REVIEW ARTICLE

William C. Oliver, Jr, MD

Paul G. Barash, MD
Section Editors

State-of-the-Art Mechanical Ventilation

Marcin Karcz, MD, MSc,* Alisa Vitkus, BA,* Peter J. Papadakos, MD,* David Schwaiberger, MD, and
Burkhard Lachmann, MD, PhD

HE CONCEPT OF artificial respiration was first recognized in the 16th century by Vesalius.1 However, it was
not until the 20th century that mechanical ventilation became a
widely used therapeutic modality. Bjorn Ibsen successfully
applied positive-pressure ventilation to a population of patients
with polio-induced respiratory paralysis during the 1952 Copenhagen outbreak, reducing their overall mortality from
around 85% in July 1952 to 15% in March the following
year.1,2 This intervention is now seen as the birth of modern
mechanical ventilation as a method to manage acute respiratory
failure, and the intervention also heralded the development of
the modern intensive care unit (ICU).
The provision of respiratory support by positive-pressure
ventilation is a core function of the ICU. Internationally, about
a third of patients admitted to ICUs currently receive mechanical ventilation for more than 12 hours.3 Recent international
epidemiologic studies have revealed that the median age of
patients receiving mechanical ventilatory support is 63 years
(interquartile range, 48-73 years), and almost 40% of patients
are female.3-9 The majority of ventilated patients (65%) receive fewer than 24 hours of ventilatory support as a component of their routine anesthetic and postoperative management
after major surgery such as cardiac, aortic, or neurosurgery.3,5-9
The other major patient groups include the critically ill with
severe primary respiratory disease (13%), patients with head
or chest trauma (10%), and those with poisoning/deliberate
self-harm (8%) in whom the duration of mechanical ventilation is more variable.3,5-9
Mechanical ventilation is a supportive intervention rather
than a therapeutic one. It is hazardous and potentially injurious
to the ventilated lung, especially in the presence of an intrinsic
lung disease or a lung injury. Therefore, initiating mechanical
ventilation should be undertaken only when the balance of risk
of not intervening is considered greater than the risk of proceeding. Once initiated, mechanical ventilation should, in general, be applied for as short a duration as is possible and as
gently as possible. It is now recognized that ventilator strategies should be chosen on the basis of clinically important
outcomes rather than on the basis of their ability to alter gas
exchange in the short-term. The goal of this article was to
provide a concise review of the pathophysiology of mechanical
ventilation as well as the basic invasive mechanical ventilator
modes and settings. Noninvasive ventilation (NIV), weaning,
and extubation also are discussed.

INDICATIONS FOR INITIATING

MECHANICAL VENTILATION

Respiratory homeostasis can be thought about in terms of the

equilibrium among respiratory load, respiratory capacity, and
respiratory drive. Respiratory failure develops when 1 or more
of these elements are out of balance and is defined as the
inability of the bodys breathing apparatus to maintain adequate
gas exchange for its metabolic needs. Mechanical ventilation is,
in general, indicated when established or impending respiratory
failure exists (Table 1). This usually equates to the presence of
a PaO2 60 mmHg on a supplemental FIO2 0.6, progressively increasing PaCO2 values, and an acute respiratory acidosis with pH values below 7.25.10
Although respiratory failure can be defined precisely in
terms of blood gas tensions as described earlier, impending
respiratory failure has no clear definition. Here clinical judgment is required, and, frequently, a decision to commence
mechanical ventilation will need to be made in the absence of
arterial blood gas results.10-12 There are a multitude of clinical
presentations that prompt the consideration of mechanical ventilation. They range from patients presenting with severe respiratory distress or apnea to patients with relatively minor clinical
signs of increased work of breathing although with clearly
limited reserve. Increased work of breathing causes signs of
respiratory distress including nasal flaring, accessory muscle
recruitment, tracheal tug, intercostal recession, tachypnea,
tachycardia, worsening arrhythmias, hyper- or hypotension,
and changes in mental status.10-12 Respiratory parameters that
may act as a guide are a respiratory rate above 30, tidal volume
below 4 mL/kg of ideal body weight, and a vital capacity below

From the Departments of *Anesthesiology, Surgery, and Neurosurgery, University of Rochester, Rochester, NY; and Department of
Anesthesiology and Operative Intensive Care, Charite Universitats
Median Berlin, Campus Verchow Klinikum Humbolt University, Berlin, Germany.
Address reprint requests to Marcin Karcz, MD, MSc, Department of
Anesthesiology, University of Rochester, 601 Elmwood Avenue, Rochester, NY 14642. E-mail: Marcin_Karcz@urmc.rochester.edu
2011 Elsevier Inc. All rights reserved.
1053-0770/xx0x-0001$36.00/0
doi:10.1053/j.jvca.2011.03.010
Key words: mechanical ventilation, barotrauma, lung recruitment,
surfactant, modes of ventilation

Journal of Cardiothoracic and Vascular Anesthesia, Vol xx, No x (Month), 2011: pp xxx

KARCZ ET AL

Table 1. Classification of Acute Respiratory Failure

Failure of oxygenation
(hypoxemia)

Pneumonia, hydrostatic pulmonary

edema, exacerbation of asthma,
pulmonary embolus

Failure of ventilation
(hypercapnia)
Hypoventilation

Reduced respiratory drive, drug

intoxication, head trauma,
cerebrovascular accident
Impaired respiratory pump Respiratory muscle fatigue,
function
neuromuscular disease, chest
wall trauma/deformity
Increased dead space
Emphysema, pulmonary embolus,
cystic fibrosis
Increased work of breathing (any
Increased CO2 production
cause), fever, excessive
carbohydrate intake

Modified with permission.10

15 mL/kg of ideal body weight with subjective respiratory

distress, which all suggest a need for respiratory support10-12
(Table 2).
VENTILATOR-INDUCED LUNG INJURY

The mechanisms of ventilator-induced lung injury largely

have been investigated in animal models.13,14 Initially, there are
two discrete processes which occur in sequence: an acute
phase, which is exemplified by interstitial and pulmonary edema; as well as surfactant dysfunction, followed by a sub-acute
phase typified by inflammation.15-17
The combined effects of increased filtration and increased
permeability contribute to acute edema. The transcapillary hydrostatic pressure, which is the pressure responsible for driving
fluid out of the extra-alveolar pulmonary vessels, is increased in
two ways.18,19 In the first instance, it is increased by a reduction
in the interstitial pressure around the extra-alveolar vessels
resulting from (1) increased surface tension due to surfactant
dysfunction, and (2) stretching open of the interstitial space by
lung overinflation15-17 (Fig 1). It is also increased by an elevation in extra-alveolar hydrostatic pressure, which occurs in
response to the decreased caliber of intra-alveolar vessels
caused by the raised alveolar pressure.15-17
There are a number of possible mechanisms for surfactant
dysfunction. Surfactant release from type-2 alveolar cells is
enhanced by high-volume ventilation, but the increased surface
area of the alveoli increases the rate at which surfactant is
released into the conducting airways and eventually exceeds
the rate of production.18 Furthermore, high tidal volume ventilation increases the conversion of the large aggregate surfactant
into epithelial cells and, eventually, the basement membrane
itself may give way, leading to alveolar hemorrhage.19,20 Alveolar type-2 cells, which usually occupy the alveolar corners,
appear to be relatively spared in this process.21,22
Breaches in the cell membrane increase the intracellular
calcium concentration, provoking the mobilization, coalescence, and exocytosis of intracytoplasmic patches of lipid vesicles at the site of damage to the cell membrane.23-31 Molecules
that are positioned at the junction between the cells cytoskel-

eton and transmembrane connectors to adjacent cells and tissues sense the cellular deformation. These molecules trigger a
number of processes involved in cellular remodeling and repair,23-31 such as the activation of genes involved in paracrine
signaling. This results in the production of factors such as
transforming growth factor (TGF-1) and basic fibroblast
growth factor, as well as genes involved in the synthesis of
fibronectin, collagen, and matrix metalloproteinase.23-31
It remains to be elucidated whether the responses mentioned
above are directly responsible for the activation of proinflammatory genes, whether their activation arises secondary to cell
necrosis and the exposure of the basement membrane, or
whether it is due to both mechanisms.26 However, it is now
clear that the subacute response to stretch injury is an inflammatory reaction that draws neutrophils to the lung parenchyma
and macrophages to the alveolar air spaces. Moreover, hyperoxia further intensifies this process.26 Cytokines, which can be
detected in lung lavage, are produced by the inflammatory
reaction and may then enter the systemic circulation to cause
organ damage at other sites.26,32,33
The use of high-peak inspiratory lung volumes and avoidance of positive end-expiratory pressure (PEEP) during mechanical ventilation have a combined effect on the release of
proinflammatory mediators from the lung tissue into the airways.34 The cytokine levels are reduced at a level of 10 cmH2O
of PEEP at comparable peak inspiratory lung volumes, or by
lowering the peak inspiratory lung volume when ventilating
with zero PEEP.35 Although suggested, it still remains to be
proven if ventilation-induced, pulmonary-derived inflammatory mediators might be responsible for the multiple organ
failure seen in patients with severe lung injury.36
The Role of Pulmonary Mechanics
In order for clinicians to set the upper pressure or volume
limits for noninjurious mechanical ventilation, it would be
useful to detect the end-inspiratory lung pressure or volume at
which pulmonary overdistention takes place.36-38 An upper
inflection point, which is said to mark the end of alveolar
recruitment or the beginning of lung overdistention (Fig 2) is
often seen after inspection of the static inflation pressurevolume curve from the functional residual capacity to vital
capacity, which can now be measured on some modern ventilators. The exact significance of the upper inflection point is not
known, however, as the pressure-volume curves are time-consuming and awkward to measure, and there is no evidence that
using the upper inflection point is any more effective than using
the lowest possible inflating pressure.24,39 The lower inflection
Table 2. Clinical Parameters Associated With Respiratory Failure
Respiratory Parameter

Usual
Range

Respiratory
Failure

Respiratory rate (breaths/min)

Vital capacity (mL/kg IBW)
Tidal volume (mL/kg IBW)
Oxygenation, PaO2 (mmHg)
Ventilation, PaCO2 (mmHg)

12-25
30-70
5-8
75-100
35-45

30
15
3-4
60
55

Abbreviation: IBW, ideal body weight.

Modified with permission.10

MECHANICAL VENTILATION

Fig 1. The effect of surfactant degradation and alveolar overinflation on interstitial pressure. The diagram on the left represents a pulmonary
interstitial space with a central blood vessel surrounded on 3 sides by air spaces lined by surfactant. Under conditions of overinflation (right),
the interstitial pressure is reduced by being stretched open by the adjacent air spaces as well as a significant increase in the air space surface
tension caused by surfactant degradation. (Copyright 2008 Cambridge University Press. Reprinted with permission of Cambridge University
Press.46) (Color version of figure is available online.)

point (LIP), which is said to represent the beginning of alveolar

recruitment, is at the low-volume end of the static inflation
pressure-volume curve24,40-43 (Fig 2). Although, there is now
sufficient evidence that alveolar recruitment occurs throughout
the inflation phase, there remains considerable uncertainty
about the events at a cellular level that constitute alveolar
recruitment and that are responsible for the transition from a
lower compliance to higher compliance state.24,40-43 Several
studies in animals suggest that ventilation in which the LIP is
crossed repeatedly is injurious, and that this damage can be
avoided by setting PEEP above the LIP.24,40-43 However, evidence of this is lacking in humans.
The comparison of high versus low PEEP by the Acute
Respiratory Distress Syndrome Clinical Network, in which
there were no outcome differences among the groups, did not
select the high PEEP on the basis of the LIP.44 The two clinical
studies that have selected high PEEP on the basis of the LIP21,45

also used lower tidal volumes in the high PEEP group, making
it impossible to isolate the effect of the higher PEEP from that
of the lower tidal volume. In addition to the LIP, which is on
the inspiratory limb of the pressure-volume curve, there is also
an inflection on the deflation limb that is sometimes called the
expiratory inflection point (EIP) or closing volume that
often occurs at a lower pressure than the LIP but at a greater
lung volume41-43,46 (Fig 2). It is believed by some that PEEP
should be set at or above the EIP after a recruitment maneuver
on the basis that this inflection is caused by an increase in the
rate of alveolar collapse.41-43,46 Thus far, however, EIP has been
substituted for the optimal SpO2 in clinical studies.41-43,46
The recruitable lung is present in two forms, although not
formally recognized as such: a potentially recruitable lung and
a tidally recruited form.46 The potentially recruitable lung is the
part of the lung that is not opened by the pressure excursions of
normal ventilation but can be opened by a high-pressure recruitment maneuver.34,46 A variety of such maneuvers have
been described in the literature and have been shown in both
animals and humans to improve lung mechanics and oxygenation. Identification of the critical closing pressure on the
deflation limb of the pressure-volume curve (Fig 2) allows
PEEP to be set at a pressure that is often lower than the
LIP.41-43,46 Thus, although most investigators agree that the
maintenance of PEEP is beneficial, the method of determining
the appropriate level for maximum benefit has not been decided
yet.47
MECHANISMS OF MECHANICAL
VENTILATORY SUPPORT

Fig 2. Static inflation and deflation pressure-volume curves. The

inflation limb indicates paired measurements of inflating pressure
plotted against lung volume from functional residual capacity
(FRC) to total lung capacity (TLC). An ideal inflation pressurevolume has a lower inflection point (LIP) and an upper inflection
point (UIP), but in practice these points cannot always be identified. The presence of the deflation limb signifies that the lung has
hysteresis. As with the inflation limb, an ideal deflation limb has
an inflection, which is known as the expiratory inflection point
(EIP) and which is said to represent the onset of alveolar collapse.
(Modified with permission.24)

Positive-pressure mechanical ventilation is available as either total support (controlled mechanical ventilation) or partial
support (assisted mechanical ventilation). In total support, the
ventilator does all the work during ventilation.3,11 This may
occur in patients under general anesthesia, patients who are
paralyzed, or patients who are comatose. In these situations, the
ventilator provides all the work needed to trigger and deliver
breaths. During partial support, the ventilator simply assists the
patient during breathing.48,49
Most commonly, the ventilator assists a breath that has been
initiated by the patient by delivering the volume through a

KARCZ ET AL

flow-targeted or a pressure-targeted mechanism.50,51 Presently,

however, total support and partial support frequently are present in one mode (eg, assist control), and whether the breaths are
assisted breaths or controlled breaths can be assessed by the
absence or presence of the patients trigger effort.50 It is important to note the number of assisted breaths relative to the
number of controlled breaths because this may help to determine the integrity of the central nervous system and the depth
of sedation when changes to the ventilator setting are being
considered.
There are 4 phases during each ventilatory cycle: trigger
phase (breath initiation), flow delivery phase, cycle phase
(breath termination), and expiratory phase.50 Breaths can be
initiated during the trigger phase by 3 mechanisms: (1) a
machine timer, in which breaths are initiated by a timer in the
machine set by the clinician; (2) a pressure change (pressure
trigger), in which patient effort decreases the airway/circuit
pressure by a preset amount to trigger the ventilator (pressure
sensitivity); and (3) a flow change, (flow trigger) in which
patient effort draws from the circuit and machine breaths are
initiated when flow into the patient exceeds the set flow threshold (flow sensitivity).52-54
As soon as a breath is triggered, the inspiratory valve in the
ventilator opens, and the flow is delivered. The flow delivery is
controlled by a target or limit set by the clinician for the
ventilator during inspiration. Two commonly used targets or
limits are: (1) flow target, which is a flow rate and pattern set
by the clinician and during which airway pressure varies, and
(2) pressure target, which is an inspiratory pressure limit set by
the clinician and during which flow and volume vary.50-54
The flow delivery phase is followed by the cycle phase
during which the machine terminates a breath by any of the 4
commonly used cycle-off criteria: (1) volume, in which a
breath is terminated when a target volume is achieved; (2) time,
in which a breath is terminated when a set inspiratory time is
achieved; (3) flow, in which a breath is terminated when
inspiratory flow has fallen to a set level; and (4) pressure, in
which a breath is terminated when a set inspiratory pressure is
achieved.50,55,56 These 4 cycle-off mechanisms also are used
commonly to classify mechanical ventilation into volume cycled, time cycled, flow cycled, and pressure cycled, respectively.50,55
Expiration then follows the cycle phase. It is mostly passive
and depends on lung recoil pressure (elastance) and airway/
circuit resistance.57 The product of compliance and airway
resistance is called the time constant (TC).57 Patients who
have a long TC (eg, chronic obstructive pulmonary disease
[COPD] and asthma) will need a longer expiratory time to
empty the lung completely, whereas patients with a short TC
(eg, acute respiratory distress syndrome [ARDS] and pulmonary fibrosis) can empty the lung quickly.50,57 A patient may
sometimes use accessory muscles to actively exhale the gas.
This may be seen frequently during acute exacerbations of
COPD and asthma.57
BASIC MODES OF MECHANICAL VENTILATION

The classification and nomenclature describing modes of

ventilation are confusing. A working group currently is being
established with the aim of unifying the terms used internation-

ally.58,59 In daily practice, 4 basic modes of positive-pressure

ventilation commonly are used: volume-assist control (VAC),
pressure-assist control (PAC), synchronized intermittent mandatory ventilation (SIMV), and pressure-support ventilation
(PSV). Airway pressure-release ventilation (APRV), a relatively newer ventilation mode, can be thought of as a variant of
inverse-ratio ventilation, intended for use with spontaneously
breathing patients. The common modes of mechanical ventilation described in this section are summarized in Table 3.
Volume-Assist Control Ventilation
In the VAC ventilation, the operator determines the tidal
volume to be delivered by a flow-targeted mechanism over a set
duration until a preset tidal volume is reached.11,50 A breath can
be initiated by the machine timer (control mode) or by the
patient (assist mode).50,60,61 The ventilator terminates the breath
(volume cycle-off) and allows expiration to proceed.18 The
clinician also sets the respiratory rate, peak inspiratory flow,
FIO2, and PEEP. The ventilator will effectively deliver a predetermined minute volume, which is an advantage when the
patient is unable to make an inspiratory effort and the underlying lung mechanics are normal.11,50 Pressure in the airway
will be dependent on resistance to airflow and the compliance
of the respiratory system. If the airway resistance is high or the
lungs and/or chest wall are stiff, excessive airway pressure may
result, with potentially damaging effects.11,50,60,61 To avoid this,
pressure limits can be set to provide pressure-limited volumecontrol ventilation.1,19
Therefore, the dependent variables are the pressures (peak
airway and plateau pressure).56 The inspiratory time (Ti) is
determined by the ratio of tidal volume (VT) and inspiratory
flow (Ti VT/flow rate).56 Patients who are placed on the VAC
mode breathe at a respiratory rate that is at least equal to the set
rate, and each breath (whether it is machine triggered or patient
triggered) has the same VT.56 Thus, if a patient stops triggering
the breath, he/she will receive at least a minute ventilation that
is equal to the preset rate times the VT.56 One other advantage
of this mode is that patients can be fully rested on the ventilator,
except for triggering, assuming that the peak inspiratory flow is
adequate.56
Traditional guidelines for determining the tidal volume to be
delivered to a particular patient were based on a value of 10 to
15 mL/kg of ideal body weight.62 Although this may be reasonable in the otherwise normal lung, there is now compelling
evidence that delivering such volumes in the injured lung is
deleterious.21,33,63,64 It may result in repetitive overdistention of
alveoli with endothelial, epithelial, and basement membrane
damage and increased microvascular permeability otherwise
referred to as volutrauma.21,33,63,64 This volutrauma may be as
harmful, if not more, to the lungs as barotrauma. Therefore,
current practice may rely on lower tidal volumes (6-8 mL/kg
ideal body weight), especially in patients with intrinsic lung
disease and alterations in resistance and compliance of the
respiratory system.21,64,65 VAC ventilation is best used in patients with normal resistance and compliance. It frequently is
used intraoperatively when patients with relatively normal pulmonary function receive endotracheal intubation and mechanical ventilation during surgical procedures. With poor compli-

MECHANICAL VENTILATION

Table 3. Mechanisms of Mechanical Ventilation

Trigger
Modes

Total support
CMV
Partial support
AC
SIMV
APRV
BIPAP
PSV
Tube Compensation

Types of Breaths

Breath Strategy

Ventilator

Patient

Cycle

Mandatory

Assisted

Spontaneous

Volume limited
Pressure limited

Yes
Yes

No
No

Volume
Time

Yes
Yes

No
No

No
No

Volume limited
Pressure limited
Volume limited
Pressure limited
Pressure limited
Pressure limited
Pressure limited

Yes
Yes
Yes
Yes
Yes
Yes
No

Yes
Yes
Yes
Yes
Yes
Yes
Yes

Yes
Yes
Yes
Yes
Yes
Yes
No

Yes
Yes
Yes*
Yes*
No
No
Yes

No
No
Yes*
Yes*
Yes
Yes
No

No

Yes

Volume
Time
Volume
Time
Time
Time
Flow, pressure,
or time
Flow

No

No

Yes

Type of breaths
Mandatory: breaths are initiated by the ventilator and the ventilator performs the work of inspiration during those breaths.
Assisted: breaths are initiated by the patient, but the ventilator performs at least some of the work of inspiration for those patient-initiated
breaths.
Spontaneous: breaths are initiated by the patient and the patient performs the entire work of inspiration for those patient-initiated breaths.
Abbreviations: CMV, controlled mechanical ventilation; AC, assist control; BIPAP, biphasic positive airway pressure.
*Note that there is overlap among the types of breaths that can be generated during various modes of ventilation. This overlap is dependent
on the ventilator settings. As examples, APRV and SIMV are capable of assisted breaths (pressure support added) or spontaneous breaths (no
pressure support added). Both assisted and spontaneous breaths depend on the patients ability to trigger the ventilator.
Exception would be the addition of pressure support available with bilevel ventilation (Puritan Bennett, Pleasanton, CA).

ance or high resistance, the higher plateau pressure may lead to

barotrauma and increased mortality in patients with ARDS and
other types of pulmonary parenchymal disease.66 The advantage of VAC is that a constant VT is delivered even with a
changing resistance and compliance.66
The peak inspiratory pressure should be monitored as
changes in it reflect changes in resistance and compliance of the
respiratory system.62 High pressures (30 cmH2O) require a
survey that should start at the patient and work back toward the
ventilator including a check for kinking of the circuit or endotracheal tube (ETT), obstruction to the ETT or major airways
by mucus, auscultation to assess if there are bilateral breath
sounds (to rule out mainstem intubation) and to rule out bronchospasm, a radiograph to evaluate increasing alveolar space
disease (pneumonia or ARDS), or external factors impeding
respiratory excursion (ie, pneumothorax, restrictive diseases of
the thorax, and abdominal distention).62
Manipulation of the inspiratory time can be used to decrease
the peak inspiratory pressure because increasing the inspiratory
time decreases the inspiratory gas flow rate, thereby decreasing
it. However, longer inspiratory times (eg, approaching I:E
ratios of 1:1) may be relatively uncomfortable for the patient
who is awake because the normal I:E ratio is 1:3 or 1:4.67
Additionally, reversing the I:E ratio may result in air trapping
and auto-PEEP. If the peak airway pressure is unacceptably
high, the pressure-assist control mode may be chosen.67 The
problem with the VAC mode is that patients tend to hyperventilate as they come out of deep sedation, thereby resulting in
hypocapnia and respiratory alkalosis. In addition, patients who
demand high inspiratory flow may fight the ventilator if the
flow rate is set too low.67
In VAC ventilation, the operator can select the shape of the

inspiratory flow waveform, usually either a square wave (ie,

constant flow) or a decelerating waveform.66,68 The selection of
one over the other may influence airway pressures and also may
affect the homogeneity of ventilation throughout the lungs. In
special circumstances such as severe hypoxemic respiratory
failure, a decelerating inspiratory flow waveform may be helpful, and this pattern has been described as being similar to
pressure-controlled ventilation (PCV).66,68
Pressure-Assist Control Ventilation
In PAC ventilation, a preset airway pressure above PEEP is
delivered over a selected inspiratory time. The dependent variables are VT and inspiratory flow.69,70 Delivered tidal volumes
vary with alterations in the airway resistance or compliance.69,70
The ventilator continues to deliver the breath until a preset Ti
is reached (time cycle-off).69 The breath is then terminated and
expiration follows. The clinician sets respiratory rate, inspiratory pressure, and Ti, in addition to FIO2 and PEEP.69,71
Patients who are placed on PAC mode breathe at a respiratory rate that is equal to the set rate, and each breath has the
same preset inspiratory pressure.72,73 The magnitude of VT,
however, depends on the resistance and compliance of the
respiratory system and sometimes on the Ti.72-74 Thus, if a
patient stops triggering the breath, he/she will continue to
breathe at a rate that is equal to the preset rate, but the minute
ventilation will vary depending on the VT the patient receives.72-74
The inspiratory flow rate depends on the airway pressure and
respiratory system compliance, achieving high levels initially
and decelerating toward 0 near the end of inspiration.74-76
Because inspiratory pressure is the limiting variable, changes in

respiratory system mechanics (ie, compliance and/or resistance) will result in changes in the delivered VT and minute
ventilation.66,77 However, given that the peak inspiratory pressure (PIP) is controlled, the risk of barotrauma is less compared
with the VAC mode.66,77
Despite avoiding potentially injurious high airway pressures,
the target minute ventilation may not necessarily be
achieved.66,67,77 This means that the relationship among clinician-set variables and ventilation targets may not be quite as
intuitive or straightforward as with the VAC mode.66,67,77
With specific types of commonly used ICU ventilators such
as the Servo 300 (Siemens-Elema, Solna, Sweden) or 900C
(Siemens-Elema, Solna, Sweden), PAC is pressure limited and
time cycled so that when the preset level of pressure is
achieved, it is held for a preset time (inspiratory time), after
which exhalation begins.75 With the newer generation of ventilators, regardless of whether pressure or volume ventilation is
chosen, the type of flow waveform (square-wave or decelerating) can be chosen.78-80 The decelerating flow pattern used in
the PAC mode may help in the recruitment of alveoli with long
time constants (high resistance and low compliance), and,
thereby, over time improves the compliance.78-80 The time
constant of the respiratory system is proportional to the compliance and the resistance. When a longer time is allowed for
equilibration, a higher percentage of airway pressure will equilibrate throughout the lungs. In contrast, lungs that have decreased compliance have a shorter time constant. Therefore,
pressure-limited ventilation may be particularly beneficial in
patients with decreased compliance related to high airway
resistance or alveolar space disease such as pneumonia or
ARDS.78,80
In the critically ill, lung compliance because of lung injury is
often heterogenous. Achieving ventilation in the stiffer lung
segments may require prolonged inspiratory time, and delivering this is generally conceptually more easily achieved with the
PAC mode than with VAC ventilation.81
Like the VAC mode, the PAC mode can allow patients to
fully rest, except for triggering.18 One major advantage of the
PAC mode compared with the VAC mode is that the plateau
pressure can be regulated with greater ease, which is an important consideration in patients with ARDS during ventilation
using the lung-protective strategy. Decelerating flow patterns in
PAC improve the distribution of ventilation in a lung with
heterogenous mechanical properties.67
The PAC mode also is useful in patients who are ventilated
using a cuffless ETT, such as neonates, children, and patients
with a bronchopleural fistula. Under these conditions, the PAC
mode continues to attempt to pressurize the airway for the
duration of the Ti despite the volume loss through the leak.50 In
addition, because of the high variable inspiratory flow needed
to deliver the volume, the PAC mode may be more comfortable
for some patients who have strong respiratory drive and demand high flow that cannot be satisfied by the fixed flow in the
VAC mode.82,83 This is especially important in the critically ill,
in whom lung compliance because of lung injury is often
heterogenous. Achieving ventilation in the stiffer lung segments may require prolonged inspiratory times, and delivering
this is generally conceptually more easily achieved with the
PAC than with the VAC mode.84

KARCZ ET AL

The inspiratory time is set with PAC ventilation and because

most pressure ventilators actually time cycle (end-inspiration
based on the inspiratory time) and do not pressure cycle (endinspiratory when the preset pressure is achieved), increasing the
inspiratory time will increase the mean airway pressure and,
hence, the exhaled VT. This is in contrast to what occurs with
VAC ventilation in which extending the inspiratory time decreases the PIP but does not affect VT.72-74
During PAC ventilation, the exhaled VT should be monitored
to assess the ongoing changes in the resistance and compliance
of the respiratory system as opposed to monitoring the PIP
during volume-limited ventilation.74 A decrease in the exhaled
VT should prompt a thorough investigation into its cause that
includes the same steps as outlined previously for investigating
an increase in PIP during volume-limited ventilation. In patients with severe lung disease, the goal of pressure-limited
ventilation is to achieve a plateau pressure of less than 30
cmH2O.85-89 Using the plateau pressure eliminates the resistance imposed by the ETT and the major conducting airways,
thereby approximating the pressures that occur within the alveoli. The plateau pressure is measured by holding a breath at
the end of inspiration. With a pause at the end of inspiration,
the pressure within the circuit declines from the high level that
occurs at the start of the breath to a baseline or plateau level.90
PAC Ventilation Versus VAC Ventilation
There has been an ongoing debate about whether PAC or
VAC ventilation is superior. In reality, if set up appropriately,
both modes are likely equivalent in supporting gas exchange,
hemodynamics, and pulmonary mechanics. One advantage of
PAC is that the clinician easily can regulate inspiratory pressure in patients who need a protective lung strategy (eg, patients with ARDS). It is also easier to adjust Ti and thus the
inspiratory-expiratory (I:E) ratio in the PAC mode in patients
who need to maintain high mean airway pressure for oxygenation. In addition, the PAC mode provides higher initial flow to
meet the strong demands in some critically ill patients compared with the VAC mode.91 This approach improves patientventilator synchrony and decreases inspiratory work of breathing.82,83 Overall, a greater proportion of the pressure-time curve
for the PAC mode lies in the zone of optimum ventilation and
perfusion. The decelerating waveform in the PAC mode also
may produce other advantages. Because the bulk of the tidal
volume is delivered early in the respiratory cycle, the mean
airway pressure over the duty cycle is increased.74 Modell and
Cheney92 showed that decelerating waveforms improve oxygenation in the setting of diffuse lung injury when compared
with accelerating and square wave patterns of tidal-volume
delivery. Both of the latter profiles result in lower mean airway
pressures and presumably produce less recruitment of poorly
ventilated lung units.
Conversely, the VAC mode has the ability to deliver a
constant VT and guarantee minute ventilation regardless of
changes in lung mechanics. However, because the airway pressure is a dependent variable, it may not be as easy to monitor
the alveolar pressure in patients with ARDS because an inspiratory pause maneuver needs to be performed to obtain the
plateau pressure.89 The fixed flow used to deliver VT also may

MECHANICAL VENTILATION

Table 4. Advantages and Disadvantages of PAC and VAC

Ventilation
PAC ventilation
Advantages
Peak alveolar pressure is limited
Flow responds to patient demand
Increased patient-ventilator synchrony
Disadvantages
Tidal volume variable
PaCO2 variable
VAC ventilation
Advantages
Tidal volume constant
PaCO2 constant
Easily identifiable changes in peak inspiratory pressure as
impedance changes
Disadvantages
Peak alveolar pressure variable
Inability to respond to changes in patient ventilator
demand

be inadequate in some patients who have high flow demand.89

The advantages as well as disadvantages of both PAC and VAC
ventilation are summarized in Table 4.
Synchronized Intermittent Mandatory Ventilation
Throughout continuous mandatory ventilation, the operator
selects a breath frequency that the ventilator then delivers.50,55
Continuous mandatory ventilation typically is used during elective general anesthesia, particularly when muscle relaxants are
used.50,55 It requires no interaction between the ventilator and
the patient; in fact, during continuous mandatory ventilation the
ventilator will continue to deliver what the operator has set,
regardless of whether the patient is making any respiratory
effort or not.59 However, when caring for the critically ill, it is
desirable for patients to initiate some or all of their breaths.
There is no need for the ventilator to take into account the
patients own inspiratory effort in timing its delivered breaths
at each extreme, that is either of complete mandatory breath
delivery or of no mandatory breath delivery (spontaneous
breathing).59 However, in between those extremes, there is a
need for the ventilator to be responsive to the patients efforts
when determining when to deliver a breath. If the ventilator
attempts to deliver a mandated breath while the patient is
beginning to exhale, very high airway pressures may result.59
Similarly, problems might arise if the ventilator attempts to
deliver a mandated breath just as the patient had completed an
inspiration.
To avoid these problems, the ventilator needs to be able to
detect when a patient is breathing in or out and time the
mandatory breath delivery appropriately.59 The ventilator can
detect what the patient is doing by measuring either changes in
flow or pressure within the breathing circuit. This ventilation
mode is called SIMV. In the traditional intermittent mandatory
ventilation (IMV) mode, machine-triggered (mandatory) breaths
are delivered at a preset frequency by a flow-targeted volumecycled (volume IMV) or pressure-targeted time-cycled (pressure
IMV) mechanism.50,59

Between mandatory breaths, the patient can breathe spontaneously. There are 2 problems with the original design of the
IMV mode: (1) it is possible for the patient and the ventilator
to inspire in series, thus stacking 1 breath on top of another
and leading to high airway pressures; and (2) the workload of
spontaneous breaths remains quite high because the patient still
has to open a demand valve and inspire without assistance
through an endotracheal tube.50,59 The first problem has been
addressed by fitting a sensor in the ventilator to detect and
synchronize the patients spontaneous breaths (up to the mandatory rate) in a manner similar to the assist-control mode.93
Thus, the S in SIMV denotes the ability of this mode to
synchronize the mandatory breath with the patients own inspiratory effort.93 The synchronization decreases the conflicts
between the patients breathing efforts and mandatory machine
breaths. The 2nd problem of increased work of breathing during spontaneous breaths is solved by introducing pressure support for the spontaneous breaths.93 Thus, in the SIMV mode,
the patient receives 3 types of breaths: the control (mandatory)
breaths that are flow-targeted time cycled (as in pressure IMV
mode), assisted (synchronized) breaths that are also flow-targeted volume cycled or pressure-targeted time-cycled, and
spontaneous breaths that can be pressure supported.93
In clinical practice, SIMV and PSV are frequently combined
and are prescribed as one setting (SIMV/PSV). The ventilator
delivers the set respiratory rate using SIMV, but patient-initiated breaths beyond the set respiratory rate are delivered using
PSV. The purpose of adding PSV for patient-initiated breaths is
to overcome the resistance of the endotracheal tube and ventilator circuit. The necessary level of pressure support is unknown and generally estimated. Resistance of the endotracheal
tube is related to the tube diameter and inspiratory flow rate.94
With small ETTs (eg, 7 mm), a pressure-support level 10
cmH2O may be needed to overcome the resistance,95,96 and
levels of pressure support higher than that required to overcome
resistance will augment the tidal volume.
The IMV mode was developed initially as a method of
partial ventilator support to facilitate liberation from mechanical ventilation.59 The demand valve placed in the breathing
system allows the patient to breathe spontaneously while also
receiving mandatory breaths. As the patients respiratory function improves, the number of mandatory breaths decreases. The
patient can be extubated when he/she is breathing with minimal
mandatory breaths. Large clinical trials, however, show that
SIMV is associated with a higher number of weaning failures
compared with PSV,97 and SIMV tends to liberate patients
more slowly from mechanical ventilation than PSV or T-piece
methods.98
Pressure-Support Ventilation
PSV is a pressure-triggered mode in which the patients
inspiratory effort is supported by a preset inspiratory pressure
in the usual range of 5 to 15 cmH2O.99 Inspiration is initiated by
the patient and is terminated when the flow falls below a
specific level. In this mode, the patient determines the respiratory rate, inspiratory time, and tidal volume.99,100 Unlike the
previous modes, PSV assists only breaths initiated by the
patient.99 This may enhance patient-ventilator synchrony and

provide patient comfort.91 Patients with unstable respiratory

function or respiratory drive, however, may not be ventilated
adequately with pressure support alone. Furthermore, patients
who are heavily medicated with narcotics and sedatives may
not benefit from this mode alone.
The signal that marks the nearing of the end of inspiration is
a decrease in the inspiratory flow (usually to a value of 25% of
the maximum inspiratory flow achieved during that breath), and
this cycles the ventilator to end the delivery of the target
inspiratory pressure.99 During PSV, the delivery of a specific
tidal volume is not ensured. It is possible that PSV may deliver
more assistance than is needed or that the support is insufficient
because it is inherently difficult to judge the correct amount of
pressure support needed by an individual patient at any particular time.99,100
PSV may be used to overcome the work of breathing imposed by the ETT and the ventilator circuit.95,101-103 If a patient
is doing well at a low level of PSV, it may be predictive that the
patient will do well with extubation. PSV is a popular weaning
mode for adults.102,103 Weaning from mechanical ventilation
should be a gradual process. The work of breathing through an
ETT tube may be unreasonably high and could lead to respiratory muscle failure in susceptible patients.102,103 However,
there is no evidence to support this view; in fact, several large
clinical trials have shown equivalence between PSV and Tpiece weaning.102,103
Many ventilators can be set to a mode called automatic tube
compensation. This mode is a type of PSV that applies a
sufficient level of positive pressure to overcome the work of
breathing imposed by the endotracheal tube, which can vary
from breath to breath. Automatic tube compensation often is
used for a spontaneous breathing trial (SBT). Patients who
undergo a SBT with automatic tube compensation are more
likely to successfully tolerate their trial than those who receive
continuous positive airway pressure alone.104 In addition, many
ventilators have the option of combining automatic tube compensation with other modes, so that resistance of the endotracheal tube has no impact on ventilation.
Airway Pressure Release Ventilation
APRV is a newer mode of ventilation and was first described
by Stock et al in 1987.105,106 It is a form of bilevel assisted
ventilation using continuous positive airway pressure (CPAP)
with periodic pressure releases, either to a lower CPAP pressure or to atmospheric pressure.107,108 These periodic releases
provide a background tidal volume and respiratory rate enabling carbon dioxide clearance, whereas the periods of sustained CPAP produce a high mean airway pressure resulting in
lung recruitment and effective oxygenation.107,108 Unrestricted
spontaneous breathing throughout the ventilator cycle is
achieved via an active exhalation valve that opens during
inspiration as well as the traditional expiratory opening. The
active exhalation valve enables continuous control of airway
pressure and compensates for pressure variations normally
found in the ventilator circuit.109 If the airway pressure drops
below the set level because of spontaneous inspiration, gas is
supplied rapidly to ensure a return to the preset pressure
level.110

KARCZ ET AL

Unrestricted spontaneous breathing throughout the ventilator

cycle also enables carbon dioxide clearance.111,112 Advantages
claimed over conventional ventilation include superior lung
recruitment, higher mean airway pressure but lower peak airway pressure, superior hemodynamic and renal/splanchnic perfusion, and the patients ability to breathe spontaneously from
the time of intubation to the point of separation from the
ventilator.111,112 Supporters suggest a theoretically lower risk of
barotrauma and accelerated weaning, but these claims remain
unproven.111,112
In contrast to conventional ventilation, in which short sharp
breaths are delivered to cyclically inflate the lung from a low
resting volume to a higher volume with PEEP used to prevent
derecruitment and inspiratory pressures limited to prevent excessive tidal volumes, the sustained periods of CPAP maintain
a high resting lung volume.113-116 The CPAP pressures delivered are dominant in determining mean airway pressure, which,
in turn, essentially determines the lung volume and therefore
governs oxygenation. Intermittent low-frequency (16/min)
pressure releases produce an exhaled tidal volume resulting in
carbon dioxide clearance.113-116
The decrease in lung volume resulting from the pressure
releases is controlled by the pressure gradient and the release
time. Tidal volumes are limited by raising the lower pressure
level or alternatively by reducing the release time, prematurely
terminating expiratory airflow and producing intrinsic PEEP. In
essence, excessive tidal volumes signify derecruitment, and
small tidal volumes imply gas trapping.113-116
Based on current literature, APRV is indicated in patients
with acute lung injury (ALI) and ARDS as well as after major
surgery to recruit atelectasis adjacent to the diaphragm and to
restore pulmonary gas exchange while improving cardiovascular and extrathoracic organ function.113,114,117,118 Because the
increase in transalveolar pressure is localized to the areas near
the diaphragm and is caused by a decrease in intrapleural
pressure, the concomitant decrease in intrathoracic pressure
contributes to improved cardiovascular function.113,114,119 Areas
of atelectasis not adjacent to the diaphragm may not be recruited successfully by spontaneous breathing during APRV.120
The reduced requirement for sedation during APRV helps to
decrease the doses of vasopressors and positive inotropes,
while maintaining stable cardiovascular function, and shortens
the duration of ventilator support.113 However, the true benefits
of APRV in terms of maintaining hemodynamic stability and
improved aeration are lost when patients are not breathing
spontaneously (at which point, the mode is essentially PAC).
APRV and its related modes are used infrequently in patients
with severe obstructive airways disease or a high ventilatory
requirement because hyperinflation, high alveolar pressure, and
pulmonary barotrauma may result.117
Biphasic Positive Airway Pressure
Biphasic positive airway pressure has been available for
more than 20 years and was first described by Hrmann et al121
and Baum et al.122 This mode originally was described as a
combination of pressure controlstyle ventilation with unrestricted spontaneous breathing during both high- and lowpressure settings. This is in contrast to traditional PCV, which

MECHANICAL VENTILATION

does not allow spontaneous breathing at the upper pressure

level.123 BIPAP differs from PSV given that spontaneous
breaths are allowed by the ventilator without synchronized
support, as opposed to support of each spontaneous breath,
available in PSV.124,125 However, although BIPAP may be
categorized as a partial ventilatory mode suitable for weaning,
if a patient is not breathing spontaneously, BIPAP is equivalent
to time-cycled PCV.
The use of the term BIPAP in European literature originally created misunderstanding in North America. The term
BiPAP is reserved for noninvasive, positive-pressure ventilation offered by Respironics (Carlsbad, CA). Ventilator companies are prevented from using the term BIPAP by law in
North America, and this has led to the use of terms such as
bilevel on the Puritan Bennett 840 ventilators (Puritan Bennett, Pleasanton, CA) and Bivent on the Servo 300 range
(Siemens-Elema, Solna, Sweden).
Furthermore, definitional differences of BIPAP and APRV
are confusing within the literature. Hedenstierna and Lattuada124 stated that APRV frequently is called BIPAP in Europe. However, while being a continuum of the same concept
(ie, allowing spontaneous breathing during time-cycled
changes in airway pressure), there are some distinct differences. BIPAP conventionally maintains the high-pressure setting for more traditionally acceptable inspiratory times,
whereas APRV always implies an inverse ratio.125,126 Therefore, APRV can be regarded as a special setting or extension of
BIPAP.121 APRV can be used to maintain a high mean airway
pressure for the majority of the respiratory cycle with only brief
pressure releases.
APRV usually is reserved for patients in the more acute
phase of ALI/ARDS, whereas BIPAP can be viewed as a
mode applicable for patients with acute and resolving ALI
who are moving into the weaning phase.121,123 However,
BIPAP can be applied with varying time and pressure durations
that enable it to mimic other modes of ventilation. Clinical studies
have compared these 2 modes to a variety of other ventilation
modes including SIMV, PSV, and inverse-ratio volume control.
Significant findings of studies on BIPAP and APRV have shown
improvements in V/Q match and oxygenation and reductions in
the work of breathing and peak inspiratory pressures.127-131
Setting and Using the Ventilator
The initial ventilator setup plays an important role in patient
care and significantly affects patient physiology.50 There is
much evidence to suggest that the mode and style of ventilation
will affect not only patient comfort but also the time of support.11 The settings may produce volume and pressure trauma if
improper levels of tidal volume and pressure are set.11 There is
growing evidence that the initial tidal volume can affect morbidity and mortality.11
The primary objective of mechanical ventilation is to improve patient outcome by decreasing the work of breathing and
reversing life-threatening hypoxemia or hypercarbia. Sometimes, however, the goal is merely to support patients for
airway protection or inconsistent respiratory drive such as in
patients with a seizure, stroke, or drug overdose.12 An additional objective in patients with acute respiratory failure is to

unload respiratory muscles and relieve respiratory distress.12

These objectives should be achieved with special attention
given to minimizing injuries associated with mechanical ventilation. Ventilator-induced lung injuries include both O2 toxicity and overstretched lungs.12 Furthermore, atelectasis and
alveolar collapse can affect levels of surfactant in the lung and
also be important in the release of cytokines and transmigration
of bacteria both into and out of the lung.19 Therefore, a rational
approach must be taken when treating patients with respiratory
failure who are admitted to the ICU.11
Generally speaking, partial support modes such as PSV can
be applied safely to patients who have adequate central respiratory drive to support ventilation.55,132-134 In patients who have
a tendency for apnea (eg patients with elevated intracranial
pressure, drug overdose, or brainstem stroke), a mode that
provides guaranteed minute ventilation is preferable such as
assist-control or IMV.55,132-134 Patients who are deeply sedated
and possibly paralyzed also fall into the latter category.55,132-134
The patients ability to initiate a breath should be reevaluated
before switching from assist-control modes to PSV.18
It is best to start to place the patient on an FIO2 of 1.0 on
arrival to the ICU as a baseline to evaluate the patients lung
physiology.10 The level of hypoxia also can be evaluated at this
time as well as the level of shunt for this level of oxygen. Such
data will allow the practitioner to decide whether lung recruitment is necessary. According to the findings from the Acute
Respiratory Distress Syndrome Network trial of low-tidal-volume ventilation (Respiratory Management in Acute Lung Injury [ARMA] trial), a large multicenter trial, the ventilator
should be set with normal physiologic tidal volumes of 6 to 8
mL/kg (ideal body weight) as opposed to the traditional approach using 10 to 15 mL/kg.135
PEEP refers to the pressure in the airway at the end of
expiration that exceeds atmospheric pressure.11,34 It is used
mainly to stabilize lung units and improve oxygenation in
patients with hypoxia and to replicate normal lung physiology.11,19 Therefore, PEEP should be titrated using the inflection
points from the pressure-volume curve.24,136 The ideal point is
between the lower and upper inflection points where lung
compliance is maximal.24,136 A good strategy for selecting a
PEEP for optimized mechanical ventilation is to set the level
just above the lower inflection point and maintain plateau
airway pressures below the upper inflection point (Fig 2).24,136
The concept of best or optimal PEEP has evolved over the
years since first being described in 1975.137 Suter et al138
defined the best PEEP as the level of PEEP with the highest
oxygen transport, which is the product of cardiac output and
oxygen content. This PEEP correlates with the highest total
respiratory compliance, the highest mixed venous oxygen tension, and the lowest VD/VT. Civetta et al139 defined the optimal
PEEP as the level of PEEP with the lowest intrapulmonary
shunt and without compromising cardiac output. More recently,
the endpoint for PEEP application is the lowest level of PEEP
that provides an adequate PaO2 at an FIO2 of less than 0.5.140
Increasing PEEP beyond this level to obtain optimum values
for various other endpoints, such as the production of maximum oxygen transport, maximum static pulmonary compliance, shunt less than 15% to 20%, minimal arterial end-tidal
CO2 gradient, decreased mixed venous oxygen tension, and

10

minimum FIO2 will not be clinically helpful and may be harmful.137,140,141

The cardiovascular effects of PEEP depend on the severity of
respiratory failure, the level of PEEP, the intravascular volume,
the contractility of the heart, and the pulmonary vasculature.142
In healthy subjects without respiratory failure, PEEP decreases
cardiac output mainly because of increased intrathoracic pressure, resulting in decreased venous return. PEEP also causes
pulmonary parenchymal overdistention, which makes the lung
come in close contact with the left ventricle, changing compliance and interfering with ventricular function.143,144 In addition,
PEEP increases pulmonary pressure and resistance, resulting in
right ventricular dilation, which causes an intraventricular septum shift toward the left ventricle.142 The leftward septal shift
decreases left ventricular diastolic filling, resulting in decreased
stroke volume and cardiac output. Also, unilateral pulmonary
hyperinflation may cause a neural reflex, resulting in a decreased cardiac output and heart rate.142 Moreover, humoral
depression of myocardial contractility also may be a factor.
Such deleterious effects of PEEP are more apparent in individuals with limited cardiovascular reserve.143,144
Although PEEP is applied only at the end of expiration; in
actuality, the alveolar and transpulmonary pressures are highest
during inspiration and are associated with the greatest negative
hemodynamic effects.142-144 In patients with underlying left
ventricular failure and filling pressure more than 18 mm, PEEP
may increase cardiac output by increasing coronary arterial
oxygen content, augmenting systolic function, or reducing venous return. The decreased venous return may produce a shift
in the Starling curve to filling pressures associated with better
myocardial function.142,143
In patients with respiratory failure, the cardiac output usually
increases or does not change for PEEP up to optimum levels
because of an increase in oxygenation with resultant improvement of cardiac performance.142-144 However, cardiac output
decreases when PEEP exceeds the individuals optimum PEEP.
Furthermore, hypotension during PEEP therapy may be exacerbated by hypovolemia.
In the setting of patients with a head injury, there is no
evidence to suggest that PEEP levels below or equal to 10
cmH2 will affect intracranial pressure. In both closed head
injury and ALI, the PEEP level should be titrated to maximize oxygenation.145-147 It is important to closely monitor
for auto-PEEP (intrinsic PEEP), which is caused by inadequate time for lung emptying in the setting of increased
airway resistance and expiratory flow limitation.145-147 Adverse effects thereof include increased work of breathing,
risk of barotrauma or volutrauma, and hemodynamic compromise.145-147
In summary, patients who receive mechanical ventilation
should be assessed frequently to determine whether the current
ventilator settings remain appropriate because the diseases or
conditions that prompt the initiation of mechanical ventilation
may change rapidly. If a patients respiratory status is worsening, more machine support may be needed. In contrast, if the
patient is improving rapidly, machine support should be decreased to keep pace with the changing demands of the patient.
Many patients become uncomfortable with excessive ventilator
support when their respiratory status is improving. If the ven-

KARCZ ET AL

tilator settings are not accommodating, the patient may fight

the ventilator. This, in turn, may lead to excessive sedation and
may prolong ventilator weaning and ICU stay. Thus, always
fit the ventilator to the patient, not the patient to the ventilator.
ALTERNATIVE MODES OF VENTILATION

In recent years, more complex ventilatory modes have been

introduced to better support a growing number of patients with
complex lung mechanics. In this section, the authors give an
overview of 3 such modes: proportional-assist ventilation,
high-frequency oscillatory ventilation, and NAVA.
Proportional-Assist Ventilation
Proportional-assist ventilation (PAV) was developed by
Younes et al148,149 in 1992 as a spontaneous mode designed to
deliver ventilator support based on continuous measurement of
the patients ventilatory parameters. This mode became commercially available in Europe in 1999 and was approved in the
United States in 2006 and made available on the Puritan Bennett 840 ventilator (Puritan Bennett Co, Boulder, CO). Currently, PAV is available as proportional pressure support on
Drger Evita 4 and XL ventilators (Drger Medical, Lbeck,
Germany). In this mode, there are no set targets of pressure,
volume, or flow, but instead the airway pressure is increased or
decreased in proportion to the patient effort via positive feedback control using respiratory elastance and resistance as the
feedback signals.150,151
The pressure applied by the ventilator during PAV, as opposed to PSV, is a function of patient effort whereby the greater
the inspiratory effort, the greater is the increase in applied
pressure. The operator sets the percentage of support to be
delivered by the ventilator.152,153 The ventilator, in turn, intermittently measures the compliance and resistance of the patients respiratory system and the instantaneous patient-generated flow and volume and, on the basis of these, delivers a
proportional amount of inspiratory pressure.152,153 In PAV, as in
PSV, all breaths are spontaneous. The patients respiratory
drive determines the respiratory rate and inspiratory time,
whereas FIO2 and PEEP are set by the clinician. The other
settings required are the percentage of volume assist and the
percentage of flow assist. The percentage of volume assist is
what overcomes the elastance, whereas the percentage of flow
assist overcomes resistance. These assist settings routinely are
set at 80%.153 Tidal volumes are variable; however, in recent
reports, the tidal volumes were within the lung-protective range
(6-8 mL/kg, plateau pressure 30 cmH2O).154,155
PAV has been described as the only mode to be designed
primarily on a physiologic level rather than relying on the
technical abilities of ventilators.148 The hemodynamic profile is
similar to that in PSV. A distinct advantage of PAV is the
ability to respond to rapid changes in ventilatory effort associated with increased elastance and resistance that occur in patients with respiratory failure. This enables respiratory muscle
unloading during increases in inspiratory effort and improves
patient comfort because of a reduction in the work of breathing148,151,156 as well as patient-ventilator interaction.157 Two

MECHANICAL VENTILATION

randomized clinical trials have shown improved patient comfort during NIV with PAV compared with PSV.158,159
One common finding in several observational studies is that
PAV allows a greater tidal volume variability than does
PSV.156,159-162 Furthermore, the incidence of more missed triggers with intubated patients as the PSV level is increased does
not occur with PAV.157,163-165 Negative aspects associated with
PAV include difficulties with accurate measurement of elastance and resistance in spontaneously breathing patients or
those receiving partial support and the confounding effects
imposed by endotracheal tube resistance and the presence of
auto-PEEP.153,166 Difficulty in determining the appropriate settings for the percentage of volume and flow assist has discouraged the adoption of this mode into mainstream clinical practice.
High-Frequency Oscillatory Ventilation
High-frequency oscillatory ventilation (HFOV) was first described in 1952 by Emerson and was developed clinically in the
early 1970s by Lunkenheimer.167 It was approved by The US
Food and Drug Administration for use in infants in 1991 and
for children in 1995.168 The adult model has been available
since 1993, but it was not approved until 2001 as Sensormedics
3100B (Viasys Healthcare, Yorba Linda, CA). HFOV has been
identified as an alternative method of applying low tidal volume, controlled-pressure ventilation in the setting of ARDS.169
In patients who develop ARDS or ALI and consequently
have reduced lung compliance and impaired oxygenation,169
HFOV attempts to deal with the potential risks of mechanical
ventilation including barotrauma, volutrauma, atelectrauma,
and oxygen toxicity. Furthermore, it can be considered when
conventional ventilation fails to safely and adequately provide
respiratory support. High-frequency ventilation generally is
deemed beneficial for patients with severe pulmonary failure
because it uses much smaller tidal volumes than conventional
ventilation, maintains the lungs/alveoli open on the deflation
limb of the pressure-volume curve at a relatively constant
airway pressure and thus may prevent atelectrauma and barotrauma, and improves ventilation/perfusion (V/Q) matching by
ensuring uniform aeration of the lung.170
HFOV uses an oscillatory pump to deliver a respiratory rate
of 3 to 15 Hz (up to 900 breaths/min) through the endotracheal
tube. This rate is so fast that the airway pressure merely
oscillates around a constant mean airway pressure. The respiratory rate is set directly by the clinician. The mean airway
pressure is set by adjusting the inspiratory flow rate and an
expiratory back-pressure valve (similar to applied PEEP).171
Some pumps allow the mean airway pressure to be set directly.
The constant mean airway pressure maintains alveolar recruitment, avoids low end-expiratory pressures, and avoids
high peak airway pressures. It also impacts oxygenation. Specifically, a higher mean airway pressure is associated with
better oxygenation. HFOV induces a higher mean airway pressure than most modes of mechanical ventilation. The tidal
volume (also called amplitude) is small during HFOV, usually
less than or equal to the anatomic deadspace. The amplitude
depends on the ETT size and respiratory frequency; a smaller
amplitude results when the endotracheal tube is small or the
respiratory frequency is high.172

11

Most studies of HFOV have been performed in adults with

ALI/ARDS.173-175 In the largest multicenter trial, 148 patients
with ALI/ARDS were assigned randomly to undergo mechanical ventilation using HFOV or PCV.173 The PCV settings
targeted a tidal volume of 6 to 10 mL/kg of actual body weight.
The HFOV group had lower mortality rate that was not statistically significant (37% v 52%). The same group also had
significantly higher mean airway pressure and PaO2/FIO2 ratio
although these differences did not persist beyond 24 hours.
A meta-analysis of 6 randomized trials (365 patients), including the trial just described, found that adults with ALI/
ARDS who received HFOV had significantly lower hospital
mortality or 30-day mortality than those who received conventional mechanical ventilation alone (39% v 49%).176 A limitation of this meta-analysis was that some of the trials that were
included did not use low-tidal-volume ventilation in their control groups, which could bias the results in favor of HFOV.
When trials that allowed tidal volumes 8 mL/kg were excluded and the meta-analysis repeated, there was a trend toward
lower mortality among patients who received HFOV. These
results indicated that the repeat meta-analysis was too small to
exclude or confirm a clinically important effect and additional
trials are necessary to compare the effects of HFOV and low
tidal-volume ventilation on mortality.
This mode usually is reserved for ARDS patients for whom
conventional ventilation is failing. A recently published protocol171 suggests considering HFOV when there is oxygenation
failure (FIO2 0.7 and PEEP 14 cmH2O) or ventilation
failure (pH 7.25 with tidal volume 6 mL/kg predicted body
weight and plateau airway pressure 30 cmH2O). This mode is
contraindicated when there is known severe airflow obstruction
or intracranial hypertension.171
Furthermore, it is suggested that HFOV at a respiratory rate
greater than 6 Hz may be required because the usual respiratory
rate of 3 to 6 Hz results in airway pressures that potentially are
not lung protective. The feasibility of this approach was shown
by a single-center, prospective cohort study of 30 patients with
ARDS who were receiving HFOV after failing conventional
lung-protective ventilation.177 Among the patients whose respiratory rates exceeded 6 Hz (range, 6-15 Hz), most were able to
meet their oxygenation (PaO2, 55-80 mmHg) and ventilator
goals (pH, 7.25-7.35).
The high respiratory rate shortens the expiratory time, potentially causing auto-PEEP and dynamic hyperinflation. The
plateau airway pressure (alveolar pressure) and mean airway
pressure are likely to increase if auto-PEEP and dynamic hyperinflation develop, elevating the risk of pulmonary barotrauma and hemodynamic instability. This occurs despite a
lower peak airway pressure conferred by the smaller tidal
volumes. In 1 trial, the risk of pulmonary barotrauma or hemodynamic instability was the same for patients receiving HFV
compared with those receiving an alternative mode of mechanical ventilation.171
There are also complications unique to the type of HFV. As
an example, HFJV is associated with necrotizing tracheobronchitis, ETT mucus inspissation, and the variability of cardiac
output.178 Proper gas humidification reduces the likelihood of
necrotizing tracheobronchitis or ETT mucus inspissation.

12

KARCZ ET AL

Neurally Adjusted Ventilatory Assist

NONINVASIVE VENTILATION

al179

NAVA was first introduced by Sinderby et

in 1999 and
subsequently used on the Servo-I ventilator (Maquet, Bridgewater, NJ) in 2007. This mode was developed in an attempt to
overcome the limitations of PAV while maintaining all of its
potential advantages.153 NAVA is a partial ventilatory support
mode that uses the electrical activity of the diaphragm to
control patient-ventilator interaction.180 The electrical activity
of the diaphragm represents the final neural output of the
respiratory centers to the diaphragm and is therefore able to
both trigger and cycle a breath. Breaths remain pressure controlled.180
With NAVA, the pressure delivered during inspiration is
proportional to the electrical activity of the diaphragm.180 The
pressure level can be adjusted based on patient effort and the
proportionality setting.180 Depending on the patients response
to the delivered pressure, an increase in the NAVA level may
increase the delivered pressure (if electrical activity of the
diaphragm is unchanged) or it could suppress electrical activity
of the diaphragm and instead deliver a constant level of assist
or some level in between.180
NAVA requires an esophageal catheter that measures the
electrical signal to the diaphragm (Edi).180 The Edi catheter
is similar to a standard nasogastric tube in diameter and
length but has a series of electrodes that measure the Edi.
NAVA is triggered by the Edi signal, and the sensitivity can
be set, like pressure triggering or flow triggering.180 The
minimum Edi signal is recorded, and the sensitivity is based
on an increase in the signal above that reference value.
NAVA cycling occurs when Edi drops to approximately
70% of its peak value.180
Since the initial article in 1999,179 a series of original investigations have been published, all of which were authored or
coauthored by the NAVA inventors.180 Allo et al181 evaluated
the effects of NAVA on rabbits with ALI. They found that
ALI caused a vagally mediated atypical diaphragm-activation pattern in spontaneously breathing animals.181 The addition of PEEP restored phasic activity, and NAVA efficiently maintained respiratory muscle unloading while
delivering safe VT.181
More recently, studies with adult and neonatal patients have
been published.182,183 Brander et al182 studied 15 patients with
ALI and systematically increased the NAVA level over a
3-hour period, which reduced the respiratory drive, unloaded
the respiratory muscles, and allowed the clinician to identify an
assist level that resulted in sustained unloading, appropriate VT
(5.4-7.2 mL/kg of predicted body weight), and normal hemodynamics.182
In low birth-weight infants, Beck et al183 found that NAVA
improved patient-ventilator synchrony, even in the presence of
leaks around the ETT. This suggests that in a neonate with an
uncuffed ETT, particularly at a higher respiratory frequency,
NAVA should be advantageous. NAVA is clearly an innovative design, and it still remains in an early stage of development. Currently, there have been no long-term studies to determine if NAVA has outcome benefits.

The term NIV is used to refer to positive-pressure ventilatory support delivered through a nasal or full facemask with
different levels of pressure support set for inspiration and
expiration (frequently 10-15 and 5-8 cmH2O).134 This type of
ventilation should be distinguished from CPAP in which a
constant level of pressure support is delivered without regard
for the respiratory cycle.134 When used in the care of patients
with acute respiratory failure, NIV always should be used in a
highly monitored setting such as an ICU, step-down unit, or
emergency department.134
Conditions known to respond to NIV include exacerbations
of COPD that are complicated by hypercapnic acidosis (PaCO2
45 mmHg or pH 7.30), cardiogenic pulmonary edema, and
hypoxemic respiratory failure. NIV also may be helpful for
preventing postextubation respiratory failure.184 Despite evidence of efficacy, NIV may be underused among patients with
cardiogenic pulmonary edema or hypercapnic COPD exacerbations.184
Patients should be assessed carefully for possible contraindications to the use of NIV before its implementation. NIV
should not be used in patients with impending cardiovascular
collapse or respiratory arrest because those patients will soon
require endotracheal intubation. Patients who are unable to
protect their airway, usually from altered mental status, should
not receive NIV. Such patients are at very high risk for failure
even though it may be tempting to use NIV in this setting,
particularly when hypercarbia is present. Other contraindications include nonrespiratory organ failure, facial surgery/trauma/deformity, high aspiration risk, and a prolonged anticipated
duration of mechanical ventilation.185
Hypercapnic encephalopathy may be an exception to the rule
that severely impaired consciousness is a contraindication to
NIV.186,187 Clinicians who choose to try NIV in this setting
should monitor such patients closely. Improved consciousness
should be apparent within 1 to 2 hours after the initiation of
NIV. Patients who deteriorate or fail to improve should be
intubated promptly. The likelihood that hypercapnic encephalopathy will respond to NIV is inversely related to the severity
of the hypercapnia. Respiratory acidosis is not a contraindication to NIV.188,189
NIV can be delivered using the same modes that are used for
invasive mechanical ventilation although certain modes are
used more frequently. Assist control is the most common mode
chosen by clinicians who want a guaranteed minimal minute
ventilation.10,50 PSV is the most common mode chosen by
clinicians who want to maximize patient comfort and synchrony. CPAP often is used for patients with acute respiratory
failure because of cardiogenic pulmonary edema. Bilevel positive airway pressure delivers both inspiratory positive airway
pressure and expiratory positive airway pressure. Controlled
mechanical ventilation, IMV, SIMV, and PCV rarely are used
during NIV.10,50
After NIV is initiated, the patient should be observed closely
for the first 8 hours to troubleshoot, provide reassurance, and
monitor for deterioration.190 Improvement of the pH and arterial carbon dioxide tension (PaCO2) within one half to 2 hours
predicts success.191,192 In contrast, a patient should be consid-

MECHANICAL VENTILATION

ered to have failed NIV and promptly intubated if there is

neither stabilization nor improvement over the same time
frame. Other criteria suggesting failure are worse encephalopathy or agitation, inability to clear secretions, inability to tolerate any of the interfaces, hemodynamic instability, or decreased oxygenation.192
In general, the ability of clinicians to select patients with a
high likelihood of success is poor and NIV failure rates are
high.192-194 Two observational studies found that approximately
one third of patients who received a trial of NIV failed.3,195
According to Demoule et al,196 first-line treatment with NIV
was associated with lower mortality than with invasive mechanical ventilation (23% v 39%) in ICU patients who required
ventilatory assistance for acute respiratory failure at any time
during the ICU stay. It is unknown whether this was a consequence of selection bias (ie, less sick patients receive a trial of
NIV), fewer complications related to intubation (eg, ventilatorassociated pneumonia), or both.
In patients with acute respiratory failure, NIV has been
shown to reduce the frequency of invasive mechanical ventilation. In a meta-analysis of 7 randomized trials, NIV reduced
the need for invasive mechanical ventilation approximately
20%.197 High-quality evidence from several randomized trials
and meta-analyses indicated that NIV improves important clinical outcomes in patients having an acute exacerbation of
COPD complicated by hypercapnic acidosis.198,199 As an example, consider a meta-analysis (14 randomized trials, 758
patients) that compared standard therapy alone with NIV plus
standard therapy in patients having COPD exacerbation complicated by hypercapnia (PaCO2 45 mmHg).198 NIV decreased the mortality rate (11% v 21%), intubation rate (16% v
33%), and treatment failure (20% v 42%). Hospital length of
stay and complications related to treatment also were reduced
by NIV.
Current literature shows that NIV has several physiologic
benefits. Respiratory mechanics measured after the initiation of
NIV show a decreased respiratory rate, an increased tidal
volume, and increased minute ventilation.200,201 In addition, the
arterial oxygen tension (PaO2) tends to increase as the PaCO2
decreases. Furthermore, NIV decreases the need for intubation
and improves respiratory parameters such as dyspnea, hypercapnia, acidosis, and heart rate in patients with cardiogenic
pulmonary edema.202-206
A meta-analysis of 8 randomized trials including 461 patients compared standard medical therapy alone with standard
medical therapy plus NIV in patients with hypoxemic respiratory failure because of causes other than cardiogenic pulmonary edema.207 NIV reduced ICU mortality (17% absolute risk
reduction), intubation rate (23% absolute risk reduction), and
ICU length of stay (2-day absolute reduction).207 The metaanalysis was limited by heterogeneity across the included trials.
There are no controlled trials and little clinical experience using
NIV to manage patients with ARDS. Observational series suggest that intubation can be avoided approximately half of the
time.208,209
NIV generally is safe. Most complications are local. Some
factors that may limit the use of NIV are mask- (or interface-)
related problems such as air leaks, mask intolerance because of
claustrophobia and anxiety, and poorly fitting mask. Approxi-

13

mately 10% to 15% of patients fail to tolerate NIV because of

problems associated with the mask interface despite adjustments in strap tension, repositioning, and trial of different types
of masks.201 Other mask-related problems include facial skin
breakdown, aerophagia, inability to handle copious secretions,
and mask placement instability.
NIV in Immunosuppressed Patients
NIV may be useful in patients who are profoundly immunosuppressed, especially those with hematologic malignancy or
those who have undergone solid organ transplantation, in
whom mortality after endotracheal intubation is particularly
high. Antonelli et al210 randomized 40 patients with acute
hypoxemic respiratory failure after solid organ transplant to
conventional treatment (including high-flow oxygen by facemask) or NIV. The patients randomized to NIV had shorter
ICU stays, lower rate of endotracheal intubation, and lower
ICU mortality. In-hospital mortality did not differ significantly
between the 2 groups. A second study by Hilbert et al211
assessed the use of NIV in 52 neutropenic patients with pulmonary infiltrates and hypoxemic respiratory failure (more than
half because of hematologic malignancy and chemotherapy).
NIV resulted in fewer intubations and serious complications
and reduced ICU and hospital mortality. These studies suggest
that NIV may be beneficial in severely immunocompromised
patients with acute hypoxemic respiratory failure.
WEANING

Weaning is the process during which the patient is liberated

from mechanical support and from the ETT.212 It is important
to remember the goals of mechanical ventilation, which are to
provide adequate arterial oxygenation, achieve carbon dioxide
clearance, and relieve the work of breathing.212 At the same
time, it is important to try to avoid barotrauma, multiple organ
dysfunction, atelectasis, hemodynamic depression, nosocomial
infection, and muscular dystrophy associated with mechanical
ventilation. These factors will all have to be taken into consideration while attempting to wean from ventilator support.
Time spent in the weaning process can make up 40% to 50%
of the total duration of mechanical ventilation.10,50 As many as
20% of the mechanically ventilated patients will fail at their
first attempt of weaning; hence, choosing the right time to
discontinue mechanical ventilation is a challenge as failed
extubation followed by reintubation is associated with increased morbidity and mortality.10,212
It is important to recognize that there are stages from the
initiation of mechanical ventilation to liberation from the ventilator and these include: (1) treating the cause of acute respiratory failure, (2) suggestion that weaning may be possible, (3)
assessment of readiness to wean, (4) SBT, (5) extubation, and
(6) reintubation.10 It is important to ensure that progress is
made from 1 stage to the other as delay in weaning will expose
the patient to discomfort and complications, and will inevitably
increase the cost of care.
Assessment of Readiness to Wean
It is important to consider weaning as early as possible using
both clinical and objective assessments. A patient should meet

14

4 criteria in order to be considered ready for weaning: (1) clear

evidence of reversal or stability of cause of acute respiratory
failure, (2) adequate gas exchange as indicated by PaO2/FIO2
between 150 and 200 at a PEEP level between 5 and 8 cmH2O
and pH above 7.25, (3) cardiovascular stability (no active
myocardial ischemia or clinically significant hypotension requiring inotropes), and (4) the ability to make an adequate
inspiratory effort.213
Perhaps the best known and most widely used measure of
extubation readiness is the respiratory rate-to-tidal volume ratio, also known as the rapid shallow-breathing index or the
Yang-Tobin index.214 In their well-known study, Yang and
Tobin214 challenged the traditional markers of extubation readiness, minute ventilation, and maximal inspiratory pressure and
proposed the rapid shallow-breathing index as an alternative.
They defined the index as respiratory rate over tidal volume (in
liters), measured during spontaneous breathing for 1 minute;
low values are thereby derived from a low respiratory rate and
high tidal volume.214 Using a cutoff for the rapid shallowbreathing index of 105 maximized sensitivity and specificity.214 Their finding has since been confirmed in other prospective studies, including one that suggested that the rapid-shallow
breathing index measured after 30 minutes of minimal support
outperformed the rapid shallow-breathing index measured immediately after support is decreased.215
Spontaneous Breathing Trial
It is important to understand the concept of a SBT as it is the
next step towards discontinuation of mechanical support after a
rapid shallow-breathing index test. Before the start of SBT, a
cuff leak test to indicate the absence of laryngeal edema should
be considered in all patients. During this critical test, close
observation is very important, especially during the first few
minutes when the frequency/VT ratio should be used. If this
ratio remains between 60 and 105 breaths/L, the patient may be
allowed to continue the SBT. The initial SBT should last for at
least 30 minutes and should be with one of the modes below
with PEEP of 5 cmH2O.216,217
There are 3 choices of ventilator setting during an SBT: (1)
the T-piece circuit that provides a constant flow of oxygen past
the endotracheal tube with an extension downstream to prevent
entrainment of room air; (2) low levels of pressure support of
5 to 6 cmH2O; (3) and CPAP.218,219 The use of automated tube
compensation, which adjusts for the assumed resistance of the
ETT, may be used in SBT to compensate for a narrow
ETT.218,219 The criteria for passing an SBT include good respiratory pattern, adequate gas exchange, hemodynamic stability,
and subject comfort.218 Failure during an SBT is likely to occur
within the first 20 minutes, and the patient should be put back
on to full ventilatory support. A comprehensive review of
potential contributing factors to the failure then should be
made.
Successful completion of an SBT does not necessarily guarantee that the patient is ready for extubation as reintubation
rates are still as high as 13% to 19% using this protocol, with
a higher rate for those intubated for 48 hours.218-220 However,
it is highly predictive of successful weaning.220 The risk factors
for failure of an SBT include but are not restricted to old age,
increased severity of underlying illness, and cardiac failure.218

KARCZ ET AL

Methods of Weaning
When the patient successfully completes the SBT, weaning
then can be started by using any of the following 3 techniques:
(1) moving from assist-control ventilation to higher levels of
PSV, which can be decreased as tolerated; (2) using SIMV with
an initial higher rate, which can be decreased over time; and (3)
continuing full ventilatory support with intermittent trials of
low levels of pressure support or CPAP.218-220 Once a pressure
support level of less than 10 cm2O is reached, the patient could
be considered as ready to be extubated from a ventilatory point
of view. Success or failure of weaning will then depend on
respiratory muscle function, central nervous system drive, and
work of breathing required.218-220 If patients fail at weaning
attempts, then the goals should be (1) to choose appropriate
modes of ventilation to provide a balance between respiratory
load and capacity, (2) to prevent diaphragm muscle atrophy,
and (3) to reassess reversible factors preventing weaning.218,219
Application of Weaning Protocols
The finding that the use of standardized protocols to wean
patients from mechanical ventilation gives better results in
terms of outcome and costs less than the traditional practice of
physician-directed weaning has been emphasized by several
authors.221-223 Such protocols are used to systematically evaluate patients receiving mechanical ventilation to assess their
potential ability to be removed from mechanical support.
In a study by Ely et al,221 300 mechanically ventilated
medical patients were randomized to an intervention strategy
that included daily readiness testing with SBTs as compared
with standard care. The control patients were screened daily but
the information was not used to make weaning decisions. The
patients in the intervention group who passed a daily screen
underwent a 120-minute SBT. If this trial was passed, the
managing clinicians received a prompt for extubation. It was
noted that the intervention group experienced significant reductions in weaning time, duration of mechanical ventilation,
complication rate, and ICU costs. However, no differences
were noted in ICU or hospital length of stay, hospital costs, or
mortality.
Kollef et al222 and Marelich et al224 similarly have shown that
protocol-driven strategies result in faster weaning from mechanical ventilation, lower costs, and reduced complications as
compared with physician-directed approaches. These studies
also showed clearly that nonphysician health care professionals
can successfully and safely play a major role in executing these
protocols that improve clinical outcomes and reduce costs.
On the other hand, studies performed in a neurosurgical
ICU,225 a pediatric ICU,226 and a medical ICU at a leading
academic medical center found no superiority to a protocolized
approach.227 Although a protocol may serve as the default
approach to weaning, flexibility and clinical judgment are recommended highly as too rigid an approach needlessly prolongs
weaning and extubation.223 Therefore, protocols must be tailored to the environment in which they will be used.223 This
necessitates modifying the protocol for application to a distinct
patient population.223

MECHANICAL VENTILATION

Role of NIV in Weaning

NIV could be used in 3 different scenarios for weaning: (1)
as treatment for patients who have been extubated but have
developed acute respiratory failure within 48 hours, (2) as a
prophylactic measure after extubation for those who are at high
risk for reintubation, and (3) to wean those patients who are
intolerant of an initial weaning trial.218,219 A trial of 43 patients
with underlying lung disease, the majority of which was
COPD, showed that NIV was associated with significant reductions in the duration of invasive ventilation, intensive care
and hospital length of stay, ICU mortality, serious complications of mechanical ventilation, and cumulative 90-day survival.228 Furthermore, a meta-analysis that included this and 4
other studies found that NIV in this setting seemed to decrease
mortality, hospital length of stay, the incidence of ventilatorassociated pneumonia, and the total duration of mechanical
ventilation.229
CONCLUSION

The successful application of positive-pressure ventilation

for polio-induced respiratory paralysis during the 1952 Copenhagen outbreak marked the birth of modern mechanical ventilation as a method to manage acute respiratory failure. Acute
respiratory failure continues to remain a significant cause of
morbidity and mortality. In the United States, the annual incidence of acute respiratory failure has been reported to be as
high as 137 hospitalizations per 100,000 residents over the age
of 5 years with an exponential increase for each additional
decade up to the age of 85.230
Acute respiratory failure is very common in the ICU with as
many as 56% of all ICU patients having this diagnosis at some
point during their hospital course. Mortality rates also remain
high with as many as 30% to 35% of patients succumbing in the
hospital.9,230 Multiple extrapulmonary factors, including age,
the presence of infection or cardiovascular organ failure on
ICU admission, the development of multiple organ failure
while in the ICU, and a prior history of renal insufficiency, are
associated with the development of acute respiratory failure
and subsequent mortality.9
Ventilatory support for respiratory failure continues to evolve as
the understanding of the advantages and risks of different support
modes increases. The appropriate support for individual patients
must be chosen based on the underlying disease and physiology as
well as the advance directives of the patient.
In fewer than 15 years, noninvasive mechanical ventilation
(NIV) has become a major therapy of acute respiratory failure.
The benefit of NIV is very well established in ventilatory
failure resulting from acute exacerbations of COPD198-200 as
well as in acute cardiogenic pulmonary edema.202-206 It has been
shown that NIV is an effective treatment of hypoxemic respiratory failure in immunocompromised patients. Indications for
NIV are still increasing, especially in ventilator weaning231 and
in the postoperative setting.232 Consequently, growing evidence
of the benefits of NIV in multiple indications has led to a major
increase in NIV use.7,232 This technique may prevent intubation
not only by improving V/Q mismatching but also by preventing
the release of cytokines and bacterial translocation. Therefore,

15

it is recommended that NIV be used early on to prevent these

negative physiologic effects.
Alveolar collapse with improper mechanical ventilation has
been implicated as one of the major causes of poor outcome in
mechanically ventilated patients. Consequently, lung recruitment and alveolar stabilization have an important role. It is well
known that barotrauma from alveolar overdistention at endinspiration and repetitive alveolar collapse at end-expiration
contribute to ventilator-induced lung injury. There has been a
greatly increased use of lung recruitment based modes of
mechanical ventilation. Some of these like CPAP and bilevel
positive pressure can be aids in nonintubated patients who are
breathing spontaneously. This strategy may be an excellent bridge
to prevent intubation and long-term mechanical ventilation. Thus
by preventing atelectasis, these modes may prevent respiratory
failure and cytokine modulation and surfactant changes.
Once the need for endotracheal intubation and mechanical
ventilation has been established, the methods of achieving
adequate mechanical support must be determined. The initial
choice of ventilation mode ultimately should be left to the
discretion of the attending physician and/or institution policy.
In an urgent situation, physicians should be encouraged to use
the mode with which they are more familiar.
Advances in ventilator technology have been made in the
past decade to determine the optimal ventilator strategies for
some of the most common causes of acute respiratory failure.
Prospective clinical trials have defined important techniques
that may improve survival and limit morbidity in patients with
ALI. This, coupled with a growing understanding of respiratory
physiology, have led to an increase in the anesthesiologists
ability to care for patients. In recent years, more complex
ventilators have been introduced to better support a growing
number of patients with complex lung mechanics. With the
addition of microcomputers and feedback loops in ICU ventilators, they are better able to control and support respiratory
parameters that were adjusted manually only a few short years
ago. It is hoped that this technology will aid in the management
of patients and also reduce ventilator-induced lung injury.
Some of these modes build on the basic modes of pressure
control and assist control by providing technologic advances
that correct the limitations that historically they have had.
The management of mechanical ventilation is no longer a
hit-or-miss procedure but rather a therapy that has physiologic
endpoints along with the basic goals of oxygenation and the
removal of carbon dioxide. The ventilator strategies and settings
that are chosen from the outset will have a great impact on patient
management. Proper settings allow for improved oxygenation on
the lowest FIO2 with the least atelectasis and, subsequently, will
allow for the patient to be weaned rapidly from the ventilator.
Therefore, the accurate assessment of lung mechanics allows the
clinician to choose ventilator settings that maximize lung recruitment and prevent overdistention, thereby minimizing the risk of
adverse effects. Modulation of the mode of mechanical ventilation
occurs as the primary disease process resolves and the patient
becomes ready to assume more work of breathing.
The method of successful withdrawal of mechanic ventilation from an individual patient remains driven by clinical
judgment. Mechanically ventilated patients should be evaluated
on a daily basis for the appropriateness of a spontaneous

16

KARCZ ET AL

breathing trial, and the success or failure of the trial should be

judged based both on subjective criteria and objective measurements like the rapid shallow-breathing index. Protocols designed to identify the patients most able to be liberated successfully from mechanical support and executed primarily by
nonphysician health care professionals consistently have shown
faster withdrawals in the protocol-intervention groups than in
the traditional care patients.

Of all the technologic advances over the past 10 to 15

years, the field of mechanical ventilation has been at the
forefront. Clinicians are mandated to remain ahead of the
curve and understand the benefits of physiologic-based mechanical ventilation with the aim of ensuring that patients
receive the optimal mode of mechanical ventilation, which
minimizes the risk of ventilator-induced lung injury and
ensures that weaning occurs as rapidly as possible.

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