Critical Care Alert: HFNC Oxygen v. Noninvasive Ventilation for Management of Acute Cardiogenic Pulmonary Edema

ARTICLE: Marjanovic N, Piton M, Lamarre J, et al. High-flow nasal cannula oxygen versus noninvasive ventilation for the management of acute cardiogenic pulmonary edema: a randomized controlled pilot study. Eur J Emerg Med. 2024;31(4):267-275.

OBJECTIVE: To compare the efficacy of high-flow nasal cannula (HFNC) oxygen with noninvasive ventilation (NIV) in ED patients with acute heart failure-related respiratory failure

BACKGROUND

Approximately 1 million patients present to the ED annually for acute heart failure (AHF) in the United States, with more than 80% requiring hospitalization.¹ The number of deaths due to heart failure has significantly increased in recent years, up 38% between 2000 and 2017.² Patients with cardiogenic pulmonary edema have an overall poor prognosis with a one-year survival rate of 50%.³ Early recognition and treatment of patients in decompensated heart failure is critical.

AHF-related pulmonary edema is caused by excessive fluid accumulation in the lung’s alveoli and interstitium secondary to elevated left heart pressures which cause downstream pulmonary venous hypertension and thus increased capillary hydrostatic pressure.⁴ Diuretics and  vasodilators serve as first-line treatments in order to decrease cardiac preload and afterload. NIV has additionally served as a mainstay in treatment by increasing intrathoracic pressure and subsequently decreasing left ventricular afterload and venous return, reducing work on the heart.⁵ NIV also decreases the work of breathing. Its use has been supported by previous small randomized trials and meta-analyses demonstrating improvement in respiratory and heart rate, hypercapnia, and acidosis, with some evidence toward reduced need for intubation.^6-9 Notably, the evidence demonstrating benefit of NIV use has been largely shown in hypoxemic patients with cardiogenic pulmonary edema.

The multi-center 3CPO Randomized Control Trial published in 2008 further investigated this topic, comparing CPAP and BPAP to standard oxygen therapy in 1069 UK patients with severe cardiogenic pulmonary edema.⁹ Results of this trial demonstrated no significant difference between the 3 arms in regards to 7-day mortality, 30-day mortality, intubation rates, and rates of ICU admission. Importantly, however, patients who failed standard oxygen therapy were able to cross over to use of NIV. Therefore results may be somewhat limited by the fact that some patients initially started on nasal cannula were counted in the standard oxygen group for outcomes analysis despite actually receiving NIV.

High-flow oxygen acts to decrease physiologic dead space in the upper airway, increase the delivery of FiO₂, and provides a small amount of PEEP to improve alveolar recruitment and counteract collapsibility produced by increased interstitial fluid. Some patients additionally find it easier to tolerate HFNC than a positive pressure mask.

There is little existing literature comparing HFNC to NIV in this patient population. A small 2021 trial randomized patients with AHF-related pulmonary edema to receive either CPAP or HFNC oxygen, showing reduction in respiratory rate and subjective dyspnea in the CPAP group, but no change in rates of intubation between the two arms.¹⁰ This trial was quite limited however due to size (only 188 patients at one institution were included). Another small study published in 2020 demonstrated improvement in pH and work of breathing with use of HFNC comparable to those achieved with NIV.¹¹ Given overall small and mixed evidence thus far, the Marjanovic trial reviewed here thus sought to further explore the use of HFNC compared to NIV in patients with cardiogenic pulmonary edema.

DESIGN

This is a multicenter randomized open-label, clinical pilot study conducted in three EDs. Open-label means that the study is not blinded and both the researcher and the participant involved in the study know which treatment arm each participant is in. While feasibility studies are designed to assess whether a study can be done, a pilot study is essentially a small version of the main study and used to refine details about the main study.

Patients were randomized in a 1:1 ratio to the HFNC or the NIV group. In the NIV group, patient was given non-invasive ventilation via a mechanical ventilator set in the bi-level pressure support mode with a PEEP between 5-10 cmH₂O, and the amount of pressure support was set to a value that allowed for an expired tidal volume of 6-8 mL/kg of predicted body weight in each patient. In the HFNC group, oxygen was administered at 37 °C and 60 L/minutes. In both groups, the FiO₂ was set to a value that allowed for SpO₂ of at least 94%. Both treatments were applied for at least 1 hour and patients were switched to conventional oxygen therapy when the patient was able to maintain SpO₂ of at least 94% and a respiratory rate of < 25 breaths/min. All settings were also adjusted according to patient tolerance.

INCLUSION CRITERIA

• respiratory rate ≥25 breaths/min or signs of increased work of breathing (eg, accessory muscles use)
• clinical suspicion of cardiogenic pulmonary edema based on: dyspnea with orthopnea, bilateral rales and/or peripheral edema and/or signs of pulmonary congestion on chest radiography or lung ultrasound

EXCLUSION CRITERIA 

• urgent intubation required
• severe neurological disorder (Glasgow Coma Scale <13 points)
• hemodynamic instability (MAP <65 mmHg or requiring vasopressors)

PRIMARY AND SECONDARY OUTCOMES 

Primary: change in respiratory rate at 5, 15, 30, and 60 minutes after initiation of oxygen support (manually measured)

Secondary

• change in oxygen saturation (SpO₂)
• change in subjective dyspnea
• change in heart rate
• change in blood pressure

Other exploratory outcomes

• comfort level of allocated oxygen delivery device
• blood gas values of pH, PaO₂, PaCO₂, and lactate
• proportion of responder patients at 1 hour (respiratory rate <25 breaths/min and absence of signs of increased work of breathing, SpO₂  >92%)
• cumulative dose of diuretics and nitrate derivatives
• proportion of patients requiring NIV after ED discharge
• proportion of patients requiring intubation by day 28
• proportion of patients who died at day 28
• treatment failure at day 8 (defined as composite of premature termination of treatment before 1 h and/or death within 8 days and/or intubation within 8 days)

KEY RESULTS

• Median change in respiratory rate at 60 min of -10 breaths/min in the HFNC group and -7 breaths/min in the NIV group, (95% CI, −0.5–5.7), [P = 0.052].
• The baseline SpO₂ was 95 with HFNC and 96 with NIV with a median change at 60 min of 2 for both groups (95% CI, −1.1–2.8), [P = 0.60].
• SpO₂ values were higher within 60 min after initiation of NIV as compared to initiation of high-flow nasal oxygen [estimated difference 1% (95%CI, 0.3–2), P = 0.011]
• Patient discomfort assessed 60 min after initiation of oxygen support did not differ between the two groups, 3 points (IQR, 2; 5) versus 5 (IQR, 2; 7) (P = 0.41), in patients treated by high-flow nasal oxygen and those treated by NIV, respectively.

LIMITATIONS

• The study had a small sample size.
• Using respiratory rate as a primary outcome in this study may be challenging as 1) it is manually evaluated and thus prone to human error and bias, especially in an open-label study, and 2) decreased respiratory rate may be an indication of fatigue and thus not an outcome that is desired.
• Treatment components such as pressure support and FiO₂ were not standardized and were dependent on physician discretion and patient tolerance when titrating.
• Patients were excluded if urgent intubation was required and thus this poses two further questions: what are the indications for urgent intubation in these patients, and if the indication was a lower SpO₂ or significant work of breathing, would some of these patient have benefited from NIV or HFNC, especially given NIV has been shown in the past to reduce the risk of intubation?¹²
• More patients in the NIV group had cardiogenic pulmonary edema secondary to infection. It would be useful to learn what kind of infection patients had, especially if it was a concomitant pulmonary infection, and also the average temperature of the patient as fevers can drive respiratory rate as well.
• Nearly all previous studies that evaluated NIV use in cardiogenic pulmonary edema and demonstrated a treatment effect required hypoxemia as a diagnostic criteria for inclusion.⁶ The current study did not specify hypoxemia in the inclusion criteria and the initial SpO₂ for the patients included was in the range of 92-97%. Thus, it is possible that the oxygenation status for some or all of these patients had not decompensated enough to truly see an effect from the interventions.

EM/CCM TAKE-AWAYS

• HFNC may alleviate tachypnea in patients with cardiogenic pulmonary edema without overt hypoxemia in a similar fashion to NIV, making this a potential alternative to NIV in less critically ill patients who do not tolerate a positive pressure mask.
• In truly hypoxemic patients with acute heart failure-related pulmonary edema, NIV remains the preferred oxygenation modality based on current evidence until further evidence emerges.
• Further studies are required to compare HFNC and NIV in more critically ill patients with cardiogenic pulmonary edema before changing practice in management of true respiratory failure in this patient population.

REFERENCES

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