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Med Intensiva. 2014;xxx(xx):xxx---xxx

www.elsevier.es/medintensiva

UPDATE IN INTENSIVE CARE MEDICINE: MECHANICAL VENTILATION

New modes of assisted mechanical ventilation夽

F. Suarez-Sipmann ∗ , in representation of the Acute Respiratory Failure Working Group
of the SEMICYUC

Department of Intensive Care Medicine, Uppsala University Hospital, Hedenstierna Laboratory, Department of Surgical Sciences,
University of Uppsala, Uppsala, Sweden

KEYWORDS Abstract Recent major advances in mechanical ventilation have resulted in new exciting
Patient---ventilation modes of assisted ventilation. Compared to traditional ventilation modes such as assisted-
synchrony; controlled ventilation or pressure support ventilation, these new modes offer a number of
Assisted mechanical physiological advantages derived from the improved patient control over the ventilator. By
ventilation; implementing advanced closed-loop control systems and using information on lung mechan-
Work of breathing ics, respiratory muscle function and respiratory drive, these modes are specifically designed to
improve patient---ventilator synchrony and reduce the work of breathing. Depending on their
specific operational characteristics, these modes can assist spontaneous breathing efforts syn-
chronically in time and magnitude, adapt to changing patient demands, implement automated
weaning protocols, and introduce a more physiological variability in the breathing pattern. Clin-
icians have now the possibility to individualize and optimize ventilatory assistance during the
complex transition from fully controlled to spontaneous assisted ventilation. The growing evi-
dence of the physiological and clinical benefits of these new modes is favoring their progressive
introduction into clinical practice. Future clinical trials should improve our understanding of
these modes and help determine whether the claimed benefits result in better outcomes.
© 2013 Elsevier España, S.L. and SEMICYUC. All rights reserved.

PALABRAS CLAVE Nuevos modos de ventilación asistida

Sincronía
paciente---ventilador; Resumen Los mayores avances en ventilación mecánica de los últimos años se han producido
Ventilación mecánica en el desarrollo de nuevos modos de ventilación asistida. En comparación con los modos tradi-
asistida; cionales como la ventilación controlada-asistida o la presión de soporte, ofrecen una serie de
Trabajo respiratorio ventajas fisiológicas así como un mayor control sobre el ventilador por parte del paciente.
Basados en la utilización de algoritmos de control de asa cerrada que incorporan informa-
ción de la mecánica, la actividad de la musculatura respiratoria y del estímulo respiratorio,
estos modos están diseñados específicamente para mejorar la sincronía paciente-ventilador
y reducir el trabajo respiratorio. Dependiendo de las características de funcionamiento

夽 Please cite this article as: Suarez-Sipmann F, por el Grupo de Trabajo de Insuficiencia Respiratoria Aguda de la SEMICYUC. Nuevos modos

de ventilación asistida. Med Intensiva. 2014. http://dx.doi.org/10.1016/j.medin.2013.10.008

∗ Corresponding author.

E-mail address: fsuarez.sipmann@surgsci.uu.se

2173-5727/$ – see front matter © 2013 Elsevier España, S.L. and SEMICYUC. All rights reserved.

MEDINE-643; No. of Pages 12

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específicas de cada modo, estos pueden ayudar en los esfuerzos respiratorios espontáneos del
paciente de forma sincronizada en tiempo y magnitud, adaptarse a sus demandas, realizar
protocolos automatizados de reducción del soporte y devolver al patrón respiratorio una vari-
abilidad más fisiológica. El clínico tiene ahora a su disposición modos que permiten individualizar
y optimizar la asistencia ventilatoria mecánica en la compleja transición de la ventilación con-
trolada a la ventilación espontánea-asistida. La creciente evidencia de las ventajas fisiológicas
y clínicas de estos nuevos modos así como las nuevas posibilidades de monitorización que ofre-
cen, están llevando a su paulatina introducción en la práctica diaria. Futuros estudios permitirán
aumentar nuestro conocimiento acerca de estos modos y deberán determinar si sus beneficios
se traducen en mejores resultados clínicos.
© 2013 Elsevier España, S.L. y SEMICYUC. Todos los derechos reservados.

Introduction The former integrates information from neurological and

chemical peripheral afferents at brainstem level, while
Mechanical ventilation (MV) is a life support measure that is the voluntary or behavioral system in turn is located in
used when the respiratory system of the patient is unable to supramedullary and cortical structures. In healthy indi-
meet the metabolic demands of the body. The indications of viduals, the respiratory stimulus has three main origins:
MV range from disease processes that affect gas exchange (1) chemical, mediated by changes in PaO2 , PCO2 and pH;
to simple ‘‘switching off’’ of the respiratory control system (2) metabolic, mediated by less well known mechanisms;
during anesthesia. Mechanical ventilation is usually started and (3) a conscious origin that disappears during sleep
with a controlled ventilation phase during which the clini- phases.2 In effect, during sleep, the respiratory pattern
cian takes full control of the ventilatory process, ensuring a is almost exclusively conditioned by chemical stimuli,
minimum level of gas exchange and adequate muscle rest. which for example explains the apneas seen in response
Once the underlying disease condition has been corrected, to minor changes in PCO2 in sedated patients.3 During the
a transition phase is started in which the patient gradu- waking state, the voluntary control system is activated
ally begins to participate in the ventilatory process. In this and influences the respiratory patterns in a variable and
phase, which is referred to as assisted ventilation, the aim often unpredictable manner. As a result, patients subjected
is to provide ventilatory support synchronized in time and to assisted ventilation can develop complex respiratory
magnitude with the inspiratory effort of the patient as the patterns that affect interaction with the ventilator, thereby
level of mechanical ventilation is gradually reduced. complicating mechanical assist.
The greatest advances in MV correspond to the devel- In order to activate the muscle pump, the automatic
opment of new assisted ventilation modes. Impulsed by control system transmits the respiratory impulses along the
important technical innovations, these new modes offer the- efferents (motor neurons). The voluntary system not only
oretical advantages with respect to the traditional assisted interacts directly with the automatic system, but also has
ventilation modes such as assisted-controlled ventilation or efferents that can directly activate the muscle pump with-
pressure support ventilation. However, their slow introduc- out passing through the automatic control filter2 (Fig. 1).
tion to clinical practice and the fact that their superiority The difficulty of harmonizing the respiratory cycle gener-
in terms of clinical outcomes has not yet been firmly estab- ated by this complex RCS with the mechanical cycle of the
lished have caused the traditional modes to remain the most ventilator is reflected by the fact that both are in manifest
widely used techniques.1 asynchrony in approximately 25% of all patients.4 An ele-
The present review describes new assisted ventilation ment that contributes to this situation is the fact that the
modes that have been grouped as follows: (1) modes that traditional ventilation modes are rigid---delivering prefixed
adapt to the instantaneous inspiratory effort of the patient, volumes or pressures without taking into account the fre-
such as proportional assist ventilation (PAV) and neurally quent changes in patient demands or the changes between
adjusted ventilatory assist (NAVA); (2) automated modes the sleeping and waking states. Moreover, in the case of
that can be adapted to the patient demands, such as adap- assisted-controlled ventilation, the clinician assigns a fixed
tive support ventilation (ASV) and the NeoGanesh system inspiratory time that rarely coincides with the physiolog-
marketed as SmartCareTM ; and (3) modes that introduce bio- ically variable time set by the respiratory control center
logical variability in the ventilatory pattern, such as variable (neural time).
pressure support ventilation (V-PSV) or ‘‘noisy ventilation’’.
Assist modes adapted to the instantaneous
The challenges of assisted ventilation inspiratory effort of the patient

Assisted ventilation has the difficult task of harmonizing These modes are represented by PAV and NAVA, and have
the operation of two complex systems, i.e., patient and opened a new range of possibilities for assisted ventilation.
ventilator---each with its own control center and ventilatory Based on solid physiological principles, these techniques
pump (Fig. 1). The respiratory control system (RCS) is offer a series of theoretical advantages that make them
composed of an automatic system and a voluntary system. particularly attractive for improving patient---ventilator
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Patient Ventilator

Respiratory Ventilator control system

control system (microprocessors)
Afferents
Voluntary Ventilatory
control system pump

Pressure (cmH2O)
Chemoreceptors

Automatic

Flow (l/sec)
control system

Chemoreceptors
Stretch receptors
Muscle receptors

Efferents
Muscle
pump

Figure 1 Principles of patient---ventilator interaction. Assisted ventilation has the difficult task of harmonizing the operation of
two complex systems, i.e., patient and ventilator---each with its own control center and ventilatory pump. The respiratory control
system (RCS) is complex, and is composed of an automatic system and a voluntary system. The afferents transmit the stimuli from
the sensors (central and peripheral chemoreceptors, stretch receptors and muscle receptors) to the control system, regulating the
neural respiratory impulse. The automatic control system emits the efferents (motor neurons) that activate and regulate the muscle
pump. The voluntary system in turn can modulate the activity of the automatic system or directly activate the muscle pump.

synchrony. This is because in these modes the RCS of require sufficient patient alertness and functional integrity
the patient takes control of the respirator and is free of the RCS, which is affected by sedation.
to determine its own respiratory pattern. Consequently,
none of the entities such as volume, pressure and flow are
Proportional assist ventilation
pre-established; rather the ventilator simply assists the
pattern chosen by the patient. In both of the mentioned
Proportional assist ventilation (PAV) was introduced in the
modes the ventilator functions as an additional muscle,
early nineties,6 and represents a synchronized assist ven-
proportionally assisting the instantaneous efforts of the
tilation mode in which the ventilator provides pressure
patient over the entire inspiratory phase. In addition, and in
assistance proportional to the instantaneous effort of the
contrast to the other modes, ventilatory assist ceases at the
patient.
same time as patient effort. This affords improved harmony
between the mechanical and neural ventilatory times.
Upon taking control of the RCS, the ventilatory pattern Principles of proportional assist ventilation
recovers the characteristic variability of the natural res-
piratory pattern. Furthermore, under conditions in which In the PAV system the ventilator detects the inspiratory
the RCS is functionally intact, the afferents from the effort of the patient by precisely measuring the flow and
chemical and neural sensors modulate the intensity and volume leaving the ventilator toward the patient. Both
characteristics of the respiratory impulse. This implies that parameters are conditioned by the inspiratory decrease
both PAV and NAVA theoretically pose a lesser risk of under- in alveolar pressure which the patient generates through
or over-assistance, which often constitutes a cause of muscle contraction. The flow and volume are amplified by
asynchrony with the traditional modes.5 Both assist modes respective adjustable gain controls, and the sum of both
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4 F. Suarez-Sipmann

Pressure (cmH2O)
Flow (l/sec)
P elastic

Piston

3
Pmus Paw 1 Motor

Palv P resistive

Flow Volume AV
2
AF

Figure 2 Schematic representation of the PAV system. The PAV mode affords assistance proportional to effort through the contin-
uous measurement of the flow and volume (1) leaving the ventilator toward the patient, conditioned to the muscle pressure (Pmus)
generated by the patient and which leads to a decrease in alveolar pressure (Palv ). The flow and volume are amplified (AF and AV) by
adjustable gain controls (2), and the sum of both signals conforms the input control signal (3) that generates the pressure response
of the ventilator motor. The latter drives the piston, causing the ventilator to respond with rapid flow delivery to the patient in
proportion to his or her Palv , overcoming the elastic and resistive pressure. The pressure-time and flow-time curves resulting from
the mechanical cycle (4) show that the pressurization pattern is gradual, reaching the maximum value at the end of inspiration,
and exhibiting proportionality at all times. Note that expiratory cycling coincides with the drop in inspiratory pressure, i.e., the
cessation of inspiratory effort (second broken line), and the more physiological sinusoidal morphology of flow of the inspiratory
phase.

constitutes the control signal that generates the pressure by the ventilator is determined by the sum of the flow and
response of the ventilator. The latter reacts with the rapid volume assistance:
delivery of flow in response to this control signal (Fig. 2).
The proportionality of the assistance is determined by Pvent = (%Flow assistance) × Resistance
the motion equation of the respiratory system. According
+ (% Volume assistance) × Elastance
to this equation, the total pressure that must be applied
to insufflate the lung must overcome the resistive pressure
(flow × resistance) and the elastic retraction pressure (vol-
Because of the changing nature of respiratory mechan-
ume × elastance) of the respiratory system:
ics, the system requires frequent measurement of elastance
and resistance. There is consequently a risk of excessive
Ptotal = flow × resistance + volume × elastance or insufficient assistance in cases of estimation error or a
lack of concordance between the estimated and the actual
During assisted ventilation, the total pressure is the sum values. In the event of over-estimation, compensation is
of the pressure generated by muscle contraction of the excessive, and the expiratory cycle may be delayed, pro-
patient (Pmus ) and the pressure generated by the ventilator longing assistance beyond the cessation of inspiratory effort
(Pvent ). on the part of the patient---this being known as the ‘‘run-
away’’ phenomenon.7,8
Ptotal = Pmus + Pvent A simplified and improved form has recently been
introduced, called proportional assist ventilation with load-
The levels of flow and volume assistance are adjusted adjustable gain factors, or PAV+. This mode offers two
independently by the user. This requires an estimation of essential improvements: (1) the noninvasive and semi-
the passive mechanical characteristics, resistance and elas- continuous measurement of respiratory mechanics, allowing
tance, at the start of adjustment and on an intermittent automatic closed-loop adjustment of the assist level. This
basis. Once these are known, the pressure assist afforded measurement is made by introducing brief pauses (300 ms)
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at the end of inspiration every 8---15 respirations to esti- in patients with dynamic hyperinsufflation and intrinsic
mate resistance9 and elastance10 ; and (2) the automatic positive-end expiratory pressure (PEEP) as the traditional
adjustment of a single level of flow and volume assistance modes. Although expiratory cycling, based on flow, accom-
that becomes a constant fraction of the measured values of panies the cessation of inspiratory effort, expiratory
resistance and elastance. asynchronies have been described particularly with high
assist levels.19
Functioning of proportional assist ventilation with The PAV mode can also be used in noninvasive ventilation
(NIV). Compared with PSV, mainly in patients with chronic
load-adjustable gain factors (PAV+)
obstructive pulmonary disease (COPD), PAV usually affords
higher levels of tolerance, a better physiological response,
During ventilation in PAV+ mode, we simply need to adjust
and fewer complications.20---22 However, PAV has not been
the percentage by which the ventilator must assist patient
associated with a decrease in the need for intubation in
effort. Accordingly, an assist level of 70% means that the
comparison with PSV. This could be related to the fact that
ventilator will contribute 70% to the total pressure reached,
leakage---the main cause of disadaptation and asynchrony
leaving the remaining 30% to the patient. The proportional-
during NIV23 ---equally affects triggering in PAV and in PSV.
ity is simplified as follows:

%assistance Proportional assist ventilation and monitoring

Proportionality =
100 − %assistance
With the PAV+ system we have semicontinuous monitoring
For an assist level of 70%, the proportionality is 3; in of the elastance and resistance of the respiratory system.
other words, the system multiplies instantaneous pressure In addition to providing valuable evolutive information, it
assistance by a factor of 3. allows us to immediately assess the response to changes
After activating the inspiratory trigger through pressure in the respiratory parameters or to quickly detect possible
or flow, the inspiratory pressure progresses with the estab- complications. The system is also able to estimate and mon-
lished proportionality, following a profile identical to that of itor Pmus, which is the only unknown factor of the motion
Pmus . The result is gradual pressurization, reaching the maxi- equation. Knowing Pmus , we in turn can calculate the work
mum pressure only at the end of inspiration. In the moment of breathing, helping to select an adequate assist level with
in which the effort of the patient begins to decrease, the a view to avoiding excessive muscle work or rest.24
delivery of flow also decreases---expiratory cycling therefore
generally coinciding with the cessation of patient effort. Neurally adjusted ventilatory assist

PAV and PAV+: clinical characteristics Neurally adjusted ventilatory assist (NAVA) is a new assisted
ventilation mode synchronized and proportional to the
Many clinical studies have compared the physiological effort of the patient that has become available only in
advantages of PAV versus conventional assist modes. Marantz the last few years.25 As control signal for both assist and
et al.7 characterized the physiological response to PAV for inspiratory and expiratory cycling of the ventilator, this
among patients dependent upon mechanical ventilation. mode uses the electrical activity of the diaphragm (EAdi).
They found that during PAV, in the absence of limitations The latter is recorded via transesophageal electromyogra-
imposed by respiratory mechanics, the RCS of the patient phy using a modified nasogastric tube, also known as an
determines the tidal volume (Vt ) and the frequency in EAdi catheter, which is similar in size and function to a
response to variable assist levels. The patients tend to lower conventional nasogastric tube but equipped with several
Vt and to increase the frequency in order to maintain the microelectrodes at the distal tip for recording EAdi. Correct
chosen minute volume. This results in a reduction of the positioning of the catheter is carried out using the trans-
inspiratory pressures. esophageal electrocardiographic signal recorded through
With respect to pressure support ventilation (RSV), the same electrodes as a guide. The operator can check cor-
PAV has shown similar muscle discharge11---14 and better rect positioning (at the esophageal hiatus) on the ventilator
hypercapnia compensation.15 In response to an increase screen, based on a simple algorithm.26
in elastic loading of 30%, Kondili et al.16 recorded
greater efficiency in compensation (lesser increase of the The electrical activity of the diaphragm
work of breathing) with PAV+ than with PSV. Xirouchaki
et al. compared the effectiveness of PSV versus PAV+ The utilization of EAdi for control of the ventilator has a
in maintaining critical patients dependent upon mechan- series of theoretical advantages. In effect, EAdi is a signal
ical ventilation in assisted ventilation. They found PAV+ that directly (i.e., without calculations or estimates) mea-
to significantly increase the probability of remaining with sures the efferents from the RCS, integrating the sum of
spontaneous ventilation, in addition to considerably redu- time and space of the neural respiratory impulse that results
cing patient---ventilator asynchrony.17 Thanks precisely to in diaphragmatic activation.27 The amplitude of the signal
a decrease in patient---ventilator asynchrony, Bosma et al. depends on the degree of recruitment and on the inten-
showed PAV to afford superior sleep quality, with fewer dis- sity and frequency of triggering of the motor units, and
ruptions, in comparison with PSV.18 consequently reflects the intensity with which the patient
The PAV system depends on pneumatic triggering, and wishes to breathe.27,28 From its origin, the signal takes less
therefore has the same limitations for inspiratory cycling than 20 ms in triggering the mechanical response of the
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A B
25

Pressure (cmH2O)
20
12
EAdi peak 15
Expiratory cycling
10 70% of max EAdi 10

5
8 0
EAdi (µV)

60
6 40

Flow (l/min)
20
4 0
Inspiratory cycling
(EAdi exp + 0.5 to 2 µV) 20
2 40
EAdi expiratory
60
0
14
12
10

Edi (µV)
8
TI neural TE neural
6
4
TI mechanical TE mechanical
2
0
Time

Figure 3 EAdi signal and characteristic respiratory curves during ventilation in NAVA. (A) EAdi signal. The start of inspiration is
given by the increase in EAdi activity (first broken line) from the expiratory activity, which under normal conditions is 0. At the
point where EAdi reaches a threshold value (first dotted line), the ventilator starts assist until EAdi drops to 70% of the maximum
value (second dotted line). The neural inspiratory time comprises the period between the two solid lines, and ends when EAdi
reaches its maximum value. The mechanical ventilatory time comprises the period between the two broken lines (inspiratory and
expiratory cycling). Note that although minimal, there is a phase lag in the time between the neural and mechanical times due to
the imposed cycling criteria. (B) The curves corresponding to pressure, flow and EAdi of a cycle show the perfect inspiratory (first
broken line) and expiratory cycling synchrony produced immediately after the start of the neural time of the patient, in relation
to the cessation of inspiratory effort. In the same way as in PAV, pressurization is gradual, and in NAVA follows or parallels the
morphology of the inspiratory phase of EAdi. The NAVA level is 1, and we can see that the end-inspiratory pressure reached is
22 cmH2 O, which corresponds to EAdi (=12) × NAVA level (=1) + PEEP level (=10).
Adapted from Suarez-Sipmann et al.30 .

diaphragm29 ---this being about three to four times faster than is determined by a proportionality constant adjusted by
the pneumatic trigger response time of modern ventilators. the operator, called the NAVA level, which amplifies the
It is therefore the signal closest to the origin of the respira- instantaneous progression of EAdi during the inspiratory
tory stimulus that current technology is able to offer. phase. The pressure in the airway (Paw ) over the level of
PEEP, in each moment during inspiration, is expressed as
follows:
Functioning of the NAVA system
Paw = EAdi (␮V) × level − NAVA + PEEP
During NAVA, inspiratory cycling is determined by the detec-
tion of the elevation of EAdi over the expiratory level, with a
sensitivity threshold determined by the operator. Expiratory Different methods have been proposed for adjusting the
cycling occurs when EAdi decreases to 70% of the maxi- NAVA level, which theoretically should be that affording an
mum inspiratory value (Fig. 3). This allows adjustment of adequate level of muscle discharge. Brander et al. have
the duration of the mechanical inspiratory and expiratory described a method based on the response of Vt and Paw
times to the neural inspiratory and expiratory times of the to ascending NAVA levels.31 Starting from low levels, the
patient determined by the RCS, in a way which no other ven- authors described a double response comprising a gradual
tilatory mode is able to do.30 In addition, the NAVA system increase to a certain NAVA level beyond which Vt and Paw
eliminates the limitations of pneumatic triggering, since it is reach a plateau. The optimum NAVA level would be that
not affected by leakages or the presence of dynamic hyper- coinciding with transition from an ascending phase to the
insufflation. This defines NAVA as the ventilatory mode which plateau phase of the Vt and Paw values. Roze et al. in turn
theoretically offers the greatest level of patient---ventilator have proposed adjustment to a NAVA level that reaches 60%
synchrony. of the maximum EAdi obtained after a standardized test with
In the same way as during PAV, the inspiratory assist is minimum assist (pressure support ventilation with 7 cmH2 O
at all times proportional to the effort of the patient and and PEEP 0) with a duration of 1 h.32
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30 40 0.6

25 35 0.5
Paw peak (cmH2O)

RR flow (bpm)
30 0.4
20

CV TV
25 0.3
15
20 0.2
10 0.1
15

5 10 0.0
0.5 1 1.5 2 2.5 3 4 4 8 12 16 0.5 4 1.5 2 2.5 3 4 4 8 12 16 0. 5 1 1. 5 2 2.5 3 4 4 8 12 16
NAVA level PS NAVA level PS NAVA level PS

14 22 0.7
20
12 18 0.6
16
TV/Kg (ml/Kg)

EAdi peak (µV)

CV EAdi peak
10 14 0.5
12
8 0.4
10
6 8
0.3
6
4 4 0.2
2
2 0 0.1
0.5 1 1.5 2 2.5 3 4 4 8 12 16 0.5 1 1.5 2 2.5 3 4 4 8 12 16 0.5 1 1.5 2 2.5 3 4 4 8 12 16
NAVA level PS NAVA level PS NAVA level PS

Figure 4 Effect of different NAVA levels and pressure support. Note that in NAVA, and in contrast to pressure support ventilation
(PSV), greater assist levels do not increase the tidal volume or decrease the respiratory frequency, and the pressure in the airway
reaches a plateau with higher assist levels---corresponding to a decrease in EAdi. The increase in assist is accompanied by increased
variability in tidal volume in NAVA, while it decreases in PSV. PS: pressure support ventilation; EAdi: electrical activity of the
diaphragm; CV EAdi peak: coefficient of variation of the electrical activity of the diaphragm; CV TV: coefficient of variation of the
tidal volume; Paw : pressure in the airway; RR: respiratory frequency; TV/kg: tidal volume per kg ideal weight. *p < 0.05 versus the
lowest assist level for the same ventilatory mode. **p < 0.05 versus the highest assist level for the same ventilatory mode.
Adapted from Patroniti et al.38 .

NAVA: clinical characteristics The NAVA mode has been shown to facilitate assisted ven-
tilation also in patients with seriously impaired respiratory
Several clinical studies have evaluated and compared function. In this respect, the NAVA mode reduced asynchrony
the physiological response to NAVA. These studies in patients subjected to extracorporeal oxygenation support
have consistently recorded significant improvement in and with severely impaired lung distensibility37 versus PSV,
patient---ventilator synchrony, a lesser over-assistance and achieved better auto-regulation of PCO2 during weaning
tendency, and greater variability of the respiratory pattern from extracorporeal oxygenation41 ---in both cases maintain-
in comparison with PSV in different groups of patients.33---40 ing protective ventilatory parameters with low Vt values.
Ineffective effort, i.e., inspiratory effort of the patient that Because of its operating characteristics, NAVA may be
is not accompanied by mechanical assist, virtually disap- particularly interesting in the context of NIV, since it is not
pears with NAVA.34 Likewise, in contrast to PSV, increments affected by leakages. In this regard, Piquilloud et al.42 and
in assist level have been shown to exert less effect upon Bertrand et al.43 reported a significant reduction of asyn-
the inspiratory and expiratory cycling times,35 ensuring chronies with NAVA versus PSV during NIV both in patients
better synchrony over a broad assist range. Patroniti et al.38 with exacerbated COPD and in hypoxemic patients.
have published a detailed description of the ventilatory
pattern during NAVA. In patients with respiratory failure,
the authors compared the response to increasing NAVA NAVA and monitoring
levels with increasing PSV levels (Fig. 4). With NAVA, the
patients maintained similar Vt and respiratory frequency The EAdi signal offers new and interesting possibilities in
values, even with high assist levels, despite an increase in respiratory monitoring. By affording a direct and continuous
Paw , which corresponded to a decrease in EAdi. In contrast, measure of the central respiratory stimulus of the patient,
during PSV, both Vt and pressure increased (up to >100% the signal allows us to evaluate the response to changes in
with the maximum level), while the frequency and EAdi assist level, detect apneas, evaluate sedation effects, and
decreased. also assess the neural respiratory stimulus. EAdi is the best
In the same way as during PAV, studies with NAVA have tool available for monitoring patient---ventilator synchrony,
shown that patients tend to select a protective tidal volume since it offers direct information on the neural inspiratory
(6 ml/kg) with moderate assist levels and a generally higher and expiratory times and their relation to the mechanical
respiratory frequency. times. It allows us to determine the neural frequency (the
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real frequency of the patient), thereby enhancing the value Figure 5 schematically represents the principles of the
of this variable in determining the degree of patient stress functioning and control system of ASV. The operator estab-
or wellbeing. A number of indices derived from the EAdi lishes a target percentage minute-volume based on the body
signal have recently been described. Neuroventilatory effi- weight of the patient.
ciency, measured as Vt /EAdi, indicates the capacity of the
diaphragm to generate volume, standardized with respect to
the neuronal stimulus. In one same parameter it integrates % Vmin × ideal weight
Vmin =
information on the respiratory stimulus, diaphragmatic 1000 in adult patients
function, and respiratory loading, and has been shown to
be a good predictor of weaning.44,45 Neuromechanical effi-
ciency, measured as Paw /EAdi during an occlusion in which Under normal conditions, % Vmin is 100%, with the possi-
the patient inhales against a closed valve, provides an esti- bility of choosing between 25 and 300%, depending on the
mate of the capacity of the diaphragm to generate force in conditions of the patient.
relation to the neural inspiratory effort. Based on neurome- It should be remembered here that minute-volume is the
chanical efficiency, Bellani et al. have derived a method to sum of the alveolar ventilation volume (the ‘‘effective’’
estimate Pmus from EAdi, thereby producing more objective volume) and the dead space volume. Accordingly, ASV incor-
information for determining the best NAVA level.46 porates the estimation of dead space in its algorithm, and
which the system assumes to be 2.2 ml/kg. The ASV sys-
tem then adjusts the level of pressure and respiratory
Automated modes adaptable to patient frequency cycle-to-cycle, following its algorithm to main-
demands tain the ventilatory pattern according to the established
target minute-volume, in consistency with the mechanical
These modes encompass closed-loop control modes that characteristics of the respiratory system and the spon-
incorporate algorithms and control rules which transfer taneous respiratory frequency of the patient. Inspiratory
physiological and clinical reasoning principles to auto- cycling uses the conventional pneumatic trigger by pressure
mated assist protocols. According to different physiological or flow, while expiratory cycling is by flow as in the case of
and clinical objectives, these modes automatically adjust PSV.
the pressure or minute-volume levels administered to the
patient, adapting to the needs of the latter over time.
Adaptive support ventilation (ASV) performs cycle-to-cycle
adjustments of tidal volume (through changes in pressure) ASV: clinical characteristics
and respiratory frequency, adapting them to changes in
respiratory mechanics. NeoGanesh or SmartCareTM in turn Due to its ‘‘mixed’’ nature, ASV has been studied both as
performs adjustments, in cycles of several minutes, in deliv- controlled mode and as assist mode. Most clinical studies
ered pressure support ventilation, adapting the levels to the have focused on examining ASV under passive ventilation
changing conditions of the patient. The aim is to simulate (controlled) conditions, comparing it with other modes,
clinical reasoning in order to avoid under- or over-assistance and specifically evaluating whether ASV yields protective
and to achieve a decrease of the automated support. parameters (low Vt and Paw ) in an automated and efficient
way.
As assist mode (which is what interests us in this review),
Adaptive support ventilation
ASV has been studied mainly as a mode designed to facili-
tate weaning. It has been shown to be a safe and effective
Adaptive support ventilation (ASV), described in the early
technique that simplifies the weaning process in the post-
nineties, is based on the physiological principle described
operative period of heart surgery49---51 and in patients with
by Otis and Mead47,48 which establishes that for a given level
COPD,52 and is moreover associated with a lesser consump-
of alveolar ventilation there is an optimum respiratory fre-
tion of resources. In comparative studies, ASV has not been
quency that results in less work of breathing---a kind of ‘‘law
found to shorten the mechanical ventilation times in heart
of minimum effort’’. According to this principle, in order
surgery,50,51 though shortened times have been recorded in
to reach one same alveolar ventilation level at very low
COPD patients, where Kirakli et al. observed a shortening of
frequencies, we require a greater Vt , increasing the work
the weaning time of over 24 h compared with PSV.53
to overcome the elastic load of the respiratory system. In
The best comparative clinical study to date on the effect
contrast, at high frequencies, the work of breathing must
of ASV upon patient---ventilator synchrony was published by
increase to overcome the resistive load, with a pattern cha-
Tassaux et al. In comparison with synchronized intermittent
racterized by rapid shallow breathing. Between these two
ventilation (SIMV-PSV), these authors found ASV to improve
extremes lies the optimum combination of frequency and
synchrony, reducing the muscle load for a similar delivered
volume for achieving the desired alveolar ventilation.
minute-volume.54
The ASV mode has recently received improvements, with
Functioning of ASV addition to the algorithm of closed-loop control for end-
expiratory CO2 (etCO2 )55 and oxygen saturation. The result
Unlike the other examined modes, ASV in fact is a mixed is an evolved ASV system called IntelliVentTM , which allows
mode that can function as a controlled or assisted mode us to implement a protective ventilatory strategy in both
according to the contribution of the patient. the control phase and in assistance to weaning.56
+Model
ARTICLE IN PRESS
New modes of assisted mechanical ventilation 9

Values entered by the clinician

Body weight
Target % min vol
Pmax, PEEP, FiO2

Mechanics of the respiratory system Flow/volume curve

Pinsp Compliance, resistance, PEEPi Expiratory time constant

Calculation of
I:E respiratory frequency

Tidal
volume

Pinsp Pinsp
FR FR
VT
Target
Pinsp Pinsp IsoVM
FR FR curve

FR Respiratory
Target frequency

Figure 5 Functioning of ASV. Before starting, the clinician enters the data referred to patient weight, percentage minute-volume
(estimated a priori according to the patient and disease condition), FiO2 , PEEP and the maximum inspiratory pressure limit (Pmax ).
Analysis of the flow-volume curve determines the expiratory time constant, and minimum squares fitting is used to calculate the
respiratory mechanics and the presence of intrinsic PEEP. The closed-loop control algorithm of the ASV system adjusts the inspiratory
pressure according to the iterative equation derived from Otis and Mead. The combinations of target minute-volume and frequency
are continuously adjusted to reach and keep the patient on the minute-isovolumetric curve (IsoVM).
Adapted from Tassaux et al.54 .

Automated adjustment of pressure support: weaning process. This zone of wellbeing is derived from the
NeoGanesh-SmartCareTM patient characteristics (body weight, type of illness, size of
the endotracheal tube, type of humidifier). The values are
NeoGanesh and its commercial version SmartCareTM consti- entered by the clinician in the ventilator, and determine the
tute an automated, knowledge-based weaning technique. limits of Vt , frequency and etCO2 , and the PSV adjustments
The control algorithm incorporates rules for action based required. The automated weaning protocol involves auto-
on clinical reasoning, in an attempt to reproduce the PSV mated adaptation of the PSV level followed by an automated
adjustments which the clinician would decide in the same PSV reduction phase, and finally an automated spontaneous
context. breathing test.

Functioning of SmartCareTM SmartCareTM : clinical characteristics

The control algorithm of the system uses the values of SmartCareTM is able to facilitate the weaning process,
Vt , respiratory frequency and etCO2 . These values are reducing resource consumption and shortening the time
averaged every two minutes (every 5 min in the case of on mechanical ventilation. Clinical studies have reported
changes in pressure level) and provide the algorithm with somewhat discordant findings in relation to such benefits,
a ‘‘ventilatory diagnosis’’. The system responds as follows: depending on whether the control group included57 or did
(1) it reduces the level of PSV in the case of diagnosed over- not include58 weaning protocols and sufficient resources
assist (e.g., the combination of high Vt with low frequency (patient/nurse ratio).59 In the most recent multicenter study
and etCO2 ); (2) it increases assist in the event of insuffi- involving 92 patients with over 24 h of mechanical ventila-
cient assistance (increasing frequency together with other tion, automated weaning shorted the duration of mechanical
additional criteria); and (3) it introduces no changes in the ventilation by one day, and also lessened the need for
case of normal ventilation. The aim is to move the patient tracheostomy compared with a protocolized conventional
toward a zone of respiratory wellbeing in order to start the weaning group.60
+Model
ARTICLE IN PRESS
10 F. Suarez-Sipmann

Variable pressure support ventilation (noisy capacity to adapt to the changing patient needs. The new
ventilation) modes allow the patient a total control of the ventilatory
process, causing the ventilator to act as an accessory muscle
Variability is an intrinsic characteristic not only of the res- in synchrony with patient inspiratory effort. New modes that
piratory system but also of any complex biological system, incorporate increasingly complex closed-loop or knowledge-
and the loss of such variability is generally associated with based control systems are paving the way toward gradual
functional impairment.61 There is a growing evidence of the automatization of the mechanical ventilation process. It
beneficial effect of variability, understood as cycle-to-cycle can be expected that such modes and automatization will
changes in Paw and Vt and/or respiratory frequency, upon gradually find their way into routine clinical practice. The
the respiratory system.62 All the new assist modes described results of future studies will help us to better define their
thus far introduce respiratory variability, the latter being advantages, indications and benefits in assisting patients
determined to one degree or other by the patient. Variable subjected to mechanical ventilation.
pressure support ventilation (V-PSV) introduces random vari-
ability in the levels of pressure support ventilation, resulting
in a ventilatory pattern that is variable but independent of
Conflicts of interest
the demands of the patient and his or her inspiratory effort.
The author serves as a consultant to Maquet Critical Care.

Functioning of variable ventilation

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