Ventilator-associated pneumonia prevention : WHAP , positive end-expiratory pressure , or both ?

Approximately 25% of all infections acquired in intensive care units are due to ventilatorassociated pneumonia (VAP) (1). Since VAP causes substantial additional morbidity and mortality (2), preventing this complication is extremely important. Despite numerous investigations on its etiology, epidemiology, diagnosis and treatment, studies of prevention of VAP have lagged behind. Also, preventive measures have frequently been ignored. Only recently, a more rigorous effort to effectively apply sets of measures (so-called bundles) for the prevention of VAP has been put forward (3,4). Preventive bundles often include early weaning, hand hygiene, aspiration precautions, and prevention of contamination at times summarized with the acronym WHAP (5). Most ventilated patients with acute lung injury/acute respiratory distress syndrome receive positive end-expiratory pressure (PEEP) of 5–12 cm H2O (6). PEEP improves oxygenation by keeping lung regions open that otherwise would collapse. Although higher PEEP levels may further improve oxygenation and reduce ventilator-associated lung injury, the percentage of potentially recruitable lung tissue varies per patient (7). In addition, clinical outcomes have been shown to be similar in a direct comparison of lower and higher PEEP levels ( 12 cm H2O) (8, 9). Patients without acute lung injury/acute respiratory distress syndrome receive PEEP less frequently. A previous international study showed 75% of patients to be ventilated with 5 cm H2O of PEEP, and 31% of patients to be ventilated without PEEP (10). A more recent report showed levels of PEEP increased only minimally over the last decade (11). No clinical study has evaluated the direct influence of ventilator settings, in particular the use of PEEP on the incidence and outcome of VAP. In this issue of Critical Care Medicine, Manzano et al. (12) report results of a randomized controlled trial in one trauma and two general intensive care units in two university hospitals. Patients with normal chest roentgenogram and PaO2/FiO2 250 mm Hg were randomly allocated to receive mechanical ventilation with no PEEP or PEEP of 5–8 cm H2O. The number of patients who developed hypoxemia was significantly higher in the no-PEEP group (54% vs. 19%). The most striking clinical outcome difference was the incidence of VAP. Clinical suspicion of VAP was recorded in 22 patients (35%) in the no-PEEP group and ten patients (16%) in the PEEP group (relative risk 0.44 [95% confidence interval 0.23–0.84]). VAP was microbiologically confirmed in 16 patients (25%) in the no-PEEP group and six patients (9%) in the PEEP group (relative risk 0.37 [95% confidence interval 0.15–0.84]). Hospital mortality rate was not affected by the use of PEEP. The data are in line with preclinical studies. Atelectasis has been shown to aggravate the course of experimental pneumonia. van Kaam et al. (13) examined the effect of reducing the degree of atelectasis by exogenous surfactant and/or open lung ventilation (with the use of PEEP) on bacterial growth and translocation in a piglet model of pneumonia after surfactant depletion. Exogenous surfactant and open lung ventilation attenuated bacterial growth and translocation, at least in part via a reduction in atelectasis. Of note, the same group reported on high PEEP levels to promote bacterial translocation in experimental pneumonia (14). Unfortunately, diagnosing VAP remains a major challenge. In the present study, clinical suspicion of VAP required the presence of new, persistent, or progressive radiographic infiltrate on chest roentgenogram plus at least two of the following criteria: fever 38°C or hypothermia 35°C, leukocytosis 12 10/L or leukopenia 3 10/L, or purulent tracheobronchial secretions. Presence of VAP had to be confirmed by culture of endotracheal aspirate ( 10 colony forming unit/mL). We are undecided whether this was an adequate approach. First, clinical suspicion of VAP may have been influenced by the chosen strategy (no PEEP or PEEP) more than the development of infection itself. Indeed, radiographic abnormalities are dependent on the level of PEEP and lung inflation at the time the chest roentgenogram is taken. A higher PEEP level may erroneously give the impression that infective infiltrates, atelectasis, or permeability edema are not present when radiographic translucency seems normal (15). Second, fever and hypothermia, as well as leukocytosis and leukopenia, are frequently encountered in the critically ill and do not always reflect infection. Third, although 10 colony forming unit/mL in pulmonary secretions may be a sign of infection, it may also reflect colonization. The authors might better have chosen to culture tracheobronchial secretions of all patients, irrespective of clinical suspicion of VAP. Furthermore, serial measurements of biological markers of VAP, such as serum procalcitonin and soluble triggering receptor expressed on myeloid cells 1 in bronchoalveolar lavage fluid, may have provided an opportunity to strengthen their conclusions regarding the absence or presence of infection. The large difference in incidence of VAP between the no-PEEP and PEEP groups did not affect mortality rates, nor did the higher incidence of VAP prolong length of intensive care unit or hospital stay or the number of ventilation days in the no-PEEP group. This is surprising regarding the substantial additional morbidity and mortality of VAP (2). The question remains whether PEEP prevented *See also p. 2225.