Online Medical Reference

Noninvasive Positive Pressure Support

Loutfi S. Aboussouan, MD

Eduardo Mireles-Cabodevila, MD

Published: March 2014


Noninvasive ventilation is the delivery of mechanical ventilation without the need for artificial airway through the larynx or trachea. The traditional method to administer noninvasive ventilation was through devices that generated negative pressures (i.e., noninvasive negative pressure ventilation), such as the cuirass or the iron lung. In the past 2 decades, noninvasive positive pressure ventilation (NIPPV) emerged as one of the most important advances in the management of both acute and chronic respiratory failure. 1-3 This modality of ventilator management, considered to include continuous positive airway pressure (CPAP), 4 carries significant advantages. In the acute setting, it is an alternative to intubation with a goal to preserve normal physiologic functions (coughing, swallowing, feeding, speech), decrease airway injury, and prevent respiratory tract infections. In the outpatient setting, it provides ventilatory support, again preserving normal physiologic functions while allowing ambulation, travel and care at home. In this review, we summarize the different modalities of this assisted ventilation technique, review their indications and contraindications in specific conditions both in the acute hospital setting and in chronic conditions managed at home.

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Modalities of Noninvasive Positive Pressure Support

The first step in understanding noninvasive mechanical ventilation is to understand the nomenclature. The term noninvasive positive pressure ventilation refers not only to the "mode," but to the fact that instead of using the traditional negative pressure (e.g., with an iron lung) now we use positive pressure to achieve ventilation. That is, we can use a pressure or volume-controlled mode (both generate positive pressure) to deliver ventilation. Thus, the basic concept of NIPPV is the application of positive pressure during the respiratory cycle (inspiration and expiration). The simplest application is that of continuous positive pressure through the respiratory cycle, which is named CPAP. The next level of sophistication is the administration of two different levels of pressure, one for inspiration and one for the expiratory phase. As technology has advanced, so have the devices and the techniques that control how the delivery of pressure (mechanical breaths) are started (triggered), controlled (targeted), and ended (cycled). Thus, numerous modes of noninvasive ventilation are available, each with a proprietary brand name. The literature is plagued with different names and acronyms to refer to the same mode of ventilation (Table 1). Importantly, many modes intended for invasive mechanical ventilation can also be delivered in a noninvasive form. Below we present the modes that are mainly used in NIPPV.

Table 1: Modes of Noninvasive Ventilation
Mode Variations Description
Continuous positive airway pressure (CPAP) Keeps the airway pressure at the operator set
value throughout the respiratory cycle.
               Auto-adjusting positive airway pressure CPAP level is adjusted according to proprietary
algorithms to minimize apneas or hypoventilation
events related to airway obstruction.
Bilevel positive airway pressure Two different airway pressures are used during the
respiratory cycle, inspiratory (IPAP) and expiratory
positive airway pressure (EPAP).
               Auto-titrating bilevel positive airway pressure IPAP and EPAP are adjusted based on proprietary
algorithm to minimize airway obstructive events.
               Adaptive servo-ventilation IPAP is adjusted for each inspiration with a goal to
maintain a moving target ventilation set at 90% of the
patient's recent average minute ventilation. Another
algorithm uses prior peak flows to target the level of
IPAP. Goal is to treat Cheyne-Stokes
respiration/central sleep apnea.
               Volume-assured pressure support IPAP is adjusted to achieve a target tidal volume set
by the operator. Goal is to correct hypoventilation.
Volume-controlled ventilation Operator sets the target tidal volume, patient will
receive same tidal volume irrespective of lung
characteristics unless alarms are triggered.

The names of the modes may change between manufacturers, as well as the algorithms to titrate settings. Several modes of mechanical ventilation can be delivered with home and critical care ventilators; we focused on those reviewed in the manuscript.

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Pressure-Controlled Devices

Continuous Positive Airway Pressure (CPAP)

CPAP is most commonly used for the treatment of obstructive sleep apnea,5 and in the treatment of sleep-disordered breathing associated with congestive heart failure.6 It also has a role in the management of acute pulmonary edema, for the support of ventilation in conditions with coexistent obstructive sleep apnea and obesity hypoventilation syndrome (OHS),7 and the overlap syndrome (coexistence of sleep apnea and chronic obstructive pulmonary disease [COPD]).8

CPAP applies a constant level of positive pressure at the airway opening during spontaneous breathing thereby acting as a pneumatic splint which maintains airway patency in sleep apnea.9 In patients with pulmonary edema, the positive intrathoracic pressure from CPAP can reduce preload and afterload with improvement in cardiac index and reduced work of breathing.10-11 The device also increase functional residual capacity but does not directly augment the tidal volume. As such, it is more effective in hypoxemic compared with hypercapnic states.

Bilevel Positive Airway Pressure

Bilevel positive airway pressure is a versatile modality of NIPPV used in both acute care and chronic conditions. It is the mainstay of ventilatory support in patients with acute respiratory failure from diverse causes, with most of the evidence supporting its use in the acute setting for COPD exacerbations and cardiogenic pulmonary edema.12 It is also extensively used in chronic conditions including obstructive sleep apnea, sleep-disordered breathing associated with congestive heart failure, conditions associated with hypoventilation such as central sleep apnea,13 the OHS,14-15 severe stable COPD,16 neuromuscular disease, and restrictive pulmonary diseases.16

Bilevel positive airway pressure ventilation cycles between a higher inspiratory positive airway pressure (IPAP) and a lower expiratory positive airway pressure (EPAP). The gradient between IPAP and EPAP augments the tidal volume, thereby maintaining alveolar ventilation, reducing the PaCO2 in conditions of hypoventilation, reducing the work of breathing, unloading the respiratory muscles, lowering diaphragmatic pressure swings, reducing respiratory rate, and eliminating or supporting diaphragmatic work. The EPAP is set to maintain upper airway patency, improve functional residual capacity, and counteract the threshold loading effects of auto-PEEP in obstructive lung diseases.17-19  The breathing is triggered by a spontaneous patient effort. Additionally, in some patients, a set back up rate can be set such as in conditions associated with central apneas (with absence of spontaneous efforts), persistent hypercapnia (to augment minute ventilation), or neuromuscular diseases (when spontaneous breath could be so weak that they fail to trigger the device).

Adaptive Servo-Ventilation (ASV)

ASV is used in patients with Cheyne-Stokes respiration/central sleep apnea syndrome (CSR-CSA), in patients with congestive heart failure, and in patients with the complex sleep apnea syndrome. This type of device adjusts the degree of pressure support for each inspiration with a goal to maintain a moving target ventilation set at 90% of the patient's recent average ventilation. The aim is to stabilize breathing and reduce respiratory alkalosis which can trigger apnea re-entry cycles which are often part of the pathogenesis of those disorders.20

Volume-Assured Pressure Support

Volume-assured pressure support is predominantly used in patients with chronic hypoventilation such as those with the OHS, neuromuscular diseases and COPD. A particular potential benefit is that volume-assured pressure support adapts to changes in the respiratory system characteristics to deliver the target tidal volume. This is of particular interest in conditions (e.g., neuromuscular diseases) where a fixed pressure setting may become inappropriate as the disease progresses.

In these devices, a target tidal volume or alveolar ventilation is set, and the device adjusts the pressure support to reach that target. The advantage of this mode of ventilatory support is to guarantee a delivered tidal volume despite variability in patient effort, airways resistance and lung or chest wall compliance.

Comparison with Volume-Controlled Devices

Whereas pressure-controlled devices are the most commonly used modalities for noninvasive support of ventilation in both acute and chronic setting, volume-controlled ventilators are also available, most often as adaptations of devices intended for use via tracheostomy. These devices provide a constant volume, with mechanical breaths triggered by the patient's effort (with assisted breaths) or a time instruction such as back up rate (for controlled breaths).

Tolerance of pressure-controlled devices may be better than with volume-controlled devices. For instance in a nonrandomized trial of noninvasive ventilation in patients with amyotrophic lateral sclerosis, the tolerance of pressure-controlled devices was 70% vs. 30% for volume-controlled devices (P = 0.08).21 In another study, the oxygen cost of breathing was reduced with a pressure-controlled device but not with a volume-controlled device.22 In a randomized trial of pressure- vs. volume-controlled ventilation in patients with chronic respiratory failure, there were similar effects on gas exchange and leak volumes, but more gastrointestinal side effects with volume-controlled ventilation.23 For patients in whom cough is also impaired, as may occur with decreased lung volumes or with concomitant bulbar dysfunction in patients with neuromuscular disease, a volume-controlled ventilator can be used to facilitate air stacking for cough assistance.24

Nocturnal NIPPV in the Outpatient Setting

Obstructive Sleep Apnea–Hypopnea Syndrome (OSAHS)

OSAHS is estimated to affect 2% of women and 4% of men,25 and is characterized by recurrent episodes of upper airway obstruction during sleep associated with arousals and/or desaturation. Symptoms of OSAHS include excessive daytime sleepiness, choking-gasping during sleep, recurrent awakenings from sleep, daytime fatigue, impaired concentration.26 Additionally, long-standing OSAHS has been linked in prospective studies to the development of hypertension,27-30 coronary artery heart disease,31-32 hypercoagulability,33-34 and stroke or death from any cause.35-36 OSAHS is also associated with an increase in the rate and severity of motor vehicular accidents,37 increased healthcare utilization, reduction of work performance and occupational injuries.38

There is substantial evidence for the potential benefits of NIPPV (most commonly CPAP) in OSAHS, with improvements in sleep quality, sleepiness, cognitive impairment and quality of life,5,39 decreased motor vehicle accidents,40 reduced blood pressure,30,41-42improved metabolic syndrome,43 decreased cardiovascular (myocardial infarction or stroke) events,31 and mortality.44

There is no evidence that bilevel positive airway pressure improves adherence or efficacy in the management of OSAHS compared with CPAP. However, current guidelines propose bilevel positive airway therapy as an option in patients who require high pressures for OSAHS control or those who cannot tolerate exhaling against a high fixed CPAP pressure.13

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Complex Sleep Apnea Syndrome

Complex sleep apnea syndrome is a sleep-related breathing disorder characterized by the emergence of significant central sleep apnea or Cheyne-Stokes respiration after control of obstructive events with the application of NIPPV in patients who have OSAHS. Key pathophysiologic mechanisms of complex sleep apnea include restoration of upper airway patency by NIPPV, increased controller gain, and a reduced CO2 reserve, such that the arterial PaCO2 frequently drops below a hypocapnic apneic threshold thereby triggering central apneas.45-46 CPAP can reduce the controller gain and increase the CO2 reserve,46 with resolution of complex sleep apnea in about 50% of patients after several weeks on CPAP.47 Otherwise, the ideal NIPPV device for use in complex sleep apnea should have the capability of providing enough pressure to resolve the OSAHS while maintaining proper ventilatory support during central apneas without fluctuations of PaCO2 which could further worsen the dysregulated ventilatory control. For patients who do not correct the complex sleep apnea on CPAP alone, ASV is one such management option which appears to be superior to bilevel positive airway pressure and to CPAP.48-49

Sleep Disorders with Cardiac Dysfunction

Obstructive Sleep Apnea Coexisting with Congestive Heart Failure

The prevalence of OSAHS in patients with impaired left ventricular ejection fraction is 11% to 53%.50 The combination of OSAHS with congestive heart failure can be synergistically detrimental. OSAHS can worsen congestive heart failure by causing periodic increase in negative intrathoracic pressure, and by compounding the already increased sympathetic nervous activity of heart failure.51 Conversely, heart failure can cause central apneas (see next section) which can lead to complete pharyngeal obstruction at the end of the central events in the absence of a negative intrathoracic pressure.52-53

CPAP reduces systolic blood pressure and improves left ventricular systolic function in medically treated patients with heart failure and coexisting obstructive sleep apnea.54-55 Further, in a prospective nonrandomized study, there was a 24% death rate in heart failure patients with untreated obstructive sleep apnea, compared with no deaths in patients treated with CPAP, but the difference was not significant (P = 0.07).56 Bilevel positive airway pressure therapy was found to be more effective in improving cardiac function compared with CPAP in a randomized trial of patients with both stable congestive heart failure and OSAHS.57

Cheyne-Stokes Respiration/Central Sleep Apnea in the Setting of Congestive Heart Failure

Cheyne-Stokes respiration is characterized by a cyclic periodic crescendo decrescendo change in breathing amplitude sometimes separated by central apneas or hypopneas during sleep. The periodicity in breathing and hyperpnea may in part be due to an increase in circulation time,58 whereas hyperventilation and increased chemoreceptor responsiveness from pulmonary congestion, decrease the arterial PaCO2 during sleep to below the hypocapnic apneic threshold, and trigger central apneas and hypopneas.59-60

In a randomized trial of CPAP in this clinical setting (the CANPAP trial), compared with optimal medical therapy alone, CPAP and optimal medical therapy improved the ejection fraction, reduced central sleep apnea, improved nocturnal oxygenation, and improved the 6-minute walking distance, but without a survival benefit.6 The absence of a survival benefit may be due to a potential reduction of preload with CPAP in patients who were preload dependent, or failure to control central apneas with CPAP in several patients. In a post-hoc analysis, the heart transplantation-free survival was significantly greater in the subgroup of patients in whom CPAP effectively suppressed central sleep apneas to <15 events/hour.61

Other NIPPV modalities such as bilevel positive airway pressure with back-up rate and ASV have been shown in some studies to be superior to CPAP in controlling respiratory events in this setting, with ASV being the most effective in controlling central, mixed and complex sleep apnea.48-49 Whether more effective resolution of obstructive and central events with these treatment modality translates into improved mortality and transplantation free survival rates remains to be determined.

Restrictive Pulmonary Diseases

Obesity Hypoventilation Syndrome

OHS refers to the presence of daytime hypercapnia (PaCO2> 45 mm Hg) in obese individuals (body mass index > 30 kg/m2), in the absence of other cause of hypoventilation. Although OSAHS is a significant risk factor for the development of OHS, about 10% of patients with OHS do not have OSAHS,62 and diurnal hypercapnia can persist in about 40% of patient with OHS after successful CPAP treatment.7 In addition to the body mass index and the apnea-hypopnea index, mean overnight oxygen saturation, and severity of restrictive pulmonary function are factors found to be associated with daytime hypercapnia.63

An initial trial of CPAP is warranted in OHS, with responders to CPAP tending to have less restriction, more severe sleep apnea, and adequate oxygenation.64-65 Bilevel positive airway pressure therapy can be tried in patients who fail to be controlled on CPAP alone. In a study of patients with OHS who failed initial CPAP treatment, volume-assured pressure support lowered PaCO2 compared with bilevel positive airway pressure alone, but did not further improve oxygenation, sleep quality, or quality of life.66

Neuromuscular Diseases and Thoracic Cage Abnormalities

The pathophysiology of hypoventilation in neuromuscular disease and thoracic care abnormalities is predominantly due to restrictive lung disease. In patients with neuromuscular disease, this restrictive impairment is compounded by a supine drop in vital capacity due to diaphragmatic weakness,67 and by atonia normally present in rapid eye movement (REM) sleep which results in a shift in the burden of breathing to the already weak diaphragm during REM sleep.68

Noninvasive ventilation, consisting of bilevel positive airway pressure, volume-assured positive pressure, or volume ventilation, can support nocturnal ventilation in such patients with improvements in daytime hypercapnia,69 a reduction in the oxygen cost of breathing,22 an increase in the ventilatory response to CO2,69 and improved lung compliance.70 Longer-term studies indicate an improvement in survival and quality of life in patients with amyotrophic lateral sclerosis with this intervention.71-72

Potential contraindications to starting NIPPV in this population include upper airway obstruction, failure to clear secretions despite optimal noninvasive support, inability to achieve mask fit, and intolerance of the intervention.24, 73

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Chronic Hypercapnic Failure Due to Severe COPD

One particular challenge in patients with COPD is respiratory muscle weakness and fatigue associated with hyperinflation which imposes a mechanically unfavorable diaphragm configuration,74 the systemic manifestations of COPD, malnutrition, and the resistive load of airway obstruction.

Although NIPPV in patients with COPD would be expected to relieve the respiratory muscle fatigue, a randomized trial of NIPPV in patients with severe COPD showed that the intervention had only marginal benefits in reducing dyspnea, did not reduce exacerbations or hospitalizations at 6 months, and did not improve the 1-year survival.75 However, appropriate selection of patients with daytime hypercapnia and superimposed nocturnal hypoventilation,76 and selection of higher inspiratory pressures,75,77may result in more favorable outcomes. For instance, a randomized controlled trial of NIPPV plus long-term oxygen therapy (LTOT) compared with LTOT alone in hypercapnic COPD, demonstrated a survival benefit in favor of NIPPV and LTOT (hazard ratio 0.6).78 Further, in a randomized trial, compared with low intensity NIPPV (mean IPAP 14 cm H2O, back up rate 8/min), the use of settings that aimed to maximally reduce PaCO2 (mean IPAP 29 cm H2O with back up rate 17.5/min) increased the daily use of NIPPV by 3.6 hours/day, improved exercise-related dyspnea, daytime PaCO2, FEV1, vital capacity and health-related quality of life,77 without disrupting sleep quality.79 The advantages of NIPPV in the setting of hypercapnic COPD appear to augment those of pulmonary rehabilitation with improved quality of life, gas exchange, exercise tolerance and decline of lung function.80

There are no specific advantages in the types of device used to provide ventilatory support. In a randomized trial in patients with stable hypercapnic COPD managed at home, there was no difference in gas tensions, oxygen saturation, lung function, exercise capacity, or adherence between volume-assured and pressure preset bilevel NIPPV.81

Overlap Syndrome (COPD and OSAHS)

The overlap syndrome is a combination of chronic respiratory disease (generally referring to COPD) and OSAHS.82 The exaggerated oxygen desaturation during sleep in patients with this combination increases the risk of hypoxemia, hypercapnia and pulmonary hypertension.83 Additionally, there is an increased risk of death and COPD hospitalization in patients with the overlap syndrome.8

Treatment with CPAP in the overlap syndrome improved survival and decreased hospitalization in patients.8 Note that additional nocturnal oxygen therapy may be warranted when significant chronic respiratory illness coexists with sleep apnea.8

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NIPPV in Acute Respiratory Failure

With appropriate patient selections and indications, NIPPV in the acute care setting can avoid the complications and discomfort associated with invasive ventilation, facilitate and accelerate extubation, improve patient outcome, reduce mortality, decrease hospital length of stay, and decrease the cost of care. Key factors to consider to achieve those outcomes include the local expertise and skill,1-2,84 the general indications and contraindications shown in Table 2, and the specific disease indications with the strength of the recommendation as shown in Table 3. Without those general principles, NIPPV may delay a necessary intubation, with the consequent increased mortality risks of such a delay.85

Table 2: Indications and Contraindications to NIPPV in the Acute Care Setting1-3,84
Subjective dyspnea with respiratory rate >25 breaths /min
Use of accessory muscles
PaCO2 >45 mm Hg with pH ≤ 7.35
PaO2/FiO2 <200 mm Hg
Conscious and cooperative (with possible exception of COPD: see text)
Proper mask fit
Contraindications (any of the following):
Severe hypoxemia (PaO2/FiO2 <75),
Severe acidemia
Multi organ failure or slowly reversible disease (in short term)
Upper airway obstruction
Anatomic abnormalities that interfere with gas delivery (e.g., facial burn or trauma)
Respiratory arrest/apnea
Cardiac arrest and hemodynamic or cardiac instability
Uncooperative patient
Encephalopathy with inability to protect airways and a high risk of aspiration
Increased risk of aspiration: copious secretions, vomiting or severe gastrointestinal bleeding
Recent airway or gastrointestinal surgery
Inability to fit mask
Criteria for discontinuation of NIPPV and intubation
Mask intolerance and poor adherence
Failure to improve dyspnea, gas exchange (e.g., PaO2/FiO2 ≤146 [or ≤175 for ARDS] after 1 hr of NIPPV)
Failure to improve mental status within 30 min
Hemodynamic instability, cardiac ischemia or arrhythmias
Difficulties with secretions management

ARDS, acute respiratory distress syndrome; COPD, chronic obstructive pulmonary disease; NIPPV, noninvasive positive pressure ventilation.

Table 3: Specific Conditions in which NIPPV or CPAP Have Been Used in the Acute Setting, Categorized by Level of Evidence and Strength of Recommendation*1-2,123
Level of Evidence Strength of Recommendation† Location
A:  High
Severe exacerbation of COPD (pH < 7.35 with hypercarbia) Recommend NIPPV ICU, RCU, ward
Cardiogenic pulmonary edema ‡ Recommend NIPPV or CPAP ICU, RCU
B:  Moderate
Immunocompromised with hypoxemic failure Suggest NIPPV ICU, RCU
Facilitate weaning in patients with COPD Suggest NIPPV ICU, RCU
Preventive after extubation in patients with high reintubation risk (chronic lung disease/ PaCO2 > 45) Suggest NIPPV ICU
Extubation failure in patients without COPD Suggest against use of NIPPV ICU
C:  Low
ALI/ARDS Recommend against CPAP

Option for NIPPV
Asthma/status asthmaticus Option for NIPPV ICU, RCU
Extubation failure in patients with COPD Option for NIPPV ICU
Facilitate weaning in patients without COPD Option for NIPPV ICU, RCU
Preventive after extubation in patients with low reintubation risk Suggest against use of NIPPV ICU

* In this table NIPPV is bilevel positive airway pressure support. CPAP is separately mentioned where appropriate.
†Recommend: strong strength of recommendation for (use it) or against (don't use it) NIPPV/CPAP; suggest: weak strength of recommendation for (probably use it) or against (probably don't use it) NIPPV/CPAP, careful monitoring advised; option: no recommendation can be made (insufficient evidence), an option to use NIPPV in carefully selected and monitored minority of patients.
‡ In most recent review, no evidence of survival benefit.88
ALI, acute lung injury; ARDS, acute respiratory distress syndrome; COPD, chronic obstructive pulmonary disease; CPAP, continuous positive airway pressure; ICU, intensive care unit; NIPPV, noninvasive positive pressure ventilation; RCU, respiratory care unit.

Acute Exacerbations of COPD

NIPPV is currently considered a standard of care practice in patients with exacerbations of COPD, based on several high quality studies.17-19,86 The advantages of NIPPV include reduced treatment failure (defined as mortality, need for intubation, or intolerance) such that the number needed to treat (NNT) to prevent one treatment failure was 5, a reduced risk of intubation (NNT = 5), a reduction in mortality (NNT = 8), and a reduced risk of complications (NNT = 3), and reduced hospital length of stay by about 3 days.19

NIPPV should be started early (i.e., before severe acidosis) in the course of a COPD exacerbation with a PaCO2 > 45 mm Hg.19 Otherwise, in patients with mild COPD exacerbations (pH > 7.35), NIPPV was poorly tolerated and was no more effective than standard medical therapy in preventing the occurrence of acute respiratory failure, improving mortality or reducing length of hospitalization.18 However, in patients with severe respiratory acidosis (pH < 7.25) where NIPPV failure rates are > 50%, a trial of NIPPV may be justified, even in the presence of hypercapnic encephalopathy, provided there are no other indications for invasive support, and provided facilities for prompt endotracheal intubation are available.1

Characteristics of the NIPPV settings that may be important to consider in such patients include higher levels of positive end-expiratory pressure, more sensitive inspiratory triggers and faster pressure rise time, which may result in faster normalization of pH, improved tolerance, and greater decrease in pCO2.87

Cardiogenic Pulmonary Edema

NIPPV rapidly improves dyspnea, respiratory and metabolic abnormalities, and should be considered in cardiogenic pulmonary edema associated with severe respiratory distress. In a large randomized trial comparing CPAP or NIPPV to standard oxygen therapy in acute pulmonary edema, the combined noninvasive treatment arms (CPAP and NIPPV) significantly reduced dyspnea score, heart rate, acidosis and hypercapnia, within the first hour after the start of treatment.88 However, there was no significant treatment effect in the 7- or 30-day mortality, rates of intubation, rates of admission to the critical care unit, or in the mean length of hospital stay.88

In contrast, smaller randomized trial and meta-analyses showed decreased intubation and mortality rates with NIPPV.89-91 The differences may be due to characteristics of the Gray study including much lower intubation rates (2.9% overall compared to 20% with conventional therapy in other trials), higher mortality, and methodology differences with a 15% rate of crossover from standard therapy to NIPPV. The presence of hypercapnia may identify a particular subgroup in which the intervention may reduce intubation rates.92

CPAP is equally recommended as other forms of NIPPV (Table 3) as there was no difference in outcomes with CPAP as opposed to other NIPPV devices in that context.88,90,93-94

Immunocompromised Host with Acute Respiratory Failure

The use of NIPPV in the setting of respiratory failure in the immunocompromised host is particularly challenging since, unlike its use in COPD exacerbation or cardiogenic pulmonary edema, the underlying pathophysiology of respiratory dysfunction may not be readily reversible. Therefore, its application in this group may need to follow clearly defined indications.

In a randomized study of NIPPV for respiratory failure following solid organ transplantation, NIPPV improved oxygenation, reduced endotracheal intubations, reduced the intensive care unit (ICU) length of stay and mortality, but with no change in overall hospital mortality.95 In another study of immunosuppressed patients from various causes, those randomized to NIPPV had fewer endotracheal intubations, fewer serious complications, with a reduced ICU and hospital mortality.96

Finally, in a large retrospective review of patients with hematologic malignancy, 46% of patients receiving noninvasive ventilation, eventually required invasive ventilation.97 However, those who were able to continue noninvasive ventilation had a lower mortality compared with invasive ventilation.97

Predictors of failure of noninvasive ventilation in hypoxemic immunocompromised patients include higher illness severity as measured by the Simplified Acute Physiology Score (SAPS), a higher respiratory rate while on NIPPV, later initiation of NIPPV after ICU admission, the need for vasopressors, renal replacement therapy, and the presence of acute lung injury (ALI).98-99 Despite these caveats, NIPPV is recommended by some as a first-line intervention in patients with mild-to-moderate acute respiratory failure.97,99

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An international consensus report states that NIPPV techniques should be considered in selected patients (hypercapnic respiratory insufficiency, especially in COPD patients and possibly obesity) to shorten the duration of intubation, but should not be routinely used as a tool for extubation failure.100 In the subset of patients with COPD and hypercapnia, NIPPV can be used in the prevention of acute respiratory failure after extubation,101-104 and to support breathing in patients who fail a spontaneous breathing trial.105-108

Treatment of Respiratory Failure after Extubation

Two randomized controlled studies compared NIPPV with standard care in respiratory failure developing after discontinuation of mechanical ventilation in patients who met predetermined criteria of readiness for extubation.85,109 Patients randomized to NIPPV had a longer time to reintubation, but there was no difference in the rate of reintubation or in the ICU length of stay, suggesting that NIPPV may have delayed a necessary intubation. Moreover, one study showed a increased ICU mortality in the NIPPV compared with the standard group (25 vs. 14% respectively).85

Prevention of Respiratory Failure after Extubation

Other studies took the approach of using NIPPV immediately after extubation to prevent respiratory failure rather applying NIPPV after the development of respiratory failure.101-104

With this approach, two randomized studies, in patients successfully weaned but considered to be at risk for reintubation, showed that those randomized to NIPPV had a lower rate of reintubation and a reduced moratlity.102-103 The risks for reintubation included a PaCO2 >45 mm Hg, consecutive weaning failure, chronic heart failure or other comorbidity, weak cough and stridor in the Nava study,103 and COPD, chronic bronchitis, bronchiectasis, obesity hypoventilation, sequelae of tuberculosis, chest wall deformity, or chronic persistent asthma in the Ferrer study.102

In another study using historical controls in patients with obesity and hypercapnia, NIPPV in the 48 hours post-extubation in patients with a body mass index >35 kg/m2 reduced the rate of respiratory failure, reduced the ICU and lengths of hospital stay, and reduced hospital mortality.104

Otherwise, in the largest available trial there was no reduction in extubation failure with preventive NIPPV in patients who were at lower risk of extubation failure.110

Facilitate Weaning

Several studies randomized mechanically ventilated patients who had failed a spontaneous breathing trial to an accelerated wean group of patients who were extubated and received NIPPV vs. a conventional wean group who receive pressure support weaning via mechanical ventilation.105-108 Most patients developed hypercapnia during the spontaneous breathing trials and the majority of the patients had COPD. A meta-analysis of the randomized studies using of this approach concluded that, compared with continued invasive ventilation, noninvasive ventilation decreased mortality (relative risk, 0.41), reduced ventilator associated pneumonia (relative risk, 0.28), and reduced total duration of mechanical ventilation (by a weighted mean difference of 7.33 days).111 The benefits appeared to be most significant in patients with COPD.111

Asthma and Status Asthmaticus

Invasive ventilation in patients with status asthmaticus is particularly challenging due to the conflicting demands of maintaining ventilation despite severe airway obstruction. Noninvasive ventilation therefore provides an attractive alternative in such patients. In an earlier prospective study NIPPV was shown to progressively improve the pH and the PaCO2 over a period of 12 to 24 hours, and reduce the respiratory rate.112 Two subsequent small randomized trials of NIPPV in an emergency room setting for patients with exacerbations of asthma have shown that the intervention improved the FEV1,113-114 and reduced hospitalizations.113 One additional randomized trial was prematurely terminated due to a physician treatment bias that favored NIPPV, with preliminary results showing a trend for decreased intubation rates, length of hospital stay and hospital charges in the treatment group.115

Despite these initial favorable results, NIPPV remains controversial in patients with status asthmaticus.116 NIPPV can be tried in an appropriate ICU environment,117 in select patients with mild-to-moderate respiratory distress (respiratory rate > than 25 breaths/min, use of accessory muscles to breathe, difficulty speaking), an arterial pH of 7.25–7.35, and a PaCO2 of 45–55mm Hg.118 Patients with impending respiratory failure or inability to protect the airway would not be NIPPV candidates.117-188

As with other obstructive impairments such as COPD, specific settings to be considered may include a higher inspiratory pressure,114 and lower extrinsic PEEP so as not to compound intrinsic PEEP.117

Acute Lung Injury and the Acute Respiratory Distress Syndrome

The most challenging application of NIPPV may be in the patients with ALI and the acute respiratory distress syndrome (ARDS). A meta-analysis of the topic concluded that such an approach was unlikely to have any significant beneficial outcomes.119 Since then, a prospective study demonstrated that NIPPV was successful in improving gas exchange and avoiding intubation in 54% of patients, with consequent reduction in ventilator-associated pneumonia and lower ICU mortality rate.120 Similarly, a randomized trial showed that NIPPV compared with controls decreased the respiratory rate and improved PaO2/FiO2, reduced intubations (5% vs. 21% respectively, P = 0.04), reduced organ failure (14% vs. 74% respectively, P < 0.001), and showed a trend for reduced mortality (5% vs. 26% respectively, P = 0.09).121

Careful selection of patients is necessary with the following factors identified as predictors of NIPPV failure: a SAPS II >34, severe hypoxemia (such as a PaO2/FiO2 <175 after 1 hour of NIPPV), shock, or metabolic acidosis.120,122 At this point, ARDS/ALI managed by NIPPV is best done in the ICU setting.

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In the out-patient setting, NIPPV is most commonly used in sleep apnea where it has demonstrated short-term benefits with improved daytime alertness and reduced fatigue, as well as long-term benefits with a reduction in adverse cardiovascular risks. Other conditions were NIPPV can be used in the outpatient setting include the management of patients with central sleep apnea in the setting of congestive heart failure, neuromuscular diseases, and stable hypercapnic COPD.

The convenience and simplicity of NIPPV delivered through a nasal and/or oral interface has greatly expanded the use of noninvasive ventilation for the management of acute respiratory failure in acute settings. The advantages of NIPPV over more invasive approaches are that it preserves normal physiologic functions such as coughing, swallowing, feeding, and speech, and prevents tracheal, laryngeal injury, and respiratory tract infections. The studies reviewed here show that the best level of evidence for the efficacy of NIPPV is for acute hypercarbic or hypoxemic respiratory failure in conditions such as COPD exacerbation, cardiogenic pulmonary edema and the immunocompromised patients. As the use of NIPPV expands, care must be given not to apply NIPPV indiscriminately for less well-established indications (such as unconscious patients, post-extubation failure, ALI or ARDS), in the presence of severe hypoxemia or acidemia, or after failure to improve dyspnea or gas exchange. The use of NIPPV in these situations may delay a necessary intubation along with the concomitant risks of such a delay, including death.85

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