Nosocomial pneumonia is an important cause of morbidity and mortality in hospitalized patients. Diagnosis and treatment continues to challenge clinicians and stimulate investigators. Prevention of this serious infection has been the focus of numerous studies, conferences and professional documents. Nosocomial pneumonia prevention strategies may be directed at the ventilator circuit (frequency of tubing circuit changes and gas humidification strategies), the endotracheal tube (intubation orifice, secretion drainage and suctioning) or body position (kinetic bed therapy and semirecumbancy). Other nonpulmonary approaches are pharmacologic (selective digestive decontamination and stress ulcer prophylaxis) or nutritional (the type, site and timing of enteral feeds).

The largest number of published randomized trials in intensive care medicine have evaluated selective digestive decontamination and stress ulcer prophylaxis. Five meta-analyses [1,2,3,4,5] suggest that selective digestive decontamination confers a large, clinically important and statistically significant reduction in nosocomial pneumonia rates (common odds ratio approximately 0.30, 95% CI 0.28–0.48). Nevertheless, selective digestive decontamination is not widely used, in part due to concern about long-term microbial resistance patterns and antibiotic costs [6]. Stress ulcer prophylaxis trials have been recently summarized in a meta-analysis suggesting that sucralfate, as compared with histamine-2-receptor antagonists or antacids, is associated with a trend toward a lower rate of nosocomial pneumonia (common odds ratio 0.78, 95% CI 0.60–1.01) [7]. Other experiments show that modifying gastric pH with acidified enteral feeds decreases gastric colonization, thereby supporting this underlying biologic rationale [8]. However, sucralfate is not considered of proven benefit due to the possibility that sucralfate confers a protective effect only when compared with gastric pH-altering drugs (which themselves are associated with a modest increase in nosocomial pneumonia compared to control) [7].

Kinetic bed therapy has been reviewed in a meta-analysis of six trials in seriously and critically ill patients, which indicated a significantly lower rate of pneumonia and atelectasis in patients receiving continuous postural oscillation [9]. A less expensive and adaptable pneumonia prevention strategy focussing on body position has been studied in three randomized trials [10,11,12]. Torres et al [10] found that after instillation of radioactive technetium sulfur colloid into the stomach, radioactive counts in endobronchial secretions were significantly higher in samples obtained while patients were supine than when they were semirecumbent. In another study, scintigraphic evidence of esophageal reflux was found in 81% of patients in the supine position compared to 64% in the semirecumbent position [11]. Orozco-Levi et al administered nasogastric technetium sulfur colloid and found that radioactive counts in endobronchial secretions increased over time, but were higher in the supine than the semirecumbent position [12]. Although a causal relationship between pneumonia and this secondary endpoint of aspiration of gastric contents has not been convincingly demonstrated, these trials are in keeping with the gastropulmonary route of infection.

The gastropulmonary route of infection is a concept at least two decades old [13], support for which is derived from multiple human observational studies and experimental evidence [14, 15]. Enteral nutrition, compared to parenteral nutrition, is associated with decreased translocation in animals and decreased infectious morbidity in critical illness in humans [16]. Accordingly, it holds the promise of affording protection against nosocomial pneumonia. However, enterally feeding critically ill patients is often associated with intolerance, thereby predisposing them to aspiration pneumonia. The goal of this systematic review is to critically appraise and summarize the randomized trials of nutritional strategies and their influence on nosocomial pneumonia in critically ill patients.

The results of these 10 trials of feeding strategies, either individually or in aggregate, provide inconclusive evidence about the relation between enteral nutrition and nosocomial pneumonia. These studies enrolled a total of 582 patients and contribute 117 cases of pneumonia. The single trial showing a significantly lower pneumonia rate associated with jejunal enteral nutrition over parenteral nutrition [24] has not been translated into widespread clinical policy, perhaps due to the inconvenience and expertise required for jejunostomy tubes. Aside from concerns about type I and II error when interpreting the trials in this review, there are other relevant outcomes addressed by some, but not all of these studies, including effects on nutritional markers and adverse outcomes such as catheter sepsis and patient comfort. Readers are referred to the original articles for these important details.

Factors such as cost, and ease with which the feeding strategy can be employed, are additional issues that bear on the interpretation and application of these trial results in practice. Intensivists also consider evidence from observational studies when making clinical decisions. Given these provisos, it is not surprising that definitive statements about enteral nutrition and lung infection are not forthcoming. Some guidelines from the Center for Disease Control on the prevention of nosocomial pneumonia [32] focus on gastropulmonary approaches. Stress ulcer prophylaxis with an agent that does not increase gastric pH was `suggested for implementation in many hospitals and supported by suggestive clinical and epidemiologic studies and a strong theoretical rationale'. Other interventions labelled as `unresolved for which no recommendations were made' included jejunal feeding, intermittent enteral feeding and selective digestive decontamination. In the American Thoracic Society statement on prevention of hospital-acquired pneumonia in adults [33], some prophylactic interventions were classified as having `probable effectiveness, used widely in some clinical settings', such as distal enteral nutrition, semi-erect positioning, and sucralfate. Selective digestive decontamination was considered `of unproven value used on a limited investigational or clinical basis'.

Nutrition is integral to the care of an ICU patient. The method, site and timing of enteral nutrition may have a protective or predisposing influence on the risk of nosocomial infection [34], though strong proof from experiments in humans does not currently exist. Although a meta-analysis of published and unpublished trials of general surgical and trauma patients suggested a lower pneumonia rate in patients receiving enteral nutrition vs total parenteral nutrition [35], published data from ventilated medical ICU patients are sparse, and generalizing to other populations may not be reasonable. Interventions requiring further investigation with large rigorous studies of ICU patients include those discussed in this review, as well as the size of feeding tubes [36], their insertion site, where the tubes are located in the gastrointestinal tract [37], feeding advancement schedules, and the effect of prokinetic drugs [38].