A 63-year-old man with severe chronic obstructive pulmonary disease (COPD) presents with one week of increasing sputum, cough, and dyspnea. His respiratory rate is 26/minute and oxygen saturation is 86% on room air (RA). He is lethargic and appears mildly uncomfortable, but he responds appropriately to questions in three- to four-word sentences. He is tachypneic with accessory muscle use and has diffuse wheezes throughout his bilateral lung fields. His initial room air arterial blood gas (ABG) is 7.32/68/86/32. Chest radiograph is notable for flattened hemidiaphragms without focal opacity. The patient is placed on oxygen and receives prednisone with nebulized albuterol and ipratropium, but his dyspnea and tachypnea persist. Due to his respiratory distress, bilevel positive airway pressure (BiPAP) is considered.
What are the clinical indications for noninvasive positive pressure ventilation (NPPV)?
NPPV assists ventilation by delivering positive expiratory and/or inspiratory pressure without the use of an endotracheal tube. Theoretically, NPPV is a preferred method of ventilation as it may eliminate the need for endotracheal intubation and its associated morbidity and mortality, including airway trauma, loss of airway defense mechanisms (ventilator-associated pneumonia), mechanical ventilation (barotrauma), and disruption of speech and swallowing.1
NPPV is generally delivered via full-face mask or nasal mask. Nasal mask is often preferred for patient comfort, though air leaks occur with mouth breathing. There is no difference between nasal and full-face masks in outcomes including intubation rates and mortality.2,3,4 NPPV can be delivered via a portable or standard ventilator using the same modes available for endotracheal intubation, though pressure-cycled ventilators utilizing continuous positive airway pressure (CPAP) and BiPAP are most common. CPAP delivers air at a continuous fixed pressure throughout the respiratory cycle. BiPAP delivers positive pressure at alternating levels—higher for inspiration and lower for expiration. Guidelines suggest choosing a mode based on the etiology and pathophysiology of the respiratory failure and leveraging local comfort and expertise.2,3
In general, good candidates for NPPV display signs of tachypnea and dyspnea due to hypoxic or hypercapnic respiratory failure but are hemodynamically stable, without excessive secretions, and can protect their airway and achieve a proper seal with the mask.3 Difficulty may arise due to patient intolerance, claustrophobia, gastric distention, and poor fit that leads to air leak or skin erosion. With initiation of NPPV, patients should be followed in a care setting with the capacity for frequent monitoring and, if needed, quick access to invasive airway management. Monitoring should include patient comfort and ability to tolerate the device, vital signs, breathing pattern, oxygen saturation, ABG, and mental status. This initial evaluation may help predict the success of NPPV (see Table 2). Appropriately chosen candidates who do well with NPPV often demonstrate respiratory turnaround in a relatively brief interval.2,3
Review of the Data
NPPV is increasingly utilized in a variety of clinical situations. In 2000, the American Thoracic Society published consensus guidelines on the use of NPPV in acute respiratory failure.2 More recently, the Canadian Medical Association developed clinical guidelines for the use of NPPV in the acute-care setting.4 Clinical scenarios in which there is evidence for the efficacy of NPPV include severe exacerbations of COPD, cardiogenic pulmonary edema, immunosuppressed patients with pulmonary infiltrates, and hypoxia; it can also be used as a bridge to extubation in COPD patients.1-4
Acute exacerbation of COPD. Several randomized controlled trials (RCT) and meta-analyses have assessed the potential benefits of NPPV in patients with acute exacerbations of COPD. In COPD, NPPV improves gas exchange and facilitates respiratory muscle rest to decrease the work of breathing, which allows for respiratory recovery and time to effectiveness of standard therapies.5 Multiple trials have demonstrated that the addition of NPPV to usual care decreases intubation and mortality rates, as well as hospital lengths of stay (LOS).5-8
A Cochrane review of eight RCTs comparing NPPV with usual care noted a greater than 50% reduction in risk of intubation, and a number needed to treat (NNT) of eight patients to prevent one death.5 Quon and colleagues also compared NPPV to usual care in a meta-analysis of 14 trials.6 Eleven of these trials evaluated hospital mortality, which was decreased by 55% in patients receiving NPPV. Twelve trials assessed need for intubation, which decreased by 65%. In these trials, BiPAP was the most commonly used modality (see Table 3, for a comparison of NPPV modalities). Study patients had an average pH of 7.31 with an average PaCO2 of 68 mmHg. It was noted that the beneficial effects of NPPV increased as pH decreased. An earlier meta-analysis from Keenan and colleagues supported this notion, noting that the subgroup of patients with pH <7.3 benefited most in terms of decreased rates of intubation, hospital LOS, and hospital mortality.7 In this 2003 study, patients with relatively mild exacerbations of COPD did not benefit from the addition of NPPV to usual care. Based on the amount of positive evidence, NPPV is recommended in patients experiencing severe exacerbations of COPD as evidenced by a pH <7.35 and relative hypercarbia.1,2,4,7
Cardiogenic pulmonary edema. In patients with acute cardiogenic pulmonary edema, NPPV has been found to be beneficial, decreasing mortality, rates of intubation, and hospital LOS. Physiologically, NPPV augments cardiac output, improves respiratory mechanics, and decreases afterload.10 Cardiogenic edema is variably defined and has a number of causes elucidated in an analysis of 11 RCTs conducted by Masip and colleagues. These causes included acute coronary syndrome (31%), hypertension (27%), congestive heart failure (14%), and a combination of respiratory infection, arrhythmia, volume overload, and treatment noncompliance (28%).9 In this analysis, CPAP and BiPAP demonstrated a combined 43% reduction in mortality and a 57% reduction in intubation. More recently, Peter and colleagues described a statistically significant reduction in hospital mortality and the need for intubation with CPAP, while BiPAP only demonstrated a statistically significant decrease in need for intubation.10 Thus, there appears to be some evidence that CPAP is the preferred NPPV mode in patients with acute cardiogenic pulmonary edema. Despite inclusion of a recent, large RCT showing no benefit of NPPV versus usual care in cardiogenic pulmonary edema, the overall positive effect of NPPV persisted, particularly when the cause of pulmonary edema was acute coronary syndrome.11
Weaning after intubation. NPPV has been evaluated as a method to facilitate early extubation, as a measure to prevent extubation failure, and as a treatment modality for respiratory failure following extubation, with mixed results.12,13 In 1998, a small trial compared the use of NPPV in COPD patients to facilitate early extubation with a standard weaning protocol. In this population, early NPPV resulted in better weaning rates with shorter times of mechanical ventilation (10 vs. 16 days), fewer days in the ICU, and improved 60-day survival rates (92% vs. 72%).3,14 In another RCT not limited to COPD patients, Grault and colleagues found that NPPV reduced the duration of intubation (4.5 vs. 7.6 days) but was not associated with benefits in ICU length of stay or survival previously described.3,15 Thus, though NPPV may be beneficial in facilitating early extubation in COPD patients, it is not recommended in other patient populations.4
NPPV has also been evaluated as a measure to prevent respiratory failure in patients at high risk for extubation failure. When applied immediately after extubation in patients with COPD and obesity, NPPV reduced reintubation rates and ICU mortality.3,4 In 2004, Esteban and colleagues examined NPPV in patients who had respiratory failure following extubation. In this setting, NPPV was ineffective at preventing reintubation and had no survival benefit.
In summary, NPPV may facilitate early extubation and prevent extubation failure in appropriate patients, such as those with COPD, but is unlikely to be beneficial and is not recommended in patients with existing respiratory failure after extubation.4,15
Immunosuppressed patients. A 2001 single-center, randomized-controlled trial by Holbert and colleagues demonstrated decreased intubation rates and mortality with the application of NPPV in immunosuppressed patients with hypoxemic respiratory failure, fever, and pulmonary infiltrates.16
In this study, immunosuppression occurred most commonly as a result of malignancy. In the group receiving NPPV alternating with oxygen (at least 45 minutes of NPPV alternated every three hours with periods of spontaneous breathing), the rate of subsequent intubation decreased to 46%, compared with 77% in those receiving oxygen alone. The mortality rate was 38% in the NPPV group, as compared with 69% in the standard treatment group.
Though the outcomes in immunocompromised patients with hypoxemia, fever, and pulmonary infiltrates were very poor (38% mortality even with NPPV), this small study and recent guidelines suggest a trial of NPPV in this population.4,16
Other indications. NPPV has been applied in multiple other clinical scenarios, including exacerbation of asthma, community-acquired pneumonia, acute lung injury, and bronchoscopy in hypoxemic patients. It has also been evaluated in the postsurgical period and in chest trauma. There are mixed and less robust data in these various applications, and larger controlled trials are lacking.
In asthma exacerbation, NPPV may improve dyspnea, but data regarding outcomes (intubation, mortality) are lacking. A 2005 Cochrane review concluded that data remain controversial due to insufficient evidence, and guidelines make no recommendations concerning NPPV in asthma exacerbation.4,17 Similarly, in community-acquired pneumonia without prior history of COPD, there is no major role for NPPV.1,3,4 Limited data suggest that NPPV lacks efficacy in preventing post-surgical respiratory failure, though it may be useful in treating existing respiratory failure or preventing intubation in patients following lung resection or abdominal surgery.1,4 In hypoxemic patients undergoing bronchoscopy, NPPV may improve oxygenation (lower respiratory rates and improved PaO2 to FiO2 ratios, compared with oxygen alone) as well as hemodynamics (minimizing the drop in mean arterial pressure). However, outcome data are lacking and the data set is small.4,18 In acute lung injury/acute respiratory distress syndrome, data are also limited, but NPPV appears to have a high failure rate and confers little benefit.1,4
Back to the Case
The patient was admitted to the hospital and placed on BiPAP for approximately 1.5 hours. The patient’s respiratory rate improved to 20/minute and he appeared increasingly comfortable and alert. A repeat ABG revealed improved hypercarbia and acidosis. He was continued on steroids and antibiotics and eventually was weaned from BiPAP and discharged home.
NPPV is an effective method to decrease mortality, intubation rates, and duration of ICU stay in severe exacerbations of COPD, cardiogenic pulmonary edema, immunosuppressed patients with pulmonary infiltrates, and hypoxia, and as a bridge to extubation in COPD patients.
Dr. Kraynek is an internal medicine resident in the Department of Medicine at the University of Washington School of Medicine in Seattle. Dr. Best is assistant professor of medicine in the Division of General Internal Medicine at the University of Washington School of Medicine.
- Ambrosino N, Vagheggini G. Noninvasive positive pressure ventilation in the acute care setting: where are we? Euro Resp J. 2008;31:874-856.
- American Thoracic Society. International Consensus Conferences in Intensive Care Medicine: Noninvasive Positive Pressure Ventilation in Acute Respiratory Failure. Am J Respir Crit Care Med. 2001;163:283-291.
- Liesching T, Kwok H, Hill N. Acute applications of noninvasive positive pressure ventilation. Chest. 2003;124:699-713.
- Keenan S, Sinuff T, Burns K, et al. Clinical practice guidelines for the use of noninvasive positive pressure ventilation and noninvasive continuous positive airway pressure in the acute care setting. CMAJ. 2001;183:E195-E214.
- Lightowler J, Wedzicha J, Elliot M, Ram F. Noninvasive positive pressure ventilation to treat respiratory failure resulting from exacerbations of chronic obstructive pulmonary disease: Cochrane systematic review and meta-analysis. BMJ. 2003;326:185.
- Quon B, Gan W, Sin D. Contemporary management of acute exacerbations of COPD: a systematic review of the metaanalysis. Chest. 2008;133:756-766.
- Keenan S, Sinuff T, Cook D, Hill, N. Which patients with acute exacerbation of chronic obstructive pulmonary disease benefit from noninvasive positive pressure ventilation? Ann Intern Med. 2003;138:861-870.
- Scala R, Naldi M, Archinucci I, Conigilo G, Nava S. Noninvasive positive pressure ventilation in patients with acute exacerbations of COPD and varying levels of consciousness. Chest. 2005;128:1657-1666.
- Masip J, Roque M, Sanchez B, Fernandez R, Subirana M, Exposito J. Noninvasive ventilation in acute cardiogenic pulmonary edema. JAMA. 2005;294:3124-3130.
- Peter J, Moran J, Phillips-Hughes J, Graham P, Bersten A. Effect of non-invasive positive pressure ventilation (NIPPV) on mortality in patients with acute cardiogenic pulmonary oedema: a meta-anaylsis. Lancet. 2006;367:1155-1163.
- Weng C, Zhao Y, Liu Q, et al. Meta-analysis: noninvasive ventilation in acute cardiogenic pulmonary edema. Ann Intern Med. 2010;152:560-600.
- Keenan S, Sinuff T, Cook D, Hill N. Does noninvasive positive pressure ventilation improve outcome in acute hypoxemic respiratory failure? A systematic review. Crit Care Med. 2004;32:2516-2523.
- Esteban A, Frutos-Vivar F, Fergusun N, et al. Noninvasive positive pressure ventilation for respiratory failure after extubation. N Engl J Med. 2004;350:2452-2460.
- Nava S, Ambrosino N, Clinie E, et al. Noninvasive mechanical ventilation in the weaning of patients with respiratory failure due to chronic obstructive pulmonary disease: a randomized, controlled trial. Ann Intern Med. 1998;128:721-728.
- Grault C, Daudenthun I, Chevron V, et al. Noninvasive ventilation as a systematic extubation and weaning technique in acute on chronic respiratory failure: a prospective, randomized controlled study. Am J Respir Crit Care Med. 1999;160:86-92.
- Hilbert G, Gruson D, Vargas F, et al. Noninvasive ventilation in immunosuppressed patients with pulmonary infiltrates, fever, and acute respiratory failure. N Engl J Med. 2001;344:481-487.
- Ram FSF, Wellington SR, Rowe BH, Wedzicha JA. Non-invasive positive pressure ventilation for treatment of respiratory failure due to severe acute exacerbations of asthma. Cochrane Database of Systematic Reviews. 2005, Issue 3.
- Antonelli M, Conti G, Rocco M, et al. Noninvasive positive pressure ventilation vs. conventional oxygen supplementation in hypoxemic patients undergoing diagnostic bronchoscopy. Chest. 2002;121:1149-1154.