British Journal of Anaesthesia 107 (1): 74–82 (2011)

Advance Access publication 24 May 2011 . doi:10.1093/bja/aer114

Emerging modes of ventilation in the intensive care unit

N. I. Stewart 1, T. A. J. Jagelman 1 and N. R. Webster 2*
1
Intensive Care Unit, Aberdeen Royal Infirmary, Foresterhill Road, Aberdeen AB25 2ZN, UK
2
Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK
* Corresponding author. E-mail: n.r.webster@abdn.ac.uk

Summary. Potentially harmful effects of positive pressure mechanical ventilation have

Editor’s key points been recognized since its inception in the 1950s. Since then, the risk factors for and
† Novel techniques in mechanisms of ventilator-induced lung injury (VILI) have been further characterized.
pulmonary ventilation are Publication of the ARDSnet tidal volume trial in 2000 demonstrated that a ventilator
emerging and may offer strategy limiting tidal volumes and plateau pressure in patients with acute respiratory
improved outcome. distress syndrome was associated with a 22% reduction in mortality. Since then, a
† These include airway variety of ventilator modes have emerged seeking to improve gas exchange, reduce
pressure release ventilation, injurious effects of ventilation, and improve weaning from the ventilator. We review
high-frequency oscillatory here emerging ventilator modes in the intensive care unit (ICU). Airway pressure release
ventilation, ventilation seeks to optimize alveolar recruitment and maintain spontaneous ventilatory
proportional-assist effort. It is associated with improved indices of respiratory and cardiovascular
ventilation, and neutrally
physiology, but data to support outcome benefit are lacking. High-frequency oscillatory
adjusted ventilator assist.
ventilation is associated with improvements in gas exchange, but outcome data are
† Most techniques are based in conflicting. Extracorporeal modes of ventilation continue to evolve, and extra-corporeal
applied physiology and
CO2 removal is a technique that could be used in non-specialist ICUs. Proportional-assist
observed improvements in
ventilation and neutrally adjusted ventilator assist are modes that vary level of
comfort, physiological
measures, or both.
assistance with patient ventilatory effort. They result in greater patient-ventilator
synchrony, but at present there is no evidence of a reduction in the duration of
† None has yet been
mechanical ventilation or outcome benefit. Although the use of many of these modes is
demonstrated convincingly
to improve survival or
likely to increase in intensive care units, further evidence of a beneficial effect is
shorten intensive care unit desirable before they are recommended.
stay. Keywords: APRV; ECMO; oscillator; ventilation

Mechanical positive pressure ventilation has formed the factor for their development.2 However, in the 1980s and
mainstay of respiratory support in the intensive care unit 1990s, more subtle harmful effects of ventilation were ident-
(ICU) since the 1950s. After the 1952 Copenhagen polio ified. An increase in vascular filtration pressures associated
epidemic, Lassen1 reported the experience of 316 patients with high tidal volume ventilation leads to disruption of
with respiratory paralysis and/or bulbar dysfunction who the endothelium, epithelium, and basement membranes,
required tracheostomy, ventilation, postural drainage, or and ensuing leakage of fluid, protein, and blood into pul-
a combination of these. At times, up to 200 medical monary tissue and air spaces.3 This establishes an inflam-
students were used to hand-ventilate up to 70 patients matory process that has effects beyond the lungs.4 The
concurrently. In his report, he identified several disadvan- diffuse alveolar damage that can occur is pathologically
tages of positive pressure ventilation, including: ‘When indistinguishable from other causes of acute lung injury
bag ventilation is administered for weeks there is a risk (ALI) and acute respiratory distress syndrome (ARDS).5 It
of emphysema’, ‘If bag ventilation is not administered cor- became apparent from radiological studies6 that these con-
rectly venous return may be reduced, leading to lowered ditions did not lead to homogeneous lung damage as pre-
cardiac output and a state of shock’, and ‘The weaning viously thought, but dependent and patchy oedema and
period from positive pressure ventilation is not infrequently atelectasis resulted in significantly reducing the volume of
difficult’. aerated lung, leading to stretch and over-distension of
As positive pressure ventilation evolved as a treatment healthy areas, if traditional tidal volumes (10–15 ml kg21)
strategy for respiratory failure, the harmful effects became were applied during mechanical ventilation.
further recognized. Barotrauma, such as pneumothorax In 2000, the publication of the ARDSnet tidal volume trial,7
or surgical emphysema, were, for many years, the major a randomized controlled trial (RCT) including 861 patients,
recognized form of ventilator-induced lung injury (VILI), established that patients with ALI or ARDS who received
and high inflation pressures an obvious and recognized risk 6 ml kg21 tidal volumes with a maximum plateau pressure

& The Author [2011]. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved.
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Emerging modes of ventilation in ICU BJA
of 30 cm H2O had a 22% lower mortality than those who patients. APRV with spontaneous ventilation was found to
received 12 ml kg21 and a maximum plateau pressure of be associated with decreased intrapulmonary shunt and
50 cm H2O. This established firmly that mechanical venti- dead space, and increased PaO2 and oxygen delivery.
lation must not only optimize alveolar recruitment and Sydow and colleagues15 compared APRV with volume-
provide adequate oxygenation and carbon dioxide removal, controlled inverse ratio ventilation patients with ALI, and
but minimize iatrogenic harm to already damaged lung. found that APRV was associated with 30% lower peak
The principles of mechanical ventilation in the ICU are inspiratory pressures, and significant improvement in alveo-
thus to maintain adequate gas exchange, avoid cyclical lar –arterial oxygen tension difference/fractional inspired
closure, and reopening of already damaged alveoli and over- oxygen tension (AaDO2/F IO2 ) and venous admixture.
distension of healthy alveoli. Advances in ventilator technol- The relatively high mean airway pressure attained with
ogy have led to an explosion in the variety of ventilators APRV might be expected to have adverse haemodynamic
available that utilize these principles to either improve consequences. However, investigators have demonstrated
gas exchange in critical hypoxaemia, further reduce the increased stroke volume, cardiac index,14 and improved
harmful effects of mechanical ventilation, or aid weaning renal blood flow and glomerular filtration rate16 with APRV
from ventilation. This article will review a selection of compared with conventional ventilatory modes. Others
emerging ventilator modes. have demonstrated no change in haemodynamic variables.15
It is possible that maintenance of diaphragmatic ventilation
leads to less reduction in intrathoracic venous return than is
Airway pressure release ventilation seen with conventional ventilation (CV).
Airway pressure release ventilation (APRV) was first described The maintenance of spontaneous breathing has potential
in 1987.8 It combines relatively high levels of continuous benefits for weaning ventilatory support; however, studies
positive airway pressure; typically .20 cm H2O in the first have been conflicting. APRV has been associated with a
instance (termed Phigh) with time cycled ‘releases’ at a reduction in sedation requirements, duration of ventilation,
lower pressure; usually 0 cm H2O (termed Plow) (Fig. 1). It length of ICU stay,17 reduced incidence of ventilator-
aims to maintain spontaneous breathing at Phigh, thus main- associated pneumonia, and improved sedation-agitation
taining diaphragmatic ventilation9 of more dependent, scores18 compared with conventional ventilatory modes.
better perfused areas of the lung that are not usually well However, other studies have not found any difference in
ventilated during mechanical ventilation.10 In order to aid these variables.19 20 Studies comparing APRV with CV have
ventilation and CO2 elimination, Phigh is briefly released, typi- so far all been small and it is not clear whether APRV
cally for ,1 s. Increasing the duration of release (Tlow) risks conveys benefits beyond the improvements in cardiovascular
alveolar derecruitment if long enough to allow the loss if and respiratory physiology reported. Interpreting the evi-
intrinsic PEEP. As time at Phigh (Thigh) normally considerably dence is difficult as there are no consensus definition criteria
exceeds Tlow Paw is maintained, yet high plateau pressures for APRV21 and some studies reporting to use APRV are using
are avoided. It is the marked inverse inspiratory:expiratory ventilatory modes that would be more conventionally
ratio; typically in the region of 8:1– 10:1 that defines APRV described as biphasic positive airways pressure (BIPAP).22
compared with other pressure-controlled ventilatory modes.
In ALI and ARDS, alveolar recruitment is both time- and
pressure-dependent. The threshold opening pressure and High-frequency oscillatory ventilation
time required for recruitment varies throughout the lung, Interest in high-frequency ventilation arose in 1915 when Hen-
as it is dependent on radial traction of opening alveoli on derson and colleagues23 observed that effective ventilation
each other.11 A porcine model of ALI suggests that there is occurs in panting dogs, even with tidal volumes lower than
a considerable variation in both the inspiratory and expira- anatomical dead space. However, it was the 1970s before
tory time constants of different areas of the lung. Some systems were designed that could effectively achieve oscil-
lung units may take up to 10 s to recruit, and may de-recruit latory ventilation in animal models.24 25 This led to the devel-
with as little as 0.8 s of pressure release.12 APRV therefore opment of high-frequency oscillatory ventilators that are now
offers potential advantages over conventional ventilatory commercially available for adults and children. High-frequency
modes in terms of alveolar recruitment. Yoshida and col- oscillatory ventilation (HFOV) uses an oscillating piston pump
leagues13 investigated 18 patients with ARDS who received and a bias gas (flow rate) of 20– 40 litre min21 to generate a
either pressure support ventilation (PSV) or APRV and had ventilatory frequency typically between 180 and 900 bpm
helical computed tomography of their chest twice in 3 and a tidal volume typically 1 –2 ml kg21 which is usually
days. They found that patients who received APRV had a less than anatomical dead space (Fig. 2). The mean pressure
reduction in atelectatic areas from 41% to 19% (P¼0.008) (Paw) and F IO2 ) are adjusted to maintain oxygenation, and
and an increase in normally aerated lung from 29% to 43% the oscillatory pressure amplitude (△P) and frequency are
(P¼0.008); compared with 39 –29% (P¼0.379) and 39 –44% adjusted to optimize CO2 removal. The value of △P determines
(P¼0.445) in patients who received PSV. tidal volume, but the pressure changes measured in the circuit
Putensen and colleagues14 evaluated the effects of APRV are greatly attenuated in the tracheal tube and large airways
and PSV on the ventilation/perfusion ratio of 24 ARDS such that the pressure changes in the alveoli are considerably

75
BJA Stewart et al.

PHIGH

PLOW

THIGH TLOW

Fig 1 APRV waveforms.

intrathoracic venous return) and a lack of portable equip-

Large airways
ment. It is also necessary to wean patients using convention-
al ventilator modes before extubation. I.V. fluid loading may
be required before commencement of HFOV in order to
Paw prevent haemodynamic compromise. Adjusting ventilatory
support in response to changes in gas exchange is less intui-
tive than with conventional modes, for example, hypercapnia
is often managed by reducing ventilatory frequency.
Alveoli The first case series of HFOV use in adults was by Fort and
colleagues31 in 1997 where they described their experience
of 17 adults with severe ARDS, failing on conventional venti-
Paw
latory strategies, in whom HFOV was used. The age range
was 16–82 yr and severity of illness was high, with a mean
APACHE II score of 23.3 (7.5), PaO2 /FIO2 ratio of 66.13 mm
Fig 2 Pressure changes in the large airways vs the alveoli during Hg, and oxygenation index (OI) [(Paw×FIO2 ×100)/PaO2 ] of
oscillatory ventilation. 48.56 cm H2O kPa21. The peak inspiratory pressure and
PEEP before commencing HFOV was 54 and 18 cm H2O,
respectively. They demonstrated a significant improvement
lower. Alveolar ventilation occurs predominantly through in both PaO2 /FIO2 ratio and OI over the 48 h of the study
acceleration of molecular diffusion, although other mechan- and an overall survival of 53% in a group in whom HFOV
isms including Pendelluft, Taylor dispersion (mixing related to was being used as a rescue strategy. They did not demon-
laminar gas flow), and cardiogenic mixing (oscillations strate any significant change in cardiac output, oxygen deliv-
related to transmitted cardiac pulse) are thought to contrib- ery, heart rate, or arterial pressure with HFOV. Mehta and
ute.26 The overall effect is that the mean pressure (Paw) deliv- colleagues32 also demonstrated a significant improvement
ered is higher than with conventional modes of ventilation, in PaO2 /FIO2 ratio within 8 h of commencing HFOV in 24
maintaining alveolar recruitment, but plateau pressure can patients failing on conventional ventilatory strategies. They
be maintained below 30 cm H2O and FIO2 often reduced. As demonstrated a significant decrease in cardiac output and
△P is greatly attenuated in the alveoli, cyclical collapse and an increase in central venous pressure and pulmonary
over-distension is avoided, thus theoretically reducing artery occlusion pressure; but no significant changes in
ventilator-induced lung injury (VILI). However, whether heart rate, arterial pressure, or vasopressor requirements.
attenuation of △P applies equally to normal, compliant The Multicentre Oscillatory Ventilation for Acute Respirat-
airways and rigid consolidated airways is not known. ory Distress Syndrome (MOAT) trial33 was the first RCT com-
Animal studies27 28 have demonstrated reduced inflamma- paring HFOV with conventional ventilatory strategies in
tory mediators such as platelet activating factor, thromboxane adults. One hundred and forty-eight patients with ARDS
B2, and tumour necrosis factor a with HFOV compared with CV. and receiving CV were randomized to either continue with
Others have demonstrated a reduction in pathological features CV or receive HFOV. The primary outcome was survival
such as hyaline membrane formation, polymorphonuclear without the need for mechanical ventilation at 30 days.
leucocyte infiltration, and improved indices of gas exchange in The HFOV group had a significant improvement of PaO2 /FIO2
animal models of ALI.29 30 ratio initially, although this did not persist beyond the first
Potential disadvantages of HFOV include increased 24 h. There was no significant difference between haemo-
requirement for sedation and neuromuscular block, noise dynamic variables. The percentage of patients alive without
(which leads to difficulty with clinical examination), haemo- mechanical ventilation at day 30 was 36% and 31% in the
dynamic instability (as a result of increased Paw reducing HFOV and CV groups, respectively (P¼0.686). In the HFOV

76
Emerging modes of ventilation in ICU BJA
group, 30 day mortality was 37% and 52% in the CV group controversial, since only 75% of patients allocated to the
(P¼0.102). However, this study was powered to demonstrate ECMO arm of the study actually received it and the benefit
equivalence rather than mortality. In addition, the study was seen may have been related to transfer to a tertiary centre
performed before the publication of the ARDSnet tidal experienced in managing patients with severe acute respirat-
volume trial,7 and the CV group did not receive a lung protec- ory failure; while the control patients were managed in the
tive ventilatory strategy that would now be considered pre- referring hospitals. ECMO has been used extensively as
ferable for such patients. rescue therapy in adults failing with conventional ventilatory
Bollen and colleagues34 have also published an RCT of strategies, particularly during and following the 2009 H1N1
HFOV vs CV, although their trial was stopped early due to influenza pandemic. Observational data from Australasian
poor recruitment. They failed to demonstrate a significant patients37 with confirmed or suspected H1N1 pneumonitis
difference in mortality between the HFOV- and CV-treated treated with ECMO reported 21% mortality at the end of
groups (43% vs 33%, P¼0.59), or in indices of gas exchange. the study period, compared with a .90% mortality seen in
The results of this trial are difficult to interpret due to its both groups in the first RCT.40
small size (61 patients) and difference in baseline OI ECMO is an invasive procedure requiring specific skills and
(HFOV¼25, CV¼18). personnel, as wide-bore cannulae are required (typically
The results of these two trials and six others are included 21–23 FG in adults) to gain the flow rate necessary to
in the meta-analysis conducted by Sud and colleagues.35 achieve adequate oxygenation (typically 3.5– 5 litre min21).
This includes two trials recruiting exclusively children. In Thus, it is likely that ECMO in this form will continue to be pro-
the 365 patients for whom mortality data were available, vided in specialist centres and remain outside the remit of
they found that patients assigned to HFOV had a significantly the majority of ICUs. As is the case with the normal lung,
lower mortality (risk ratio 0.77, P¼0.03) compared with those high blood flow rates are required because oxygen is
assigned to CV. They also found that HFOV was associated carried predominantly bound to haemoglobin (total concen-
with significantly lower treatment failure (hypoxaemia, tration in blood being 200 ml litre21). Transfer of oxygen
refractory hypercapnia, hypotension, barotrauma), resulting across the membrane is saturation-dependent (mixed
in discontinuation of the assigned therapy (risk ratio 0.67, venous and membrane inlet being around 65–70%); there
P¼0.04). The applicability of these findings is limited by the is an upper limit of oxygen carriage because saturation
heterogeneity of the trials, and the lack of lung protective cannot exceed 100%. In contrast, CO2 is predominantly
ventilation used in the control groups of most of the trials carried dissolved in blood, as bicarbonate (normal being
included. around 500 ml litre21); and in this case, there is (theoreti-
HFOV has an established role in the management of cally) no maximum. Transfer of CO2 across the membrane
refractory hypoxaemia in neonates, although its role in is partial pressure-dependent.41 Given that human CO2 pro-
adults is not yet clear. Data from extracorporeal membrane duction is 250 ml min21, it is conceivable that an efficient
oxygenation (ECMO) studies suggest that HFOV is presently system could achieve CO2 clearance at considerably lower
in widespread use as a rescue strategy in patients with flows than conventional ECMO, thus utilizing a system invol-
refractory hypoxaemia.36 37 The effects of frequency and ving flows and cannulae comparable with renal replacement
Paw on degree of VILI seen with HFOV are not known, and therapy.
parallels with CV are probably misleading. Two large multi- The use of extracorporeal CO2 removal (ECCO2R) in
centre randomized trials are currently being conducted, humans was first reported in the 1980s.42 43 Gattinoni and
OSCAR based in the UK (ISRCTN10416500) and OSCILLATE colleagues reported a case series of 43 patients with severe
based in Canada (ISRCTN87124254), which each aim to acute respiratory failure of parenchymal origin. They
recruit more than 1000 patients with early ARDS using low instituted veno-venous extracorporeal CO2 removal with
tidal volume ventilatory strategies as a control. Until these combinations of femoral –jugular, dual-lumen femoral, and
studies report the beneficial effects of HFOV for adults in saphenous– saphenous cannulation. The circuit incorporated
the post-ARDSnet era remain uncertain. two membrane lungs with a total area of 9 m2 which were
ventilated with a humidified mixture of 15 litre min21 each
of oxygen and air. Patients’ lungs were ventilated with low
Extracorporeal ventilation frequency, positive pressure ventilation at a rate of 3– 5
ECMO was first utilized in the management of respiratory bpm, with PEEP of 15–25 cm H2O and peak inspiratory
failure in the 1970s.38 Since then the Extracorporeal Life pressure of 35–45 cm H2O. Mortality was 51.2% in a group
Support Organisation has a registry of more than 27 000 neo- of patients who fulfilled exactly the same entry criteria
nates, 9000 children, and 2500 adults who have been treated as a previous study which had a mortality of .90%.40 They
with ECMO.39 The first RCT investigating the role of ECMO in concluded that low flow positive pressure ventilation made
adults with severe acute respiratory failure in the era of possible because CO2 was removed using ECCO2R was likely
lung protective ventilatory strategies (the CESAR trial)36 to be less harmful than conventional positive pressure venti-
suggests a significant reduction in death or severe disability lation, and that this accounted for the apparent improve-
in those allocated to an ECMO-based management protocol ment in mortality. In 1994, Morris and colleagues44
compared with CV (relative risk¼0.69). This trial has proved published the results of an RCT in which 40 patients with

77
BJA Stewart et al.

severe ARDS were randomized to either CV or ECCO2R and

pressure-controlled inverse ratio ventilation. There was no
significant difference in 30 day mortality, although this was
a small study in real terms.
More recently a pumpless extracorporeal device (inter-
ventional Lung Assist; iLA, Fig. 3) has been developed
which utilizes cannulae in the femoral artery and vein,
with a very low resistance, high efficiency membrane for
gas exchange. It utilizes relatively small cannulae (13–15
FG arterial, 15– 17 FG venous) and the driving pressure is
the arterio-venous pressure difference. Preliminary experi-
ence of 90 patients with ARDS demonstrated an improve-
ment in mean PaO2 /F IO2 ratio from 58 mm Hg before
institution to 82 mm Hg after 2 h and 101 mm Hg after
24 h.45 Hypercapnia was promptly and rapidly reversed,
with mean PaCO2 after 2 h decreasing from 60 to 36 mm FA FV
Hg. This allowed a significant reduction in peak inspiratory
pressure, FIO2 , and minute ventilation over the first 24 h. A
Flow probe
further study from the same group demonstrated significant
reductions in plateau pressure, tidal volume, and PaCO2 and
increase in PaO2 /F IO2 ratio and pH within 2 h of commencing O2
iLA.46 This system utilizes percutaneous cannulae and
single-use, pump-free circuits that could be used in any
ICU. Flow required for adequate CO2 removal can be as
low as 1–1.5 litre min21. iLA has been used to facilitate
the transfer of patients by air or road from hospitals to a
specialized ECMO unit when the patient’s condition dictated
conventional transfer was not possible.47 One possible
concern with iLA is vascular complications; in the initial Fig 3 The iLA-system. A passive femoro-femoral shunt flow
study,44 there was a serious complication rate of 24%, the generated by the arterial pressure passes a lung assist device
most common of which was limb ischaemia, and although (in the box), in which an oxygen flow is inserted. Reproduced
most patients recovered after removal of the arterial cannu- with permission from Zimmerman and colleagues.47 & The
lae one required an amputation. The serious complication Board of Management and Trustees of the British Journal of
rate was lower in the further study at 11.9%,46 which the Anaesthesia 2005. All rights reserved. For Permissions, please
email: journals.permissions@oxfordjournals.org.
authors believe was related to ultrasound assessment of
vessels before cannulation and selection of smaller cannu-
lae where appropriate. Proportional-assist ventilation
Although the iLA system conveys the advantage of pump- Proportional-assist ventilation (PAV) seeks to optimize the
less technology, an alternative system has been developed degree of ventilatory support delivered according to the
which utilizes a dual-lumen 14 FG femoral venous cannula patient’s ventilatory drive. It utilizes the rate and volume of
that can effectively reduce PaCO2 at flow rates of around 350 gas flow in the inspiratory limb of the ventilator circuit and
ml min21. It utilizes a membrane surface area of just 0.33 user-determined gain factors (to account for the elastic and
m2. As part of a management strategy which incorporates resistive opposing forces) to deliver pressure support in pro-
reduction in tidal volume to ,6 ml kg21 in patients with per- portion to patient effort.49 This is according to the ‘equation
sistent ARDS, Terragni and colleagues48 have demonstrated of motion’, which states that the pressure applied in the respir-
an improvement in CT morphological features of lung injury atory muscles must overcome elastic forces; proportional to
and a reduction of inflammatory cytokines in bronchoalveolar volume and the resistive forces; proportional to flow rate
lavage fluid. (Fig. 4). The ventilatory support delivered to the patient can
If CO2 removal can be adequately achieved with an extra- be varied both in terms of volume assist (VA) and flow assist
corporeal circuit which has an equivalent cannula and circuit (FA). The support delivered can change on a breath-to-breath
to haemofiltration, it has the potential to be accessible to the basis, introducing patient-controlled variability to the breath-
majority of ICUs. If CO2 removal is no longer a necessary ing pattern rather than having one imposed by the settings
requirement of lung ventilation, it has the potential to signifi- of the ventilator.49 If the patient generates more respiratory
cantly reduce plateau pressure, tidal volume, and cyclical effort, more support will be delivered.
alveolar collapse and distension and thus the injurious fea- In initial physiological trials, PAV has been found to suc-
tures of mechanical ventilation. Whether this translates to cessfully unload respiratory muscles, and decrease sensation
an outcome benefit remains unanswered. of breathlessness in acute respiratory failure.50 51 PAV

78
Emerging modes of ventilation in ICU BJA
by using the neural stimulus to those respiratory muscles
Pmus=V¥E+V’¥R to trigger the ventilator simultaneously with muscular
effort.61
With PAV: Pmus=V¥(E-VA)+V’¥(R-FA)
This triggering is achieved through detection of the elec-
Pmus=pressure in respiratory muscles trical activity of the diaphragm (EAdi) as it is stimulated by
V=volume displacement R=resistive forces
V’=flow rate VA=volume assist the respiratory centre via the phrenic nerve by means of an
E=elastic forces FA=flow assist array of bipolar electrodes mounted on a nasogastric tube.
Signals from each electrode are amplified and filtered to
Fig 4 The equation of motion. remove noise and interference from other electrical activity
such as that generated by the heart or oesophageal peristal-
sis. Analysis of signals recorded from pairs of electrodes
successfully allows patients to adapt their breathing pattern allows determination of the position of the electrically acti-
after a hypercapnic stimulus in a manner closer to normal vated diaphragm and tracking of this position, as it moves
physiology than those on PSV; minute ventilation is along the array during respiratory movements. This results
enhanced in PAV by increasing tidal volume rather than in reliable isolation and recording of EAdi throughout inspi-
rate.51 PAV has also been shown to adapt to artificial increase ration.61 62 This signal can then be passed to a connected
in respiratory work better than PSV; minute ventilation was ventilator triggering it to deliver support. In the event of
maintained by increasing the delivered pressure rather than loss of EAdi signal, the ventilator defaults to conventionally
by increased rate and was associated with less increase in delivered breaths.
respiratory muscle work and dyspnoea.52 The other apparent In addition to triggering the ventilator, EAdi is used to
advantage of PAV over PSV is an improvement in patient- determine the level of pressure support provided. As EAdi is
ventilatory synchrony by reducing the occurrence of missed recorded and passed to the ventilator in real time, and
efforts, where the patient makes effort to attempt to take since it varies both through a single inspiration and
a breath but fails to trigger the ventilator.53 54 between inspirations, the amount of support provided can
One limitation of PAV is a requirement to quantify the be continuously adjusted in direct proportion to the acti-
elastic and restrictive properties of the lung in each patient vation of the diaphragm. The ventilator is set to deliver
before ventilator settings can be determined. If this is not support by applying a gain factor, or NAVA level (in cm H2O
carried out and the gain factors over correct these properties, mV21), to the recorded EAdi. Thus, the pressure delivered
then a phenomenon called ‘run away’ can develop where the increases with EAdi through a breath until the cycling-off cri-
ventilator enters a positive feedback loop where the pressure teria are reached, typically a defined percentage decrease in
delivered by the ventilator generates sufficient flow and EAdi. Since EAdi is centrally controlled by the patient’s respir-
volume delivery to trigger further increase in pressure.50 53 atory centre via the phrenic nerve, the ventilator is essen-
As lung mechanics are not static it has been suggested tially coupled to this system and is also under the control
that for PAV to be effective, continuous monitoring is necess- of the patient.61
ary in order to ensure run away is avoided.50 52 Neurally adjusted ventilatory assist has been successfully
The addition of automated techniques to measure ela- used in a range of patients and situations, including neonatal
stance55 and resistance56 without interruption of ventilation and paediatric populations,63 – 66 adults with ARDS,67 or acute
has been termed PAV+.57 In this mode, the gain factors are respiratory failure of postoperative68 or mixed causes69 – 73
continuously adjusted to account for a user-determined frac- and also in conjunction with other means of respiratory
tion of measured elastance and resistance which should support such as ECMO.74 – 76 It has also been demonstrated
prevent over- or under-assist in the context of changing to effectively offload respiratory muscle work, both in
lung dynamics. PAV+ has been demonstrated to be safe healthy subjects77 and the critically ill.72 Of particular impor-
and feasible in patients, both awake56 and asleep57 and tance for the safe use of this technology is the finding that at
require fewer adjustments to ventilator settings and sedation the highest NAVA levels, where the inspiratory muscles are
than PSV.58 59 As yet, outcome data for PAV+ are limited, but almost completely offloaded, there is a reduction in electrical
it has been shown to reduce patient ventilator dyssyn- activity in the diaphragm and therefore a limitation to the
chrony59 60 and to be associated with a lower failure rate pressure delivered.77 This feedback has potential advantages
in ventilator weaning than PSV.58 59 Until more studies in the patient ventilated with NAVA in avoiding injurious tidal
comparing outcome on PAV+ with conventional ventilator volumes.
modes, its best use or superiority cannot be determined. One benefit of NAVA appears to be improvement in
patient-ventilator synchrony when compared with com-
Neurally adjusted ventilatory assist monly used PSV.64 69 – 71 Patients ventilated with NAVA do
If a pressure or flow change within the ventilator circuit is not experience the increased tidal volumes and reduced
used to initiate a ventilator-supported breath, there is inevi- ventilatory frequency seen at higher levels of PSV. 67 69 – 71
tably some delay between the initiation of effort by the res- As such, NAVA should prevent dynamic hyperinflation which
piratory muscles and the delivery of support. Neurally has been implicated as the major factory in asynchrony,67
adjusted ventilatory assist (NAVA) aims to avoid this delay and since asynchrony has been associated with longer ICU

79
BJA Stewart et al.

stays,78 it may be expected, although has yet to be demon- variables could include pulmonary resistance, elastance,
strated, that the use of NAVA may shorten patient stay in ICU. and compliance but perhaps the ventilator will be able to
As expected, NAVA is also associated with shorter trigger automatically compensate for gas exchange disturbances
delays between the onset of inspiratory effort and the deliv- also. On another track, it may be that with developments
ery of support,67 70 71 and it has been reported that NAVA in gas exchange membrane technology connecting a
eliminates ‘wasted efforts’ where a patient makes inspiratory patient to a mechanical ventilator may be a thing of the
effort but fails to trigger the ventilator.70 71 This contributes past. In the future, we would ask for the patient to be con-
to NAVA, reducing the work of breathing by ensuring the res- nected to the gas exchange membrane in much the same
piratory muscles are supported throughout inspiration and way that we use continuous haemofiltration circuits at
energy is not wasted in failed attempts to initiate support. present.
Karagiannidis and colleagues74 have investigated the role
of NAVA on patients requiring ECMO. The alternative source of
oxygenation and elimination of carbon dioxide allows venti- Conclusions
latory drive, and hence EAdi, to decrease. Patients appear to The modalities available for mechanical ventilation in the
automatically adopt a lung-protective pattern of ventilation, ICU continue to expand and evolve. While there is evidence
with low tidal volumes and respiratory frequency, while that many of these modes confer benefit in terms of gas
retaining the ability to vary that pattern and hence retain exchange,14 15 31 – 33 we know from previous trials that an
control of CO2 and acid –base homeostasis that may other- improvement in gas exchange does not necessarily correlate
wise become deranged when such a pattern is imposed. with an improvement in outcome.7 80 Until we have evidence
The pattern of breathing of patients on NAVA is inherently of outcome benefit from RCTs, these strategies will remain
variable as opposed to the uniform breaths of fixed rate and unproven.
volume or pressure of normal ventilation.72 This is of particu-
lar significance for ventilator weaning where increased varia-
bility following removal of ventilator support has been Conflict of interest
associated with greater success of maintained separation
None declared.
from the ventilator.79
Another reported benefit of NAVA is that successful venti-
lation with NAVA demonstrates the presence of an intact
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