Choosing Wisely: Non-invasive ventilation in patients with acute respiratory failure from pneumonia

Authors:  Skyler Lentz, MD (@skylerlentz, Assistant Professor in the Departments of Surgery and Medicine, Divisions of Emergency Medicine and Pulmonary & Critical Care, University of Vermont Medical Center), Patricia Ruth Atchinson, DO (@roo_atchinson, Critical Care Fellow and Instructor in Medicine, Department of Medicine, Dartmouth-Hitchcock Medical Center), and Matthew A. Roginski, MD, MPH (@mattroginski, Assistant Professor of Medicine, Sections of Emergency Medicine and Critical Care Medicine, DHART Assistant Medical Director, Dartmouth-Hitchcock Medical Center) // Edited by: Alex Koyfman, MD (@EMHighAK) and Brit Long, MD (@long_brit)

Case

A 65-year-old male presents from home by EMS to your ED with acute respiratory distress in the setting of 3 days of cough, fever, and progressive dyspnea. Per EMS report, the patient was hypoxemic with an O2saturation in the 70s on room air, but now has an oxygen saturation of 96% on a non-rebreather mask at 15 liters per minute. He’s tachypneic, but per EMS report looks more comfortable. An ABG on arrival shows a pH of 7.30, PaCO239 mm Hg, PaO2of 80 mm Hg on an FiO2of 0.5; with PaO2:FiO2of 160. His chest X-ray shows a new right middle lobe consolidation, and the presentation is consistent with community acquired pneumonia. What is the next best step in oxygen therapy?

Introduction

Non-invasive positive pressure ventilation (NiPPV) is increasingly being used in ED patients with respiratory failure of all types, including pneumonia. Frequently, pneumonia can be managed with appropriate antibiotics and supportive care, but some patients progress to respiratory failure. The best non-invasive respiratory support for hypoxemic respiratory failure from pneumonia is controversial, but data suggest it may notalways be NiPPV, i.e. BiPAP™ or CPAP (1-3). Newer therapies such as high-flow nasal cannula (HFNC) seem to offer advantages over NiPPV in treating patients with pneumonia who do not require immediate intubation.

Background of NiPPV

NiPPV refers to the delivery of pressure to support your patient’s breathing via a tight-fitting mask rather than by the insertion of an endotracheal tube. A patient’s inspiratory effort will trigger the non-invasive ventilator to deliver inspiratory flow to target a set pressure. Respiratory effort is supported through setting an inspiratory positive airway pressure (IPAP) and an expiratory positive airway pressure (EPAP, also called PEEP). This constitutes bilevel positive pressure ventilation, or BiPAP™. The tidal volume (Vt) delivered will be variable based on the amount of set support the patient receives, lung compliance, and patient effort. The Vt is ultimately patient-determined. When IPAP is zero, the patient is not receiving additional pressure through the inspiratory phase-they are simply receiving continuous positive airway pressure or CPAP (4).

NiPPV can support patients with increased work of breathing such as chronic obstructive pulmonary disease (COPD) and can cause reductions in preload and afterload that favorably impact patients with acute pulmonary edema (APE). The use of NiPPV in patients with COPD exacerbations decreases intubation rate with a number needed to treat (NNT) of 5 and decrease mortality with a NNT of 12 (5.) NiPPV in APE has shown to decrease intubation rates with a NNT of 8 when compared with conventional oxygenation and mortality with a NNT of 14 (3,4,6). These significant benefits have led to increased interest in broadening the application of NIV in the emergency department. The potential benefit to NiPPV is avoidance of the risk associated with invasive mechanical ventilation such as ventilator associated pneumonia, sedation, and ventilator associated lung injury. NiPPV works best for those with rapidly reversible conditions such as a COPD exacerbation or APE, rather than disease processes taking days to improve such as ARDS or pneumonia.

Pearl: Use NiPPV in COPD exacerbations and in acute pulmonary edema.

 

In pulmonary edema the PEEP (EPAP) and increased intrathoracic pressure helps by recruiting additional alveoli to aid in gas exchange and redistributing lung water out of the alveoli. While the physiologic effects are volume dependent, positive intrathoracic pressure can decrease preload and left ventricular afterload, which can in turn increase cardiac output in a patient suffering from acute decompensated heart failure (7-8). PEEP (EPAP) also has a similar effect for atelectasis and intra alveolar fluid (purulence or edema) through allowing more alveoli to be exposed to gas. PEEP should be approached with caution with patients with dense infectious infiltrates, because increasing the PEEP may not open the affected lung zones and could over distend or harm the healthy, compliant lung. The significant benefit in COPD exacerbations comes from the pressure support (difference between IPAP and EPAP) which assists the patient’s work of breathing through lightening the workload of the respiratory musculature which can be a significant source of dyspnea (9). Similarly, your patient with pneumonia may require both PEEP for oxygenation and pressure support to assist ventilation because of respiratory muscle weakness or decreased lung compliance (“stiff lung”).

Pearl: EPAP (PEEP) helps with oxygenation whereas the pressure support (difference of IPAP-EPAP) assists with ventilation and respiratory effort.

 

NiPPV in pneumonia

Unlike COPD and APE, a clear benefit of NiPPV has not been demonstrated in those with hypoxemic respiratory failure from pneumonia (2-3). The FLORALI trial in 2015 randomized hypoxemic patients with PaO2:FiO2 ratios of <300 mm Hg, mostly from pneumonia, to receive oxygen through a facemask, HFNC, or NiPPV. While the primary outcome of patients requiring endotracheal intubation after randomization was no different among the treatment modalities, the group treated with HFNC had a decrease in 90 day mortality (1). The results of this trial support the use of HFNC over NiPPV and simple oxygen devices in patients with hypoxemic failure from pneumonia.  However, observational studies have shown NiPPV can be used successfully in patients with pneumonia who do not need emergent intubation (16,17). One retrospectivestudy compared the outcomes of patients with pneumonia initially managed by NiPPV vs invasive mechanical ventilation. In their analysis, they found a mortality benefit in those managed with NiPPV who had comorbid COPD and heart failure (10). HFNC is being actively studied in patients with exacerbations of COPD and heart failurebut does not yet have the supporting evidence in these patients that NiPPV does. NiPPV interface may be an important factor: one study using NiPPV via helmet in hypoxemic respiratory failure showed reduced mortality and intubation rate as compared to the usual facemask (21). Because of the absence of randomized controlled trials, guidelines do not offer an answer as to whether NiPPV should be used in pneumonia or which patients may benefit the most from NiPPV as compared to HFNC or early intubation (3). After reviewing the literature, we recommend reserving NiPPV to those with pneumonia and comorbid heart failure or COPD, as these patients have been shown to respond more favorably (10). We favor HFNC in those with pure hypoxemic respiratory failure from pneumonia and no element of heart failure or COPD (1).

Pearl: If pure hypoxemia from pneumonia, HFNC is probably the best option, but if there is comorbid COPD or pulmonary edema, NiPPV can be trialed.

 

The mechanism behind the potentially increased mortality in those treated with NiPPV over HFNC is not clearly understood, and the mortality benefit of HFNC is debated in the literature (11,12). It has been hypothesized that the pressure-supported NiPPV may lead to large, injurious tidal volumes (Vt) resulting in greater rates of lung injury (1, 13). In most patients, a protective Vt of < 6-8 ml/kg is impossible to achieve with NiPPV (14). Alternatively, it may be a delay in intubation and mechanical ventilation that is harmful. Esteban et al. in 2004 found that admitted patients who had been extubated to NiPPV had a delay in reintubation and higher mortality than those patients who were extubated and required reintubation after standard oxygen therapy (15).  Similarly, a longer duration of NiPPV before intubation is associated with increased mortality (16).  Patient factors associated with NiPPV failure include worsening oxygen at 1 hr of therapy (PaO2:FiO2ratio decreasing); greater amount of infiltrates on CXR; higher illness severity including shock, persistently elevated heart rate, and respiratory rate; and decreased level of consciousness (13,16,17). Successful NiPPV management is associated with improving oxygenation (PaO2:FiO2ratio improving) after 1 hr of NiPPV, improvement of respiratory rate at 1 hr, and lower illness severity (16,17).

Pearl: NiPPV may cause worse outcomes in patients with pneumonia by delivering injurious Vt and by a delay in recognition of failure.

 

If your patient with pneumonia is meeting criteria for acute respiratory distress syndrome (ARDS), that is a PaO2:FiO2 (P:F) ratio of < 300 mm Hg with a PEEP >5 and bilateral infiltrates not caused by cardiogenic pulmonary edema (18), use NiPPV with caution. NiPPV and HFNC have both been used successfully in those with mild ARDS (P:F 200-300 mm Hg) (1,19). However, those with moderate (P:F< 200) or severe ARDS (P:F <100) have very high rates (>40%) of NiPPV failure, and one study suggests higher mortality in those with a P:F ratio of < 150 mm Hg managed with NiPPV as compared to those managed with early intubation and mechanical ventilation (1,19-20). In practice, a patient with pneumonia or ARDS who is hypoxemic and failing to improve on NiPPV, is severely ill, has a high mortality, has a high rate of NiPPV failure, and needs to be intubated with a lung protective strategy of high PEEP and low tidal volume with 6 mL/kg of ideal body weight.

Pearl: Do not delay intubation and lung protective mechanical ventilation in your patient with pneumonia or moderate to severe ARDS that is failing to improve on NiPPV.

 

Conclusions

The management of pneumonia includes respiratory support and appropriate antibiotics. For those not requiring immediate intubation, HFNC or NiPPV may be used to prevent deterioration and need for invasive mechanical ventilation. HFNC is best in those with pure hypoxemic respiratory failure from pneumonia. If there is comorbid COPD or pulmonary edema, NiPPV can be trialed cautiously. If NiPPV is used, the emergency physician must assess frequently for signs of failure, as a delay in intubation is associated with increased mortality. Look for a persistently high respiratory rate or persistent tachycardia, worsening or no improvement oxygenation, and/or alterations in mental status etc. as evidence for failure, and let that guide your decision to intubate early. The use of NiPPV and HFNC in pneumonia and other types of respiratory failure is an area of active research, and we look forward to new evidence clarifying the role of non-invasive support in pneumonia.

 

Case Conclusion

You repeat a blood gas 1 hour after arrival, and despite the improvement in his oxygenation on the monitor, you note that his P:F ratio is falling. He also appears tired. After a discussion with the patient and his wife, you intubate the patient and initiate ventilation with 6 mL/kg predicted ideal body weight. He tolerates the procedure well and is admitted to the intensive care unit, where he has an uneventful course and is extubated 4 days later.

 

Key Points

  • NiPPV has a proven benefit in COPD exacerbation and cardiogenic pulmonary edema, but its use in pneumonia is controversial.
  • High Flow Nasal Cannula may have a mortality benefit in pure hypoxic respiratory failure when compared with NiPPV and should be your first choice for those patients with pneumonia but without hypercapnia.
  • Trial NiPPV in those with pneumonia and comorbid heart failure or COPD.
  • One potential disadvantage to NiPPV is the potential for delay in intubation, which is associated with worse outcomes. If your patient is on NiPPV, frequent reassessmentis required. Intubation may be needed if the patient fails to improve.
  • Consider early intubation when the patient’s PaO2:FiO2 is low and decreases after 1 hour, when the patient has persistently elevated HR and RR, or if the patient develops acute changes in mental status.

 

References/Further Reading

  1. Jean-Pierre Frat et al. “High Flow Oxygen through Nasal Cannula in Acute Hypoxemic Respiratory Failure.” The New England Journal of Medicine 2015;372:2185-96.
  2. Valley, T et al. Association Between Noninvasive Ventilation and Mortality Among Older Patients With Pneumonia. Crit Care Med. 2017 March; 45(3): e246–e254. doi:10.1097/CCM.0000000000002076.
  3. Keenan, S et al. Clinical practice guidelines for the use of noninvasive positive-pressure ventilation and noninvasive continuous positive airway pressure in the acute care setting. 2011 Feb 22;183(3):E195-214. doi: 10.1503/cmaj.100071. Epub 2011 Feb 14.
  4. Masip, J. Non-invasive ventilation. Heart Fail Rev (2007) 12: 119-24.
  5. Osadnik CR, Tee VS, Carson-Chahhoud KV, Picot J, Wedzicha JA, Smith BJ. Non-invasive ventilation for the management of acute hypercapnic respiratory failure due to exacerbation of chronic obstructive pulmonary disease. Cochrane Database of Systematic Reviews 2017, Issue 7. Art. No.: CD004104. DOI: 10.1002/14651858.CD004104.pub4.
  6. Vital FMR, Ladeira MT, Atallah ÁN. Non-invasive positive pressure ventilation (CPAP or bilevel NPPV) for cardiogenic pulmonary oedema. Cochrane Database of Systematic Reviews 2013, Issue 5. Art. No.: CD005351. DOI: 10.1002/14651858.CD005351.pub3.
  7. Tobin MJ. Principles and Practice of Mechanical Ventilation. 3rd 2013. McGraw-Hill Companies.
  8. Pinsky MR. Cardiovascular issues in respiratory care. Chest 2005;128: 592S-597S.
  9. Manning HL, Schwartzstein RM. Pathophysiology of dyspnea. N Engl J Med. 1995 Dec 7;333(23):1547-5.
  10. S Stefan et al. The comparative effectiveness of noninvasive and invasive ventilation in patients with pneumonia. Journal of Critical Care 2018; 43:190-196.
  11. Leeies et al. High-flow oxygen via nasal cannulae in patients with acute hypoxemic respiratory failure: a systematic review and metaanalysis. Syst Rev. 2017 Oct 16;6(1):202.
  12. Ni, YN et al. Can High-flow Nasal Cannula Reduce the Rate of Endotracheal Intubation in Adult Patients with Acute Respiratory Failure Compared with Conventional Oxygen Therapy and Noninvasive Positive Pressure Ventilation? A Systematic Review and Meta-analysis. CHEST 2017; 151(4):764-775
  13. Girault, C et al. Non-invasive ventilation in hypoxemic acute respiratory failure: is it still possible? Intensive Care Med (2017) 43:243–245.
  14. Carteaux, G. Failure of Noninvasive Ventilation for De Novo Acute Hypoxemic Respiratory Failure: Role of Tidal Volume. Crit Care Med 2016;44:282–29.
  15. Esteban, A et al. Noninvasive positive-pressure ventilation for respiratory failure after extubation. N Engl J Med 2004;350:2452-60.
  16. Carrillo, A., Gonzalez-Diaz, G., Ferrer, M. et al. Non-invasive ventilation in community-acquired pneumonia and severe acute respiratory failure. Intensive Care Med (2012) 38: 458.
  17. Nicolini, at et al. Early non-invasive ventilation treatment for respiratory failure due to severe community-acquired pneumonia. Clinical Respiratory Journal 2016;10:98-103.
  18. The ARDS Definition Task Force. Acute Respiratory Distress Syndrome: The Berlin Definition. 2012;307(23):2526-2533.
  19. Chawla, R. et al. Acute respiratory distress syndrome: Predictors of noninvasive ventilation failure and intensive care unit mortality in clinical practice. Journal of Critical Care 31 (2016) 26–30.
  20. Bellani, G et al. Noninvasive Ventilation of Patients with Acute Respiratory Distress Syndrome Insights from the LUNG SAFE study. Am J Respir Crit Care Med. 2017 Jan 1;195(1):67-77.
  21. Patel, BK. Effect of Noninvasive Ventilation Delivered by Helmet vs Face Mask on the Rate of Endotracheal Intubation in Patients With Acute Respiratory Distress Syndrome, A Randomized Clinical Trial. JAMA. 2016;315(22):2435-2441.

2 thoughts on “Choosing Wisely: Non-invasive ventilation in patients with acute respiratory failure from pneumonia”

  1. Hi Skyler, interesting post.
    Key points:
    -COPD and ACPE
    Robust evidence on the beneficial effect of NiPPV in severe COPD exacerbation and ACPE in terms of intubation and mortality reduction.
    -PNEUMONIA
    Much weaker evidence for High Flow Nasal Cannula. The suggestion to use HFNC is largely based on the Florali Study (1) which is a negative study. The primary outcome – ETI at 28 days – was not met, whereas mortality at 90 days (!) was the secondary outcome and was in favour of HFNC, but the study suffers from some methodological flaws (2), and was highly criticised also in the FOAMed world.
    More data exist on the efficacy of NiPPV, both CPAP and BiLevel/BiPAP™, predominantly in the immunocompromised population (3), but also in immunocompetent patients, where is able to improve oxygenation (4,5) and reduce clinical failure when applied early in the ED (6).
    The strongest data, however, is the risk of worsening when NiPPV leads to a delayed ETI and increased mortality, as you suggested nicely also in the title of your post.
    In summary, we teach our trainees to select the right patients according to their history and severity of oxygen impairment (RR and P/F ratio), bearing in mind that hypoxemic pneumonia patients may deteriorate rapidly.

    History
    1. Immunocompromised:
    -mild hypoxemia, no distress — go with O2; go with HFNC if initial distress
    -moderate-severe hypoxemia — go with NiPPV (either CPAP or BiLevel) — check within 1h

    2. Immunocompetent, non-hypercapnic:
    -mild hypoxemia, no distress — go with O2; go with HFNC if initial distress
    -moderate hypoxemia– go with NiPPV (either CPAP or BiLevel) — check within 1h
    -severe hypoxemia– prepare for ETI; in the meantime, you may try NiPPV and monitor closely

    3. Immunocompetent, hypercapnic-COPD:
    -mild hypoxemia, no distress — go with O2; go with HFNC if initial distress
    -go with NiPPV

    References/Further Reading
    1. Jean-Pierre Frat et al. “High Flow Oxygen through Nasal Cannula in Acute Hypoxemic Respiratory Failure.” The New England Journal of Medicine 2015;372:2185-96.
    2. Prina E et al. High-flow nasal cannula in hypoxemic patients: should I stay or should I go? 2016;1–2.
    3. Ferrer M et al. The use of non-invasive ventilation during acute respiratory failure due to pneumonia, 2012;23:420–428.
    4. L’Her E. Physiologic Effects of Noninvasive Ventilation during Acute Lung Injury. 2005;172:1112–1118.
    5. Cosentini R et al. Helmet continuous positive airway pressure vs oxygen therapy to improve oxygenation in community-acquired pneumonia: a randomized, controlled trial. Chest 2010;138:114–120
    6. Brambilla AM et al. Helmet CPAP vs. oxygen therapy in severe hypoxemic respiratory failure due to pneumonia. Intensive Care Med 2014;40:942–949

  2. Thank you for your comments. I agree with your points, in particular matching the appropriate patient with the proper respiratory support whether it be simple oxygen, HFNC, NIV or early intubation. It is clear that there is not a single answer. As you mention, most importantly the patient must be reassessed as lack of improvement and unrecognized failure is harmful.

    The immunosuppressed is an interesting population. The literature seems to yield different results in regards to the the benefit of NIV in this group and which immunosuppressed subpopulation may benefit the most.

    I look forward to future research.

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