Because VAP has been associated with increased morbidity, longer hospital stays, increased health care costs, and higher mortality rates, prevention of this infection is a major challenge for intensive care medicine. A number of preventive strategies have been tested, and a number of recommendations have been published.120,190–194 However, evaluation of the impact of such interventions is a complex issue. Three methodologic difficulties make the measurement of potential efficacy of prevention strategies for VAP of limited value: (1) the difficulty of obtaining an accurate diagnosis of VAP (in fact, only patients who develop true VAP are likely to benefit from preventive measures), (2) the difficulty of precisely determining the impact of prophylactic measures on the overall mortality of a general ICU population (i.e., to identify preventable deaths directly attributable to VAP among all deaths occurring in a population of ventilated ICU patients), and (3) the difficulty of assessing the consequences of a preventive measure on a potentially pathogenic mechanism—a surrogate outcome (e.g., to determine the exact role played by prevention or reduction or modulation of tracheal colonization in modifying the development of VAP).
Conventional Infection Control Approaches
These measures should be the first step taken in any prevention program.195 The design of the ICU has a direct effect on the potential for nosocomial infections. Adequate space and lighting, proper functioning of ventilation systems, and adequate facilities for hand washing lead to lower infection rates.196 However, it should be kept in mind that physical upgrading of the environment does not per se reduce the infection rate unless personnel attitude and practices are improved. In any ICU, one of the most important factors is probably the team that staffs it: the number, quality, and motivation of its medical, nursing, and ancillary members. The team should include a sufficient number of nurses to avoid having them move from one patient to another and to avoid working under constant pressure.197 The importance of personal cleanliness (education and awareness programs) and attention to aseptic procedures (simple barrier isolation methods based on the use of disposable gowns and nonsterile gloves) must be emphasized at every possible opportunity. It is clear that careful monitoring, decontamination, and compliance with the usage guidelines of respiratory equipment decrease the incidence of nosocomial pneumonia.198 In any case, hand washing or hand rubbing with alcohol-based solutions remains uncontested as the most important infection control practice.197,199
A bacterial monitoring policy facilitates the early recognition of colonization and infection and has been associated with statistically significant reductions in nosocomial infection rates.200 The focal point for infection control activities in the ICU is a surveillance system designed to establish and maintain a database that describes endemic rates of nosocomial infection. Awareness of the endemic rates enables recognition of the onset of an epidemic when infection rates rise above a calculated threshold.
Preventing infection by modifying host risk has focused on treatment of underlying diseases and complications and control of antibiotic use. Adoption of an antibiotic policy restricting the prescription of broad-spectrum agents and useless antibiotics is of major importance.201 Simple, safe, inexpensive, logical, but unproven measures, including the use of physiotherapy,202 the judicious use and prompt removal of nasogastric tubes,43 and removal of tubing condensate, may have tremendous impact on the frequency of nosocomial pneumonia in mechanically ventilated patients.124
Specific Prophylaxis Against VAP
Since invasive MV is a risk factor for VAP, strategies that reduce its duration may reduce its incidence. Optimization of weaning protocols is a first way to reduce the duration of exposure to risk.203,204 Noninvasive ventilation is an alternative approach to the use of artificial airways to avoid infectious complications and injury of the trachea in patients with acute respiratory failure. Many observations and studies, unfortunately small and not blinded, suggest that patients who tolerate noninvasive ventilation have a lower incidence of pneumonia than those intubated tracheally, whatever the possible explanations: noninvasive ventilation itself or differences in disease severity, in the distribution of risk factors for VAP, or in the duration of exposure to each of the two ventilation methods.205–208 However, although seven randomized trials have compared noninvasive ventilation with conventional MV for prevention of pneumonia, only one could demonstrate a statistically significant benefit in favor of noninvasive ventilation.204,209–214
Apart from these protocols aiming at reducing the duration of mechanical ventilation, seven prophylactic approaches have been studied: semirecumbent positioning, oscillating and rotating beds, continuous or intermittent aspiration of subglottic secretions, ventilator circuits management, methods of enteral feeding, stress ulcer prophylaxis, and antibiotic use, including selective digestive decontamination.
Supine patient positioning has been shown to be independently associated with the development of VAP.37 Placing ventilated patients in a semirecumbent position to minimize reflux and aspiration of gastric contents is a simple measure, although some practical problems can occur in unstable patients. Three trials have evaluated the potential efficacy of semirecumbent positioning,122,215,216 but only one measured the incidence of VAP.215 This trial, which included 86 intubated and mechanically ventilated patients, was stopped after the planned interim analysis because the frequency and risk of VAP were significantly lower for the semirecumbent group. These findings were confirmed indirectly by demonstration that the head position of the supine patient during the first 24 hours of MV was an independent risk factor for acquiring VAP.215 No adverse effects were observed in patients assigned to semirecumbent positioning.
Semirecumbent positioning is a low-cost, low-risk preventive approach that merits being considered in all ventilated patients, whenever feasible.
Oscillating and Rotating Beds
Immobility in critically ill patients treated with MV results in atelectasis and impaired secretions drainage and potentially predisposes to pulmonary complications, including VAP. Oscillating and rotating beds may help in preventing pneumonia.217–224 Six randomized trials, including mostly surgical and trauma patients, ventilated or not, summarized in a meta-analysis by Choi and Nelson225 have compared continuous lateral rotational therapy with standard beds for the prevention of nosocomial pneumonia. The meta-analysis found a statistically significant reduction in the risk for pneumonia, principally concerning early-onset (<5 days) pneumonia, and a decreased duration of ICU stay. However, five of these studies were limited to surgical patients or those with neurologic impairment. The sixth study, which included primarily medical patients, found no significant benefit.219 A recent randomized, controlled trial of medical and surgical patients not included in the meta-analysis also found no benefit to oscillating beds.226 Some adverse events have been described with these beds, including disconnection of catheters or pressure ulceration; in addition, nursing care potentially is complicated with oscillating beds. Despite the cost of such beds, cost-benefit analyses performed in those studies seem favorable, mainly due to the shorter duration of the ICU stay.
Although oscillating or rotating beds have no apparent benefit in general populations of medical patients, there is reasonably good evidence that this practice may be effective in surgical patients or patients with neurologic problems. Use of these beds in these select patient populations therefore should be considered.
Aspiration of Subglottic Secretions
Continuous or intermittent aspiration of oropharyngeal secretions has been proposed to avoid chronic aspiration of secretions through the tracheal cuff of intubated patients. Aspiration of subglottic secretions requires the use of a specially designed endotracheal tube with a separate lumen that opens into the subglottic region. Three randomized, controlled trials have studied aspiration of subglottic secretions for the prevention of VAP.227–229 Mahul and colleagues227 found that pneumonia was significantly less frequent in patients with endotracheal tubes having a separate dorsal lumen for hourly suctioning of stagnant secretions above the cuff than in others and that VAP development was delayed. Similarly, in a 3-year prospective, randomized, controlled study, Valles and colleagues228 documented a lower VAP rate when continuous subglottic aspiration was performed. However, this difference was fully explained by the VAP occurring during the first week, whereas late-onset pneumonias were more frequent in the aspiration group. Furthermore, detailed microbiologic analysis demonstrated that this reduction concerned only pneumonia due to H. influenzae or gram-positive cocci. The incidence of VAP due to P. aeruginosa or Enterobacteriaceae did not differ between the two groups.228 Kollef and colleagues229 performed a randomized trial on 343 post–cardiac surgery patients to compare continuous subglottic aspiration and standard postoperative medical care. Although those authors found similar rates of VAP in both groups, VAP episodes occurred significantly later in patients receiving subglottic aspiration than in those treated conventionally. No difference in mortality rates was observed in these three studies. Whereas no adverse events were reported with aspiration of subglottic secretions in the three studies just reported, experimental data have suggested the possibility of tracheal damage in sheeps intubated with this type of tube.230
Aspiration of subglottic secretions is a promising strategy for the prevention of early-onset VAP but cannot be recommended for general use because of the mixed results in the literature. Further study of this approach is warranted.
Ventilator Circuit Management
Decreased frequency of ventilator circuit changes, replacement of heated humidifiers by heat and moisture exchangers, decreased frequency of heat and moisture exchanger changes, and closed suctioning systems all have been tested for preventing VAP. Four randomized trials of decreased frequency of ventilator circuit changes have been published231–234 comparing changes every 2 days, 7 days, and no scheduled change and did not find any significant differences in the rate of VAP, as summarized in a recent meta-analysis.235 One meta-analysis summarized the results of five randomized, controlled trials that compared the effects of heated humidifiers and heat and moisture exchangers on the risk of VAP.194 Only one out of these five studies found a significant reduction of VAP rate with the use of heat and moisture exchangers.236 The efficacy of both humidification strategies seems comparable; however, two studies reported increased rates of endotracheal tube occlusion with the use of heat and moisture exchangers.194 Another potential caveat of these devices includes an increased resistive load resulting in difficulties in the ventilation and weaning process of patients with severe ARDS.237 Finally, one study evaluated the impact of less frequent changes (daily versus every 5 days) of heat and moisture exchangers on the development of VAP.238 No differences in the VAP rates were observed.
A policy of no circuit changes or infrequent circuit changes is simple to implement, does not lead to increased development of VAP, and costs less than frequent, regular circuit changes. Such a policy should be considered in all mechanically ventilated patients. The favorable impact of the use of heat and moisture exchangers on the risk of VAP has to be confirmed before being recommended for general use.
To avoid hypoxia, hypotension, and contamination of suction catheters entering the tracheal tube, investigators have examined closed suctioning systems.239–241 While some found a nonsignificantly lower prevalence rate of VAP for patients managed with the closed system compared with those with the open system,241 others not only failed to show a statistically significant protective effect of the closed system on the incidence of VAP but also observed an increased frequency of endotracheal colonization associated with the closed device.239 At the present time, use of theses devices cannot be recommended for preventing VAP.
Methods of Enteral Feeding
Nearly all patients receiving mechanical ventilation have a nasogastric tube inserted to manage gastric and enteral secretions, prevent gastric distention, or provide nutritional support. The nasogastric tube may increase the risk for gastroesophageal reflux, aspiration, and VAP.43 Four randomized, controlled trials have evaluated various methods of enteral feeding aimed at preventing VAP: postpyloric or jejunal feeding (versus gastric feeding), the use of motility agents (metoclopramide versus placebo), acidification of feeding (with addition of hydrochloric acid), and intermittent (versus continuous) feeding.242–245 These studies did not find differences in the incidence of VAP and/or mortality rates. Potentially serious adverse effects have been observed in patients receiving acidified feeding (gastrointestinal bleeding) or intermittent enteral feeding (increased gastric volume and lower volumes of feeding). Thus, to date, methods of enteral feeding aimed to reduce the incidence of VAP cannot be recommended for routine use.
Gastric colonization by potentially pathogenic organisms has been shown to increase with decreasing gastric acidity.246 Thus medications that decrease gastric acidity (antacids, H2 blockers) may increase organism counts and increase the risk for VAP. In contrast, medications that do not affect gastric acidity, such as sucralfate, may not increase this risk.
Seven meta-analyses of more than 20 randomized trials have evaluated the risk for VAP associated with the methods used to prevent gastrointestinal bleeding in critically ill patients.97,98,100,105,106,247,248 Four of these seven meta-analyses reported a significant reduction in VAP incidence with sucralfate therapy compared with H2 blockers97,100,106 and three a statistically significant mortality benefit.98,100,105
However, the relationships between prophylaxis of stress ulcer and prophylaxis of VAP are complex: (1) VAP is a possible indirect consequence of the use of drugs that raise the stomach pH, (2) gastrointestinal bleeding is a serious complication in critically ill patients at high risk for stress ulcer (e.g., patients with coagulopathy or the need for prolonged mechanical ventilation) but is extremely rare in patients at low to moderate risk, (3) the largest randomized trial comparing ranitidine with sucralfate showed that ranitidine was superior in preventing gastrointestinal bleeding and did not increase the risk of VAP,107 and (4) the risk of VAP is unknown when accurate methods of enteral feeding or other preventive measures are used in combination with stress ulcer prophylaxis.
Clinicians must weigh the potential benefit of sucralfate (with potentially less VAP and more gastrointestinal bleeding) versus H2 blockers (with potentially more VAP and less gastrointestinal bleeding) and probably limit stress ulcer prophylaxis to high-risk patients.
Selective Digestive Decontamination
There is theoretical interest in using topical antibiotics to sterilize the oropharynx and stomach in mechanically ventilated patients, with the goal of reducing the incidence of VAP.249 Several groups have used topical prophylactic antibiotics for selective decontamination of the oropharynx and digestive tract (SDD) in patients at high risk for nosocomial pneumonia. The SDD regimen usually includes a short course of systemic antibiotic therapy, such as cefotaxime, trimethoprim, or a fluoroquinolone, and nonabsorbable local antibiotic prophylaxis consisting of a combination of an aminoglycoside, polymyxin B, and amphotericin.249 Since the original studies published by Stoutenbeck and colleagues250,251 in 1984, which demonstrated a decrease of the overall infection rate in patients receiving the SDD regimen, more than 40 randomized, controlled trials and 7 meta-analyses have been published.91,252–258 All seven meta-analyses reported a significant reduction in the risk of VAP, and four reported a significant reduction in mortality.91,254,255,257 No mortality benefit occurred with topical prophylaxis alone.91,252,254,257 However, a clear consensus as to the effectiveness of SDD has not been established owing to limitations and methodologic deficiencies of the studies analyzed.104,259 Furthermore, the impact of SDD on the emergence of resistant organisms is currently unknown but potentially important.260,261
Conclusions drawn based on meta-analyses of SDD studies may be summarized as follows: (1) SDD reduces the incidence of VAP and, when a combined topical and systemic regimen is used, may reduce mortality, (2) an inverse relationship has been described between methodologic quality of the studies and benefit, questioning the overall value of results reported in the meta-analyses, (3) the long-term effects of SDD on emergence of resistance and risk of superinfections currently are unknown, and finally, (4) the impact of SDD on the duration of MV, ICU stay, and hospital stay appears to be limited. Thus, at present, this approach cannot be recommended for overall populations of ICU patients treated with MV, although SDD may be effective for specific populations, particularly surgical or trauma patients.
Early attempts at systemic prophylaxis with parenteral antibiotics alone against pneumonia clearly were unsuccessful.262,263 In contrast, recent studies showed that a short-course antibiotic regimen in patients with structural coma or severe burns was an effective prophylactic strategy to decrease the VAP rate.92 The influence of rotating of antibiotics (generally associated with restrictive use) in the ICU on VAP prevalence was investigated recently by comparing successive periods during which one antibiotic was used in place of another for the empirical treatment of suspected gram-negative bacterial infections. Some investigators found that VAP occurred significantly less frequently during the after period compared with the before period.264–266