Articles
Epidemiological characteristics, practice of ventilation, and clinical outcome in patients at risk of acute respiratory distress syndrome in intensive care units from 16 countries (PRoVENT): an international, multicentre, prospective study

https://doi.org/10.1016/S2213-2600(16)30305-8Get rights and content

Summary

Background

Scant information exists about the epidemiological characteristics and outcome of patients in the intensive care unit (ICU) at risk of acute respiratory distress syndrome (ARDS) and how ventilation is managed in these individuals. We aimed to establish the epidemiological characteristics of patients at risk of ARDS, describe ventilation management in this population, and assess outcomes compared with people at no risk of ARDS.

Methods

PRoVENT (PRactice of VENTilation in critically ill patients without ARDS at onset of ventilation) is an international, multicentre, prospective study undertaken at 119 ICUs in 16 countries worldwide. All patients aged 18 years or older who were receiving mechanical ventilation in participating ICUs during a 1-week period between January, 2014, and January, 2015, were enrolled into the study. The Lung Injury Prediction Score (LIPS) was used to stratify risk of ARDS, with a score of 4 or higher defining those at risk of ARDS. The primary outcome was the proportion of patients at risk of ARDS. Secondary outcomes included ventilatory management (including tidal volume [VT] expressed as mL/kg predicted bodyweight [PBW], and positive end-expiratory pressure [PEEP] expressed as cm H2O), development of pulmonary complications, and clinical outcomes. The PRoVENT study is registered at ClinicalTrials.gov, NCT01868321. The study has been completed.

Findings

Of 3023 patients screened for the study, 935 individuals fulfilled the inclusion criteria. Of these critically ill patients, 282 were at risk of ARDS (30%, 95% CI 27–33), representing 0·14 cases per ICU bed over a 1-week period. VT was similar for patients at risk and not at risk of ARDS (median 7·6 mL/kg PBW [IQR 6·7–9·1] vs 7·9 mL/kg PBW [6·8–9·1]; p=0·346). PEEP was higher in patients at risk of ARDS compared with those not at risk (median 6·0 cm H2O [IQR 5·0–8·0] vs 5·0 cm H2O [5·0–7·0]; p<0·0001). The prevalence of ARDS in patients at risk of ARDS was higher than in individuals not at risk of ARDS (19/260 [7%] vs 17/556 [3%]; p=0·004). Compared with individuals not at risk of ARDS, patients at risk of ARDS had higher in-hospital mortality (86/543 [16%] vs 74/232 [32%]; p<0·0001), ICU mortality (62/533 [12%] vs 66/227 [29%]; p<0·0001), and 90-day mortality (109/653 [17%] vs 88/282 [31%]; p<0·0001). VT did not differ between patients who did and did not develop ARDS (p=0·471 for those at risk of ARDS; p=0·323 for those not at risk).

Interpretation

Around a third of patients receiving mechanical ventilation in the ICU were at risk of ARDS. Pulmonary complications occur frequently in patients at risk of ARDS and their clinical outcome is worse compared with those not at risk of ARDS. There is potential for improvement in the management of patients without ARDS. Further refinements are needed for prediction of ARDS.

Funding

None.

Introduction

Invasive mechanical ventilation is a frequently applied intervention in patients in the intensive care unit (ICU).1, 2 Although ventilation is usually seen as a life-saving strategy, it has strong potential to worsen pre-existing lung injury.3 Ventilation strategies aimed at preventing lung overdistension through use of low tidal volumes (VT ≤6 mL/kg predicted bodyweight [PBW]) improved the outcome (ie, decreased mortality) of patients in the ICU with acute respiratory distress syndrome (ARDS).4, 5 Thus, low VT is seen as the key element of so-called lung-protective ventilation in patients with this life-threatening complication of critical illness. In a meta-analysis of individual patient data from three randomised controlled trials,6 ventilation strategies aimed at avoiding repetitive opening and closing of atelectatic lung tissue through use of high positive end-expiratory pressure (PEEP >10 cm H2O) were beneficial in patients with moderate or severe ARDS. Therefore, several guidelines recommend the use of higher rather than lower PEEP in patients with moderate-to-severe ARDS.7, 8

Research in context

Evidence before this study

We searched MEDLINE, Embase, CINAHL, and Web of Science with the terms (“mechanical ventilation”) AND (“ARDS” OR “acute respiratory distress syndrome”) AND (“high risk” OR “LIPS”), with no date or language restrictions. We excluded studies of patients not receiving mechanical ventilation and those in paediatric populations. We did not find any study specifically assessing mechanical ventilation and outcomes in patients according to their risk of acute respiratory distress syndrome (ARDS) based on the Lung Injury Prediction Score (LIPS). Findings of a study using the original LIPS database suggested that clinicians seemed to respond to ARDS with a low initial tidal volume (VT). Initial VT, however, was not associated with development of post-intubation ARDS or other outcomes. Nevertheless, this study assessed neither the proportion of patients at risk of ARDS nor possible differences in mechanical ventilation between this group of patients and those not at risk of ARDS.

Added value of this study

Our study is the first to focus specifically on the proportion of patients at risk of ARDS, ventilatory management of the disorder, and clinical outcomes, including pulmonary complications and mortality. Our study was prospective, with consecutive collection of data from patients and the inclusion of several intensive care units (ICUs) from different countries and continents, increasing its generalisability. We provided detailed descriptions of ventilatory parameters, pulmonary complications, and clinical outcomes. The proportion of patients at risk of ARDS was high, and clinical outcomes were worse in this subgroup than were those of patients not at risk of ARDS.

Implications of all the available evidence

Most patients on ventilation in the ICU do not have ARDS; however, a considerable number of individuals are at risk of this life-threatening complication. Early implementation of protective ventilation and other strategies in patients at risk of ARDS could be associated with better outcomes. Our results add to existing knowledge about epidemiological characteristics and outcomes of patients with ARDS, as described in the LUNG SAFE study, and could be useful in planning future studies and understanding previous findings about mechanical ventilation in patients in the ICU. Further refinements for prediction of ARDS are needed.

Growing evidence suggests that ventilation not only worsens but also induces lung injury, particularly in patients at risk of ARDS.3, 9 Moreover, meta-analyses of observational studies and randomised controlled trials indicate improved outcomes with use of low VT during ventilation in patients in the ICU who did not have ARDS at the start of ventilation.10, 11, 12, 13 Convincing evidence, however, remains scarce.14 Associations between ventilation at low VT and increased need for sedation and prolonged use of muscle paralysis are some reasons why clinicians remain reluctant to use low VT in patients without ARDS.14 Whether PEEP benefits patients without ARDS is even more uncertain.9, 15, 16, 17 Risk of overdistension with higher PEEP, potentially inducing additional lung injury, has made clinicians reluctant to use PEEP as liberally in patients with uninjured lungs compared with in those with ARDS.18, 19

Preventing ARDS might be a more effective strategy than treating the disorder, with respect to improving outcomes of critically ill patients. One major obstacle to preventive studies is the inability to predict which patients are likely to develop ARDS.20 Epidemiological data suggest that the syndrome is present rarely at admission, but develops over a period of hours to days in a subset of patients at risk of ARDS,20 with considerable negative effects on outcome. Although lung protection has the potential to improve outcomes in this subset of patients in particular, we do not know how ventilation is currently managed in these patients and whether management differs from that in patients not at risk of ARDS.

As part of the PROtective VEntilation (PROVE) Network, we undertook the PRactice of VENTilation in critically ill patients without ARDS at onset of ventilation (PRoVENT) study to establish the epidemiological characteristics and clinical outcomes of patients at risk of ARDS, to describe and compare ventilation management in patients at risk of ARDS versus individuals not at risk, and to ascertain whether ventilation at higher VT is associated with higher prevalence of ARDS.

Section snippets

Study design and participants

PRoVENT is an investigator-initiated, international, multicentre, observational, cohort study undertaken at 119 ICUs in 16 countries worldwide (appendix pp 10–12). Part of the study protocol (appendix pp 26–60) has been published previously.21 Study sites were recruited through direct contact made by members of the PRoVENT steering committee and potential national coordinators. Approved national coordinators contacted local coordinators, who sought approval from their respective institutional

Results

Between January, 2014, and January, 2015, 183 ICUs in 20 countries expressed interest in participating in the PRoVENT study, and 119 ICUs in 16 countries met inclusion criteria (appendix pp 10–12). Of 3023 individuals screened for the study, 1021 patients were included; the main reason for exclusion was that they did not receive invasive ventilation (figure 1). 86 patients had ARDS at the start of ventilation and their data were only included in post-hoc analyses. Baseline characteristics of

Discussion

Around a third of patients undergoing invasive ventilation were at risk of ARDS. Roughly half of those without ARDS received a VT greater than 8 mL/kg PBW, and the VT did not differ between patients at risk of ARDS and those not at risk; moreover, the VT was remarkably similar to that administered to patients with ARDS at onset of ventilation. PEEP was higher in patients at risk of ARDS compared with those not at risk; however, PEEP was lower than in patients with ARDS at onset of ventilation.

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