Incidence and prognosis of ventilator-associated tracheobronchitis (TAVeM): a multicentre, prospective, observational study

Summary

Background

Ventilator-associated tracheobronchitis has been suggested as an intermediate process between tracheobronchial colonisation and ventilator-associated pneumonia in patients receiving mechanical ventilation. We aimed to establish the incidence and effect of ventilator-associated tracheobronchitis in a large, international patient cohort.

Methods

We did a multicentre, prospective, observational study in 114 intensive care units (ICU) in Spain, France, Portugal, Brazil, Argentina, Ecuador, Bolivia, and Colombia over a preplanned time of 10 months. All patients older than 18 years admitted to an ICU who received invasive mechanical ventilation for more than 48 h were eligible. We prospectively obtained data for incidence of ventilator-associated lower respiratory tract infections, defined as ventilator-associated tracheobronchitis or ventilator-associated pneumonia. We grouped patients according to the presence or absence of such infections, and obtained data for the effect of appropriate antibiotics on progression of tracheobronchitis to pneumonia. Patients were followed up until death or discharge from hospital. To account for centre effects with a binary outcome, we fitted a generalised estimating equation model with a logit link, exchangeable correlation structure, and non-robust standard errors. This trial is registered with ClinicalTrials.gov, number NCT01791530.

Findings

Between Sept 1, 2013, and July 31, 2014, we obtained data for 2960 eligible patients, of whom 689 (23%) developed ventilator-associated lower respiratory tract infections. The incidence of ventilator-associated tracheobronchitis and that of ventilator-associated pneumonia at baseline were similar (320 [11%; 10·2 of 1000 mechanically ventilated days] vs 369 [12%; 8·8 of 1000 mechanically ventilated days], p=0·48). Of the 320 patients with tracheobronchitis, 250 received appropriate antibiotic treatment and 70 received inappropriate antibiotics. 39 patients with tracheobronchitis progressed to pneumonia; however, the use of appropriate antibiotic therapy for tracheobronchitis was associated with significantly lower progression to pneumonia than was inappropriate treatment (19 [8%] of 250 vs 20 [29%] of 70, p<0·0001; crude odds ratio 0·21 [95% CI 0·11–0·41]). Significantly more patients with ventilator-associated pneumonia died (146 [40%] of 369) than those with tracheobronchitis (93 [29%] of 320) or absence of ventilator-associated lower respiratory tract infections (673 [30%] of 2271, p<0·0001). Median time to discharge from the ICU for survivors was significantly longer in the tracheobronchitis (21 days [IQR 15–34]) and pneumonia (22 [13–36]) groups than in the group with no ventilator-associated lower respiratory tract infections (12 [8–20]; hazard ratio 1·65 [95% CI 1·38–1·97], p<0·0001).

Interpretation

This large database study emphasises that ventilator-associated tracheobronchitis is a major health problem worldwide, associated with high resources consumption in all countries. Our findings also show improved outcomes with use of appropriate antibiotic treatment for both ventilator-associated tracheobronchitis and ventilator-associated pneumonia, underlining the importance of treating both infections, since inappropriate treatment of tracheobronchitis was associated with a higher risk of progression to pneumonia.

Funding

None.

Introduction

Although mechanical ventilation is a potentially life-saving intervention, it is associated with significant risks and complications¹ such as ventilator-associated lower respiratory tract infections, including ventilator-associated pneumonia and ventilator-associated tracheobronchitis.² Although ventilator-associated pneumonia is associated with increased morbidity and duration of mechanical ventilation in the intensive care unit (ICU), tracheobronchitis has been proposed to be an intermediate stage between colonisation of the lower respiratory tract and pneumonia, with uncertain effects on clinical outcomes.³ Other data suggest that ventilator-associated tracheobronchitis might be a separate entity to pneumonia that independently contributes to increased length of stay in the ICU and longer duration of mechanical ventilation.⁴

Research in context

Evidence before the study

Findings from single-centre studies have identified ventilator-associated tracheobronchitis as an intermediate process between tracheobronchial colonisation and ventilator-associated pneumonia, and suggest a beneficial effect of antibiotic treatment in patients with ventilator-associated tracheobronchitis. Before initiating this study, we searched the scientific literature with the terms “ventilator-associated tracheobronchitis”, “mechanical ventilation-associated lower respiratory tract infections”, “ventilator-associated pneumonia”, “VAT”, and “VAP”, without any date or language restrictions. We excluded studies of patients not receiving mechanical ventilation and paediatric populations. We did not find any meta-analyses, but we identified observational studies and two randomised controlled trials. The findings from these studies showed no differences in duration of mechanical ventilation or length of stay in an intensive care unit (ICU) between patients who did and did not receive antibiotics for treatment of ventilator-associated tracheobronchitis or ventilator-associated pneumonia. The aim of our study was to establish the incidence of ventilator-associated tracheobronchitis in a large international cohort of mechanically ventilated patients, and its effect on their outcomes.

Added value of this study

This is the first multicentre, first international, and largest study described in the scientific literature focusing specifically on the clinical effect of mechanical ventilation-associated lower respiratory tract infections, including both ventilator-associated tracheobronchitis and ventilator-associated pneumonia. It will add value to the existing evidence because of its prospective design, the consecutive collection of data from patients without exclusion criteria (ie, readmitted patients and patients who had been previously tracheostomised were not included), the strict diagnostic criteria, the detailed description of the microbiological techniques used, and the adjustment of survival for potential confounders.

Implications of all the available evidence

The future implication for daily clinical practice is that ventilator-associated tracheobronchitis is a very frequent infectious complication of mechanical ventilation and increases the risk of developing pneumonia. Tracheobronchitis has a similar incidence to ventilator-associated pneumonia and also significantly affects patient outcomes, because it increases the duration of mechanical ventilation and length of stay in an ICU similarly to ventilator-associated pneumonia, but with lower mortality. The use of appropriate antibiotic treatment was associated with improved outcomes, both for tracheobronchitis and pneumonia, underlining the importance of treating both infections since inappropriate treatment of tracheobronchitis was associated with a higher risk of progression to pneumonia. Finally, we acknowledge that on the basis of the findings from our study combined with existing evidence, a consensus on the diagnosis and management of ventilator-associated tracheobronchitis is urgently needed.

An improved understanding of ventilator-associated tracheobronchitis could have important implications for early diagnosis, initiation of antimicrobials, and prevention. However, the concept of ventilator-associated tracheobronchitis is controversial, by contrast with ventilator-associated pneumonia, and several important questions remain unanswered, such as its definition, degree of overlap with ventilator-associated pneumonia (if any), diagnostic criteria, and appropriate treatment regimens, amidst a shortage of clinical data.⁵

In the TAVeM study, we aimed to measure the incidence of ventilator-associated tracheobronchitis, and establish its effects on patient outcomes and the effect of appropriate antibiotic treatment on progression from tracheobronchitis to pneumonia.