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Documente Cultură
doi: 10.1111/nicc.12205
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
INTRODUCTION
Acute respiratory distress syndrome (ARDS) is a type
Authors: S Parissopoulos, PhD(c), MMedSci, BSc (Intensive Care of acute and diffuse lung injury characterized by severe
Pathway), RN, Lecturer in Nursing, Department of Nursing, Technological
inflammation, increased pulmonary vascular perme-
Educational Institute (T.E.I.) of Athens, Egaleo, Greece; M DA Mpouzika,
PhD, MSc, RN, Lecturer in Critical Care Nursing, School of Nursing, Cyprus ability and loss of aerated lung tissue (Carlucci et al.,
University of Technology, Limassol, Cyprus; F Timmins, PhD, MSc, MA, 2014). The first description of ARDS appeared in 1967,
FFNRCSI, BNS, BSc (Open), BA (Open), RNT, RGN, Associate Professor, when Ashbaugh et al. (1967) described 12 patients with
School of Nursing and Midwifery, Trinity College, Dublin, Ireland acute respiratory distress, in order to differentiate it
Address for correspondence: S Parissopoulos, Lecturer, Department
from immaturity and infant respiratory distress (Oeck-
of Nursing, Technological Educational Institute (T.E.I.) of Athens, Egaleo
12243, Athens, Greece.
ler and Hubmayr, 2007).
E-mail: spariss@teiath.gr Currently, there are no specific therapies for ARDS
that are widely and unequivocally recommended,
except for mechanical ventilation with low tidal for the underlying disease process to improve and for
volumes (TVs) (Girard and Bernard, 2007; Petrucci lung tissue to recover. Hence, a particular challenge
and De Feo, 2013). Patient management focuses on to ICU nurses is the effective care of those ventilated
supportive therapy, avoiding complications and iden- patients who are suffering from ARDS. The treatment
tifying/treating the underlying cause (Bastarache of a patient with ARDS in ICU increases workload con-
et al., 2011). Even though the management of ARDS siderably, and specialist knowledge is required. Addi-
has improved in the last 20 years and survival rates tionally, as newer technology is increasingly common
have shown some improvement (Walkey et al., 2012), in ICU, which addresses the complex treatment (e.g.
it is unclear whether this is the result of improvements newer models of ventilators) and monitoring needs
in ARDS management and/or overall advancements of patients, this too necessitates specialist knowledge
in critical care medicine (Erickson et al., 2009; Car- and advanced clinical decision-making skills by ICU
lucci et al., 2014). However, among patients who nurses. Therefore, developing and retaining this spe-
receive low TV ventilation, mortality rates remain cialist knowledge is challenging, especially as there
high, so additional treatments for ARDS are needed is also some controversy around treatment modali-
(Walkey et al., 2012). Reports also suggest that ARDS ties that can compound confusion in relation to best
is still under-diagnosed in clinical practice (Fröhlich evidence-based practice.
et al., 2013).
Table 1 Common risk factors for ARDS (York and Kane, 2012) 2007). Therefore, the manner in which mechanical
ventilator support is applied has the potential to exac-
Direct lung injury Indirect lung injury erbate lung injury further due to the application of
TVs to the (reduced) area of non-consolidated alveoli
Aspiration of gastric contents Acute pancreatitis
Acute bacterial pneumonia Burns
(Hong et al., 2010) and the development of inflam-
Lung contusions Cardiopulmonary bypass matory mediators associated with large TV usage
Near drowning Drug reaction (Determann et al., 2010). This sort of evidence calls for
Neurogenic pulmonary oedema Drug overdose ICU nurses and doctors to be aware of the risks that
Toxic inhalation (fumes or smoke) Fractures (multiple and long bone) ARDS and non-ARDS patients undergo while they
Toxic inhalation Upper airway obstruction are mechanically ventilated. Nevertheless, there is evi-
Upper airway obstruction Sepsis and septic shock
dence that some critically ill patients are still ventilated
Pulmonary vasculitis Severe bleeding
Transplantation (bone or lung) with higher than desired TV (Fröhlich et al., 2013; Rose
Non-cardiogenic shock et al., 2014), despite recognition of the potential inju-
Trauma rious effects to the lungs of high TV with mechanical
Multiple transfusions or ventilation.
transfusion-associated acute
lung injury (TRALI)
Diagnosis and definition of ARDS
ARDS, acute respiratory distress syndrome.
As ARDS symptoms may not manifest for up to 72 h
after the initial insult, making association with the
(Tremblay and Slutsky, 2006) such as over-distension cause is sometimes difficult (Fröhlich et al., 2013).
of the diminished volume of functional lung tissue in There has been a significant change in the definition
ARDS (Burns et al., 2011). There is also susceptibility of ARDS and acute lung injury (ALI) since 2012 in
due to decreased respiratory system compliance, order to address its under-recognition of ARDS. ARDS
and lungs are heterogeneously affected (Gatti- was for long time considered the most severe form
noni et al., 2001) as some areas of the lung (often of hypoxic ALI, which resulted in respiratory failure
dependent regions) are atelectatic, consolidated, less related to non-cardiogenic pulmonary oedema (York
compliant and thus less available for ventilation and Kane, 2012). In 1994, the American-European
while other areas (usually non-dependent regions) Consensus Conference (AECC) on ARDS had made a
appear and behave normally (Gattinoni and Pesenti, statement with recommendations and definitions
2005). in order to improve standardization of clinical
The pathophysiologic process of ARDS can be research (Bernard et al., 1994). This statement has
divided into three phases: acute exudative, fibropro- been used in most of the ARDS research. ALI was
liferative and resolution (Carlucci et al., 2014). No designated for patients with significant hypoxaemia
matter its aetiology (Table 1), which may include [ratio of partial pressure of arterial oxygen to frac-
direct and indirect lung injuries (York and Kane, tion of inspired oxygen (PaO2 /FiO2 ) <300 mmHg],
2012), the alveolar-capillary membranes become leaky, while ARDS represented the subset of ALI patients
allowing fluids as well as proteins and blood cells to with the most severe lung injury (PaO2 /FiO2 ratio
enter the interstitial space (Carlucci et al., 2014). This <200 mmHg).
results in less fluid being pulled into the capillaries More recently, consensus was achieved in a panel
due to increased oncotic pressure. The consequence is of experts convened in 2011 who agreed that ARDS
non-cardiogenic pulmonary oedema, one of the key is a type of acute diffuse, inflammatory lung injury,
findings in ARDS patients. Furthermore, the lungs leading to increased pulmonary vascular perme-
present an increase in hyaline membrane forma- ability, increased lung weight and loss of aerated
tion, development of fibroblasts, greater than before lung tissue (Ranieri et al., 2012). The clinical hall-
number of alveolar type II cells, as well as inacti- marks were deemed hypoxaemia and bilateral
vation of pulmonary surfactant. Interstitial fibrosis radiographic opacities, associated with increased
may also develop. Together, these factors worsen venous admixture, increased physiological dead
gas exchange, decrease lung compliance and pro- space and decreased lung compliance. The mor-
duce areas of atelectasis adjacent to normal tissue, all phological hallmark of the acute phase is diffuse
of which increase the work of breathing (York and alveolar damage (e.g. oedema, inflammation, hya-
Kane, 2012). line membrane or haemorrhage) (Pooler, 2009).
Overall, a markedly reduced volume of lung is avail- A draft definition proposed three mutually exclusive
able for ventilation in ARDS (Oeckler and Hubmayr, categories of ARDS based on degree of hypoxaemia:
Table 2 The Berlin definition of ARDS (Ranieri et al., 2012) and reformulated the radiologic criterion (Costa and
Amato, 2013). However, as Costa and Amato suggest
Acute respiratory distress syndrome (2013), more studies are needed in order to evaluate
empirically the new diagnostic criteria and they pro-
Timing Within 1 week of a known clinical insult or
pose potential improvements. They suggest the use of
new or worsening respiratory symptoms
Chest imaging∗ Bilateral opacities – not fully explained by data over the first 24 h to reclassify the severity of the
effusions, lobar/lung collapse or nodules disease and the use of compliance to stratify each oxy-
Origin of oedema Respiratory failure not fully explained by genation category.
cardiac failure or fluid overload. Need
objective assessment (e.g.
echocardiography) to exclude hydrostatic RESULTS ON TREATMENT
oedema if no risk factor is present INTERVENTIONS
Oxygenation† The findings were synthesized and are presented in
Mild 200 mmHg < PaO2 /FiO2 ≤ 300 mmHg with
thematic categorization. Overall, the analysis focused
PEEP or CPAP ≥5 cm H2 O‡
on empirical studies, meta-analyses and one Cochrane
Moderate 100 mmHg < PaO2 /FiO2 ≤ 200 mmHg with
PEEP ≥5 cm H2 O review. It is important to note that only two guidelines
Severe PaO2 /FiO2 ≤ 100 mmHg with PEEP ≥5 cm for practice were retrieved, where the respective work-
H2 O ing groups reviewed the available evidence according
to the principles of the Grading of Recommendations
ARDS, acute respiratory distress syndrome; CPAP, continuous positive airway
Assessment, Development and Evaluation (GRADE)
pressure; FiO2 , fraction of inspired oxygen; PaO2 , partial pressure of arterial
system. This is a system that guides reviewers in the
oxygen; PEEP, positive end-expiratory pressure.
∗ Chest radiograph or computed tomography scan. assessment of quality of evidence from high (A) to very
† If altitude is higher than 1000 m, the correction factor should be calculated as low (D), and assists them in determining the strength
follows: [PaO2 /FiO2 (barometric pressure/760)]. of recommendations as 1 (strong recommendation) or 2
‡ This may be delivered non-invasively in the mild acute respiratory distress (weak suggestion) (Dellinger et al., 2013; Claesson et al.,
syndrome population. 2015).
Conventional treatment of ARDS continues to be
mild (200 mmHg < PaO2 /FiO2 ≤ 300 mmHg), moder- supportive, involving methods to optimize oxygena-
ate (100 mmHg < PaO2 /FiO2 ≤ 200 mmHg) and severe tion and allow time for the underlying disease process
(PaO2 /FiO2 ≤ 100 mmHg) and four ancillary variables to improve and for lung tissue to recover (Wong and
for severe ARDS: radiographic severity, respira- Vuylsteke, 2011), as no effective pharmacological ther-
tory system compliance (≤40 mL/cm H2 O), positive apies have been found (Williams, 2013). Treatment for
end-expiratory pressure (PEEP) (≥10 cm H2 O) and cor- ARDS is multifaceted and relies on parameters of ven-
rected expired volume per minute (≥10 L/min). This tilation, commonly used medication, positioning the
draft ‘Berlin’ definition was empirically evaluated patient and its effects on gas exchange, fluid manage-
using patient-level meta-analysis of 4188 patients with ment and nutritional support (York and Kane, 2012).
ARDS from four multi-centre clinical data sets and 269 For the purposes of this article, the discussion will
patients with ARDS from three single-centre data sets focus on optimal mechanical ventilation techniques.
containing physiologic information. The four ancillary However, it is important to remember that successful
variables did not contribute to the predictive validity approaches to treatment rely on a holistic approach
of severe ARDS for mortality and were removed from aimed at treating the condition and its contributory fac-
the final definition (Table 2). tors (York and Kane, 2012).
The clinical implications of the Berlin definition
of ARDS are of immense importance as a link is Principles in mechanical ventilation
maintained to prior definitions with diagnostic crite- Mechanical ventilation represents the main therapeu-
ria of timing, chest imaging, origin of oedema and tic support to maintain acceptable pulmonary gas
hypoxaemia (Ferguson et al., 2012). For the bilateral exchange whilst treating the underlying disease. Most
opacities on chest radiograph criterion, a reference patients will require a period of ventilatory support
set of chest radiographs was developed to enhance (Burns et al., 2011). It is worth noting that inappro-
inter-observer reliability. Overall, the Berlin definition priately applied mechanical ventilation may cause
created a criterion of acuteness of disease onset, reclas- ARDS or increase its severity (Ranieri et al., 2012).
sified the oxygenation criterion, included a minimum Therefore, it is vital that clinicians caring for venti-
PEEP value for the diagnosis, redefined the exclusion lated patients have appropriate levels of specialist
criterion based on the presence of hydrostatic oedema knowledge and skills to manage patient–ventilator
interactions, recognize complications and intervene In the systematic meta-analysis by Putensen et al.
appropriately. (2009), the authors tried to determine whether ventila-
This specialist knowledge owes a lot to earlier clini- tion with low TV and limited airway pressure or higher
cal and experimental studies that implicated the deliv- PEEP improved outcomes for patients with ARDS.
ery of excessive mechanical stress through mechanical They concluded that routine use of low TV is benefi-
ventilation in the generation or perpetuation of lung cial and reduces mortality. A recent Cochrane review
injury (Carlucci et al., 2014). It has been accepted for showed that a gentler form of mechanical breathing
some time that mechanical ventilation may cause strain could reduce mortality in the short term, by 26% on
and shear forces on lung epithelial and endothelial average, but the effects in the long term were still
cells (Gattinoni and Pesenti, 2005) which increases local uncertain or unknown (Petrucci and De Feo, 2013).
inflammation (Held et al., 2001; Walkey et al., 2012). We now know that higher TVs can over-inflate and
Early studies suggested that ventilation strategies that injure remaining areas of normal lung tissue (Bas-
(1) limited TVs, (2) limited plateau pressures and (3) tarache et al., 2011). Key goals to mechanical venti-
limited both of these parameters were beneficial in pre- lation in ARDS include the following: maintaining
venting or reducing damage in ARDS patients (Brower safe alveolar pressures, preventing overstretch injury,
et al., 2000). However, this research may also reflect the re-expanding collapsed alveoli and preventing further
less advanced ventilator models that were in use at collapse and avoiding the atelectrauma that can be
that time. Nowadays, mechanical ventilators are able to caused by shear forces of tearing open the alveoli (Bas-
deliver mandatory and spontaneous breaths in a more tarache et al., 2011). Dellinger et al. (2013) recommend
sensitive manner, offering varying levels of weaning that clinicians should use as a starting point the objec-
support to patients from the early stages of critical tive of reducing TV over 1–2 h from its initial value
illness. 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
Lung protective ventilation strategies plateau pressures be measured and that the initial
Nowadays, the main supportive therapy for ARDS is upper limit goal for plateau pressures in a passively
positive pressure mechanical ventilation to help main- inflated lung should be ≤30 cm H2 O (grade 1B). If the
tain adequate oxygenation (Carlucci et al., 2014). LPV plateau pressure remains >30 cm H2 O after reduction
may be delivered, either by close monitoring of peak of TV to 6 mL/kg PBW, their guidelines suggest that
and plateau pressure with a volume-controlled mode TV may be reduced further to as low as 4 mL/kg PBW
or through the use of pressure-controlled modes (Este- (Dellinger et al., 2013). The importance of maintaining
ban et al., 2000, 2008). At the same time, LPV using a plateau pressure ≤30 cm H2 O becomes more appar-
low TV is the standard of care. ent as this is also highly recommended (strong evi-
In relation to the appropriate size of TV in mechan- dence) by another guideline on mechanical ventilation
ical ventilation, providing a TV of 10–12 mL/kg of in adults with ARDS, authored by the Clinical Practice
predicted body weight (PBW) is a practice that is old Committee of the Scandinavian Society of Anaesthe-
and therefore historical. The recommended approach sia and Intensive Care Medicine task force (Claesson
to treatment with LPV is to aim for or set the initial et al., 2015).
TV at 6 mL/kg of PBW (evidence grade 1A) (Dellinger As the syndrome progresses and lung tissue
et al., 2013; Carlucci et al., 2014) or 5–8 mL/kg of PBW becomes more damaged, there is a call for syn-
(Claesson et al., 2015). Other lung protective ventila- chronized management. There should be a fine
tion strategies (LPVS) include moderate to high PEEP, balance of the use of FiO2 , taking into considera-
high-frequency oscillatory ventilation (HFOV), extra- tion that the likelihood of oxygen toxicity increases
corporeal membrane oxygenation (ECMO) therapy, with prolonged use of FiO2 > 60%. In addition, the
prone positioning and inhaled pulmonary vasodila- ventilation-perfusion mismatch and intrapulmonary
tors, although definitive trials identifying consistently shunting lead to severe hypoxia (York and Kane,
improved patient outcomes are still needed (Rose, 2012). Lowering TVs often leads to higher number
2010; Claesson et al., 2015). At this point, it is worth of respiratory rates; 15–25 breaths/min are common,
noting that most of the studies and reviews up to 2012 in order to maintain an adequate minute ventilation
had adopted the AECC definition of ARDS, where the for gas exchange (York and Kane, 2012). With these
term ALI was reserved for PaO2 /FiO2 ≤ 300 mmHg, higher respiratory rates, patients are more likely
whereas the term ARDS represented the subset of to air trap gas resulting in auto-PEEP or intrinsic
ALI patients with the most severe lung injury, with PEEP (Durante et al., 2002). This is especially true
PaO2 /FiO2 ≤ 200 mmHg. when the inspiratory-to-expiratory ratio becomes
closer to 1:1 or is inversed with inspiration longer Guidelines for Management of Severe Sepsis and
than expiration. However, it is hypothesized that Septic Shock’ (Dellinger et al., 2013), PEEP ought to be
auto-PEEP may play a key role in the success of the low used to avoid alveolar collapse (atelectotrauma) (grade
TV/high respiratory rate treatment modality (Durante 1B) and higher levels of PEEP to be used only for those
et al., 2002). with sepsis-induced moderate to severe ARDS (grade
It is accepted practice that LPV may be applied 2C). This is also supported by Claesson et al. (2015)
with either volume- or pressure-controlled ventila- (weak suggestion).
tion. In volume-controlled ventilation, the ventilator However, what remains unanswered is how to select
delivers a specific TV with little concern as to the the optimal PEEP level that assists in lung recruit-
pressure required to deliver the breath. Practitioners ment without causing lung over-distention (Walkey
set a ‘high pressure limit’ to ensure that excessive et al., 2012). In relation to PEEP titration (Dellinger
pressures are not reached. Reports support that when et al., 2013), many approaches have been published,
the ARDS patient’s pressure climbs and reaches or including the following: (1) the use of a PEEP/FiO2
exceeds plateau pressures of 30 cm H2 O, the health ratio, where PEEP is based on severity of oxygena-
care team may consider using pressure-controlled tion deficit and guided by the FiO2 required to main-
ventilation (Sulemanji et al., 2009). In this case, the tain adequate oxygenation (Brower et al., 2004; Meade
ventilators deliver a practitioner-set pressure, whereas et al., 2008); (2) the use of the inflection points of the
the TV varies based on the patient’s lung compliance lung pressure-volume curve (Amato et al., 1998); and
and airway resistance. By using a preset pressure, (3) the titration of PEEP to a maximal plateau pressure
the team can ensure that the ARDS patient maintains of 30 cm H2 O (Mercat et al., 2008). Even so, the best
safe plateau pressures. Pressure-controlled ventilation method to determine the optimal PEEP level for each
also allows regulation of injurious peak inspiratory patient is unclear and is an important area of further
pressures. However, no study has identified the supe- research (Walkey et al., 2012).
riority of pressure-controlled ventilation over low TV
strategies using volume control (weak suggestion) Rescue therapies
(Dellinger et al., 2013; Claesson et al., 2015). Same Early implementation of optimal ventilation is crucial
principles should be used irrespective of mode, as a to minimize further deterioration in lung function
number of observational trials in mechanically ven- (Williams, 2013). However, although the aforemen-
tilated patients have also demonstrated a decreased tioned strategies will improve oxygenation for most
risk of developing ARDS when smaller TVs are used patients, these efforts will be insufficient in the most
(Determann et al., 2010). Accordingly, high TVs and critically ill ARDS patients (York and Kane, 2012).
high plateau pressures should be avoided in patients at Knowing that the underlying lung injury often contin-
risk of developing ARDS, including those with sepsis ues to worsen despite optimal medical management,
(Dellinger et al., 2013). clinicians must be aware of other available strate-
Permissive hypercapnia occurs as a consequence gies that may provide support for their patients and
of mechanical ventilation, when the health care team improve overall outcomes. Despite appropriate treat-
allows the carbon dioxide levels to climb, in lieu of ment, condition of some patients with ARDS continues
further damaging the lungs from excessive ventilation, to deteriorate (Carlucci et al., 2014). The following res-
especially when plateau pressure exceeds 30 cm H2 O cue therapies might be considered for patients with
(Laffey et al., 2009). When using permissive hypercap- severe refractory hypoxaemia.
nia, the health care team typically maintains the PaCO2 The health care team may consider using HFOV as
< 80 mmHg and the pH > 7⋅2. In addition, the PaO2 also a treatment option for the most critically ill. HFOV
should remain > 60 mmHg. utilizes a respiratory rate ranging from approxi-
PEEP and its titration appear to be another impor- mately 240–600 breaths/min (Fessler and Hess, 2007;
tant factor as well. A PEEP > 5 cm H2 O is usually York and Kane, 2012). This ventilation strategy is an
required to avoid lung collapse (Gattinoni et al., 2006). ‘open-lung’ technique keeping the lung alveoli well
Overall, high levels of PEEP have not conclusively recruited to promote additional gas exchange (Fessler
shown an improved survival (Brower et al., 2004; and Hess, 2007). Two recent trials have shown no
Meade et al., 2008; Mercat et al., 2008). Putensen et al. survival benefit and a possible increased mortality
(2009) suggest that higher PEEP strategies with low risk with the use of this type of ventilation in ARDS.
TV ventilation do not improve hospital mortality and Based on these results, HFOV is currently not rec-
cannot be recommended in unselected patients with ommended (Rose, 2010; Carlucci et al., 2014; Wilson
ARDS, although they may prevent life-threatening and Matthay, 2014; Claesson et al., 2015) as standard
hypoxaemia. According to the ‘2012 International practice.
ECMO therapy is another additional intervention Its use is also recommended by the task force on
that has been examined in patients with severe ARDS sepsis-induced ARDS (grade 2B) (Dellinger et al.,
with hypoxaemia that is refractory to conventional 2013).
ventilation management (Ranieri et al., 2012; Williams, In the past two decades, inhaled vasodilators such
2013). Although the current evidence is not suffi- as inhaled nitric oxide (iNO) and inhaled epoprostenol
cient to make finite recommendations for ECMO (the synthetic form of prostacyclin) have been consid-
therapy versus conventional management, results of ered as a potential rescue therapy for severe, refractory
some studies using ECMO in ARDS are described hypoxemia in ARDS patients (Arumpanayil, 2013). The
as encouraging, so consideration of transfer to an therapy is considered to selectively recruit blood flow
experienced ECMO centre is warranted (Walkey et al., to the ventilated alveoli and spare non-ventilated areas
2012; Carlucci et al., 2014; Wilson and Matthay, 2014). of lung parenchyma (Collins and Blank, 2011). The
Perner et al. (2015) recommend the development of delivery of the aerosolised vasodilator has proven to
tools in order to select patients who could benefit increase arterial oxygenation and decrease pulmonary
from ECMO, as the delivery of ECMO is an expensive artery pressure (PAP). They have been used as adjuncts
option. to LPVS in severe refractory hypoxaemia, but neither
Prone positioning may improve oxygenation by of these modalities has proven survival benefit in any
recruiting dependent lung units, redistributing blood study.
flow to the more unaffected lung regions, decreasing Despite iNO being effective in transiently improv-
ventilation-perfusion mismatching and facilitating ing oxygenation in some patients, all trials have
clearance of respiratory secretions (Carlucci et al., concluded that iNO does not improve the outcome in
2014). However, it requires a coordinated effort and ARDS patients and impaired renal function may be
expertise in the process of turning and positioning crit- a side effect (Adhikari et al., 2007; Perner et al., 2015).
ically ill patients in order to avoid complications. Any Perner et al. suggest that there is a need to evaluate
previous experience of the ICU team should therefore the use of iNO during LPV as a rescue therapy prior
be considered (Wilson and Matthay, 2014), and Perner to ECMO, when mechanical ventilation and prone
et al. (2015) suggest that prone positioning should be positioning have failed to improve gas exchange. As
done according to well-defined medical and nursing for inhaled epoprostenol, it may improve oxygenation
protocols in each ICU. in refractory hypoxaemia and it has been gaining
Studies on prone positioning and improvement in favour as an equally effective but easier to admin-
ARDS patients have reported similar, non-significant ister and less expensive modality as compared with
overall effects, that might be explained by the fact that iNO (Arumpanayil, 2013). Finally, based on the lack
these trials enrolled patients of variant ARDS severity of evidence in support of these therapies, inhaled
with different degrees of hypoxaemia (Perner et al., vasodilator therapy is not recommended as standard
2015). However, three meta-analyses support a signif- practice for ARDS (Perner et al., 2015). Table 3 sum-
icant benefit for reducing mortality in patients with marizes the recommendations for ventilation in ARDS
severe ARDS (Kopterides et al., 2009; Sud et al., 2010; patients.
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 DISCUSSION – IMPLICATIONS FOR
positioning. Additionally, two meta-analyses on ARDS PRACTICE
suggest that low TVs and prone positioning may need Both primary and secondary end points are inconsis-
to be applied concurrently in order to bring about more tently reported in the ARDS literature, which make it
consistent evidence on survival benefit. Tonelli et al. difficult for clinicians to interpret research findings and
(2014) showed significant mortality benefit when low translate them into practice guidelines. For example,
TVs and prone positioning were used in patients with there is lack of standardization in the time period in
severe ARDS, and Beitler et al. (2014) demonstrated which mortality in ARDS studies is reported, and this
that prone positioning was associated with a significant variability makes it rather difficult for researchers to
decrease in the relative risk of mortality only in studies compare the effects of different interventions (Tonelli
using low baseline TV of < 8 mL/kg PBW. Despite et al., 2014), and for clinicians to translate research into
the heterogeneity between empirical studies, Claesson evidence-based guidelines for practice. In addition,
et al. (2015) suggest the use of prone positioning for 16 h studies of ARDS suffer from heterogeneity regarding
for the first week in moderate to severe ARDS patients the underlying disease process and also the timing
(weak suggestion) as it appears to be a safe approach of inclusion following ARDS development (Claesson
in an ICU with expertise and previous experience. et al., 2015).
Ventilation mode: volume-controlled and pressure-controlled ventilation is Weak suggestion, very low quality evidence (Claesson et al., 2015)
equally beneficial or detrimental
Pressure limitation during mechanical ventilation: plateau pressure ≤30 cm H2 O Strong recommendation due to large effect on mortality (Claesson et al., 2015)
Sepsis-induced ARDS: plateau pressures to be measured and initial upper limit Strong recommendation, grade 1B (Dellinger et al., 2013)
goal for plateau pressures in a passively inflated lung to be ≤30 cm H2 O
Tidal volume limitation during mechanical ventilation: small TVs of Strong recommendation due to large effect on mortality (Claesson et al., 2015)
5–8 mL/kg PBW
Sepsis-induced ARDS: target a tidal volume of 6 mL/kg PBW Strong recommendation, grade 1A (Dellinger et al., 2013)
PEEP >5 cm H2 O to be applied to avoid alveolar collapse at end of expiration (1) Strong recommendation, grade 1B (Dellinger et al., 2013), (2) Weak
(atelectotrauma) suggestion, moderate quality evidence (Claesson et al., 2015)
Sepsis-induced moderate or severe ARDS: Strategies based on higher rather Weak suggestion, grade 2C (Dellinger et al., 2013)
than lower levels of PEEP
High frequency oscillatory ventilation (HFOV) has shown no demonstrable Strong recommendation, high-quality evidence (Claesson et al., 2015)
effect on mortality and therefore it is not recommended as standard practice
Extracorporeal membrane oxygenation (ECMO): current evidence is not No recommendations (Walkey et al., 2012)
sufficient
Prone positioning: patient with ARDS to be treated in the prone position for at Weak suggestion, very low quality evidence (Claesson et al., 2015)
least 16 h/day
Sepsis-induced ARDS: prone positioning to be provided to patients with a Weak suggestion, grade 2B (Dellinger et al., 2013)
PaO2 /FiO2 ratio ≤100 mmHg in facilities that have experience with such
practices
Inhaled pulmonary vasodilators: inhaled nitric oxide and inhaled epoprostenol: No recommendations (Claesson et al., 2015)
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 is heralded as one of the biggest advances in the field.
sepsis and resultant multiple organ failure (York and This strategy of ventilation management requires
Kane, 2012). With the exception of mechanical ven- constant surveillance and decision making by a multi-
tilation with low TVs and plateau pressure ≤ 30 cm disciplinary team. It is vital that ICU nurses caring for
H2 O, the rest of the discussed interventions are not ARDS patients have appropriate levels of ventilator
widely and unequivocally recommended (Girard management knowledge (Girard et al., 2008) and that
and Bernard, 2007; Claesson et al., 2015). At the same they can recognize complications, so that they inter-
time, Tonelli et al. (2014) urge caution with examining vene in a timely manner (Rose, 2006). This requires
single trials in isolation due to possible biases (Ioan- advanced knowledge of normal lung physiology as
nidis, 2005). For example, several trials in which the well as pathophysiology, in-depth understanding
intervention showed a potential beneficial effect were of ventilator technology, its clinical application and the
stopped early, which can inflate estimates of treatment current evidence for effective ventilation strategies.
effects (Putensen et al., 2009). Furthermore, in order At the same time, there is urgency for nurses to
to understand fully which treatments can actually address patient needs in a holistic manner rather than
reduce mortality in ARDS, it is critical and necessary as a ventilator exercise, because morality rates cannot
to examine an entire range of research with different be attributed solely to one single factor of patient man-
modalities, instead of focusing on single interventions agement (Dellinger et al., 2013). For example, there is
(Ioannidis and Karassa, 2010). also marked variability in the monitoring and ther-
It is acknowledged that the focus of ARDS research apeutic interventions (Jones, 2011). In the absence of
has shifted beyond ICU discharge to long-term out- standardized monitoring and intervention protocols,
comes of the patients (Guérin and Girbes, 2014). For nurses’ compliance with recommended LPVS can be
example, ARDS patients surviving their ICU stay, suboptimal. The use of standardized protocols is an
demonstrated decreased physical quality of life in important strategy for reducing practice variations
the very long term (Herridge et al., 2011). Even so, across disciplines (Jones, 2011).
reduction in mortality with LPV using low TVs and Another issue is that despite ARDS research demon-
pressure limitation with plateau pressure ≤30 cm H2 O strating a reduction in mortality (Petrucci and De
• 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.
• 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.
life after acute respiratory distress syndrome: a meta-analysis. Girard TD, Kress JP, Fuchs BD, Thomason JWW, Schweickert WD,
Intensive Care Medicine; 32: 1115–1124. Pun BT, Taichman DB, Dunn JG, Pohlman AS, Kinniry PA,
Durante G, Turco M, Rustichini L, Cosimini P, Giunta F, Hud- Jackson JC, Canonico AE, Light RW, Shintani AK, Thompson
son LD, Slutsky AS, Ranieri VM. (2002). ARDSNet lower tidal JL, Gordon SM, Hall JB, Dittus RS, Bernard GR, Ely EW. (2008).
volume ventilator strategy may generate intrinsic position Efficacy and safety of a paired sedation and ventilator weaning
end-expiratory pressure in patients with acute respiratory dis- protocol for mechanically ventilated patients in intensive care
tress syndrome. American Journal of Respiratory and Critical Care (Awakening and Breathing Controlled trial): a randomised
Medicine; 165: 1271–1274. controlled trial. Lancet; 371: 126–134.
Dwan K, Gamble C, Williamson PR, Kirkham JJ. (2013). Systematic Guérin C, Girbes AR. (2014). Improved ICU outcomes in ARDS
review of the empirical evidence of study publication bias patients: implication on long-term outcomes. Intensive Care
and outcome reporting bias – an updated review. PLoS One; Medicine; 40: 448–450.
8: e66844. Guérin C, Reignier J, Richard JC, Beuret P, Gacouin A, Boulain T,
Erickson SE, Martin GS, Davis JL, Matthay MA, Eisner MD, Mercier E, Badet M, Mercat A, Baudin O, Clavel M, Chatellier
NIH NHLBI ARDS Network. (2009). Recent trends in acute D, Jaber S, Rosselli S, Mancebo J, Sirodot M, Hilbert G, Bengler
lung injury mortality: 1996-2005. Critical Care Medicine; 37: C, Richecoeur J, Gainnier M, Bayle F, Bourdin G, Leray V,
1574–1579. Girard R, Baboi L, Ayzac L. (2013). Prone positioning in severe
Esteban A, Alia I, Gordo F, de Pablo R, Suarez J, Gonzalez acute respiratory distress syndrome. New England Journal of
G, Blanco J. (2000). Prospective randomized trial comparing Medicine; 368: 2159–2168.
pressure-controlled ventilation and volume-controlled venti- Held HD, Boettcher S, Hamann L, Uhlig S. (2001). Ventilation-
lation in ARDS. Chest; 117: 1690–1696. induced chemokine and cytokine release in associated with
Esteban A, Ferguson ND, Meade MO, Frutos-Vivar F, Apezteguia activation of nuclear factor-KB and is blocked by steroids.
C, Brochard L, Raymondos K, Nin N, Hurtado J, Tomicic V, American Journal of Respiratory and Critical Care Medicine; 163(3
González M, Elizalde J, Nightingale P, Abroug F, Pelosi P, Pt 1): 711–716.
Arabi Y, Moreno R, Jibaja M, D’Empaire G, Sandi F, Matamis Herridge MS, Tansey CM, Matte A, Tomlinson G, Diaz-Granados
N, Cooper A, Guest CB, Mazer CD, Mehta S, Stewart TE, Kud-
D, Montañez AM, Anzueto A, VENTILA Group. (2008). Evolu-
low P, Cook D, Slutsky AS, Cheung AM, Canadian Critical
tion of mechanical ventilation in response to clinical research.
Care Trials. (2011). Functional disability 5 years after acute res-
American Journal of Respiratory and Critical Care Medicine; 177:
piratory distress syndrome. New England Journal of Medicine;
170–177.
364: 1293–1304.
Esteban A, Frutos-Vivar F, Muriel A, Ferguson ND, Penuelas O,
Hong CM, Xu DZ, Lu Q, Cheng Y, Pisarenko V, Doucet D,
Abraira V, Raymondos K, Rios F, Nin N, Apezteguia C, Violi
Brown M, Aisner S, Zhang C, Deitch EA, Delphin E. (2010).
DA, Thille AW, Brochard L, Gonzalez M, Villagomez AJ, Hur-
Low tidal volume and high positive end-expiratory pressure
tado J, Davies AR, Du B, Maggiore SM, Pelosi P, Soto L, Tomi-
mechanical ventilation results in increased inflammation and
cic V, D’Empaire G, Matamis D, Abroug F, Moreno RP, Soares
ventilator-associated lung injury in normal lungs. Anesthesia
MA, Arabi Y, Sandi F, Jibaja M, Amin P, Koh Y, Kuiper MA,
and Analgesia; 110: 1652–1660.
Bulow HH, Zeggwagh AA, Anzueto A. (2013). Evolution of
Ioannidis JP. (2005). Why most published research findings are
mortality over time in patients receiving mechanical ventila-
false. PLoS Medicine; 2: e124.
tion. American Journal of Respiratory and Critical Care Medicine;
Ioannidis JP, Karassa FB. (2010). The need to consider the wider
188: 220–230.
agenda in systematic reviews and meta-analyses: breadth,
Ferguson ND, Fan E, Camporota L, Antonelli M, Anzueto A, Beale
timing, and depth of the evidence. BMJ; 341: c4875.
R, Brochard L, Brower R, Esteban A, Gattinoni L, Rhodes A,
Jones TL. (2011). A retrospective exploration of patient-ventilator
Slutsky AS, Vincent JL, Rubenfeld GD, Thompson BT, Ranieri monitoring intensity, therapeutic intervention intensity, and
VM. (2012). The Berlin definition of ARDS: an expanded ratio- compliance with lung protective guidelines in a cohort of
nale, justification, and supplementary material. Intensive Care patients with adult respiratory distress syndrome. Worldviews
Medicine; 38: 1573–1582. on Evidence-Based Nursing; 8: 40–50.
Fessler JE, Hess DR. (2007). Does high-frequency ventilation Kacmarek R, Sulemanji D, Villar J. (2012). Acute respiratory dis-
offer benefits over conventional ventilation in adult patients tress syndrome. In: Spiro S, Silvestri G, Agusti A, (eds), Clinical
with acute respiratory distress syndrome? Respiratory Care; 52: Respiratory Medicine. 4th edn. Philadelphia: Saunders.
595–608. Kalhan R, Mikkelsen M, Dedhiya P, Christie J, Gaughan C, Lanken
Fröhlich S, Murphy N, Doolan A, Ryan O, Boylan J. (2013). Acute P, Finkel B, Gallop R, Fuchs BD. (2006). Underuse of lung
respiratory distress syndrome: underrecognition by clinicians. protective ventilation: analysis of potential factors to explain
Journal of Critical Care; 28: 663–668. physician behaviour. Critical Care Medicine; 34: 300–306.
Gattinoni L, Pesenti A. (2005). The concept of “baby lung.”. Inten- Kopterides P, Siempos II, Armaganidis A. (2009). Prone position-
sive Care Medicine; 31: 776–784. ing in hypoxemic respiratory failure: meta-analysis of ran-
Gattinoni L, Caironi P, Pelosi P, Goodman LR. (2001). What has domized controlled trials. Journal of Critical Care; 24: 89–100.
computed tomography taught us about the acute respiratory Laffey JG, O’Croinin D, McLoughlin P, Kavanagh BP. (2009). Per-
distress syndrome? American Journal of Respiratory and Critical missive hypercapnia – role in protective lung ventilator strate-
Care Medicine; 164: 1701–1711. gies. In: Pinsky MR, Brochard L, Mancebo J, Hedenstierna G,
Gattinoni L, Caironi P, Cressoni M, Chiumello D, Ranieri VM, (eds), Applied Physiology in Intensive Care Medicine. New York:
Quintel M, Russo S, Patroniti N, Cornejo R, Bugedo G. (2006). Springer; 241–150.
Lung recruitment in patients with the acute respiratory Meade MO, Cook DJ, Guyatt GH, Slutsky AS, Arabi YM, Cooper
distress syndrome. New England Journal of Medicine; 354: DJ, Davies AR, Hand LE, Zhou Q, Thabane L, Austin P, Lap-
1775–1786. insky S, Baxter A, Russell J, Skrobik Y, Ronco JJ, Stewart TE,
Girard TD, Bernard GR. (2007). Mechanical ventilation in ARDS: Lung Open Ventilation Study Investigators. (2008). Ventilation
a state-of-the-art review. Chest; 131: 921–929. strategy using low tidal volumes, recruitment maneuvers, and
high positive end-expiratory pressure for acute lung injury Rose L, Kenny L, Tait G, Mehta S. (2014). Ventilator settings
and acute respiratory distress syndrome: a randomized con- and monitoring parameter targets for initiation of continuous
trolled trial. JAMA; 299: 637–645. mandatory ventilation: a questionnaire study. Journal of Criti-
Mercat A, Richard JC, Vielle B, Jaber S, Osman D, Diehl JL, Lefrant cal Care; 29: 123–127.
JY, Prat G, Richecoeur J, Nieszkowska A, Gervais C, Bau- Sigurdsson MI, Sigvaldason K, Gunnarsson TS, Moller A, Sigurds-
dot J, Bouadma L, Brochard L, Expiratory Pressure (Express) son GH. (2013). Acute respiratory distress syndrome: nation-
Study Group. (2008). Positive end-expiratory pressure setting wide changes in incidence, treatment and mortality over 23
in adults with acute lung injury and acute respiratory distress years. Acta Anaesthesiologica Scandinavica; 57: 37–45.
syndrome: a randomized controlled trial. JAMA; 299: 646–655. Sud S, Friedrich JO, Taccone P, Polli F, Adhikari NK, Latini R,
Oeckler RA, Hubmayr RD. (2007). Ventilator-associated lung Pesenti A, Guerin C, Mancebo J, Curley MA, Fernandez R,
injury: a search for better therapeutic targets. European Respi- Chan MC, Beuret P, Voggenreiter G, Sud M, Tognoni G, Gatti-
ratory Journal; 30: 1216–1226. noni L. (2010). Prone ventilation reduces mortality in patients
Perner A, Citerio G, Bakker J, Bassetti M, Benoit D, Cecconi with acute respiratory failure and severe hypoxemia: sys-
M, Curtis JR, Doig GS, Herridge M, Jaber S, Joannidis M, tematic review and meta-analysis. Intensive Care Medicine; 36:
Papazian L, Peters MJ, Singer P, Smith M, Soares M, Torres A, 585–599.
Vieillard-Baron A, Timsit JF, Azoulay E. (2015). Year in review Sulemanji D, Marchese A, Garbini P, Wysocki M, Kacmarek RM.
in Intensive Care Medicine 2014: II. ARDS, airway manage- (2009). Adaptive support ventilation: an appropriate mechan-
ment, ventilation, adjuvants in sepsis, hepatic failure, symp- ical ventilation strategy for acute respiratory distress syn-
toms assessment and management, palliative care and support drome? Anesthesia; 111: 863–870.
for families, prognostication, organ donation, outcome, organ- Tonelli AR, ZeinJ AJ, Ioannidis JPA. (2014). Effects of interven-
isation and research methodology. Intensive Care Medicine; 41: tions on survival in acute respiratory distress syndrome: an
389–401. umbrella review of 159 published randomized trials and 29
Petrucci N, De Feo C. (2013). Lung protective ventilation meta-analyses. Intensive Care Medicine; 40: 769–787.
strategy for the acute respiratory distress syndrome. The Tremblay LN, Slutsky AS. (2006). Ventilator-induced lung injury:
Cochrane Library; 2013: CD003844. DOI: 10.1002/14651858. from bench to bedside. Intensive Care Medicine; 32: 24–33.
CD003844.pub4. Villar J, Blanco J, Anon JM, Santos-Bouza A, Blanch L, Ambros A,
Phua J, Badia JR, Adhikari NK, Friedrich JO, Fowler RA, Singh Gandia F, Carriedo D, Mosteiro F, Basaldua S, Fernandez RL,
JM, Scales DC, Stather DR, Li A, Jones A, Gattas DJ, Hallett D, Kacmarek RM. (2011). The ALIEN study: incidence and out-
Tomlinson G, Stewart TE, Ferguson ND. (2009). Has mortal- come of acute respiratory distress syndrome in the era of lung
ity from acute respiratory distress syndrome decreased over protective ventilation. Intensive Care Medicine; 37: 1932–1941.
time? A systematic review. American Journal of Respiratory and Walkey AJ, Summer R, Ho V, Alkana P. (2012). Acute respi-
Critical Care Medicine; 179: 220–227. ratory distress syndrome: epidemiology and management
Pooler C. (2009). Disorders of ventilation and gas exchange. In: approaches. Clinical Epidemiology; 4: 159–169.
Porth CM, Matifin G, (eds), Pathophysiology: Concepts of Altered Williams KE. (2013). Extracorporeal membrane oxygenation for
Health States. Philadelphia: Wolters Kluwer; 701–738. acute respiratory distress syndrome in adults. AACN Advanced
Putensen C, Theuerkauf N, Zinserling J, Wrigge H, Pelosi P. (2009). Critical Care; 24: 149–158.
Meta-analysis: ventilation strategies and outcomes of the acute Wilson JG, Matthay MA. (2014). Mechanical ventilation in acute
respiratory distress syndrome and acute lung injury. Annals of hypoxemic respiratory failure: a review of new strategies
Internal Medicine; 151: 566–576. for the practicing hospitalist. Journal of Hospital Medicine; 9:
Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Cald- 469–475.
well E, Fan E, Camporota L, Slutsky AS, The ARDS Definition Wong I, Vuylsteke A. (2011). Use of extracorporeal life support
Task Force. (2012). Acute respiratory distress syndrome: the to support patients with acute respiratory distress syndrome
Berlin definition. JAMA; 307: 2526–25233. due to H1N1/2009 influenza and other respiratory infections.
Rose L. (2006). Advanced modes of mechanical ventilation: impli- Perfusion; 26: 7–20.
cations for practice. AACN Advanced Critical Care; 17: 145–158. York NL, Kane C. (2012). Trends in caring for adult respiratory
Rose L. (2010). Clinical application of ventilator modes: ventila- distress syndrome patients. Dimensions of Critical Care Nursing;
tory strategies for lung protection. Australian Critical Care; 23: 31: 153–158.
71–80.