April 18, 2016

Ventilator-Associated Pneumonia in ARDS Patients: The Impact of Prone Positioning

A Secondary Analysis of the PROSEVA Trial

Ventilator-associated pneumonia (VAP) may complicate acute respiratory distress syndrome (ARDS) and is difficult to diagnose. Whether or not VAP is a risk factor for mortality in ARDS patients is still a matter of debate.

This ancillary study specifically dedicated to VAP (1) is from a prospective multi-centre randomised control trial on early prone positioning in severe ARDS patients (PaO2/FiO2<150 mmHg under FiO2>0.6 and PEEP≥5 cmH2O)(2). In this study, the investigators aimed to explore a) the relationship between prone position and VAP, hypothesising that prone positioning could reduce incidence of VAP, and b) whether VAP increases mortality in ARDS patients with current management (lung-protective ventilation (tidal volume = 6 mL/Kg + neuromuscular blockade strategy).

Prone positioning was randomised, with duration of at least 16 consecutive hours, following protocol. In suspected VAP cases diagnosis was made by each center’s investigator in charge of the protocol, based on quantitative bronchoalveolar lavage fluid (> 104) or tracheal aspirate (> 107) cultures; VAP cases were then subject to central, independent adjudication, blinded to position group.

The cohort consisted of 466 (229 supine – 237 prone) patients recruited during 42 months; 20% of patients developed a first VAP episode of VAP and median time from intubation to VAP 12 (7-12) days. Most common microorganism isolated was Pseudomonas aeruginosa. Initial antibiotic therapy was appropriate in 81.7% of cases, without differences between position groups. The incidence rate did not differ between groups: 1.18 (0.86-1.60) and 1.54 (1.15-2.02) per 100 invasive mechanical ventilation days for supine and prone position, respectively (p=0.10) that was on contrary with the initial study hypothesis. The authors claimed that this result may be partially explained by the lower mortality in the prone group.

ICU mortality rate did not differ significantly by VAP status (33.3% versus 25.5% for VAP and no-VAP, respectively, p=0.28). However, when VAP was treated as time-dependent variable, a significant association between VAP occurrence and risk of death during ICU stay was found:  HR 1.65, 1.05-2.61, p<0.05 and HR 2.21 (1.39-3.52, p<0.05) after adjustment for confounding factors (univariate Cox model). The results were essentially the same when interaction between VAP and the position group was taken into account.

The main limitations of the study include the following: VAP risk factors were not assessed after inclusion; mistakenly, a higher cut-off was used for tracheal aspirates cultures that decreased the sensitivity of the method for VAP diagnosis; the vast majority of the cohort were patients with medical admission.

Take home message
In severe ARDS prone positioning did not reduce the incidence of VAP. VAP in patients with severe ARDS was associated with increased mortality however, the fact that the cohort consisted vastly of patients with medical admission, limits the generalisability of the results.

Article Review was submitted by Drs Barbara Borgatta and Despoina Koulenti on behalf of the WG on Pneumonia.


1.    Ayzac L, Girard R, Baboi L, Beuret P, Rabilloud M, Richard JC, Guérin C.Ventilator-associated pneumonia in ARDS patients: the impact of prone positioning. A secondary analysis of the PROSEVA trial. Intensive Care Med. 2015 Dec 23. [Epub ahead of print] PubMed PMID: 26699917.
2.    Guérin C, Reignier J, Richard JC, Beuret P, Gacouin A, Boulain T, Mercier E, Badet M, Mercat A, Baudin O, Clavel M, Chatellier D, Jaber S, Rosselli S, Mancebo J, Sirodot M, Hilbert G, Bengler C, Richecoeur J, Gainnier M, Bayle F, Bourdin G, Leray V, Girard R, Baboi L, Ayzac L; PROSEVA Study Group. Prone positioning in severe acute respiratory distress syndrome. N Engl J Med 2013; 6: 368(23):2159-68. PubMed PMID: 23688302.

Aricle review for the Journal Club on behalf of the WG on pneumonia provided by
Dr Barbara Borgatta and Dr Despoina Koulenti

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