101 MECHANICAL VENTILATION

NEIL R. MACINTYRE, MD

INTRODUCTION Positive-Pressure Ventilation and Cardiac Considerations in Choosing Ventilator

POSITIVE-PRESSURE MECHANICAL Function Settings for Different Forms of
VENTILATOR DESIGN FEATURES COMPLICATIONS OF POSITIVE- Respiratory Failure
Gas Delivery Systems PRESSURE MECHANICAL RECENT INNOVATIONS IN
Subsystems of Mechanical Ventilators VENTILATION MECHANICAL VENTILATORY
Ventilator-Induced Lung Injury SUPPORT
PHYSIOLOGIC EFFECTS OF POSITIVE-
PRESSURE MECHANICAL Oxygen Toxicity Innovative Strategies for “Lung
VENTILATION Patient-Ventilator Interface Complications Protection”
Ventilation and Respiratory System Patient-Ventilator Dys-synchrony Automated Weaning Strategies
Mechanics Pulmonary Infectious Complications Optimizing Synchrony During Interactive
Alveolar Recruitment and Gas Exchange Breaths
APPLYING MECHANICAL
Mechanical Loads VENTILATORY SUPPORT
Patient-Ventilator Interactions Mechanical Ventilatory Support Involves
Tradeoffs

INTRODUCTION tive with patient efforts. Pneumatic, electronic, or micro-

Mechanical ventilation is the process of using a device (ven-
tilator) to support, partially or totally the delivery of gas to
the lungs. The desired effect of mechanical ventilation is to
maintain adequate levels of PO2 and PCO2 in arterial blood
while also unloading the inspiratory muscles. Although
negative-pressure chambers or wraps might fulfill this defi-
nition, this discussion focuses on the use of devices that use
positive airway pressures.
Positive-pressure mechanical ventilation is used widely.
In the United States, about 1 to 3 million patients annually
are estimated to receive mechanical ventilatory support
outside the operating room.1 Traditionally, this support has
been provided in intensive care unit (ICU) settings, but there
are clear trends toward expanding the venues to subacute
facilities, long-term care facilities, and the home. As the
number of elderly increases and as more aggressive surgical
and immunosuppressive therapies are developed, the need
for mechanical ventilation in all of these venues is likely to
increase.1 In addition, increasing concerns about wide-
spread outbreaks of respiratory pandemics has led many
government agencies to stockpile large numbers of mechan-
ical ventilators.2
POSITIVE-PRESSURE
MECHANICAL VENTILATOR
DESIGN FEATURES
GAS DELIVERY SYSTEMS
Positive-Pressure Breath Controller
Most modern ventilators utilize piston/bellows systems, tur-
bines, or controllers of high-pressure sources to drive gas
flow.3,4 Tidal breaths are generated by this gas flow and can
either be controlled entirely by the ventilator or be interac-
processor systems provide for various breath types. In
general, these can be classified by what initiates the breath
(trigger variable), what regulates gas delivery during the
breath (target or limit variable), and what terminates the
breath (cycle variable).5,6
Breath triggers are generated by either a change in pres-
sure or flow initiated by patient effort (assisted/supported
breath) or by a set time (controlled breath). During the
breath, gas delivery is regulated to meet a target or limit
variable, which is generally either a set flow or a set inspira-
tory pressure. The breath is then terminated by a cycle vari-
able, which can either be a set volume, a set inspiratory
time, or a set flow. A high-pressure cycle variable is usually
also present to limit lung over distention. Figure 101-1 uses
this classification scheme to describe the five most common
breath types available on the current generation of ventila-
tors: volume assist (VA), volume control (VC), pressure assist
(PA), pressure control (PC), and pressure support (PS).
Mode Controller/Feedback Systems
The availability and delivery logic of different breath types
define the “mode” of mechanical ventilatory support.3,5,6
The mode controller is an electronic, pneumatic, or
microprocessor-based system that is designed to provide the
proper combination of breaths according to set algorithms
and feedback data (conditional variables) (Table 101-1).
The simplest mode is assist-control ventilation (ACV),
which can provide either flow-targeted volume-cycled
breaths (volume assist-control ventilation [VACV]) or pressure-
targeted time-cycled breaths (pressure assist-control ventila-
tion [PACV]). A simple feedback system is employed with
ACV that guarantees a set number of positive-pressure
breaths. If the patient’s underlying respiratory rate exceeds
this guarantee, all breaths are patient-triggered breaths (VA
or PA breaths). If the patient’s respiratory rate is below this
guarantee, the ventilator will “make up the difference” with
mandatory (controlled) breaths (VC or PC breaths).
1761
1762 PART 3  •  Clinical Respiratory Medicine

VOLUME VOLUME PRESSURE PRESSURE PRESSURE

CONTROL ASSIST CONTROL ASSIST SUPPORT

Set pressure Set pressure Set pressure

pressure
Circuit

+
0
−
Set ti Set ti

Set flow Set flow Set minimal flow

in
Flow

0
out
increasing

Set volume Set volume

Volume

Machine Patient Machine Patient Patient

triggered triggered triggered triggered triggered
Figure 101-1  Circuit pressure, flow, and volume tracings over time depicting the five basic breaths available on most modern mechanical ventila-
tors. Breaths are classified by the variables that determine the trigger (machine time or patient effort), target/limit (ti, set flow or set pressure), and cycle
(set volume, set time, or set flow). The solid lines represent set or independent responses, and the dashed lines represent dependent responses. In all of
these breaths, pressure is usually a “backup” cycle variable designed to terminate gas delivery if circuit pressure rises above an alarm limit.

Table 101-1  Breath Types Available on Common Modes of
Mechanical Ventilation*
BREATH TYPES AVAILABLE†
Mode VC VA PC PA
Volume assist—control X X
Pressure assist—control X X
Volume SIMV X X
Pressure SIMV X X
Pressure support
*In addition to the five “basic” breaths depicted in Figure 101-1, this table
†
also includes spontaneous unassisted/unsupported breaths.
VC, volume control; VA, volume assist; PC, pressure control; PA, pressure
assist; PS, pressure support; Sp, spontaneous unassisted.
SIMV, synchronized intermittent mandatory ventilation.
Another relatively simple mode is synchronized intermit-
tent mandatory ventilation (SIMV), which can provide either
flow-targeted volume-cycled breaths (volume SIMV) or
pressure-targeted time-cycled breaths (pressure SIMV). Like
ACV, SIMV guarantees a set minimal number of positive-
pressure breaths. Unlike ACV, however, if the patient’s respi-
ratory rate exceeds this guarantee, the ventilator will
provide assisted breaths up to the set rate and then allow
unassisted (simple SIMV mode) or flow-cycled pressure
support breaths (SIMV + PS mode) thereafter. If the patient’s
respiratory rate is below the set guarantee, the ventilator
will again “make up the difference” with mandatory (con-
trolled) breaths. Note that although PS breaths are often
provided during SIMV, PS breaths can also be provided as a
stand-alone mode without any guaranteed breaths (pres-
sure support ventilation). Importantly, many modern
systems also have algorithms to generate breaths when an
apnea is detected; this represents a safety feature for modes
with either low or no set guaranteed rates in case patient
respiratory efforts are suddenly reduced or absent.
In recent years, more sophisticated feedback systems
PS Sp have been developed for these basic modes and are now
available on many modern devices. These include pressure-
regulated volume control (PRVC), volume support (VS), and
X X adaptive support ventilation (ASV).
X X
PRVC (also known by proprietary names such as “VC+,”
“Autoflow,” and others) is an assist-control PACV that uses
X
tidal volume as a feedback control for continuously adjust-
ing the pressure target.7 The clinician sets a tidal volume
target, and the ventilator then automatically sets the inspi-
ratory pressure within a clinician-set range to achieve
this goal.
VS is also based on a feedback design using patient-
triggered, pressure-targeted, flow-cycled PS breaths. If a
patient’s respiratory drive exceeds the clinician-set guaran-
teed rate, some PRVC systems will provide additional
patient-triggered, time-cycled PRVC breaths while others
will provide patient-triggered flow-cycled VS breaths. It is
important to note that, with both PRVC and VS breaths, an
improvement in respiratory mechanics will result in a lower
applied inspiratory pressure, whereas a worsening in respi-
ratory mechanics will result in a higher applied inspiratory
pressure. Similarly, increasing respiratory effort by the
patient will result in a lower applied inspiratory pressure,
whereas decreasing respiratory effort by the patient will
result in a higher applied inspiratory pressure.
ASV is also an assist-control, pressure-targeted, time-
cycled mode of ventilation PACV that utilizes respiratory
system mechanics to set the tidal volume-frequency
pattern.8 The clinician sets only a desired minute ventila-
tion and patient weight (for estimating anatomic dead
space). Using controlled breaths, ASV initially calculates

resistance and compliance, as well as the expiratory time
constant (resistance × compliance). The ASV algorithm
then adjusts the frequency–tidal volume pattern to mini-
mize ventilator work (integral of pressure over volume) and
thus conceptually to minimize applied forces to the lungs.
The breathing pattern is also modulated by incorporating
the expiratory time constant to avoid air trapping. As respi-
ratory mechanics change, the frequency–tidal volume
pattern is automatically adjusted to maintain minimal ven-
tilatory work. In contrast, if patient efforts are triggering
breaths with ASV, it behaves much like VS.
SUBSYSTEMS OF MECHANICAL VENTILATORS
Effort (Demand) Sensors
Current ventilators have sensors that detect patient effort,
thus allowing for a number of interactions between the
patient and the ventilator.9-11 Examples include patient-
triggered breaths in which the ventilator initiates flow in
response to patient demand and pressure-targeted/limited
breaths in which the ventilator adjusts flow in response
to patient demand (see “Patient-Ventilator Interactions”
later). These sensors are usually either pressure or flow
transducers in the ventilatory circuitry and are character-
ized by their sensitivity (the circuit pressure or flow change
needed to initiate a ventilator response) and their responsive-
ness (the time needed to provide this response).12
Gas Blenders
Blenders mix air and O2 to produce a fractional concentration
of O2 in inspired gas (FIO2) ranging from 0.21 to 1.0. On
newer systems, blenders are also available for other gases
such as heliox, nitric oxide (NO), and anesthetic agents.
Humidifiers
With the upper airway bypassed by tracheal intubation,
sufficient heat and moisture must be added to the inspired
gas mixtures to avoid mucosal desiccation. Active humidi-
fiers utilize external water sources and electrical power to
adjust blended gas mixtures to near body conditions (tra-
cheal temperature of > 35° C, water content of > 40 mg/L).13
Heated wire circuits help facilitate this by preventing con-
densation and “rainout” in the ventilator tubing. Passive
humidifiers use simple heat/moisture exchange devices in
the ventilator circuit that reutilize heat and moisture
trapped from expired gas. These disposable units can usually
supply adequate heat and moisture (i.e., > 30° to 33° C and
> 28 to 32 mg/L H2O) for many patients, particularly those
receiving mechanical ventilation for only short periods
of time.13
Expiratory Pressure Generator
Positive end-expiratory pressure (PEEP), or positive airway
pressure throughout expiration, can be generated to help
maintain alveolar patency and improve ventilation-perfusion
  matching (see “Physiologic Effects of Positive-Pressure
( V/Q)
Mechanical Ventilation” later). PEEP is usually applied by
regulating pressure in the expiratory valve of the ventilator
system but can also be applied by providing a continuous
flow of source gas during the expiratory phase. Some expira-
tory valves have measurable resistance even when fully
101  •  Mechanical Ventilation 1763
open; this may result in inadvertent PEEP.14 As discussed in
more detail later, a positive alveolar pressure may be present
at end expiration if the expiratory time is inadequate for
the lung to return to its “resting volume” or if significant
flow limitation exists. Such inadvertent PEEP is referred to
as intrinsic PEEP (PEEPi), or as “auto-PEEP,” “occult PEEP,”
or “air trapping.”15
Gas Delivery Circuit
The circuit linking the ventilator to the patient usually con-
sists of flexible tubing that often contains pressure or flow
sensors, closed suctioning systems, and an exhalation
valve. It is important to remember that, because this tubing
has measurable compliance (2 to 4 mL/cm H2O are repre-
sentative values), high circuit pressures may induce signifi-
cant amounts of delivered gas to distend the circuitry rather
than to enter the patient’s lungs.
Patient–Ventilator Circuit Interface
Positive-pressure ventilation is usually delivered through a
tube inserted into the patient’s airway (orotracheal or naso-
tracheal tube or tracheostomy). These tubes generally have
air-filled balloons, which are inflated to provide a proper
airway seal. An alternative to the tracheal tube is a mask
system. Both full-face and nasal masks have been utilized
with a variety of ventilatory support systems and modes.16
Leaks around masks, however, can be significant and thus
ventilatory support modes using masks must be able to
provide adequate volumes and proper inspiratory timing. To
this end, special mask ventilators with pressure-targeted
and either time-cycled or leak-compensated, flow-cycled
capabilities have been developed.16
Aerosol Generators (see Chapter 11)
Therapeutic aerosols (e.g., bronchodilators, steroids, vaso-
dilators, antibiotics) can be delivered through the ventila-
tor circuitry17 either by in-line nebulizers or by special
adapters designed for metered-dose inhalers. Lung deposi-
tion is generally less in an intubated than in a nonintu-
bated patient because the endotracheal tube serves as a
significant barrier to aerosol delivery. Higher dosing is thus
advisable.
The location of the aerosol generator in the ventilator
circuit can affect deposition. The optimal site appears to be
in the inspiratory limb several centimeters proximal to the
patient’s “wye” connector.17 This location allows either
nebulized medications or a metered-dose actuation to
“charge” the inspiratory limb of the circuit during exhala-
tion. Aerosol particle velocity is also slowed and becomes
the leading portion of the next inspiration, both of which
facilitate delivery.
Monitors and Graphic Displays
Although electronic and microprocessor-based systems
have considerable internal monitoring of electronic and
pneumatic function, the three variables generally displayed
for clinical use are circuit pressures, flows, and volumes.18
Pressure sensors in the esophagus to estimate pleural pres-
sures are also available.19 Alarms can be utilized on all of
these monitors.6,20 Importantly, trending capabilities for up
to 72 hours or more are now available on many modern
systems. Most modern positive-pressure ventilators also
1764 PART 3  •  Clinical Respiratory Medicine
have oxygen sensors in the circuitry to ensure that the
desired FIO2 is being delivered. In addition, some ventilators
may also have analyzers for measuring exhaled carbon
dioxide and inhaled therapeutic gases such as NO or heliox.
PHYSIOLOGIC EFFECTS
OF POSITIVE-PRESSURE
MECHANICAL VENTILATION
VENTILATION AND RESPIRATORY SYSTEM
MECHANICS (see Chapter 5)
Alveolar Ventilation and the Equation of Motion
Alveolar ventilation is the term for the delivery of fresh gas
to the gas exchange regions of the lungs. Mathematically,
this is expressed as:
V A = f × (VT − VD)
where V A = alveolar ventilation, f = breathing frequency,
VT = tidal volume, and VD = wasted ventilation or dead space.
V A needs to be adequate to eliminate the carbon dioxide
production ( V CO2) while maintaining a reasonable arterial
PCO2 (and pH) according to the following relationship:
PaCO2 = (V CO2 /V A) × 800
The lungs are inflated by mechanical ventilation when pres-
sure and flow are applied at the airway opening. These
applied forces overcome respiratory system compliance
(both lung and chest wall components), airway resistance,
and respiratory system inertance and lung tissue resistance
to effect gas flow.21,22 For simplicity, because inertance and
tissue resistance are relatively small, they can be ignored
yielding the simplified equation of motion:
Driving pressure = (flow × resistance)
+ (volume/system compliance)
In the mechanically ventilated patient, this relationship is
expressed as:
∆Pcir + ∆Pmus = (V × R) + (VT/CRS)
where ΔPcir is the change in ventilator circuit pressure
above baseline (peak pressure minus set end-expiratory
pressure: Ppeak − PEEP); ΔPmus is patient inspiratory
muscle pressure generation (if present); V is the flow into
the patient’s lungs; R is the resistance of the circuit, artifi-
cial airway, and natural airways combined; VT is the tidal
volume; and CRS is the respiratory system compliance. If
there is PEEPi, it must be overcome by muscle and circuit
pressure before flow and volume can be delivered and thus
PEEPi will add to the driving pressure requirement.
During an inspiratory hold at end-inspiration in a patient
who is not making respiratory efforts (i.e., no-flow condi-
tion: V = 0, Pmus = 0), the ventilator circuit pressure “pla-
teaus” at a pressure commonly referred to as the plateau
pressure (Pplat). In this way, the components of Pcir can be
determined. Specifically, the difference in Pcir during flow
and during no-flow (the “peak to plateau difference”) allows
for a calculation of total inspiratory resistance:
R = (Ppeak − Pplat)/V ration (or both). PEEPi increases with increased minute
Also, when V = 0 at end-inspiration, Pplat – PEEP allows
calculation of the static respiratory system compliance:
CRS = VT/(Pplat − PEEP)
Separating chest wall and lung compliance (CCW and CL,
respectively) requires measurement of esophageal pressure
(Pes) to estimate pleural pressure.22a With this measure-
ment, the inspiratory change in Pes (ΔPes) can be used in
the following calculations:
CCW = VT/∆Pes
CL = VT/(Pplat − PEEP − ∆Pes)
In clinical practice, because CCW is usually quite high and
ΔPes is thus quite low, Pplat alone is often taken as an
approximation of end inspiratory lung-distending pressure.
However, there are many situations in which there is a stiff
chest wall and this crude approximation is not valid (e.g.,
obesity, acute respiratory distress syndrome [ARDS], ascites,
surgical dressings). Under these situations, the impact of a
stiff chest wall must be considered when using these mea-
surements to assess lung stretch.19,23,24
Flow-Targeted Versus Pressure-Targeted Breaths
There are two basic approaches to delivering positive-
pressure breaths: flow targeting and pressure targeting (see
Fig. 101-1).3,5 With flow targeting (breaths 1 and 2 in Fig.
101-1), the clinician sets the inspiratory flow; circuit pres-
sure is then the dependent variable. With pressure targeting
(breaths 3 through 5 in Fig. 101-1), the clinician sets an
inspiratory pressure target (with either time or flow as the
cycling criterion); flow and volume are then the dependent
variables (i.e., varying with the lung mechanics and patient
effort). With a flow-targeted breath, changes in compliance,
resistance, or patient effort will change Pcir (but not flow);
in contrast, with a pressure-targeted breath, similar changes
in compliance, resistance, or effort will cause a change of
tidal volume (but not Pcir) (see dashed lines in Fig. 101-1).
Each strategy has advantages.25 For flow-targeted
breaths, a minimal tidal volume is guaranteed. For pressure-
targeted breaths, the rapid initial flow and subsequent
adjustable flow of pressure targeting may enhance gas
mixing and patient synchrony (see discussions “Distribu-
tion of Ventilation” and “Patient-Ventilator Interactions”
later).
Pressure-targeted breaths can also be modified with a
volume feedback feature described earlier for PRVC and VS
breaths to combine the enhanced gas mixing and patient-
ventilator synchrony effects of a pressure-targeted breath
with a certain volume guarantee. However, it is important
to realize that providing a volume guarantee negates the
pressure-limit feature set by the clinician because, with
PRVC/VS, worsening respiratory system mechanics will
drive applied pressures up. Another potential problem with
PRVC/VS is that it may not adequately unload the patient
if patient effort inappropriately increases due to pain or
anxiety.26
PEEPi and the Ventilatory Pattern
PEEPi is the positive alveolar end-expiratory pressure that
arises because of inadequate expiration, caused by either
inadequate expiratory time or airway collapse during expi-
 101  •  Mechanical Ventilation 1765

NORMAL LOW REGIONAL CL NORMAL HIGH REGIONAL RAW

Positive Positive
pressure pressure
breath breath

A B
Figure 101-2  The distribution of ventilation in lung models with heterogeneous mechanical properties. Models of the lung are shown as two units
with homogeneous mechanical properties (normal): (A) with abnormal compliance distribution (low regional lung compliance [CL]) and (B) abnormal
resistance distribution (high regional airway resistance [RAW]). Note that in situations with heterogeneous lung mechanics, positive-pressure breaths are
preferentially distributed to “healthier” regions of the lung and can produce regional overdistention—even when a normal-sized tidal volume is delivered.
Note that in the obstructed example (high regional RAW), the overdistention may be transitory as gas moves from the low-resistance to the high-resistance
unit over time (pendelluft). (Redrawn from MacIntyre NR: Mechanical ventilatory support. In Dantzker D, MacIntyre NR, Bakow E, editors: Comprehensive respiratory
care. Philadelphia, 1995, WB Saunders, p 453.)

ventilation, decreased expiratory time fraction, and the
increased respiratory system expiratory time constant (the
product of resistance and compliance).27
The development of PEEPi will have different effects on
flow-targeted compared with pressure-targeted ventilation.
In flow-targeted ventilation, the constant delivered flow and
volume (and thus ΔPcir) in the setting of a rising PEEPi will
increase both the Ppeak and the Pplat. In contrast, in
pressure-targeted ventilation, the set Pcir limit coupled with
a rising PEEPi level will decrease ΔPcir and thus the deliv-
ered tidal volume (and minute ventilation). Importantly,
this may help limit the build-up of PEEPi.
In the patient without respiratory effort, PEEPi can be
recognized in two ways. First, when PEEPi is produced by
an inadequate expiratory time, analysis of the flow graphic
will show that expiratory flow has not returned to zero
before the next breath is given. Second, PEEPi in alveoli with
patent airways can be quantified during an expiratory hold
maneuver that permits equilibration of the PEEPi with
Pcir.27
In the patient with active respiratory effort, PEEPi can be
assumed to be present if the expiratory flow has not reached
zero before the next breath begins. However, the expiratory
hold maneuver cannot be interpreted in an actively breath-
ing patient. As noted in more detail later, in an actively
breathing patient, PEEPi can function as an inspiratory
threshold load. This is best quantified by using Pes to esti-
mate pleural pressures. With this technique, the change in
Pes before a change in Pcir is a reflection of the threshold
load imposed by PEEPi (see “Patient-Ventilator Interac-
tions” later).
Distribution of Ventilation
A positive-pressure tidal breath must be distributed among
the millions of alveolar units in the lung.28,29 Factors affect-
ing this distribution include patient-related factors: regional
resistances, compliances, and functional residual capaci-
ties. Breaths will tend to distribute more to units with high
compliance and low resistance and away from obstructed
or stiff units (Fig. 101-2A, Low Regional CL). This creates
the potential for regional overdistention of healthier lung
units, even in the face of “normal”-sized tidal volumes (see
“Ventilator-Induced Lung Injury” later).
The flow pattern set on the ventilator may also affect
ventilation distribution. For example, when there are
marked inhomogeneities in airway resistance, slow and
constant flows will tend to distribute gas more evenly
(although consequent shorter expiratory times may worsen
air trapping).28 In addition, inspiratory pauses can also
allow pendelluft action to fill slowly filling alveoli (Fig.
101-2B, High Regional RAW). In contrast, when there is
parenchymal lung injury with minimal inhomogeneities in
airway resistance, initially rapid flows with subsequent
deceleration (typically seen in pressure-targeted breaths)
may distribute gas more evenly and will pressurize lung
units rapidly, producing a higher mean inspiratory alveolar
pressure for a given breath volume.30
It should be noted that more uniform ventilation distribu-
tion does not necessarily mean better V/Q  matching (i.e.,
more homogeneous ventilation distribution may actually
worsen V/Q  matching in a lung with inhomogeneous per-
fusion). Because of all these considerations, predicting
which flow pattern will optimize ventilation-perfusion
matching is difficult and often requires trial and error.
ALVEOLAR RECRUITMENT AND GAS EXCHANGE
Because of alveolar flooding, inflammatory exudates,
and collapse, parenchymal lung injury leads to V/Q   mis-
matching and shunts.31 In many (but not all) of these
disease processes, substantial numbers of collapsed alveoli
can be recruited during a positive-pressure ventilatory
cycle.32-35Additional recruitment can sometimes be pro-
vided with the use of formal recruitment maneuvers or pro-
longation of inspiratory time.36,37 The application of PEEP is
designed to prevent derecruitment during exhalation.
1766 PART 3  •  Clinical Respiratory Medicine
Recruitment Maneuvers
Recruitment maneuvers (RMs) can be performed using sus-
tained inflations (e.g., 30 to 40 cm H2O) for up to 30 to 120
seconds, by transient elevations of the PEEP-tidal volume
settings, and by single or multiple “sighs” that take the lung
briefly to near total lung capacity.36 To avoid patient inspira-
tory or expiratory efforts, additional sedation or even neu-
romuscular blockade may be used. Importantly, RMs can
have adverse hemodynamic consequences; close monitor-
ing of the patient is mandatory during RMs. RMs provide
initial alveolar recruitment only—maintenance of recruit-
ment requires setting PEEP appropriately to prevent subse-
quent derecruitment.36
Inspiratory Time Prolongations
A positive-pressure breath produces a flow magnitude and
a flow profile that, as noted previously, can affect ventilation
  Prolonging inspiratory time,
distribution (and thus V/Q).
generally by adding a pause, often in conjunction with a
rapid decelerating flow (i.e., pressure-targeted breath), has
several physiologic effects. First, the longer inflation period
may recruit more alveoli.38,39 Second, increased gas mixing
time may improve V/Q   matching in parenchymal lung
38
injury (pendelufft). Third, the development of PEEPi from
consequently shorter expiratory times can have effects
similar to those of applied PEEP (see earlier).39 It should be
noted, however, that the distribution of PEEPi, which is
most pronounced in lung units with long expiratory time
constants, may be different from that of applied PEEP and
  may also be different with intrinsic
thus the effects on V/Q
compared with applied PEEP. Fourth, because these long
inspiratory times significantly increase total intrathoracic
pressures, cardiac output may be reduced (see “Positive-
Pressure Ventilation and Cardiac Function” later). And
finally, inspiratory-to-expiratory ratios that exceed 1 : 1
(so-called inverse-ratio ventilation) are uncomfortable,
and patient sedation/paralysis is often required unless a
relief mechanism allows spontaneous breathing during the
inflation period (see “Airway Pressure Release Ventilation”
later).
Positive End-Expiratory Pressure
PEEP is defined as an elevated airway pressure at the end
of expiration.32 As noted earlier, PEEP can be produced
by either expiratory circuit valves (applied PEEP) or inade-
quate expiratory times in lung units with long expiratory
time constants (PEEPi).21,22,38 Note that expiratory muscle
contraction can also raise intrathoracic pressures at end-
expiration, but this does not have the same effects on the
lungs because transpulmonary pressure is not increased.
PEEP helps to recruit or maintain alveolar units open,
providing several potential benefits. First, recruited alveoli
  matching and gas exchange throughout the
improve V/Q
ventilatory cycle.32 Second, as discussed in more detail later,
patent alveoli throughout the ventilatory cycle are not
exposed to the risk of injury from the shear stress of repeated
opening and closing.40,41 Third, open alveoli with intact sur-
factant monolayers improve lung compliance.42 This is the
rationale behind applying PEEP after an RM: recruited
alveoli are on the deflation limb of the pressure-volume
relationship and thus the pressure required to maintain
recruitment is lower than that required for initial
recruitment.
PEEP, however, can also be detrimental. Because the tidal
breath is delivered on top of the baseline PEEP, end-
inspiratory pressures are usually raised by the application
of PEEP (although this increase may be less than the actual
added PEEP because of improved compliance). This increase
must be considered if the lung is at risk for regional over-
distention (see “Ventilator-Induced Lung Injury” later).
Moreover, since parenchymal lung injury is often quite het-
erogeneous, appropriate PEEP in one region may be subop-
timal in another and excessive in yet another.35,43,44
Optimizing PEEP is thus a balance between recruiting the
recruitable alveoli in diseased regions without overdistend-
ing already recruited alveoli in healthier regions. Another
potential detrimental effect of PEEP is that it raises mean
intrathoracic pressure, thereby compromising cardiac
filling in susceptible patients (see “Positive-Pressure Ventila-
tion and Cardiac Function” section later).
MECHANICAL LOADS
Mechanical loads describe the physical requirements of
ventilation with a single value, either the pressure-time
product (PTP—the integral of pressure over time) or work
(W—the integral of pressure over volume).21,22 Because
mechanical loads correlate with inspiratory muscle oxygen
demands,45-47a the concept of load is useful in considering
inspiratory muscle energy requirements during spontane-
ous or interactive ventilatory support. Moreover, as
described in more detail later, load referenced to muscle
strength and/or endurance properties (e.g., PTP or W
divided by muscle pressure-generating capability) can be
used to set levels of partial ventilatory support or predict
spontaneous breathing capabilities.47
Compliance, resistance, flow, and volume all contribute
to the magnitude of the load per breath. During spontane-
ous breaths, Pcir is zero and integrating Pes over time or
volume (referenced to the passive inflation pressure)
describes the load borne by the inspiratory muscles to
inflate the lungs. During a controlled breath, integrating
Pcir over time or volume describes the load borne by the
ventilator to inflate the entire respiratory system (lungs
and chest wall) and integrating Pes over time or volume
describes the loads imposed by the chest wall only. During
interactive breaths the load is shared between patient and
ventilator.48
Under heavy loading conditions (e.g., the patient with
abnormal respiratory system mechanics and thus high
pressure requirements), the duration of pressure (i.e., the
PTP) correlates better with muscle energetics and fatigue
potential than does the volume moved with pressure (i.e.,
work).45,46 Indeed, during ventilation requiring high pres-
sures, multiplying PTP by the inspiratory time fraction and
referencing this to the maximal pressure that the inspira-
tory muscles can generate results in the pressure-time index
(PTI). Muscle fatigue can be expected if the PTI value
exceeds 0.15.48,49 The concern with high pressure loads in
patients receiving partial ventilatory support is one of the
rationales for providing ventilator pressure assistance with
every spontaneous effort (i.e., pressure-assisted or sup-
ported breaths), as opposed to supporting only some breaths

as in intermittent mandatory ventilation without pressure
support (see “Patient-Ventilator Interactions” later).50
Inspiratory muscle overload is one of the major determi-
nants of continuing ventilator dependency and can result
either from excessive mechanical loads or from inspiratory
muscle dysfunction. Excessive mechanical loads can result
from disease or from inappropriate ventilatory assistance
(see “Patient-Ventilator Interactions” later). Clinically,
inspiratory muscle overload is manifested by rapid, shallow
breathing patterns, paradoxical abdominal motion, and
patient distress. Inspiratory muscle dysfunction can be a
result of the systemic inflammatory response syndrome,
metabolic disturbances, drugs (e.g., steroids, previous use
of neuromuscular blockers), malnutrition, or malposition-
ing (i.e., diaphragm flattening from lung overinflation).51
Finally, insufficient loading may also affect inspiratory
muscles. Specifically, controlled mechanical ventilation
without any patient effort, perhaps for as little as 24 hours,
may produce muscle changes similar to disuse atrophy—a
condition described as ventilator-induced diaphragmatic dys-
function (VIDD).52-54
PATIENT-VENTILATOR INTERACTIONS
Mechanical ventilation modes that permit spontaneous
ventilatory activity are termed “interactive” modes. These
interactions can range from simple triggering of mechani-
cal breaths to more complex processes affecting delivered
flow patterns and breath timing. Interactive modes allow for
muscle “exercise,” which, when performed at nonfatiguing
or physiologic levels, may prevent VIDD and facilitate
fatigue recovery.11,52-54 In addition, permitting spontaneous
patient ventilatory activity with “comfortable” interactive
modes may reduce the need for the sedation and/or neuro-
muscular blockers that may otherwise be used to prevent
patients from “fighting the ventilator.”11,55 Interactions take
place during all three phases of breath delivery: breath trig-
gering, flow delivery, and breath cycling and are described
in detail later in “Patient-Ventilator Dys-synchrony.”
POSITIVE-PRESSURE VENTILATION AND
CARDIAC FUNCTION
In addition to affecting ventilation and ventilation distribu-
tion, positive-pressure ventilation can also affect cardio­
vascular function.56-58 In general, as mean intrathoracic
pressure increases, right ventricular filling decreases
and cardiac output/pulmonary perfusion consequently
decreases. This is the rationale for using volume repletion
to maintain cardiac output in the setting of high intratho-
racic pressure. Of note, the effect of reduced cardiac filling
on cardiac output may be partially counteracted by improve-
ment in left ventricular function due to elevated intratho-
racic pressure, which can reduce left ventricular afterload.59
Importantly, in patients with left heart failure, the reduced
cardiac filling and reduced left ventricular afterload effects
of elevated intrathoracic pressure may improve cardiac
function to the point that the removal of intrathoracic pres-
sure may worsen cardiac function and thereby produce
weaning failure.60
Intrathoracic pressures can also influence distribution of
perfusion. The relationship of alveolar pressures to perfu-
101  •  Mechanical Ventilation 1767
sion pressures in the three-zone West lung model helps
explain this.61 Specifically, the dependent lung is generally
in a zone 3 (capillary distention) state. As intra-alveolar
pressures rise, however, zone 2 and zone 1 (capillary
 
collapse/dead space) regions can appear, creating high V/Q
units. Indeed, increases in dead space can be a consequence
of ventilatory strategies employing high ventilatory pres-
sures, as well as with those producing PEEPi.
Positive-pressure mechanical ventilation can affect other
aspects of cardiovascular function. Specifically, dyspnea,
anxiety, and discomfort from inadequate ventilatory support
can lead to stress-related catecholamine release with subse-
quent increases in myocardial oxygen demands and risk of
dysrhythmias.60 In addition, coronary blood vessel oxygen
delivery can be compromised by inadequate gas exchange
from the lung injury coupled with low mixed venous PO2
due to high oxygen consumption demands by the inspira-
tory muscles.
COMPLICATIONS OF
POSITIVE-PRESSURE
MECHANICAL VENTILATION
VENTILATOR-INDUCED LUNG INJURY
The lung can be injured when it is stretched excessively.
The most obvious injury is barotrauma: alveolar rupture
presenting as extra-alveolar air in the mediastinum (pneu-
momediastinum), pericardium (pneumopericardium), sub-
cutaneous tissue (subcutaneous emphysema), pleural
space (pneumothorax), or vasculature (air emboli).62 The
risk for extra-alveolar air increases as a function of the
magnitude and duration of alveolar overdistention. Thus
interactions of respiratory system mechanics and mechan-
ical ventilation strategies (high regional VT and PEEP—
both applied and intrinsic) that produce regions of
excessive alveolar stretch create alveolar units at risk for
rupture.
Even without producing extra-alveolar air and rupture,
mechanical ventilation can induce ventilator-induced lung
injury (VILI).62a,62b In experimental animals, acute lung
injury can be produced by mechanical ventilation strategies
that stretch the lungs beyond the normal maximum volume
(at transpulmonary distending pressures of 30 to 35 cm
H2O).63-65 In engineering parlance, this is termed mechani-
cal “stress.”66 A number of clinical trials clearly indicate
that ventilator strategies exposing the injured human lung
to transpulmonary pressures in excess of 30 to 35 cm H2O
are associated with lung injury.67-70 Importantly, VILI may
be more than simply a consequence of excessive end-
inspiratory stretch. Even in the setting of transpulmonary
pressures less than 30 cm H2O, excessive tidal stretch from
repetitive cycling of the lung with tidal volumes in excess of
8 to 10 mL/kg ideal body weight (IBW) may contribute to
VILI.67,68 Interestingly, this VILI risk may be better quanti-
fied by referencing the tidal volume to the resting lung
volume and can be termed mechanical “strain.”66 Other
ventilatory pattern factors, such as the frequency of
stretch71 or the acceleration/velocity of stretch,72 may also
be involved in the development of VILI. VILI appears to be
1768 PART 3  •  Clinical Respiratory Medicine

potentiated by a shear stress phenomenon that takes place
when injured alveoli repetitively open and collapse during
the ventilatory cycle (i.e., cyclical atelectasis).40,73,74 Vascu-
lar pressure elevations may also contribute to VILI.75
VILI likely develops regionally when low-resistance/
high-compliance units receive a disproportionately high
regional tidal volume in the setting of high alveolar distend-
ing pressures (see Fig. 101-2). This can be appreciated
using computed tomography under circumstances when
pressures required for recruitment of diseased atelectatic
regions simultaneously produce overdistention in already
open, less-diseased regions (Fig. 101-3).76 Regional protec-
tion of these healthier lung units is the rationale for using
“lung-protective” ventilator strategies that accept less than
normal values for pH and arterial PCO2 in exchange for
lower (and safer) distending pressures (see “Applying
Mechanical Ventilatory Support” later).77 Interestingly,
data suggest that a permissive respiratory acidosis might
also have therapeutic effects on alveolar injury from VILI,
although the clinical applicability of this observation is
not clear.78
VILI is manifest pathologically as diffuse alveolar
damage.40,63,64,79 Moreover, VILI is associated with cytokine
release79,80 and bacterial translocation,81 which are impli-
cated in the systemic inflammatory response with multior-
gan dysfunction that results in VILI-associated mortality.
OXYGEN TOXICITY
Very high inspired oxygen concentrations can cause oxidant
injury in airways and lung parenchyma.82 Much of the data
supporting this concept, however, has come from animals
that often have quite different tolerances to oxygen than
humans. It is thus not clear what the “safe” oxygen concen-
tration or duration of exposure is in sick humans. Most
consensus groups have argued that FIO2 values less than
0.4 are safe for prolonged periods of time and that FIO2
values of greater than 0.70 should be avoided if possible.
Interestingly, several observational trials suggest that even
with a “safe” FIO2 less than 0.4, maintaining an arterial PO2
greater than 120 to 130 mm Hg may produce systemic
oxygen toxicity over time.83,84

1500 450

400
1250 high PEEP
350
Lung volume (mL)

1000 300

250
750 moderate PEEP
200

500 150
no PEEP
100
250
50

0 0
0 5 10 15 20 25 30 −900 −700 −500 −300 −100 0 100
Airway pressure (cm H 2 O) Hounsfield units (HU)

moderate
no PEEP PEEP high PEEP

Figure 101-3  Effects of positive airway pressure in a lung with heterogeneous injury. The upper left panel shows the almost linear pressure-volume
relationships as positive airway pressure is applied to the lungs. At the bottom are three representative CT lung slices at low, midrange, and maximal
airway pressure. In the lung at low airway pressure (no PEEP, lower left), note the substantial atelectasis in the dependent lung regions, which is progres-
sively reduced as airway pressure is increased (moderate PEEP and high PEEP, in the right two images). The upper right panel depicts the distribution of
Hounsfield units (HUs) in each of these three CT slices, at low pressure (dark blue), at midrange airway pressure (brown), and at the highest airway pressure
(light green). Note that, although increasing pressure progressively reduces the number of atelectatic units (those with CT numbers near zero), these same
pressures simultaneously increase the number of overdistended lung units elsewhere in the lungs (those with CT numbers < −900 HU). (From Vieira SR,
Puybasset L, Lu Q, et al: A scanographic assessment of pulmonary morphology in acute lung injury. Am J Resp Crit Care Med 159:1612–1623, 1999.)

PATIENT-VENTILATOR INTERFACE
COMPLICATIONS
The patient must be connected to the ventilator via ventila-
tor circuitry and an artificial airway. Problems with this
interface can lead to complications. The most obvious issue
is disconnection from the ventilator (including artificial
airway dislodgment). Disconnections have been reported in
up to 8% to 13% of ventilated patients85 and, if left uncor-
rected, can be fatal. Because circuit pressure and flow can
be maintained despite the disconnection of the ventilator
from the patient (e.g., if the airway is in the esophagus or if
the disconnected circuit remains partially occluded), it is
critical that carefully set, redundant (i.e., pressure, flow, and
even exhaled carbon dioxide) alarms are present.6 Other
complications of the patient-ventilator interface include
obstructions from secretions, circuit leaks, airway injury
from inadequate heat/humidity, tracheal injury from the
artificial airway, and loss of delivered tidal volume in a com-
pliant circuit.
PATIENT-VENTILATOR DYS-SYNCHRONY
Patient-ventilator dys-synchrony describes the delivery of a
breath from a mechanical ventilator that is not matched to
patient effort. As noted earlier, this can take place during
the triggering process, flow delivery, and breath cycling.
Ventilator Breath Triggering
Ventilators may sense a spontaneous effort by either an
airway pressure drop or an airway flow change.9,10,86 Even
with modern sensors, there is unavoidable dys-synchrony
in the triggering process. First, a certain level of sensor
insensitivity must be incorporated to avoid artifacts trigger-
ing the ventilator (i.e., “auto-triggering” due to cardiogenic
oscillations). Second, even when the patient effort has been
sensed, there is an inherent delay (up to 100 msec or more)
in activating a valving system to open and achieve target
airway flow (system responsiveness). Both of these factors
can result in significant “isometric-like” pressure loads on
the inspiratory muscles during the triggering process. In
addition, in the setting of air trapping and PEEPi, the ele-
vated end-expiratory alveolar pressure acts as a triggering
threshold load on the inspiratory muscles. Under these con-
ditions, judicious use of applied PEEP can equilibrate expi-
ratory pressure throughout the lungs and the ventilator
circuit to reduce this triggering load.87,88
Excessive triggering can also result from auto-triggering
as noted earlier or from the triggering of a second breath
when the mechanical breath cycles before the termination
of patient effort (“breath stacking”). A recently described
phenomenon, “entrainment,” can also result in a double
breath.89 Entrainment can be seen during a machine-
triggered breath when the delivered gas flow elicits an effort.
Sometimes this simply extends the breath, but if the effort
persists beyond machine breath termination, a second
breath can be triggered.
Ventilator-Delivered Flow Pattern
During an interactive breath, inspiratory muscles are con-
tracting90,91 and the ventilator flow delivery should be ade-
quate to provide proper muscle unloading. This does not
101  •  Mechanical Ventilation 1769
mean that muscle loads are eliminated. Instead, it means
that a delivered flow pattern is associated with a muscle
loading pattern that resembles normal, comfortable breath-
ing11 (“synchronous” flow delivery).
In general, flow synchrony is best assessed by clinical
assessment and analyzing the graphic representation of
circuit pressure over time.11,92 Flow synchrony is manifest
clinically as a relaxed patient who does not appear dyspneic.
In contrast, flow dys-synchrony is often manifest as tachy-
pnea, air hunger (dyspnea), and the appearance of “flow
starvation.”11 With synchronous flow delivery, the circuit
pressure graph should maintain either a steady baseline
profile (a CPAP breath) or a convex upward shape (assisted/
supported breath) indicating that flow is proportional to
demand. Dys-synchrony (and imposed loading) is said to
exist when the circuit pressure graph is literally “sucked
downward” by effort in excess of flow delivery, often below
the baseline11,93 (Fig. 101-4).
Breath Cycling
Cycling dys-synchrony can arise in one of two ways. First,
if the mechanical breath lasts beyond the duration of
patient effort, an inadequate expiratory time may develop
(along with air trapping) and/or patient expiratory efforts
may be required to terminate the breath.11 This can be a
particular concern when using PS breaths in obstructive
airway disease—the relatively steady inspiratory flow with
PS in these patients coupled with the PS flow-cycling algo-
rithm may significantly delay breath termination.94 Second,
if the mechanical breath terminates before the patient
effort is finished, the patient may be left demanding addi-
tional flow without any being delivered. Significant imposed
Dys-synchronous Synchronous
· ·
V V
Flow
VT VT
Volume
PAW PAW
Pressure
2 4 6 2 4 6
Figure 101-4  Flow and pressure pattern differences during dys-
synchronous and synchronous breaths in a patient with a vigorous
inspiratory effort. Depicted are flow (upper panel), volume (middle panel),
and pressure (lower panel) for a dys-synchronous flow-targeted breath
(left) and a more synchronous pressure-targeted breath (right) with
matched mean flow, inspiratory time, and tidal volume. Note that, during
the flow-targeted breaths (left), the fixed flow does not respond to the
vigorous inspiratory effort, resulting in the circuit pressure being “sucked”
downward (solid arrow). In contrast, with the pressure-targeted breath,
flow adjusts and increases to meet the inspiratory effort better (dashed
arrow). (Redrawn from Yang LY, Huang YC, MacIntyre NR: Patient-ventilator
synchrony during pressure-targeted versus flow-targeted small tidal volume
assisted ventilation. J Crit Care 22:252–257, 2007.)
1770 PART 3  •  Clinical Respiratory Medicine
loading and, as noted earlier, double breath triggering may
result.11
Clinical Implications
Determining the prevalence of patient-ventilatory dys-
synchrony is difficult because studies examining this
question have used heterogeneous patient populations
and different definitions of dys-synchrony, methods of
detection, duration and timing of observation, and ventila-
tory modes.11,95 Triggering dys-synchronies have been the
most well studied. Depending on patient population, venti-
lator settings, and measurement techniques, triggering
dys-synchronies have been reported in 26% to 82% of
mechanically ventilated patients. Not surprisingly, trigger
dys-synchronies were more common in patients with COPD
and those at risk for intrinsic PEEP development.11,95 Double
triggering is the other commonly reported triggering dys-
synchrony but is generally described in less than 10% of
patients in these various studies.11,95
The incidence of other forms of dys-synchrony (flow dys-
synchrony and cycle dys-synchrony) has not been as well
characterized. However, a retrospective evaluation of the
National Institutes of Health ARDS Network small tidal
volume study reported cycling dys-synchronies associated
with double triggering in 9.7% of all breaths analyzed.96
Indeed, it is likely that patient-ventilatory dys-synchrony is
ubiquitous if any patient is observed long enough during
assisted/supported mechanical ventilation, especially if
more sophisticated monitors (e.g., Pes or diaphragmatic
electromyograms) are employed to detect patient effort.
Although there is no doubt that many dys-synchronies
are subtle and of little clinical relevance, significant dys-
synchronies may be missed, thus overloading respiratory
muscles and producing patient discomfort, which is a
frequently cited indication for the administration of seda-
tives.11,95 This may impact ventilator duration because high
sedation usage is linked to longer ventilator use. Indeed,
several observational studies have noted more days of
mechanical ventilation and even trends toward higher mor-
tality in patients with trigger dys-synchronies taking place
more than 10% of the time.95
Managing Dys-synchronies
Synchronous ventilator settings first require setting the
trigger to as sensitive a setting as possible (without auto-
triggering). If PEEPi is creating a triggering load, attempts
should be made to minimize PEEPi and then judicious use
of applied PEEP added to counterbalance the imposed trig-
gering load as described later. If entrainment is present,
reducing sedation and the need for a mandatory (con-
trolled) breath rate should be re-assessed.
Flow synchrony is often easier to achieve with variable
flow pressure-targeted breaths, as noted earlier. Pressure-
targeted breaths can also allow for adjustments in the rate
of pressure rise and can compensate for endotracheal tube
resistance, as means of further enhancing synchrony (see
“Recent Innovations in Mechanical Ventilatory Support”
later). If flow-targeted breaths are desired, synchrony can
be addressed with adjustments in flow magnitude and
profile (sine wave, square wave, decelerating pattern).
Importantly, because the patient’s respiratory drive is mod-
ulated by mechanical feedback from the lungs and thorax,
modes that avoid multiple different breath types (i.e., avoid-
ing SIMV) tend to facilitate flow synchrony.11 Finally, breath
duration should be optimized for comfort and for elimina-
tion of double breaths by using adjustments in the cycle
variable (volume, time, or flow).
Two new modes (proportional assist ventilation [PAV] and
neurally adjusted ventilatory assistance [NAVA]) have been
used over the past decade to enhance synchrony further.
These are described in more detail later in “Recent Innova-
tions in Mechanical Ventilatory Support.”
PULMONARY INFECTIOUS COMPLICATIONS
Mechanically ventilated patients are at risk for pulmonary
infections for several reasons.97 First, the natural glottic
closure protective mechanism is compromised by an endo-
tracheal tube. This permits continuous seepage of oropha-
ryngeal material into the airways. Second, the endotracheal
tube itself impairs the cough reflex and serves as an addi-
tional potential portal for pathogens to enter the lungs. This
is particularly important if the circuit is contaminated.
Third, airway and parenchymal injury both from the under-
lying disease and from management complications make
the lung prone to infections. Fourth, the ICU environment
itself, with its heavy antibiotic use and presence of sick
patients in close proximity, increases risk for a variety of
infections.
Preventing ventilator-associated pneumonia (VAP) is criti-
cally important because the development of VAP heavily
influences both length of stay and mortality.97-100 Care
“bundles” linked to better outcomes include handwashing,
elevating the head of the bed, oral care with chlorhexidine,
and carefully chosen antibiotic regimens for other infec-
tions. Management strategies that avoid breaking the integ-
rity of the circuit (e.g., by changing the circuit only when
visibly contaminated) also appear to be helpful.98,99 Con-
tinuous drainage of subglottic secretions may be another
simple way of reducing lung contamination by oropharyn-
geal material.98,99 More controversial are devices to cleanse
the endotracheal tube or make it resistant to biofilm
buildup.101
Another concept explored in small trials is the use
of aerosolized antibiotics in patients with purulent secre-
tions to reduce progression of tracheobronchitis to
ventilator-associated pneumonia.102 Finally, prompt discon-
tinuation of ventilatory support when clinically appropri-
ate will help minimize the time patients are exposed to
infection risks.
APPLYING MECHANICAL
VENTILATORY SUPPORT
MECHANICAL VENTILATORY SUPPORT
INVOLVES TRADEOFFS
The goals of providing adequate support while minimizing
the risk of VILI and other complications involves tradeoffs.
Specifically, the need for potentially injurious pressures,
volumes, and supplemental O2 must be weighed against the
benefits of supporting gas exchange. To this end, a
“re-thinking” of gas exchange goals has taken place over

the past 2 decades so that now, pH levels as low as 7.15 to
7.20 and PO2 values as low as 55 mm Hg are often consid-
ered acceptable in order to protect the lung.70,78,103 Ventila-
tor settings are thus selected to provide at least this level of
gas-exchange support while meeting three mechanical
goals: (1) provision of enough PEEP to recruit the “recruit-
able” alveoli, (2) avoidance of a PEEP-tidal volume combi-
nation that unnecessarily overdistends lung regions at
end-inspiration, and (3) limiting tidal volumes to the physi-
ologic range. These goals embody the concept of a lung-
protective mechanical ventilatory strategy. Currently, these
principles guide recommendations for the specific manage-
ment of various forms of respiratory failure.104-107
CONSIDERATIONS IN CHOOSING VENTILATOR
SETTINGS FOR DIFFERENT FORMS OF
RESPIRATORY FAILURE
Parenchymal Lung Injury
Parenchymal lung injury means injury that involves the air
spaces and the interstitium of the lung.31-35 In general,
parenchymal injury stiffens lungs and decreases lung
volumes. It is important to realize that there are often
marked regional differences in the degree of mechanical
abnormalities, which interact with the particular ventila-
tory strategy. This is because delivered gas will preferentially
go to the more normal regions, those with higher compli-
ance and lower resistance, rather than to abnormal regions
(see Fig. 101-2). A “normal-sized” tidal volume may thus
be distributed preferentially to the healthier regions, result-
ing in a regional overdistention injury. Parenchymal injury
can also affect the airways, especially the bronchioles and
alveolar ducts. These narrowed and collapsible small
airways can also reduce regional ventilation to injured lung
units, leading to regions of air trapping and possibly cyst
formation during the healing phase.
Gas-exchange abnormalities in parenchymal lung injury
are a consequence of alveolar consolidation, flooding, and/
or collapse producing a maldistribution of ventilation and
resulting in V/Q  mismatching and shunts.31-35 Because
  mismatching and shunt are more of an issue than
V/Q
dead space in parenchymal lung disease, hypoxemia tends
to be more of a clinical problem than carbon dioxide
elevation.
Frequency-tidal volume settings for patients with parenchy-
mal lung injury must focus on limiting end-inspiratory
stretch. The benefit of reducing stretch in improving
outcome has been suggested by several clinical trials67-70,108
but has been most convincingly demonstrated by the
National Institutes of Health (NIH)-sponsored ARDS Network
Trial in which a ventilator strategy using a VT of 6 mL/kg
predicted body weight (PBW) as compared with 12 mL/kg
PBW led to a 10% absolute reduction in mortality.70 Thus
initial VT settings should start at 6 mL/kg PBW.68,109 More-
over, strong consideration should be given to reducing this
setting further if end-inspiratory Pplat exceeds 30 cm
H2O.67-70 Increases in the VT settings might be considered if
there is marked patient discomfort or suboptimal gas
exchange provided that the subsequent Pplat values do not
exceed 30 cm H2O.67-70 Respiratory rate settings are then
adjusted to control pH. Unlike the case in obstructive
101  •  Mechanical Ventilation 1771
diseases, the potential for air trapping in parenchymal lung
injury is low if the breathing frequency is less than 35
breaths/min; air trapping may not develop even at frequen-
cies exceeding 50 breaths/min.
There is controversy as to whether neuromuscular blockade
(NMB) and totally machine-controlled mechanical ventila-
tion should be used in the initial 24 to 48 hours of paren-
chymal lung injury. NMB use producing flaccid ventilatory
muscles reduces total body oxygen demands and eliminates
potential dys-synchronous interactions. Indeed, one study
in patients with severe hypoxemia (arterial PO2/FIO2 ratios
< 120) showed improved mortality with NMB use for 48
hours.110 However, as noted earlier, ventilatory muscles
inactive for as little as 24 hours are at risk for VIDD and
long-term disability.52-54 Moreover, the use of NMB usually
requires substantial sedative use. As a consequence, many
authorities would argue that assisted/supported breaths
are preferable early in the course of mechanical ventilatory
support. The inspiratory time and the I : E ratio in parenchy-
mal injury is set with consideration of several issues. The
usual initial I : E ratio setting is 1 : 2 to 1 : 4, the normal and
the most comfortable setting. The flow graphic should also
be assessed to ensure that cycle synchrony is present and
the expiratory time is adequate to avoid air trapping. An I : E
ratio greater than 1 : 1 is referred to as inverse-ratio ventila-
tion (IRV). In severe respiratory failure, IRV can be employed
as an alternative to increasing PEEP to improve V/Q   match-
ing.38,39 The beneficial mechanisms involved include longer
mixing times, recruitment of slowly filling alveoli, and
development of PEEPi. A variation on IRV is airway pressure
release ventilation (APRV).111-115 APRV incorporates the
ability to breathe spontaneously during the long inflation
period of a pressure-controlled breath—a feature that may
enhance recruitment and gas mixing. APRV is discussed in
more detail in “Recent Innovations in Mechanical Ventila-
tion” later.
The PEEP/FIO2 settings are optimized using both mechan-
ical and gas-exchange considerations. Conceptually, in
setting the PEEP level in parenchymal lung injury, the goal
is to provide ventilator settings between the upper and lower
inflection points on the deflation limb of the pressure-
volume curve.116 The most direct mechanical approaches
use the static pressure-volume plot to set the PEEP and VT.
This traditionally involves multiple VT/Pplat measurements
and requires considerable clinician time along with patient
sedation or even neuromuscular blockade and is not widely
used. Another mechanical approach uses step changes in
PEEP to determine the PEEP level that gives the best compli-
ance.117 A simpler mechanical approach analyzes the Pcir
profile during a constant-flow breath (stress index) to detect
overdistention (late rising profile) or collapse/reopening
injury (early rising profile).118 With all of these approaches,
a recruitment maneuver can be used to recruit the maximal
number of recruitable alveoli before setting the PEEP. FIO2
adjustments are then set as low as clinically acceptable.
PEEP can also be guided by gas-exchange criteria, usually
involving algorithms that adjust PEEP and FIO2 according
to certain targets. Note that constructing a PEEP/FIO2
algorithm is usually an empirical exercise in balancing dis-
tending pressure, arterial O2 saturation, and FIO2 and
depends on the clinician’s perception of the relative “toxici-
ties” of high thoracic pressures, high FIO2, and low arterial
1772 PART 3  •  Clinical Respiratory Medicine
24
PEEP (cm H2O)
20
16
12
8 the threshold load the patient must overcome to trigger
4 mechanical breaths, as noted earlier.
0 The gas-exchange abnormalities in the setting of worsen-
0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0
FIO2
Targets: PO2 55-80, Pplat  30-35
Figure 101-5  Two positive end-expiratory pressure (PEEP)/FIO2 algo-
rithms that have been used in National Institutes of Health Acute Res-
piratory Distress Syndrome Network clinical trials. Plotted are FIO2 on
the horizontal axis and PEEP on the vertical axis. With both approaches,
the oxygenation target (PaO2 55 to 80 mm Hg, SPO2 88% to 95%) and the
maximal allowable plateau pressure (35 cm H2O) is the same. Patients
are moved in steps up and down the algorithm according to these targets.
The two algorithms depicted either focus on higher PEEP levels (“high
PEEP”—brown bars) or lower PEEP levels (“low PEEP”—blue bars).
(Courtesy Art Wheeler, MD, personal communication and Ref. 70.)
O2 saturation. Although most of the reported PEEP/FIO2
algorithms generally target modest levels of oxygenation
(e.g., arterial PO2 55 to 80 mm Hg or SO2 88% to 95%), they
tend to segregate into approaches that focus either on
higher PEEP levels (“high PEEP” algorithms) or lower PEEP
levels (“low PEEP” algorithms) (Fig. 101-5). Several trials
have compared high versus low PEEP algorithms in con-
junction with low tidal volume/limited Pplat strategies in
patients with ARDS.119-121 A meta-analysis of trials with
mild ARDS (arterial PO2/FIO2 > 200) compared with more
severe ARDS (arterial PO2/FIO2 < 200) demonstrated that
higher PEEP strategies had a significant mortality benefit in
more severe ARDS, whereas low PEEP strategies showed a
trend toward a potential benefit in mild ARDS.122
In patients with abnormal chest wall mechanics (i.e., stiff
chest walls from obesity, anasarca, abdominal compart-
ment syndrome, and even systemic inflammation), the reli-
ance on circuit airway pressures to guide ventilator settings
will ignore the effect of elevated pleural pressures on reduc-
ing transpulmonary pressure, the ultimate determinant of
VILI and alveolar recruitment. Under these circumstances,
clinicians should consider modest empirical increases in
applied PEEP and allowances of an increased Pplat beyond
the limits described earlier. Alternatively, an esophageal
catheter to measure Pes could be inserted to assess trans-
pulmonary pressure directly and adjust settings accord-
ingly.19,123 Indeed, one clinical trial using Pes to guide PEEP
settings suggested improved outcomes.123
Obstructive Airway Disease
Increases in airway resistance lead to respiratory failure
from airflow obstruction and create two important patho-
physiologic changes. First, the increased pressures required
for airflow may overload inspiratory muscles, producing a
“ventilatory pump failure” in which spontaneous minute
ventilation becomes inadequate for gas exchange. Second,
the narrowed airways create regions of lung that cannot
properly empty and return to their normal “resting volume,”
thereby producing PEEPi.27 These regions of overinflation
create dead space and put inspiratory muscles at a substan-
tial mechanical disadvantage that further worsens muscle
function. Overinflated regions may also compress more
healthy regions of the lung, impairing V/Q   matching.
Regions of air trapping and PEEPi also function to increase
ing airflow obstruction are several. First, although there
may be a transient hyperventilation due to dyspnea in the
asthmatic patient, the worsening respiratory failure in
obstructive lung disease is generally characterized by a
falling minute ventilation as inspiratory muscles fatigue in
the face of airflow obstruction. The result is termed hyper-
capnic respiratory failure. Second, as noted earlier, regional
lung compression and regional hypoventilation produce
  mismatch that results in progressive hypoxemia. Alve-
V/Q
olar inflammation and flooding, however, are not charac-
teristic features of respiratory failure due to pure airflow
obstruction, and thus shunts are less of an issue than in
parenchymal lung injury. Third, overdistended regions of
the lung coupled with underlying emphysematous changes
in some patients result in capillary loss and increasing dead
space. This wasted ventilation further compromises the
ability of the inspiratory muscles to supply an adequate
ventilation for alveolar gas exchange. These emphysema-
tous regions also have low recoil properties, which can
worsen air trapping. Fourth, hypoxemic pulmonary vaso-
constriction coupled with chronic pulmonary vascular
changes in some airway diseases overload the right ventri-
cle, further decreasing blood flow to the lung and increasing
dead space further.
Frequency-tidal volume settings in obstructive diseases
are chosen on the basis of many considerations similar to
those in parenchymal lung injury. Specifically, tidal volumes
should be in the 6 to 8 mL/kg (IBW) range with Pplat
targets of less than 30 cm H2O.67-70 In obstructive diseases,
however, clinicians should also be aware that high peak
airway pressures, even in the presence of acceptable values
for Pplat, may transiently subject regions of the lung to
periods of overdistention injury (see Fig. 101-2). Finally,
setting the VT should also take into consideration the poten-
tial to develop PEEPi with its consequent impact on Pplat
elevations and the risk of overdistention injury.
The ventilatory rate is used to control pH. Unlike the situ-
ation in parenchymal disease, however, the elevated airway
resistance (and often the low recoil pressures of emphy-
sema) greatly increase the potential for PEEPi and thus limit
the range of breath rates available. Indeed, reductions in
both VT and ventilatory rate to levels resulting in hypoven-
tilation and “permissive (or even “therapeutic”78 ) hyper-
capnia” may be an appropriate tradeoff to limit PEEPi
development and overdistention.
The I : E ratio in obstructive lung disease is generally set
as low as possible to minimize the development of air trap-
ping. For the same reason, approaches using IRV strategies
are almost always contraindicated.
The PEEP/FIO2 settings assume a different role in obstruc-
tive lung disease than in parenchymal lung disease. Because
alveolar recruitment is less of an issue and overdistention
is more of an issue in obstructive lung injury than in paren-
chymal lung injury, the strategy in using the PEEP/FIO2

steps in Figure 101-5 should probably be shifted more
toward the use of FIO2 for oxygenation support instead of
PEEP. A specific role for PEEP in the obstructed patient arises
when PEEPi serves as an added inspiratory threshold load
on the patient attempting to trigger a breath, as described
earlier. Under these conditions, judicious application of
circuit PEEP (at levels up to 75% to 85% of PEEPi) can
“counterbalance” PEEPi throughout the ventilator cir-
cuitry to reduce this triggering load and facilitate the trig-
gering process.87,88
In severe airflow obstruction, the use of the low-density
gas helium can help facilitate ventilation. Helium mixtures
are is available as 80 : 20, 70 : 30, or 60 : 40 helium : oxygen
breathing gas mixtures (heliox) and can both reduce patient
inspiratory work and facilitate lung emptying (recall that
driving pressure decreases and/or flow increases as gas
density decreases).124 However, to date there have been no
studies demonstrating improved outcomes with the use of
heliox. With a helium : oxygen gas mixture, it should be
remembered that many flow sensors must be recalibrated
to account for the change in gas density.
Finally, it is important to note that noninvasive ventila-
tion has been demonstrated most convincingly to improve
outcomes in patients with obstructive diseases.125 In setting
up noninvasive ventilation, the same principles described
previously for invasive mechanical ventilation also apply
(see Chapter 102).
Neuromuscular Respiratory Failure
The risk of VILI is generally less in a patient with neuromus-
cular failure (e.g., central nervous system injury, drug
overdoses, anesthesia) because lung mechanics are often
near normal and regional overdistention less likely. More
“generous” VTs (e.g., up to 10 mL/kg PBW) have thus been
proposed as being useful to improve comfort, maintain
recruitment, prevent atelectasis, and avoid hypercarbia that
may adversely affect central nervous system function.
However, this notion has been challenged recently by clini-
cal trials of patients with normal lungs in the perioperative
period showing reduced postoperative complications when
VTS are used in the 6 to 8 mL/kg (IBW) range. Regardless
of VT settings, maximal distending pressures should be kept
as low as possible while still being compatible with the other
goals noted previously.67-70
Mode selection in neuromuscular disease patients is often
determined by patient comfort and reliability of the respira-
tory drive. PEEP, even at low levels, is often beneficial at
preventing derecruitment (atelectasis) in these patients,
who are often supine and unable to clear secretions or sigh.
Recovering Respiratory Failure—“Weaning” and
Discontinuation Process
As respiratory failure stabilizes and begins to reverse, clini-
cal attention shifts to the process of ventilator withdrawal.
Unfortunately, a number of large clinical trials have clearly
demonstrated that current assessment/management strat-
egies are not optimal, resulting in considerable delay in ven-
tilator withdrawal.125,126 Such delay leads to increased
length of ICU stay, increased costs, prolonged exposure to
circuit pressure, and increased risk of infection. Attempts
to speed withdrawal, however, must be balanced against the
101  •  Mechanical Ventilation 1773
risk of premature withdrawal with consequent loss of
airway patency, aspiration, and inspiratory muscle fatigue.
An evidence-based task force125 has recommended a two-
step process:
1. Consider a patient a candidate for withdrawal if (a) the
lung injury is stable/resolving, (b) the gas exchange is
adequate with low PEEP/FIO2 requirements, (c) the
hemodynamics are stable without pressors, and (d) the
patient has the capability to initiate spontaneous breaths.
2. In these patients, perform a spontaneous breathing trial
(using T-piece, CPAP, or pressure support at 5 cm H2O)
for 30 to 120 minutes. Assessments should include the
ventilatory pattern, gas exchange, hemodynamics, and
comfort. Patients “passing” this trial should be consid-
ered for ventilator withdrawal.
In patients passing the spontaneous breathing trial (SBT),
separate assessments are required to determine if the arti-
ficial airway can be removed. These involve cough strength,
suctioning frequency, and, to a certain extent, the ability to
follow commands.125 Cuff leak, a bedside test that may dem-
onstrate whether there is airway edema or compression
around the endotracheal tube that could lead to postextu-
bation airway obstruction, does not appear to be an impor-
tant predictor of success, except perhaps in the setting of
prior upper airway injury. Extubation failures can be
expected in 10% to 20% of all extubations. Many of these
involve airway protection issues and thus indicate the
need for prompt reintubation. However, in some patients,
especially those with chronic obstructive pulmonary
disease, an extubation failure caused by increasing inspira-
tory muscle overload might be managed by noninvasive
ventilation.127,128
In patients failing the SBT, a stable and comfortable level
of support should be provided until the next SBT.125 Fre-
quent (e.g., every 2 to 12 hours) support reductions are
usually not necessary because they have not been shown to
speed up the withdrawal process and only serve to consume
resources and expose the patient to the risks of muscle over-
load. Repeat assessments for SBTs, however, should be done
daily.125,126 Importantly, aggressive strategies to reduce
sedation can accelerate this process.129 Indeed, some have
advocated “spontaneous awakening trials” coupled to SBTs,
but it is not clear if this approach is superior to carefully
targeted sedation protocols.130
A common problem seen in patients recovering from
respiratory failure but still deemed in need of an artificial
airway is the presence of large VTs despite low levels of
ventilatory support (e.g., inspiratory pressure levels of 5 cm
H2O). Under these circumstances, a search should be made
for causes of an excessive respiratory drive such as pain,
metabolic acidosis, or anxiety, and these issues should be
addressed. Most would argue that, in the absence of revers-
ible causes, sedation should not be used simply to lower
the VT.
Regardless of the clinical scenario, whenever assisted-
supported breaths are used, attention must be paid to assur-
ing synchronous interactions. As noted earlier, this first
means addressing the appropriateness of respiratory drive
to ensure that reversible causes of excess drive (e.g., pain,
anxiety, acidosis) are managed and then providing settings
1774 PART 3  •  Clinical Respiratory Medicine
that maximize trigger sensitivity. It also ensures proper flow
and cycle synchrony.
RECENT INNOVATIONS
IN MECHANICAL
VENTILATORY SUPPORT
INNOVATIVE STRATEGIES FOR
“LUNG PROTECTION”
Several innovations introduced recently may assist clini-
cians in reducing ventilator-induced lung injury. Among
the more interesting are airway pressure release ventilation
(APRV) and high-frequency ventilation (HFV). In addition,
ventilating patients in the prone position, although not
novel, can also be viewed as an interesting strategy to facili-
tate lung protective ventilation.
Airway Pressure Release Ventilation
APRV (also known as biphasic ventilation, bilevel ventilation,
and bilevel positive airway pressure) is a time-cycled, pressure-
targeted form of ventilatory support.111-115 It is actually a
modification of pressure-targeted SIMV that allows sponta-
neous breathing (with or without PS) during both the infla-
tion and deflation phases.
The putative advantages of this approach are similar to
others that utilize long inspiratory times. Specifically, the
long inflation phase recruits more slowly filling alveoli and
raises mean airway pressure without increasing applied
PEEP (although PEEPi can develop with short deflation
periods). Unlike older IRV strategies that required paralysis,
however, the additional spontaneous efforts during infla-
tion may enhance both recruitment and cardiac filling
when compared with other controlled forms of support.
Although IRV strategies are usually reserved for severe
forms of respiratory failure in which airway pressures and
FIO2 levels are approaching potentially injurious levels, the
comfort and recruitment potential associated with APRV
may prompt consideration of its use even in less severe
forms of lung injury.
Good gas exchange has been demonstrated with APRV in
several small observational clinical trials, often with lower
maximal airway pressures than used with control ventila-
tion.111 However, the end-inspiratory lung distention in
APRV may not be less than that provided during other
forms of support (and, indeed, it could be substantially
higher) because spontaneous VTs can expand the lung
beyond the volume at the APRV set pressure. In the few
randomized studies that compare APRV to a true lung-
protective strategy, no differences in important outcomes
have been found.113-115
High-Frequency Ventilation
HFV uses high breathing frequencies (120 to 900 breaths/
min in the adult) coupled with small VTs (usually < ana-
tomic dead space and often < 1 mL/kg IBW at the alveolar
level) to provide gas exchange in the lungs.131 Gas transport
under these seemingly unphysiologic conditions may
involve such mechanisms as Taylor dispersion, coaxial
flows, and augmented diffusion.132
HFV can be supplied by either jets or oscillators. Jets
inject high-frequency pulses of gas into the airways. Oscil-
lators literally vibrate a fresh bias flow of gas delivered at
the tip of the endotracheal tube. Because of this, oscillatory
HFV has sometimes been referred to as “CPAP with a
wiggle.”
The putative advantages of HFV are twofold. First, the
small alveolar tidal pressure swings minimize cyclical over-
distention and derecruitment. Second, a high mean airway
pressure can also prevent derecruitment. Interestingly,
mean pressures used during HFV are often reported to
exceed the 30 to 35 cm H2O threshold employed during
conventional ventilation. This tolerance of a higher mean
pressure with HFV may be explained by a better maintained
alveolar structure with a slowly applied (albeit vibrating)
constant pressure as opposed to cyclical brief tidal
pressures.133
Clinical experience with HFV has been most extensive in
the neonatal and pediatric age groups where a number of
trials show improved long-term lung function when HFV is
used in acute respiratory failure.134,135 Although adult expe-
rience with HFV is less, a meta-analysis of randomized trials
using HFV in adult respiratory failure suggested an outcome
benefit to HFV.136 Two large subsequent trials, however,
have called this conclusion into question. In one, mortality
was identical in both the HFV and lung-protective conven-
tional strategy137; in the other, the trial was stopped early
because of increased mortality in the HFV group.138 Of
concern in both of these trials was the use of many centers
that had little or no previous experience with HFV. Never-
theless, both trials make it clear that HFV, if used, is best
reserved for patients failing conventional lung protective
strategies and should be employed by clinicians experienced
in the use of HFV.
Positive-Pressure Ventilation in
the Prone Position
Mechanical ventilation of patients in the prone position
offers several physiologic advantages.139 Chief among
these are two mechanisms that can improve ventilation
distribution. First, the heart no longer rests on the left
lower lobe and this allows better ventilation distribution
to that region. Second, the sternum is restricted in its
ability to move outward. This functionally stiffens the
chest wall and forces a more even distribution of positive
pressure.
Prone positioning has its challenges, primarily from a
nursing perspective. The act of proning requires careful
teamwork (although automated proning beds exist). More
importantly, management of vascular lines, feeding tubes,
artificial airways, ostomies, and so on need careful atten-
tion because they can be easily dislodged. Avoiding facial
pressure sores also requires careful nursing care.
There have been a number of randomized controlled
trials of proning in patients with ARDS and, until recently,
despite consistently better oxygenation, no consistent
outcome benefit could be demonstrated.139 However, the
largest study to date focusing on ARDS patients with arte-
rial PO2/FIO2 ratios less than 150 recently showed a signifi-
cant mortality benefit to lung protective mechanical
ventilation provided in the prone position for more than 16
hours/day.140

AUTOMATED WEANING STRATEGIES
Over the years, a number of attempts have been made to
“automate” the weaning process.7 An early example is
minimum minute ventilation, which adjusted the intermit-
tent mandatory breath rate according to the level of spon-
taneous ventilation. The concept behind automated
weaning was that significant clinician time could be saved
and ventilatory support could be automatically reduced
in a timely fashion on the basis of simple ventilator
measurements.
Volume support (VS, also known by trade names such as
“Automatic Pressure Ventilation”) is a newer strategy with
the potential for automatic support reduction.7 As described
earlier, VS is a pressure support mode that uses tidal volume
as a feedback control for continuously adjusting the pres-
sure support level. Proponents claim that this approach
could “automatically” wean a patient by reducing pressure
support as patient effort increases and respiratory system
mechanics improve. Conversely, pressure support would
increase if patient effort diminished or respiratory system
mechanics worsened. Similarly, it has also been suggested
that VS may be a useful way to maintain a more constant
level of partial support in patients with fluctuating levels of
effort related to drugs or neurologic conditions. All of these
effects have been demonstrated in small studies focused on
patients with rapidly recovering respiratory failure.7
Unfortunately, the simplicity of VS may introduce prob-
lems.7,26 For instance, if the volume set by the clinician is
excessive for patient demand, a recovering patient may not
attempt to take over the work of breathing for that volume
and thus weaning may not progress. In addition, if the
pressure level increases in an attempt to maintain an
inappropriately high-set VT in the patient with airflow
obstruction, PEEPi may result. Conversely, if the volume
set by the clinician is not adequate for patient demand,
a patient may not receive adequate support. Under these
conditions, a patient will perform excessive work to main-
tain a certain VT even as the inspiratory pressure is being
reduced. A transient increase in patient demand from pain
or anxiety could also result in inappropriate support reduc-
tion with VS.26
Adaptive support ventilation (ASV) has a sophisticated
algorithm to adjust the ventilatory pattern during machine-
triggered breaths as described earlier. However, ASV per-
forms similarly to VS during patient-triggered breaths.
Small clinical studies have demonstrated that ASV can
automatically wean ventilatory support safely.141 However,
large trials comparing ASV weaning to regular daily SBT
strategies have not been done.
Another commercially available feedback system for
weaning pressure-targeted breaths uses not only VT but
also respiratory rate and end-tidal carbon dioxide to adjust
ventilator settings.142 Randomized trials with this system,
however, have not shown faster ventilator withdrawal when
compared with strategies using protocols for regular
SBTs.143
Inherent in all of these automated weaning systems is the
notion that gradual support reductions (weaning) in
between SBTs facilitates ventilator withdrawal—a notion
that has little, if any, evidence supporting it in patients
recovering from acute respiratory failure.144 Two clinical
101  •  Mechanical Ventilation 1775
scenarios, however, may be amenable to these automated
approaches: The first is the patient rapidly recovering from
sedatives/anesthesia where these systems can alert clini-
cians to the return of adequate spontaneous efforts. The
second is the patient requiring prolonged mechanical ven-
tilation who has failed multiple SBTs. Under these circum-
stances, an automated support reduction system could
serve as a diagnostic tool alerting the clinician to recovery
of respiratory function and the possibility of reinstating
SBTs.
OPTIMIZING SYNCHRONY DURING
INTERACTIVE BREATHS
Interactive breaths are commonly used during mechanical
ventilatory support to improve comfort (and reduce seda-
tion), especially during the recovery phase of respiratory
failure. As noted previously, interactive breaths need to be
synchronous with patient efforts during all three phases of
breath delivery: trigger, flow delivery, and cycle. A number
of recent innovations have been introduced and are
reviewed here.
Although all of these innovations have conceptual appeal
and have been shown to perform as designed in both bench
testing and small clinical observational trials, patient out-
comes, including sedation needs, ventilator days, or patient
comfort assessments, have generally not been studied. Nev-
ertheless, their straightforward designs, ease of operation,
and safety make these innovations appropriate to consider
in patients receiving interactive breaths.
Endotracheal Tube Resistance Compensation
The endotracheal tube provides a significant resistance to
flow during both inspiration and expiration. During the
inspiratory phase, this means that pressure build-up in the
airways “lags” behind the pressure build-up in the ventila-
tor circuitry. Thus the “square” wave of pressure in the
circuitry provided by a pressure-targeted breath is distorted
in the airways to a slower rise of pressure. This may create
significant initial flow dys-synchrony in patients with vigor-
ous inspiratory efforts. During expiration, a similar gradi-
ent between airway pressures and set circuit PEEP can
develop.
One way to address this is to target ventilator pressures
to a measured tracheal pressure distal to the endotracheal
tube. Unfortunately, readings from intra-airway pressure
sensors over prolonged periods are not reliable. Another
approach is to account for endotracheal tube resistance
mathematically in the ventilator flow delivery pattern.145,146
Known by various trade names (e.g., “Automatic Airway
Compensation,” “Automatic Tube Compensation”), this
approach initially provides an inspiratory pressure higher
than the set pressure target. As inspiration proceeds, this
delivered pressure then tapers to the set inspiratory pres-
sure target. This compensation mechanism can also operate
in expiration with an initial expiratory airway pressure
below the set PEEP that then rises to the set PEEP. A more
square wave pattern of inspiratory and expiratory tracheal
pressures is the result.145,146
Applying endotracheal tube resistance compensation
is relatively straightforward. Clinicians must input the
characteristics of the endotracheal tube. Thereafter, the
1776 PART 3  •  Clinical Respiratory Medicine
ventilator provides the appropriate circuit pressure profile
during both inspiration and expiration to create the desired
square wave pattern in the trachea. Although outcome
studies using this compensation approach have not been
done, the conceptual appeal should make it a consideration
in virtually all patients receiving assisted/supported
pressure-targeted breaths—especially those with vigorous
inspiratory efforts.
Pressure Rate of Rise (Slope) Adjusters
The original design for pressure-targeted breaths (pressure
support and pressure assist-control) had a programmed
flow delivery algorithm that attempted to reach the target
inspiratory pressure quickly, without causing an uncom-
fortable overshoot. Newer ventilators, however, allow the
clinicians to adjust the rate of rise of this pressure (slope
adjusters), and clinical studies have suggested that slope
adjustment could significantly enhance flow synchrony in
many patients.147 Specifically, these studies found that a
rapid rate of rise was often desired in a patient with vigorous
flow demands, whereas a much slower rate of rise was often
preferable in patients with less vigorous demands.
There are several approaches to setting the slope adjuster.
The most direct way is to use the circuit pressure graph and
adjust the slope to create a “smooth square wave” appear-
ance to the circuit pressure profile. Studies have also shown
that an optimal slope setting correlates with the greatest VT
for a given pressure setting.147 Patient comfort should
always be considered in determining optimal slope
settings.
Pressure Support Cycle Adjusters
Pressure support breaths have a flow cycling mechanism to
terminate the breath. On earlier machines, a set flow termi-
nation criterion was usually set by the manufacturer (e.g.,
25% to 35% of peak flow). Although this set flow was often
effective, it could sometimes terminate breaths too early in
patients with long inspiratory demands and it could some-
times terminate too late, typically in patients with obstruc-
tive airway disease. In this latter situation, air trapping
could also be made worse because of the resulting shorter
expiratory time.
There are several approaches to improving cycle syn-
chrony with pressure support. One is to switch from pres-
sure support to a pressure-assist breath (patient-triggered,
pressure-targeted, time-cycled breath as is usually available
on most machines providing pressure ACV if the set rate is
turned low or off). This breath provides direct clinician
control of inspiratory time and thus of cycling. Another
strategy is to adjust the pressure slope setting described pre-
viously on pressure support breaths. A rapid peak initial
flow will have a correspondingly high flow cycle variable
(and thus short inspiratory time); a very slow peak initial
flow will have a correspondingly low flow cycle variable
(and thus long inspiratory time).
A newer approach is to allow adjustments of the flow
criteria of the pressure support cycle to assure appropriate
synchrony of the cycle with the end of patient effort.148 As
with other adjustments of interactive breaths, airway pres-
sure graphics and assessments of patient comfort should
guide adjustments. Proper breath synchrony is character-
ized by a comfortable patient without evidence on the
circuit pressure graph of continued inspiratory effort after
cycling (premature cycling) or of expiratory efforts begin-
ning during the inspiratory phase (delayed cycling).
Although no outcome studies have been performed using
these cycle adjusters, their physiologic appeal, ease of use,
and apparent safety should make them a consideration in
virtually every patient receiving pressure support.
Proportional Assist Ventilation
Proportional assist ventilation (PAV) is a novel approach to
assisted ventilation in which the clinician sets the “gain” on
patient-generated flow and volume.149-150 In PAV, there is
thus no set pressure, flow, or volume. Instead, the sensed
patient effort is boosted according to a proportion of the
measured work of breathing set by the clinician.
PAV requires that “test breaths” (controlled breaths with
fixed flow and volume) be given. This allows for the calcula-
tion of respiratory system mechanics, which can be coupled
with the measured ventilation to calculate work of breath-
ing (resistive and elastic ventilatory muscle loads). These
load calculations are repeated at regular intervals in order
to maintain reliable inputs for the PAV algorithm.
PAV breaths are patient-initiated breaths triggered in a
conventional way using circuit pressure or flow sensors.
Thereafter, the ventilator continues to monitor flow and
volume demanded by the patient and puts a clinician-set
“gain” on this demand to augment flow and pressure in
proportion to the desired reduction in the patient’s work of
breathing. The PAV breath cycles when sensed flow demand
has ceased.
Like pressure-targeted breaths, PAV flow delivery varies
with patient effort; unlike pressure-targeted breaths, pres-
sure also varies with patient effort. The conceptual upside
to PAV is that flow and cycle synchrony should be enhanced
over conventional flow- or pressure-targeted breaths.
Another conceptual upside is that patient-driven tidal
volume variability with its theoretical lung protective ben-
efits may be enhanced.151 The downside, however, is that,
unlike conventional pressure-targeted breaths, there is no
minimum pressure or flow provided. Thus PAV must be used
with caution in patients with unreliable ventilatory drives
from either disease or drugs. Indeed, with all patients on
PAV, careful monitoring and backup support modes should
be available.
Most clinical studies with PAV have shown enhanced syn-
chrony compared with conventional modes.149-156 However,
it is not clear what the ideal PAV gain(s) should be in various
clinical settings. Moreover, to date, there have been no good
randomized trials looking at important outcome benefits
(e.g., ventilator duration, sedation needs, mortality) when
PAV is compared with conventional assisted/supported
ventilation.
Neurally Adjusted Ventilatory Assistance
Neurally adjusted ventilatory assistance (NAVA) utilizes the
diaphragmatic electromyographic (EMG) signal to trigger,
adjust flow, and cycle assisted breaths.153,157 NAVA requires
placement of a unique esophageal catheter with an array
of diaphragm EMG sensors. These sensors detect the onset,
intensity, and termination of inspiratory efforts directly.

Like PAV, a clinician-set gain is then applied, which deter-
mines flow and pressure delivery in proportion to the EMG
signal.
The conceptual benefit to NAVA is that synchrony with
all three phases of breath delivery (trigger, gas delivery, and
cycle) should be enhanced over conventional flow- or
pressure-targeted breaths. Like PAV, another conceptual
benefit is that patient-driven tidal volume variability with
its theoretical lung protective benefits may be enhanced.
Also like PAV, the downside is that there is no minimum
pressure or flow provided. Thus, like PAV, NAVA must be
used with caution in patients with unreliable ventilatory
drives from either disease or drugs. Moreover, with NAVA,
there is also concern about the stability of the EMG signal
coming from a catheter that can move within the esopha-
gus. Thus all patients on NAVA require careful monitoring
and backup support modes.
Most clinical studies with NAVA have shown enhanced
synchrony compared with conventional modes.158-161
However, like PAV, it is unclear what the optimal EMG gain
setting(s) should be in various clinical settings. To date
there have been no good randomized trials looking at impor-
tant outcome benefits (e.g., ventilator duration, sedation
needs, mortality) when NAVA is compared with conven-
tional assisted/supported ventilation.
Key Points
■ Positive-pressure breaths are characterized by three
variables: the breath trigger, the flow delivery target
(pressure or flow), and the cycle criteria.
■ The interactions of positive-pressure breaths and
respiratory system mechanics are described by the
equation of motion: Pressure = (flow × resistance) +
(volume/system compliance).
■ In lungs with collapsed alveoli, alveolar recruitment is
accomplished by transient increases in positive-
pressure inflation and is maintained by positive end-
expiratory pressure.
■ Ventilator-induced lung injury can be caused by
several mechanisms, including alveolar overdistention
and repetitive alveolar collapse/reopening.
■ Removing mechanical ventilatory support expedi-
tiously requires regular sedation adjustments and
assessments of spontaneous breathing capabilities.
101  •  Mechanical Ventilation 1777
Complete reference list available at ExpertConsult.
Key Readings
ACCP/AARC/SCCM Task Force: Evidence based guidelines for weaning
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2001.
Brander L, Ranieri VM, Slutsky AS: Esophageal and transpulmonary pres-
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injury. Crit Care Med 34(5):1556–1558, 2006.
Briel M, Meade M, Mercat A, et al: Higher vs lower positive end-expiratory
pressure in patients with acute lung injury and acute respiratory dis-
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865–873, 2010.
Brower RG, Hubmayr RD, Slutsky AS: Lung stress and strain in acute
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