[ Critical Care How I Do It ]

Setting and Titrating Positive

End-Expiratory Pressure
Scott J. Millington, MD; Pierre Cardinal, MD; and Laurent Brochard, MD

Although maintaining some amount of positive end-expiratory pressure (PEEP) seems essen-
tial, selecting and titrating a specific level for patients with ARDS remains challenging despite
extensive research on the subject. Although an “open lung” approach to ventilation is popular
and has some degree of biological plausibility, it is not without risk. Furthermore, there is no
clear evidence-based guidance regarding initial PEEP settings or how to titrate them early in the
course of the illness. Many busy clinicians use a “one-size-fits-all” approach based on local
medical culture, but an individualized approach has the potential to offer significant benefit.
Here we present a pragmatic approach based on simple measurements available on all venti-
lators, focused on achieving balance between the potential risks and benefits of PEEP.
Acknowledging “best PEEP” as an impossible goal, we aim for a straightforward method to
achieve “better PEEP.” CHEST 2022; 161(6):1566-1575

KEY WORDS: ARDS; critical care; mechanical ventilation

The application of positive end-expiratory Although this pragmatic approach is

pressure (PEEP) was first described in the
1930s1,2 and came into common use for
treating ARDS in the 1960s.3 In the
intervening 50 years, a clear consensus
around how to manage PEEP in general, and
for patients with ARDS specifically, has
remained elusive.4 The current article offers
an approach to selecting an initial PEEP
value and to titrating it over the initial period
of the acute illness for patients with ARDS.
Rather than aiming for “best PEEP,” an
illusory and impossible-to-achieve goal, we
focus on “better PEEP” using a simple
stepwise approach centered around easy-to-
measure variables and focused on both the
potential benefits and harms of PEEP.
necessarily an oversimplification of an
extremely complicated topic, it should
be viewed through the lens of harm
reduction: in many cases, PEEP levels are
set, due to lack of time or experience, at an
arbitrary level based on local habit and
medical culture. This “one-size-fits-all”
approach can be made better via a
straightforward approach that offers some
patient-specific adjustments. Although this
method is based on evidence where
available, it places special emphasis on
practicality. A protocol requiring unusual
equipment or a significant investment in
time will simply be left by the wayside in a
busy real-world ICU. The opinions

ABBREVIATIONS: ACP = acute cor pulmonale; DP = driving pressure;
EIT = electrical impedance tomography; PEEP = positive end-
expiratory pressure; Pes = esophageal pressure; POCUS = point-of-
care ultrasound; Pplat = plateau pressure; RII = recruitment-to-inflation
index; RV = right ventricular; TPP = transpulmonary pressure; Vrec =
volume of lung recruited; VT = tidal volume
AFFILIATIONS: From the University of Ottawa/The Ottawa Hospital
(S. J. Millington and P. Cardinal), Ottawa, ON, Canada; Keenan
Research Centre, Li Ka Shing Knowledge Institute (L. Brochard), St.
Michael’s Hospital, Unity Health Toronto, Toronto, ON, Canada; and
the Interdepartmental Division of Critical Care Medicine (L. Bro-
chard), University of Toronto, Toronto, ON, Canada.
CORRESPONDENCE TO: Scott J. Millington, MD; email: smillington@
toh.ca
Copyright Ó 2022 American College of Chest Physicians. Published by
Elsevier Inc. All rights reserved.
DOI: https://doi.org/10.1016/j.chest.2022.01.052

1566 How I Do It [ 161#6 CHEST JUNE 2022 ]

expressed here are those of the authors, and other
equally valid approaches exist.
Case Example
A 60-year-old man with type 2 diabetes, hypertension,
and obesity is transferred to the ICU with severe
hypoxemia in the context of a worsening community-
acquired pneumonia and is intubated shortly thereafter.
Ten minutes’ postintubation, his PaO2 is 80 mm Hg on
an FIO2 of 0.7, with a PEEP level set at 8 cm H2O. He is
placed on volume control ventilation with a tidal volume
(VT) of 400 mL (6 mL/kg predicted body weight). With
the patient still under the effects of neuromuscular
blockade from the induction of anesthesia, a plateau
pressure (Pplat) of 28 cm H2O is measured, yielding a
static lung compliance of 20 mL/cm H₂O. His oxygen
saturation level is 94%. His BP drops after intubation,
requiring an infusion of norepinephrine (0.2 mg/kg per
minute). He has evidence of end-organ dysfunction,
including a lactate level of 4.0 mM/L and a creatinine
level of 225 mM/L. Should his level of PEEP be adjusted?
Basic Principles
A full review of the complex pulmonary physiology
affecting patients with ARDS is beyond the scope of the
current article, but two approaches to mechanical
ventilation are worth considering briefly. Protective lung
ventilation5 uses low VT (typically 4-6 mL/kg based on
predicted body weight, reflecting lung size at baseline) to
reduce ventilator-induced lung injury by decreasing
volutrauma (hyperinflation-induced shear injury),
barotrauma (alveolar rupture and potential
pneumothorax), biotrauma (the release of inflammatory
mediators secondary to both processes), and even
atelectrauma (the theoretical shear stress induced by the
cyclical collapse and re-opening of alveoli6). The Pplat is
typically kept strictly below 30 cm H2O,7 and permissive
hypercapnia is often allowed. This approach is
considered the standard of care for patients with ARDS,
but there is good evidence to suggest that it is frequently
not applied.8 Data suggest that lower tidal volumes may
be of more benefit to patients with reduced lung
compliance, which is of particular interest in the era of
COVID-19.9,10
The open lung concept, first described 30 years ago,11
was initially a proposal to use recruitment maneuvers
followed by higher PEEP levels to reduce atelectrauma.
An open lung approach should always be combined with
a protective lung ventilation strategy, but unfortunately
there is no agreed upon method to determine ideal PEEP
chestjournal.org
and no consensus as to the role of recruitment
maneuvers. Higher PEEP levels have been compared
with lower values in several studies12-14; some secondary
outcome improvements have been reported, but a
mortality benefit remains elusive. Such studies are
difficult to interpret for several reasons, including
patient heterogeneity with respect to the amount of
recruitable lung. Some patients may recruit additional
lung with higher PEEP and benefit from an open lung
strategy, whereas others may not recruit and thereafter
be harmed by higher volumes and pressures. Other
publications showing benefit are difficult to apply at the
bedside as they generally use experimental models of
lung injury with highly recruitable lungs,15 different
from the physiology often seen in patients with ARDS.
Great uncertainty remains with respect to choosing a
PEEP value, and safety concerns around “aggressive”
recruitment maneuvers persist.13
Step 1: Pick a Starting PEEP
Deliberations around ideal PEEP levels must begin with
a starting value. Two straightforward options exist here,
with the priority being to select a safe level in the
immediate postintubation period. The first method,
perhaps best named the “Gattinoni” method,16 is the
simpler of the two. Using a standard Berlin definition of
severity, patients with ARDS and a PaO2/FIO2 ratio of
200 to 300 would be classified as mild, 100 to 200 as
moderate, and < 100 as severe. Initial PEEP values
would then be set as follows: 5 to 10 cm H2O for mild,
10 to 15 cm H2O for moderate, and 15 to 20 cm H2O
for severe. We suggest favoring the lower of the two
values in most cases as the initial setting, given that
hemodynamic concerns often predominate immediately
after intubation.
Alternatively, a starting PEEP can be selected using the
well-known titration table from the Acute Respiratory
Distress Syndrome Clinical Network (ARDSNet) trial17;
this widely known resource is designed for titrating
PEEP later in the course of illness, but here it can be
borrowed to aid in selecting a starting value. In selecting
between the low-PEEP and high-PEEP options, we
suggest starting with the low-PEEP table in anticipation
of postintubation hypotension. Using this method, a
patient requiring an FIO2 of 0.5 (either preintubation or
immediately postintubation) would be started on either
8 or 10 cm H2O of PEEP. Of note, both methods often
yield similar starting values, but the Gattinoni method is
easier and avoids the ultra-high PEEP recommendations
(as high as 24 cm H2O) that the ARDSNet table can
1567
recommend if the FIO2 is 1. High levels of PEEP, as a rule
of thumb, should be reserved for patients with diffuse
involvement (three or four quadrants on chest
radiograph or CT imaging) or morbid obesity.18,19
Step 2: Think About Potential Harms of PEEP
Excessive PEEP can be harmful, with two main
problems to consider. It is well known for causing
hypotension; higher PEEP levels result in increased
intrathoracic pressure, thereafter increasing right atrial
pressure and decreasing venous return. Excessive PEEP
also compresses intra-alveolar vessels and increases
pulmonary vascular resistance, potentially resulting in
right ventricular (RV) dysfunction. Here, the net effect is
a decrease in left ventricular preload and thereafter
cardiac output. However, a “minimal” PEEP is also
important because extensive lung collapse with
insufficient PEEP can cause high pulmonary vascular
resistance and RV dysfunction.20 Although the precise
relationship between lung volume and pulmonary
vascular resistance is difficult to ascertain a priori,
ventilation:perfusion matching is an important and
challenging aspect of PEEP selection, and a parallel
assessment of hemodynamic and ventilator effects is
always warranted.
Assessing the harmful hemodynamic effects of PEEP can
be done in several ways, with the most straightforward
being a simple assessment of BP. If the patient is
hypotensive, and especially if they show evidence of end-
organ dysfunction, then consideration should be given
to lowering PEEP. This is particularly important if the
starting PEEP level was high, or if hypovolemia, chronic
RV dysfunction, or pulmonary hypertension is
suspected. In its most straightforward application, this
can be achieved by lowering PEEP, waiting 5 to 10 min,
and reassessing BP.
A more precise but labor-intensive approach involves
assessing RV function via point-of-care ultrasound
(POCUS) (Fig 1). The phenomenon in which high PEEP
results in RV dysfunction in the context of ARDS is
known as acute cor pulmonale (ACP); this process is
often mitigated by keeping Pplat below 28 cm H2O21 and
driving pressure (DP) below 15 cm H2O22 (see Step 3:
Think About Benefits of Higher PEEP for a full
discussion regarding DP).
A detailed review of echocardiographic RV assessment is
beyond the scope of the current paper and is covered in
detail elsewhere.23 A basic POCUS RV examination is
achievable with modest training and can be performed
1568 How I Do It
via a transthoracic or transesophageal approach.
Assessing RV size and function is quickly done,
reproducible, and repeatable. In the context of shock or
hypotension, the right ventricle is assessed, the PEEP
level is lowered (perhaps by as much as 5 cm H2O to
make ultrasound changes easier to discern), and the
POCUS examination is then repeated. Improvements in
RV size or function with lower PEEP levels, especially if
the BP also improves, suggest the presence of ACP and
may motivate the adoption of a lower PEEP level.
Although remaining mindful of the risks of excessive
PEEP, it is also important to remember that insufficient
PEEP may result in enough de-recruitment to place the
right ventricle at risk of circulatory failure.24
The second potential harm of higher PEEP to consider
involves alveolar overdistention and the resultant risk of
volutrauma and barotrauma. This risk is more
pronounced in patients with less recruitable lung, and
there is no clearly agreed upon method or evidence for
determining the best PEEP to reduce such trauma. One
pragmatic method to screen for potential overdistention
involves using best DP measurements, which are
described in detail in Step 3. Here, DP is used as a
surrogate for compliance; better (lower) DP with a
reduction in PEEP suggests that overdistention may
indeed have been present. Targets to consider include
keeping Pplat < 30 cm H2O (or perhaps 28 cm H2O to
avoid ACP21) and DP roughly below 15 cm H2O.25
Targeting a lower dead space may also reduce the risk of
excessive lung distension induced by PEEP. Although
the precise measurement of dead space requires
specialized equipment, the effect of PEEP on PaCO2
levels is a reasonable surrogate, provided that other
ventilator settings (eg, VT and respiratory rate) are not
altered at the same time. An increase in PaCO2 of 5% to
10% (or more) following an increase in PEEP suggests
hyperinflation, although this effect can be exacerbated
by hypovolemia.
Step 3: Think About Benefits of Higher PEEP
Having made efforts to minimize its deleterious effects,
PEEP can thereafter be adjusted to optimize oxygenation
and reduce atelectrauma. One mechanism by which
higher PEEP improves oxygenation is alveolar
recruitment; keeping open previously collapsed (but
perfused) lung regions increases the available surface
area for gas exchange and diminishes intrapulmonary
shunt.
Unfortunately, better oxygenation (as assessed either by
improved oxygen saturation levels or a higher PaO2/FIO2
[ 161#6 CHEST JUNE 2022 ]
Figure 1 – A-D, Assessment of the right ventricle (RV) using transthoracic echocardiography. A, Normal parasternal short-axis view, with a normally
sized RV (*) and normally positioned interventricular septum (#). B, Normal apical four-chamber view, with a normally sized RV (*). C, Parasternal
short-axis view showing a severely dilated RV (*) and displaced interventricular septum (#). D, Apical four-chamber view showing a severely dilated RV
(*) and right atrium (#).

ratio) with higher PEEP does not necessarily translate
into improved oxygen delivery. PEEP can improve
arterial oxygenation yet decrease oxygen delivery by
reducing cardiac output26; lower cardiac output
preferentially reduces perfusion to nonventilated or very
poorly ventilated alveoli, thereby decreasing
intrapulmonary shunt.26 As such, improvements in
oxygenation are difficult to definitively interpret unless
reliable measurements of cardiac output are taken at the
same time. One must also remember that roughly
20% of patients have a patent foramen ovale, in which
case differences in oxygenation may reflect changes in
the degree of intracardiac shunting rather than changes
in lung recruitment.27 It is reasonable to use the severity
of hypoxemia as a parameter to help select the initial
PEEP (as described in Step 1) and to be cautiously
optimistic when oxygenation improves with higher
PEEP, understanding that PEEP titration may be further
refined using other parameters.
The second theoretical benefit of more PEEP involves a
reduction in atelectrauma. This is another longer term
and more theoretical benefit, but there is some suggestion
that it may be particularly important for patients with
severe ARDS.18 Although there is no clearly agreed-upon
method for determining the best PEEP to reduce
atelectrauma, a stepwise down-titration approach,28 in
which PEEP levels are first raised to a relatively high level
(eg, 10 cm H2O above the initial setting) and then slowly
decreased, is appealing primarily due to its sound
physiological rationale. The hysteresis (difference
between the inflation and deflation limbs) observed in the
classic pressure-volume curve (Figs 2A, 2B) reflects
differences between opening and closing pressures of
individual lung units. As such, higher PEEP can be
thought of as a force used to prevent airway closure and
de-recruitment of already opened alveolar units; the
purpose of the subsequent stepwise down-titration is to
select the lowest PEEP level that maintains recruitment.
To guide PEEP selection, we suggest calculating the DP
at different PEEP levels (Fig 2C), keeping in mind
several important caveats described here. Assuming the
VT is not changed between measurements at different

chestjournal.org 1569
Figure 2 – A, Mechanical ventilation waveforms A
showing (from top to bottom) flow, Paw, Pes, and PL

Flow (L/s)
vs time. The third breath is obtained by reducing 1.0
inspiratory flow to < 10 L/min. The abrupt change 0.5
in slope of the Paw waveform is AOP, the pressure 0.0
required to reopen the airways. Initially, when Paw is −0.5
lower than the AOP, the inspiratory airflow pres-
−1.0

PL (cm H2O) Pes (cm H2O) Paw (cm H2O)

surizes the ventilator circuit but does not increase
lung volume. The lungs begin to inflate once the Paw 40
increases above AOP (third breath); the slope of the AOP
30
pressure-time curve observed beyond AOP reflects the
compliance of the respiratory system. B, A pressure/ 20
volume ventilator waveform showing hysteresis; the 10
LIP is shown, but this is more likely to reflect AOP
(the minimal pressure needed to reopen the airways 28
or keep them open, as opposed to the optimal level for 24
lung recruitment as is classically taught). C, Simu-
lated ventilator waveform showing the effect of an 20
inspiratory hold (*) on Paw (large arrow); driving
16
pressure (#) can be calculated as plateau pressure
20
(small arrow) minus positive end-expiratory pressure
(dashed arrow). Adding an inspiratory pause of 0.2 s 10
following every breath allows for continuous moni- 0
toring of plateau and driving pressures. AOP ¼ −10
airway opening pressure; LIP ¼ lower infection −20
point; Paw ¼ airway pressure; Pes ¼ esophageal
pressure; PL ¼ transpulmonary pressure. 0 20 25 30 35 40 45 50 55
Time (s)
B
Volume

LIP / AOP

0 5 10 15 20 25 30
Pressure

PEEP levels (and that there is no intrinsic PEEP), short (0.2 or 0.3 s) pause to the end of each breath to
changes in DP can only be explained by changes in continuously monitor Pplat.
compliance:
The formula for DP is [DP ¼ Pplat – PEEP], and
VT therefore the compliance equation can be simplified to:
Compliance ¼
Pplat  PEEP
VT
Compliance ¼
DP
Both VT and PEEP are known values. Pplat is measured
by performing an end-inspiratory pause, which can be Finally, with VT, a known and stable value (especially
either be done as a manual maneuver or by adding a if a volume-controlled mode of ventilation is

1570 How I Do It [ 161#6 CHEST JUNE 2022 ]

 C
Pressure
Flow
Volume
Figure 2 – (Continued).
selected), the equation can be rearranged as:
1
DP f
Compliance
Therefore, a lower DP value indicates better respiratory
system compliance. If DP decreases at a higher level of
PEEP, the trial of higher PEEP is considered successful,
especially in light of improved oxygenation and absent
hemodynamic deterioration. If DP does not change,
optimal compliance has potentially been achieved. If DP
increases, then compliance has worsened, possibly
indicating over-distension (as discussed in Step 2
earlier), and consideration should be given to lowering
PEEP. In simple terms, PEEP is adjusted to achieve the
lowest DP possible, keeping in mind other important
targets such as oxygenation and hemodynamics.
Patients with obesity and with ARDS merit special
consideration given the extra weight applied to their
lungs, which tends to create or worsen atelectasis,
especially in the supine position and under anesthesia.
Higher PEEP levels may be needed to counter the effect
of this imposed load. Accepting a higher than usual Pplat
level for patients with obesity may be necessary and is
safe insofar as it does not automatically reflect lung
overdistention. A linear relationship between high BMI
and end-expiratory esophageal pressure (Pes) has been
described29 for patients with ARDS (Pes, described in
chestjournal.org
*
detail in Step 4, serves to estimate pleural pressure). The
relationship suggests that intrathoracic pressure
increases by approximately 2.5 cm H2O for every
10 kg/m2 of BMI beyond 30 kg/m2. Although this has
not been prospectively validated, this formula might
serve as a quick guide to the amount of extra PEEP
needed or the additional pressure acceptable for patients
with obesity. Similar accommodation for higher
pressures may need to be made in other special
circumstances such as abdominal compartment
syndrome or major chest wall deformities, but here,
evidence-based guidance is unavailable.
Prone positioning, although increasingly popular,
presents an additional challenge for PEEP titration. In
the supine position, PEEP is set essentially as a
compromise between the necessary pressure to recruit
the dependent (and recruitable) part of the lung, without
overly distending the nondependent (nonrecruitable)
part. Interestingly, in the prone position, these two
elements are much more homogeneous, and their
response to PEEP is less influenced by gravity.30 This
suggests that an optimal PEEP level in terms of risk/
benefit is present over a much larger range in the prone
position. Therefore, when switching to a prone position,
the PEEP level can most likely be left unchanged, or
perhaps decreased slightly due to the additional
recruitment offered by prone positioning.
1571
 1

Flow (L/s)
0

−1

30
Paw (cm H2O)

20

10

PEEP 5 PEEP 10 PEEP 15

Pressure

PEEP 15 cm H2O Plateau

Δ10 cm H2O
PEEP 5 cm H2O
Flow

Set VT Exhaled VT
Volume

VT released Predicted exhaled VT

Exhaled VT recruitment

Time

Figure 3 – Top: Flow vs time (top) and pressure vs time (bottom) curves obtained on volume-assist control ventilation with constant inspiratory flow at
different levels of PEEP. A convex ascending limb (dotted arrow, PEEP 5) may indicate recruitment of alveolar units during inspiration (suggesting
insufficient PEEP), whereas a concave ascending limb (dotted arrow, PEEP 15) may indicate overdistension (suggesting excessive PEEP). Modified from:
Henderson WR, Chen L, Amato MBP, Brochard LJ. Fifty years of research in ARDS. Respiratory mechanics in acute respiratory distress syndrome. Am
J Respir Crit Care Med. 2017;196(7):822-833. Bottom: Ventilator curves illustrating the calculation of the recruitment-to-inflation index. The exhaled
VT (red arrow) is measured at higher PEEP, and then the PEEP level is suddenly dropped (in this case by 10 cm H2O), and the total released VT is
displayed by the ventilator at the end of exhalation. The predicted exhaled VT (blue arrow) is based on the compliance at low PEEP multiplied by delta
PEEP, and the recruited volume (or exhaled VT recruitment trapped by PEEP; green arrow) is measured after subtracting the inspired VT. The recruited
volume is then divided by the change in PEEP (here 10 cm H2O) to yield the compliance of the recruited lung. Finally, the compliance of the recruited
lung is indexed to the compliance at the lower PEEP level to yield the recruitment-to-inflation index. These calculations are facilitated by the use of an
online calculator (see https://rtmaven.com). PEEP ¼ positive end-expiratory pressure; VT ¼ tidal volume.

1572 How I Do It [ 161#6 CHEST JUNE 2022 ]

Caveats in Using Compliance or DP for PEEP
Titration
There are limits when using DP to titrate PEEP levels.
Compliance (and DP) can be paradoxically improved by
intra-tidal recruitment-derecruitment (the lung opening
and closing that occurs within each breath31), and which
can confound interpretation. Therefore, concluding that
there is harmful overdistention or derecruitment should
be reserved for situations in which different PEEP levels
produce clear and significant changes in DP.
Overdistention may also be assessed by examining the
shape of the pressure curve during volume-controlled
ventilation; an upward concavity of the pressure-time
curve suggests a significant drop in compliance (Fig 3).32
In addition, overall respiratory system compliance
comprises contributions from both the lungs and chest
wall, and, therefore, changes in measured compliance
may reflect changes at the level of the chest wall and
not necessarily the lungs. Both recruitment (which
increases compliance) and overdistention (which
decreases compliance) may occur in different parts of
the lungs simultaneously when PEEP is increased.
Therefore, the overall compliance of the system may
not change (or it may even increase), whereas some
areas of the lungs, especially in nondependent areas,
are being overdistended30; this problem is not unique
to DP and indeed exists for all methods for setting
PEEP. Finally, it is unclear how often measurements,
DP or otherwise, should be taken and how often PEEP
should be re-assessed. Repeated measurements are
limited by the need to have the patient deeply sedated
and/or paralyzed, although a technique to measure DP
during spontaneous modes of ventilation has been
described.33
Step 4: Consider More Advanced Options
Some centers may have specific advanced equipment
available, and some clinicians may have a particular
expertise that allows consideration of other techniques.
Evidence in general is lacking, but each has interesting
potential advantages.
Esophageal balloon manometry is a minimally invasive
technique whereby Pes, measured via a modified
nasogastric tube, is used as a surrogate for pleural
pressure. Transpulmonary pressure (TPP), the net
distending pressure exerted on the alveoli, is then
estimated using [TPP ¼ Pplat – Pes]; PEEP can thereafter
be adjusted to achieve a specific TPP. Although this
technique is straightforwardly performed, it is subject to
chestjournal.org
various artifacts and assumptions, and evidence of
benefit has not been shown.34 It seems to be of particular
interest for patients with morbid obesity and with
ARDS, for reducing ventilator dyssynchrony, and in
patients with moderately severe disease.35
Electrical impedance tomography (EIT) is based on the
distinct impedance of gas vs various types of tissues,
with impedance defined as the inverse of conductivity.
Increasing the quantity of air in the lungs, for example,
increases impedance. EIT creates a distribution map
suggesting zones of collapse, normal aeration, and
overdistention. PEEP can thereafter be titrated to
achieve the highest electrical impedance in the
thorax, suggesting the greatest amount of aerated lung.
EIT can also suggest the presence of predominant
hyperinflation and be an incentive to reduce PEEP.36
This tool is not widely available and merits more
extensive study.
The recruitment-to-inflation index (RII) is a novel
bedside technique that seeks to estimate, in one breath,
the volume of lung recruited (Vrec) when moving
abruptly from higher to lower PEEP levels (Fig 3). The
compliance of that recruited lung can then be calculated
and indexed to the compliance measured at the lower
PEEP level (estimating the compliance of the “baby
lung”), yielding the RII. Lower RII values suggest a lack
of recruitability and raise concerns that most of the
“extra” pressure applied at higher PEEP will serve
primarily to over-distend normal lung segments instead
of recruiting previously collapsed ones. This technique
does not require specialized equipment and is easily
performed (see video on https://rtmaven.com).
However, it lacks supporting patient outcome data thus
far (although a randomized controlled trial is
ongoing37), and, although it identifies potential
recruitability, it is less able to identify a specific target
PEEP level.
There are other approaches to PEEP that are well
described but may have a different effect than initially
proposed. For example, setting the PEEP to a level
slightly above the lower inflection point of the pressure-
volume curve is a well-known technique described in
every critical care textbook. In reality, beyond being
difficult to accurately identify, for most cases, this low
inflection point represents a somewhat recently
rediscovered phenomenon known as airway opening
pressure (Fig 2A),38,39 which signifies the minimal value
required to open the airway rather than the optimal
PEEP. It can be measured by a pressure-time curve when
1573
insufflating the lung at a low flow rate (see video on
https://rtmaven.com).
Finally, very informative studies have used sequential
CT scans to determine a PEEP at which the greatest
volume of lung is recruited. Although CT scans are an
excellent research tool, transporting critically ill patients
to the radiology department is impractical, and
computation of lung recruitment is complex.
Conclusions
Finding the “best” PEEP for a patient with ARDS is
impossible with current technology, and the path to
“better” PEEP is far from straightforward. We present a
pragmatic protocol with three main principles: (1)
choose a safe starting PEEP; (2) consider the harms of
higher PEEP, specifically hemodynamic compromise
and overdistention; and (3) consider the benefits of
higher PEEP, specifically better oxygenation and less
atelectrauma (when the lung is indeed recruitable). Our
approach will be correctly criticized as a dramatic
oversimplification but should be viewed through a lens
of harm reduction in considering the number of patients
with ARDS who currently receive a blind PEEP
prescription with no attempt at individualization. Here,
the imperfect should be embraced: “Give them the third
best to go on with; the second best comes too late, the
best never comes.”
Acknowledgments
Financial/nonfinancial disclosures: None declared.
References
1. Poulton EP, Oxon DM. Left-sided heart failure with pulmonary
edema: its treatment with the “pulmonary plus pressure machine.”.
Lancet. 1936;228(5904):981-983.
2. Barach AL, Martin J, Eckman M. Positive pressure respiration and
its application to the treatment of acute pulmonary edema. Ann
Intern Med. 1938;12(6):754-795.
3. Ashbaugh D, Bigelow DB, Petty T, Levine B. Acute respiratory
distress in adults. Lancet. 1967;290(7511):319-323.
4. Papazian L, Aubron C, Brochard L. Formal guidelines: management
of acute respiratory distress syndrome. Ann Intensive Care.
2019;9(1):1-18.
5. Laffey JG, Kavanagh BP. Ventilation with lower tidal volumes as
compared with traditional tidal volumes for acute lung injury.
N Engl J Med. 2000;343(11):812.
6. Slutsky AS. Lung injury caused by mechanical ventilation. Chest.
1999;116(1):9S-15S.
7. Villar J, Martín-Rodríguez C, Domínguez-Berrot AM, et al.
A quantile analysis of plateau and driving pressures: effects on
mortality in patients with acute respiratory distress syndrome
receiving lung-protective ventilation. Crit Care Med. 2017;45(5):843-
850.
8. Qadir N, Bartz RR, Cooter ML. Variation in early management
practices in moderate-to-severe ARDS in the United States: the
Severe ARDS: Generating Evidence Study. Chest. 2021;160(4):1304-
1315.
1574 How I Do It
9. Goligher EC, Costa ELV, Yarnell CJ, et al. Effect of lowering Vt on
mortality in acute respiratory distress syndrome varies with
respiratory system elastance. Am J Respir Crit Care Med.
2021;203(11):1378-1385.
10. Marini JJ, Gattinoni L. Management of COVID-19 respiratory
distress. JAMA. 2020;323(22):2329-2330.
11. Lachmann B. Open up the lung and keep the lung open. Intensive
Care Med. 1992;18(6):319-321.
12. Kacmarek RM, Villar J, Sulemanji D. Open lung approach for the
acute respiratory distress syndrome: a pilot, randomized controlled
trial. Crit Care Med. 2016;44(1):32-42.
13. Cavalcanti AB, Suzumura EA, Laranjeira LN. Effect of lung
recruitment and titrated positive end-expiratory pressure (PEEP)
vs low PEEP on mortality in patients with acute respiratory distress
syndrome: a randomized clinical trial. JAMA. 2017;318(14):1335-
1345.
14. Hodgson CL, Cooper DJ, Arabi Y, et al. Maximal recruitment open
lung ventilation in acute respiratory distress syndrome (PHARLAP).
A phase II, multicenter randomized controlled clinical trial. Am J
Respir Crit Care Med. 2019;200(11):1363-1372.
15. van Kaam AH, Haitsma JJ, De Jaegere A. Open lung ventilation
improves gas exchange and attenuates secondary lung injury in a
piglet model of meconium aspiration. Crit Care Med. 2004;32(2):
443-449.
16. Gattinoni L, Carlesso E, Cressoni M. Selecting the ‘right’ positive
end-expiratory pressure level. Curr Opinion Crit Care. 2015;21(1):
50-57.
17. Acure Respiratory Distress Syndrome Network, Brower RG,
Matthay MA, et al. Ventilation with lower tidal volumes as
compared with traditional tidal volumes for acute lung injury and
the acute respiratory distress syndrome. N Engl J Med. 2000;342(18):
1301-1308.
18. Constantin JM, Jabaudon M, Lefrant JY. Personalised mechanical
ventilation tailored to lung morphology versus low positive end-
expiratory pressure for patients with acute respiratory distress
syndrome in France (the LIVE study): a multicentre, single-blind,
randomised controlled trial. Lancet Respir Med. 2019;7(10):870-880.
19. De Santis Santiago R, Teggia Droghi M, Fumagalli J. High pleural
pressure prevents alveolar overdistension and hemodynamic
collapse in ARDS with class III obesity. Am J Respir Crit Care Med.
2020;203(5):575-584.
20. Duggan M, McCaul CL, McNamara PJ. Atelectasis causes vascular
leak and lethal right ventricular failure in uninjured rat lungs. Am J
Respir Crit Care Med. 2003;167(12):1633-1640.
21. Jardin F, Vieillard-Baron A. Is there a safe plateau pressure in
ARDS? The right heart only knows. Intensive Care Med. 2007;33(3):
444-447.
22. Mekontso Dessap A, Boissier F, Charron C. Acute cor pulmonale
during protective ventilation for acute respiratory distress syndrome:
prevalence, predictors, and clinical impac. Intensive Care Med.
2016;42(5):862-870.
23. Vieillard-Baron A, Prin S, Chergui K, Dubourg O, Jardin F. Echo-
Doppler demonstration of acute cor pulmonale at the bedside in the
medical intensive care unit. Am J Respir Crit Care Med.
2002;166(10):1310-1319.
24. Katira BH, Giesinger RE, Engelberts D. Adverse heart-lung
interactions in ventilator-induced lung injury. Am J Respir Crit Care
Med. 2017;196(11):1411-1421.
25. Amato MB, Meade MO, Slutsky AS, et al. Driving pressure and
survival in the acute respiratory distress syndrome. N Engl J Med.
2015;372(8):747-755.
26. Dantzker DR, Lynch JP, Weg JG. Depression of cardiac output is a
mechanism of shunt reduction in the therapy of acute respiratory
failure. Chest. 1980;77(5):636-642.
27. Mekontso Dessap A, Boissier F, Leon R, Carreira S, Campo FR,
Lemaire F, Brochard L. Prevalence and prognosis of shunting across
patent foramen ovale during acute respiratory distress syndrome.
Crit Care Med. 2010;38(9):1786-1792.
[ 161#6 CHEST JUNE 2022 ]
28. Hickling KG. Best compliance during a decremental, but not
incremental, positive end-expiratory pressure trial is related to open-
lung positive end-expiratory pressure: a mathematical model of
acute respiratory distress syndrome lungs. Am J Respir Crit Care
Med. 2001;163(1):69-78.
29. Coudroy R, Vimpere D, Aissaoui N. Prevalence of complete airway
closure according to body mass index in acute respiratory distress
syndrome. Anesthesiology. 2020;133(4):867-878.
30. Katira BH, Osada K, Engelberts D. Positive end-expiratory pressure,
pleural pressure, and regional compliance during pronation: an
experimental study. Am J Respir Crit Care Med. 2021;203(10):1266-
1274.
31. Jonson B, Richard JC, Straus C, Mancebo J, Lemaire F, Brochard L.
Pressure-volume curves and compliance in acute lung injury:
evidence of recruitment above the lower inflection point. Am J Respir
Crit Care Med. 1999;159(4):1172-1178.
32. Ranieri VM, Zhang H, Mascia L. Pressure-time curve predicts
minimally injurious ventilatory strategy in an isolated rat lung
model. Anesthesiology. 2000;93(5):1320-1328.
33. Bellani G, Grassi A, Sosio S. Driving pressure is associated with
outcome during assisted ventilation in acute respiratory distress
syndrome. Anesthesiology. 2019;131(3):594-604.
34. Beitler JR, Sarge T, Banner-Goodspeed VM, et al. Effect of titrating
positive end-expiratory pressure with an esophageal pressure-guided
chestjournal.org
strategy vs an empirical high PEEP-Fio2 strategy on death and days
free from mechanical ventilation among patients with acute
respiratory distress syndrome: a randomized clinical trial. JAMA.
2019;321(9):846-857.
35. Madahar P, Talmor D, Beitler JR. Transpulmonary pressure-
guided ventilation to attenuate atelectrauma and hyperinflation
in acute lung injury. Am J Respir Crit Care Med. 2021;203(8):
934-937.
36. Yoshida T, Piraino T, Lima CAS, Kavanagh BP, Amato MBP,
Brochard L. Regional ventilation displayed by electrical impedance
tomography as an incentive to decrease positive end-expiratory
pressure. Am J Respir Crit Care Med. 2019;200(7):933-937.
37. National Institutes of Health Clinical Center. Careful ventilation in
acute respiratory distress syndrome (COVID-19) (CAVIARDS).
NCT03963622. ClinicalTrials.gov. National Institutes of Health;
2019. Updated March 15, 2022. https://clinicaltrials.gov/ct2/show/
NCT03963622
38. Chen L, Del Sorbo L, Grieco DL, et al. Airway closure in acute
respiratory distress syndrome: an underestimated and
misinterpreted phenomenon. Am J Respir Crit Care Med.
2018;197(1):132-136.
39. Hedenstierna G, L, Chen L, Brochard L. Airway closure, more
harmful than atelectasis in intensive care?. Intensive Care Med.
2020;46(12):2373-2376.
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