**3.5 Postoperative patients**

336 Chronic Obstructive Pulmonary Disease – Current Concepts and Practice

Signs of increased work of breathing, accessory muscle use, pursed lips breathing

Acute or chronic ventilatory failure (best indication), PaC02 >45 mmHg, pH <7.35

Severe haemodynamic instability with or without cardiac ischemia or arrhythmia

[NPPV= non-invasive positive pressure ventilation; PaC02: arterial partial pressure of carbon dioxide;

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

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

Inability to protect the airway and/or high risk of aspiration

Recent facial, upper airway or upper gastrointestinal surgery

Pa02: arterial partial pressure of oxygen; Fi02: fraction of inspired oxygen]

the face of deterioration and to select the patients for extubation.

Table 1. Indications and contraindications for NPPV in ARF

from consideration for early extubation (Hill 2004).

**Indications** 

**Contraindications** 

Absolute

Relative

 Increased dyspnea-moderate to severe Tachypnea (>25 breaths per minute)

Hypoxaemia (use caution), Pa02/Fi02 ratio < 200

and abdominal paradox

 Cardiac or respiratory arrest Severe encephalopathy Unable to fit mask

 Severe gastrointestinal bleeding Agitated, uncooperative state Upper airway obstruction

 Inability to clear secretions Multiple organ failure

**3.4 After planned extubation** 

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 and avoid reintubation and its complications.

### **3.6 Do-not-intubate patients**

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 removed at any time (Hill 2004).

#### **3.7 Overlap syndrome**

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

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

Noninvasive Positive-Pressure Ventilation Therapy in Patients with COPD 339

provided convincing evidence that survival in COPD is prolonged by NPPV. Further work is also required to evaluate the effect of NPPV on reducing frequency and severity of COPD exacerbation. The general consensus, however, is that there is insufficient evidence to recommend NPPV for routine use in stable hypercapnic COPD (Kolodziej et al. 2007; Wijkstra et al. 2003). Despite the insufficient evidence, the ACCP consensus group opined that a trial of NPPV was justified with a symptomatic but stable and optimally treated patient who has daytime PaCO2 > 55 mm Hg, if OSA had been excluded. For PaCO2 between 50 and 54 mm Hg, , the ACCP consensus group suggested that there should be evidence of worsening hypoventilation during sleep, as suggested by a sustained (> 5 min) desaturation during use of the usual oxygen supplementation. In addition, the need for repeated hospitalizations was

The other limitation of NPPV use in patients with stable hypercapnic COPD is poor compliance to NPPV in this group of patients. Criner et al., found that only 50% of COPD patients were still using NPPV after 6 months, compared to 80% for neuromuscular patients (Criner et al. 1999). Reasons for poor adherence are unclear, but probably include the advanced age of COPD patients, frequent occurrence of co morbidities and cognitive defects, lack of motivation and appropriate/inefficient setting of NPPV. Close follow-up is

The latest edition of The International Classification of Sleep Disorders: Diagnostic and Coding Manual (ICSD-2) subsumes a broad range of disorders under the heading ''Sleep Related Hypoventilation/hypoxemic Syndromes.'' (American Academy of Sleep Medicine. 2005). Some are quite common, such as COPD with worsening gas exchange during sleep; while some are exceedingly rare, such as congenital central hypoventilation syndrome. The ICSD-2 manual recommended the use of NPPV in addition to optimal treatment of the underlying disorder in selected subgroups of the patients (Casey, Cantillo, & Brown 2007). In normal subjects, minute ventilation changes little, whereas minute ventilation in COPD patients falls approximately 16% from wakefulness to non REM sleep and almost 32% during REM sleep, compared to wakefulness, largely as a result of decreased tidal volumes. The greater drop in minute ventilation in subjects with COPD may reflect increased dependence on accessory muscles that become hypotonic during sleep, particularly in REM

sleep leading to Sleep Related Hypoventilation/hypoxemic Syndrome due to COPD.

NPPV devices are used during sleep to treat patients with Sleep Related Hypoventilation/ hypoxemic syndromes. Compelling evidence exists to support the use of NPPV during sleep in the management of selected Sleep Related Hypoventilation/ hypoxemic syndromes. NPPV has been used in Sleep Related Hypoventilation/ hypoxemic due to central respiratory control disturbances, restrictive thoracic cage disorders, neuromuscular diseases and the obesity hypoventilation syndrome. A select subgroup of COPD patients also appears to have improved sleep after treatment with NPPV but specific characteristics that describe this subgroup well remain to be elucidated. It is unclear whether exclusively nocturnal hypoxemia in these patients will be deleterious and therefore whether isolated sleep-related hypoxemia should be treated. COPD patients with clear evidence of hypoventilation while awake as evidenced by daytime hypercapnia are a reasonable starting target group. Those COPD

deemed a justification for a trial of NPPV (ACCP consensus conference 1999).

probably helpful to optimize compliance rates.

**3.9 Sleep related hypoventilation/Hypoxemia due to COPD** 

patients as compared to COPD- only patients (Marin et al. 2010) . One RCT and another study using a historical cohort showed reduction of mortality in overlap syndrome with NPPV (McEvoy et al. 2009; Windisch et al. 2009). In the study by Windisch et al., intensive pressure settings (average inspiratory pressure 28 cm H2O, average expiratory pressure 5 cm H2O and a high respiratory rate of about 21 breaths/min) were used with inhospital acclimatization and improvement in spirometry and arterial blood gas were reported (Windisch et al. 2009) . Finally, BPAP may be more comfortable and effective than CPAP in lowering CO2 and increasing tidal volume for patients with overlap syndrome, COPD component of which is much more related to moderate to severe hypercapnia and more prominent than the OSAS component.

#### **3.8 Severe stable COPD/Chronic respiratory failure in patients with COPD**

Despite the reported benefits of NPPV application in COPD patients with ARF, the role of NPPV in chronic respiratory failure (CRF) remains controversial. COPD patients with both increased hypercapnia and sleep-disordered breathing may be the ones, who are most likely to benefit from NPPV (Hill 2004). However the evidence to support the use of NPPV in CRF in the setting of severe stable COPD has been less consistent. COPD treatment guidelines does not recommend NPPV treatment routinely in end stage stable hypercapnic COPD in addition to conventional treatment (Global Initiative for Chronic Obstructive Lung Disease [GOLD] 2010).

Once hypercapnia develops, 2-year mortality is approximately 30-40% (Foucher et al. 1998). The reported studies show some physiological benefits for the use of NPPV in stable COPD, but clear survival benefit has not yet been demonstrated (Leger et al. 1994; Jones et al. 1998; Tuggey, Plant, & Elliott 2003). All of these and most other studies used a moderately aggressive ventilation to treat stable hypercapnic COPD patients and so an impressive reduction in hypercapnia was not achieved. In contrast, more aggressive form of ventilation with mean IPAP of up to 30 cmH20 or even higher was used in recent studies by Windish et al. and a remarkable reduction of PC02 was achieved (Windisch et al. 2002; Windisch et al. 2005; Windisch et al. 2006). Another RCT also has shown an improvement in survival with the application of nocturnal NPPV in end stage chronic hypercapnic COPD. The authors reported that the use of higher IPAP levels sufficient to be cardioprotective (but not to awake central respiratory drive) may result in greater treatment benefits (McEvoy et al. 2009). High intensity NPPV therefore offers a new and promising therapeutic option in the treatment of patients with CRF. High intensity NPPV is better tolerated in patients with severe chronic hypecapnic COPD and has been shown to be superior to the conventional and widely used form of low intensity NPPV in controlling nocturnal hypoventilation (Dreher et al. 2010). Nevertheless, higher leak volume, side effects and impairments in sleep quality are the main disadvantages of this modality.

NPPV might rest the chronically fatigued muscles and increase the muscle strength during daytime, could improve sleep time and efficiency, and sleep disordered breathing with episodes of hypoventilation. NPPV use in a select proportion of patients with severe stable COPD can improve gas exchange, exercise tolerance, dyspnea, work of breathing, frequency of hospitalisation, health-related quality of life and functional status (Kolodziej et al. 2007). Inconsistency in the effectiveness of all assessed outcomes may be due to the variability in degree of lung hyperinflation and NPPV levels and duration of use. As yet, no study has

patients as compared to COPD- only patients (Marin et al. 2010) . One RCT and another study using a historical cohort showed reduction of mortality in overlap syndrome with NPPV (McEvoy et al. 2009; Windisch et al. 2009). In the study by Windisch et al., intensive pressure settings (average inspiratory pressure 28 cm H2O, average expiratory pressure 5 cm H2O and a high respiratory rate of about 21 breaths/min) were used with inhospital acclimatization and improvement in spirometry and arterial blood gas were reported (Windisch et al. 2009) . Finally, BPAP may be more comfortable and effective than CPAP in lowering CO2 and increasing tidal volume for patients with overlap syndrome, COPD component of which is much more related to moderate to severe hypercapnia and more

Despite the reported benefits of NPPV application in COPD patients with ARF, the role of NPPV in chronic respiratory failure (CRF) remains controversial. COPD patients with both increased hypercapnia and sleep-disordered breathing may be the ones, who are most likely to benefit from NPPV (Hill 2004). However the evidence to support the use of NPPV in CRF in the setting of severe stable COPD has been less consistent. COPD treatment guidelines does not recommend NPPV treatment routinely in end stage stable hypercapnic COPD in addition to conventional treatment (Global Initiative for Chronic Obstructive Lung Disease

Once hypercapnia develops, 2-year mortality is approximately 30-40% (Foucher et al. 1998). The reported studies show some physiological benefits for the use of NPPV in stable COPD, but clear survival benefit has not yet been demonstrated (Leger et al. 1994; Jones et al. 1998; Tuggey, Plant, & Elliott 2003). All of these and most other studies used a moderately aggressive ventilation to treat stable hypercapnic COPD patients and so an impressive reduction in hypercapnia was not achieved. In contrast, more aggressive form of ventilation with mean IPAP of up to 30 cmH20 or even higher was used in recent studies by Windish et al. and a remarkable reduction of PC02 was achieved (Windisch et al. 2002; Windisch et al. 2005; Windisch et al. 2006). Another RCT also has shown an improvement in survival with the application of nocturnal NPPV in end stage chronic hypercapnic COPD. The authors reported that the use of higher IPAP levels sufficient to be cardioprotective (but not to awake central respiratory drive) may result in greater treatment benefits (McEvoy et al. 2009). High intensity NPPV therefore offers a new and promising therapeutic option in the treatment of patients with CRF. High intensity NPPV is better tolerated in patients with severe chronic hypecapnic COPD and has been shown to be superior to the conventional and widely used form of low intensity NPPV in controlling nocturnal hypoventilation (Dreher et al. 2010). Nevertheless, higher leak volume, side effects and impairments in sleep

NPPV might rest the chronically fatigued muscles and increase the muscle strength during daytime, could improve sleep time and efficiency, and sleep disordered breathing with episodes of hypoventilation. NPPV use in a select proportion of patients with severe stable COPD can improve gas exchange, exercise tolerance, dyspnea, work of breathing, frequency of hospitalisation, health-related quality of life and functional status (Kolodziej et al. 2007). Inconsistency in the effectiveness of all assessed outcomes may be due to the variability in degree of lung hyperinflation and NPPV levels and duration of use. As yet, no study has

**3.8 Severe stable COPD/Chronic respiratory failure in patients with COPD** 

prominent than the OSAS component.

quality are the main disadvantages of this modality.

[GOLD] 2010).

provided convincing evidence that survival in COPD is prolonged by NPPV. Further work is also required to evaluate the effect of NPPV on reducing frequency and severity of COPD exacerbation. The general consensus, however, is that there is insufficient evidence to recommend NPPV for routine use in stable hypercapnic COPD (Kolodziej et al. 2007; Wijkstra et al. 2003). Despite the insufficient evidence, the ACCP consensus group opined that a trial of NPPV was justified with a symptomatic but stable and optimally treated patient who has daytime PaCO2 > 55 mm Hg, if OSA had been excluded. For PaCO2 between 50 and 54 mm Hg, , the ACCP consensus group suggested that there should be evidence of worsening hypoventilation during sleep, as suggested by a sustained (> 5 min) desaturation during use of the usual oxygen supplementation. In addition, the need for repeated hospitalizations was deemed a justification for a trial of NPPV (ACCP consensus conference 1999).

The other limitation of NPPV use in patients with stable hypercapnic COPD is poor compliance to NPPV in this group of patients. Criner et al., found that only 50% of COPD patients were still using NPPV after 6 months, compared to 80% for neuromuscular patients (Criner et al. 1999). Reasons for poor adherence are unclear, but probably include the advanced age of COPD patients, frequent occurrence of co morbidities and cognitive defects, lack of motivation and appropriate/inefficient setting of NPPV. Close follow-up is probably helpful to optimize compliance rates.

#### **3.9 Sleep related hypoventilation/Hypoxemia due to COPD**

The latest edition of The International Classification of Sleep Disorders: Diagnostic and Coding Manual (ICSD-2) subsumes a broad range of disorders under the heading ''Sleep Related Hypoventilation/hypoxemic Syndromes.'' (American Academy of Sleep Medicine. 2005). Some are quite common, such as COPD with worsening gas exchange during sleep; while some are exceedingly rare, such as congenital central hypoventilation syndrome. The ICSD-2 manual recommended the use of NPPV in addition to optimal treatment of the underlying disorder in selected subgroups of the patients (Casey, Cantillo, & Brown 2007).

In normal subjects, minute ventilation changes little, whereas minute ventilation in COPD patients falls approximately 16% from wakefulness to non REM sleep and almost 32% during REM sleep, compared to wakefulness, largely as a result of decreased tidal volumes. The greater drop in minute ventilation in subjects with COPD may reflect increased dependence on accessory muscles that become hypotonic during sleep, particularly in REM sleep leading to Sleep Related Hypoventilation/hypoxemic Syndrome due to COPD.

NPPV devices are used during sleep to treat patients with Sleep Related Hypoventilation/ hypoxemic syndromes. Compelling evidence exists to support the use of NPPV during sleep in the management of selected Sleep Related Hypoventilation/ hypoxemic syndromes. NPPV has been used in Sleep Related Hypoventilation/ hypoxemic due to central respiratory control disturbances, restrictive thoracic cage disorders, neuromuscular diseases and the obesity hypoventilation syndrome. A select subgroup of COPD patients also appears to have improved sleep after treatment with NPPV but specific characteristics that describe this subgroup well remain to be elucidated. It is unclear whether exclusively nocturnal hypoxemia in these patients will be deleterious and therefore whether isolated sleep-related hypoxemia should be treated. COPD patients with clear evidence of hypoventilation while awake as evidenced by daytime hypercapnia are a reasonable starting target group. Those COPD

Noninvasive Positive-Pressure Ventilation Therapy in Patients with COPD 341

ventilators. CPAP as the name implies, requires the airway pressure not to change between inspiration and expiration. However BPAP therapy was originally conceived with the idea of varying the administered pressure between the inspiratory and expiratory cycles. BPAP is the commonly used pressure preset method. BPAP devices deliver separately adjustable inspiratory positive airway pressure (IPAP) and expiratory positive airway pressure (EPAP). The IPAP and EPAP levels are adjusted to maintain upper airway patency, and the pressure

Three modes of NPPV were also defined according to principles of cycling of inspiration. NPPV devices can be used in the 1) **spontaneous mode** (the patient cycles the device from EPAP to IPAP), 2) the **spontaneous timed (ST)**/assisted-controlled (AC) mode (a backup rate is available to deliver IPAP for the set inspiratory time if the patient does not trigger an IPAP/EPAP cycle within a set time window otherwise patient the device from EPAP to IPAP), 3) the **timed (T)** /pressure controlled (PC) mode (patient cannot trigger and cycle the

**Volume assured pressure support / volume target BPAP (VT-BPAP)** which is a hybrid mode of volume preset and pressure support ventilation was available by the end of the 1990s. Release of dual portable ventilators providing either pressure support ventilation or volume preset ventilation opened the way for new potent turbine pressure support ventilators able to deliver real volume ventilation with the average volume assured pressure support ventilation mode which represents a flexible way for managing the most difficult patients (Storre et al. 2006). Patient delivers the target tidal volume by the support of adjusted pressure support range. VT-BPAP has been developed in which the IPAP-EPAP difference is automatically adjusted to deliver a target tidal volume (Storre et al. 2006;

**Proportional Assist Ventilation** is another mode still under investigation. It provides a level of ventilatory assistance which is proportional to the patient's respiratory effort throughout the respiratory cycle. Some studies reported better comfort and tolerance with proportional assist ventilation but found no differences in rates of mortality or intubation (Fernandez-Vivas et al. 2003; Gay, Hess, & Hill 2001). Guidelines make no recommendation about the use of proportional assist ventilation versus pressure support ventilation in patients who are

Interfaces connect the patient's airway to the NPPV tubing. The main six interfaces for NPPV are nasal mask, full face or oronasal mask, total face mask, helmet mask, nasal pillow or plugs and mouthpieces. Usually made of silicone, masks need to be carefully fitted to the individual to obtain optimum results. Variations include the bubble-type mask, and gel masks. Mask fit can be enhanced using mask cushions and seal/support rings which are

**Nasal mask:** Nasal mask covers nose and does not cover mouth so allows speaking, drinking and cough also reduces the risk of vomiting and asphyxia. Disadvantages of nasal masks are air leaks if mouth opens, possible nasal skin damage and the need for patent nasal passages. **Oronasal /Full face mask:** Oronasal mask cover the nose and mouth and can prove valuable in patients with nasal airway blockage or acute confusional state. Oronasal mask is

support (PS=IPAP-EPAP), which augments ventilation.

inspiration- inspiratory time and respiratory rate are fixed).

Ambrogio et al. 2009; Janssens, Metzger, & Sforza 2009; Jaye et al. 2009)

receiving NPPV for ARF, due to lack of sufficient evidence.

**6. Selection of interface** 

supplied with the mask.

patients who also show continued sleep disruption or worsening hypercapnia and nocturnal hypoventilation despite oxygen therapy should be further investigated probably with polysomnography to rule out other sleep related breathing disorders. Finally we need to define optimal NPPV and interface design and settings in hopes of improving compliance of long-term therapy for all types of appropriate patients, who are likely to benefit from NPPV.
