Article respiratory disorders

Update on Mechanical Ventilatory Strategies

Martin Keszler, MD* Educational Gaps
With a large number of modalities of mechanical ventilation to choose from and paucity of
Author Disclosure good clinical studies, clinicians face the difficult task of selecting the best tools to utilize
Dr Keszler disclosed he and the optimal strategies to employ in order to minimize ventilator-associated lung injury.
has been a consultant
to and received research Abstract
support and lecture Mechanical ventilation is essential for survival of many extremely premature infants,
but all forms of positive pressure ventilation are to some degree injurious to the lungs.
honoraria from Draeger
A variety of sophisticated devices are used to provide respiratory support, yet substan-
Medical, Inc; that he is
tial uncertainty remains regarding the optimal ways in which these tools can be used to
on the advisory board minimize ventilator-associated lung injury. A good understanding of the unique as-
and speaker bureau of pects of respiratory physiology of extremely preterm infants is key to obtaining the
Ikaria, Inc; and that he is greatest benefit from modern ventilator technology. Early lung volume recruitment
a consultant and on the with adequate end-expiratory pressure, avoidance of volutrauma during the immediate
postnatal period, and noninvasive respiratory support as the initial strategy are now
advisory board for
accepted as important factors in minimizing lung injury. Volume-targeted ventilation
Discovery Laboratories,
combined with optimal lung volume strategies to ensure that the tidal volume is evenly
Inc. and has received distributed throughout an open lung seems to be the best approach to lower the in-
research support from cidence of bronchopulmonary dysplasia.
the company. This
commentary does
contain a discussion of Objectives After completing this article, readers should be able to:
an unapproved/ 1. Understand the unique aspects of neonatal respiratory physiology and the complexity
investigative use of of patient–ventilator interactions during synchronized mechanical ventilation.
a commercial product/ 2. Know the key factors involved in ventilator-associated lung injury and the ventilation
device. strategies designed to minimize them.
3. Understand the importance and principles of the open lung concept.
4. Be familiar with the basic operating principles of various modes of volume-targeted
ventilation, their advantages, and indications for use.

Introduction
Mechanical ventilation (MV) remains an essential tool in NICUs, especially in extremely
low gestational age (GA) neonates. In a large cohort analysis of extremely preterm infants,
89% were mechanically ventilated during the first day after birth, and nearly 95% of survivors
were ventilated at some point during their hospital stay. (1) The Surfactant, Positive Pressure,
and Oxygenation Randomized Trial (SUPPORT) trial found that 83% of infants assigned to
noninvasive support required intubation at some point during their hospitalization. (2) A
recent study focusing on infants less than 28 weeks’ GA documented a 74% rate of intuba-
tion. (3) The Continuous Positive Airway Pressure or Intubation (COIN) trial, which in-
cluded only 25- to 28-week GA infants who breathed at birth, reported that 46% of
infants assigned to noninvasive support ultimately required endotracheal intubation and
MV. (4) These studies demonstrate that MV remains an indispensable tool in NICUs, even
in the era of noninvasive respiratory support. However, although MV may be life-saving, it

*Department of Pediatrics, Warren Alpert Medical School of Brown University, and Director of Neonatal Respiratory Services,
Women and Infants Hospital, Providence, RI.

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respiratory disorders mechanical ventilatory strategies

is associated with significant complications, including inflammatory response to the development of bronchopul-
ventilator-associated lung injury (VALI) and neurodevel- monary dysplasia (BPD). One of the consequences of the
opmental impairment. shift in clinical practice away from invasive ventilation is
With improved survival of preterm infants, focus has that fewer infants now receive MV, and this reduction
shifted from reducing mortality to reducing the persis- has led to decreased levels of experience for trainees
tently high incidence of chronic lung disease and neuro- and practitioners. Infants who now receive MV tend to
developmental impairment. Although high-frequency be smaller and more immature than those ventilated
ventilation was once seen as the answer to this need, 10 or 15 years ago and may remain ventilated for
inconsistent results and continued concerns about the extended periods for reasons not related to their lung dis-
hazards of inadvertent hyperventilation have limited its ease. Data from clinical trials conducted many years ago
acceptance as first-line therapy in infants who have may therefore not be applicable to the extremely imma-
uncomplicated respiratory distress syndrome. Instead, ture infants who now constitute the majority of ventilated
the focus has shifted to avoiding intubation and MV in infants.
the first place; use of noninvasive respiratory support In the closing years of the 20th century, a new gener-
has become generally accepted as the best way to reduce ation of microprocessor-based ventilators with advanced
VALI. Surfactant is now increasingly administered with- features enabling effective synchronized ventilation be-
out prolonged MV, thus potentially preserving the came widely available. However, it is essential to recognize
well-documented benefits of surfactant replacement that better technology alone will not improve outcomes;
therapy while avoiding the risks associated with MV. unless used with care and with optimal ventilation strate-
Administration of nebulized surfactant during nasal con- gies, these machines cannot materially affect outcomes.
tinuous positive airway pressure (CPAP) is a potentially The goal of this review was to discuss the unique chal-
attractive approach that is currently under investigation. lenges of ventilating extremely low GA neonates, review
Nasal ventilation may augment an immature infant’s the basic modes of synchronized ventilation, describe
inadequate respiratory effort without the complications the various approaches of volume-targeted ventilation
associated with endotracheal intubation. This ap- (VTV), and emphasize key aspects of lung-protective ven-
proach may reduce the incidence of ventilator-associated tilation strategies with conventional MV.
pneumonia and thus avoid the contribution of postnatal

Basic Ventilator Terminology

The rapid evolution of ventilator technology with in-
Abbreviations creasing availability of a variety of complex modes of re-
A/C: assist/control spiratory support has led to a great deal of confusion in
BPD: bronchopulmonary dysplasia terminology. Because different manufacturers employ
CPAP: continuous positive airway pressure catchy proprietary nomenclature to describe similar
ETT: endotracheal tube modes of ventilation, communication between users of
FIO2: fraction of inspired oxygen different devices has become increasingly difficult. Prag-
GA: gestational age matic considerations led to the adoption of the “universal
MMV: mandatory minute ventilation ventilator” designed to ventilate the entire spectrum of
MV: mechanical ventilation patients from the 150-kg adult to the 400-g extremely
NAVA: neurally adjusted ventilatory assist low GA neonate, as the industry standard. It is not clear
PRVC: pressure-regulated volume control that all of these devices function as effectively at the low-
PEEP: positive end-expiratory pressure est end of the patient spectrum, as they are primarily de-
PIP: peak inflation pressure signed for the much larger adult market. These devices
PSV: pressure support ventilation offer a variety of modes, the safety and efficacy of which
SIMV: synchronized intermittent mandatory ventilation have never been evaluated in newborn infants. Detailed
VALI: ventilator-associated lung injury discussion of the terminology is beyond the scope of this
VCV: volume-controlled ventilation article, but to ensure clarity of understanding, the basic
VG: volume guarantee terminology for modes that are commonly used in new-
VT: tidal volume born infants is reviewed.
VTV: volume-targeted ventilation Basic modes of MV may be classified according to 3
characteristics:

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1. How is the inflation initiated? simply small adults. To optimally utilize the complex
2. How is gas flow controlled during the inflation? devices at our disposal, we need to be aware of the
3. How is the inflation terminated? many unique aspects of a newborn infant’s respiratory
physiology.
Inflations can be initiated at a fixed rate without regard
to patient inspiratory effort. This mode is known as con-
trolled MV and is used in patients who are heavily sedated Lung Mechanics
or paralyzed. In awake patients, assisted—also known as Small infants who have poorly compliant lungs have very
synchronized or patient-triggered—ventilation modes short time constants and normally have rapid respiratory
are used where inflations are triggered by the patient’s in- rates with very short inspiratory times to match their
spiratory effort. lung mechanics. They have limited muscle strength and
The primary control variable for gas flow during the cannot develop strong inspiratory flow or pressure. This
inflation is either pressure (pressure-controlled/pressure- situation imposes great technological challenges on de-
limited ventilation) or tidal volume (VT; volume-controlled vice design, especially in terms of triggering ventilator
ventilation [VCV]). inflations, inflation termination, and VT measurement.
Inflation termination occurs when a set inflation time Suboptimal trigger devices may lead to excessive trigger
has elapsed (time-cycled), when inflation flow decelerates delay with asynchrony, failure to trigger or terminate in-
to a certain percent of peak flow (flow-cycled), or when flation, and errors in VT measurement or delivery.
a set VT is delivered (volume-cycled) (Fig 1).
In addition to the basic modes, a variety of hybrid Uncuffed Endotracheal Tubes
modes now exist that combine features of several of Uncuffed endotracheal tubes (ETT) have traditionally
the basic types, as will be discussed in subsequent been used in newborn infants because of concern about
paragraphs. pressure necrosis of the tracheal mucosa and the small
size of the tubes that makes inflatable cuffs difficult to in-
Unique Challenges in MV of Newborn Infants corporate. For this reason, some degree of leak around
Individuals involved in the care of critically ill newborn the ETT is present in most infants, especially after pro-
infants should be keenly aware that newborns are not longed ventilation, because the larynx and trachea pro-
simply small children, any more than children are gressively dilate from the cyclic stretch of thousands of
inflations per day. Leak is greater during inflation, be-
cause the pressure gradient driving the leak is greater
and because the airways distend with the higher inflation
pressure. Therefore, it is important to measure both in-
spiratory and expiratory VT, with the latter more closely
approximating the volume of gas that had entered the
lungs. The leak varies from moment to moment because
the ETT is inserted only a short distance beyond the
larynx and thus the leak will change with any change
in the infant’s head position or a slight tension on
the ETT.

Measurement of VT
The importance of accurate VT measurement in any sort
of VCV/VTV of extremely small infants is obvious, con-
sidering that infants weighing 400 to 1,000 g require VT
in the range of 2 to 5 mL. Unfortunately, most ventilators
Figure 1. Basis of classification of ventilation modes: How is
measure flow and volume at the junction of the ventilator
the inflation initiated, how is the gas flow controlled during
inflation, and how is the breath terminated? circuit and the ventilator. This approach is convenient
A/C[assist control; PSV[pressure support ventilation; SIMV[ and avoids extra wires and the added instrumental dead
synchronized intermittent mandatory ventilation; TCPL[time- space of a flow sensor. However, in neonates, this remote
cycled, pressure-limited ventilation; VCV[volume-controlled placement results in major inaccuracy of VT measurement
ventilation. because when the VT is measured at the ventilator end

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of the circuit, the value does not account for compression lungs, because the VT measurement does not account for
of gas in the circuit, distention of the circuit, or leak compression of gas in the circuit/humidifier and distention
around the ETT. The loss of volume in the circuit is pro- of the compliant circuit. Furthermore, the variable leak
portional to the volume and compliance of the ventilator around uncuffed ETT makes accurate control of delivered
circuit and humidifier, relative to the volume and compli- VT very difficult with traditional volume-controlled modes.
ance of the patient’s lungs. In large subjects with cuffed One study did demonstrate the feasibility of VCV in small
ETT, the volume measured at the ventilator correlates preterm infants when special measures are taken to com-
reasonably well with the actual VT entering the lungs, pensate for these problems. (5) In that study, the set VT
and the volume loss to compression of gas in the circuit was manually adjusted at frequent intervals to achieve a
can be automatically corrected. In tiny infants whose target exhaled VT measured by using an optional proximal
lungs are very small and noncompliant, the loss of volume flow sensor at the airway opening.
to the circuit is much larger and not easily corrected, es-
pecially in the presence of a significant ETT leak. Pressure-Controlled Ventilation
Intermittent positive pressure ventilation using time-
Pressure-Limited Ventilation Versus VCV cycled, pressure-limited ventilators remains the most
Volume-Controlled Ventilation widely used mode of neonatal ventilation. This practice
VCV delivers a constant, preset VT with each inflation. In evolved as a direct consequence of the difficulties with
theory, these volume ventilators allow the operator to traditional VCV described earlier. The basic design of
select VT and rate, thereby directly controlling minute ven- these devices is similar to a T-piece circuit with continu-
tilation. The ventilator delivers the preset VT into the cir- ous flow of gas and a valve that directs gas flow into the
cuit, generating whatever pressure is needed, up to a patient or allows it to continue around the circuit. A
safety popoff, which is generally set at ‡40 cm H2O. pressure-limiting valve controls the maximum pressure
A maximum inflation time is also set as an additional in the circuit during inflation (peak inflation pressure
safety measure. Inflation ends when the set VT has been [PIP]) and another maintains a set level of positive pres-
delivered or when the maximum inflation time has elapsed. sure during the expiratory phase (positive end-expiratory
The latter ensures that with very stiff lungs, the ventilator pressure [PEEP]).
does not maintain inflation for a prolonged period trying The basic settings include inflation and exhalation
to deliver the set VT. Figure 2 contrasts the salient fea- time (which together determine the ventilator rate),
tures of pressure and volume ventilation. PIP, PEEP, circuit flow, and fraction of inspired oxygen
The major limitation of volume-controlled ventilators (FIO2). During inflation, the expiratory valve closes, the
is that what they really control is the volume injected into circuit is pressurized, and gas flows into the patient in
the ventilator circuit, not the VT that enters the patient’s proportion to the PIP and compliance of the lungs. Once
the pressure within the patient circuit reaches the PIP, ad-
ditional gas escapes through the pressure-limiting valve.
When the inflation time has elapsed, the expiratory valve
opens, allowing circuit pressure to fall rapidly to the level
of PEEP. The valve remains open with circuit pressure at
the PEEP level with fresh gas flowing in the circuit avail-
able for spontaneous breathing, until the end of the ex-
piratory time, at which point the valve closes again and
the cycle repeats. Modern ventilators are more advanced
and use low circuit gas flows during the expiratory phase,
generating additional flow to meet the patient’s demand
as needed during spontaneous breathing or mechanical
inflation, but functionally they differ very little from
the traditional devices. These pressure-limited ventilators
overcome the difficulties associated with VCV and are
simple to use. Their chief disadvantage is that VT delivery
is not directly controlled; the VT is a dependent variable
Figure 2. Key features of volume-controlled ventilation that changes as a function of inflation pressure and (some-
compared with pressure-limited ventilation. times rapidly) changing lung compliance.

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 respiratory disorders mechanical ventilatory strategies

Basic Assisted Ventilation Modes Pressure Support Ventilation

Synchronized Intermittent Mandatory Pressure support ventilation (PSV) is a flow-cycled, rather
Ventilation than time-cycled, pressure-limited mode that supports
Synchronized intermittent mandatory ventilation (SIMV) every spontaneous breath similar to the way A/C does.
is a time-cycled, pressure-limited mode that provides a set With flow cycling, inflation is terminated when inflation
number of mechanical inflations synchronized with the in- flow declines to a preset threshold, usually 10% to 20%
fant’s spontaneous respiratory effort, if present. Spontane- of peak flow. This feature eliminates inflation hold
ous breaths in excess of the set rate are not supported, (prolonged inflation time, which keeps the lungs at peak
resulting in uneven VT and potentially a high work of inflation) and thus provides more optimal synchrony.
breathing during weaning. This issue is especially impor- PSV is often used to support spontaneous breathing
tant in extremely small infants who have narrow ETT in between low-rate SIMV to overcome the problems
whom the high airway resistance, along with the infant’s associated with inadequate spontaneous respiratory
limited muscle strength and the mechanical disadvantage effort and high ETT resistance. Alternately, in some de-
of the infant’s excessively compliant chest wall, result in vices, PSV can be used as a standalone technique, much
small, ineffective VT with a high dead space:VT ratio. like A/C.
Thus, the very small VT results in re-breathing of dead
space gas and contributes little to effective alveolar venti- Trigger Technology
lation (alveolar ventilation ¼ minute ventilation – dead- An effective trigger device must be sensitive enough to be
space ventilation). To maintain adequate alveolar minute activated by a small preterm infant, avoid autotriggering,
ventilation with the limited number of mechanical infla- and must have a very rapid response time to match the
tions provided by the ventilator in SIMV mode, these in- short inflation times and rapid respiratory rates of small
flations must use relatively large VT. preterm infants. The situation is further complicated by
the ubiquitous and variable leak of gas around uncuffed
Assist/Control ETT. Common types of triggering devices used in clinical
Assist/control (A/C) is also a time-cycled, pressure-limited care and their relative advantages are listed in the Table.
mode, in which every spontaneous breath is supported Evidence supports flow-triggering with a flow sensor at
by the ventilator. This approach results in more uniform the ETT adaptor as the best compromise that is widely
VT and lower work of breathing. A set rate of mandatory available at present. (6) An emerging technology, which
inflations provides a minimum rate in case of apnea. A is currently available only on the Servo-i ventilator
backup rate slightly below the infant’s spontaneous (Maquet Medical Systems, Wayne, NJ), uses the electri-
breathing rate should be chosen so as not to preempt cal activity of the diaphragm, as assessed by transesopha-
spontaneous breaths. Because the infant controls the geal electromyography to trigger inflation. This method
ventilator rate, support is gradually withdrawn by low- is attractive because it has a short trigger delay, does
ering the PIP, rather than the ventilator rate. This not require a flow sensor, and is not affected by ETT
approach decreases the amount of support provided leakage. (7) However, it cannot currently be used in-
to each breath, allowing the infant to gradually take over dependent of the neurally adjusted ventilatory assist
the work of breathing. One reason for the apparent (NAVA) mode, which has not been adequately evalu-
reluctance to adopt this mode seems to be this slightly ated in small preterm infants who have immature respi-
less intuitive weaning strategy. ratory control.

Table. Available Modes of Triggering/Synchronization

Method Advantages Disadvantages
Pressure No added dead-space Poor sensitivity, long trigger delay, high work of
breathing
Airflow Sensitivity, rapid response Added dead space, leak may cause autotriggering
Surface capsule Rapid response, no added dead- Susceptible to artifact with incorrect position;
space limited availability
Electrical activity of the No added dead-space, very rapid Costly, somewhat invasive; limited availability
diaphragm response, not affected by leak

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respiratory disorders mechanical ventilatory strategies

Although flow triggering has emerged as the method

of choice, it is not free from drawbacks. Inline placement
of the flow sensor adds w0.8 mL of dead space to the
breathing circuit. This added instrumental dead space
becomes a larger proportion of the VT as the infant’s size
decreases. Autotriggering in the presence of a leak
around the ETT can lead to cycling at an excessive rate,
hypocapnia, or air-trapping. This is because leak flow dur-
ing the expiratory phase will be misinterpreted as inspira-
tory effort. The problem can be corrected by decreasing
trigger sensitivity, but because the leak flow is highly
variable, frequent adjustments are needed. Moreover,
with a less sensitive trigger, increased patient effort is
needed and the trigger delay increases, both of which
are highly undesirable. Most devices now allow a fixed
amount of leak compensation, but this does not account
for the variability of the leak. One device, the Draeger
Babylog (Draeger Medical, Inc, Telford, PA), offers
an effective solution to this problem, using a proprietary
technology to determine the leak flow throughout the Figure 3. The tidal volume entering the lungs (vertical axis) is
respiratory cycle and electronically correcting the mea- the result of the transpulmonary pressure: the combination of
sured flow. This method effectively eliminates the the negative pressure generated by the patient’s inspiratory
leak-related problems, allowing the trigger sensitivity effort and the positive inflation pressure from the ventilator.
to remain high with rapid response time and minimal Because the patient contributes to each inflation, there is
work to trigger the device. continuous respiratory muscle training. During weaning from
assist control, the pressure generated by the ventilator is
Choice of Assisted Ventilation Modes gradually reduced, allowing the patient to take over pro-
In the absence of large randomized trials to definitively gressively more of the work of breathing.
prove the superiority of one mode, the relative merits
of A/C and SIMV, the two most widely used modalities
of synchronized ventilation, continue to be debated. As illustrated in Fig 3, the VT with synchronized ventila-
Short-term clinical trials found that A/C, compared with tion is the result of the sum of the negative intrapleural
SIMV, resulted in substantially smaller and less variable pressure generated by the infant and the positive inflation
VT, less tachypnea, more rapid weaning from MV, and pressure generated by the ventilator. This transpulmo-
smaller fluctuations in blood pressure. (8)(9)(10)(11) In nary pressure, together with the compliance of the respi-
very premature infants who have correspondingly small ratory system, determines the resulting VT. Thus, as
ETT, SIMV may not provide optimal support because ventilator inflation pressure is decreased during weaning,
of high airway resistance and work of breathing, but many the infant gradually takes over a greater proportion of
clinicians still use it, especially for weaning from MV. This the work of breathing and, in the process, achieves effec-
choice seems to be based largely on tradition but also on tive training of the respiratory muscles. Ultimately, the
the superficially plausible assumption that fewer mechani- ventilator pressure is decreased to the point when it only
cal breaths are inherently less damaging. This belief ignores overcomes the added resistance of the ETT and circuit, at
the fact that the slower rate is accomplished at the expense which point the infant should be extubated.
of larger VT, a factor that is more injurious than frequency.
Furthermore, the concept that ventilator rate must be low- Principles Underlying Lung-Protective
ered before extubation is deeply ingrained, although con- Ventilation Strategies
tradicted by available data. (10) Limitations of Pressure as a Primary Control
Many clinicians also mistakenly believe that assisting Variable
every breath prevents respiratory muscle training. This Pressure-limited ventilation became the default mode in
concern reflects a lack of understanding of the complex our NICUs because early attempts to use VCV proved to
patient–ventilator interaction during assisted ventilation. be impractical in small preterm infants. Pressure-limited

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 respiratory disorders mechanical ventilatory strategies

ventilation remains the primary mode of ventilation in contribute to an increased risk of intraventricular hemor-
many centers because of its simplicity and immunity from rhage. Low VT also leads to inefficient gas exchange due
the effects of large ETT leak. Better intrapulmonary gas dis- to the increased dead space: VT ratio; in time, it results
tribution due to the decelerating gas flow pattern and the in atelectasis with increased oxygen requirement, de-
presumed benefit of directly controlling PIP were also seen creased lung compliance, and maldistribution of VT
as advantages. The major drawback of pressure-limited leading to regional volutrauma. Clearly, some form of
ventilation is that VT varies with changes in lung compli- VTV with relatively tight control of VT delivery during
ance, which may occur rapidly in the immediate postnatal MV is a desirable goal and remains the main reason why
period with resorption of lung fluid, optimization of lung VCV is still the standard of care in adult and pediatric
volume, and administration of exogenous surfactant. When respiratory support.
compliance improves, inadvertent hyperventilation and
lung injury from excessively large VT (volutrauma) may Importance of the Open Lung Strategy
occur, unless the inflation pressure is quickly reduced. As Despite a substantial body of evidence accumulated over
few as six excessively large breaths can negate the benefits many years, the critical importance of distributing the VT
of surfactant therapy. (12) Therefore, relying on manual evenly into an optimally aerated lung has not been widely
adjustment of inflation pressure may be ineffective in appreciated. This concept requires special emphasis,
preventing lung injury. In one study, inadvertent hyper- because the benefits of VTV cannot be realized without
ventilation to PaCO2 less than 25 mm Hg occurred in ensuring that this VT is distributed evenly throughout the
w30% of ventilated newborn infants during the first day lungs. The admonition of Burkhard Lachman more than
after birth, (13) indicating that hypocapnia continues to 20 years ago to “open the lung and keep it open” (21)
be a common problem despite increasing awareness of has been ignored by many during conventional MV de-
its dangers. spite its sound physiologic basis and strong experimental
evidence in its favor. Adequate end-expiratory pressure
Ventilator-Associated Lung Injury may be more important than small VT. (22)(23) Further-
Despite extensive evidence that excessive volume, not more, in the presence of atelectasis, the nondependent
pressure, is the key determinant of VALI, “baro-phobia” (ie, aerated) lung was the most injured area of the lungs.
remains widespread. It is important to recognize that
high inflation pressure causes lung injury only if it results
in excessive VT. Dreyfuss et al (14) demonstrated 20
years ago that severe acute lung injury occurred in small
animals ventilated with large VT, irrespective of whether
that volume was generated by positive or negative infla-
tion pressure. In contrast, animals exposed to the same
high inflation pressure but in whom VT was limited to
a physiologic volume by external binding of the chest
and abdomen experienced much less acute lung injury.
This landmark article and other similar preclinical studies
clearly demonstrate that excessive VT, not pressure by it-
self, is responsible for lung injury. (15)(16) Together
with increasing recognition of the well-documented dan-
gers of inadvertent hyperventilation, (17)(18)(19) the
appreciation of the key role of volutrauma in VALI con-
stitutes a powerful argument in favor of adoption of VT as Figure 4. In the presence of extensive atelectasis, as seen in
the primary control variable in MV. (20) the right lower corner, there are two populations of alveoli
with very different critical opening pressures. From LaPlace’s
Insufficient VT is also undesirable. With a fixed inflation
law, we know that the already aerated alveoli have a lower
pressure, insufficient VT may occur because of a decrease
critical opening pressure; therefore, the tidal volume will
in lung compliance, increase in airway resistance, airway enter the already aerated portion of the lung, which becomes
obstruction, air-trapping, or decreased spontaneous re- overexpanded with each inflation, leading to volutrauma,
spiratory effort. Inadequate VT results in hypercapnia, while the atelectatic portion is also damaged by outpouring of
increased work of breathing, increased oxygen consump- protein-rich edema fluid that inactivates surfactant.
tion, agitation, fatigue, and atelectasis, and it could COP[critical opening pressure; FRC=functional residual capacity.

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respiratory disorders mechanical ventilatory strategies

(24) This phenomenon occurs because, in the presence a level just above the point when derecruitment (signaled
of extensive atelectasis, even a normal, physiologic VT will by deteriorating oxygenation) begins to avoid overexpan-
result in overexpansion of the aerated portion of the sion. It is important to understand that there is no single
lungs. These aerated alveoli are more compliant than “safe” PEEP level. Optimal PEEP must be tailored to the
the atelectatic portion of the lungs (LaPlace’s law). degree of lung injury (ie, lung compliance). For infants
Therefore, the gas will preferentially enter the already who have healthy lungs and thus normal lung compli-
open alveoli and lead to overexpansion with subsequent ance, PEEP of 3 cm H2O is adequate and PEEP of 6
volutrauma/biotrauma (Fig 4). Atelectasis results in ac- cm H2O may result in overexpansion of the lungs with
cumulation of protein-rich fluid leading to surfactant in- circulatory impairment and elevated cerebral venous
activation and release of inflammatory mediators. Shear pressure. Conversely, atelectatic, poorly compliant lungs
forces and uneven stress in areas in which atelecta- may require PEEP levels of 8 to 10 cm H2O or more to
sis and overinflation coexist add to the damage. The achieve adequate alveolar recruitment and improve the
repeated collapse and re-expansion of alveoli with low ventilation/perfusion ratio. Because we seldom ventilate
end-expiratory volume contribute further to VALI. infants who have healthy lungs, PEEP of less than 5 cm
Collectively, this process is known as atelectotrauma. H2O should be used infrequently.
The “open lung concept” (25) is central to minimiz-
ing VALI, regardless of other aspects of ventilation Importance of Optimizing Initial Respiratory
strategy. Support
The importance of optimizing lung inflation has long The immediate postnatal period when air breathing is ini-
been recognized by users of high-frequency oscillatory tiated is a critical period that may determine the subse-
ventilation (HFOV), in which the optimal lung volume quent pulmonary outcome. There is a strong evidence
strategy has become standard practice and is widely un- base in support of initial respiratory support strategies
derstood to be the key to its success. (26) There are aimed at facilitating lung fluid clearance and helping
a number of animal studies indicating that conventional the preterm infant who has insufficient chest wall rigidity
ventilation with the open lung concept can achieve sim- to establish functional residual capacity in the delivery
ilar degrees of lung protection as HFOV, suggesting that room. Positive pressure ventilation with high pressure
optimizing lung volume, rather than frequency, is the key and excessively large VT values must be avoided. The
factor. (25)(27)(28) However, the clinical application of T-piece resuscitator is best suited for accomplishing this
the open lung concept with conventional ventilation has goal because of its ability to provide consistent, con-
not been extensively evaluated in clinical trials. (26) The trolled inflation pressure and consistent PEEP. Initial
failure to actively embrace the open lung concept may be FIO2 should be between 0.30 and 0.40 for preterm in-
based on the paucity of evidence from human trials of fants and 0.21 for term infants. FIO2 should be promptly
how to best achieve it. In clinical practice, lung volume titrated to maintain target saturation according to pub-
recruitment seems to be best achieved by applying ade- lished normograms. The use of sustained inflations to
quate PEEP, preferably very soon after birth. A number rapidly establish normal functional residual capacity and
of studies indicate that an oxygen-guided bedside recruit- optimal gas distribution may be beneficial and is currently
ment strategy during high-frequency ventilation is feasi- the focus of active investigation. Although physiologically
ble. (29)(30)(31) There are limited data for a similar attractive and supported by several preclinical and clinical
maneuver during conventional ventilation, (32) but this studies, there is currently insufficient evidence to recom-
strategy has been successfully used by the group of Lista mend sustained inflation as standard practice.
in Milan and others for some time. (33)
The general strategy of optimizing lung volume relies General Principles of MV
on oxygenation as determined by using pulse oximetry as Based on the principles outlined here, the following gen-
a proxy for ventilation/perfusion matching and thus lung eral guidelines of MV can be formulated. The overarch-
volume. If FIO2 remains greater than 0.30, PEEP is in- ing goal of MV is to support adequate gas exchange with
creased in increments of 0.5 to 1 cm H2O every 5 to 10 a minimum of adverse effects on the infant’s lungs, hemo-
minutes until FIO2 falls below 0.30, or until there is no dynamics, and brain. Longer duration of ventilation is as-
further improvement in oxygenation with incremental sociated with increased likelihood of chronic lung disease,
PEEP change, or a maximum PEEP of 10 cm H2O is late-onset sepsis, and neurodevelopmental impairment;
reached. Once lung recruitment is achieved, the lungs be- therefore, extubation at the earliest possible time is desir-
come more compliant, and PEEP needs to be reduced to able. Ventilation strategies should be individualized to

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 respiratory disorders mechanical ventilatory strategies

address each patient’s specific condition, but the key ob- primary control variable, the inflation pressure will fall
jectives are to improve lung compliance, reduce oxygen as lung compliance and patient inspiratory effort improve,
requirement, prevent surfactant inactivation, and ensure resulting in real-time weaning of pressure, as opposed
even VT distribution by recruiting optimal lung volume to intermittent manual lowering of pressure in response
and preventing atelectasis. The second key element of to blood gases. This method avoids excessive VT and
lung-protective ventilation strategies is to minimize vol- achieves a shorter duration of MV. A recent meta-analysis
utrauma and hypocapnia, the preventable elements of that included a combination of several different modali-
lung and brain injury, by avoiding excessively large VT. ties of VTV documented a number of advantages of VTV
This goal is best accomplished by the use of one of the compared with pressure-limited ventilation: VTV signifi-
volume-targeted modes available on the ventilators in cantly reduced the combined outcome of death or BPD,
common use in North America, following the guidelines as well as the risk of pneumothorax, and it significantly
outlined later in this review. shortened the duration of MV. (35) Another more inclusive
Mild permissive hypercapnia and minimal FIO2 to meta-analysis also documented decreased risk of severe in-
achieve adequate oxygen saturation (88%–93%) are traventricular hemorrhage or periventricular leukomalacia.
generally considered appropriate. There is no evidence (36) Although very supportive, these meta-analyses do
to support the routine use of sedation, and infants not provide the definitive evidence of the superiority of
should therefore be allowed to breathe spontaneously. VTV because the studies included in the analyses were
Routine suctioning should be avoided because it leads small and diverse and many of the key outcomes reported
to derecruitment, transient hypoxemia, and perturba- in the meta-analysis were not prospectively collected or
tion of cerebral hemodynamics. When secretions are defined. In some of the studies, other variables beyond
detected by auscultation or by perturbation of the flow volume versus pressure targeting also differed. All the
waveform, gentle rapid suctioning without instillation included studies focused on short-term physiologic out-
of normal saline is indicated. comes, and none included BPD as a primary outcome.
The choice of SIMV or A/C is, to some extent, a matter Except for one follow-up study based on a parental ques-
of personal preference and practice style. There is little dif- tionnaire, no long-term pulmonary or developmental out-
ference between the two methods in the acute phase of comes have been reported.
respiratory failure. In a patient who has little or no respi-
ratory effort or is heavily sedated and/or paralyzed, we are Volume Guarantee
really providing simple intermittent mandatory ventilation, VG is a mode that is available on the Draeger Babylog
regardless of the ventilator mode selection. The differences 8000þ and the newer VN 500 (Draeger Medical, Inc),
between SIMV and A/C or PSV become more pro- as well as the Leoni Plus (Heinen þ Löwenstein GmbH,
nounced during weaning and are especially important in Bad Ems, Germany), which is not available in the United
the smallest infants who have narrow ETT. Prolonged States. More recently, a version of this mode has been im-
ventilation with low SIMV rates should be avoided in these plemented on the Avea ventilator (CareFusion, San
infants because it imposes an undesirably high work of Diego, CA). The VG mode, as implemented on the
breathing. To a significant degree, this problem may be Draeger device, has been studied more thoroughly than
overcome by adding PSV to the spontaneous breaths dur- other modes of VTV. (37) Specific clinical guidelines for
ing SIMV. (34) Although this approach is effective, it adds VG have been published. (38)(39) VG has been shown
complexity and does not seem to have any advantage over to be more effective when used with A/C than with
PSV used alone, as long as atelectasis is avoided by using an SIMV. (40) The choice of appropriate VT depends on
adequate level of PEEP. the infant’s size and basic synchronization mode. One
size does not fit all. The smallest infants require a larger
Volume-Targeted Ventilation VT on a per-kilogram basis, due to the proportionally
There are important differences in how volume targeting larger impact of fixed instrumental dead space of the flow
is achieved with various devices, and their relative efficacy sensor. (41) Infants less than 600 g need a VT of 5.5 to 6
has not been established. The ability to achieve more sta- mL/kg, whereas those greater than 600 g will likely
ble VT and a reduction in hypocapnia has only been dem- achieve adequate ventilation with a VT of 4.5 to 5.5
onstrated with volume guarantee (VG), not with the mL/kg. These values were established for A/C; SIMV
other modalities of VTV. However, the primary benefit requires slightly larger values for the same alveolar minute
of VTV probably rests in the ability to regulate VT, re- ventilation because fewer breaths are supported and vol-
gardless of how that goal is achieved. When VT is the ume-targeted. When starting with VG, the inflation

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pressure limit should initially be set 3 to 5 cm H2O above compliance compensation decreases with lower infant
the level estimated to be sufficient to achieve a normal weights and often results in wide swings of apparent
VT. If the target VT cannot be reached with this setting, VT among children weighing 750 to 1,000 g. Therefore,
increase the pressure limit until the desired VT is gener- the compliance compensation feature is generally not
ated. It is important to make sure the ETT is not kinked, used in small preterm infants. Substantial loss of VT to
malpositioned in the mainstem bronchus or obstructed compression of gas in the circuit occurs; the set VT must
on the carina. Significant volutrauma and/or air leak account for this and typically must be two to three times
could result from failure to recognize single-lung intuba- larger than the target VT at the airway opening. If the in-
tion. If changing from pressure-limited ventilation, the fant is being switched from a pressure-limited mode,
pressure limit should be increased by 3 to 5 cm H2O from a common approach to setting the initial volume target
baseline to allow the microprocessor to adjust working is to set the target volume either: (1) to match the inspi-
pressure as needed. Pressure limit is subsequently ad- ratory volumes generated by pressure-limited ventilation;
justed to be w20% above the current working pressure or (2) to generate pressures similar to those being used in
and adjusted periodically as lung compliance improves pressure-limited ventilation. If the infant is being begun
and working pressure comes down. If the ventilator is un- de novo on PRVC, the usual method of choosing the tar-
able to reach the target VT with the set inflation pressure get VT is the same as that used with VCV (as discussed in
limit, an alarm will sound. This alarm serves as an early the following text). If a proximal flow sensor is available,
warning system that should prompt an evaluation of it should be used to directly measure the exhaled VT and
the reason for this change. Subsequent adjustments of adjust the set value to achieve an exhaled VT of w5 mL/kg.
VT should be guided by arterial blood gas measurement. Similar to other VTV modalities, the pressure needed to
Over time, with development of BPD, which results in achieve the target VT comes down automatically, as lung
more heterogeneous inflation and air trapping, a modestly compliance and patient effort improve. The target VT
higher VT is required even with permissive hypercapnia. should not be reduced below 4 mL/kg exhaled volume
(42) at the airway opening for the same reasons as described in
In the VN 500 ventilator, the leak-compensated VT the previous section on VG.
value should be selected in the ventilator default
setting to minimize artifacts caused by ETT leakage. Volume Ventilation Plus
The Babylog 8000 uses the uncorrected VT measure- Volume Ventilation Plus (Puritan Bennett 840, Covidien,
ment, which begins to progressively underestimate the Mansfield, MA ) is a complex mode that combines two
true VT with increasing ETT leak, potentially resulting different dual-mode, volume-targeted breath types: Vol-
in inadvertent hypocapnia. This commonly occurs if a pre- ume Control Plus for delivery of mandatory breaths in
term infant remains intubated for more than 2 weeks, be- A/C and SIMV, and Volume Support for delivery of spon-
cause of stretching of the larynx, and may require taneous breaths in the spontaneous breathing mode. The
reintubation with a larger ETT. ventilator adjusts inflation pressure to target inflation VT.
As long as the pH is low enough for the infant to have Because VT is not routinely measured at the ETT, it is
a respiratory drive, weaning occurs automatically, in real functionally similar to VC and PRVC modes described
time, and requires fewer blood gas measurements. VT earlier. Thus, the selection of volume setting reflects the
should normally not be weaned to less than 4 mL/kg to proximal VT and must allow for the loss of volume to com-
avoid shifting all the work of breathing to the infant. When pression in the ventilator circuit. Proximal flow sensor use
the infant is able to maintain good gas exchange with low is recommended where available with the same aforemen-
inflation pressure, extubation should be attempted. tioned targets. As noted earlier, avoidance of inadvertent
mainstem bronchus intubation is essential.
Pressure-Regulated Volume Control
The pressure-regulated volume control (PRVC) mode Volume-Targeted Ventilation
on the Servo-i ventilator uses the VT of the previous VTV as implemented on the Hamilton G5 (Hamilton
breath, measured at the ventilator end of the circuit, to Medical, Reno, NV) is a mode similar to VG that adjusts
regulate the inflation pressure needed to achieve the de- the inflation pressure in response to any deviation of mea-
sired VT. The compliance (“tubing”) compensation func- sured VT from the target value. This relatively new mode
tion is only effective when there is no significant ETT has no published literature on its effectiveness, but it
leak, and even then, it is only an approximation of the seems to have functionality similar to standard VG, and
true exhaled VT. In addition, the reliability of the therefore similar guidelines should be applied to its use.

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 respiratory disorders mechanical ventilatory strategies

Volume Limit uncuffed ETT. Specifically, the common problem of pe-

Some pressure-limited ventilators, such as the Bear Cub riodic breathing would be accentuated by the ventilator
750 and the older-generation Avea (CareFusion), use with less support being generated during hypopnea and
a simple volume limit function that merely terminates in- excessive assist provided when the infant becomes agi-
spiration when the maximum allowed VT is delivered, tated. Because the system by necessity responds to inspi-
which may result in very short inflation times. These have ratory flow and volume, a large leak around the ETT
now been supplanted by more sophisticated algorithms in would be interpreted as a large inspiration and given cor-
the newer generation of ventilators. respondingly high level of inflation pressure, potentially
leading to dangerously large VT. Only limited clinical
data regarding this technique are available in preterm in-
Volume-Controlled Ventilation
fants, and it remains experimental.
The volume control mode on all devices directly controls
the volume of gas delivered to the ventilator circuit (also
known as Vdel), not the volume of gas delivered to the
Neurally Adjusted Ventilator Assist
NAVA is a potentially attractive approach that uses the
patient. Substantial loss of volume to compression of
patient’s own respiratory control to drive the ventilator.
gas in the circuit occurs; the set volume (Vdel) must ac-
(44) The device detects electrical activity of the dia-
count for this loss and typically must be two to three
phragm by using bipolar electrodes mounted on a modi-
times larger than the target exhaled VT at the airway
fied nasogastric feeding tube positioned at the level of the
opening. A common approach to the use of VC is to ad-
diaphragm to trigger and modulate inspiration. Based on
just Vdel settings until clinically adequate chest excur-
an arbitrary “NAVA number,” which represents the gain
sion and air entry are achieved, and then make further
applied to the electrical signal from the diaphragm, the
adjustments based on blood gas measurements. An alter-
ventilator automatically adjusts the level of support in
native and preferred approach is to measure exhaled VT
proportion to the inspiratory effort. NAVA is still an un-
by using a flow sensor at the airway opening, which is
proven therapy in newborn infants, but the concept is at-
then used to adjust the set Vdel needed to achieve an ap-
tractive because the system is not affected by leak around
propriate exhaled VT. As discussed earlier, the same cau-
the ETT. However, like PAV, NAVA is a positive feed-
tion needs to be exercised to avoid inadvertent mainstem
back system that assumes that the respiratory control cen-
bronchus intubation.
ter is mature, which is not a valid assumption in the
Each ventilator functions differently, and it is critical
preterm infant. Incorporating minimal and maximal sup-
that users become familiar with the specific features of
port levels may overcome this limitation, but this ap-
their device. Readers are referred to user manuals of their
proach has yet to be fully validated.
respective devices for further guidance. A ventilator is
only a tool in the hands of the clinician; a tool that can
be used well or not. Yet, we talk of “ventilator-induced
Airway Pressure Release Ventilation
Airway pressure release ventilation is a technique de-
lung injury” as though the machines were to blame for
signed to achieve lung volume recruitment and relies
the undesirable outcome. Perhaps the term “physician-
on patient’s spontaneous breathing to achieve the bulk
induced lung injury” is more appropriate, for we are
of minute ventilation. The technique consists of main-
the ones that select the ventilator settings.
taining a relatively high inflation pressure for the bulk
of a respiratory cycle with periodic “release” of this pres-
Novel Techniques of Assisted Ventilation sure for brief periods. (45) This alternating pattern of low
Proportional Assist Ventilation and high pressure can be thought of as extreme inverse
Proportional assist ventilation is a technique that is not ratio ventilation. It also bears some similarity to the var-
currently available in North America. It is based on the ious forms of biphasic CPAP. Airway pressure release
principle of elastic and resistive unloading of the respira- ventilation is usually used as a rescue technique, and un-
tory system, designed to overcome the added workload like biphasic CPAP, the upper pressure level “P high” is
imposed by poor lung compliance and high airway and maintained for majority of the cycle “T high.” The pres-
instrumental resistance. (43) The device uses a positive sure to which the lungs are released is called “P low,” and
feedback algorithm to generate inflation pressure in pro- the release time is called “T low.” The technique has pri-
portion to patient effort. This approach assumes a mature marily been used in adult patients who have acute lung
respiratory control center and a closed, leak-free system, injury, where there may be some short-term benefits in
neither of which is true in the preterm infant with terms of oxygenation. No clear survival advantage or

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respiratory disorders mechanical ventilatory strategies

reduction in complications has been demonstrated. that closed loop systems will begin to be adapted to neo-
There is insufficient evidence to assess the utility of this natal care in the future to facilitate weaning and extubation.
technique in newborn infants, with only a handful of case In the meantime, unit protocols designed to facilitate
reports available and no controlled trials. There should weaning from MV may be the best available approach. (49)
seldom be a need for such rescue techniques if lung-
protective ventilation strategies are used from the outset. Conclusions
A variety of new modalities and techniques have become
Closed Loop Systems available for the treatment of respiratory failure in the past
A variety of “closed loop” forms of “intelligent” ventila- decade. Our understanding of how to optimally use these
tion have been implemented on ventilators designed for devices, while continuing to improve, lags behind the pace
adult use. VG and PRVC were the first examples of this of technological innovation. Moreover, improvements in
sort of servo-regulation, but they modulate only a single outcomes such as BPD are increasingly difficult to demon-
variable, the inflation pressure, to target a fixed VT . strate, as each incremental improvement gets us closer to
Other examples include mandatory minute ventilation what may be an irreducible minimum. Early establishment
(MMV, Draeger V500, Draeger Medical, Inc), which of optimal lung volume, careful avoidance of high inflation
is potentially useful for infants who have inconsistent re- pressures in the delivery room, and appropriate titration of
spiratory effort. MMV is a modification of SIMV with FIO2 may be key to minimizing lung injury. Avoidance of
PSV and will maintain a low rate of mandatory inflations MV by means of early CPAP with or without surfactant
as long as the patient’s spontaneous effort, augmented by administration may still be the most effective way to reduce
PSV, is adequate to meet the preset MMV target and in- the risk of chronic lung disease. For infants who do require
crease the SIMV rate in a proactive fashion if the pro- MV, the combination of VTV, combined with the open
jected MV is falling short. (46) Although conceptually lung strategy, seems to offer the best chance of reducing
attractive, the utility of this approach has not been clearly the risk of chronic lung disease.
demonstrated; similar goals can be achieved with the use
of volume-targeted modes and PSV. Adaptive Support
Ventilation (Hamilton Medical) may be thought of as
an internal “electronic ventilator protocol” that offers American Board of Pediatrics Neonatal-Perinatal
continuous measurement of lung mechanics to adjust Content Specifications
ventilation parameters to optimize support. (47) This • Plan the ventilatory therapy for infants
mode recognizes spontaneous respiratory activity and with respiratory failure of different
etiologies.
automatically switches the patient between mandatory
• Know the indications for and techniques
pressure-controlled inflations and spontaneous pressure- of positive pressure ventilation (PPV).
supported breaths. The clinician determines the desired • Know the effects and risks of PPV.
minute ventilation, and the algorithm determines the op-
timal respiratory rate/VT combination according to the
patient’s respiratory mechanics. There is no information
to judge the safety and efficacy of this mode in newborn Editor’s Note
infants. SmartCare is another automated weaning system For additional reading on this subject, please see the fol-
available on the adult Draeger V500 (Draeger Medical, lowing articles in NeoReviews: Lan WC, Bhutani V. Core
Inc). (48) The program implements a continuous weaning concepts: neonatal tidal volume: physiologic, techno-
protocol by using a pressure support mode by adjusting logic, and clinical considerations. NeoReviews. 2011;12
the level of support based on measurements of respira- (11):e652–e660 and Mammel M, King N. Picking your
tory rate, VT, and end-tidal carbon dioxide measure- next ventilator. NeoReviews. 2010;11(9):e484–e494.
ment. SmartCare maintains the patients at a minimal
level of support that is tolerated and automatically ini- References
tiates a spontaneous breathing test when patients meet 1. Walsh MC, Morris BH, Wrage LA, et al; National Institutes of
predefined criteria. Child Health and Human Development Neonatal Research Net-
None of these systems, with the possible exception of work. Extremely low birthweight neonates with protracted venti-
lation: mortality and 18-month neurodevelopmental outcomes.
MMV, is ready for implementation in newborn infants be- J Pediatr. 2005;146(6):798–804
cause of the many unique aspects of neonatal respiratory 2. Finer NN, Carlo WA, Walsh MC, et al; SUPPORT Study Group
physiology and pathophysiology. It is likely, however, of the Eunice Kennedy Shriver NICHD Neonatal Research

e248 NeoReviews Vol.14 No.5 May 2013

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 respiratory disorders mechanical ventilatory strategies

Network. Early CPAP versus surfactant in extremely preterm in premature infants treated with high-frequency jet ventilation.
infants. N Engl J Med. 2010;362(21):1970–1979 Pediatrics. 1996;98(5):918–924
3. Stoll BJ, Hansen NI, Bell EF, et al; Eunice Kennedy Shriver 20. Clark RH, Slutsky AS, Gerstmann DR. Lung protective
National Institute of Child Health and Human Development strategies of ventilation in the neonate: what are they? Pediatrics.
Neonatal Research Network. Neonatal outcomes of extremely 2000;105(1 pt 1):112–114
preterm infants from the NICHD Neonatal Research Network. 21. Lachmann B. Open up the lung and keep the lung open.
Pediatrics. 2010;126(3):443–456 Intensive Care Med. 1992;18(6):319–321
4. Morley CJ, Davis PG, Doyle LW, Brion LP, Hascoet JM, Carlin 22. Caruso P, Meireles SI, Reis LF, Mauad T, Martins MA,
JB; COIN Trial Investigators. Nasal CPAP or intubation at birth Deheinzelin D. Low tidal volume ventilation induces proinflamma-
for very preterm infants. N Engl J Med. 2008;358(7):700–708 tory and profibrogenic response in lungs of rats. Intensive Care
5. Singh J, Sinha SK, Clarke P, Byrne S, Donn SM. Mechanical Med. 2003;29(10):1808–1811
ventilation of very low birth weight infants: is volume or pressure 23. Monkman SL, Andersen CC, Nahmias C, et al. Positive end-
a better target variable? J Pediatr. 2006;149(3):308–313 expiratory pressure above lower inflection point minimizes influx of
6. Dimitriou G, Greenough A, Cherian S. Comparison of airway activated neutrophils into lung. Crit Care Med. 2004;32(12):
pressure and airflow triggering systems using a single type of 2471–2475
neonatal ventilator. Acta Paediatr. 2001;90(4):445–447 24. Tsuchida S, Engelberts D, Peltekova V, et al. Atelectasis causes
7. Beck J, Brander L, Slutsky AS, Reilly MC, Dunn MS, Sinderby alveolar injury in nonatelectatic lung regions. Am J Respir Crit
C. Non-invasive neurally adjusted ventilatory assist in rabbits with Care Med. 2006;174(3):279–289
acute lung injury. Intensive Care Med. 2008;34(2):316–323 25. van Kaam AH, de Jaegere A, Haitsma JJ, Van Aalderen WM,
8. Mrozek JD, Bendel-Stenzel EM, Meyers PA, Bing DR, Connett Kok JH, Lachmann B. Positive pressure ventilation with the open
JE, Mammel MC. Randomized controlled trial of volume-targeted lung concept optimizes gas exchange and reduces ventilator-induced
synchronized ventilation and conventional intermittent mandatory lung injury in newborn piglets. Pediatr Res. 2003;53(2):245–253
ventilation following initial exogenous surfactant therapy. Pediatr 26. van Kaam AH, Rimensberger PC. Lung-protective ventilation
Pulmonol. 2000;29(1):11–18 strategies in neonatology: what do we know—what do we need to
9. Chan V, Greenough A. Comparison of weaning by patient know? Crit Care Med. 2007;35(3):925–931
triggered ventilation or synchronous intermittent mandatory ven- 27. Vázquez de Anda GF, Hartog A, Verbrugge SJ, Gommers D,
tilation in preterm infants. Acta Paediatr. 1994;83(3):335–337 Lachmann B. The open lung concept: pressure-controlled ventila-
10. Dimitriou G, Greenough A, Griffin F, Chan V. Synchronous tion is as effective as high-frequency oscillatory ventilation in
intermittent mandatory ventilation modes compared with patient improving gas exchange and lung mechanics in surfactant-deficient
triggered ventilation during weaning. Arch Dis Child Fetal Neo- animals. Intensive Care Med. 1999;25(9):990–996
natal Ed. 1995;72(3):F188–F190 28. van Kaam AH, Dik WA, Haitsma JJ, et al. Application of the open-
11. Hummler H, Gerhardt T, Gonzalez A, Claure N, Everett R, lung concept during positive-pressure ventilation reduces pulmonary
Bancalari E. Influence of different methods of synchronized inflammation in newborn piglets. Biol Neonate. 2003;83(4):273–280
mechanical ventilation on ventilation, gas exchange, patient effort, 29. De Jaegere A, van Veenendaal MB, Michiels A, van Kaam AH.
and blood pressure fluctuations in premature neonates. Pediatr Lung recruitment using oxygenation during open lung high-
Pulmonol. 1996;22(5):305–313 frequency ventilation in preterm infants. Am J Respir Crit Care
12. Björklund LJ, Ingimarsson J, Curstedt T, et al. Manual Med. 2006;174(6):639–645
ventilation with a few large breaths at birth compromises the 30. Miedema M, de Jongh FH, Frerichs I, van Veenendaal MB, van
therapeutic effect of subsequent surfactant replacement in imma- Kaam AH. Changes in lung volume and ventilation during lung
ture lambs. Pediatr Res. 1997;42(3):348–355 recruitment in high-frequency ventilated preterm infants with re-
13. Luyt K, Wright D, Baumer JH. Randomised study comparing spiratory distress syndrome. J Pediatr. 2011;159(2):199–205.e2
extent of hypocarbia in preterm infants during conventional and 31. Tingay DG, Mills JF, Morley CJ, Pellicano A, Dargaville PA.
patient triggered ventilation. Arch Dis Child Fetal Neonatal Ed. Indicators of optimal lung volume during high-frequency oscilla-
2001;84(1):F14–F17 tory ventilation in infants. Crit Care Med. 2013;41(1):237–244
14. Dreyfuss D, Saumon G. Role of tidal volume, FRC, and end- 32. Rimensberger PC, Cox PN, Frndova H, Bryan AC. The open
inspiratory volume in the development of pulmonary edema following lung during small tidal volume ventilation: concepts of recruitment
mechanical ventilation. Am Rev Respir Dis. 1993;148(5):1194–1203 and “optimal” positive end-expiratory pressure. Crit Care Med.
15. Hernandez LA, Peevy KJ, Moise AA, Parker JC. Chest wall 1999;27(9):1946–1952
restriction limits high airway pressure-induced lung injury in young 33. Castoldi F, Daniele I, Fontana P, Cavigioli F, Lupo E, Lista G.
rabbits. J Appl Physiol. 1989;66(5):2364–2368 Lung recruitment maneuver during volume guarantee ventilation
16. Dreyfuss D, Saumon G. Ventilator-induced lung injury: lessons of preterm infants with acute respiratory distress syndrome. Am
from experimental studies. Am J Respir Crit Care Med. 1998;157 J Perinatol. 2011;28(7):521–528
(1):294–323 34. Osorio W, Claure N, D’Ugard C, Athavale K, Bancalari E.
17. Graziani LJ, Spitzer AR, Mitchell DG, et al. Mechanical Effects of pressure support during an acute reduction of synchro-
ventilation in preterm infants: neurosonographic and developmen- nized intermittent mandatory ventilation in preterm infants.
tal studies. Pediatrics. 1992;90(4):515–522 J Perinatol. 2005;25(6):412–416
18. Fujimoto S, Togari H, Yamaguchi N, Mizutani F, Suzuki S, 35. Wheeler K, Klingenberg C, McCallion N, Morley CJ, Davis
Sobajima H. Hypocarbia and cystic periventricular leukomalacia in PG. Volume-targeted versus pressure-limited ventilation in the
premature infants. Arch Dis Child. 1994;71(2):F107–F110 neonate. Cochrane Database Syst Rev. 2010;(11):CD003666
19. Wiswell TE, Graziani LJ, Kornhauser MS, et al. Effects of 36. Morley CJ. Volume-limited and volume-targeted ventilation.
hypocarbia on the development of cystic periventricular leukomalacia Clin Perinatol. 2012;39(3):513–523

NeoReviews Vol.14 No.5 May 2013 e249

Downloaded from http://neoreviews.aappublications.org/ at UCSF Kalmanovitz Library & CKM on November 30, 2014
respiratory disorders mechanical ventilatory strategies

37. Keszler M. State of the art in conventional mechanical birth weight infants with evolving chronic lung disease. Neonatol-
ventilation. J Perinatol. 2009;29(4):262–275 ogy. 2007;92(1):1–7
38. Keszler M. Clinical guidelines for the use of volume guarantee: 44. Bordessoule A, Emeriaud G, Morneau S, Jouvet P, Beck J.
practice guidelines for the bedside. Clin Perinatol. 2007;34(1): Neurally adjusted ventilatory assist improves patient-ventilator
116e1–116e4 interaction in infants as compared with conventional ventilation.
39. Klingenberg C, Wheeler KI, Davis PG, Morley CJ. A practical Pediatr Res. 2012;72(2):194–202
guide to neonatal volume guarantee ventilation. J Perinatol. 2011; 45. Daoud EG, Farag HL, Chatburn RL. Airway pressure release
31(9):575–585 ventilation: what do we know? Respir Care. 2012;57(2):282–292
40. Abubakar K, Keszler M. Effect of volume guarantee combined 46. Claure N, Gerhardt T, Hummler H, Everett R, Bancalari E.
with assist/control vs synchronized intermittent mandatory venti- Computer-controlled minute ventilation in preterm infants
lation. J Perinatol. 2005;25(10):638–642 undergoing mechanical ventilation. J Pediatr. 1997;131(6):
41. Nassabeh-Montazami S, Abubakar KM, Keszler M. The impact 910–913
of instrumental dead-space in volume-targeted ventilation of the 47. Petter AH, Chioléro RL, Cassina T, Chassot PG, Müller XM,
extremely low birth weight (ELBW) infant. Pediatr Pulmonol. Revelly JP. Automatic “respirator/weaning” with adaptive support
2009;44(2):128–133 ventilation: the effect on duration of endotracheal intubation and
42. Keszler M, Nassabeh-Montazami S, Abubakar K. Evolution of patient management. Anesth Analg. 2003;97(6):1743–1750
tidal volume requirement during the first 3 weeks of life in infants 48. Lellouche F, Mancebo J, Jolliet P, et al. A multicenter
<800g ventilated with volume guarantee. Arch Dis Child Fetal randomized trial of computer-driven protocolized weaning from
Neonatal Ed. 2009;94:F279–F282 mechanical ventilation. Am J Respir Crit Care Med. 2006;174(8):
43. Schulze A, Rieger-Fackeldey E, Gerhardt T, Claure N, Everett 894–900
R, Bancalari E. Randomized crossover comparison of proportional 49. Sant’Anna GM, Keszler M. Weaning infants from mechanical
assist ventilation and patient-triggered ventilation in extremely low ventilation. Clin Perinatol. 2012;39(3):543–562

NeoReviews Quiz
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1. A family practice resident is rotating through the NICU and notes that she is very familiar with ventilator
management in adults. What is an aspect of mechanical ventilation that is unique to neonates?
A. Neonates have very long time constants and long inspiratory times to match their lung mechanics.
B. Due to their very small airways, preterm infants will exhibit virtually no leak around the endotracheal tube,
even with uncuffed tubes.
C. There are minimal differences between ventilating critically ill adults and infants; the main difference is
adjusting the tidal volume according to weight, with other parameters being similar.
D. When inspiratory and expiratory tidal volumes are measured, the inspiratory volume will usually better
approximate actual volume of gas entering the lungs, as that will have been specified exactly by the
ventilator.
E. The leak around the endotracheal tube may vary from moment to moment depending on the positioning of
the infant’s head or changes in tension on the tube.

2. A 28-week-gestational-age male with respiratory distress syndrome is being treated with synchronized
intermittent mandatory ventilation (SIMV), set at a rate of 32/minute. Which of the following is true?
A. This mode will deliver a consistent tidal volume for at least 32 breaths per minute.
B. Spontaneous breaths in excess of 32 times per minute will not be supported by the ventilator.
C. If the infant is breathing spontaneously at a high respiratory rate, the spontaneous breaths will usually
have higher tidal volume than supported breaths.
D. As the ventilator is synchronized, if the infant is breathing at a rate of 20/minute, the ventilator will
provide an average of 20 breaths per minute.
E. As the ventilator provides a consistent and high pressure, there is no need to be concerned about dead
space when using this mode in premature infants.

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 respiratory disorders mechanical ventilatory strategies

3. A 28-week-gestational-age female is being supported on a mechanical ventilator with a time-cycled,

pressure-limited mode in which every spontaneous breath is supported by the ventilator, with a backup rate.
What mode of ventilation is this?
A. Synchronized intermittent mandatory ventilation.
B. Pressure limit–volume guaranteed ventilation.
C. Assist/Control.
D. Intermittent mandatory ventilation with time-cycle support.
E. This type of ventilation is not available for neonates.

4. A 24-week-gestational-age male is receiving mechanical ventilation using pressure-limited ventilation. Which

of the following is most correct in terms of potential limitations and adverse consequences of pressure-limited
ventilation?
A. Tidal volume can vary with changes in lung compliance, particularly after surfactant administration,
resulting in inadvertently large tidal volume delivery and lung injury.
B. As high pressures are more worrisome than high volumes in regard to lung injury, monitoring of pressure is
more important in order to avoid chronic lung disease.
C. With pressure-limited ventilation, this infant is primarily at risk for hypocapnia, and not hypercapnia, as
ventilation will almost always be very effective with this mode.
D. A difficulty of pressure-limited ventilation is the lack of ability to directly control peak inspiratory
pressure.
E. Long-term lung injury caused by excessive tidal volumes is usually caused over the course of several weeks
of pressure-limited ventilation.

5. You are caring for a 1-day-old 31-week-gestational-age female with respiratory distress syndrome, who has
received one dose of surfactant. The infant is on volume targeted ventilation (VTV). Which of the following is
true regarding VTV?
A. Meta-analyses have shown that while VTV reduces need for surfactant therapy, there is no difference in the
outcomes of death, pneumothorax, or duration of ventilation.
B. An advantage of VTV is that the key measurement of 5 ml/kg target tidal volume is the same for all infants
regardless of size or other parameters, making it easier to remember the correct setting.
C. If the ventilator appears to be delivering 5 ml/kg effectively with relatively low pressures (peak inspiratory
pressure of 12-15), this is a sign that the lungs are equally well aerated.
D. With tidal volume as the primary control variable, inflation pressure will fall as lung compliance improves
and result in weaning of pressure.
E. Volume guarantee is a mode that will work with synchronized intermittent mandatory ventilation, but not
with assist/control mode.

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 Update on Mechanical Ventilatory Strategies
Martin Keszler
NeoReviews 2013;14;e237
DOI: 10.1542/neo.14-5-e237

Updated Information & including high resolution figures, can be found at:
Services http://neoreviews.aappublications.org/content/14/5/e237
References This article cites 48 articles, 9 of which you can access for free at:
http://neoreviews.aappublications.org/content/14/5/e237#BIBL
Subspecialty Collections This article, along with others on similar topics, appears in the
following collection(s):
Fetus/Newborn Infant
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nfant_sub
Neonatology
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b
Pulmonology
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Respiratory Tract
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 Update on Mechanical Ventilatory Strategies
Martin Keszler
NeoReviews 2013;14;e237
DOI: 10.1542/neo.14-5-e237

The online version of this article, along with updated information and services, is
located on the World Wide Web at:
http://neoreviews.aappublications.org/content/14/5/e237

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