European Heart Journal: Acute Cardiovascular Care (2021) 10, 1103–1111 ORIGINAL SCIENTIFIC PAPER

doi:10.1093/ehjacc/zuab078

Helmet continuous positive airway pressure vs.

high flow nasal cannula oxygen in acute
cardiogenic pulmonary oedema: a randomized
controlled trial

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Adi Osman1, Gabriele Via2, Roslanuddin Mohd Sallehuddin1,
Azma Haryaty Ahmad1, Sow Kai Fei3, Azlizawati Azil1, Francesco Mojoli4,5,
Chan Pei Fong1, Guido Tavazzi 4,5*
1
Resuscitation & Emergency Critical Care Unit, Trauma and Emergency Department, Raja Permaisuri Bainun Hospital, Ipoh, Perak, Malaysia; 2Department of Anesthesia and inten-
sive care, Cardiac Anesthesia & Intensive Care—Istituto Cardiocentro Ticino, Lugano, Switzerland; 3Trauma and Emergency Department, Penang General Hospital, Jalan
Residensi, George Town, Penang, Malaysia; 4Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, DEA Piano -1, Fondazione IRCCS Policlinico
S. Matteo, Viale Golgi 19, 27100 Pavia, Italy; and 5Department of Anesthesia and Intensive Care Unit, Fondazione IRCCS Policlinico S. Matteo, Pavia, Italy

Received 26 April 2021; revised 16 August 2021; editorial decision 18 August 2021; accepted 20 August 2021; online publish-ahead-of-print 11 October 2021

Aims Non-invasive ventilation represents an established treatment for acute cardiogenic pulmonary oedema (ACPO) al-
though no data regarding the best ventilatory strategy are available. We aimed to compare the effectiveness of hel-
met CPAP (hCPAP) and high flow nasal cannula (HFNC) in the early treatment of ACPO.
...................................................................................................................................................................................................
Methods Single-centre randomized controlled trial of patients admitted to the emergency department due to ACPO with
and results hypoxemia and dyspnoea on face mask oxygen therapy. Patients were randomly assigned with a 1:1 ratio to receive
hCPAP or HFNC and FiO2 set to achieve an arterial oxygen saturation >94%. The primary outcome was a reduc-
tion in respiratory rate; secondary outcomes included changes in heart rate, PaO2/FiO2 ratio, Heart rate, Acidosis,
Consciousness, Oxygenation, and Respiratory rate (HACOR) score, Dyspnoea Scale, and intubation rate. Data
were collected before hCPAP/HFNC placement and after 1 h of treatment. Amongst 188 patients randomized,
hCPAP was more effective than HFNC in reducing respiratory rate [-12 (95% CI; 11–13) vs. -9 (95% CI; 8–10),
P < 0.001] and was associated with greater heart rate reduction [-20 (95% CI; 17–23) vs. -15 (95% CI; 12–18),
P = 0.042], P/F ratio improvement [þ149 (95% CI; 135–163) vs. þ120 (95% CI; 107–132), P = 0.003] as well as in
HACOR scores [6 (0–12) vs. 4 (2–9), P < 0.001] and Dyspnoea Scale [4 (1–7) vs. 3.5 (1–6), P = 0.003]. No differen-
ces in intubation rate were noted (P = 0.321).
...................................................................................................................................................................................................
Conclusion Amongst patients with ACPO, hCPAP resulted in a greater short-term improvement in respiratory and hemo-
dynamic parameters as compared with HFNC.
...................................................................................................................................................................................................
Trial Clinical trial submission: NMRR-17-1839-36966 (IIR). Registry name: Medical Research and Ethics Committee of
registration Malaysia Ministry of Health. Clinicaltrials.gov identifier: NCT04005092. URL registry: https://clinicaltrials.gov/ct2/
show/NCT04005092.
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* Corresponding author. Tel: þ39 0382 503711, Fax: þ39 0382 503008, Email: guido.tavazzi@unipv.it
C The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.
Published on behalf of the European Society of Cardiology. All rights reserved. V
1104 A. Osman et al.

Graphical Abstract

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...........................................................................................................................................................................................
Keywords Acute cardiogenic pulmonary oedema • Helmet CPAP • High flow nasal cannula • Dyspnoea • Randomized
controlled trial

..
Introduction .. However, no studies have compared CPAP and HFNC in patients
.. with cardiogenic pulmonary oedema.
Non-invasive ventilation (NIV) is well-established in acute respiratory
.. We sought to evaluate the best respiratory strategy between
..
failure to support cardiac and respiratory function and avoid intub- .. hCPAP and HFNC in patients admitted to the Emergency
..
ation with its related complications, such as pneumonia,1 delirium,2 .. Department with hypoxemia due to ACPO.
and excessive sedation contributing to the acquired weakness.3 ..
..
Dyspnoea and arterial hypoxemia are reported in up to 90% of ..
patients presenting with acute cardiogenic pulmonary oedema .. Methods
..
(ACPO)4 with gas exchange alterations significantly affecting out- ..
come.5 NIV is thus recommended as the first-line management of
.. Study design and setting
.. Consecutive patients admitted to the Emergency Department of Raja
ACPO.6,7 ..
Helmet continuous positive airway pressure (hCPAP) allows the
.. Permaisuri Bainun Hospital from January 2018 to December 2018 with a
.. diagnosis of ACPO and fulfilling the study inclusion criteria were enrolled.
delivery of high airway positive pressure throughout the respiratory ..
.. Ethical approval from the medical research and ethics committee of
cycle with minimal air leak whereas high flow nasal cannula (HFNC)
... Malaysia Ministry of Health had been granted [NMRR-17-1839-36966
delivers a limited, amount of positive end-expiratory pressure (PEEP) .. (IIR)]. Written informed consent was obtained from the patient or the
through high-flow heated, humidified air/oxygen gas mix. Recently, ..
.. next of kin. Hospital Raja Permaisuri Bainun Clinical Research Centre
hCPAP has shown to be superior, in terms of efficacy and outcome, .. (CRC), an independent Malaysian data and safety monitoring board con-
to face mask in ARDS patients,8 whereas HFNC was associated with .. tinuously monitored safety and study conduct.
..
more ventilator free-days and lower mortality rate in those with .. Written informed consent for enrolment and consent to continue and
hypoxemic respiratory failure as compared with NIV.9
.. to use patient data was obtained from each patient or a legal surrogate.
Non-invasive ventilation strategy in cardiogenic pulmonary oedema
..
The investigators vouched for the accuracy and completeness of the data
and analyses, and the fidelity of the trial to the protocol. Patients were
not involved in the design of the study.
Participants
Acute cardiogenic pulmonary oedema was defined as the concomitant
presence of the following clinical criteria: sudden onset of respiratory dis-
tress/respiratory failure, signs of respiratory fatigue, orthopnea, bilateral
rales on auscultation, pulmonary congestion on chest radiograph, and
sonographic interstitial syndrome (multiple, bilateral, and homogeneously
distributed B-lines at lung ultrasound), without medical history or signs
suggesting pulmonary aspiration or infection.6,10
Inclusion criteria for randomization of ACPO patients were (i) older
than 18 years, (ii) respiratory rate >30 b.p.m., and (iii) pulse oximetry sat-
uration (SpO2) <90% with oxygen >_15 L/min via reservoir facemask.
Patients were excluded if they had one or more of the following: (i)
altered mental status (GCS < 8), (ii) hemodynamically instability requiring
vasopressors or inotropes/cardiogenic shock/cardiac arrest, (iii) respira-
tory distress due to primary lung cause, (iv) clinical need for urgent intub-
ation, or (v) acute myocardial ischemia requiring urgent percutaneous
coronary intervention.
Randomization
The trial statistician provided a computer-generated assignment se-
quence (random numbers) with a 1:1 ratio variable-block randomization,
and stratification according to the trial protocol. Sequentially numbered,
sealed, and opaque envelopes were used to conceal randomized alloca-
tion. The person responsible for the randomization was not part of the
clinical team.
Intervention
The study protocol is described in Supplementary material online,
Material S1. Upon admission to the emergency room, patients were sup-
ported with oxygen via a non-rebreathing facemask at 15 L/min. Once a
diagnosis of ACPO was established and the protocol screening per-
formed, patients who fulfilled the inclusion criteria were randomized to
receive either hCPAP or HFNC.
Helmet CPAP was delivered through a transparent plastic helmet with
a silicone neck collar (allowing adequate sealing and internal pressure
maintenance) and with gas inlet and outlet ports (CASTAR, Starmed,
Italy). The inlet port was connected to an air and oxygen blender (Air
Liquide, France). The outlet port was connected to a mechanical PEEP
spring valve (CASTAR, Starmed, Italy). Patient neck circumference was
measured to choose the appropriate helmet size (small, medium, and
large). The gas flow was set at a minimum of 40 L/min to prevent
rebreathing.11 Inspired oxygen fraction (FiO2) was set up to 0.6 and PEEP
was initially set at 5 cmH2O, then titrated upward with increments of 3–5
cmH2O (if needed), to achieve oxygen saturation >94%.8,12
HFNC (delivered with Hamilton mechanical ventilator, C3S,
INTELLiVENT, Switzerland) was administered using dedicated nasal can-
nulae connected to an air-oxygen blender, allowing adjustment of FiO2
between 0.21 and 1.0, and delivery of gas flow up to 60 L/min through a
heated humidifier (Hamilton H900, Switzerland). The gas mixture flowed
through a circuit at a temperature of 37 C and absolute humidity of 44
mg/L to the patients. Large or medium nasal cannulae were chosen to fit
patients’ nostrils size. HFNC was first set at a gas flow of 50 L/min. FiO2
was then titrated to the lowest value compatible with the target >94%
SpO2 and maintained throughout the study period.
In addition to the study intervention, patients received a standard
treatment based on their clinical profile, in accordance with acute heart
failure guidelines.10 No sedative agents were given to patients.
1105
.. Predefined failure criteria included: intolerance to NIV or HFNC, wor-
.. sening of respiratory failure (respiratory >35 breaths/min, haemodynamic
..
.. instability or hypotension, SpO 2 < 92%, P/F ratio <200, or signs of
.. increased work of breathing13) heart rate >120 beats/min or >30% in-
.. crease above baseline, mean arterial pressure (MAP) increase >30%
..
.. above baseline before intervention,14 and deterioration of consciousness
.. (Glasgow Coma Scale <_ 8). If one or more of these criteria were met at
..
.. any time during the trial intervention, the patient was escalated to intub-
.. ation and excluded from the protocol. At the end of the 60-min protocol,
..
.. the ventilatory support was continued at the discretion of the treating
.. physician.
.. A two-points data collection was performed: at emergency depart-
..
.. ment admission, before the start of the assigned treatment, and at the
.. end of the observation period (1 h).
Downloaded from https://academic.oup.com/ehjacc/article/10/10/1103/6386418 by guest on 17 January 2022
..
..
.. Outcome measures
..
.. The primary endpoint was the reduction of respiratory rate after 1 h of
.. treatment. The respiratory rate was measured directly by the investiga-
..
.. tors with a timer and by chest auscultation and observation of chest
.. movement during the respiratory cycle, over 1 min.15 Inter-observer vari-
..
.. ability for respiratory rate assessment was performed on 30 patients with
.. ACPO (Supplementary material online, Appendix Table S1).
.. Secondary outcomes included the difference in (i) Heart rate; (ii)
..
.. HACOR score; (iii) Arterial oxygenation PaO2 and (iv) P/F ratio; (v)
.. Dyspnoea scale;16 (vi) Intubation rate during the observation timeframe
..
.. planned by the protocol.
.. HACOR is a scoring system used to predict NIV failure in hypoxemic
..
.. patients; the acronym stands for Heart rate, Acidosis, Consciousness
.. (GCS), Oxygenation (PaO2/FiO2 ratio), and Respiratory rate. A score >5
.. at 1 h predicts >80% risk of NIV failure.17
..
..
.. Sample size
..
.. The sample size was calculated using G*Power Software version 3.1.9.4,
.. (University of Kiel, Germany, Copyright 1992–2019) based on the
..
.. expected size of the primary endpoint effect.18
.. Since there had been no study that to our knowledge directly com-
..
.. pared hCPAP and HFNC for respiratory rate reduction in adult hypoxae-
.. mic ACPO, we referred to previous studies comparing hCPAP and
..
.. HFNC in a paediatric population19 and comparing the reduction in re-
.. spiratory rate resulting from HFNC and conventional oxygen therapy in
.. adult hypoxaemic ACPO patients.14 Based on Makdee et al.,14 we esti-
..
.. mated a change from 31 breaths/min (±3.7) to 22 breaths/min (±4.1) in
.. HFNC group, and a comparable reduction from 31 breaths/min (±3.9) to
..
.. 25 (±3.6) breaths/min in the hCPAP control group, to be a significant re-
.. spiratory rate reduction after 1 h of intervention. A sample size of 94
..
.. patients per group was deemed necessary to obtain a trial power of 90%,
.. a 1% type I error (two-sided tests), and a 10% attrition rate.
..
..
.. Statistical analysis
..
.. Data analyses were performed using SPSS (Ver.22, 2013 IBM
.. Corporation, USA). Data were analysed based on a per-protocol analysis.
.. For continuous variables, results for each group were presented as means
..
.. (95% CI) or median (interquartile range), according to the data distribu-
.. tion shape and type (nominal or ordinal). Dichotomous data were pre-
..
.. sented as numbers and percentages.
.. Respiratory rate difference and other normally distributed secondary
..
.. outcomes were calculated using repeated measure independent t-test.
.. Ordinal or skewed numerical data were analysed using Mann–Whitney U
.. test. Chi-square tests (or two-tailed Fisher’s exact tests when appropri-
..
. ate) were performed for categorical data for intubation rate. All tests
1106 A. Osman et al.

..
were two-tailed with a P-value of <0.05 were considered statistically .. Respiratory failure and related hypoxaemia play an important det-
significant. .. rimental role in the pathophysiological vicious cycle of myocardial
..
.. perfusion mismatch.20 Gas exchange derangements in AHF patients
.. presenting with dyspnoea are indeed significantly related to out-
Results ..
.. come6 and NIV is currently recommended as first-line therapy from
.. the pre-hospital setting.21 Rapid resolution of respiratory distress and
Characteristics of the patients ..
.. hypoxaemia may interrupt the pathophysiological cascade that other-
Out of the 897 patients presenting with dyspnoea and screened .. wise induces an oxygen demand/supply imbalance, leading to ische-
..
throughout the study period (January 2018–December 2018), only .. mia and eventually cardio-circulatory failure.22,23
219 were eligible and enrolled. Thirteen patients refused to partici- .. Positive end-expiratory pressure application results in better al-
..
pate and a total of 206 patients underwent randomization (Figure 1). .. veolar ventilation with an oxygenation improvement, which may turn
A total of 188 patients (94 patients hCPAP; 94, HFNC) completed .. into a reduction in the work of breathing and LV oxygen demand,
..
the study protocol (Figure 1). There was no significant difference in .. enhancing oxygen delivery to the myocardium.24,25 Additionally, be-

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terms of baseline patient characteristics (Table 1).
..
.. sides the reduction in venous return which may be detrimental in
The median PEEP level used in the hCPAP group was 9 (8.7–10.3 .. patients with right ventricular dysfunction or severe hypovolemia,
..
cmH2O). .. PEEP has favourable effects on haemodynamics by decreasing trans-
.. mural pressure26,27 This combined preload and afterload decrease
..
Primary outcome .. may altogether concur to a favourable effect on cardiac output.26,27
Both hCPAP and HFNC significantly improved the respiratory .. PEEP can be delivered by several means, more consistently and to a
rate [respectively from 35 (95% CI 34–36) to 23 (95% CI 22–24) ... greater extent through a closed circuit with an expiratory valve
..
P 0.012 and from 33 (95% CI 32–25) to 25 (95% CI 24–25) P .. (CPAP) than with a sole high-flow gas mixture. CPAP use has previ-
0.001—Table 2], although hCPAP led to a greater mean respira-
.. ously been demonstrated in randomized trials to improve haemo-
..
tory rate difference reduction at 1-h as compared with HFNC .. dynamics in patients with cardiogenic pulmonary oedema as
.. compared to oxygen therapy alone28 or other kinds of non-invasive
group [respectively—12 (95% CI; 11–13) vs. 9 (95% CI; 8–10) ..
breaths/min—P < 0.001—Table 2]. .. ventilation.29,30 hCPAP was recently shown to be superior to face
.. masks CPAP in ARDS patients, by increasing the number of
..
Secondary outcomes .. ventilator-free days and reducing ICU length of stay, as well as 90-day
.. mortality due to helmet’s neck seal without substantial air leak.8
Both hCPAP and HFNC led to a significant improvement in heart ..
rate, PaO2, P/F ratio (<0.001), HACOR score, and Dyspnoea scale
.. The beneficial effects of HFNC include CO2 washout from the
..
(Table 2). However, heart rate difference after the 1-h treatment was .. upper airways, reduction of the work of breathing, and generation of
.. positive end-expiratory pressure (PEEP).31–33 However, the PEEP
greater in hCPAP [-20 b.p.m. (95% CI; 17–23)], compared to the ..
HFNC group [-15 b.p.m. (95% CI; 12–18)]. The mean PaO2 change .. level may be difficult to measure in clinical practice, and predictably
.. unstable (i.e. PEEP may vary with patient’s mouth opening).34
was significantly higher in hCPAP f[þ89 (95% CI; 81–98)] vs. HFNC ..
group [þ72 (95% CI; 64–79)] mmHgg as the P/F ratio variation
.. Recent practical guidelines strongly recommend HFNC (moderate
.. certainty) only in hypoxemic respiratory failure, while conditional
(hCPAP group: þ149; 95% CI; 135–163) [HFNC group:þ120 (95% ..
.. recommendation (moderate certainty) pertains to post-extubation
CI; 107–132)].The median HACOR score difference was more sig- .. and post-operative high-risk/obese patients.35 No recommendations
nificant in the hCPAP group in contrast to the HFNC group [6 ..
.. exist in the ACPO setting due to the lack of data. A single random-
(0–12) vs. 4 (2–9), respectively] as the dyspnoea scale difference was .. ized study has been published in patients with ACPO as yet, demon-
[4 (1–7) vs. 3.5 (1–6)]. Other parameters including PaCO2 and pH
..
.. strating HFNC superiority as compared to conventional oxygen
variations were not significantly different between the two groups, as .. therapy in terms of respiratory rate reduction and earlier respiratory
well as the intubation rate (Table 2). Seven patients in hCPAP (7%)
..
.. distress resolution, but without any significant difference in 7-day
and eleven in HFNC (11%) groups were intubated for worsening of .. mortality and intubation rates.14
..
respiratory failure according to predefined failure criteria (P 0.32) .. With the present study, we aimed at starting to fill these gaps in
(Table 1). ..
.. knowledge, and compared, for the first time to our knowledge,
There was also no statistically significant difference in 28 days mor- .. hCPAP and HFNC therapy in the early stage of ACPO treatment.
tality between hCPAP and HFNC groups: 9 (10%) patients vs. 14
..
.. Steps of increasing support were represented for hCPAP by upward
(15%) patients, respectively, died (P 0.266) (Table 2). .. titration of flow rate and PEEP and for HFNC only of FiO2 (as the
..
.. exact PEEP level cannot be determined nor guaranteed, being de-
.. pendent on the flow rate and mouth opening of the patients).
Discussion ..
.. Considering the physiological effect of PEEP application to heart and
.. lung function, the significantly greater respiratory rate improvement
In this single-centre randomized controlled clinical trial, hCPAP led ..
.. observed in the hCPAP group may at least partly be attributed to the
to a greater reduction in respiratory rate as compared with HFNC. It .. effective maintenance of constant higher PEEP levels, and the conse-
was also associated with a more significant heart rate decrease, ..
.. quent more beneficial effect in terms of work of breathing reduction
PaO2/FiO2, respiratory failure score, and dyspnoea scale .. and haemodynamic improvement.36
improvement.
Non-invasive ventilation strategy in cardiogenic pulmonary oedema 1107

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Figure 1 Of the 897 patients initially screened, 219 fulfilled the inclusion criteria. Thirteen of them refused to participate in the study. Amongst
those included in the trial, 7 in the helmet CPAP and 11 patients in the high flow nasal cannula group patients required oro-tracheal intubation and
were excluded by the final analysis according to the pre-defined exclusion criteria (Supplementary material online, Material S1-study protocol).

..
Although NIV and HFNC do not differ in preventing the risk of se- .. therapy and face mask NIV in patients with acute hypoxemic respira-
vere hypoxaemia during intubation,37 HFNC yields greater comfort .. tory failure.9 A recent meta-analysis demonstrated that HFNC
..
and lower 90-day mortality, when compared with standard oxygen .. decreases although this did not translate into a mortality benefit. the
1108 A. Osman et al.

Table 1 Baseline characteristics of the study population

Helmet CPAP n 5 94 HFNC n 5 94 P-value

....................................................................................................................................................................................................................
Gender, male, n (%) 60 (64) 63 (67) 0.759b
Female, n (%) 34 (36) 31 (33)
Age (years), mean (95% CI) 60.9 (58.3–63.4) 60.5 (57.3–63.6) 0.844c
Ethnicity, n (%) 0.257b
Malay 40 (42.5) 44 (46.8)
Chinese 22 (23.4) 22 (23.4)
Indian 31 (33.0 23 (24.5)
Others 1 (1.1) 5 (5.3)
BMI, mean (95% CI)a 28 (27–29) 29 (28–29) 0.304c

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Comorbidities
Hypertension, n (%) 75 (80) 65 (69) 0.132b
Heart disease, n (%) 48 (51) 49 (52) 0.884b
Chronic kidney disease, n (%) 32 (34) 27 (29) 0.53b
Diabetes mellitus, n (%) 68 (72) 55 (59) 0.07b
Causes of ACPO, n (%)
Hypertension, n (%) 67 (71) 65(69) 0.750b
Ischemia, n (%) 22 (23) 21(22) 0.862b
Primary arrhythmia, n (%) 3 (0.3) 4 (0.4) 1.000b
Valve disease, n (%) 2 (0.2) 4 (0.4) 0.174b
HFrEF, n (%) 51 (54) 53 (56) 0.769b
HFpEF, n (%) 43 (46) 41 (44) 0.771b
Standard medical treatment given in
1h
Isosorbide dinitrate, n (%) 76 (81) 66 (70) 0.13b
Furosemide, n (%) 64 (68) 55 (59) 0.23b
Main indication for intubation, n (%) n = 101 n = 105
Intolerance to NIV 1 (1) 0 (0)
Worsening respiratory failure 5 (5) 9 (9)
Deterioration of consciousness 1 (1) 2 (2)

ACPO, acute cardiogenic pulmonary oedema; CI, confidence interval; IQR, inter-quartile range; HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with
reduced ejection fraction; PEEP, positive end expiration pressure.
a
Calculated as weight in kilograms divided by height in square meters.
b
Chi-square or Fisher’s exact test.
c
Independent t-test.

..
need for intubation.38 In our population a higher, although not signifi-
cant, intubation rate was observed in such group.
The results of our study confirm that patients with ACPO benefit
from respiratory support and suggest that hCPAP may be superior in
improving early haemodynamic and respiratory parameters and
patients’ clinical conditions when compared with HFNC. This is con-
sistent with data from a recent physiological study comparing CPAP
to HFNC in acute hypoxemic respiratory failure, which demon-
strated similar results in terms of PaO2/FiO2, respiratory rate, dys-
pnoea improvement, and comfort level.39
Given the importance of supportive respiratory strategies in hypo-
xemic respiratory failure patients with acute cardiovascular insuffi-
ciency, more data from adequately powered RCTs on the best
.. ventilatory approach in this context (including interfaces and ventila-
.. tory settings) are highly advocated.
..
..
.. Limitations
..
.. Our study has several limitations. It was conducted in a single-centre,
.. with a high prevalence of south-Asian population, and an admission
..
.. rate of around 6–10 patients per day; this may limit the external valid-
..
.. ity for other centres with a different setting. Secondly, we excluded
.. patients presenting with acute myocardial infarction or hypercarbia,
..
.. patients who may have higher NIV failure rates and the worst out-
.. come. Thirdly, the 60-min intervention duration is likely inadequate
..
.. to evaluate the long-term efficacy of both interventions, as well as to
.. include hard end-points, such as mortality and shock during the
Table 2 Primary and seconday outcomes

hCPAP HFNC HFNC vs.

.......................................................................................................... .......................................................................................................... hCPAP
Studied 0-h 1-h Absolute P-value 0-h 1-h Absolute P-value Absolute
parameter difference difference difference
Mean (95% CI) P-value
.................................................................................................................................................................................................................................................................................................
Primary outcome
.................................................................................................................................................................................................................................................................................................
Respiratory rate 35 23 12 0.012c 33 25 9 <0.001c <0.001a
(34–36) (22–24) (11–13) (32–25) (24–25) (8–10)
Secondary outcome
.................................................................................................................................................................................................................................................................................................
Mean arterial pressure 106 96 10 <0.001c 102 92 9 <0.001c <0.001a
(101–111) (92–100) (8–12) (96–108) (89–96) (7–12)
Heart rate 112 92 20 0.002c 111 95 15 <0.001c 0.042a
(109–115) (89–95) (17–23) (108–113) (93–98) (12–18)
Non-invasive ventilation strategy in cardiogenic pulmonary oedema

pH 7.35 7.37 0.02 <0.001c 7.38 7.39 0.009 0.350c 0.381a

(7.33–7.37) (7.35–7.38) (0.0–0.04) (7.36–7.40) (7.37–7.40) (0.01–0.03)
PaO2 87.26 176.52 89.26 0.016c 91.37 163.10 71.73 0.01c 0.003a
(83–92) (168.10–185.94) (80.79–92.95) (83.88–98.85) (154.05–172.15) (64.11–79.36)
PaCO2 36.45 36.40 0.05 <0.001c 36.62 36.60 0.02 0.984c 0.945a
(34.21–38.70) (34.20–38.60) (-1.2–1.3) (34.49–38.75) (34.80–38.41) (-1.58–1.61)
P/F ratio 145 294 149 <0.001c 152 272 120 <0.001c 0.003a
(138–153) (280–308) (135–163) (140–164) (257–287) (107–132)
HACOR Score, 8 3 6 <0.001d 7 4 4 <0.001d <0.001b
median [4–15] [0–10] [0–12] [0–14] [0–8] [2–9]
(IQR)
Dyspnoea scale, 6 2 4 <0.001d 5 2 3.5 <0.001d 0.003b
median [2–10] [1–7] [1–7] [2–10] [0–5] [1–6]
(IQR)

CI, confidence interval; Dyspnoea Score, dyspnoea severity score measured using an unmarked 100 mm VAS card that had mark with ‘I can breathe normally’, at one end corresponding to patients’ normal baseline breathing which score
‘0’ and on the other end ‘I can’t breathe at all’, which score ‘10’ representing the worst difficulty perceived by patients; HACOR Score, 25-point score based on Heart Rate, Acidosis, Consciousness, Oxygenation, and Respiratory Rate;
hCPAP, helmet continuous positive airway pressure; HFNC, high flow nasal cannula; IQR, interquartile range; P/F ratio, PaO2/FiO2 ratio.
a
Independent t-test.
b
Mann–Whitney U test.
c
Paired t-test.
d
Wilcoxon signed ranks test.
1109

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1110 A. Osman et al.

..
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.. failure of the European Society of Cardiology (ESC)Developed with the special
.. contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J
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