPAP. Bilevel positive airway pressure (BPAP) may be preferred if the patient experiences difficulty in exhaling against a fixed pressure or has persistent intermittent hypoxemia despite adequate airflow (Kushida et al. 2006). Supplemental oxygen can be added to NPPV to eliminate persistent intermittent nocturnal hypoxemia (Kakkar & Berry 2007). In a cohort of overlap syndrome patients, CPAP added to long term oxygen treatment as compared to long term oxygen treatment resulted in a survival benefit with 5 years-survival rates of 71% and 26%, respectively (Machado et al. 2010). In another study including COPD and overlap syndrome patients, CPAP therapy eliminated the additional risk of mortality due to OSA in overlap syndrome

**3.5 Postoperative patients** 

**3.6 Do-not-intubate patients** 

removed at any time (Hill 2004).

**3.7 Overlap syndrome** 

and avoid reintubation and its complications.

patients with overlap syndrome (Mayos et al. 2001).

#### **Indications**


#### **Contraindications**

#### Absolute


#### Relative


[NPPV= non-invasive positive pressure ventilation; PaC02: arterial partial pressure of carbon dioxide; Pa02: arterial partial pressure of oxygen; Fi02: fraction of inspired oxygen]

Table 1. Indications and contraindications for NPPV in ARF

early extubation in COPD patients with NPPV are controversial, some showing significant benefit and the other showing no important benefit, but no attributable harm in either (Girault et al. 1999; Ferrer et al. 2003). Intubated COPD patients are appropriate candidates for early extubation by NPPV, but clinicians are advised to be cautious when selecting patients. The inability to sustain 5–10 min of unassisted breathing, a prior difficult intubation, multiple co-morbidities, copious secretions, a weakened cough, or the need for high levels of pressure support prior to extubation (>20 cm H2O) should exclude patients from consideration for early extubation (Hill 2004).

#### **3.4 After planned extubation**

Extubation failure occurs after 5-20% of planned (Epstein, Ciubotaru, and Wong 1997) and 40-50% of unplanned extubation (Chevron et al. 1998) NPPV may prevent the need for reintubation if applied immediately after planned extubation. NPPV is recommended to be used after planned extubation in patients who are considered to be at high risk of recurrent respiratory failure, but only in centres that have expertise in this type of therapy (Grade 2B recommendation) (Keenan et al. 2011). We should be careful to avoid delays in intubation in the face of deterioration and to select the patients for extubation.
