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Noninvasive ventilation versus oxygen therapy in patients with acute

respiratory failure

Article  in  Current Opinion in Anaesthesiology · January 2019

DOI: 10.1097/ACO.0000000000000705

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REVIEW

CURRENT
OPINION Noninvasive ventilation versus oxygen therapy
in patients with acute respiratory failure
Jean-Pierre Frat a,b, Florent Joly a, and Arnaud W. Thille a,b

Purpose of review
High-flow nasal cannula oxygen therapy (HFOT) is becoming an alternative to noninvasive ventilation (NIV)
and standard oxygen in management of patients with acute respiratory failure.
Recent findings
Patients with de novo acute respiratory failure should be managed with HFOT rather than NIV. Indeed, the
vast majority of patients with de novo respiratory failure meet the criteria for ARDS, and NIV does not seem
protective, as patients generate overly high tidal volume that may worsen underlying lung injury. However,
NIV remains the first-line oxygenation strategy in postoperative patients and those with acute hypercapnic
respiratory failure when pH is equal to or below 7.35. During preoxygenation, NIV also seems to be
more efficient than standard oxygen using valve-bag mask to prevent profound oxygen desaturation. In
postoperative cardiothoracic patients, HFOT could be an alternative to NIV in the management of acute
respiratory failure.
Summary
Recent recommendations for managing patients with acute respiratory failure have been established on
the basis of studies comparing NIV with standard oxygen. Growing use of HFOT will lead to new studies
comparing NIV versus HFOT in view of more precisely defining the appropriate indications for each
treatment.
Keywords
acute respiratory failure, high-flow oxygen therapy, ICU, noninvasive ventilation

INTRODUCTION with chronic lung disease as during chronic obstruc-

Oxygen therapy is the first-line strategy of oxygen-
ation in cases of acute respiratory failure. Noninva-
sive strategies of oxygenation, that is, noninvasive
positive pressure ventilation (NIV) and, more
recently, high-flow nasal cannula oxygen therapy
(HFOT) aim to decrease the need for intubation and
the risk of nosocomial infection [1]. However, defi-
nition of acute respiratory failure is not well estab-
lished, the criteria most widely used in clinical
studies being a respiratory rate between 20 or
25 breaths/min, clinical signs of respiratory failure,
and hypoxemia commonly defined with a PaO2/
FiO2 ratio below 200 or 300 mmHg. De novo acute
respiratory failure includes hypoxemic patients
without underlying chronic lung disease or cardio-
genic pulmonary edema, and hypercapnia is
uncommon in this setting. The main causes for de
novo acute respiratory failure in nearly three quar-
ters of the cases are pneumonia [2]. Acute hypercap-
nic respiratory failure includes patients with PaCO2
exceeding 45 mmHg and occurs mainly in patients
tive pulmonary disease (COPD) exacerbation.
When acute respiratory failure is related to
COPD exacerbation, NIV is the first-line strategy
of choice [3], whereas HFOT may be more beneficial
in patients with de novo acute respiratory failure [2].
The physiological effects of these oxygenation sup-
ports include the improvement in oxygenation and
in alveolar ventilation and decrease in work of
breathing. Although physiological effects of NIV
are clearly beneficial in hypercapnic patients, they
could be deleterious in hypoxemic patients
without hypercapnia, where HFOT could avoid
a
Médecine Intensive Réanimation, CHU de Poitiers and bINSERM CIC
1402 - ALIVE, Faculté de Médecine et Pharmacie, Université de Poitiers,
Poitiers, France
Correspondence to Jean-Pierre Frat, Médecine Intensive Réanimation,
CHU de Poitiers, 2 rue la Milétrie, 86021 Poitiers Cedex, France.
Tel: +33 5 49 44 40 07; e-mail: jean-pierre.frat@chu-poitiers.fr
Curr Opin Anesthesiol 2019, 32:000–000
DOI:10.1097/ACO.0000000000000705

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Intensive care and resuscitation
KEY POINTS
 HFOT should be rather applied than NIV in patients
with de novo respiratory failure, the vast majority of
whom meet the criteria for ARDS.
 NIV does not seem protective for patients with de novo
acute respiratory failure, because of overly high tidal
volumes generated by patients and overly low levels of
PEEP set.
 Recent findings suggest that spontaneous breathing with
high tidal volumes may worsen lung injury in patients
with de novo respiratory failure.
 In contrast, NIV remains the first-line oxygenation
strategy in patients with acute hypercapnic respiratory
failure with acute respiratory acidosis (pH is equal to or
below 7.35).
 NIV is recommended to manage postoperative patients
having respiratory failure, whereas HFOT could be
an alternative.
superimposed lung injury. Otherwise, the place of
HFOT as opposed to NIV and standard oxygen needs
to be determined for preoxygenation during the
intubation procedure in view of decreasing the risk
of profound oxygen desaturation, and during the
postextubation period for postoperative patients in
view of decreasing the risk of reintubation.
NONINVASIVE VENTILATION VERSUS
HIGH-FLOW NASAL CANNULA OXYGEN
THERAPY IN PATIENTS WITH DE NOVO
RESPIRATORY FAILURE
The clinical benefits of HFOT have been reported in
patients with de novo respiratory failure, before
understanding the mechanisms whereby HFOT is
effective. These mechanisms have been recently
described and include high oxygenation, upper air-
ways washout [4], and increase in lung volumes
favouring reduction of work of breathing [5–8].
Many of these physiological effects have been dem-
onstrated by analysing oesophageal pressure swings
and lung impedance changes with electrical imped-
ance tomography, reflecting changes in lung vol-
umes [5–8]. In a physiological study conducted in
16 healthy volunteers, electrical impedance tomog-
raphy showed an increase in end-expiratory lung
impedance, and a more uniform distribution of
alveolar ventilation under HFOT as compared with
spontaneous breathing with room air or seated posi-
tion [8]. In 15 patients with acute respiratory failure,
end expiratory lung volumes increased after appli-
cation of HFOT [7] and patients decreased their
2 www.co-anesthesiology.com
inspiratory effort. These effects were heightened
when the flow rate increased from 20 to 60 l/min
in the system: the higher the flow rate, the higher
the reduction in the inspiratory effort and the
higher the lung recruitment [5,6].
The use of NIV in patients with de novo respira-
tory failure remains debated because of the lack of
evidence regarding its benefit [2,9–17]. Accordingly,
the recent European/American clinical practice
guidelines could not establish any recommendations
&&
for its use in this setting [18 ]. Indeed, the rates of
intubation are particularly high in these patients,
ranging from 30 to 60%, and although NIV may
decrease the risk of intubation as compared with
standard oxygen, no significant difference was found
in terms of mortality by pooling all randomized
controlled trials [2,9–17]. To date, only one large-
scale, randomized, controlled trial has compared NIV
versus standard oxygen and high-flow oxygen ther-
apy in 310 patients with de novo respiratory failure
[2]. In this study, mortality was lower using HFOT
alone than using HFOT with NIV sessions, thereby
suggesting deleterious effects of NIV.
However, NIV is not uncommonly used, around
10–15% of patients with de novo acute respiratory
failure [19] or acute respiratory distress syndrome
&&
(ARDS) [20 ]. In the recent, international cohort study
including 2813 ARDS patients, among the 15%
patients managed with NIV, those with severe hypox-
emia (PaO2/FiO2 <150 mmHg) had a higher ICU-mor-
&&
tality than those invasively ventilated [20 ,21].
Consequently, why is noninvasive ventilation
associated with mortality? Are noninvasive
ventilation settings appropriate for the
management of patients with de novo acute
respiratory failure?
Several recent studies have suggested that ARDS
might be considered early in patients breathing
spontaneously without mechanical ventilation
&& &&
[22 ,23 ], although mechanical ventilation is
needed to meet the criteria for ARDS according to
the Berlin definition [24]. In a recent study analyz-
ing 127 patients with pulmonary bilateral infiltrates
and a PaO2/FIO2 ratio 300 mmHgor less under stan-
dard oxygen, 120 (94%) fulfilled the criteria for
ARDS within the first 24 h after NIV initiation,
meaning that these patients could be identified
early in the emergency room in view of applying
&&
the best oxygen strategy [22 ]. Another study has
compared biomarker levels of inflammatory and
injury in hypoxemic patients with pulmonary bilat-
eral infiltrates either breathing spontaneously or
&&
under mechanical ventilation [23 ]. After propen-
sity-score matched analysis, the pattern of
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inflammatory biomarkers was similar in the 39
patients managed with HFOT and in the 39 intu-
bated patients with usual criteria for ARDS.
In the above-mentioned cohort study of patients
managed with NIV for ARDS, positive end expiratory
pressure (PEEP) levels were lower as compared with
PEEP levels in patients managed with invasive venti-
&&
lation [20 ]. This can potentially lead to a high
driving pressure and high transpulmonary pressure
compromising lung protection [25]. In this line, a
recent sub-analysis of a randomized controlled study
found that a tidal volume greater than 9 ml/kg of
predicted body weight after 1 h of NIV was a factor
strongly associated with intubation and mortality
&&
[26 ]. By contrast, time to intubation was not signif-
icantly different between survivors and nonsurvi-
vors, suggesting that poor outcomes were not
because of delayed intubation. Pressure-support lev-
els did not differ between patients who needed intu-
bation and the others. Only tidal volumes differed
and were higher in patients who were intubated,
suggesting a probable consequence of a high patient
inspiratory effort [27]. An observational study includ-
ing patients managed with NIV for de novo acute
respiratory failure reported that a tidal volume above
9.5 ml/kg of predicted body weight was associated
with an increased risk of intubation [27]. Moreover,
nearly half of the patients under NIV generated tidal
volumes exceeding 10 ml/kg despite a target tidal
volume between 6 and 8 ml/kg.
These recent studies suggest that patients man-
aged with NIV for de novo acute respiratory failure
or ARDS have an increased risk of mortality, poten-
tially caused by inappropriate ventilatory setting
with overly low PEEP levels and high tidal volumes,
resulting from the inadequate synchronization of
high inspiratory efforts and pressure support. A
recent review elucidated the concept of patient
self-inflicted lung injury (P-SILI) to explain the
potential deleterious effects of spontaneous ventila-
&&
tion [28 ]. Patients with de novo respiratory failure
who breathe spontaneously may worsen their lung
injury by generating high inspiratory efforts, lead-
ing to high tidal volumes and subsequent high
transpulmonary pressures that can promote local
lung strains, capillary leak and lung edema
&&
[28 ,29]. Ventilator-induced lung injury is well
demonstrated in intubated patients under invasive
mechanical ventilation and previous studies in
ARDS patients have shown that reduction in tidal
volumes clearly decreased mortality [30]. Surpris-
ingly, tidal volumes generated under NIV has sel-
dom been mentioned in previous studies [9–17],
suggesting that until recently, lung injury poten-
tially induced by NIV had not been considered.
Therefore, question remains about the impact of a
0952-7907 Copyright ß 2019 Wolters Kluwer Health, Inc. All rights reserved.
Noninvasive ventilation versus oxygen therapy Frat et al.
protective NIV entailing low levels of pressure-sup-
port and high levels of PEEP to avoid high tidal
volumes, to favor alveolar recruitment and to mini-
mize ventilator-induced lung injury.
Is there any way to apply a ‘protective
noninvasive ventilation’?
In a monocenter study, 83 patients with ARDS
already treated by NIV were randomized to continue
with NIV delivered through a standard facemask or
through a helmet [31]. Patients treated with helmet
had markedly lower intubation and mortality rates
than those treated with facemask.
Obviously, the interface may have an important
effect, but above all, ventilator settings were signifi-
cantly different between groups: patients treated
with helmet had higher PEEP (8 versus 5 cm H2O)
and lower pressure support levels (8 versus 11 cm
H2O) than those with facemask, a factor that may
have reduced lung injury. Unfortunately, measure-
ment of actual tidal volumes is not feasible using
helmet, and as a result, it is uncertain that tidal
volumes were indeed lower with helmet than with
facemask. The long-term follow-up data of these
patients confirms these results with 1-year mortality
significantly lower in patients treated with helmet
than in those treated with facemask (43 versus 69%;
P ¼ 0.017) [32 ]. However, these findings do not
&
justify application of helmet in this setting and a
large multicenter randomized controlled trial would
be needed to confirm these results. Future research
should assess the real impact of helmet vs. protective
NIV with a facemask applied with low levels of
pressure-support and high levels of PEEP, and may
evaluate the beneficial effects of HFOT in patients
with de novo respiratory failure.
NONINVASIVE VENTILATION VERSUS
HIGH-FLOW NASAL CANNULA OXYGEN
THERAPY IN EMERGENCY DEPARTMENT
Previous studies conducted in the emergency
departments compared HFOT with standard oxygen
in heterogeneous populations of patients with
pneumonia, cardiogenic pulmonary edema and
COPD exacerbation [33–35]. Results were mainly
changes in physiological parameters including
reduced dyspnea and increased pulse oximetry
under HFOT [33–35]. One randomized study includ-
ing 128 patients having cardiogenic pulmonary
edema showed a more rapid decrease in respiratory
rate within the first 15 min of treatment with HFOT
as compared with conventional oxygen [36].
Another randomized controlled study compared
HFOT with NIV in 204 patients requiring NIV
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mainly for COPD exacerbation (39% of patients)
[37]. HFOT was noninferior to NIV as concerned
need for intubation and decision to apply alternate
therapy [37].
Consequently, HFOT seems to be an alternative
to standard oxygen as first line therapy in manage-
ment of patients with acute respiratory failure. How-
ever, NIV remains the recommended treatment for
cardiogenic pulmonary edema and COPD exacerba-
&&
tion with respiratory acidosis [18 ], whereas HFOT
may be applied as alternate treatment in case of
NIV intolerance.
NONINVASIVE VENTILATION IN PATIENTS
WITH ACUTE HYPERCAPNIC
RESPIRATORY FAILURE
The beneficial effects of NIV in COPD patients are well
demonstrated [3,38]. By pooling all randomized con-
trolled trials, a Cochrane review has recently con-
cluded that NIV decreased the risk of mortality by
&
46% as compared with standard oxygen [39 ]. Recent
European/American clinical practice guidelines have
strongly recommended NIV for COPD patients with
acute-on-chronic respiratory failure associated with
acute respiratory acidosis (pH  7.35) [18 ]. However,
&&
NIV is not recommended in patients with hypercapnia
who are not acidotic or as a mean to prevent the
&&
development of respiratory acidosis [18 ].
Numerous patients admitted to ICU for acute
hypercapnic respiratory failure have never undergone
sleep analyses and pulmonary function tests. Two
recent prospective single-center cohorts reported that
more than half of these patients had severe sleep apnea
syndrome with thus a theoretical indication of con-
tinuous application of NIV during the night applied
with high PEEP levels (around 8–10 cmH2O) to pre-
vent obstructive sleep apnea [40,41].
A number of COPD patients are treated by NIV
in ICU with a do-not-intubate order because of poor
quality of life. In a recent meta-analysis focusing on
2000 patients treated by NIV for acute respiratory
failure with a do-not-intubate order, a large propor-
tion of COPD patients survived to hospital discharge
(68%) whereas it was only 37% for patients with
malignancy and 41% for those with pneumonia
[42]. Unfortunately, quality of life in survivors has
been poorly assessed.
Lastly, only observational studies in patients of
mild severity [43,44] or case reports in patients with
severe respiratory acidosis have reported the efficacy
of HFOT in reversion of acute respiratory failure
[45,46]. Future studies should assess whether HFOT
could be an alternative to NIV or to standard oxygen
in COPD patients in terms of reducing the risk
of intubation.
4 www.co-anesthesiology.com
NONINVASIVE VENTILATION VERSUS
HIGH-FLOW NASAL CANNULA OXYGEN
THERAPY FOR PREOXYGENATION OF
HYPOXEMIC PATIENTS
Unlike the operating room, intubation procedure in
ICU carries a high risk of life-threatening complica-
tions including severe oxygen desaturation in 20–
25% of cases, usually defined as a drop of pulse oxime-
try below 80% [47,48]. Cardiac arrest is the ultimate
catastrophic complication, which can occur in 2–3%
of intubation procedure in ICU, and is strongly related
to hypoxemia or absence of preoxygenation before
&
intubation [49 ]. One previous randomized controlled
study including a small sample of patients in ICU
found a lower incidence of severe oxygen desaturation
using NIV as compared with standard valve-bag mask
during intubation procedure [50]. A more large-scale
trial including 201 patients failed to demonstrate any
benefits of NIV as a preoxygenation strategy to reduce
organ dysfunction compared with standard valve-bag
&
mask [51 ]. However, patients treated by NIV prior to
preoxygenation, probably with severe hypoxemia,
had a higher risk of severe oxygen desaturation when
preoxygenation with standard valve-bag mask was
applied, suggesting that NIV should probably not be
discontinued for preoxygenation.
A prospective before–after study reported a
reduction in episodes of severe oxygen desaturation
using HFOT as preoxygenation rather than standard
oxygen [52]. However, these results have not been
confirmed in the different randomized controlled
trials carried out to date [53–55]. Last, one pilot
study has reported that combining NIV and HFOT
was superior to NIV alone in maintaining high pulse
oximetry, but provided no answer as to whether or
not NIV alone was superior to HFOT [56].
A large prospective multicenter randomized
controlled trial including more than 300 hypoxemic
patients was carried out with the aim of assessing
whether NIV is superior to high-flow oxygen ther-
apy [57]. The study was just completed and
will probably help to establish recommendations
on preoxygenation.
NONINVASIVE VENTILATION TO PREVENT
REINTUBATION AFTER EXTUBATION
Several studies have shown beneficial effects of NIV
in postoperative patients [58,59], by decreasing the
risk of intubation in patients with acute respiratory
failure after abdominal and thoracic surgery as com-
pared with standard oxygen. The recent European/
American clinical practice guidelines suggest NIV as
&&
first-line therapy for these patients [18 ]. However,
one multicenter, randomized noninferiority study
including 830 cardiothoracic postoperative patients
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showed that HFOT was as efficient to NIV in pre-
venting or resolving acute respiratory failure [60,61].
In contrast, NIV should not be applied in ICU
patients who develop acute respiratory failure after
&&
planned extubation [18 ]. Two randomized con-
trolled trials compared NIV versus standard oxygen
and reported either an absence of impact on outcomes
or an increased mortality rate using NIV [62,63].
CONCLUSION
To conclude, recent studies suggest application of
HFOT in place of standard oxygen in patients with
de novo acute respiratory failure. NIV remains the
gold standard in management of patients with acute
acidosis because of COPD exacerbation. However,
further studies will determine whether HFOT alone
or HFOT associated with NIV could be better means
of managing patients with COPD exacerbation,
postoperative patients having postextubation respi-
ratory failure or during intubation procedure.
Acknowledgements
The authors wish to thank Jeffrey Arsham for reviewing
and editing the original English-language manuscript.
Financial support and sponsorship
None.
Conflicts of interest
A.W.T. reports travel expenses coverage to attend scien-
tific meetings from Fisher & Paykel, Covidien, Maquet,
and General Electrics, and no personal income from any
company.
J.P.F. reports consulting fees from Fisher & Paykel and
SOS oxygene.
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Volume 32  Number 00  Month 2019