Journal of
Personalized
Medicine
Review
Personalized Noninvasive Respiratory Support in the
Perioperative Setting: State of the Art and Future Perspectives
Giovanni Misseri 1,† , Luciano Frassanito 2,† , Rachele Simonte 3, *, Tommaso Rosà 2,4 ,
Domenico Luca Grieco 2,4 , Alessandra Piersanti 2 , Edoardo De Robertis 3 and Cesare Gregoretti 1,5
Citation: Misseri, G.; Frassanito, L.;
Simonte, R.; Rosà, T.; Grieco, D.L.;
Piersanti, A.; De Robertis, E.;
Gregoretti, C. Personalized
Noninvasive Respiratory Support in
the Perioperative Setting: State of the
Art and Future Perspectives. J. Pers.
Med. 2024, 14, 56. https://doi.org/
10.3390/jpm14010056
Academic Editor: Fernando
Ramasco-Rueda
Received: 27 November 2023
Revised: 18 December 2023
Accepted: 26 December 2023
Published: 30 December 2023
Copyright: © 2023 by the authors.
Licensee MDPI, Basel, Switzerland.
This article is an open access article
distributed under the terms and
conditions of the Creative Commons
Attribution (CC BY) license (https://
creativecommons.org/licenses/by/
4.0/).
J. Pers. Med. 2024, 14, 56. https://doi.org/10.3390/jpm14010056
1 Fondazione Istituto “G. Giglio” Cefalù, 90015 Palermo, Italy; giovannimisseri1987@gmail.com (G.M.);
c.gregoretti@gmail.com (C.G.)
2 Department of Emergency, Intensive Care Medicine and Anaesthesia, Fondazione Policlinico Universitario A.
Gemelli IRCCS, 00165 Rome, Italy; luciano.frassanito@policlinicogemelli.it (L.F.);
tommasoros22@gmail.com (T.R.); domenicoluca.grieco@policlinicogemelli.it (D.L.G.);
alessandra.piersanti@policlinicogemelli.it (A.P.)
3 Department of Medicine and Surgery, University of Perugia, 06123 Perugia, Italy; edoardo.derobertis@unipg.it
4 Istituto di Anestesiologia e Rianimazione, Università Cattolica del Sacro Cuore, 00165 Rome, Italy
5 Department of Surgical, Oncological and Oral Science (Di.Chir.On.S.), University of Palermo,
90133 Palermo, Italy
* Correspondence: rachele.simonte@gmail.com
† These authors contributed equally to this work.
Abstract: Background: Noninvasive respiratory support (NRS), including high-flow nasal oxygen
therapy (HFNOT), noninvasive ventilation (NIV) and continuous positive airway pressure (CPAP),
are routinely used in the perioperative period. Objectives: This narrative review provides an
overview on the perioperative use of NRS. Preoperative, intraoperative, and postoperative respiratory
support is discussed, along with potential future areas of research. Results: During induction of
anesthesia, in selected patients at high risk of difficult intubation, NIV is associated with improved
gas exchange and reduced risk of postoperative respiratory complications. HFNOT demonstrated an
improvement in oxygenation. Evidence on the intraoperative use of NRS is limited. Compared with
conventional oxygenation, HFNOT is associated with a reduced risk of hypoxemia during procedural
sedation, and recent data indicate a possible role for HFNOT for intraoperative apneic oxygenation
in specific surgical contexts. After extubation, “preemptive” NIV and HFNOT in unselected cohorts
do not affect clinical outcome. Postoperative “curative” NIV in high-risk patients and among those
exhibiting signs of respiratory failure can reduce reintubation rate, especially after abdominal surgery.
Data on postoperative “curative” HFNOT are limited. Conclusions: There is increasing evidence
on the perioperative use of NRS. Use of NRS should be tailored based on the patient’s specific
characteristics and type of surgery, aimed at a personalized cost-effective approach.
Keywords: CPAP; HFNOT; ICU; mechanical ventilation; noninvasive respiratory support (NRS);
noninvasive ventilation (NIV); perioperative care; postoperative pulmonary complications
1. Introduction
Perioperative care, also known as perioperative medicine, is the practice of patient-
centered, multidisciplinary, and integrated medical care from the preoperative phase to
the postoperative recovery [1]. “Anesthesiomics” [2] embeds this holistic and personalized
approach intended to provide high-quality care, minimize complications, and reduce
requirement of postoperative intensive care unit (ICU) admission and hospital length of
stay (LOS).
Perioperative respiratory complications are a leading cause of morbidity and mor-
tality. General anesthesia induces a loss of muscle tone and a cephalic displacement of
the diaphragm, yielding reduction of functional residual capacity due to atelectasis and
https://www.mdpi.com/journal/jpm
J. Pers. Med. 2024, 14, 56 2 of 19

postoperative hypoxemia. These mechanisms lead to perioperative respiratory dysfunction

and predispose to postoperative pulmonary complications (PPCs) [3,4]. These include
postoperative hypoxemia, atelectasis, pneumonia, acute respiratory failure, and acute
respiratory distress syndrome, which may prompt the use of mechanical ventilation [5].
PPCs are a prominent cause of prolonged hospitalization and mortality [6]. Several scores
have been developed to predict the occurrence of PPCs [7,8], the emergence of which
is related to surgical factors (intraoperative positional changes, diaphragmatic splinting,
direct surgical injury to the lungs, pleura, diaphragm, chest wall, abdominal wall, or to the
nerves supplying the respiratory muscles) and patient factors and comorbidities (advanced
age, smoking, cardiovascular and respiratory comorbidities, obesity, pregnancy).
Current research is aimed at optimizing perioperative oxygenation and mechanical
ventilation for specific cohorts of patients in different surgical subspecialties [9,10].
Thus, efforts have been made to adopt personalized strategies, with the aim to reduce
perioperative respiratory complications [11] and improve postoperative patients’ outcome
and recovery.
The incidence of acute respiratory failure after surgery is variable: the need for reintu-
bation and invasive mechanical ventilation among unselected surgical patients is approxi-
matively 5–10% but can be as high as 30–50% in high-risk patients undergoing abdominal
and cardiac surgery [12,13].
Preserving perioperative respiratory function is a mainstay for ensuring safe anesthesia
administration, success of surgical procedures, and uneventful recovery. The perioperative
use of noninvasive respiratory support (NRS) may be associated with improved respiratory
function and reduced PPCs. The term NRS is used in reference to noninvasive ventilation
(NIV), continuous positive airway pressure (CPAP), and high-flow nasal oxygen therapy
(HFNOT) [14,15].
This narrative review’s aim is to give an overview (Figure 1) on the perioperative
use of NRS across different surgical subspecialties and patient populations. Each of the
three perioperative periods (preoperative, intraoperative, and postoperative) is discussed,
highlighting the rationale and evidence (Table 1, Figure 2) on perioperative NRS use and
the future areas of research in terms of personalized care.
Table 1. Landmark studies on NRS use in the perioperative period (ARF: acute respiratory failure;
COPD: chronic obstructive pulmonary disease; COT: conventional oxygen therapy; ICU: intensive
care unit; GA: general anesthesia; NRS: noninvasive respiratory support; HFNOT: high-flow nasal
oxygen therapy; THRIVE: transnasal humidified rapid-insufflation ventilatory exchange; NIV: non-
invasive ventilation; PACU: postanesthesia care unit; RM: recruitment maneuver).

Study Timing for NRS NRS

Design Population Studied Findings
(Ref), Year Application Modality
66 morbidly obese
Preoxygenation with NIV+RM
3 groups:
more effectively leads to an
Futier et al. Randomized (a) COT, Preoxygenation
NIV increase in end-expiratory lung
[16], 2011 controlled trial (b) NIV, before intubation
volume with better
(c) NIV+RM after
oxygenation compared to COT
intubation
Prospective, 23 morbidly obese
CPAP groups had a
Coussa et al. randomized, 2 groups: Oxygenation after
CPAP significantly higher PaO2 after
[17], 2004 single-blinded (a) CPAP = 10 cmH20 induction
tracheal intubation
study (b) CPAP= 0 cmH20
J. Pers. Med. 2024, 14, 56 3 of 19

Table 1. Cont.

Study Timing for NRS NRS

Design Population Studied Findings
(Ref), Year Application Modality
39 patients with
preoperative
FEV1 < 70% scheduled NIV group had better
for elective lobectomy oxygenation and lung volumes
Prospective, for cancer in the immediately
Perrin et al. Pre- and
randomized 2 groups: NIV postoperative period, with a
[18], 2007 postoperative
clinical trial (a) without NIV better oxygenation until day 3
(b) with NIV postoperative and lower
for 7 days at home hospital LOS
before surgery and for
3 days postoperatively
Preoxygenation
With a median apnea time of
and continuing as
14 min, no episode of oxygen
postoxygenation
desaturation < 90% was
Prospective, 25 patients with during induction
Patel et al. recorded. THRIVE is an
observational, anticipated difficult of anesthesia and THRIVE
[19], 2015 efficient way to mitigate the
cross-sectional airways neuromuscular
risk of hypoxemia following
blockade until a
anesthesia induction and
definitive airway
neuromuscular blockade
was secured
The frequency of rescue
interventions due to
118 patients scheduled hypercapnia, desaturations,
Prospective, for laryngeal and acidosis was higher for
During short
randomized, microsurgery high-flow nasal oxygen
Min et al. apneic procedures
parallel-group, 2 groups: HFNOT therapy (HFNOT) compared to
[20], 2022 (pre- and
noninferiority (a) HFNOT group tracheal intubation. This led to
postinduction)
study (b) tracheal intubation the conclusion that HFNOT is
groups not noninferior to tracheal
intubation in terms of
sustaining oxygenation
125 adult patients
scheduled for elective
surgery
5 groups:
(a) 0.25 L·min−1,
endotracheal tube;
(b) 2 L·min−1, continuous In anesthetized No differences between groups
Single-center jaw thrust; and paralyzed with respect to decrease in
Riedel et al.
randomized (c) 10 L·min−1, continuous adults prior to HFNOT lung impedance or curve
[21], 2022
controlled trial jaw thrust; intubation for progression over the
(d) 70 L·min−1, continuous 15 min of apnea observation period
jaw thrust; and
(e) 70 L·min−1, continuous
laryngoscopy with a
McGrath MAC video
laryngoscope (Medtronic,
Dublin, Ireland)
The use of HFNOT was linked
to enhanced oxygenation,
15 randomized decreased requirement for
controlled trials airway intervention, and
Systematic Nasal cannula
Tao et al. compared HFNOT with reduced interruption of
review and during endoscopic HFNOT
[22], 2022 COT in patients procedures in patients
meta-analysis procedures
undergoing endoscopic undergoing bronchoscopy and
procedures gastrointestinal endoscopic
procedures (moderate-
quality evidence)
J. Pers. Med. 2024, 14, 56 4 of 19

Table 1. Cont.

Study Timing for NRS NRS

Design Population Studied Findings
(Ref), Year Application Modality
9 RCTs representing
Neither HFNOT nor NIV had
1865 patients at high risk
impact on mortality rates. But
Pairwise and for or with established NIV and
Zayed et al. both NIV and HFNOT had
network postoperative Postoperative time CPAP vs.
[23], 2020 lower postoperative
meta-analysis respiratory failure HFNOT
reintubation rates compared
comparing NIV, HFNOT,
to COT
and COT
24 patients with acute The use of NIV in patients with
hypoxemic respiratory acute hypoxemic respiratory
Randomized insufficiency after lung insufficiency after lung
Auriant et al.
prospective resection Postoperative time NIV resection can reduce the need
[24], 2001
trial 2 groups: for invasive endotracheal
(a) NIV mechanical ventilation and
(b) no NIV reduce mortality rates
209 patients with severe
Randomized
hypoxemia after major
controlled, CPAP group had a lower
Squadrone elective abdominal
unblinded Postoperative time Helmet intubation rate, occurrence rate
et al. surgery
study with CPAP of pneumonia, infection,
[25], 2005 2 groups:
concealed and sepsis
(a) oxygen
allocation
(b) oxygen + CPAP
830 patients undergoing
cardiothoracic surgery
Multicenter,
Stephan with ARF in the Postoperative HFNOT was not inferior to
randomized, HFNOT vs.
et al. postoperative period period for at least NIV. No significant differences
noninferiority NIV
[26], 2015 2 groups: 4 h per day found for ICU mortality
trial
(a) HFNOT group
(b) NIV group
NIV is associated with a
significant improvement in
oxygenation before tracheal
intubation and benefits in
29 articles on obese oxygenation, clearance of CO2 ,
Qualitative Just before and
Carron et al. patients comparing and pulmonary function after
review and after induction NIV
[27], 2016 perioperative NIV (all induction. Postoperative NIV
meta-analysis of GA
modalities) vs. COT is associated with a decreased
risk of respiratory
complications, but not of
reintubation and unplanned
ICU admission
150 COPD patients
2 groups:
Post hoc
(a) Patients treated with NIV group had a lower
Thille et al. analysis of a Prophylactic NIV NIV vs.
NIV alternating reintubation rate. No
[28], 2021 randomized after extubation HFNOT
with HFNOT differences in mortality in ICU
controlled trial
(b) Patients treated with
HFNOT alone
Prophylactic HFNOT
demonstrates a reduction in
reintubation and the need for
11 RCTs enrolling
increased respiratory support
2201 patients. Preventing
Chaudhuri Systematic when compared to COT during
10 comparing HFNOT intubation in HFNOT vs.
et al. review and the immediate postoperative
to COT. postoperative NIV
[29], 2020 meta-analysis period after cardiothoracic
1 comparing HFNOT patients
surgery. This positive effect is
to NIV
likely attributed to patients at a
high risk and/or those
with obesity
J. Pers. Med. 2024, 14, 56 5 of 19

Table 1. Cont.

Study Timing for NRS NRS

Design Population Studied Findings
(Ref), Year Application Modality
83 patients undergoing
A 2 h session of HFNOT after
Single-center, major gynecological
Frassanito extubation improved
open-label, surgery Immediately after
et al. [30], HFNOT postoperative oxygen exchange
randomized 2 groups: extubation
2023 and reduced atelectasis
trial
J. Pers. Med. 2024, 14, x FOR PEER REVIEW (a) HFNOT 3 of 19
compared with a COT strategy
(b) COT

Figure 1. Infographic on the personalized perioperative use of noninvasive respiratory support

Figure 1. Infographic on the personalized perioperative use of noninvasive respiratory support
(CPAP: continuous positive airway pressure; CO2: carbon dioxide; HDU: high-dependency care
(CPAP: continuous positive airway pressure; CO2 : carbon dioxide; HDU: high-dependency care
unit; ICU: intensive care unit; NIV: noninvasive ventilation; NRS: noninvasive respiratory support,
unit; ICU:
PACU: intensive care unit;
postanesthesia unit; noninvasive
care NIV: ventilation; pulmonary
PPCs: postoperative NRS: noninvasive respiratoryTHRIVE:
complications; support,
PACU: postanesthesia care unit; PPCs: postoperative pulmonary
transnasal humidified rapid-insufflation ventilatory exchange). complications; THRIVE: transnasal
humidified rapid-insufflation ventilatory exchange).
Table 1. Landmark studies on NRS use in the perioperative period (ARF: acute respiratory failure;
COPD: chronic obstructive pulmonary disease; COT: conventional oxygen therapy; ICU: intensive
care unit; GA: general anesthesia; NRS: noninvasive respiratory support; HFNOT: high-flow nasal
oxygen therapy; THRIVE: transnasal humidified rapid-insufflation ventilatory exchange; NIV:
noninvasive ventilation; PACU: postanesthesia care unit; RM: recruitment maneuver).

Study Timing for NRS NRS

Design Population Studied Findings
(Ref), Year Application Modality
66 morbidly obese
3 groups: Preoxygenation with NIV+RM more effectively
Preoxygenation
Futier et al. Randomized (a) COT, leads to an increase in end-expiratory lung
before NIV
[16], 2011 controlled trial (b) NIV, volume with better oxygenation compared to
intubation
(c) NIV+RM after COT
intubation
Prospective, 23 morbidly obese
Coussa et al. randomized, 2 groups: Oxygenation CPAP groups had a significantly higher PaO2
CPAP
[17], 2004 single-blinded (a) CPAP = 10 cmH20 after induction after tracheal intubation
study (b) CPAP= 0 cmH20
 randomized gynecological reduced atelectasis compared with a COT
trial surgery strategy
2 groups:

J. Pers. Med. 2024, 14, 56 6 of 19

(a) HFNOT
(b) COT

Figure 2. Simplified algorithm for the perioperative use of noninvasive respiratory support.
Figure 2. Simplified algorithm for the perioperative use of noninvasive respiratory support.

2. Preoperative use
Useof
ofNoninvasive
Noninvasive Ventilation
Ventilation and CPAP
Preoxygenation before general anesthesia induction is a well-established procedure
designed to increase oxygen reserves, in the attempt attempt toto delay
delay oxyhemoglobin
oxyhemoglobin desaturation
desaturation
and prolong
prolongapneaapneatime.
time.TheThe
term apneic
term oxygenation
apneic refers refers
oxygenation to continuous oxygen flowing
to continuous oxygen
from upper
flowing from airways
upper to alveolito
airways after anesthesia
alveoli induction induction
after anesthesia and duringand theduring
apneic the
phase [31].
apneic
phasePreoxygenation
[31]. with NIV limits alveolar collapse and atelectasis formation, which are
responsible for hypoventilation,
Preoxygenation with NIV low perfusion–ventilation
limits alveolar collapse and coupling and hypoxemia
atelectasis formation, [31,32].
which
are responsible for hypoventilation, low perfusion–ventilation couplingthe
Through these mechanisms, NIV delays hypoxemia onset and lengthens apneic
and period,
hypoxemia
with a prominent
[31,32]. Through clinical effect in high-risk
these mechanisms, patients,
NIV delays such as those
hypoxemia with
onset anddifficult airways,
lengthens the
patientsperiod,
apneic undergoing
with abariatric
prominentsurgeries,
clinicaloreffect
emergency anesthesia
in high-risk for the
patients, critically
such ill [33].
as those with
Futier
difficult et al. [16]
airways, showed
patients that the combination
undergoing of NIVorfollowed
bariatric surgeries, emergency by early recruitment
anesthesia for the
maneuvers can
critically ill [33]. lead to an average increase in end-expiratory lung volume of approxi-
mately 700 mL
Futier when
et al. [16] compared
showed that to conventional
the combination bag-mask
of NIVpreoxygenation.
followed by early Thisrecruitment
increase in
end-expiratory lung volume after NIV-based preoxygenation
maneuvers can lead to an average increase in end-expiratory lung volume might be attributed to the
of
recruitment of collapsed alveoli, consequently boosting oxygen
approximately 700 mL when compared to conventional bag-mask preoxygenation. This reserves [34].
In the
increase in subgroup of obese
end-expiratory lungpatients,
volume NIV significantly
after NIV-based increases functionalmight
preoxygenation residualbe
capacity, improves ventilation–perfusion ratio, and improves cardiac output [35]. When
compared to spontaneous breathing, NIV can achieve a higher oxygenation within a shorter
time frame [16] and increase duration of nonhypoxic apnea [36], making it particularly
valuable in morbidly obese patients. Of note, a 5 min trial of CPAP during preoxygenation
in obese patients has been shown to improve arterial partial pressure of oxygen (PaO2 )
after tracheal intubation compared to controls [17].
Preoperative CPAP may benefit patients with obstructive sleep apnea (OSA), a condi-
tion often undiagnosed before surgery and posing a substantial risk, including hypoxemia,
J. Pers. Med. 2024, 14, 56 7 of 19

hypercapnia, arrhythmias, myocardial ischemia, delirium, and unplanned ICU admis-

sions [37]. Robust evidence for perioperative NIV use in this patient group is limited,
but preoperative CPAP may control disease severity, reduce postoperative pulmonary
dysfunction, and increase patient familiarity with the therapy [38].
Only few studies evaluated presurgical home/hospital NIV programs aiming at im-
proving ventilatory status and familiarizing the patients with the NIV technique that will
be applied after surgery. Perrin et al. [18] found that oxygenation and lung volumes were
significantly better in patients using preoperative home NIV for 7 days before surgery than
patients randomized to usual preoperative care. Of note, the incidence of major atelectasis
was 14% in the NIV group and 39% in the control group. When considering cardiovascular
and thoracic surgery, atelectasis are more commonly observed as postoperative complica-
tions, dramatically heightening the risk of respiratory distress. Prophylactic preoperative
use of NIV has been proposed with the aim to reduce major PPCs after elective aortic
surgery [39], demonstrating a reduction of early postoperative atelectasis and shortening
ICU and hospital LOS.
The preOVNI study [40] investigated whether preoperative NIV could reduce PPCs
after lung cancer surgery. In this randomized controlled trial (RCT), adult patients under-
going lung cancer resection were randomized to preoperative NIV (at least 7 days and
4 h/day) or conventional preoperative treatment. The authors concluded that there was
no difference in PPCs between groups (42.6% in NIV group and 44.8% in no-NIV group).
The rate of pneumonia was greater in the no-NIV group, but statistical significance was not
achieved (28.0 vs. 37.7%, respectively; p = 0.08).
In conclusion, NIV represents a safe and effective tool for preoperative oxygenation,
with a relevant clinical effect in patients prone to anesthesia-induced functional residual
capacity loss and at high risk of difficult intubation with prolonged apnea following
anesthesia induction.

3. Preoperative and Intraprocedural Use of High-Flow Nasal Oxygen Therapy

High-flow nasal oxygenation therapy (HFNOT) is an NRS technique that delivers
high flows (60–80 L/min) of a heated, humidified, and blended air/oxygen mixture via
specifically designed nasal cannulas [41].
A recent systematic review and meta-analysis on peri-intubation use of HFNOT
revealed that apneic time and PaO2 measured after preoxygenation or after intubation
were similar with HFNOT and conventional oxygen therapy (COT). In addition, the use
of HFNOT also conferred no advantage in terms of peri-intubation hypoxemia, serious
complications, or 28-day mortality [42]. However, it might be misleading to draw any
conclusions for patients at higher risk of peri-intubation hypoxemia, as the mean apnea
time in the selected studies was only <2 min.
In 2015, Patel et al. [19] coined the term transnasal humidified rapid-insufflation
ventilatory exchange (THRIVE) to indicate the delivery of 100% oxygen at 70 L/min using
the Optiflow THRIVETM apparatus (Fisher and Paykel Healthcare Ltd., Auckland, New
Zealand) to adult patients with difficult airways undergoing otorhinolaryngologic surgery.
The authors reported a median apnea time of 14 min and no episode of oxygen desaturation
(SpO2 < 90%), proving that this approach represents an efficient way to mitigate the risk of
hypoxemia following anesthesia induction and neuromuscular blockade [19]. Since then,
a large body of evidence coming from studies conducted in the surgical population and
during procedural sedation has elucidated the physiological mechanisms of this approach,
as well as the important differences when the technique is applied to apneic or unparalyzed
patients [43–46].
Provision of effective and extended oxygenation by HFNOT during rapid-sequence
induction of anesthesia and during apnea has been examined in several settings [43,47–51],
with some evidence also coming from morbidly obese patients, where HFNOT allowed
prolonging of apnea time to 75 s compared to conventional facemask ventilation [52].
J. Pers. Med. 2024, 14, 56 8 of 19

Tremey et al. [53] also described a “without the hands” technique for general anes-
thesia induction using HFNOT for preoxygenation and periprocedural oxygenation until
tracheal intubation.
Hypercapnia is the most common complication with HFNOT and affects the overall
apnea time. In an RCT including 118 patients undergoing laryngeal microsurgery under
neuromuscular blockade, Min et al. [20] showed that, despite providing prolonged periods
of apnea time, incidence of rescue interventions because of hypercapnia, desaturations,
and acidosis was more frequent for HFNOT compared to tracheal intubation. The pattern
of carbon dioxide (CO2 ) rise (linear or nonlinear) as well as exact mechanisms regarding
the extent of CO2 removal during HFNOT still need to be fully characterized. Some of
the mechanisms involved were investigated in bench models: under apneic conditions,
enhanced CO2 clearance may be explained by an interaction between entrained and highly
turbulent supraglottic flow vortices created by HFNOT and cardiogenic oscillations that
favor gas mixing [44,46].
Forsberg et al. [49] hypothesized that the increased difference in arterial and end-tidal
CO2 in combination with high arterial oxygen levels, that were noted during apnea in
patients undergoing laryngeal surgery and neuromuscular blockade during THRIVE [43],
could be attributed to increased oxygen absorption and compression atelectasis, with sub-
sequent shunt and loss of lung volume. However, lung volume changes assessed over time
by electrical impedance tomography, albeit indicating an increased ventilation–perfusion
mismatch, resulted in comparable reductions in lung volume during application of THRIVE
and in mechanically ventilated patients. Comparable decreases in lung volumes estimated
by electrical impedance tomography were also observed by Riedel et al. [21] when applying
flow rates between 0.25 L/min and 70 L/min of humidified 100% oxygen in anesthetized
and paralyzed adults, thus demonstrating that the induced increase in functional resid-
ual capacity occurring during spontaneous breathing [54] could not be replicated under
general anesthesia [49]. Nevertheless, those conclusions cannot be prescinded from the
consideration that respiratory mechanics differs significantly between paralyzed and un-
paralyzed states. With paralysis, dead space gas mixing and microventilation induced
by pharyngeal pressure variations are inevitably altered [55]. However, a recent five-arm
RCT [56] observed that differing flow rates of humidified 100% oxygen during apnea
induced comparable arterial CO2 increases, thus questioning the existence of an additional
ventilatory effect attributable to HFNOT [57].
Hypercapnia and desaturation are common concerns highlighted in most of the re-
ported studies on procedural sedation. Other complications include gastric insufflation
and airway ignition, the latter being theoretically possible in the case of concomitant use of
lasers for surgical procedures. As a consequence, the need for cautious monitoring and a
backup airway management plan, in particular when neuromuscular blockade is applied,
is of primary importance [58].
Transcutaneous CO2 monitoring could be applied during procedural sedation. It is
an accurate noninvasive alternative to arterial blood sampling, which provides clinically
acceptable accuracy particularly when the sensor is applied to the earlobe [59].
The safety profile of HFNOT in procedural sedation, or whenever neuromuscular
blockade is not needed, is less controversial [60]. A systematic review and meta-analysis
including 15 RCTs (4451 patients) published in 2022 [22] showed with moderate-quality
evidence that application of HFNOT compared to COT was associated with improved
oxygenation, decreased need for airway intervention, and reduced procedure interrup-
tion in patients undergoing bronchoscopy and gastrointestinal endoscopic procedures.
Those results were confirmed by another meta-analysis [61] evaluating the same outcome
measures in 19 RCTs (4121 patients). Although 11 of the included studies coincided with
those analyzed by Tao et al. [22], the latter included pediatric, cardiology, dental, and
endovascular settings.
The effectiveness and safety of THRIVE as a stand-alone airway and breathing tech-
nique for airway management were recently evaluated during brief operative hystero-
J. Pers. Med. 2024, 14, 56 9 of 19

scopies under general anesthesia. In their study, Yuanyuan et al. [62] showed a reduced
incidence of hypoxia, airway-related interventions, and involuntary movements during
surgery in the THRIVE group when compared to COT, with high satisfaction scores both
for anesthesiologists and gynecologists.
Frassanito et al. [63], in a pilot study including 20 patients undergoing operative
hysteroscopies with the use of THRIVE apparatus, reported adequate gas exchange with
acceptable short-term mean maximum transcutaneous CO2 levels of 51 ± 7 mmHg, no
need for rescue airway interventions, and optimal comfort for the patients.

4. Postoperative Use of Noninvasive Ventilation (NIV)

Noninvasive ventilation (NIV) is widely used in the postoperative period to both
treat (“therapeutic” or “curative” approach) and prevent (“preemptive” or “prophylactic”
approach) postoperative acute respiratory failure [64]. There is a growing interest in its use
in weaning strategies, bolstered by recent trials on early extubation practices (“facilitative”
approach) [65].
The rationale behind its postoperative use resides on the improvement of alveolar
ventilation due to reversal of atelectasis, which improves oxygenation and, partially, work
of breathing. In addition, NIV does not require an artificial airway and it is achieved
through interfaces which may be customized to improve adherence to treatment [66].
Current guidelines recommend NIV use for preventing postextubation respiratory
failure in high-risk patients (moderate certainty of evidence), but not in low-risk patients
(conditional recommendation, very low certainty of evidence) [67]. Regarding surgical
patients, NIV finds a possible therapeutic application in the case of postextubation estab-
lished respiratory failure (conditional recommendation, moderate certainty of evidence).
However, there is no clear recommendation on the preventive use of NIV in the postopera-
tive period.
The joint ESA/ESICM guidelines on NRS in the hypoxemic peri-operative/periprocedural
patient [68] suggest using noninvasive positive pressure ventilation or CPAP immediately
after extubation for hypoxemic patients at risk of developing acute respiratory failure after
abdominal surgery (Grade 1B).
Patients requiring postoperative NIV should be admitted in predefined areas, such as
postanesthesia care units (PACUs), ICUs, or high-dependency care units (HDUs), where
a close monitoring of vital parameters, blood gas exchanges, and multidisciplinary eval-
uation can be performed [69,70] to avoid delayed intubation in case of deterioration of
their condition.

4.1. NIV as Preventive Strategy in the Postoperative Period

The use of NRS after extubation in the postoperative period aims to mitigate the
occurrence of acute respiratory failure and PPCs. So far, several risk scores have been
validated to allow early identification of patients at higher risk for deterioration, thus
preventing extubation failure [71]. Several trials have been performed with the purpose to
analyze the effectiveness of preventive early NIV after major surgery, finding beneficial
effects on PPC prevention [12,72].
Despite these findings, conflicting evidence emerges from larger randomized trials and
meta-analysis. These inconsistencies are possibly explained by distinct target populations
for whom postoperative NIV is used, suggesting that different modes of NRS may be
successful when applied following specific types of surgery.
Zayed et al. [23] conducted a pairwise meta-analysis of nine RCTs on HFNOT, NIV,
and COT after major surgery in patients at high risk for or with established postoperative
acute respiratory failure. They found that neither HFNOT nor NIV influenced mortality
rates. However, lower postoperative reintubation rates were observed with NIV or HFNOT
over COT. Subgroup analysis showed lower reintubation rates with NIV after abdominal
surgery (odds ratio (OR) 0.51 95% CI [0.26–0.87], whereas after cardiothoracic surgery
J. Pers. Med. 2024, 14, 56 10 of 19

reintubation rates were lower with both HFNO and NIV when compared to COT (OR 0.08
95% CI [0.03–0.21] and OR 0.08 95% CI [0.03–0.19], respectively).
The PRISM trial [73], a pragmatic clinical effectiveness trial investigating the real-
world implementation of CPAP in PACUs, found that preventive CPAP started early after
major open abdominal surgery does not reduce the incidence of postoperative pneumonia,
reintubation rates, or death at 30 days. Therefore, its adoption as a preventive measure
against PPCs could not be supported.
A recent systematic review and meta-analysis on the routine use of postoperative NRS
after elective surgery [74], including 38 trials and 9782 patients, found that compared with
standard care, the use of CPAP, NIV, or HFNOT did not reduce the incidence of pneumonia.
In accordance with the previous findings, an open, multicenter RCT including patients at
high risk for PPCs (Assess Respiratory Risk in Surgical Patients in Catalonia [7] (ARISCAT)
score ≥ 45) showed that the preventive use of NIV has no beneficial effects over usual
care in the incidence of postoperative acute respiratory failure. In this study, patients were
randomly assigned to intermittent prophylactic face-mask NIV for 6–8 h per day or usual
postoperative care, with the primary outcome being in-hospital acute respiratory failure
within 7 days after surgery [75].

4.2. NIV as Therapeutic Strategy in the Postoperative Period

Therapeutic strategies are applied with the aim of avoiding reintubation and invasive
mechanical ventilation in case of an already established postoperative acute respiratory
failure. According to ERS/ATS 2017 clinical practice guidelines [67], NIV should be applied
in these circumstances (conditional recommendation, moderate certainty of evidence) as a
therapeutic strategy.
Several studies have shown that therapeutic NIV is able to improve clinical outcomes
of patients undergoing major abdominal [12,76,77] and thoracic [24] surgery. Beneficial
effects of postoperative therapeutic NIV have also been found in transplant procedures [78].
In their systematic review and meta-analysis, Faria et al. [72] found that compared to
COT, CPAP or NIV may reduce the rate of tracheal intubation (risk ratio (RR) 0.25; 95%
confidence interval (CI) 0.08 to 0.83; low-quality evidence). However, no differences were
found for mortality (low-quality evidence) and hospital LOS. In addition, there was insuffi-
cient evidence to prove a potential link between postoperative NRS and complications such
as anastomotic leakages, sepsis, and pneumonia-related sequalae. It is worth remembering
that after abdominal surgery, the risk of gastric insufflation rises when pressure reaches
values higher than 25 cmH2 O. Hence, in upper-gastrointestinal surgical procedures, the
risk of anastomotic leakage should be reduced by maintaining the pressure support level
below 6–8 cmH2 O [64].
Squadrone et al. [25] studied 209 consecutive patients who had undergone elective
major abdominal surgery and developed postoperative hypoxemia. The patients were
randomized to receive either COT or helmet CPAP in the recovery room. Patients receiving
helmet CPAP had a lower reintubation rate (1% vs. 10%; p = 0.005) and a lower occurrence
of pneumonia (2% vs. 10%, p = 0.02), infection (3% vs. 10%, p = 0.03), and sepsis (2% vs.
9%; p = 0.03) than patients treated with COT. When considering patients readmitted to an
ICU with postoperative acute respiratory failure, NIV successfully prevented reintubation
in 67% of cases.
In a multicenter RCT conducted among patients with acute respiratory failure after
abdominal surgery, NIV use reduced the need for reintubation and for invasive mechanical
ventilation and was associated with fewer healthcare-related infections when compared to
COT [77].

4.3. Use of NIV after Specific Major Surgery Settings

The use of NIV after major cardiac and thoracic surgical procedures is a very attractive
issue. Patients undergoing cardiac and thoracic surgeries are at higher risk of developing
PPCs because of underlying pulmonary and cardiovascular dysfunctions. In these cases,
J. Pers. Med. 2024, 14, 56 11 of 19

preventive NIV may reduce PPC occurrence by reducing left ventricular preload and after-
load, followed by an improvement of cardiac and respiratory functions [69]. Contradictory
results emerge from studies conducted so far.
In their single randomized trial, Auriant et al. [24] found that NIV after lung resection
decreased the frequency of intubation from 50.0% to 20.8% (p = 0.035) and mortality (13%
vs. 38%; p = 0.045). In contrast with these findings, an RCT aiming to investigate whether
prophylactic postoperative NIV could prevent acute respiratory postoperative conditions in
COPD patients who had undergone lung resection surgery did not find any advantage on
postoperative outcome. The authors found that acute respiratory failure rate was 18.8% in
the prophylactic NIV group and 24.5% in controls (p = 0.20), reintubation rates were similar
in the prophylactic NIV and control group (10/181 (5.5%) and 13/179 (7.2%), respectively,
p = 0.53), and mortality rates were 5 and 2.2% in the control and prophylactic NIV groups,
respectively (p = 0.16) [79].
The Bilevel Positive Airway Pressure Versus Optiflow study [26] was the first large,
multicenter randomized controlled noninferiority trial comparing HFNOT and NIV in
830 patients developing hypoxemia during the spontaneous breathing trial or after extuba-
tion following cardiothoracic surgery. Treatment failure, defined as reintubation, switch to
the other treatment, or premature discontinuation of the assigned treatment, was similar in
both groups (21% for HFNOT and 21.9% for NIV, for the three strategies combined; absolute
risk difference 0.9%, 95% CI −4.9% to 6.6%, p = 0.003), as were reintubations (14% in both
groups). A post hoc analysis showed that there were no differences in the proportion of
patients with treatment failure between HFNOT and NIV when these techniques were
used as a weaning strategy or as a therapeutic strategy (27% for HFNOT vs. 28% for NIV,
p = 0.93). When considering a preventive strategy for high-risk patients, treatment failure
was lower in the HFNOT group than in the NIV group.
Interestingly, a recent network meta-analysis of 16 trials enrolling 3011 patients [80]
found that NIV significantly reduced the incidence of PPCs when compared to standard of
care (RR 0.67, 95% CI: 0.49 to 0.93; absolute risk reduction (ARR) 7.6%, 95% CI: 1.6–11.8%;
low certainty) and the incidence of atelectasis (RR 0.65, 95% CI: 0.45 to 0.93; ARR 19.3%,
95% CI: 3.9–30.4%; moderate certainty); however, prophylactic NIV was not associated with
a decreased reintubation rate or reduced short-term mortality. Further analysis showed
that the highest ranked treatment for reducing the incidence of PPCs was NIV (83.0%),
followed by HFNOT (62.5%), CPAP (44.3%), and standard of care treatment (10.2%).
Due to a restrictive syndrome and decreased chest wall compliance, obese patients are
at higher risk of hypoxemia and PPCs. Increased body mass index is directly correlated
with a loss of functional residual capacity by up to 50% of the preoperative values, with
morbidly obese patients having significantly more atelectasis than nonobese patients,
before induction, after tracheal extubation, and 24 h following laparoscopic surgery [81].
In addition, different comorbidities such as OSA, obesity hypoventilation syndrome, and
cardiovascular and metabolic diseases are to be considered as predisposing factors for
PPCs [12].
The obese patient, with or without OSA, might not respond to supplemental oxygen
administration, being prone to postoperative oxygen desaturation and hypoxic episodes.
Postoperative NIV could, therefore, mitigate the risk of extubation failure and the incidence
of PPCs. However, evidence on the use of NIV after bariatric surgery is still limited.
A recent retrospective analysis evaluated the efficacy of short-term NIV use in reducing
postextubation acute respiratory failure after biliointestinal bypass in obese patients in the
PACU setting. The authors found an improvement of PaO2 (67.91 ± 3.03 vs. 60.14 ± 4.17,
p < 0.001) and SpO2 (93.95 ± 2.09, p < 0.001) values in the NIV group, with usual post-
operative care (oxygen therapy via a Venturi mask) being significantly associated with
postoperative acute respiratory failure (RR 0.51, CI: 0.27 to 0.96, p < 0.05) [82].
Huerta et al. [83] adopted NIV in morbidly obese patients undergoing sleeve gas-
trectomy and open bariatric surgery, demonstrating that NIV increases PaO2 during the
postoperative period (PaO2 : 78.87 ± 8.31 in NIV group vs. 64.27 ± 6.33 in oxygen group).
J. Pers. Med. 2024, 14, 56 12 of 19

In addition, they found that only 15 out of more 1000 patients presented major anastomotic
leaks, with only two cases related to postoperative NIV use.
The perioperative application of NIV in obese patients with positive airway pres-
sure < 20 cmH2 O is rarely a cause of NIV-related anastomotic leakage [84].
According to the meta-analysis conducted by Carron et al. [27], the postoperative
use of NIV among obese patients was associated with a decreased risk of respiratory
complications (RR 0.33, 95% CI: 0.16 to 0.66, p = 0.002) but not of reintubation after tracheal
extubation (RR 0.41, 95% CI: 0.09 to 1.82, p = 0.3657) and unplanned ICU admission (RR 0.43,
95% CI: 0.16 to 1.15, p = 0.0937).

5. Postoperative Use of High-Flow Nasal Oxygen Therapy

The use of HFNOT has been widely studied and adopted after extubation of critically
ill patients [85,86], particularly as a prophylactic measure to reduce the need for respiratory
support escalation [68,87,88]. A series of RCTs evaluated the use of HFNOT with respect to
COT [89] and NIV [90–92] in critically ill patients. Although initial trials demonstrated that
HFNOT prevents reintubation in unselected cohorts of critically ill patients and performs
as well as NIV in high-risk patients [93,94], recent data indicate that prophylactic HFNOT
in all patients does not reduce the reintubation rate if patients treated with COT can receive
a trial of rescue NRS (either HFNOT or NIV) before intubation [89,95]. In high-risk or
obese patients, prophylactic NIV combined with HFNOT performs better than HFNOT
alone [28,41]. This evidence indicates that HFNOT, even if not alternated with NIV, plays a
crucial role in improving weaning outcome. Whether this evidence can be translated to
patients undergoing general anesthesia has to be demonstrated by ongoing investigations.
The use of HFNOT has recently been proposed as part of an enhanced recovery
program after major surgeries in patients at high risk for respiratory complications. This
approach could improve functional recovery and reduce hospital LOS, with potential
implications for reduced healthcare costs [96,97].
The effectiveness of preemptive HFNOT has been studied after cardiothoracic and
abdominal surgery [26,98,99]. While data suggest that preemptive HFNOT can prevent
respiratory support escalation in postcardiac surgery patients, with HFNOT being noninfe-
rior to NIV in hypoxemic patients [26], results in thoracic surgery may vary, likely due to
differing control strategies or patient population [98,100]. In a randomized trial conducted
after lung resection, patients receiving HFNOT showed a lower arterial CO2 and a reduced
risk of postoperative hypercapnia than those treated with a Venturi mask [98]. In a meta-
analysis by Chaudhuri et al. [29], prophylactic HFNOT reduced the rate of reintubation
and respiratory support escalation when compared to COT in the immediate postoperative
period after cardiothoracic surgery, an effect likely driven by patients at high risk and/or
obesity. Positive pressure effect given by HFNOT application reverses atelectasis by increas-
ing end-expiratory lung volume, finally reducing alveolar shunt fraction and enhancing
arterial oxygenation [54,101,102]. Consistently with this, a recent randomized trial [30]
involving patients undergoing major gynecological surgery in the Trendelenburg position
showed that a preemptive two-hour HFNOT session following extubation improved post-
operative oxygenation if compared to conventional Venturi mask oxygen therapy. This was
primarily attributed to a reduction in atelectasis in the dorsal lung regions. Additionally,
a quarter of patients in the HFNOT group received the assigned treatment with no sup-
plemental oxygen, emphasizing that the beneficial effects of HFNOT were mainly due to
high flow rather than supplemental oxygen provision [103,104]. However, HFNOT after
extubation did not reduce the incidence of postoperative hypoxemia nor improved any
other clinical outcome in patients at intermediate-to-high risk of PPCs [99]. The difference
in outcomes between these studies may arise from population characteristics: patients
undergoing laparoscopy in the Trendelenburg position had a higher incidence of postoper-
ative hypoxemia compared to those of the OPERA trial [99], and patients undergoing lung
resection may be at especially high risk of postoperative hypercapnia. Nevertheless, data
J. Pers. Med. 2024, 14, 56 13 of 19

from a recent meta-analysis did not support the routine use of postoperative CPAP, NIV, or
HFNOT to prevent the occurrence of PPCs or pneumonia after surgery in adults [74].
Preemptive HFNOT may provide physiological benefits in specific patient subgroups
but may not have a big impact in terms of patient-centered outcomes [99], especially when
NIV use before reintubation is possible [89,95]. Therefore, preemptive postextubation HFNOT
in surgical patients at low risk of PPCs necessitates a meticulous personalized assessment.

6. Future Perspectives: Artificial Intelligence and Machine Learning

Artificial intelligence and machine learning have the potential to personalize perioper-
ative management and mechanical ventilation strategies for patients needing respiratory
support [105]. Machine-learning models are complex mathematical constructs which
could help the perioperative identification of patients at higher risk for deterioration while
pointing out factors which could be optimized.
Optimization of perioperative respiratory support could be reached with the use of
these models, and future research might focus on these issues in order to curb PPCs in
high-risk patients undergoing major surgery. A recent study [106] validated a machine-
learning model to predict and identify patients at high risk of NIV failure. The timely
assessment of NIV efficacy and subsequent clinical decision are particularly crucial: if a
patient is predicted to have a high risk of NIV failure, strict clinical monitoring could be
provided and earlier reintubation considered, thus reducing mortality.
Several studies on critically ill patients have shown that machine-learning models may
accurately predict extubation failure with remarkable accuracy [107] and identify patients
in whom duration of mechanical ventilation might be longer [108]. However, there is a
substantial paucity of data regarding the application of these tools in subjects undergoing
general anesthesia. Therefore, development of new algorithms should be promoted to
improve confidence and translate these approaches to everyday clinical practice.
Genomic data are increasingly applied in medicine, and the most difficult challenge to
overcome is the huge amount of data generated and the difficulties related to translating
these findings to clinical practice. With special reference to mechanical ventilation, there is
no doubt that it has a direct impact on patients’ lung physiology. While ventilator-induced
lung injury has been extensively explored, only a few experimental studies report that
vigorous breathing effort during spontaneous ventilation can worsen lung injury and cause
a phenomenon that has been termed patient self-inflicted lung injury [109]. The genetic
determinants for these respiratory complications are unknown. However, the identification
of novel therapeutic targets and the optimal NRS to apply is essential for progress in the
understanding of these respiratory complications and for limiting their occurrence.

7. Conclusions
This narrative review revise much of the existing evidence on perioperative NRS use,
reporting the most influential studies on the topic. What emerges is that personalized
medicine is progressively shaping anesthesia practice and perioperative medicine, also
for NRS. The evidence gathered so far brings profound implications for current clinical
practice and should promote a careful reappraisal of guidelines on the perioperative use of
NRS, especially when high-risk patients are considered.
Use of NRS should be tailored based on the patient’s specific characteristics and type
of surgery, aiming at a personalized cost-effective approach.

Author Contributions: G.M.: conceptualization, methodology, resources, writing—original draft,

writing—review and editing; L.F.: methodology, writing—original draft, writing—review and editing,
resources, supervision, project administration; R.S.: methodology, resources, writing—original draft,
visualization; T.R.: writing—original draft, writing—review and editing; D.L.G.: writing—original
draft, resources; A.P.: writing—original draft, resources; E.D.R.: conceptualization, writing—review
and editing, supervision; C.G.: conceptualization, writing—review and editing, supervision, project
administration; G.M. and L.F. equally contributed as first authors. All the authors approved the
submitted version and agree to be personally accountable for their own contributions and for ensuring
J. Pers. Med. 2024, 14, 56 14 of 19

that questions related to the accuracy or integrity of any part of the work, even ones in which the
author was not personally involved, are appropriately investigated, resolved, and documented in the
literature. All authors have read and agreed to the published version of the manuscript.
Funding: This research was supported by Fisher & Paykel Healthcare (Auckland, New Zealand).
Institutional Review Board Statement: Not applicable.
Informed Consent Statement: Not applicable.
Data Availability Statement: Not applicable.
Conflicts of Interest: Giovanni Misseri declares a patent in association with the University of Palermo,
Italy (No 102019000020532, Italian Ministry of Economic Development); Luciano Frassanito received
honoraria from Edwards Lifesciences Ltd. for scientific advice; Domenico Luca Grieco received
honoraria from GE Healthcare, Intersurgical, Fisher&Paykel, Gilead, and Pfizer for lectures, and
discloses research grants by GE Healthcare and Fisher&Paykel. Cesare Gregoretti received honoraria
for lectures or consultancies from Vivisol, Philips, Mindray, and Air Liquid, and declares a patent in
association with the University of Palermo, Italy (No 102019000020532, Italian Ministry of Economic
Development). Edoardo De Robertis received honoraria from Drager, GE, Baxter, MSD, Fresenius,
and Fisher&Paykel for lectures or consultancies. All the other authors declare no conflicts of interest.
All other authors declare no conflict of interest.

Abbreviations
ARF acute respiratory failure
ARISCAT (score) Assess Respiratory Risk in Surgical Patients in Catalonia (score)
ARR absolute risk reduction
CI confidence interval
CO2 carbon dioxide
COPD chronic obstructive pulmonary disease
COT conventional oxygen therapy
CPAP continuous positive airway pressure
GA general anesthesia
HDU high-dependency care unit
HFNOT high-flow nasal oxygen therapy
ICU intensive care unit
LOS length of stay
NIV noninvasive ventilation
NRS noninvasive respiratory support
OR odds ratio
OSA obstructive sleep apnea
PACU postanesthesia care unit
PaO2 arterial partial pressure of oxygen
PPCs postoperative pulmonary complications
RCT randomized controlled trial
RM recruitment maneuver
RR risk ratio
THRIVE transnasal humidified rapid-insufflation ventilatory exchange

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