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Severe Hypoxemic Respiratory Failure : Part

1 −−Ventilatory Strategies
Adebayo Esan, Dean R. Hess, Suhail Raoof, Liziamma George and
Curtis N. Sessler

Chest 2010;137;1203-1216
DOI 10.1378/chest.09-2415
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CHEST Postgraduate Education Corner
CONTEMPORARY REVIEWS IN CRITICAL CARE MEDICINE

Severe Hypoxemic Respiratory Failure


Part 1—Ventilatory Strategies
Adebayo Esan, MD; Dean R. Hess, PhD, RRT, FCCP; Suhail Raoof, MD, FCCP;
Liziamma George, MD, FCCP; and Curtis N. Sessler, MD, FCCP

Approximately 16% of deaths in patients with ARDS results from refractory hypoxemia, which
is the inability to achieve adequate arterial oxygenation despite high levels of inspired oxygen
or the development of barotrauma. A number of ventilator-focused rescue therapies that can
be used when conventional mechanical ventilation does not achieve a specific target level of
oxygenation are discussed. A literature search was conducted and narrative review written to
summarize the use of high levels of positive end-expiratory pressure, recruitment maneuvers,
airway pressure-release ventilation, and high-frequency ventilation. Each therapy reviewed
has been reported to improve oxygenation in patients with ARDS. However, none of them
have been shown to improve survival when studied in heterogeneous populations of patients
with ARDS. Moreover, none of the therapies has been reported to be superior to another for
the goal of improving oxygenation. The goal of improving oxygenation must always be bal-
anced against the risk of further lung injury. The optimal time to initiate rescue therapies, if
needed, is within 96 h of the onset of ARDS, a time when alveolar recruitment potential is the
greatest. A variety of ventilatory approaches are available to improve oxygenation in the setting of
refractory hypoxemia and ARDS. Which, if any, of these approaches should be used is often
determined by the availability of equipment and clinician bias. CHEST 2010; 137(5):1203–1216

Abbreviations: ALI 5 acute lung injury; APRV 5 airway pressure-release ventilation; CPAP 5 continuous positive
airway pressure; HFOV 5 high-frequency oscillatory ventilation; HFPV 5 high-frequency percussive ventilation;
IBW 5 ideal body weight; mPaw 5 mean airway pressure; OI 5 oxygenation index; DP 5 pressure amplitude of oscillation;
PCIRV 5 pressure-controlled inverse-ratio ventilation; PCV 5 pressure-controlled ventilation; PEEP 5 positive end-
expiratory pressure; Pplat 5 plateau pressure; RCT 5 randomized controlled trial; VCV 5 volume-controlled
ventilation

Theon ARDS
American-European Consensus Conference
1
standardized the definition of acute
Such an approach affords a survival benefit and is
standard care.3
lung injury (ALI) and ARDS on the basis of the fol- Patients with ARDS who are placed on lung-
lowing clinical parameters: acute onset of severe protective mechanical ventilation may have an
respiratory distress; bilateral infiltrates on frontal chest improvement in oxygenation and disease severity
radiograph; absence of left atrial hypertension, a pul- within 24 h; their mortality is 13% to 23%4,5; and
monary capillary wedge pressure ⱕ 18 mm Hg, or no they should be continued on lung-protective venti-
clinical signs of left heart failure; and severe hypox- lator settings. In patients with little improvement in
emia (ALI, PaO2ⲐFIO2 ratio ⱕ 300 mm Hg; ARDS, PaO2 ⲐFIO2 ratio in the first 24 h after instituting
PaO2ⲐFIO2 ratio ⱕ 200 mm Hg). The definition does mechanical ventilation, the observed mortality is sig-
not take into consideration, however, the etiology nificantly higher and varies from 53% to 68%.4,5 In
(pulmonary or extrapulmonary) or the level of positive one study, setting PEEP at 10 cm H2O allowed better
end-expiratory pressure (PEEP) required. More than differentiation of ARDS and ALI. After the PEEP
80% of patients with ARDS require intubation and trial, about one-third of patients initially classified as
mechanical ventilation.2 A lung-protective ventilation having ARDS were reclassified as having ALI, and
strategy should be used with a tidal volume of 4 to 9% had a PaO2ⲐFIO2 ratio of . 300 mm Hg. The
8 mLⲐkg ideal body weight (IBW), a plateau pressure mortality rates for reclassified categories were 45%
(Pplat) of ⱕ 30 cm H2O, and modest levels of PEEP. for ARDS, 20% for ALI, and 6% for others.6

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Another parameter that may identify patients with ognized early in the course of ARDS (, 96 h) when
severe ARDS is a PEEP requirement of ⱖ 15 cm H2O. the potential for alveolar recruitment is greatest.17-20
to maintain adequate oxygenation. Indirect evidence Consideration also should be given to transferring
for this parameter comes from Kallet and Branson,7 patients with refractory hypoxemia to a center with
who reviewed data for 197 patients from 16 studies. established expertise in caring for such patients.21-23
They determined that 84% of patients with ARDS What is the physiologic basis for rescue therapies
had a lower inflection point of ⱕ 15 cm H2O on in severe ARDS? In the lungs of patients with ARDS,
the pressure-volume curve, suggesting that a PEEP there are alveoli that are relatively normal, that
of ⱖ 15 cm H2O may identify severe ARDS. In a are collapsed but recruitable, and that are nonre-
series of 47 patients with ARDS, refractory hypox- cruitable.24 Rescue methods are used to recruit the
emia was associated with a 16% mortality rate collapsed, but potentially recruitable alveoli. Alveolar
among ARDS deaths.8 In the same vein, Luhr et al2 recruitment reduces the shunt fraction, reduces dead
reported that patients with a PaO2ⲐFIO2 ratio of space, and improves compliance. Another important
, 100 mm Hg required more aggressive therapy physiologic concept is optimally matching ventilation
for oxygenation. and perfusion.
The oxygenation index (OI) incorporates the The primary focus should be on prevention of
severity of oxygenation impairment (PaO2ⲐFIO2 ratio) refractory hypoxemia rather than on reversing it after
and mean airway pressure into a single variable: it develops. If small tidal volumes and adequate levels
of PEEP are used and careful attention given to fluid
OI 5 (FIO2 3 mPaw 3 100)/PaO2 status and patient-ventilator synchrony, the need for
rescue therapy may be obviated in many cases.25 Res-
(where mPaw 5 mean airway pressure). The OI is used cue therapies can be categorized arbitrarily as ventila-
more commonly in neonatal and pediatric patients but tory and nonventilatory strategies. Nonventilatory
also has been used in adults with ARDS and may be a interventions, such as neuromuscular blockade, inhaled
better predictor of poor outcome than the PaO2ⲐFIO2 vasodilator therapy, prone positioning, and extracor-
ratio.9-12 A high OI 12 to 24 h after the onset of ARDS poreal life support, are discussed in a companion
and rising values of OI from persistent ARDS have article forthcoming in the June 2010 issue of CHEST,26
been shown to be independent risk factors for whereas ventilatory approaches are addressed here.
mortality.10-12 An OI of . 30 is reported to represent Use of rescue therapies is controversial, as, to our
failure of conventional ventilation and may be con- knowledge, none to date has been shown to reduce
sidered an indication for nonconventional modes of mortality when studied in large heterogeneous popu-
ventilation.9,13-16 lations of patients with ARDS. However, some rescue
For the purpose of this article, we have used the fol- therapies have been shown to improve oxygenation,
lowing definition of refractory hypoxemia: PaO2ⲐFIO2 which may be important as a short-term goal in the
ratio of , 100 mm Hg or inability to maintain Pplat 16% of patients deteriorating with hypoxemic respi-
, 30 cm H2O despite a tidal volume of 4 mLⲐkg IBW ratory failure.8 When instituting rescue strategies, an
or the development of barotrauma. An OI of . 30 also attempt should be made to assess for alveolar recruit-
categorizes a patient as having refractory hypoxemic ment. If alveolar recruitment is demonstrated, higher
respiratory failure. We define high ventilator require- levels of PEEP should be considered.27-30 Other res-
ment as an FIO2 of ⱖ 0.7 mm Hg and a PEEP of cue therapies include airway pressure release ventila-
. 15 cm H2O or Pplat . 30 cm H2O with a tidal volume tion (APRV),31 high-frequency oscillatory ventilation
of , 6 mLⲐkg IBW. This requirement should be rec- (HFOV),32 and high-frequency percussive ventilation
(HFPV).33,34 In patients demonstrating very severe
hypoxemic respiratory failure, defined as a PaO2Ⲑ
Manuscript received October 9, 2009; revision accepted January FIO2 ratio of , 60 mm Hg,27 consideration of extra-
14, 2010.
Affiliations: From the New York Methodist Hospital (Drs Esan, corporeal life support,35 HFOV, or HFPV may be
Raoof, and George), Division of Pulmonary and Critical Care appropriate.
Medicine, Brooklyn, NY; Respiratory Care Services (Dr Hess), Because there are no data establishing the superi-
Massachusetts General Hospital, Boston, MA; and Pulmonary
and Critical Care Medicine (Dr Sessler), Virginia Commonwealth ority of one rescue mode over another,36 the choice of
University, Richmond, VA. rescue therapy is based on equipment availability and
Correspondence to: Suhail Raoof, MD, FCCP, Division of Pul- clinician expertise. Some clinicians may choose not to
monary and Critical Care Medicine, New York Methodist Hospi-
tal, 506 Sixth St, Brooklyn, NY 11215; e-mail: sur9016@nyp.org use a rescue therapy, which is legitimate on the basis
© 2010 American College of Chest Physicians. Reproduction of the level of available evidence. If a rescue therapy
of this article is prohibited without written permission from the does not result in improved oxygenation or if compli-
American College of Chest Physicians (www.chestpubs.orgⲐ
siteⲐmiscⲐreprints.xhtml). cations from the therapy occur, that rescue therapy
DOI: 10.1378/chest.09-2415 should be abandoned.

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Thus, a reasonable evidence-based approach might an increase in PEEP will have a marginal effect on
be one in which lung-protective ventilation is used shunt and PaO2, and it may contribute to overdistension
(volume and pressure limitation with modest PEEP). of already-open alveoli,41 which could lead to increased
This approach may require permissive hypercapnia risk for ventilator-induced lung injury and increased
(ie, a higher-than-normal PaCO2)37 and permissive dead space and might potentially result in redistribu-
hypoxemia (ie, a lower-than-normal PaO2).38 If a clin- tion of pulmonary blood flow to nonventilated regions
ical decision is made to implement rescue therapy for of the lungs. If an increase in PEEP results in alveolar
the patient with ARDS and refractory hypoxemia, recruitment, then the strain (distribution of pressure) in
one or more of the strategies described in this article the lungs is reduced. On the other hand, if an increase
can be used. in PEEP increases transpulmonary pressure, then the
In this narrative review, we discuss ventilatory stress (change in size of the lungs during inflation) on
techniques that have been used in the setting of the lungs is increased. PEEP may adversely affect PaO2
refractory hypoxemia in patients with ARDS. A in the presence of unilateral lung disease.42
PubMed search was conducted, with each strategy The potential for recruitment can be identified in
used as a key term. We narrowed the search to arti- an individual patient by use of a short (30-min) trial
cles published in English and those that studied of increased PEEP. If an increase in PEEP results in
human subjects. We broadened the search to include minimal improvement (or worsening) of PaO2, an
additional articles, as appropriate, from the reference increase in dead space (increased PaCO2) with stable
lists of those identified from our primary search. minute ventilation, and worsening compliance, then
alveolar recruitment is minimal.43 Conversely, if an
Positive End-Expiratory Pressure increase in PEEP results in a large increase in PaO2,
a decrease in PaCO2, and improved compliance, it sug-
Increasing the level of PEEP often is the first con- gests significant recruitment. Some have suggested a
sideration when the clinician is faced with a patient decremental rather than an incremental PEEP trial.44,45
with refractory hypoxemia. If PEEP results in alve- With this approach, PEEP is set to ⱖ 20 cm H2O and
olar recruitment, the shunt is reduced, and PaO2 then decreased to identify the level that produces the
increases. Three randomized controlled trials (RCTs) best PaO2 and compliance.
have evaluated modest vs high levels of PEEP in The stress index was recently proposed to assess
patients with ALI and ARDS (Table 1).27,28,39 Although the level of PEEP to avoid overdistension.29 This
none of these studies reported a survival advan- approach uses the shape of the pressure-time curve
tage for use of higher PEEP, each reported a higher during tidal volume delivery. Worsening compliance
PaO2ⲐFIO2 ratio in the higher PEEP group. More- as the lungs are inflated (upward concavity; stress index,
over, two of the studies reported lower rates of refrac- . 1) suggests overdistension, and the recommenda-
tory hypoxemia, death with refractory hypoxemia, tion is to decrease PEEP (Fig 1). Improving compli-
and use of rescue therapies.27,28 Gattinoni and ance as the lungs are inflated (downward concavity;
Caironi40 argued for the use of higher PEEP on the stress index, , 1) suggests tidal recruitment and poten-
basis of fewer pulmonary deaths and absence of tial for additional recruitment, thus a recommenda-
reported complications with this strategy. tion to increase PEEP.
The National Heart, Lung, and Blood Institute ARDS The use of an esophageal balloon to assess intra-
Clinical Trials Network39 and Meade et al27 set individ- pleural pressure has been advocated to allow more
ualized PEEP using a table of FIO2-PEEP combina- precise setting of PEEP.30,46 If pleural pressure is high
tions based on oxygenation. Mercat et al28 individual- relative to alveolar pressure (ie, PEEP), there may be
ized PEEP to a level set to reach a plateau pressure of potential for alveolar derecruitment, which is most
28 to 30 cm H2O. Post hoc analysis of data from their likely seen with a decrease in chest wall compliance,
study suggested that compared with ARDS, mild lung such as occurs with abdominal compartment syndrome,
injury may be associated with less benefit and more pleural effusion, or obesity. In this case, it is desirable
adverse effects from higher levels of PEEP. Thus, a to keep PEEP greater than pleural pressure. Unfor-
strategy of a higher PEEP and lower tidal volume with tunately, artifacts in esophageal pressure, especially
a plateau pressure target of 28 to 30 cm H2O should in supine patients who are critically ill, make it very
not be used in patients with ALI. Moreover, critics difficult to measure absolute pleural pressure
have argued that the low PEEP (5-9 cm H2O) used in accurately.47-50 Although it is important to consider
the control group in Mercat et al may have been exces- pleural pressure when setting PEEP, the use of an
sively conservative and a suboptimal control. esophageal balloon may not be required. In patients
The benefit of PEEP in patients with refractory hyp- with abdominal compartment syndrome, bladder
oxemia might depend on the potential for alveolar pressure may be useful to assess intraabdominal pres-
recruitment.24 If the recruitment potential is low, then sure, the potential collapsing effect on the lungs, and

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involves a sustained high-pressure inflation using
pressures of 30 to 50 cm H2O for 20 to 40 s.51,56 A sus-
tained inflation usually is achieved by changing to a
continuous positive airway pressure (CPAP) mode
and setting the pressure to the desired level. Pressure-
controlled breaths can be applied in addition to the
sustained high pressure.18,57 Another approach is to
use intermittent sighs, using three consecutive sighs
set at a pressure of 45 cm H2O.59 An extended sigh
also has been used in which there is a stepwise increase
in PEEP and a decrease in tidal volume over 2 min to
a CPAP level of 30 cm H2O for 30 s.60 Another method
applies an intermittent increase in PEEP for 2 breathsⲐ
Figure 1. Graphic representation of the stress index. Flow and min.55 Pressure-controlled ventilation (PCV) of 10 to
airway pressure vs time are displayed for three examples of stress 15 cm H2O with PEEP of 25 to 30 cm H2O to reach a
index categories. The ventilator is set for constant-flow inflation. peak inspiratory pressure of 40 to 45 cm H2O for 2 min
The stress index is derived from the airway pressure waveform
between the dashed lines. For stress index values , 1, the airway also has been used as a recruitment maneuver.57 Prone
pressure curve presents a downward concavity, suggesting a con- positioning61 and HFOV62 also have been used to
tinuous decrease in elastance (or increase in compliance) during improve alveolar recruitment.
constant-flow inflation, and further recruitment of alveoli is likely.
For stress index values . 1, the curve presents an upward con- Just as it is unclear which, if any, recruitment
cavity, suggesting a continuous increase in elastance (decrease maneuver is superior to another, the optimal pressure,
in compliance), and excessive positive end-expiratory pressure duration, and frequency of recruitment maneuvers has
may be present. Finally, for a stress index value 5 1, the curve is
straight, suggesting the absence of tidal variations in elastance. not been established. Many patients require increased
Pao 5 airway pressure. (Reprinted with permission from the sedation, paralysis, or both during the application of a
American Thoracic Society.29) recruitment maneuver. Studies using a decremental
PEEP trial after a recruitment maneuver have reported
the amount of PEEP necessary to counterbalance significant oxygenation benefits for at least 4 to 6 h.18,44
this effect.48 However, it is unclear whether this finding was due to
The available evidence does not clearly indicate the recruitment maneuver, the PEEP titration strategy,
the best method to select PEEP in patients with or both. An improvement in oxygenation with a
ARDS. Various options are listed in Table 2. A PEEP recruitment maneuver may indicate that the level of
setting of 0 cm H2O generally is accepted to be PEEP is too low. A recruitment maneuver may be of
harmful in the patient with ARDS. A PEEP setting of limited benefit when higher levels of PEEP are used.63
8 to 15 cm H2O is appropriate in most patients with A recent systematic review reported the acute
ARDS. Higher levels of PEEP should be used in physiologic effects of a recruitment maneuver in
patients for whom a greater potential for recruitment approximately 1,200 patients.52 Oxygenation was sig-
can be demonstrated. Care must be taken to avoid nificantly increased after a recruitment maneuver
overdistension when PEEP is set. Higher PEEP set- (Fig 2). Hypotension (12%) and desaturation (8%)
tings may be required in patients with refractory hyp- were the most common complications of recruitment
oxemia; however, a PEEP of . 24 cm H2O seldom is maneuvers. Serious adverse events, such as barotrauma
required. In the decision-making for each patient, (1%) and arrhythmia (1%), were infrequent. The overall
the potential benefit of high levels of PEEP should mortality was similar to observational studies of
be balanced against the risk of harm (ventilator- patients with ALI (38%). The finding of improved
induced lung injury, barotrauma, hypotension). oxygenation was more common in the following sub-
groups: difference between pre- and post-recruitment
Lung Recruitment Maneuvers maneuver PEEP (ⱕ 5 cm H2O vs . 5 cm H2O), baseline
PaO2ⲐFIO2 ratio (, 150 mm Hg vs ⱖ 150 mm Hg), and
A recruitment maneuver is a transient increase baseline respiratory system compliance (, 30 mLⲐcm
in transpulmonary pressure intended to promote H2O vs ⱖ 30 mLⲐcm H2O).
reopening of collapsed alveoli 52-54 and has been Many of the studies of recruitment maneuvers
shown to open collapsed alveoli, thereby improving reported a rapid decline in oxygenation gains, some
gas exchange.17,18,55-58 However, to our knowledge, within 15 to 20 min of the maneuver.52 The applica-
there have been no RCTs demonstrating a mortality tion of higher levels of PEEP after a recruitment
benefit from this improvement in gas exchange. maneuver may affect the sustainability of the effect.
A variety of techniques have been described as Whether improvements in oxygenation associated with
recruitment maneuvers (Table 3).52,54 One approach recruitment maneuvers result in reduced lung injury

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Table 1—Summary of Results of Three Randomized Controlled Trials of Lower vs Higher Levels of PEEP

Study Control Group Experimental Group Major Findings


ALVEOLI 39
Volume assist-control. Vt 5 6 mLⲐkg Volume assist-control. Vt 5 6 mLⲐkg Higher Pao2ⲐFio2 ratio in high PEEP group
IBW; Pplat ⱕ 30 cm H2O. Combinations IBW; Pplat ⱕ 30 cm H2O. (220 6 89 vs 168 6 66) on day 1. Higher
of PEEP and Fio2 to maintain Pao2 Combinations of PEEP and Fio2 compliance in the higher-PEEP group
(55-80 mm Hg) or SpO2 (88%-95%). to maintain Pao2 (55-80 mm Hg) or (39 6 34 vs 31 6 15 mLⲐcm H2O) on day 1.
PEEP on days 1-4 was 8.3 6 3.2 cm Spo2 (88%-95%). PEEP on days 1-4 Mortality before hospital discharge (low
H2O. n 5 273 was 13.2 6 3.5 cm H2O. In the first PEEP, 24.9%; high PEEP, 27.5%; P 5 .48).
80 patients, recruitment maneuvers Ventilator-free days (low PEEP, 14.5 6 10.4 d;
of 35-40 cm H2O for 30 s. n 5 276 high PEEP, 13.8 6 10.6 d; P 5 .50). Incidence
of barotrauma (low PEEP, 10%; high
PEEP, 11%; P 5 .51).
LOV27 Volume assist-control. Vt 5 6 mLⲐkg Pressure control. Vt 5 6 mLⲐkg Higher Pao2ⲐFio2 ratio in higher-PEEP group
IBW; Pplat ⱕ 30 cm H2O. Combinations IBW; Pplat ⱕ 40 cm H2O. (187 6 69 vs 149 6 61) on day 1. Higher
of PEEP and Fio2 to maintain Pao2 Combinations of PEEP and Fio2 Pplat in the high-PEEP group (30.2 6 6.3
(55-80 mm Hg) or Spo2 (88%-93%). to maintain Pao2 (55-80 mm Hg) or vs 24.9 6 5.1). The higher-PEEP group had
PEEP on days 1-3 was 9.8 6 2.7 cm Spo2 (88%-93%). PEEP on days 1-4 lower rates of refractory hypoxemia (4.6%
H2O. n 5 508 was 14.6 6 3.4 cm H2O. Recruitment vs 10.2%; P 5 .01), death with refractory
maneuvers after each disconnect hypoxemia (4.2% vs 8.9%; P 5 .03), and
from the ventilator of 40 cm H2O previously defined eligible use of rescue
for 40 s. n 5 475 therapies (5.1% vs 9.3%; P 5 .045). Twenty-
eight day mortality (high PEEP, 28.4%;
low PEEP, 32.3%; P 5 .2). Incidence of
barotrauma (high PEEP, 11.2%; low PEEP,
9.1%; P 5 .33).
EXPRESS28 Volume assist-control. Vt 5 6 mLⲐkg Volume assist-control. Vt 5 6 mLⲐkg Higher Pao2ⲐFio2 ratio in higher-PEEP group
IBW. Moderate PEEP (5-9 cm H2O). IBW. PEEP set to reach Pplat of (218 6 97 vs 150 6 69) on day 1. Higher
n 5 382 28-30 cm H2O (14.6 6 3.2 cm H2O) compliance in the high-PEEP group
on day 1. n 5 385 (37.2 6 22.7 mLⲐcm H2O vs 33.7 6 14.3
mLⲐcm H2O) on day 1. The increased
PEEP group had higher median number
of ventilator-free days (7 d vs 3 d; P 5 .04),
organ failure-free days (6 d vs 2 d; P 5 .04),
and use of adjunctive therapies. Incidence
of barotraumas (high PEEP, 6.8%; low
PEEP, 5.8%; P 5 .57).
ALVEOLI 5 Assessment of Low Tidal Volume and Elevated End-Expiratory Pressure to Obviate Lung Injury Trial; EXPRESS 5 Expiratory
Pressure Trial; IBW 5 ideal body weight; LOV 5 Lung Open Ventilation Trial; PEEP 5 positive end-expiratory pressure; Pplat 5 plateau pressure;
SpO2 5 oxygenation by pulse oximetry; Vt 5 tidal volume.

and improved outcomes remains to be determined. ment. However, caution must be exercised to avoid
Some studies have shown a survival advantage with a overdistension with excessive levels of PEEP.
lung-protective ventilation strategy incorporating
recruitment maneuvers,51,64 whereas others have Pressure-Controlled Ventilation
not.27 The potential for lung recruitment likely varies
considerably among patients,24 which likely affects In patients with severe ARDS, some clinicians
the response to a recruitment maneuver. choose PCV as an alternative to volume-controlled
The routine use of recruitment maneuvers is not ventilation (VCV) based on several lines of rea-
recommended at this time. Given that they pose little soning. First, the peak inspiratory pressure is lower
risk of harm if the patient is carefully monitored on PCV, but this is related to the flow pattern
during their application and that some patients may during pressure control and, for the same tidal vol-
have a dramatic improvement in oxygenation with ume delivery, there is no difference in plateau pres-
their application,57 recruitment maneuvers may play sure for PCV and VCV. Second, patient-ventilator
a role in patients who develop life-threatening refrac- synchrony is believed to be better with PCV.
tory hypoxemia. It is prudent to avoid the use of However, Kallet et al66 reported that the work of
recruitment maneuvers in patients with hemody- breathing is not better with PCV than with VCV
namic compromise and those at risk for barotrauma.65 during lung-protective ventilation in patients who
If the application of a recruitment maneuver results are actively breathing. Moreover, the active inspi-
in an important improvement in oxygenation, higher ratory effort resulted in an increase in tidal vol-
levels of PEEP should be used to maintain recruit- ume such that lung-protective ventilation may have

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Table 2—Methods for Selecting PEEP

Method Description
3,27,39
Incremental PEEP This approach uses combinations of PEEP and Fio2 to achieve the
desired level of oxygenation or the highest compliance.
Decremental PEEP44,45 This approach begins with a high level of PEEP (eg, 20 cm H2O), after
which PEEP is decreased in a stepwise fashion until derecruitment
occurs, typically with a decrease in Pao2 and decrease in compliance.
Stress index measurement29 The pressure-time curve is observed during constant-flow inhalation
for signs of tidal recruitment and overdistension.
Esophageal pressure measurement30,46 This method estimates the intrapleural pressure by using an esophageal
balloon to measure the esophageal pressure and subsequently
determine the optimal level of PEEP required.
Pressure-volume curve guidance51 PEEP is set slightly greater than the lower inflection point.
See Table 1 for expansion of the abbreviation.

been violated in many patients.66 Third, some clini- enthusiasm for this ventilatory approach, a number
cians expect an improvement in gas exchange with of subsequent controlled studies reported no ben-
PCV. With PCV, the pressure waveform approxi- efit or marginal benefit of PCIRV over more conven-
mates a rectangle, and flow decreases during the tional approaches to ventilatory support in patients
inspiratory phase. The resulting increased mean with ARDS.68,77-80 The elevated mean airway pres-
airway pressure and lower end-inspiratory flow sure and auto-PEEP that occur with PCIRV also
theoretically should improve gas exchange. However, may adversely affect hemodynamics. Because this
on many current-generation ventilators, a descend- approach can be very uncomfortable for the patient,
ing ramp of flow can be used with VCV, and this may sedation and paralysis often are required. On the
result in similar findings with PCV and VCV with a basis of the available evidence, there is no clear ben-
descending ramp waveform.67-70 With careful atten- efit for PCIRV in the management of patients with
tion to tidal volume, plateau pressure, PEEP, and ARDS. The likelihood of an improvement in oxygen-
inspiratory time, the differences between PCV and ation with PCIRV is small, and the risk of auto-PEEP
VCV are minor, and neither is clearly superior to the and hemodynamic compromise is great.81-83
other. It is also worth pointing out that the ARDSNet
trial was conducted with VCV.3 Airway Pressure Release Ventilation

Pressure-Controlled Inverse-Ratio APRV is a mode of ventilation designed to allow


Ventilation patients to breathe spontaneously while receiving
high airway pressure with an intermittent pressure
Following reports71-75 of improved oxygenation release (Fig 3). The high airway pressure maintains
with pressure-controlled inverse-ratio ventilation adequate alveolar recruitment. Oxygenation is deter-
(PCIRV) published 20 years ago, considerable enthu- mined by high airway pressure and FIO2. The timing
siasm for this method was generated. The approach and duration of the pressure release (low airway pres-
to PCIRV is to use an inspiratory time greater than the sure) as well as the patient’s spontaneous breathing
expiratory time to increase mean airway pressure determine alveolar ventilation (PaCO2). The ventilator-
and, thus, improve arterial oxygenation. PCIRV most determined tidal volume depends on lung compli-
often is used with PCV, although VCV with inverse ance, airway resistance, and the duration and timing
ratio also has been described.76 Following the initial of the pressure-release maneuver.

Table 3—Different Lung Recruitment Maneuvers

Recruitment Maneuver Method


51,56
Sustained high-pressure inflation Sustained inflation delivered by increasing PEEP to 30-50 cm H2O for 20-40 s
Intermittent sigh59 Three consecutive sighsⲐmin with the tidal volume reaching a Pplat of 45 cm H2O
Extended sigh60 Stepwise increase in PEEP by 5 cm H2O above baseline with a simultaneous stepwise decrease
in tidal volume over 2 min leading to implementing a CPAP level of 30 cm H2O for 30 s
Intermittent PEEP increase55 Intermittent increase in PEEP from baseline to set level for 2 consecutive breathsⲐmin
Pressure control 1 PEEP57 Pressure control ventilation of 10-15 cm H2O with PEEP of 25-30 cm H2O to reach a peak
inspiratory pressure of 40-45 cm H2O for 2 min
CPAP 5 continuous positive air pressure. See Table 1 legend for expansion of other abbreviation.

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© 2010 American College of Chest Physicians
that the expiratory flow reaches 50% to 75% of the
peak expiratory flow.
Crossover studies have reported improvements
in physiologic end points with APRV.31,85,86,90-92 These
studies reported that APRV required lower inflation
pressure and less sedation and often produced
better oxygenation than other forms of mechanical
ventilation. Putensen et al87 randomized 30 trauma
patients to APRV or PCV. With APRV, the inotropic
support was lower, and the duration of ventilatory
support and length of ICU stay were shorter. How-
ever, these findings are debatable because patients
randomized to the conventional ventilation group
were paralyzed for the initial 72 h of support. The
Figure 2. The relationship between oxygenation (Pao2ⲐFio2 ratio) largest RCT of APRV84 was terminated early for
after the application of a recruitment maneuver (post-RM) with
baseline (pre-RM) oxygenation in each individual study presented. futility after recruiting 58 out of a targeted 80 sub-
Oxygenation was significantly increased post-RM (Pao2ⲐFio2 ratio, jects. At 28 days, there were no statistical differences
139 mm Hg vs 251 mm Hg; P , .001). PⲐF 5 Pao2ⲐFio2. (Reprinted in the number of ventilator-free days. In addition,
with permission from the American Thoracic Society.52)
mortality at 28 days and at 1 year was similar. How-
ever, the authors used prone positioning in both
An active exhalation valve allows the patient to arms, which is known to improve the oxygenation in
breathe spontaneously throughout the ventilator- 60% to 70% of patients; thus, prone position may
imposed pressures, although spontaneous breathing have eclipsed any oxygenation differences between
typically occurs only during high airway pressure the two groups. Additionally, the ventilator used to
due to the short time at low airway pressure. Dia- provide APRV in the test group is not designed
phragmatic contraction associated with spontaneous to provide APRV and required modification to the
breaths during APRV may recruit dependent (dorsal) expiratory limb.
juxtadiaphragmatic alveoli, thus reducing shunt and Spontaneous breathing during high airway pres-
improving oxygenation. Because high airway pres- sure has the potential to generate negative pleural
sure usually is much longer than low airway pres- pressures that may add to the stretch applied from
sure, APRV is functionally the same as PCIRV in the ventilator. This situation must be considered
the absence of spontaneous breathing. Because the when evaluating the maximal stretch to which the
patient’s ability to breathe spontaneously is pre- lungs are exposed. Neumann et al88 reported tidal
served, APRV allows for a prolonged inspiratory volumes of approximately 1 L and large pleural pres-
phase without the need for heavy sedation and sure swings with APRV. There is concern that these
paralysis. relatively large tidal volumes and transpulmonary
Various time ratios for high-to-low airway pres- pressures could contribute to the risk of ventilator-
sure have been used with APRV, ranging from 1:1 to induced lung injury. The potential benefits of
9:1 in different studies.84-88 In order to sustain opti- improved oxygenation and reduced need for sedation
mal recruitment, the greater part of the total time make APRV an attractive ventilator mode.89 However,
cycle (80%-95%) occurs at high airway pressure. In without RCTs demonstrating improved patient out-
order to minimize derecruitment, the time spent at comes, routine use of this mode cannot be recom-
low airway pressure is brief (0.2-0.8 s in adults).89 mended. If APRV is used, auto-PEEP and tidal vol-
Neumann et al88 demonstrated that spontaneous ume must be closely monitored.
inspiratory and expiratory time intervals are indepen-
dent of the time at high to low airway pressure cycle High-Frequency Oscillatory Ventilation
because patients who are breathing spontaneously
can maintain their innate respiratory drive during High-frequency ventilation is any application of
high and low airway pressure; thus, the release phase mechanical ventilation with a respiratory rate of . 100
does not reflect the only expiratory time. If the time breathsⲐmin. This can be achieved with a small tidal
at low airway pressure is too short, expiration may volume and rapid respiratory rate with conven-
be incomplete, and intrinsic PEEP may result.88 tional mechanical ventilation, various forms of exter-
However, creating intrinsic PEEP is, by design, nal chest wall oscillation, HFPV, high-frequency jet
required with some approaches to APRV in which ventilation, or HFOV, which currently is the form of
low airway pressure is set to 0 cm H2O.89 With this high-frequency ventilation most widely used in adult
approach, the time at low airway pressure is set such critical care.62,93-95 It delivers a small tidal volume by

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© 2010 American College of Chest Physicians
oscillating a bias gas flow in the airway. The oscillator high mPaw may result in improved alveolar recruit-
has an active inspiratory and expiratory phase. A ment with less risk of overdistension, thus providing
frequency of 3 to 15 Hz can be used, although lower improved gas exchange and lung protection. HFOV
rates (3-6 Hz) are used in adults. Nevertheless, higher also has been combined with other strategies, such as
rates are feasible and may result in smaller tidal recruitment maneuvers,100 inhaled nitric oxide,101 and
volumes and decreased risk for lung injury.96 prone positioning.102
HFOV oscillates the gas delivered to pressures Most of the evidence for HFOV has been from
above and below the mean airway pressure(mPaw). small observational studies,9,19,103,104 often in the set-
The mPaw and FIO2 are the primary determinants ting of refractory hypoxemia. These studies have
of oxygenation, whereas the pressure amplitude of shown that HFOV is safe and effective, resulting in
oscillation (DP) and the respiratory frequency are the improvements in oxygenation and providing ample
determinants of CO2 elimination. The tidal volume ventilation in adult patients with severe ARDS.
varies directly with DP and inversely with frequency.95 There have been only two RCTs of HFOV in adult
The mPaw is initially set to a level approximately patients with ARDS.32,105 Derdak et al32 random-
5 cm H2O above that with conventional ventilation, ized 148 patients to receive either HFOV or conven-
and DP is set to induce “wiggle,” which is visible to tional ventilation. The HFOV group showed an early
the patient’s mid-thigh.96,97 Much of the pressure improvement in the PaO2ⲐFIO2 ratio, but this was
applied to the airway is attenuated by proximal not sustained beyond 24 h. There was a nonsignifi-
airways and does not reach the alveoli, resulting in a cant trend toward a lower 30-day mortality in the
small tidal volume that may be less than dead HFOV group (37% vs 52%; P 5 .102). A criticism of
space.98,99 The delivery of a small tidal volume and a this trial is that patients in the conventional ventilation

Figure 3. Display of airway pressure and flow vs time during airway pressure-release ventilation.
Spontaneous breaths occur at a high pressure level, leading to a pressure release to a lower pressure
level, as seen in this figure. During this mode, ventilation occurs by intermittent switching between
the two pressure levels while allowing spontaneous breathing to occur in either phase of the ventilator
cycle. Because time at low airway pressure is brief, in practice, spontaneous breathing occurs primarily
during the time of high airway pressure. Maintaining an adequate level of time during a high airway
pressure enhances alveolar recruitment, whereas keeping time short prevents alveolar collapse during
the release to low airway pressure. CPAP 5 continuous positive air pressure; Paw 5 airway pressure;
T High 5 time at high airway pressure; T Low 5 time at low airway pressure; V̇5 flow. (Reprinted with per-
mission from the Intensive Care On-line Network.89)

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© 2010 American College of Chest Physicians
group were ventilated with relatively large tidal vol- The use of HFOV may improve oxygenation in
umes, which may have contributed to the high mor- patients with refractory hypoxemia. However, there
tality in the control group.93 Bollen et al105 reported is not sufficient evidence to conclude that HFOV
no significant difference in mortality between reduces mortality or long-term morbidity in patients
patients randomized to HFOV and those to conven- with ALI or ARDS.107
tional ventilation. A post hoc analysis, however, sug-
gested that HFOV might improve mortality in High-Frequency Percussive Ventilation
patients with a higher oxygenation index. Complica-
tions reported with HFOV are relatively infrequent HFPV was introduced in the early 1980s as the
and include barotrauma,19,32,100,104 hemodynamic Volumetric Diffusive Respirator (Percussionaire
compromise,9,104 mucus inspissations resulting in endo- Corporation; Sandpoint, ID). Compared with HFOV,
tracheal tube occlusion or refractory hypercapnia,31 only a few studies have investigated the use of HFPV
and increased use of sedation or neuromuscular in adult patients with ARDS.33,108-112 HFPV is a flow-
blocking agents.9,19,32,102,106 In the two RCTs comparing regulated, pressure-limited, and time-cycled venti-
HFOV with conventional ventilation, Derdak et al lator that delivers a series of high-frequency (200-
reported no significant effect of HFOV on hemody- 900 cyclesⲐmin) small volumes in a successive
namics, barotrauma, or mucus plugging, and Bollen stepwise stacking pattern, resulting in the formation
et al did not report any increased risk of complica- of low-frequency (upper limit, 40-60 cyclesⲐmin) con-
tions with HFOV. vective pressure-limited breathing cycles (Fig 4).34,110,113

Figure 4. High-frequency percussive ventilation. An interplay of the percussive frequency, peak inspiratory pressure (indirectly
modulated by altering the pulsatile flow rate), inspiratory and expiratory times (of both percussive and convective breaths), and the
oscillatory and demand continuous positive air pressure (CPAP) levels either singly or in combination is involved in determining mean
airway pressure as well as the degree of gas exchange. The percussions are of lower amplitude at oscillatory CPAP (baseline oscillations)
during exhalation and are of higher amplitude during inspiration as a result of the selected pulsatile flow rate (see pressure-time dis-
play). During inspiration, the lung volumes progressively increase in a cumulative, stepwise manner by continually diminishing subtidal
deliveries that result in stacking of breaths. The peak pressure is reached as a result of modulations in the flow rate of the percussive
breaths. Once an oscillatory pressure peak is reached and sustained, periodic programmed interruptions occur at specific times for
predetermined intervals to allow for the return of airway pressures to baseline oscillatory pressure levels (ie, oscillatory CPAP), thereby
passively emptying the lungs. A 5 pulsatile flow during inspiration at a percussive rate of 655 cyclesⲐmin; B 5 convective pressure-
limited breath with low-frequency cycle (14 cyclesⲐmin); C 5 demand CPAP (provides static baseline pressure); D 5 oscillatory CPAP
(provides high-frequency baseline pressure as a mean of the peak and nadir of the oscillations during exhalation); E 5 single percussive
breath; F 5 periodic programmed interruptions signifying the end of inspiration and subsequent onset of exhalation.

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An interplay of the Volume Diffusive Respirator con- quencies (300-600 cyclesⲐmin), oxygenation is
trol variables, either singly or in combination, con- enhanced, whereas at low percussion frequen-
tribute to the determination of mean airway pressure cies (180-240 cyclesⲐmin), CO2 elimination is
and gas exhange.34,109,112,114 At high percussion fre- enhanced.34,109,113

ARDS/ALI

Conventional Management
g
of ARDS/ALI

ARDSnet Guidelines

P O2/FIO2 < 100


PaO
Non-ventilatory strategies yes Or
no
to improve PaO2 Pplat > 30 cm H2O on VT 4 mL/kg IBW
(Part 2) Or
OI > 30 ?

yes

Increase PEEP by 5 - 10 cm H2O to a maximum of 20 cm H2O


and/or
Recruitment maneuver (eg, 30 - 40 cm H2O for 30 - 40 s)

SpO2 increase > 5%


Or
no yes
Low recruitment potential PaCO2 decrease High recruitment potential
Or
Compliance increase

ECLS (PaO2/FIO2 < 60)

Higher Levels of PEEP (ALVEOLI TRIAL)*


FIO2 0.3
03 0.3
03 0
0.3
3 0
0.3
3 0
0.3
3 0
0.4
4 0
0.4
4 0
0.5
5 0
0.5
5 0
0.5-
5 0
0.8
8 0
0.9
9 1
1.0
0 1
1.0
0
0.8
PEEP 5 8 10 12 14 14 16 16 18 20 22 22 22 24
cm H2O

Reassess in 6 – 24 hours

PaO2/FIO2 < 60 PaO2/FIO2 60 - 100

Consider: Consider:
HFOV/HFPV APRV
ECLS HFOV/HFPV

Figure 5. Ventilatory strategies for the management of refractory hypoxemic respiratory failure,
showing the alternative ventilator strategies that can be used in patients with acute lung injury or ARDS
with refractory hypoxemia following evaluation of the recruitment potential of the lungs. In patients with
recruitable lungs, higher levels of positive end-expiratory pressure (PEEP) or other methods of setting
appropriate levels of PEEP may be used initially.∗ However, failure of the aforementioned techniques
can result in the use of the alternative ventilatory strategies in centers familiar with their use. ∗ 5 other
methods of setting appropriate levels of PEEP include setting PEEP to reach a plateau pressure of
28 to 30 cm H2O using esophageal pressure monitoring or the stress index. ALI 5 acute lung injury;
APRV 5 airway pressure-release ventilation; ECLS 5 extracorporeal life support; ETCO2 5 end-tidal
carbon dioxide; HFOV 5 high-frequency oscillatory ventilation; HFPV 5 high-frequency percussive
ventilation. See Table 1 legend for expansion of other abbreviations.

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HFPV has been reported to improve oxygenation ALI and ARDS requiring mechanical ventilation.
and ventilation in patients with ARDS refractory to Rescue therapies may be considered in patients who
conventional ventilation, although these studies are develop refractory hypoxemia, with the use of these
small in size, few in number, and nonrandomized. In therapies based on a variety of factors, such as the
a prospective trial of seven patients with ARDS severity of hypoxemia, likelihood of alveolar recruit-
requiring increased ventilator support on conventional ment, response to the intervention, and patient char-
ventilation, Gallagher et al112 found that when the acteristics. Rescue strategies are aimed at improving
patients were switched to HFPV at the same level of alveolar recruitment (high PEEP, recruitment maneu-
airway pressure and FIO2, the patients had a signifi- vers, APRV, HFOV) and, thereby, oxygenation; how-
cant increase in PaO2, a slight reduction in PaCO2, ever, none of these modalities have been consistently
and no change in cardiac output. In another prospec- shown to improve outcome in a critically ill patient
tive study comparing HFPV and conventional venti- population. Before a trial of rescue therapy is initi-
lation in 100 adult patients with acute respiratory failure, ated, the target outcome should be established. If the
no difference was found between the two groups in rescue strategy does not achieve this end point, it
the time to reach the study end points of PaO2ⲐFIO2 should be abandoned. Nonventilatory rescue strat-
ratio . 225 or shunt , 20%.114 In the subgroup of egies, such as inhaled vasodilators, prone positioning,
patients with ARDS, HFPV provided equal oxygena- and extracorporeal life support, may be considered in
tion and ventilation at significantly lower airway pres- conjunction with the ventilatory strategies outlined in
sures, although there was no difference in the inci- this article. They are discussed in detail in part 2 of
dence of barotrauma, ICU days, hospital days, or this series, which will appear in the June 2010 issue of
mortality.114 In a retrospective series of 32 adult CHEST.26 Further research is needed to elucidate
medical and surgical patients with ARDS unresponsive how these rescue strategies may be better used to
to at least 48 h of conventional ventilation, Velmahos provide an outcome benefit.
et al33 demonstrated improved oxygenation within 1 h
of being switched to HFPV. Peak inspiratory pressure
decreased with HFPV, but mPaw increased. Although Acknowledgments
the peak inspiratory pressure decreased, peak alveolar FinancialⲐnonfinancial disclosures: The authors have reported
pressure was not reported. In 12 patients with ARDS to the CHEST the following conflicts of interest: Dr Hess
following blunt trauma who were switched to HFPV has received royalties from Impact. He was a consultant for
Respironics and Pari. He also discloses relationships with Cardinal
after failure of conventional ventilation, there was an (CaseFusion) and Ikaria. Dr George was a consultant to Eubien,
improvement in oxygenation within 12 to 24 h.108 Boehringer Ingelheim, from 2006 to 2007. She has received money
However, these improvements were not due to a rise from AstraZeneca, Pfizer, Penexel, and Talceda. Drs Esan, Raoof,
and Sessler report that no potential conflicts of interest exist with
in mPaw because there was no significant change fol- any companiesⲐorganizations whose products or services may be
lowing the switch to HFPV. The mechanisms that discussed in this article.
contribute to gas exchange in HFPV and other high-
frequency ventilatory techniques have been described References
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Severe Hypoxemic Respiratory Failure : Part 1−−Ventilatory Strategies
Adebayo Esan, Dean R. Hess, Suhail Raoof, Liziamma George and Curtis
N. Sessler
Chest 2010;137; 1203-1216
DOI 10.1378/chest.09-2415
This information is current as of September 18, 2010
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