LITERATURE REVIEW

doi: 10.1111/nicc.12205

Optimal support techniques when

providing mechanical ventilation to
patients with acute respiratory
distress syndrome
Stelios Parissopoulos, Meropi DA Mpouzika and Fiona Timmins

ABSTRACT
Background: Adult respiratory distress syndrome (ARDS) is a type of acute diffuse lung injury characterized by severe inflammation, increased
pulmonary vascular permeability and a loss of aerated lung tissue. The effects of high fraction of inspired oxygen (FiO2 ) include oxygen toxicity
manifested by damage to the lung parenchyma in the acute phase of lung injury. There is still a high mortality rate among this group of patients,
so clinically sensitive evidence-based interventions are paramount to maximize survival chances during critical care.
Aims and objectives: The aim of this article is to explore the current opinion concerning optimal mechanical ventilation support techniques
for patients with acute respiratory distress syndrome.
Search strategy, inclusion and exclusion criteria: A literature search of clinical trials and observation studies, reviews, discussion
papers, meta-analyses and clinical guidelines written in English up to 2015, derived from the databases of Scopus, CINAHL, Cochrane Library
databases and PubMed was conducted.
Conclusions: Low tidal volume, pressure limitation and prone positioning in severe ARDS patients appear to be of some benefit. More
research is required and further development and use of standardized protocols is an important strategy for reducing practice variations across
disciplines, as well as giving clear guidelines to nurses practising in critical care. There is also evidence that this syndrome is under-diagnosed and
the utilization of lung protective ventilation is still variable.
Relevance to clinical practice: It is important that nurses have underlying knowledge of both aetiology of ARDS and ventilation
management, and that they monitor patients very closely. The adoption of a low tidal ventilation protocol, which is based on quality evidence
guidelines, the value of rescue therapies and patient observation practices in the overall patient management, and the need to place emphasis
on long-term patient outcomes, all these emerge as key factors for consideration and future research. However, there is also a need for more
research that would explore the unique contribution of nurses in the management of this patient group, as it is difficult to discern this in the
current literature.
Key words: Adult intensive care • ARDS • Lung protective ventilation • Mechanical ventilation • Pressure limitation • Tidal volume

Authors: S Parissopoulos, PhD(c), MMedSci, BSc (Intensive Care
Pathway), RN, Lecturer in Nursing, Department of Nursing, Technological
Educational Institute (T.E.I.) of Athens, Egaleo, Greece; M DA Mpouzika,
PhD, MSc, RN, Lecturer in Critical Care Nursing, School of Nursing, Cyprus
University of Technology, Limassol, Cyprus; F Timmins, PhD, MSc, MA,
FFNRCSI, BNS, BSc (Open), BA (Open), RNT, RGN, Associate Professor,
School of Nursing and Midwifery, Trinity College, Dublin, Ireland
Address for correspondence: S Parissopoulos, Lecturer, Department
of Nursing, Technological Educational Institute (T.E.I.) of Athens, Egaleo
12243, Athens, Greece.
E-mail: spariss@teiath.gr
INTRODUCTION
Acute respiratory distress syndrome (ARDS) is a type
of acute and diffuse lung injury characterized by severe
inflammation, increased pulmonary vascular perme-
ability and loss of aerated lung tissue (Carlucci et al.,
2014). The first description of ARDS appeared in 1967,
when Ashbaugh et al. (1967) described 12 patients with
acute respiratory distress, in order to differentiate it
from immaturity and infant respiratory distress (Oeck-
ler and Hubmayr, 2007).
Currently, there are no specific therapies for ARDS
that are widely and unequivocally recommended,

© 2015 British Association of Critical Care Nurses 1

 Acute respiratory distress syndrome
except for mechanical ventilation with low tidal
volumes (TVs) (Girard and Bernard, 2007; Petrucci
and De Feo, 2013). Patient management focuses on
supportive therapy, avoiding complications and iden-
tifying/treating the underlying cause (Bastarache
et al., 2011). Even though the management of ARDS
has improved in the last 20 years and survival rates
have shown some improvement (Walkey et al., 2012),
it is unclear whether this is the result of improvements
in ARDS management and/or overall advancements
in critical care medicine (Erickson et al., 2009; Car-
lucci et al., 2014). However, among patients who
receive low TV ventilation, mortality rates remain
high, so additional treatments for ARDS are needed
(Walkey et al., 2012). Reports also suggest that ARDS
is still under-diagnosed in clinical practice (Fröhlich
et al., 2013).
BACKGROUND
Variability of definitions, under-diagnosis, demo-
graphic and health system differences and variations
in study designs make it difficult to estimate accu-
rately the incidence of ARDS (Bastarache et al., 2011).
Studies support that 5% of mechanically hospitalized
ventilated patients develop ARDS (Walkey et al., 2012).
ARDS still carries high mortality (typically 27–45%)
(Phua et al., 2009; Villar et al., 2011; Tonelli et al., 2014),
and although worsening oxygenation is a risk factor
for ARDS mortality, patients typically die from pro-
gressive underlying cause (serious illness or trauma)
(Sigurdsson et al., 2013), sepsis, multi-organ failure
and from refractory hypoxaemia, which accounts for
less than 15% (Villar et al., 2011; Kacmarek et al., 2012;
Esteban et al., 2013; Tonelli et al., 2014). It is worth
noting that mortality varies according to the severity
of oxygenation deficit. For example, in the Berlin
definition clinical study cohort (Ranieri et al., 2012),
mortality was 27% in patients with mild ARDS, 32% in
those with moderate ARDS and 45% in patients with
severe ARDS.
There are also short- and long-term morbidity
effects. Short-term morbidity leads to a prolonged
stay in the intensive care unit (ICU) and prolonged
ventilator dependence (Davidson et al., 1999). Those
who survive the illness have a reduced health-related
quality of life as well as cognitive impairment and
high rates of disability (Dowdy et al., 2006).
Although significant research efforts have focused
on reducing mortality rates associated with ARDS
(Williams, 2013), patients with ARDS provide a chal-
lenging situation to the ICU team in managing their
care. In fact, timely delivery of lung protective venti-
lation (LPV) appears to be beneficial in allowing time
2 © 2015 British Association of Critical Care Nurses
for the underlying disease process to improve and for
lung tissue to recover. Hence, a particular challenge
to ICU nurses is the effective care of those ventilated
patients who are suffering from ARDS. The treatment
of a patient with ARDS in ICU increases workload con-
siderably, and specialist knowledge is required. Addi-
tionally, as newer technology is increasingly common
in ICU, which addresses the complex treatment (e.g.
newer models of ventilators) and monitoring needs
of patients, this too necessitates specialist knowledge
and advanced clinical decision-making skills by ICU
nurses. Therefore, developing and retaining this spe-
cialist knowledge is challenging, especially as there
is also some controversy around treatment modali-
ties that can compound confusion in relation to best
evidence-based practice.
AIMS AND OBJECTIVES OF REVIEW
The aim of this narrative review is to provide an
overview of optimal mechanical ventilation in ARDS
patients, and to highlight areas of ambiguity in
research and clinical practice. Objectives include:
(1) to analyse and bring together quality evidence on
mechanical ventilation strategies for ARDS patients;
(2) to raise awareness on recent changes in the diagno-
sis of ARDS and on current evidence-based guidelines;
(3) to provide clear guidelines to nurses practising in
critical care.
DESIGN AND METHODS
The review method incorporated a search of Scopus,
CINAHL, Cochrane Library databases and PubMed
using the following keywords: acute respiratory dis-
tress syndrome, ventilation, tidal volume, critical care
and rescue therapies. Research papers and literature
written in English and published up to 2015 were
identified based on the relevance of their titles and
abstracts. The reference lists of the retrieved papers
were examined for additional citations, until it was felt
that papers that were considered important in ARDS
field would not be missed. This review looked at
empirical studies, systematic reviews, meta-analyses,
discussion papers, clinical articles and practice
guidelines that reported on physiological or clini-
cal outcomes of mechanical ventilation for adult ARDS
patients.
Pathophysiology in ARDS
An understanding of ARDS pathophysiology high-
lights the need to select the most appropriate
ventilation mode for patients as mechanical ven-
tilation contributes in various ways to lung injury

Table 1 Common risk factors for ARDS (York and Kane, 2012)
Direct lung injury Indirect lung injury
Aspiration of gastric contents Acute pancreatitis
Acute bacterial pneumonia Burns
Lung contusions Cardiopulmonary bypass
Near drowning Drug reaction
Neurogenic pulmonary oedema Drug overdose
Toxic inhalation (fumes or smoke) Fractures (multiple and long bone)
Toxic inhalation Upper airway obstruction
Upper airway obstruction Sepsis and septic shock
Pulmonary vasculitis Severe bleeding
Transplantation (bone or lung)
Non-cardiogenic shock
Trauma
Multiple transfusions or
transfusion-associated acute
lung injury (TRALI)
ARDS, acute respiratory distress syndrome.
(Tremblay and Slutsky, 2006) such as over-distension
of the diminished volume of functional lung tissue in
ARDS (Burns et al., 2011). There is also susceptibility
due to decreased respiratory system compliance,
and lungs are heterogeneously affected (Gatti-
noni et al., 2001) as some areas of the lung (often
dependent regions) are atelectatic, consolidated, less
compliant and thus less available for ventilation
while other areas (usually non-dependent regions)
appear and behave normally (Gattinoni and Pesenti,
2005).
The pathophysiologic process of ARDS can be
divided into three phases: acute exudative, fibropro-
liferative and resolution (Carlucci et al., 2014). No
matter its aetiology (Table 1), which may include
direct and indirect lung injuries (York and Kane,
2012), the alveolar-capillary membranes become leaky,
allowing fluids as well as proteins and blood cells to
enter the interstitial space (Carlucci et al., 2014). This
results in less fluid being pulled into the capillaries
due to increased oncotic pressure. The consequence is
non-cardiogenic pulmonary oedema, one of the key
findings in ARDS patients. Furthermore, the lungs
present an increase in hyaline membrane forma-
tion, development of fibroblasts, greater than before
number of alveolar type II cells, as well as inacti-
vation of pulmonary surfactant. Interstitial fibrosis
may also develop. Together, these factors worsen
gas exchange, decrease lung compliance and pro-
duce areas of atelectasis adjacent to normal tissue, all
of which increase the work of breathing (York and
Kane, 2012).
Overall, a markedly reduced volume of lung is avail-
able for ventilation in ARDS (Oeckler and Hubmayr,
© 2015 British Association of Critical Care Nurses
Acute respiratory distress syndrome
2007). Therefore, the manner in which mechanical
ventilator support is applied has the potential to exac-
erbate lung injury further due to the application of
TVs to the (reduced) area of non-consolidated alveoli
(Hong et al., 2010) and the development of inflam-
matory mediators associated with large TV usage
(Determann et al., 2010). This sort of evidence calls for
ICU nurses and doctors to be aware of the risks that
ARDS and non-ARDS patients undergo while they
are mechanically ventilated. Nevertheless, there is evi-
dence that some critically ill patients are still ventilated
with higher than desired TV (Fröhlich et al., 2013; Rose
et al., 2014), despite recognition of the potential inju-
rious effects to the lungs of high TV with mechanical
ventilation.
Diagnosis and definition of ARDS
As ARDS symptoms may not manifest for up to 72 h
after the initial insult, making association with the
cause is sometimes difficult (Fröhlich et al., 2013).
There has been a significant change in the definition
of ARDS and acute lung injury (ALI) since 2012 in
order to address its under-recognition of ARDS. ARDS
was for long time considered the most severe form
of hypoxic ALI, which resulted in respiratory failure
related to non-cardiogenic pulmonary oedema (York
and Kane, 2012). In 1994, the American-European
Consensus Conference (AECC) on ARDS had made a
statement with recommendations and definitions
in order to improve standardization of clinical
research (Bernard et al., 1994). This statement has
been used in most of the ARDS research. ALI was
designated for patients with significant hypoxaemia
[ratio of partial pressure of arterial oxygen to frac-
tion of inspired oxygen (PaO2 /FiO2 ) <300 mmHg],
while ARDS represented the subset of ALI patients
with the most severe lung injury (PaO2 /FiO2 ratio
<200 mmHg).
More recently, consensus was achieved in a panel
of experts convened in 2011 who agreed that ARDS
is a type of acute diffuse, inflammatory lung injury,
leading to increased pulmonary vascular perme-
ability, increased lung weight and loss of aerated
lung tissue (Ranieri et al., 2012). The clinical hall-
marks were deemed hypoxaemia and bilateral
radiographic opacities, associated with increased
venous admixture, increased physiological dead
space and decreased lung compliance. The mor-
phological hallmark of the acute phase is diffuse
alveolar damage (e.g. oedema, inflammation, hya-
line membrane or haemorrhage) (Pooler, 2009).
A draft definition proposed three mutually exclusive
categories of ARDS based on degree of hypoxaemia:
3
 Acute respiratory distress syndrome
Table 2 The Berlin definition of ARDS (Ranieri et al., 2012)
Acute respiratory distress syndrome
Timing Within 1 week of a known clinical insult or
new or worsening respiratory symptoms
Chest imaging∗ Bilateral opacities – not fully explained by
effusions, lobar/lung collapse or nodules
Origin of oedema Respiratory failure not fully explained by
cardiac failure or fluid overload. Need
objective assessment (e.g.
echocardiography) to exclude hydrostatic
oedema if no risk factor is present
Oxygenation†
Mild 200 mmHg < PaO2 /FiO2 ≤ 300 mmHg with
PEEP or CPAP ≥5 cm H2 O‡
Moderate 100 mmHg < PaO2 /FiO2 ≤ 200 mmHg with
PEEP ≥5 cm H2 O
Severe PaO2 /FiO2 ≤ 100 mmHg with PEEP ≥5 cm
H2 O
ARDS, acute respiratory distress syndrome; CPAP, continuous positive airway
pressure; FiO2 , fraction of inspired oxygen; PaO2 , partial pressure of arterial
oxygen; PEEP, positive end-expiratory pressure.
∗ Chest radiograph or computed tomography scan.
† If altitude is higher than 1000 m, the correction factor should be calculated as
follows: [PaO2 /FiO2 (barometric pressure/760)].
‡ This may be delivered non-invasively in the mild acute respiratory distress
syndrome population.
mild (200 mmHg < PaO2 /FiO2 ≤ 300 mmHg), moder-
ate (100 mmHg < PaO2 /FiO2 ≤ 200 mmHg) and severe
(PaO2 /FiO2 ≤ 100 mmHg) and four ancillary variables
for severe ARDS: radiographic severity, respira-
tory system compliance (≤40 mL/cm H2 O), positive
end-expiratory pressure (PEEP) (≥10 cm H2 O) and cor-
rected expired volume per minute (≥10 L/min). This
draft ‘Berlin’ definition was empirically evaluated
using patient-level meta-analysis of 4188 patients with
ARDS from four multi-centre clinical data sets and 269
patients with ARDS from three single-centre data sets
containing physiologic information. The four ancillary
variables did not contribute to the predictive validity
of severe ARDS for mortality and were removed from
the final definition (Table 2).
The clinical implications of the Berlin definition
of ARDS are of immense importance as a link is
maintained to prior definitions with diagnostic crite-
ria of timing, chest imaging, origin of oedema and
hypoxaemia (Ferguson et al., 2012). For the bilateral
opacities on chest radiograph criterion, a reference
set of chest radiographs was developed to enhance
inter-observer reliability. Overall, the Berlin definition
created a criterion of acuteness of disease onset, reclas-
sified the oxygenation criterion, included a minimum
PEEP value for the diagnosis, redefined the exclusion
criterion based on the presence of hydrostatic oedema
4 © 2015 British Association of Critical Care Nurses
and reformulated the radiologic criterion (Costa and
Amato, 2013). However, as Costa and Amato suggest
(2013), more studies are needed in order to evaluate
empirically the new diagnostic criteria and they pro-
pose potential improvements. They suggest the use of
data over the first 24 h to reclassify the severity of the
disease and the use of compliance to stratify each oxy-
genation category.
RESULTS ON TREATMENT
INTERVENTIONS
The findings were synthesized and are presented in
thematic categorization. Overall, the analysis focused
on empirical studies, meta-analyses and one Cochrane
review. It is important to note that only two guidelines
for practice were retrieved, where the respective work-
ing groups reviewed the available evidence according
to the principles of the Grading of Recommendations
Assessment, Development and Evaluation (GRADE)
system. This is a system that guides reviewers in the
assessment of quality of evidence from high (A) to very
low (D), and assists them in determining the strength
of recommendations as 1 (strong recommendation) or 2
(weak suggestion) (Dellinger et al., 2013; Claesson et al.,
2015).
Conventional treatment of ARDS continues to be
supportive, involving methods to optimize oxygena-
tion and allow time for the underlying disease process
to improve and for lung tissue to recover (Wong and
Vuylsteke, 2011), as no effective pharmacological ther-
apies have been found (Williams, 2013). Treatment for
ARDS is multifaceted and relies on parameters of ven-
tilation, commonly used medication, positioning the
patient and its effects on gas exchange, fluid manage-
ment and nutritional support (York and Kane, 2012).
For the purposes of this article, the discussion will
focus on optimal mechanical ventilation techniques.
However, it is important to remember that successful
approaches to treatment rely on a holistic approach
aimed at treating the condition and its contributory fac-
tors (York and Kane, 2012).
Principles in mechanical ventilation
Mechanical ventilation represents the main therapeu-
tic support to maintain acceptable pulmonary gas
exchange whilst treating the underlying disease. Most
patients will require a period of ventilatory support
(Burns et al., 2011). It is worth noting that inappro-
priately applied mechanical ventilation may cause
ARDS or increase its severity (Ranieri et al., 2012).
Therefore, it is vital that clinicians caring for venti-
lated patients have appropriate levels of specialist
knowledge and skills to manage patient–ventilator

interactions, recognize complications and intervene
appropriately.
This specialist knowledge owes a lot to earlier clini-
cal and experimental studies that implicated the deliv-
ery of excessive mechanical stress through mechanical
ventilation in the generation or perpetuation of lung
injury (Carlucci et al., 2014). It has been accepted for
some time that mechanical ventilation may cause strain
and shear forces on lung epithelial and endothelial
cells (Gattinoni and Pesenti, 2005) which increases local
inflammation (Held et al., 2001; Walkey et al., 2012).
Early studies suggested that ventilation strategies that
(1) limited TVs, (2) limited plateau pressures and (3)
limited both of these parameters were beneficial in pre-
venting or reducing damage in ARDS patients (Brower
et al., 2000). However, this research may also reflect the
less advanced ventilator models that were in use at
that time. Nowadays, mechanical ventilators are able to
deliver mandatory and spontaneous breaths in a more
sensitive manner, offering varying levels of weaning
support to patients from the early stages of critical
illness.
Lung protective ventilation strategies
Nowadays, the main supportive therapy for ARDS is
positive pressure mechanical ventilation to help main-
tain adequate oxygenation (Carlucci et al., 2014). LPV
may be delivered, either by close monitoring of peak
and plateau pressure with a volume-controlled mode
or through the use of pressure-controlled modes (Este-
ban et al., 2000, 2008). At the same time, LPV using a
low TV is the standard of care.
In relation to the appropriate size of TV in mechan-
ical ventilation, providing a TV of 10–12 mL/kg of
predicted body weight (PBW) is a practice that is old
and therefore historical. The recommended approach
to treatment with LPV is to aim for or set the initial
TV at 6 mL/kg of PBW (evidence grade 1A) (Dellinger
et al., 2013; Carlucci et al., 2014) or 5–8 mL/kg of PBW
(Claesson et al., 2015). Other lung protective ventila-
tion strategies (LPVS) include moderate to high PEEP,
high-frequency oscillatory ventilation (HFOV), extra-
corporeal membrane oxygenation (ECMO) therapy,
prone positioning and inhaled pulmonary vasodila-
tors, although definitive trials identifying consistently
improved patient outcomes are still needed (Rose,
2010; Claesson et al., 2015). At this point, it is worth
noting that most of the studies and reviews up to 2012
had adopted the AECC definition of ARDS, where the
term ALI was reserved for PaO2 /FiO2 ≤ 300 mmHg,
whereas the term ARDS represented the subset of
ALI patients with the most severe lung injury, with
PaO2 /FiO2 ≤ 200 mmHg.
© 2015 British Association of Critical Care Nurses
Acute respiratory distress syndrome
In the systematic meta-analysis by Putensen et al.
(2009), the authors tried to determine whether ventila-
tion with low TV and limited airway pressure or higher
PEEP improved outcomes for patients with ARDS.
They concluded that routine use of low TV is benefi-
cial and reduces mortality. A recent Cochrane review
showed that a gentler form of mechanical breathing
could reduce mortality in the short term, by 26% on
average, but the effects in the long term were still
uncertain or unknown (Petrucci and De Feo, 2013).
We now know that higher TVs can over-inflate and
injure remaining areas of normal lung tissue (Bas-
tarache et al., 2011). Key goals to mechanical venti-
lation in ARDS include the following: maintaining
safe alveolar pressures, preventing overstretch injury,
re-expanding collapsed alveoli and preventing further
collapse and avoiding the atelectrauma that can be
caused by shear forces of tearing open the alveoli (Bas-
tarache et al., 2011). Dellinger et al. (2013) recommend
that clinicians should use as a starting point the objec-
tive of reducing TV over 1–2 h from its initial value
towards the goal of a ‘low’ TV (approximately 6 mL/kg
PBW) achieved in conjunction with an end-inspiratory
plateau pressure ≤30 cm H2 O. They recommend that
plateau pressures be measured and that the initial
upper limit goal for plateau pressures in a passively
inflated lung should be ≤30 cm H2 O (grade 1B). If the
plateau pressure remains >30 cm H2 O after reduction
of TV to 6 mL/kg PBW, their guidelines suggest that
TV may be reduced further to as low as 4 mL/kg PBW
(Dellinger et al., 2013). The importance of maintaining
plateau pressure ≤30 cm H2 O becomes more appar-
ent as this is also highly recommended (strong evi-
dence) by another guideline on mechanical ventilation
in adults with ARDS, authored by the Clinical Practice
Committee of the Scandinavian Society of Anaesthe-
sia and Intensive Care Medicine task force (Claesson
et al., 2015).
As the syndrome progresses and lung tissue
becomes more damaged, there is a call for syn-
chronized management. There should be a fine
balance of the use of FiO2 , taking into considera-
tion that the likelihood of oxygen toxicity increases
with prolonged use of FiO2 > 60%. In addition, the
ventilation-perfusion mismatch and intrapulmonary
shunting lead to severe hypoxia (York and Kane,
2012). Lowering TVs often leads to higher number
of respiratory rates; 15–25 breaths/min are common,
in order to maintain an adequate minute ventilation
for gas exchange (York and Kane, 2012). With these
higher respiratory rates, patients are more likely
to air trap gas resulting in auto-PEEP or intrinsic
PEEP (Durante et al., 2002). This is especially true
when the inspiratory-to-expiratory ratio becomes
5
 Acute respiratory distress syndrome
closer to 1:1 or is inversed with inspiration longer
than expiration. However, it is hypothesized that
auto-PEEP may play a key role in the success of the low
TV/high respiratory rate treatment modality (Durante
et al., 2002).
It is accepted practice that LPV may be applied
with either volume- or pressure-controlled ventila-
tion. In volume-controlled ventilation, the ventilator
delivers a specific TV with little concern as to the
pressure required to deliver the breath. Practitioners
set a ‘high pressure limit’ to ensure that excessive
pressures are not reached. Reports support that when
the ARDS patient’s pressure climbs and reaches or
exceeds plateau pressures of 30 cm H2 O, the health
care team may consider using pressure-controlled
ventilation (Sulemanji et al., 2009). In this case, the
ventilators deliver a practitioner-set pressure, whereas
the TV varies based on the patient’s lung compliance
and airway resistance. By using a preset pressure,
the team can ensure that the ARDS patient maintains
safe plateau pressures. Pressure-controlled ventilation
also allows regulation of injurious peak inspiratory
pressures. However, no study has identified the supe-
riority of pressure-controlled ventilation over low TV
strategies using volume control (weak suggestion)
(Dellinger et al., 2013; Claesson et al., 2015). Same
principles should be used irrespective of mode, as a
number of observational trials in mechanically ven-
tilated patients have also demonstrated a decreased
risk of developing ARDS when smaller TVs are used
(Determann et al., 2010). Accordingly, high TVs and
high plateau pressures should be avoided in patients at
risk of developing ARDS, including those with sepsis
(Dellinger et al., 2013).
Permissive hypercapnia occurs as a consequence
of mechanical ventilation, when the health care team
allows the carbon dioxide levels to climb, in lieu of
further damaging the lungs from excessive ventilation,
especially when plateau pressure exceeds 30 cm H2 O
(Laffey et al., 2009). When using permissive hypercap-
nia, the health care team typically maintains the PaCO2
< 80 mmHg and the pH > 7⋅2. In addition, the PaO2 also
should remain > 60 mmHg.
PEEP and its titration appear to be another impor-
tant factor as well. A PEEP > 5 cm H2 O is usually
required to avoid lung collapse (Gattinoni et al., 2006).
Overall, high levels of PEEP have not conclusively
shown an improved survival (Brower et al., 2004;
Meade et al., 2008; Mercat et al., 2008). Putensen et al.
(2009) suggest that higher PEEP strategies with low
TV ventilation do not improve hospital mortality and
cannot be recommended in unselected patients with
ARDS, although they may prevent life-threatening
hypoxaemia. According to the ‘2012 International
6 © 2015 British Association of Critical Care Nurses
Guidelines for Management of Severe Sepsis and
Septic Shock’ (Dellinger et al., 2013), PEEP ought to be
used to avoid alveolar collapse (atelectotrauma) (grade
1B) and higher levels of PEEP to be used only for those
with sepsis-induced moderate to severe ARDS (grade
2C). This is also supported by Claesson et al. (2015)
(weak suggestion).
However, what remains unanswered is how to select
the optimal PEEP level that assists in lung recruit-
ment without causing lung over-distention (Walkey
et al., 2012). In relation to PEEP titration (Dellinger
et al., 2013), many approaches have been published,
including the following: (1) the use of a PEEP/FiO2
ratio, where PEEP is based on severity of oxygena-
tion deficit and guided by the FiO2 required to main-
tain adequate oxygenation (Brower et al., 2004; Meade
et al., 2008); (2) the use of the inflection points of the
lung pressure-volume curve (Amato et al., 1998); and
(3) the titration of PEEP to a maximal plateau pressure
of 30 cm H2 O (Mercat et al., 2008). Even so, the best
method to determine the optimal PEEP level for each
patient is unclear and is an important area of further
research (Walkey et al., 2012).
Rescue therapies
Early implementation of optimal ventilation is crucial
to minimize further deterioration in lung function
(Williams, 2013). However, although the aforemen-
tioned strategies will improve oxygenation for most
patients, these efforts will be insufficient in the most
critically ill ARDS patients (York and Kane, 2012).
Knowing that the underlying lung injury often contin-
ues to worsen despite optimal medical management,
clinicians must be aware of other available strate-
gies that may provide support for their patients and
improve overall outcomes. Despite appropriate treat-
ment, condition of some patients with ARDS continues
to deteriorate (Carlucci et al., 2014). The following res-
cue therapies might be considered for patients with
severe refractory hypoxaemia.
The health care team may consider using HFOV as
a treatment option for the most critically ill. HFOV
utilizes a respiratory rate ranging from approxi-
mately 240–600 breaths/min (Fessler and Hess, 2007;
York and Kane, 2012). This ventilation strategy is an
‘open-lung’ technique keeping the lung alveoli well
recruited to promote additional gas exchange (Fessler
and Hess, 2007). Two recent trials have shown no
survival benefit and a possible increased mortality
risk with the use of this type of ventilation in ARDS.
Based on these results, HFOV is currently not rec-
ommended (Rose, 2010; Carlucci et al., 2014; Wilson
and Matthay, 2014; Claesson et al., 2015) as standard
practice.

ECMO therapy is another additional intervention
that has been examined in patients with severe ARDS
with hypoxaemia that is refractory to conventional
ventilation management (Ranieri et al., 2012; Williams,
2013). Although the current evidence is not suffi-
cient to make finite recommendations for ECMO
therapy versus conventional management, results of
some studies using ECMO in ARDS are described
as encouraging, so consideration of transfer to an
experienced ECMO centre is warranted (Walkey et al.,
2012; Carlucci et al., 2014; Wilson and Matthay, 2014).
Perner et al. (2015) recommend the development of
tools in order to select patients who could benefit
from ECMO, as the delivery of ECMO is an expensive
option.
Prone positioning may improve oxygenation by
recruiting dependent lung units, redistributing blood
flow to the more unaffected lung regions, decreasing
ventilation-perfusion mismatching and facilitating
clearance of respiratory secretions (Carlucci et al.,
2014). However, it requires a coordinated effort and
expertise in the process of turning and positioning crit-
ically ill patients in order to avoid complications. Any
previous experience of the ICU team should therefore
be considered (Wilson and Matthay, 2014), and Perner
et al. (2015) suggest that prone positioning should be
done according to well-defined medical and nursing
protocols in each ICU.
Studies on prone positioning and improvement in
ARDS patients have reported similar, non-significant
overall effects, that might be explained by the fact that
these trials enrolled patients of variant ARDS severity
with different degrees of hypoxaemia (Perner et al.,
2015). However, three meta-analyses support a signif-
icant benefit for reducing mortality in patients with
severe ARDS (Kopterides et al., 2009; Sud et al., 2010;
Abroug et al., 2011), and Guérin et al. (2013) showed
a 28-day survival improvement in those patients
with moderate-to-severe ARDS who underwent prone
positioning. Additionally, two meta-analyses on ARDS
suggest that low TVs and prone positioning may need
to be applied concurrently in order to bring about more
consistent evidence on survival benefit. Tonelli et al.
(2014) showed significant mortality benefit when low
TVs and prone positioning were used in patients with
severe ARDS, and Beitler et al. (2014) demonstrated
that prone positioning was associated with a significant
decrease in the relative risk of mortality only in studies
using low baseline TV of < 8 mL/kg PBW. Despite
the heterogeneity between empirical studies, Claesson
et al. (2015) suggest the use of prone positioning for 16 h
for the first week in moderate to severe ARDS patients
(weak suggestion) as it appears to be a safe approach
in an ICU with expertise and previous experience.
© 2015 British Association of Critical Care Nurses
Acute respiratory distress syndrome
Its use is also recommended by the task force on
sepsis-induced ARDS (grade 2B) (Dellinger et al.,
2013).
In the past two decades, inhaled vasodilators such
as inhaled nitric oxide (iNO) and inhaled epoprostenol
(the synthetic form of prostacyclin) have been consid-
ered as a potential rescue therapy for severe, refractory
hypoxemia in ARDS patients (Arumpanayil, 2013). The
therapy is considered to selectively recruit blood flow
to the ventilated alveoli and spare non-ventilated areas
of lung parenchyma (Collins and Blank, 2011). The
delivery of the aerosolised vasodilator has proven to
increase arterial oxygenation and decrease pulmonary
artery pressure (PAP). They have been used as adjuncts
to LPVS in severe refractory hypoxaemia, but neither
of these modalities has proven survival benefit in any
study.
Despite iNO being effective in transiently improv-
ing oxygenation in some patients, all trials have
concluded that iNO does not improve the outcome in
ARDS patients and impaired renal function may be
a side effect (Adhikari et al., 2007; Perner et al., 2015).
Perner et al. suggest that there is a need to evaluate
the use of iNO during LPV as a rescue therapy prior
to ECMO, when mechanical ventilation and prone
positioning have failed to improve gas exchange. As
for inhaled epoprostenol, it may improve oxygenation
in refractory hypoxaemia and it has been gaining
favour as an equally effective but easier to admin-
ister and less expensive modality as compared with
iNO (Arumpanayil, 2013). Finally, based on the lack
of evidence in support of these therapies, inhaled
vasodilator therapy is not recommended as standard
practice for ARDS (Perner et al., 2015). Table 3 sum-
marizes the recommendations for ventilation in ARDS
patients.
DISCUSSION – IMPLICATIONS FOR
PRACTICE
Both primary and secondary end points are inconsis-
tently reported in the ARDS literature, which make it
difficult for clinicians to interpret research findings and
translate them into practice guidelines. For example,
there is lack of standardization in the time period in
which mortality in ARDS studies is reported, and this
variability makes it rather difficult for researchers to
compare the effects of different interventions (Tonelli
et al., 2014), and for clinicians to translate research into
evidence-based guidelines for practice. In addition,
studies of ARDS suffer from heterogeneity regarding
the underlying disease process and also the timing
of inclusion following ARDS development (Claesson
et al., 2015).
7
 Acute respiratory distress syndrome
Table 3 Recommendations for mechanical ventilation in ARDS patients
Intervention and aims
Ventilation mode: volume-controlled and pressure-controlled ventilation is
equally beneficial or detrimental
Pressure limitation during mechanical ventilation: plateau pressure ≤30 cm H2 O
Sepsis-induced ARDS: plateau pressures to be measured and initial upper limit
goal for plateau pressures in a passively inflated lung to be ≤30 cm H2 O
Tidal volume limitation during mechanical ventilation: small TVs of
5–8 mL/kg PBW
Sepsis-induced ARDS: target a tidal volume of 6 mL/kg PBW
PEEP >5 cm H2 O to be applied to avoid alveolar collapse at end of expiration
(atelectotrauma)
Sepsis-induced moderate or severe ARDS: Strategies based on higher rather
than lower levels of PEEP
High frequency oscillatory ventilation (HFOV) has shown no demonstrable
effect on mortality and therefore it is not recommended as standard practice
Extracorporeal membrane oxygenation (ECMO): current evidence is not
sufficient
Prone positioning: patient with ARDS to be treated in the prone position for at
least 16 h/day
Sepsis-induced ARDS: prone positioning to be provided to patients with a
PaO2 /FiO2 ratio ≤100 mmHg in facilities that have experience with such
practices
Inhaled pulmonary vasodilators: inhaled nitric oxide and inhaled epoprostenol:
neither of these therapeutic modalities have shown survival benefit
ARDS, acute respiratory distress syndrome; PBW, predicted body weight; PEEP, positive end-expiratory pressure; TV, tidal volume.
The leading cause of death in ARDS patients is
sepsis and resultant multiple organ failure (York and
Kane, 2012). With the exception of mechanical ven-
tilation with low TVs and plateau pressure ≤ 30 cm
H2 O, the rest of the discussed interventions are not
widely and unequivocally recommended (Girard
and Bernard, 2007; Claesson et al., 2015). At the same
time, Tonelli et al. (2014) urge caution with examining
single trials in isolation due to possible biases (Ioan-
nidis, 2005). For example, several trials in which the
intervention showed a potential beneficial effect were
stopped early, which can inflate estimates of treatment
effects (Putensen et al., 2009). Furthermore, in order
to understand fully which treatments can actually
reduce mortality in ARDS, it is critical and necessary
to examine an entire range of research with different
modalities, instead of focusing on single interventions
(Ioannidis and Karassa, 2010).
It is acknowledged that the focus of ARDS research
has shifted beyond ICU discharge to long-term out-
comes of the patients (Guérin and Girbes, 2014). For
example, ARDS patients surviving their ICU stay,
demonstrated decreased physical quality of life in
the very long term (Herridge et al., 2011). Even so,
reduction in mortality with LPV using low TVs and
pressure limitation with plateau pressure ≤30 cm H2 O
8 © 2015 British Association of Critical Care Nurses
Level of evidence and reference
Weak suggestion, very low quality evidence (Claesson et al., 2015)
Strong recommendation due to large effect on mortality (Claesson et al., 2015)
Strong recommendation, grade 1B (Dellinger et al., 2013)
Strong recommendation due to large effect on mortality (Claesson et al., 2015)
Strong recommendation, grade 1A (Dellinger et al., 2013)
(1) Strong recommendation, grade 1B (Dellinger et al., 2013), (2) Weak
suggestion, moderate quality evidence (Claesson et al., 2015)
Weak suggestion, grade 2C (Dellinger et al., 2013)
Strong recommendation, high-quality evidence (Claesson et al., 2015)
No recommendations (Walkey et al., 2012)
Weak suggestion, very low quality evidence (Claesson et al., 2015)
Weak suggestion, grade 2B (Dellinger et al., 2013)
No recommendations (Claesson et al., 2015)
is heralded as one of the biggest advances in the field.
This strategy of ventilation management requires
constant surveillance and decision making by a multi-
disciplinary team. It is vital that ICU nurses caring for
ARDS patients have appropriate levels of ventilator
management knowledge (Girard et al., 2008) and that
they can recognize complications, so that they inter-
vene in a timely manner (Rose, 2006). This requires
advanced knowledge of normal lung physiology as
well as pathophysiology, in-depth understanding
of ventilator technology, its clinical application and the
current evidence for effective ventilation strategies.
At the same time, there is urgency for nurses to
address patient needs in a holistic manner rather than
as a ventilator exercise, because morality rates cannot
be attributed solely to one single factor of patient man-
agement (Dellinger et al., 2013). For example, there is
also marked variability in the monitoring and ther-
apeutic interventions (Jones, 2011). In the absence of
standardized monitoring and intervention protocols,
nurses’ compliance with recommended LPVS can be
suboptimal. The use of standardized protocols is an
important strategy for reducing practice variations
across disciplines (Jones, 2011).
Another issue is that despite ARDS research demon-
strating a reduction in mortality (Petrucci and De
 Acute respiratory distress syndrome

Feo, 2013; Tonelli et al., 2014) and the development LIMITATIONS

of clinical guidelines supporting the use of LPVS, A range of research designs were reported on the
there are still some studies that suggest variable adop- retrieved studies, and no attempt was made to extract
tion of low TV strategy across ICUs (Kalhan et al., and pool data. This narrative review is limited as it is
2006; Fröhlich et al., 2013; Rose et al., 2014). Could not a systematic review, although it was felt that it has
this be happening due to under-diagnosis of ARDS included the most relevant and up-to-date literature in
by clinicians (Fröhlich et al., 2013)? This is an area the field of ARDS.
that would benefit from further exploration, as reports
suggest that timely recognition of ARDS and com-
mencement of PVLS are important determinants of
CONCLUSIONS
outcome and are essential for appropriate enrolment
There is a range of types of papers discussing current
to research studies (Rose, 2010). Lack of recognition
state of knowledge on ARDS and ventilation. These
by treating clinicians may result in the appropriate
papers may be clinically orientated with quality evi-
treatment being commenced too late, or not at all. In
dence guidelines for practice, randomized clinical
a recent study, only 31⋅3% of patients who fulfilled
trials, reviews, meta-analyses and discursive papers.
both clinical and pathological diagnoses of ARDS had
While low TVs, pressure limitation and prone posi-
any mention of ARDS in their clinical notes (Fröh-
tioning in patients with severe ARDS seem effective,
lich et al., 2013). The investigators concluded that not
most findings of other interventions are not corrob-
only is ARDS under-recognized by clinicians in ICU
orated consistently in large-scale evidence including
but also that ARDS diagnosis does not result always
meta-analyses (Petrucci and De Feo, 2013; Tonelli et al.,
in lower TV ventilation, as they found that those
2014). Thus, low TVs, pressure limitation and prone
with a clinical diagnosis, when corrected for body
positioning interventions are the only recommenda-
weight, were ventilated with higher TV (6⋅8 versus
tions presently receiving rigorous support (Dwan et al.,
6⋅7 mL/kg) and had higher PEEP and mean airway
2013).
pressures.
Nevertheless, it should be stressed that the utiliza-
We should also consider what kinds of barriers exist
tion itself of a standardized ventilation strategy
to the timely recognition of ARDS and application of
may be a significant step in reducing practice
an evidence-based LPVS. It could be argued that ICU
variations across disciplines, especially when the
clinicians are exposed to too much information from
frequency of both assessments and interventions
many data courses (clinical reports, monitors, results),
are addressed along with treatment goals (Jones,
and that education and feedback initiatives have had
2011). Identifying barriers in practice and focusing
questionable success in facilitating LPV. Concerns over
on evidence-based practice will streamline ARDS
patient’s discomfort, acidosis and hypoxaemia could
management, while ARDS research will benefit if
be another aspect of care we should look into (Fröh-
professionals start looking at ARDS prevention,
lich et al. 2013). In line with preventing lung injury,
long-term patient outcomes and the value of rescue
Fröhlich et al. suggest a ‘safe default state’ for all new
therapies.
patients, where the default setting for the ventilators is
Finally, it is critical that clinicians who treat patients
lung protective, and the ICU team will adjust upward
with ARDS reassess their current ventilation strate-
volumes if required.
gies, assimilate the available evidence and modify their
However, while reviewing ARDS literature, the con-
practices to ensure the highest quality of care and best
tribution of nurses to the management of ARDS is not
outcomes for their patients. Research dissemination is
sufficiently examined, as most research focuses mostly
important, as a culture of change and evidence-based
on the outcomes of mechanical ventilation, rather than
practice is prevalent in current health care services.
clinical decision-making processes or other nurse con-
Methods for increasing implementation of current
tributions. Indeed, there may be scope to advance nurs-
research findings are important opportunities for
ing practice in this field as evidence suggests benefits
future study, as the focus of ARDS clinical research
to early recognition of at-risk patients (Carlucci et al.,
over the next 10 years shifts towards the direction
2014). As part of the multidisciplinary ICU team, the
of securing more high-quality outcomes. Advancing
acute care nurse practitioner (ACNP), for example, can
nurse practice in the field, through the development
provide direct specialist care to patients in the ICU
of specialist and advanced positions, may contribute
and often get involved in quality-improvement activ-
positively to any such research endeavours and ensure
ities such as leading research, reinforcing adherence
more consistent and protocol-driven approaches to
to practice guidelines and educating the nursing staff
practice.
(Carlucci et al., 2014).

© 2015 British Association of Critical Care Nurses 9

 Acute respiratory distress syndrome
WHAT IS KNOWN ABOUT THIS TOPIC
• Acute respiratory distress syndrome (ARDS) is a type of acute diffuse lung injury characterized by severe inflammation, increased
pulmonary vascular permeability and loss of aerated lung tissue.
• ARDS remains under-recognized and this may lead to suboptimal care.
• Currently, there are no specific therapies for ARDS that are widely and unequivocally recommended, except for mechanical ventilation
with low tidal volumes and pressure limitation.
• There is a high mortality rate among ARDS patients.
• ARDS patients present a challenge for ICU nurses.
WHAT THIS PAPER ADDS
• It offers an overview of optimal ventilation techniques by reviewing quality evidence reviews and clinical guidelines.
• It clarifies ARDS research findings and translates them into easy to understand practice guidelines.
• It highlights the limited development of ARDS guidelines for mechanically ventilated patients.
• It brings up the need for further research in lung protective ventilation strategies (LPVS) and rescue therapies in ARDS.
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