1. Agency for Healthcare Research and Quality (AHRQ)
Noninvasive Positive-Pressure Ventilation for Acute Respiratory Failure: Comparative Effectiveness
Prepared for:
Agency for Healthcare Research and Quality (AHRQ)
Noninvasive Positive-Pressure Ventilation for Acute Respiratory Failure: Comparative Effectiveness
This slide set is based on a comparative effectiveness review (CER) titled Noninvasive Positive-Pressure Ventilation (NPPV) for Acute Respiratory Failure: Comparative Effectiveness, Comparative Effectiveness Review No. 68, which was developed by the Duke Evidence-based Practice Center, Durham, NC, for the Agency for Healthcare Research and Quality (AHRQ) under Contract No I and is available online at
CERs are comprehensive systematic reviews of the literature that usually compare two or more types of interventions with usual care for the same disease. For this CER, the existing body of evidence on the relative benefits and adverse effects of currently used modalities of noninvasive positive-pressure ventilation (NPPV) was reviewed. The literature included in this review was identified in searches for studies in MEDLINE®, EMBASE®, and the Cochrane Database of Systematic Reviews using relevant search terms. Studies in adults with acute respiratory failure due to chronic obstructive pulmonary disease, acute cardiogenic pulmonary edema, pneumonia, asthma, obesity hypoventilation syndrome, interstitial lung disease, and acute respiratory failure in the postoperative and post-transplantation settings were included. The review did not include children or adults in whom NPPV is contraindicated (patients with facial trauma, cardiopulmonary arrest, or shock) in its evaluation. Searches were conducted for studies published in the English language from 1990 onwards.
Reference:
Williams JW Jr, Cox CE, Hargett CW, et al. Noninvasive Positive-Pressure Ventilation (NPPV) for Acute Respiratory Failure: Comparative Effectiveness. Comparative Effectiveness Review No. 68 (Prepared by the Duke Evidence-based Practice Center under Contract No I). Rockville, MD: Agency for Healthcare Research and Quality; July AHRQ Publication No. 12-EHC089-EF. Available at

2. Outline of Material
Introduction to acute respiratory failure and the role of noninvasive positive-pressure ventilation (NPPV) modalities in managing acute respiratory failure of various etiologies
Systematic review methods
The clinical questions addressed by the comparative effectiveness review
Results of studies and evidence-based conclusions about the relative benefits and adverse effects of currently available NPPV modalities for acute respiratory failure
Gaps in knowledge and future research needs
Outline of Material
The material in this presentation covers the results and conclusions from a systematic comparative effectiveness review entitled Noninvasive Positive-Pressure Ventilation (NPPV) for Acute Respiratory Failure: Comparative Effectiveness. It begins with an introduction to acute respiratory failure and the role of NPPV in managing acute respiratory failure. It also covers methods used to plan and execute the systematic review, clinically important questions the review sought to answer, results of the review, evidence-based conclusions about relative effectiveness and safety of the currently used NPPV modalities for acute respiratory failure, gaps in knowledge, and the future research needs uncovered by the systematic review.
Reference:
Williams JW Jr, Cox CE, Hargett CW, et al. Noninvasive Positive-Pressure Ventilation (NPPV) for Acute Respiratory Failure: Comparative Effectiveness. Comparative Effectiveness Review No. 68 (Prepared by the Duke Evidence-based Practice Center under Contract No I). Rockville, MD: Agency for Healthcare Research and Quality; July AHRQ Publication No. 12-EHC089-EF. Available at
Williams JW Jr, Cox CE, Hargett CW, et al. AHRQ Comparative Effectiveness Review No. 68.
Available at

3. Background: Acute Respiratory Failure and Its Prevalence
For the purpose of this review, acute respiratory failure is defined as: significant change in a patient’s baseline gas-exchange status that occurs relatively suddenly (usually hours to days) and is potentially life threatening but does not require emergent intubation.
The annual incidence of acute respiratory failure is 77.6 to 430 patients per 100,000 in the United States and is expected to rise as the population ages.
Acute respiratory failure can stem from various causes, including:
Chronic obstructive pulmonary disease
Acute cardiogenic pulmonary edema
Pneumonia
Acute respiratory distress syndrome
Asthma
Obesity hypoventilation syndrome
Interstitial lung disease
Background: Acute Respiratory Failure and Its Prevalence
Respiratory failure is a syndrome characterized by the inability to maintain normal exchange of oxygen and carbon dioxide due to dysfunction of the respiratory system. There are two types of respiratory failure: type I is characterized by low partial pressure of oxygen in arterial blood (PaO2) with normal or low partial pressure of carbon dioxide in arterial blood (PaCO2), and type II is characterized by high PaCO2. Respiratory failure is termed acute when it develops over minutes or several days. For the purpose of this review, acute respiratory failure is defined as a significant change in a patient’s baseline gas-exchange status (given the constellation of available clinical data) that occurs relatively suddenly (usually hours to days) and is potentially life threatening but does not require emergent intubation.
The annual incidence of acute respiratory failure is estimated to be between 77.6 and 430 patients per 100,000. It is the most common reason for admission to the intensive care unit in the United States. The estimated health care costs related to critical care are approximately 0.7 percent of the annual gross domestic product, and the human and financial costs are expected to increase with an aging population.
Several conditions that affect the functioning of the respiratory system can lead to acute respiratory failure including chronic obstructive pulmonary disease, acute cardiogenic pulmonary edema, pneumonia, acute respiratory distress syndrome, asthma, obesity hypoventilation syndrome, and interstitial lung disease.
References:
Williams JW Jr, Cox CE, Hargett CW, et al. Noninvasive Positive-Pressure Ventilation (NPPV) for Acute Respiratory Failure: Comparative Effectiveness. Comparative Effectiveness Review No. 68 (Prepared by the Duke Evidence-based Practice Center under Contract No I). Rockville, MD: Agency for Healthcare Research and Quality; July AHRQ Publication No. 12-EHC089-EF. Available at
Behrendt CE. Acute respiratory failure in the United States: incidence and 31-day survival. Chest 2000;118(4): PMID:
Cartin-Ceba R, Kojicic M, Li G, et al. Epidemiology of critical care syndromes, organ failures, and life-support interventions in a suburban US community. Chest 2011;140(6): PMID:
Williams JW Jr, Cox CE, Hargett CW, et al. AHRQ Comparative Effectiveness Review No. 68. Available at
Behrendt CE. Chest 2000;118(4): PMID:
Cartin-Ceba R, Kojicic M, Li G, et al. Chest 2011;140(6): PMID:

4. Background: Invasive Ventilation for the Management of Acute Respiratory Failure
Strategies for managing acute respiratory failure depend on the underlying etiology and severity and include emergent ventilation, medications, or respiratory support.
In severe cases, acute respiratory failure requires respiratory support with invasive mechanical ventilation.
Despite the benefits of invasive ventilation in treating respiratory failure, up to 40 percent of patients die in the hospital.
Some of these deaths are directly attributable to the complications of invasive ventilation.
Additionally, patients might require prolonged invasive ventilation, leading to an adverse impact on quality of life and functional independence.
Background: Invasive Ventilation for the Management of Acute Respiratory Failure
The initial step in managing respiratory failure is identifying the etiology and determining the need for emergent ventilation. Emergent invasive ventilation is indicated in patients with cardiac arrest or shock, apnea, and a need for airway protection (e.g., coma or seizures). For patients who do not require emergent ventilation, supportive care with supplemental oxygen and/or medications (e.g., antibiotics, corticosteroids, beta-agonists, diuretics) are key strategies in managing acute respiratory failure. However, these conservative strategies are frequently insufficient in preventing further deterioration and death.
In severe cases of acute respiratory failure, respiratory support is required. Invasive ventilation (also known as conventional mechanical ventilation) is a form of respiratory support in which positive pressure delivers a mixture of air and oxygen through an endotracheal or tracheostomy tube to central airways. There are several modes/methods of invasive ventilation with variable levels of respiratory support that can be provided, thereby allowing individualization of the treatment plan.
Despite the life-saving potential of invasive ventilation in patients with respiratory failure, up to 40 percent of patients die in the hospital; some of these deaths are directly attributable to the complications of invasive ventilation and artificial airways. Additionally, many survivors of acute respiratory failure require prolonged invasive ventilation and suffer decrements in quality of life and functional independence.
References:
Williams JW Jr, Cox CE, Hargett CW, et al. Noninvasive Positive-Pressure Ventilation (NPPV) for Acute Respiratory Failure: Comparative Effectiveness. Comparative Effectiveness Review No. 68 (Prepared by the Duke Evidence-based Practice Center under Contract No I). Rockville, MD: Agency for Healthcare Research and Quality; July AHRQ Publication No. 12-EHC089-EF. Available at
Cartin-Ceba R, Kojicic M, Li G, et al. Epidemiology of critical care syndromes, organ failures, and life-support interventions in a suburban US community. Chest 2011;140(6): PMID:
Esteban A, Anzueto A, Frutos F, et al. Characteristics and outcomes in adult patients receiving mechanical ventilation: a 28-day international study. JAMA 2002;287(3): PMID:
Williams JW Jr, Cox CE, Hargett CW, et al. AHRQ Comparative Effectiveness Review No. 68. Available at
Cartin-Ceba R, Kojicic M, Li G, et al. Chest 2011;140(6): PMID:
Esteban A, Anzueto A, Frutos F, et al. JAMA 2002;287(3): PMID:

5. Noninvasive Positive-Pressure Ventilation for Managing Acute Respiratory Failure (1 of 3)
An increasingly recognized option for managing certain cases of acute respiratory failure is noninvasive positive-pressure ventilation (NPPV).
NPPV uses positive pressure to deliver a mixture of air and oxygen throughout the respiratory tree.
Patient-ventilator interfaces for NPPV include a face mask, a nasal mask, or nasal plugs.
The two most commonly used modes of NPPV are:
Continuous positive airway pressure (CPAP)
Bilevel positive airway pressure (BPAP)
Noninvasive Positive-Pressure Ventilation for Managing Acute Respiratory Failure (1 of 3)
Another important option for managing acute respiratory failure in patients who do not need emergent ventilation is noninvasive positive-pressure ventilation (NPPV). NPPV refers to a form of mechanical support in which positive pressure delivers a mixture of air and oxygen via a noninvasive interface.
NPPV can be delivered via a standard intensive care unit ventilator or a portable device. Patient-ventilator interfaces for NPPV include a face mask, a nasal mask, or nasal plugs. Although the face mask may be less comfortable and more difficult to monitor for aspiration, it provides better physiological performance (less resistance to airflow and less air leak) when compared to nasal devices.
The most commonly used modes of NPPV are continuous positive airway pressure (CPAP) and bilevel positive airway pressure (BPAP). CPAP is applied throughout the respiratory cycle of a spontaneously breathing patient. BPAP delivers two pressure levels according to the respiratory cycle and improves ventilation, oxygenation, and alveolar recruitment. BPAP provides both an inspiratory positive airway pressure and a continuous expiratory positive airway pressure.
References:
Williams JW Jr, Cox CE, Hargett CW, et al. Noninvasive Positive-Pressure Ventilation (NPPV) for Acute Respiratory Failure: Comparative Effectiveness. Comparative Effectiveness Review No. 68 (Prepared by the Duke Evidence-based Practice Center under Contract No I). Rockville, MD: Agency for Healthcare Research and Quality; July AHRQ Publication No. 12-EHC089-EF. Available at
Pierson DJ. History and epidemiology of noninvasive ventilation in the acute-care setting. Respir Care 2009;54(1): PMID:
Williams JW Jr, Cox CE, Hargett CW, et al. AHRQ Comparative Effectiveness Review No. 68. Available at
Pierson DJ. Respir Care 2009;54(1): PMID:

6. Noninvasive Positive-Pressure Ventilation for Managing Acute Respiratory Failure (2 of 3)
The use of NPPV for managing acute respiratory failure is attractive because:
It does not require endotracheal intubation or sedation.
It can be easily initiated or discontinued as needed.
It is associated with few of the nosocomial complications that occur with endotracheal intubation.
Noninvasive Positive-Pressure Ventilation for Managing Acute Respiratory Failure (2 of 3)
The use of NPPV together with supportive care during the treatment of respiratory failure is attractive because:
- It does not require either endotracheal intubation or moderate and/or deep sedation.
- It can be safely initiated or discontinued as needed.
- It is associated with few of the nosocomial complications that are associated with endotracheal intubation, such as ventilator-associated pneumonia, critical illness-associated weakness, pneumothorax, delirium, and infections associated with the invasive monitoring that is typically required during invasive life support.
NPPV is contraindicated in some patients, including those with cardiopulmonary arrest or shock (where greater airway control is required), those with facial trauma (where the interface [e.g., mask] cannot be used appropriately), those with severely impaired consciousness, those with high aspiration risk, and those who are unable to cooperate, protect the airway, or clear secretions.
References:
Williams JW Jr, Cox CE, Hargett CW, et al. Noninvasive Positive-Pressure Ventilation (NPPV) for Acute Respiratory Failure: Comparative Effectiveness. Comparative Effectiveness Review No. 68 (Prepared by the Duke Evidence-based Practice Center under Contract No I). Rockville, MD: Agency for Healthcare Research and Quality; July AHRQ Publication No. 12-EHC089-EF. Available at
Pierson DJ. History and epidemiology of noninvasive ventilation in the acute-care setting. Respir Care 2009;54(1): PMID:
Williams JW Jr, Cox CE, Hargett CW, et al. AHRQ Comparative Effectiveness Review No. 68. Available at
Pierson DJ. Respir Care 2009;54(1): PMID:

7. Noninvasive Positive-Pressure Ventilation for Managing Acute Respiratory Failure (3 of 3)
Disadvantages associated with the use of NPPV include:
It is a resource-intensive modality, requiring a significant amount of clinicians' time.
Substantial training and experience are needed for its implementation.
It is not appropriate for some patients, such as those with shock, facial trauma, cardiopulmonary arrest, severely impaired consciousness, or high aspiration risk and those who are unable to cooperate, protect the airway, or clear secretions.
Noninvasive Positive-Pressure Ventilation for Managing Acute Respiratory Failure (3 of 3)
NPPV is contraindicated in some patients, including those with cardiopulmonary arrest or shock (where greater airway control is required), those with facial trauma (where the interface [e.g., mask] cannot be used appropriately), those with severely impaired consciousness, those with high aspiration risk, and those who are unable to cooperate, protect the airway, or clear secretions.
References:
Williams JW Jr, Cox CE, Hargett CW, et al. Noninvasive Positive-Pressure Ventilation (NPPV) for Acute Respiratory Failure: Comparative Effectiveness. Comparative Effectiveness Review No. 68 (Prepared by the Duke Evidence-based Practice Center under Contract No I). Rockville, MD: Agency for Healthcare Research and Quality; July AHRQ Publication No. 12-EHC089-EF. Available at
Pierson DJ. History and epidemiology of noninvasive ventilation in the acute-care setting. Respir Care 2009;54(1): PMID:
Williams JW Jr, Cox CE, Hargett CW, et al. AHRQ Comparative Effectiveness Review No. 68. Available at
Pierson DJ. Respir Care 2009;54(1): PMID:

8. Uncertainties Related to the Use of NPPV in Managing Acute Respiratory Failure
Noninvasive positive-pressure ventilation (NPPV) has been assessed in several trials; clinically important benefits for this modality have been demonstrated in some of these trials.
However, the use of NPPV remains highly variable. Challenges related to the use of NPPV include:
Lack of physician knowledge
Low rates of perceived efficacy
Limited information on the effects of NPPV in patients with respiratory failure caused by conditions other than COPD and ACPE
This systematic review aimed to address these gaps in knowledge.
Uncertainties Related to the Use of NPPV for Managing Acute Respiratory Failure
Although noninvasive positive-pressure ventilation (NPPV) has been a readily available modality since the early 1990s and clinically important benefits for this strategy have been demonstrated in some trials, its use varies substantially across and within countries. Surveys in the United States have shown high variability in estimated use across hospitals. Barriers to using NPPV include:
- A lack of physician knowledge
- Low rates of perceived efficacy
- Limited information on the potential benefits and adverse effects of NPPV for patients with acute respiratory failure for conditions other than chronic obstructive pulmonary disease or acute cardiogenic pulmonary edema
This systematic review aimed to address some of these gaps in knowledge.
Reference:
Williams JW Jr, Cox CE, Hargett CW, et al. Noninvasive Positive-Pressure Ventilation (NPPV) for Acute Respiratory Failure: Comparative Effectiveness. Comparative Effectiveness Review No. 68 (Prepared by the Duke Evidence-based Practice Center under Contract No I). Rockville, MD: Agency for Healthcare Research and Quality; July AHRQ Publication No. 12-EHC089-EF. Available at
Williams JW Jr, Cox CE, Hargett CW, et al. AHRQ Comparative Effectiveness Review No. 68.
Available at

9. Agency for Healthcare Research and Quality (AHRQ) Comparative Effectiveness Review (CER) Development
Topics are nominated through a public process, which includes submissions from health care professionals, professional organizations, the private sector, policymakers, members of the public, and others.
A systematic review of all relevant clinical studies is conducted by independent researchers, funded by AHRQ, to synthesize the evidence in a report summarizing what is known and not known about the select clinical issue. The research questions and the results of the report are subject to expert input, peer review, and public comment.
The results of these reviews are summarized into Clinician Research Summaries and Consumer Research Summaries for use in decisionmaking and in discussions with patients. The Research Summaries and the full report, with references for included and excluded studies, are available at
Agency for Healthcare Research and Quality (AHRQ) Comparative Effectiveness Review (CER) Development
Topics are nominated through a public process, which includes submissions from health care professionals, professional organizations, the private sector, policymakers, members of the public, and others. A systematic review of all relevant clinical studies is conducted by independent researchers, funded by AHRQ, to synthesize the evidence in a report summarizing what is known and not known about the select clinical issue. The research questions and the results of the report are subject to expert input, peer review, and public comment. The results of these reviews are summarized into Clinician Research Summaries and Consumer Research Summaries for use in decisionmaking and in discussions with patients. The Research Summaries and the full report, with references for included and excluded studies, are available at
Reference:
Williams JW Jr, Cox CE, Hargett CW, et al. Noninvasive Positive-Pressure Ventilation (NPPV) for Acute Respiratory Failure: Comparative Effectiveness. Comparative Effectiveness Review No. 68 (Prepared by the Duke Evidence-based Practice Center under Contract No I). Rockville, MD: Agency for Healthcare Research and Quality; July AHRQ Publication No. 12-EHC089-EF. Available at
Williams JW Jr, Cox CE, Hargett CW, et al. AHRQ Comparative Effectiveness Review No. 68.
Available at

10. Clinical Questions Addressed by This Comparative Effectiveness Review (1 of 3)
Key Question 1: Is noninvasive positive-pressure ventilation associated with less morbidity (including from intubation), lower mortality, lower adverse events, or lower medical utilization when compared with supportive medical therapy or invasive ventilation:
In adults with chronic obstructive pulmonary disease and acute respiratory failure?
In adults with acute cardiogenic pulmonary edema?
In adults with acute respiratory failure due to other causes including pneumonia, asthma, obesity hypoventilation syndrome, and interstitial lung disease?
In adults with acute respiratory failure in selective settings, including the postoperative setting and the post-transplant setting?
Clinical Questions Addressed by This Comparative Effectiveness Review (1 of 3)
This comparative effectiveness review attempted to address four key questions. Key Question 1 is listed on this slide:
Is noninvasive positive-pressure ventilation associated with less morbidity (including from intubation), lower mortality, lower adverse events, or lower medical utilization when compared with supportive medical therapy or invasive ventilation:
a. In adults with chronic obstructive pulmonary disease and acute respiratory failure?
b. In adults with acute cardiogenic pulmonary edema?
c. In adults with acute respiratory failure due to other causes including pneumonia, asthma, obesity hypoventilation syndrome, and interstitial lung disease?
d. In adults with acute respiratory failure in selective settings, including the postoperative setting and the post-transplant setting?
Reference:
Williams JW Jr, Cox CE, Hargett CW, et al. Noninvasive Positive-Pressure Ventilation (NPPV) for Acute Respiratory Failure: Comparative Effectiveness. Comparative Effectiveness Review No. 68 (Prepared by the Duke Evidence-based Practice Center under Contract No I). Rockville, MD: Agency for Healthcare Research and Quality; July AHRQ Publication No. 12-EHC089-EF. Available at
Williams JW Jr, Cox CE, Hargett CW, et al. AHRQ Comparative Effectiveness Review No. 68.
Available at

11. Clinical Questions Addressed by This Comparative Effectiveness Review (2 of 3)
Key Question 2: Is noninvasive positive-pressure ventilation (NPPV) with bilevel positive airway pressure, when compared to NPPV with continuous positive airway pressure, associated with less morbidity, lower mortality, fewer adverse events, or less medical utilization:
In adults with chronic obstructive pulmonary disease and acute respiratory failure?
In adults with acute cardiogenic pulmonary edema?
In adults with acute respiratory failure due to other causes including pneumonia, asthma, obesity hypoventilation syndrome, and interstitial lung disease?
In adults with acute respiratory failure in selective settings including the postoperative setting and the post-transplant setting?
Clinical Questions Addressed by This Comparative Effectiveness Review (2 of 3)
This comparative effectiveness review attempted to address four key questions. Key Question 2 is listed on this slide:
Is noninvasive positive-pressure ventilation (NPPV) with bilevel positive airway pressure, when compared to NPPV with continuous positive airway pressure, associated with less morbidity, lower mortality, fewer adverse events, or less medical utilization:
a. In adults with chronic obstructive pulmonary disease and acute respiratory failure?
b. In adults with acute cardiogenic pulmonary edema?
c. In adults with acute respiratory failure due to other causes including pneumonia, asthma, obesity hypoventilation syndrome, and interstitial lung disease?
d. In adults with acute respiratory failure in selective settings including the postoperative setting and the post-transplant setting?
Reference:
Williams JW Jr, Cox CE, Hargett CW, et al. Noninvasive Positive-Pressure Ventilation (NPPV) for Acute Respiratory Failure: Comparative Effectiveness. Comparative Effectiveness Review No. 68 (Prepared by the Duke Evidence-based Practice Center under Contract No I). Rockville, MD: Agency for Healthcare Research and Quality; July AHRQ Publication No. 12-EHC089-EF. Available at
Williams JW Jr, Cox CE, Hargett CW, et al. AHRQ Comparative Effectiveness Review No. 68.
Available at

12. Clinical Questions Addressed by This Comparative Effectiveness Review (3 of 3)
Key Question 3: Is early extubation to noninvasive positive-pressure ventilation (NPPV), when compared with usual care, associated with less morbidity, lower mortality, fewer adverse events, or less medical utilization:
In adults with chronic obstructive pulmonary disease and acute respiratory failure?
In adults with acute cardiogenic pulmonary edema?
In adults with acute respiratory failure due to other causes including pneumonia, asthma, obesity hypoventilation syndrome, and interstitial lung disease?
In adults with acute respiratory failure in selective settings including the postoperative setting and the post-transplant setting?
Key Question 4: For Key Questions 1–3, do the effectiveness and risks of NPPV vary by setting and associated resources, experience and training of clinicians, and use of protocols or by patient characteristics (e.g., morbid obesity, mental status changes, overall disease burden)?
Clinical Questions Addressed by This Comparative Effectiveness Review (3 of 3)
This comparative effectiveness review attempted to address four key questions. Key Questions 3 and 4 are listed on this slide:
Key Question 3: Is early extubation to noninvasive positive-pressure ventilation (NPPV), when compared with usual care, associated with less morbidity, lower mortality, fewer adverse events, or less medical utilization:
a. In adults with chronic obstructive pulmonary disease and acute respiratory failure?
b. In adults with acute cardiogenic pulmonary edema?
c. In adults with acute respiratory failure due to other causes including pneumonia, asthma, obesity hypoventilation syndrome, and interstitial lung disease?
d. In adults with acute respiratory failure in selective settings including the postoperative setting and the post-transplant setting?
Key Question 4: For Key Questions 1–3, do the effectiveness and risks of NPPV vary by setting and associated resources, experience and training of clinicians, and use of protocols or by patient characteristics (e.g., morbid obesity, mental status changes, overall disease burden)?
Reference:
Williams JW Jr, Cox CE, Hargett CW, et al. Noninvasive Positive-Pressure Ventilation (NPPV) for Acute Respiratory Failure: Comparative Effectiveness. Comparative Effectiveness Review No. 68 (Prepared by the Duke Evidence-based Practice Center under Contract No I). Rockville, MD: Agency for Healthcare Research and Quality; July AHRQ Publication No. 12-EHC089-EF. Available at
Williams JW Jr, Cox CE, Hargett CW, et al. AHRQ Comparative Effectiveness Review No. 68.
Available at

13. Rating the Strength of Evidence From the Comparative Effectiveness Review
The strength of evidence was classified into four broad categories:
High
Further research is very unlikely to change the confidence in the estimate of effect.
Moderate
Further research may change the confidence in the estimate of effect and may change the estimate.
Low
Further research is likely to change the confidence in the estimate of effect and is likely to change the estimate.
Insufficient
Evidence either is unavailable or does not permit estimation of an effect.
Rating the Strength of Evidence From the Comparative Effectiveness Review
Throughout this slide set, strength of evidence ratings are assigned to findings of the report. Strength of evidence is typically assigned to reviews of medical treatments after assessing four domains: risk of bias, consistency, directness, and precision. Although these categories were developed to assess the strength of treatment studies, the domains also apply to studies of prevalence and screening. Available evidence for each Key Question (KQ) was assessed for each of these four domains; the domains were combined qualitatively to develop the strength of evidence for each KQ.
Reference:
Williams JW Jr, Cox CE, Hargett CW, et al. Noninvasive Positive-Pressure Ventilation (NPPV) for Acute Respiratory Failure: Comparative Effectiveness. Comparative Effectiveness Review No. 68 (Prepared by the Duke Evidence-based Practice Center under Contract No I). Rockville, MD: Agency for Healthcare Research and Quality; July AHRQ Publication No. 12-EHC089-EF. Available at
Williams JW Jr, Cox CE, Hargett CW, et al. AHRQ Comparative Effectiveness Review No. 68.
Available at

14. Overview of the Findings for NPPV Versus Supportive Medical Therapy in Patients With Acute Respiratory Failure
Mortality
Endotracheal Intubation Rate
Hospital-Acquired Pneumonia
Incident Myocardial Infarction Rates
NPPV + Supportive Medical Therapy Versus Supportive Medical Therapy Only
Decreased with NPPV. Evidence was strongest in patients with COPD or ACPE.
(OR = 0.56; 95% CI, 0.44 to 0.72)
SOE: High
(OR = 0.31; 95% CI, 0.24 to 0.41)
Decreased with NPPV. Evidence was strongest in patients with COPD.
(OR = 0.27; 95% CI, 0.15 to 0.49)
SOE: Moderate
No difference between groups. Evidence was strongest in patients with COPD or ACPE.
(OR = 1.11; 95% CI, 0.85 to 1.44).
95% CI = 95-percent confidence interval; ACPE = acute cardiogenic pulmonary edema; COPD = chronic obstructive pulmonary disease; NPPV = noninvasive positive-pressure ventilation; OR = odds ratio; SOE = strength of evidence
Overview of the Findings for NPPV Versus Supportive Medical Therapy in Patients With Acute Respiratory Failure
This slide presents an overview of the findings of the review for the use of NPPV versus supportive medical therapy in patients with acute respiratory failure of various etiologies. The details of the findings are outlined in subsequent slides.
Reference:
Williams JW Jr, Cox CE, Hargett CW, et al. Noninvasive Positive-Pressure Ventilation (NPPV) for Acute Respiratory Failure: Comparative Effectiveness. Comparative Effectiveness Review No. 68 (Prepared by the Duke Evidence-based Practice Center under Contract No I). Rockville, MD: Agency for Healthcare Research and Quality; July AHRQ Publication No. 12-EHC089-EF. Available at
Williams JW Jr, Cox CE, Hargett CW, et al. AHRQ Comparative Effectiveness Review No. 68.
Available at

15. NPPV Versus Supportive Medical Therapy in Patients With Acute Respiratory Failure (1 of 2)
Mortality and endotracheal intubation rates decreased with NPPV versus supportive care (OR for mortality = 0.56, 95% CI 0.44 to 0.72; OR for intubation rate = 0.31, 95% CI 0.24 to 0.41).
Supportive care was medical therapy.
Evidence was strongest for patients with chronic obstructive pulmonary disease and acute cardiogenic pulmonary edema; limited evidence supported an effect in postoperative and post-transplantation settings. Strength of Evidence: High
NPPV Versus Supportive Medical Therapy in Patients With Acute Respiratory Failure (1 of 2)
There was high-strength evidence that use of noninvasive positive-pressure ventilation (NPPV) reduces mortality when compared with supportive care. Thirty-nine studies compared the effects of NPPV plus supportive medical therapy with supportive medical therapy alone on the outcome of mortality; 19 of these studies were rated good in quality and 14 were rated fair in quality. Mortality rates ranged from 0–33 percent for NPPV and 0–80 percent for usual supportive care. Overall, there was a lower risk of mortality when NPPV was employed in addition to usual supportive care; the summary odds ratio (OR) was 0.56 (95-percent confidence interval [95% CI], 0.44–0.72). Effects were consistent across studies; funnel plots and test statistics did not suggest publication bias. The evidence is strongest for patients with chronic obstructive pulmonary disease (COPD) and acute cardiogenic pulmonary edema (ACPE), but limited evidence supports an effect in postoperative and post-transplant settings.
There was high-strength evidence that use of NPPV reduces endotracheal intubation rates when compared with supportive care. Thirty-nine studies compared the effects of NPPV plus supportive medical therapy with supportive medical therapy alone on the outcome of endotracheal intubation rates; 19 of these studies were rated good in quality and 14 were rated fair in quality. Intubation rates ranged from 0–62 percent for NPPV and 3–77 percent for supportive care. Overall, there was a lower risk of intubation for patients when NPPV was added to supportive care (summary OR 0.31; 95% CI, 0.24 to 0.41). Tests for heterogeneity showed moderate variability in treatment effects across studies. This evidence is strongest for patients with COPD but also supports an effect in patients with ACPE and in postoperative and post-transplant settings.
Reference:
Williams JW Jr, Cox CE, Hargett CW, et al. Noninvasive Positive-Pressure Ventilation (NPPV) for Acute Respiratory Failure: Comparative Effectiveness. Comparative Effectiveness Review No. 68 (Prepared by the Duke Evidence-based Practice Center under Contract No I). Rockville, MD: Agency for Healthcare Research and Quality; July AHRQ Publication No. 12-EHC089-EF. Available at
Abbreviations: 95% CI = 95-percent confidence interval; NPPV = noninvasive positive-pressure ventilation; OR = odds ratio
Williams JW Jr, Cox CE, Hargett CW, et al. AHRQ Comparative Effectiveness Review No. 68.
Available at

16. NPPV Versus Supportive Medical Therapy in Patients With Acute Respiratory Failure (2 of 2)
The rate of hospital-acquired pneumonia decreased with NPPV versus supportive care (OR = 0.27; 95% CI, 0.15 to 0.49); evidence was strongest for patients with chronic obstructive pulmonary disease (COPD). Strength of Evidence: Moderate
No differences in myocardial infarction rates were observed (OR = 1.11; 95% CI, 0.85 to 1.44); evidence was strongest in patients with COPD and acute cardiogenic pulmonary edema.
Strength of Evidence: Moderate
NPPV Versus Supportive Medical Therapy in Patients With Acute Respiratory Failure (2 of 2)
There was moderate-strength evidence that hospital-acquired pneumonia decreased with noninvasive positive-pressure ventilation (NPPV) versus supportive care. Nine studies assessed the effects of NPPV versus supportive care on hospital-acquired pneumonia. Rates of hospital-acquired pneumonia ranged from 0–10 percent for NPPV and from 7–24 percent for supportive care. Hospital-acquired pneumonia is defined as pneumonia that develops more than 48 hours after hospitalization but was not incubating at the time of admission. Overall, there was a lower risk of pneumonia when NPPV was employed versus usual supportive care (odds ratio [OR] = 0.27; 95-percent confidence interval [95% CI], ). There was no significant variability in treatment effects across studies.
No difference in myocardial infarction rates was observed with NPPV versus supportive care. The strength of evidence for this finding was rated moderate. Seven studies reported on the effects of NPPV versus supportive care on myocardial infarction rates; six of the studies were rated good in quality. Rates of myocardial infarction ranged from 2–30 percent for NPPV and from 0–30 percent for supportive care. Overall, there was no difference in the rate of myocardial infarction when NPPV was added to supportive care (OR = 1.11; 95% CI, ). There was no significant variability in treatment effects across studies. Most studies were in patients with ACPE (four studies), followed by studies in patients with COPD (two studies).
Reference:
Williams JW Jr, Cox CE, Hargett CW, et al. Noninvasive Positive-Pressure Ventilation (NPPV) for Acute Respiratory Failure: Comparative Effectiveness. Comparative Effectiveness Review No. 68 (Prepared by the Duke Evidence-based Practice Center under Contract No I). Rockville, MD: Agency for Healthcare Research and Quality; July AHRQ Publication No. 12-EHC089-EF. Available at
Abbreviations: 95% CI = 95-percent confidence interval; NPPV = noninvasive positive-pressure ventilation; OR = odds ratio
Williams JW Jr, Cox CE, Hargett CW, et al. AHRQ Comparative Effectiveness Review No. 68.
Available at

17. Overview of the Findings for NPPV With BPAP Versus CPAP in Patients With ACPE
Mortality
Endotracheal Intubation Rate
Hospital-Acquired Pneumonia
Incident Myocardial Infarction Rates
NPPV With BPAP Versus NPPV With CPAP in Patients With ACPE
No difference between groups. (OR = 0.89; 95% CI, 0.58 to 1.35)
SOE: Moderate
No difference between groups. (OR = 0.84; 95% CI, 0.51 to 1.38).
Not reported
No difference between groups.
(OR = 0.69; 95% CI, 0.34 to 1.40)
SOE: Low
95% CI = 95-percent confidence interval; ACPE = acute cardiogenic pulmonary edema; BPAP = bilevel positive airway pressure; COPD = chronic obstructive pulmonary disease; CPAP = continuous positive airway pressure; NPPV = noninvasive positive-pressure ventilation; OR = odds ratio; SOE = strength of evidence
Overview of the Findings for NPPV With BPAP Versus NPPV With CPAP in Patients With ACPE
This slide presents an overview of the findings of the review for the use of noninvasive positive-pressure ventilation (NPPV) with bilevel positive airway pressure (BPAP) versus NPPV with continuous positive airway pressure (CPAP) in patients with acute cardiogenic pulmonary edema (ACPE). The details the findings are outlined in subsequent slides.
Reference:
Williams JW Jr, Cox CE, Hargett CW, et al. Noninvasive Positive-Pressure Ventilation (NPPV) for Acute Respiratory Failure: Comparative Effectiveness. Comparative Effectiveness Review No. 68 (Prepared by the Duke Evidence-based Practice Center under Contract No I). Rockville, MD: Agency for Healthcare Research and Quality; July AHRQ Publication No. 12-EHC089-EF. Available at
Williams JW Jr, Cox CE, Hargett CW, et al. AHRQ Comparative Effectiveness Review No. 68.
Available at

18. Noninvasive Positive-Pressure Ventilation With BPAP Versus CPAP in Patients With ACPE
Mortality and endotracheal intubation rates did not differ significantly when providing NPPV with BPAP versus CPAP (OR for mortality = 0.89, 95% CI 0.58 to 1.35; OR for intubation rate = 0.84, 95% CI 0.51 to 1.38).
Strength of Evidence: Moderate
Myocardial infarction did not differ significantly when providing NPPV with BPAP versus CPAP (OR = 0.69, 95% CI 0.34 to 1.40).
Strength of Evidence: Low
Noninvasive Positive-Pressure Ventilation With BPAP Versus CPAP in Patients With ACPE
There was moderate-strength evidence that mortality did not differ significantly when providing noninvasive positive-pressure ventilation (NPPV) with continuous positive airway pressure (CPAP) versus bilevel positive airway pressure (BPAP). Ten studies assessed the effects of BPAP versus CPAP on mortality. Seven of the studies evaluated CPAP versus BPAP, while three studies had a third comparison arm where patients received supplemental oxygen alone. In-hospital mortality ranged from 0–25 percent for BPAP, 0–21 percent for CPAP, and 0–30 percent for oxygen alone. Overall, there was no difference in in-hospital mortality between the BPAP and CPAP groups in a random-effects model meta-analysis (odds ratio [OR] = 0.89; 95-percent confidence interval [95% CI], 0.58 to 1.35) drawn from a total of 10 studies. Mortality was generally assessed across the duration of hospitalization (nine studies), although one study reported 7-day mortality. It should be noted that fewer than 2 percent of patients enrolled in these studies carried a primary diagnosis other than acute cardiogenic pulmonary edema (ACPE). Based on direct comparisons, no conclusions can be made about the effect of BPAP versus CPAP for patients with respiratory failure of other etiologies.
Endotracheal intubation rates did not differ significantly when providing NPPV with BPAP versus CPAP. The strength of evidence for this finding was rated as moderate. Twelve studies assessed the effects of BPAP versus CPAP on endotracheal intubation rates. Eight of the studies evaluated CPAP versus BPAP, while four studies had a third comparison arm where patients received supplemental oxygen alone. Endotracheal intubation rates ranged from 0–29 percent for BPAP, 0–33 percent for CPAP, and 2.8–42 percent for oxygen alone. Based on an analysis of 12 studies, there was no difference in the incidence of endotracheal intubation between the BPAP and CPAP groups in a random-effects model meta-analysis (OR = 0.84; 95% CI, 0.51 to 1.38). No significant variability in treatment effects across studies was detected. Similar to the studies reporting on mortality, fewer than 2 percent of patients enrolled in these studies carried a primary diagnosis other than ACPE.
There was low-strength evidence that myocardial infarction rates did not differ significantly when providing NPPV with BPAP versus CPAP. Seven studies assessed the effects of BPAP versus CPAP on myocardial infarction rates. Five of the studies evaluated CPAP versus BPAP, while two studies had a third comparison arm where patients received supplemental oxygen alone. All studies were conducted in patients with ACPE. Myocardial infarction rates ranged from 0–71 percent for BPAP, 7–31 percent for CPAP, and 0–30 percent for oxygen alone. Overall, there was no significant difference in myocardial infarction rates when NPPV was applied with BPAP versus CPAP (OR = 0.69; 95% CI, 0.34–1.40). There was moderate heterogeneity in treatment effects across studies.
Reference:
Williams JW Jr, Cox CE, Hargett CW, et al. Noninvasive Positive-Pressure Ventilation (NPPV) for Acute Respiratory Failure: Comparative Effectiveness. Comparative Effectiveness Review No. 68 (Prepared by the Duke Evidence-based Practice Center under Contract No I). Rockville, MD: Agency for Healthcare Research and Quality; July AHRQ Publication No. 12-EHC089-EF. Available at
Abbreviations: 95% CI = 95-percent confidence interval; ACPE = acute cardiogenic pulmonary edema; BPAP = bilevel positive airway pressure; CPAP = continuous positive airway pressure; NPPV = noninvasive positive-pressure ventilation; OR = odds ratio
Williams JW Jr, Cox CE, Hargett CW, et al. AHRQ Comparative Effectiveness Review No. 68.
Available at

19. Other Key Findings of the Comparative Effectiveness Review (1 of 3)
Evidence from a limited number of patients (n = 405) suggested that NPPV, when compared with invasive ventilation, decreased rates of hospital-acquired pneumonia. This evidence was highest in patients with chronic obstructive pulmonary disease.
Strength of evidence: High
Evidence from a limited number of patients also suggested that rates of mortality did not differ between NPPV and invasive ventilation groups.
Strength of evidence: Low
Other Key Findings of the Comparative Effectiveness Review (1 of 3)
Four studies evaluated the relative effects of noninvasive positive-pressure ventilation (NPPV) versus invasive ventilation on hospital-acquired pneumonia in 405 patients. Overall, there was a markedly lower risk of pneumonia with NPPV (summary odds ratio [OR] = 0.15; 95-percent confidence interval [95% CI], 0.08 to 0.30). There was no significant variability in treatment effects across studies. Two of the four studies were conducted in patients with chronic obstructive pulmonary disease, while the remaining two studies were conducted in mixed patient populations.
Four studies compared NPPV to invasive ventilation and reported effects on mortality. The etiology of acute respiratory failure was COPD (two studies) and mixed (two studies). One study was of good quality; the other studies were of fair quality. The mortality rate for invasive ventilation ranged from 6–47 percent. Overall, there was no difference in mortality when NPPV was used versus invasive ventilation (summary OR = 0.61; 95% CI, 0.33 to 1.12).
Reference:
Williams JW Jr, Cox CE, Hargett CW, et al. Noninvasive Positive-Pressure Ventilation (NPPV) for Acute Respiratory Failure: Comparative Effectiveness. Comparative Effectiveness Review No. 68 (Prepared by the Duke Evidence-based Practice Center under Contract No I). Rockville, MD: Agency for Healthcare Research and Quality; July AHRQ Publication No. 12-EHC089-EF. Available at
Williams JW Jr, Cox CE, Hargett CW, et al. AHRQ Comparative Effectiveness Review No. 68.
Available at

20. Other Key Findings of the Comparative Effectiveness Review (2 of 3)
Limited evidence suggested potential benefits of noninvasive positive-pressure ventilation (NPPV) in preventing recurrent respiratory failure after extubation in high-risk patients.
Strength of Evidence: Low
Limited evidence also suggested some benefits when NPPV was used to facilitate extubation in patients with chronic obstructive pulmonary disease who were intubated for acute respiratory failure.
Other Key Findings of the Comparative Effectiveness Review (2 of 3)
Limited evidence suggested potential benefits of noninvasive positive-pressure ventilation (NPPV) in preventing recurrent respiratory failure after extubation in high-risk patients. The strength of evidence for this finding was rated low.
- Five studies assessing reintubation rates with NPPV (bilevel positive airway pressure in all studies) versus usual care reported reintubation rates ranging from 8–25 percent for NPPV and 8–28 percent for usual care. Overall, using NPPV after extubation did not decrease reintubation rates when compared with usual supportive care. However, subgroup analyses in patients at high risk for recurrent acute respiratory failure versus those at average risk showed a protective effect only for those at high risk (odd ratio [OR] = 0.43; 95-percent confidence interval [95% CI], 0.24 to 0.77).
- Two studies, both in populations at high risk for reintubation, reported rates of hospital-acquired pneumonia ranging from 6–23 percent for NPPV and 17–33 percent for usual care. Overall, using NPPV after extubation decreased hospital-acquired pneumonia rates when compared with usual supportive care (summary OR = 0.52; 95% CI, 0.28 to 0.97).
- Mortality ranged from 1–23 percent for usual care and 1–16 percent for NPPV in four studies. Overall, using NPPV after extubation did not decrease mortality (OR = 0.65; 95% CI, 0.38 to 1.10). Exploratory subgroup analyses suggested a greater effect in patients at high risk versus average risk, but the difference in effects was not statistically significant (p = 0.33).
Limited evidence also suggested that in patients with chronic obstructive pulmonary disease (COPD) who were intubated for acute respiratory failure, there was a reduction in hospital-acquired pneumonia and mortality when NPPV was used to facilitate extubation.
- Five studies reported the effects of using NPPV to facilitate extubation versus conventional weaning on mortality. For the two studies in patients with CODP, NPPV decreased mortality (summary OR = 0.17; 95% CI, 0.05–0.65). In the three studies conducted in patients with mixed etiologies of acute respiratory failure, the number of patients randomized and events (38 deaths) were small, and the results were highly variable across studies.
- Five studies reported the effects of using NPPV to facilitate extubation versus conventional weaning on hospital-acquired pneumonia. For the two studies in patients with COPD, NPPV decreased rates of hospital-acquired pneumonia (summary OR = 0.14; 95% CI, 0.04–0.48). In the three studies conducted in patients with mixed etiologies of acute respiratory failure, confidence intervals were broad and the number of patients studied were few.
Reference:
Williams JW Jr, Cox CE, Hargett CW, et al. Noninvasive Positive-Pressure Ventilation (NPPV) for Acute Respiratory Failure: Comparative Effectiveness. Comparative Effectiveness Review No. 68 (Prepared by the Duke Evidence-based Practice Center under Contract No I). Rockville, MD: Agency for Healthcare Research and Quality; July AHRQ Publication No. 12-EHC089-EF. Available at
Williams JW Jr, Cox CE, Hargett CW, et al. AHRQ Comparative Effectiveness Review No. 68.
Available at

21. Other Key Findings of the Comparative Effectiveness Review (3 of 3)
Effects of noninvasive positive-pressure ventilation (NPPV) on mortality and intubation rates were stronger in clinical trials when compared with studies conducted in clinical practice settings.
However, evidence was insufficient to permit estimation of differential treatment effects by clinician experience, system resources, or patient characteristics.
Strength of Evidence: Low
The treatment effects for NPPV on mortality and intubation rates were consistent across studies conducted in the United States or Canada versus European countries versus other countries.
Other Key Findings of the Comparative Effectiveness Review (3 of 3)
Effects of noninvasive positive-pressure ventilation (NPPV) on mortality and intubation rates appeared stronger in controlled clinical trials versus studies conducted in clinical practice settings. The strength of evidence for this finding was rated low. Of the 43 studies that compared NPPV to usual supportive care or invasive ventilation and reported mortality rates, 11 were efficacy trials, 2 were effectiveness trials, and 30 were mixed efficacy-effectiveness trials. The pooled odds ratios (ORs) for mortality were 0.56 (95-percent confidence interval [95% CI], 0.31–1.02) and 0.99 (95% CI, 0.66–1.49) for efficacy and effectiveness trials, respectively; for mixed efficacy-effectiveness trials, the pooled OR was 0.52 (95% CI, 0.41–0.66). An analysis that examined risk of intubation yielded similar results: for intubation, the pooled ORs for efficacy (n = 10), effectiveness (n = 2), and mixed efficacy-effectiveness trials (n = 25) were, respectively, 0.29 (95% CI, 0.19 to 0.46), 0.58 (95% CI, 0.16 to 2.13), and 0.29 (95% CI, 0.21 to 0.41). The difference in pooled ORs across the three categories of effectiveness was statistically significant for mortality (p = 0.02) but not for intubation (p = 0.61). It is important to note that for both mortality and intubation, there were only two effectiveness trials, which potentially render the pooled OR an unreliable estimate. Current evidence is therefore insufficient to estimate the effect of clinician experience, setting, system resources, and patient characteristics on treatment effects.
Limited evidence suggested that the treatment effects for NPPV on mortality and intubation rates were consistent across studies conducted in various geographical regions. The strength of evidence for this finding was rated low.
- Meta-analyses of 39 studies that reported on mortality showed that the pooled OR for mortality for the 25 studies conducted in Europe was 0.58 (95% CI, 0.46 to 0.73), compared with 0.58 (95% CI, 0.25 to 1.33) for the 5 studies conducted in the United States or Canada, and 0.64 (95% CI, 0.36 to 1.13) for the 13 studies conducted in other countries. The difference in pooled ORs for mortality across the three categories of countries was not statistically significant (p = 0.95).
- For the 39 studies that reported intubation rates, the pooled OR in meta-analyses was 0.33 (95% CI, 0.22 to 0.48) for the 19 studies conducted in Europe, 0.36 (95% CI, 0.20 to 0.66) for the 6 studies conducted in the United States or Canada, and 0.25 (95% CI, 0.14 to 0.43) for the 14 studies conducted in other countries. The difference in pooled odds ratios for intubation across the three categories of countries was not statistically significant (p = 0.70).
Reference:
Williams JW Jr, Cox CE, Hargett CW, et al. Noninvasive Positive-Pressure Ventilation (NPPV) for Acute Respiratory Failure: Comparative Effectiveness. Comparative Effectiveness Review No. 68 (Prepared by the Duke Evidence-based Practice Center under Contract No I). Rockville, MD: Agency for Healthcare Research and Quality; July AHRQ Publication No. 12-EHC089-EF. Available at
Williams JW Jr, Cox CE, Hargett CW, et al. AHRQ Comparative Effectiveness Review No. 68.
Available at

22. Conclusions (1 of 2)
For patients with acute respiratory failure due to severe exacerbations of COPD or ACPE, NPPV, when compared with supportive medical therapy alone, improved the:
Rate of mortality
Rate of endotracheal intubation
Rate of hospital-acquired pneumonia
In a limited number of patients, the reduction in the rate of hospital-acquired pneumonia was seen with NPPV when compared with invasive ventilation.
Conclusions (1 of 2)
For patients with acute respiratory failure due to severe exacerbations of chronic obstructive pulmonary disease or acute cardiogenic pulmonary edema (ACPE), the use of noninvasive positive-pressure ventilation (NPPV) plus supportive medical therapy was associated with reductions in mortality, intubation rates, and hospital-acquired pneumonia when compared with supportive medical therapy alone.
In a limited number of patients, the use of NPPV decreased hospital-acquired pneumonia when compared with invasive ventilation.
Reference:
Williams JW Jr, Cox CE, Hargett CW, et al. Noninvasive Positive-Pressure Ventilation (NPPV) for Acute Respiratory Failure: Comparative Effectiveness. Comparative Effectiveness Review No. 68 (Prepared by the Duke Evidence-based Practice Center under Contract No I). Rockville, MD: Agency for Healthcare Research and Quality; July AHRQ Publication No. 12-EHC089-EF. Available at
Abbreviations: ACPE = acute cardiogenic pulmonary edema COPD = chronic obstructive pulmonary disease; NPPV = noninvasive positive-pressure ventilation;
Williams JW Jr, Cox CE, Hargett CW, et al. AHRQ Comparative Effectiveness Review No. 68.
Available at

23. Conclusions (2 of 2)
Direct comparisons of NPPV with CPAP and BPAP showed similar efficacy in patients with acute cardiogenic pulmonary edema.
Limited evidence suggested the possibility of a lower benefit with NPPV in studies conducted in clinical practice settings when compared with clinical trials.
However, evidence was insufficient to assess the impact of clinician experience, system resources, and patient characteristics on the effects of NPPV.
Conclusions (2 of 2)
Direct comparisons of continuous positive airway pressure and bilevel positive airway pressure in patients with acute cardiogenic pulmonary edema showed similar efficacy.
Limited evidence suggested potential benefits of NPPV for patients with acute respiratory failure as a method to facilitate weaning from invasive ventilation or to prevent recurrent postextubation respiratory failure in those at high risk. Limited evidence also indicated that the effects of using NPPV were lower in clinical trials designed to replicate usual clinical practice.
Reference:
Williams JW Jr, Cox CE, Hargett CW, et al. Noninvasive Positive-Pressure Ventilation (NPPV) for Acute Respiratory Failure: Comparative Effectiveness. Comparative Effectiveness Review No. 68 (Prepared by the Duke Evidence-based Practice Center under Contract No I). Rockville, MD: Agency for Healthcare Research and Quality; July AHRQ Publication No. 12-EHC089-EF. Available at
Abbreviations: BPAP = bilevel positive airway pressure; CPAP = continuous positive airway pressure; NPPV = noninvasive positive-pressure ventilation
Williams JW Jr, Cox CE, Hargett CW, et al. AHRQ Comparative Effectiveness Review No. 68.
Available at

24. Gaps in Knowledge (1 of 2)
Evidence on the effects of noninvasive positive-pressure ventilation (NPPV) versus supportive care is limited in patients with:
Asthma
Interstitial lung disease
Pneumonia
Acute respiratory distress syndrome/acute lung injury
Obesity hypoventilation syndrome
Postoperative respiratory failure
Post-transplantation respiratory failure
The benefits of NPPV to assist weaning or to prevent recurrent acute respiratory failure postextubation remain uncertain.
Gaps in Knowledge (1 of 2)
The review identified several knowledge gaps in the current literature on the use of noninvasive positive-pressure ventilation (NPPV) in patients with acute respiratory failure of various etiologies which include:
- A limited number of studies assessed the effects of NPPV versus supportive care in patients with asthma, interstitial lung disease, pneumonia, acute respiratory distress syndrome/acute lung injury, or obesity hypoventilation syndrome and in patients who had undergone transplantation or other surgeries. The evidence is therefore insufficient to allow meaningful conclusions about the effects of NPPV in patients with acute respiratory failure of these etiologies.
- There is some uncertainty about the benefits of NPPV in facilitating extubation or in preventing recurrent acute respiratory failure after extubation due to the limited amount of evidence in this area.
Reference:
Williams JW Jr, Cox CE, Hargett CW, et al. Noninvasive Positive-Pressure Ventilation (NPPV) for Acute Respiratory Failure: Comparative Effectiveness. Comparative Effectiveness Review No. 68 (Prepared by the Duke Evidence-based Practice Center under Contract No I). Rockville, MD: Agency for Healthcare Research and Quality; July AHRQ Publication No. 12-EHC089-EF. Available at
Williams JW Jr, Cox CE, Hargett CW, et al. AHRQ Comparative Effectiveness Review No. 68.
Available at

25. Gaps in Knowledge (2 of 2)
It is unclear if the effects of noninvasive positive-pressure ventilation (NPPV) vary by patient characteristics such as body mass index, mental status, or overall disease burden.
The impact of NPPV versus supportive care on outcomes such as patient psychological status, quality of life, and functional status and on resource utilization require more extensive characterization.
There is uncertainty about the effects of training, staffing composition/ratios, and the use of algorithms on NPPV effectiveness.
Gaps in Knowledge (2 of 2)
Other knowledge gaps in the current literature on the use of noninvasive positive-pressure ventilation (NPPV) in patients with acute respiratory failure of various etiologies include:
- The studies assessing NPPV in patients with acute respiratory failure included in this review provided little or no information on study results by patient characteristics such as body mass index, mental status, or overall disease burden. The impact of patient characteristics on the effects of NPPV therefore remain uncertain.
- The included studies also provided limited information on outcomes such as patient psychological status, quality of life, and functional status and on resource utilization.
- The effectiveness of NPPV as implemented in routine clinical practice remains unclear. Additionally, it is unclear how clinician training, hospital staffing composition and ratios, and the use of treatment algorithms impact NPPV effectiveness.
Future research studies should aim to address these gaps.
Reference:
Williams JW Jr, Cox CE, Hargett CW, et al. Noninvasive Positive-Pressure Ventilation (NPPV) for Acute Respiratory Failure: Comparative Effectiveness. Comparative Effectiveness Review No. 68 (Prepared by the Duke Evidence-based Practice Center under Contract No I). Rockville, MD: Agency for Healthcare Research and Quality; July AHRQ Publication No. 12-EHC089-EF. Available at
Williams JW Jr, Cox CE, Hargett CW, et al. AHRQ Comparative Effectiveness Review No. 68.
Available at