Elsevier

Burns

Volume 39, Issue 2, March 2013, Pages 200-211
Burns

Review
Strategies to reduce ventilator-associated lung injury (VALI)

https://doi.org/10.1016/j.burns.2012.10.013Get rights and content

Abstract

Optimal management of the acute respiratory distress syndrome (ARDS) requires prompt recognition, treatment of the underlying cause and the prevention of secondary injury. Ventilator-associated lung injury (VALI) is one of the several iatrogenic factors that can exacerbate lung injury and ARDS. Reduction of VALI by protective low tidal volume ventilation is one of the only interventions with a proven survival benefit in ARDS. There are, however, several factors inhibiting the widespread use of this technique in patients with established lung injury. Prevention of ARDS and VALI by detecting at-risk patients and implementing protective ventilation early is a feasible strategy. Detection of injurious ventilation itself is possible, and potential biological markers of VALI have been investigated. Finally, facilitation of protective ventilation, including techniques such as extracorporeal support, can mitigate VALI.

Introduction

Acute respiratory distress syndrome (ARDS) is a clinical diagnosis with a broad definition [1]. Although encompassing a wide range of causative illnesses, the lung's response to injury is qualitatively fairly uniform. However, severity varies from subclinical acute lung injury (ALI) to ARDS, the most severe clinical manifestation of lung injury. What was previously termed ALI and ARDS has been redefined recently as mild, moderate and severe ARDS [2]. The new definition also accounts for the positive end expiratory pressure (PEEP) in the assessment of oxygenation, and requires a known risk factor for ARDS (Fig. 1 [1], [2]).

Ventilator-associated lung injury (VALI) is one of the several iatrogenic factors, including fluid overload, transfusion of blood products and ventilator-associated pneumonia (VAP), that can exacerbate lung injury (Fig. 2 [3]). It is increasingly recognised that optimal management of ARDS consists of not only the prompt recognition and treatment of the underlying cause, but also the prevention of secondary injury. Given that in the majority of cases ARDS was not evident on admission to hospital [4], prevention of ARDS has become a major focus of research efforts [5].

Primary prevention of ARDS depends on identifying patients at risk and implementing protective strategies, whilst secondary prevention aims to reduce second ‘hit’ injuries and prevent progression along the spectrum from ALI to ARDS (Fig. 3). Finally, tertiary prevention measures target the on-going neuromuscular and psychological problems in many survivors of ARDS that may persist for several years. Chronic respiratory dysfunction in survivors is relatively uncommon [6]. Strategies aimed at reducing VALI are integral to the prevention of ARDS, and this article reviews some of the core concepts and techniques used now and in development for the future.

Section snippets

Clinical and pathological features of ARDS and VALI

ARDS is characterised clinically by the severity of hypoxaemia and the radiographic evidence of pulmonary oedema (Fig. 1) [1], [2]. The syndromes themselves can be caused either by direct pulmonary insults or indirectly from extra-pulmonary injury such as sepsis or trauma [7]. Of these predisposing conditions, smoke inhalation injury is one of the strongest risk factors correlated with development of ARDS [4]. Mortality from ARDS is still around 40% and approximately 190,000 patients develop

Ventilator-associated lung injury (VALI)

Studies of mechanical ventilation in animals demonstrated less pulmonary oedema when thoraco-abdominal strapping was used to prevent chest expansion, indicating that over-distension (volutrauma) rather than airway pressure (barotrauma) mediates VALI [27], [28]. Furthermore, such injury was more severe in the absence of PEEP, suggesting that cyclic opening and closing of recruited lung units (atelectotrauma) also plays an important role [29]. The mechanisms by which volutrauma and atelectotrauma

Risk prediction scores

A multicentre observational study evaluating the lung injury prediction score (LIPS) in 5584 patients confirmed that, in the majority of cases, ARDS was not present at the time of initial hospital admission but developed over hours to days [4], [53], [54]. The LIPS model aims to quantify the risk of developing ARDS based on data acquired at hospital admission (Table 1). LIPS points are accrued both for predisposing risk factors, including emergency surgery, sepsis and gastric aspiration, and

Biomarkers

An ideal biomarker of ARDS would quantify the extent of lung injury, guide treatment and predict outcomes. Elevated levels of circulating inflammatory markers such as soluble tumour necrosis factor-alpha receptors (sTNFRs) 1 and 2, and interleukins (IL-) 6 and 8, have all been associated with adverse outcomes in patients with ARDS [43], [66], [67], but lack specificity to VALI [3]. Soluble advanced glycation end-product (sRAGE) receptors are associated with alveolar type I cell injury, and

Mitigating VALI

Not uncommonly, using lung-protective ventilation in patients with ARDS conflicts with the imperative of achieving adequate gas exchange. In these cases, adjunctive supporting modalities (high PEEP, high frequency oscillatory ventilation (HFOV), prone positioning, neuromuscular blockade and extracorporeal support) can enable lung-protective ventilation and thus reduce VALI. Techniques such as extracorporeal support achieve this by using an alternative means of gas exchange, thereby minimising

Weaning and rehabilitation

Whilst there is some evidence to guide the support of patients with acute ARDS, there is almost nothing apart from the clinician's experience to guide the process of withdrawing support, with the aim of guiding patients forward towards recovery. Being too conservative can delay rehabilitation, and may result in patients being exposed to the risk of hospital-acquired infection in intensive care units for an unnecessarily prolonged period. Conversely, being too aggressive in relaxing measures

Conclusion

It is unsurprising that there are currently no effective disease-modifying treatments for lung injury, given the wide range of insults leading to ARDS. This is compounded by the fact that the often complex and heterogeneous clinical course of ARDS results in difficulties associated with undertaking clinical trials in critically ill patients [126]. However, both the increasing realisation that ARDS more often than not develops after patients are admitted to hospital and the identification of

Conflict of interest statement

The authors have no conflict of interest.

Acknowledgements

DS and MG are supported by the NIHR Respiratory Disease Biomedical Research Unit at the Royal Brompton and Harefield NHS Foundation Trust, and Imperial College London.

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