By William H. Thompson, MD

Associate Professor of Medicine, University of Washington, Seattle

Dr. Thompson reports no financial relationships relevant to this field of study.

The use of noninvasive positive pressure ventilation (NPPV) has been studied since the 1930s, and it has been in common use for sleep-disordered breathing, chronic respiratory failure, and acute respiratory failure (ARF) for the past few decades.1 In that time, advances in technology and the data supporting its use in various clinical settings have evolved. The term NPPV typically refers to the use of expiratory positive airway pressure (EPAP) with a higher inspiratory positive airway pressure (IPAP), together referred to as bilevel positive airway pressure (BPAP, also commonly referred to as BiPAP). However, the use of continuous positive airway pressure (CPAP) also must be considered in the discussion of these devices, as the two different modalities have been used and often compared in the treatment of the various causes of ARF. In this article, the two modes of therapy will be referred to as NPPV and CPAP. It is the goal of this review to summarize the data supporting the use of NPPV and CPAP in the setting of acute hypoxic and hypercapnic respiratory failure, and to provide a practical approach to the use of this technology in the acute care setting. Its use for chronic restrictive lung disease and sleep-disordered breathing also has evolved but is beyond the scope of this review.

INDICATIONS SUPPORTED BY STRONG EVIDENCE

The two indications for use of NPPV or CPAP in the setting of ARF supported by extensive data are severe acute exacerbation of COPD (AECOPD) and cardiogenic pulmonary edema (CPE).2 In AECOPD with relative hypercarbia and respiratory acidosis (typically pH < 7.35), NPPV has been shown to improve hospital mortality, PaCO2, dyspnea scores, and length of hospital stay and decrease the need for intubation. Although CPAP has been found to improve survival and rate of hospitalization when used chronically to treat COPD-obstructive sleep apnea (OSA) overlap syndrome,3 it has not been studied enough to support or refute its usefulness in the setting of AECOPD.

Similarly, the use of NPPV and CPAP is supported in the setting of acute CPE as a means of improving oxygenation and hospital mortality and decreasing intubation rates.4 Early studies suggested a higher risk of myocardial infarction with NPPV compared to CPAP, but more recent studies have not confirmed this risk. Thus, both NPPV and CPAP can be considered. Many will use CPAP starting near 10 cm H2O for patients without hypercarbia but prefer use of NPPV when hypercarbia is a component of the ARF. Notably, there are insufficient data to support the use of either mode of therapy when respiratory failure is accompanied by either shock or acute coronary syndrome requiring urgent revascularization.

INDICATIONS SUPPORTED BY LIMITED EVIDENCE

Some data supporting the use of NPPV are available for many other indications, which include immunosuppressed patients in the setting of transplantation or chemotherapy for malignancy with chiefly hypoxic ARF or respiratory distress.5,6 For these patients, in whom ARF is associated with particularly high mortality, NPPV can reduce the need for intubation as well as improve mortality and ICU length of stay. However, predictors of failure in hematologic malignancy include high respiratory rate on NPPV, need for vasopressors, need for dialysis, acute respiratory distress syndrome (ARDS), and delay between admission to initiation of NPPV.7 In addition, recent studies, while somewhat underpowered and criticized for methodologic issues, have proposed that oxygen therapy (especially high-flow oxygen) may be equally efficacious or better than NPPV in the treatment of hypoxic respiratory failure in immunocompromised patients.8-10

Limited evidence backs the use of CPAP in those suffering from ARF after abdominal surgery and the use of NPPV for ARF after lung resection surgery. NPPV also has been used successfully, mostly in the setting of COPD, to facilitate liberation from the ventilator in those presenting with risk factors for re-intubation, which include age > 65 years, cardiac failure as the cause of intubation, APACHE II score > 12 at the time of intubation, AECOPD, and chronic hypercapnia.11 In these patients, it is important to institute NPPV soon after extubation and not wait until evidence of recurrent respiratory failure develops. No study has shown an improvement in rate of re-intubation; one study demonstrated an increase in ICU mortality among patients with established respiratory failure and for whom re-intubation was delayed by the use of NPPV.2,12

Additionally, there is growing interest but limited data in the use of NPPV in palliative care settings.13,14 As noted by Curtis et al,13 it is important to discuss the goals of NPPV therapy with patients and family in advance to clearly outline whether NPPV is being used to avoid intubation in patients who have no preset limits on advanced life support, as a substitute for intubation for those who have declined advanced life support, or as a means of palliating dyspnea.

INDICATIONS SUPPORTED BY WEAK OR NO EVIDENCE

Although NPPV and CPAP have been used in a number of settings, insufficient literature exists to support or refute its use in several clinical scenarios. These include acute asthma exacerbation, for which only small studies in relatively mild exacerbations exist,15 and severe community-acquired pneumonia, in which those who benefit most appear to be those with known COPD. Other indications for which there are insufficient data include patients presenting with chest trauma, hypoxemic patients undergoing bronchoscopy, and patients suffering from acute rapidly progressive neuromuscular disorders.

INDICATIONS WITH EVIDENCE AGAINST THE USE OF NPPV/CPAP

Worse outcomes are associated with the use of NPPV in established ARF after extubation as noted above. Minimal data support NPPV in the setting of ARDS. However, available evidence would suggest not using CPAP in the setting of ARDS in that it has not been shown to improve rate of intubation or mortality but actually may produce more adverse events.16 The recent study by Frat et al9 also suggested that high-flow oxygen through nasal cannula in hypoxemic respiratory failure (mostly for pneumonia) might be as efficacious as NPPV at preventing intubation and result in lower mortality. However, it has been criticized for the little amount of time patients in the NPPV group spent on positive pressure treatment (median of eight hours per day), the uneven distribution of septic shock in the two groups, and for lack of power for the endpoint of mortality.

MANAGEMENT OF NPPV/CPAP IN ARF

Most of the information available indicating when to start NPPV comes from the COPD and acute CPE literature. One must first decide if the patient needs mechanical assistance, and then whether there are any contraindications to NPPV/CPAP that would dictate intubation and use of mechanical ventilation. Those who demonstrate elevated PaCO2 > 45 mmHg in the setting of a low pH < 7.35 are likely candidates for NPPV or intubation. Other indications for mechanically assisted ventilation include tachypnea, use of accessory muscles, paradoxical breathing, and hypoxemia. Those with contraindications to NPPV/CPAP (see Table 1) should go on to intubation and mechanical ventilation, while those without contraindications can start on NPPV/CPAP.

For patients suffering from AECOPD, acclimation to the NPPV mask at low pressures (EPAP 4-5 cm H2O, IPAP 8-12 cm H2O) and potentially simply holding the mask to the face can be helpful. Pressures gradually increase as dictated by the patient’s tolerance and by the measured tidal volumes and vital signs. Patients presenting with acute CPE often will do well starting CPAP near 10 and adjusting based on comfort, pulse oximetry, and vitals. Elevation of the head of the bed to > 30 degrees is recommended when possible. It is important to reassess the patient in one to two hours (see Table 2), as this typically is sufficient to gauge whether the patient will benefit from NPPV/CPAP or will need to go on to invasive mechanical ventilation. Failure rates of 5-40% have been reported.17 Risk factors for failure, which may dictate elevated level of care for the patient, include agitation or diminished level of consciousness, pH < 7.2, asynchronous breathing, lack of adequate dentition, excessive air leak from the mask, excessive secretions, poor tolerance, diagnosis of ARDS or pneumonia, older age, metabolic acidosis, systolic blood pressure < 90 mmHg, and low PaO2/FiO2 ratio.18 For those seeking more complete references for a practical approach to management of NPPV and CPAP in ARF and for establishing a noninvasive ventilation program, articles by Hess et al, Davidson et al, and the Royal College of Physicians are recommended.19-21

Although most studies have suggested that most mask types (nasal, oronasal, nasal pillow, total-face, helmet) are equally effective interfaces, some data suggest the oronasal mask may result in less leak and better tolerance in the setting of ARF; thus, it is typically recommended as the first choice of masks. However, one should have a low threshold for trying other masks based on patient comfort, especially if the patient already has experience with a particular mask. Mask fit also may be affected by patient dentition and may improve if dentures are left in place. Control of mask and mouth leak are key to optimal device triggering and cycling, making mask fit one of the most important aspects of care.

Patients often are kept nil per os until it is clear that they will not require intubation and that aerophagia will not be a significant problem. However, as dictated by their responses to NPPV/CPAP and underlying medical conditions, patients usually can be given progressively longer trials off the device with concurrent liberalization of their oral intake.

TROUBLESHOOTING

Patient-ventilator asynchrony in NPPV can affect dyspnea and patient tolerance of the device significantly. It is important to assess and correct early in the course of treatment.22 Asynchrony usually centers around the device threshold for initiating a breath (triggering) and terminating a breath (cycling). An asynchrony index (AI) can be calculated as the number of asynchrony events divided by the total number of breaths (including all asynchrony events), with an AI > 10% considered severe. Vignaux et al found an AI of > 10% in 43% of 60 patients, including ineffective triggering (8%), double-triggering (15%), auto-triggering (13%), premature cycling (12%), and delayed cycling (23%).23 Asynchrony tends to correlate with magnitude of mask leak and level of pressure support (PS, the difference between IPAP and EPAP) and, thus, correction of mask leak is the first step in managing a high AI. Adjusting the sensitivity of the trigger to deliver the breath can reduce the number of missed, double, and auto-triggered breaths. Shortening the rise time, defined as the time to get from EPAP to IPAP, and increasing PS can improve dyspnea. Adjusting the cycle setting that turns off the breath, as well as adjusting the minimum and maximum inspiratory times, can improve comfort and asynchrony significantly.11 For example, patients with severe obstructive lung disease often benefit from a shorter rise time, shorter maximum inspiratory time, and a cycle setting that turns off the delivered breath at 50% of peak inspiratory flow rather than the typical 25-30%. On the other hand, patients with neuromuscular weakness who experience a lower peak inspiratory flow may experience better outcomes using a longer rise time, more sensitive trigger setting (more easily triggering the breath), and less sensitive cycle setting (maintaining the breath until 10-15% of peak inspiratory flow occurs).

Another common mistake in patients with COPD-OSA overlap syndrome is to concentrate on the AECOPD and to neglect the OSA. In an attempt to improve ventilation, the pressure support will increase gradually at the exclusion of increasing EPAP. Typically, this will lead to cyclical pressurization of the oropharynx without adequate ventilation of the lower airways because the NPPV device is working against a closed upper airway. This also leads to inability of the device to sense respiratory effort and, thus, to patient-ventilator asynchrony. In short, “opening” the upper airway with adequate EPAP can improve ventilation and tidal volume, even if it results in a lower PS.

Once the settings have been optimized to improve patient comfort, if the patient still struggles with tolerance, entertain the question of sedation. Unfortunately, sedation is a double-edged sword, which by virtue of its potential to impair respiratory drive may exacerbate the patient’s respiratory status and accelerate the failure of NPPV. As reviewed by Hess et al, use of analgesia, sedation, and restraints in this situation is quite variable from provider to provider.19 Traditionally, sedation has consisted of benzodiazepines or opiates. Studies support the use of the short-acting agent remifentanil, although it is not FDA approved for this indication. Dexmedetomidine also has data to support its use with NPPV and offers the ability to provide sedation with minimal suppression of respiratory drive.

FUTURE DIRECTIONS

The use of NPPV and CPAP in the treatment of AECOPD and CPE is well established, to the point of representing standard of care in the appropriate clinical setting. However, there certainly is need for additional investigation on many of the other potential indications that currently have little to no literature to back the use of these modalities as a means of significantly improving patient outcomes. New areas ripe for further exploration include use of these devices in the field of palliative care and in those patients who have elected not to pursue intubation. Recent data also raise the possibility that newer technology in high-flow oxygen delivery may provide an alternative and potentially superior treatment option in hypoxic respiratory failure. Additionally, new modes of noninvasive ventilation (adaptive servo ventilation, volume-assured pressure support, neurally adjusted ventilator assist, proportional assist ventilation, and others) could lead to improved control over respiratory parameters and better patient tolerance. Until further information is available, it will remain unclear as to whether these newer technologies will offer any better outcomes.

REFERENCES

  1. Barach AL, Martin J, Eckman M. Positive pressure respiration and its application to the treatment of acute pulmonary edema. Ann Intern Med 1938;12:754-795.
  2. Keenan SP, Sinuff T, Burns KE, 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 2011;183:E195-E214.
  3. Marin JM, Soriano JB, Carrizo SJ, et al. Outcomes in patients with chronic obstructive pulmonary disease and obstructive sleep apnea, the overlap syndrome. Am J Respir Crit Care Med 2010;182:325-331.
  4. Vital FMR, Ladeira MT, Atallah AN. Non-invasive positive pressure ventilation (CPAP or bilevel NPPV) for cardiogenic pulmonary oedema (Review). Cochrane Database of Systemic Review 2013;5:CD005351.
  5. Antonelli M, Conti G, Bufi M, et al. Noninvasive ventilation for treatment of acute respiratory failure in patients undergoing solid organ transplantation: A randomized trial. JAMA 2000;283:235-241.
  6. 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.
  7. Adda M, Coquet I, Darmon M, et al. Predictors of noninvasive ventilation failure in patients with hematologic malignancy and acute respiratory failure. Crit Care Med 2008;36:2766-2772.
  8. Lemiale V, Mokart D, Resche-Rigon M, et al. Effect of noninvasive ventilation vs oxygen therapy on mortality among immunocompromised patients with acute respiratory failure. JAMA 2015:314:1711-1719.
  9. Frat JP, Thille AW, Mercat A, et al. High-flow oxygen through nasal cannula in acute hypoxemic respiratory failure. N Engl J Med 2015;372:2185-2196.
  10. Frat JP, Ragot S, Girault C, et al. Effect of non-invasive oxygenation strategies in immunocompromised patients with severe acute respiratory failure: A post-hoc analysis of a randomized trial. Lancet Respir Med 2016;4:646-652.
  11. Mas A, Masip J. Noninvasive ventilation in acute respiratory failure. Int J Chron Obstruct Pulmon Dis 2014;9:837-852.
  12. Esteban A, Frutos-Vivar F, Ferguson ND, et al. Noninvasive positive-pressure ventilation for respiratory failure after extubation. N Engl J Med 2004;350:2452-2460.
  13. Curtis JR, Cook DJ, Sinuff T, et al. Noninvasive positive pressure ventilation in critical and palliative care settings: Understanding the goals of therapy. Crit Care Med 2007;35:932-939.
  14. Azoulay E, Demoule A, Jaber S, et al. Palliative noninvasive ventilation in patients with acute respiratory failure. Intensive Care Med 2011;37:1250-1257.
  15. Lim WJ, Mohammed Akram R, Carson KV, et al. Non-invasive positive pressure ventilation for treatment of respiratory failure due to severe acute exacerbations of asthma. Cochrane Database Syst Rev 2012;12:CD004360.
  16. Delclaux C, L’Her E, Alberti C, et al. Treatment of acute hypoxemic nonhypercapnic respiratory insufficiency with continuous positive airway pressure delivered by a face mask: A randomized controlled trial. JAMA 2000;284:2352-2360.
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Table 1: Contraindications to NPPV/CPAP

  • Respiratory arrest
  • Medical instability
  • Acute respiratory distress syndrome
  • Inability to protect airway
  • Excessive secretions
  • Uncooperative or agitated patient
  • Inability to fit a mask
  • Upper airway trauma or burns
  • Recent upper airway surgery
  • Severe upper gastrointestinal bleed
 

Table 2: Markers of Success After 1-2 Hours of Treatment

  • Improvement in pH and PaCO2
  • Improvement in oxygenation
  • Reduction in respiratory rate
  • Reduction in heart rate
  • Improvement in tidal volume