VAP prevention is performed through pharmacological and non-pharmacological measures that mainly focus on modifiable risk factors. With this review our intention was to approach the most consensual preventive measures that are described in guidelines drawn up by national and international scientific medical societies (Table 4 indicates the preventive measures that each guideline recommends).

The first step in the prevention of VAP is the patient evaluation in order to determine the need for invasive mechanical ventilation. MV should be avoided whenever possible,5,21,25–30 since, by using intubation, the risk of nosocomial pneumonia is increased 6–21 times.5

Although noninvasive MV is considered a feasible alternative to invasive MV in some clinical situations, it is important to perceive that it is not applicable in all patients, and therefore it cannot replace MV and endotracheal intubation in all situations. Noninvasive MV has been employed with favorable clinical results in cases of: exacerbation of chronic obstructive pulmonary disease (COPD), cardiogenic pulmonary edema, acute hypoxemic respiratory failure and in some immunosuppressed patients with pulmonary infiltrates and respiratory failure.5,31 A meta-analysis of 12 studies, in which the target population had COPD as the prevailing disease, concluded that noninvasive positive pressure MV, compared with invasive positive pressure MV, significantly decreased mortality and incidence of VAP, and the ICU and hospital length of stay.32

The use of noninvasive MV after extubation in order to prevent re-intubation and to reduce the time of MV (invasive and noninvasive) has been investigated and the results are now promising.33 However, more studies are needed in order to get a better understanding of its role in VAP prevention. Until now, the efficacy of this measure has only been proven in patients with COPD.31

The weaning from invasive MV involves a close monitoring of the patient, not only because it usually occurs in an intensive care environment, but also because the monitoring of signs and symptoms is essential in identification of a possible failure of the weaning process: increased shortness of breath, tachycardia, diaphoresis, oxygen desaturation, hypertension and increased anxiety.34

Currently, the most widely used weaning method is the spontaneous breathing trial (SBT), which allows the observation for signs of respiratory failure. During SBT the patient breathes spontaneously through the ETT, which is connected to a T-piece. The T-piece can provide a source of humidified oxygen (without mechanical ventilator), reduced levels of continuous positive airway pressure and/or pressure support ventilation for short periods of time (30min–2h).34,35

Since it is difficult to predict the duration of MV, the current guidelines recommend the use of protocols for implementing the weaning process with daily assessments of the patient, in order to assess whether there are the necessary conditions to begin the weaning process.5,26–30

Ideally, protocols of invasive MV weaning include weaning from sedatives, since it was found that this procedure contributes to the reduction of the duration of MV and the ICU length of stay and, consequently, to reduce the risk of VAP.5,26–30,36 Indeed, the overuse of sedatives is not beneficial to the weaning process, as it can inhibit the patient's breathing capacity, which is indispensable to the discontinuation of MV.

Guidelines recommend that intubation should preferably be applied with orotracheal and orogastric tubes, instead of using nasotracheal or nasogastric tubes, since oral intubation is associated with a lower incidence of VAP.5,25–29,37

One of the risk factors related with increased hospitalization is the frequent change of the ventilator circuit. Currently it is consensual that one circuit only should be used in each patient, and that it should only be changed when there is a mechanical damage or contamination (blood, vomit, or purulent secretions).26,27,29,30,37,38 This recommendation is based on the evidence that frequent changes in the ventilator circuit do not contribute to a decreased incidence of VAP.39

Bercault et al. found that an episode of transport from the ICU to another place in the hospital increases the risk of development of VAP.40 It is thought that the patient's positioning in supine position, and the frequent handling of the ventilator tubing during the transfers, may facilitate the aspiration of contaminated secretions.29 Nowadays, when an intra-hospital transfer is needed the patient should be in an inclined position and enteral nutrition (EN) should be suspended 4h before the transfer.28–30

• a)

  Elevation of the head of the bed

  Elevation of the head of the bed has the purpose of avoiding positioning the patient in supine position – a position whose leaning is 0° and is a risk factor for the development of VAP, in order to prevent gastroesophageal reflux and subsequent aspiration to the lower airways. In fact, elevation of the head of the bed is associated with a reduced risk of aspiration.27,29 A meta-analysis concluded that a head elevation of 15–30° is not sufficient to prevent the development of VAP.41 At present, elevation of the head of the bed between 30° and 45°5,25–30 is recommended, but there are already some studies and guidelines that would only consider elevation of the head of the bed at 45°.37,41 The use of the horizontal–lateral position with an elevation of 45° has shown promising results, because compared with the semi-recumbent position, it has had a lower incidence of VAP (4/10 versus 1/10).42 However, this measure is not yet included in guidelines as there are still some doubts remain to be cleared.

• b)

  Modifications in endotracheal tubes

  Modifications in ETT are intended to prevent mechanisms through which endotracheal intubation increases the risk of VAP: 1) aspiration of secretions into the lower airways, 2) mucosal injury and decreased mucociliary clearance of secretions, 3) microaspiration of secretions around the inflated cuff and 4) biofilm formation and bacterial colonization in the ETT lumen.43

  In order to replace the traditional ETT, which have polyvinylchloride in their constitution, antibacterial-coated ETT have been developed; the most studied compound is silver, which has bactericidal activity and is able to prevent biofilm formation.44 A prospective study found that intubation with silver-coated ETT is safe, delays the ETT colonization, reduces the biofilm formation and decreases the maximal bacterial burden in tracheal secretions for 7 days.45 Another prospective study concluded that patients intubated with silver-coated ETT showed lower incidence of VAP, delay in disease onset (with higher impact in the first 10 days of intubation)46 and decreased mortality.47 Up until now, no study has reached a conclusion about the influence of this preventive measure in the duration of MV, and in ICU and hospital length of stay. Therefore, this preventive measure is still not consensual among the scientific community; so far only the Spanish guidelines recommend it.30 However, it is worth noting that a cost-effectiveness study of silver-coated ETT confirmed that, although silver-coated ETT are much more expensive (60.22€) than conventional tubes (1.47€), they reduced the hospital costs from between 7085.68€ and 12034.60€ per prevented case of VAP.48

  The improvement of the ETT cuff has also been tried out, both in terms of shape as well as its inflation characteristics, in order to prevent microaspiration of subglottic secretions. The studies which analyzed ETT with polyurethane cuffs have shown good results, suggesting that they may be effective in the prevention of microaspiration of secretions to the lower airways.49–52 However, to date, none of the studies predicted the action of these tubes in the duration of MV and ICU and hospital length of stay.

  Another recommendation made by some guidelines is related to the cuff pressure. It should be checked daily, at regular intervals, and maintained between 20 and 30cm H2O: below this value the risk of pneumonia increases, and above it tracheal mucosal injuries can occur.25,29 However, the British guidelines recommends a narrower range of pressure (>25 and <30cm H2O)28 and the American guidelines only recommend a minimum value of 20cm H2O.5,27

• c)

  Aspiration of subglottic secretions

  Currently, aspiration of subglottic secretions is recommended by almost all guidelines, since studies show a reduction in the incidence of VAP when this preventive measure is used.5,25,27–30,37 The meta-analysis of Dezfulian ital. concluded that subglottic secretion drainage reduced the incidence of VAP by almost a half, and that in patients with an estimated MV time of more than 72h this measure decreased, on average, the duration of MV by 2 days, the ICU length of stay by 3 days, and delayed the onset of pneumonia by 6.8 days.53 The recommendations concerning the use of aspiration of subglottic secretions differ between guidelines. Canadian guidelines recommend it in patients who are expected to require MV for more than 72h,37 but the Spanish have reduced the time to 48h,30 and the British recommend the implementation of this measure regardless of the expected MV duration.28 Possibly the latter approach is the most sensible, because it is very difficult to predict the duration of MV.54

  There is no doubt that the use of this technique, continuously or intermittently, is effective in the prevention of VAP,55–58 but to date none of the forms of aspiration have been highlighted as the best. Currently, both are implemented in order to prevent and reduce microaspiration and, for this purpose, specific ETT have been developed. These ETT have a second lumen (aspiration lumen), which has an evacuation orifice in the edge of the cuff connected to a suction system, allowing continuous or intermittent aspiration of the subglottic secretions.25,30,59

A major aim of VAP prevention consists in reducing the colonization of the oropharynx and the digestive tract, since they represent an increased risk of microaspiration of pathogens to the lower airways.21

• a)

  Oral antiseptics

  Patients who are intubated with ETT cannot perform their daily oral hygiene, which carries a risk of biofilm colonization by pathogenic microorganisms.60 Oral antiseptics have been used in order to reduce and prevent oropharyngeal colonization by bacterial pathogens, and hence this is a viable alternative since it can be implemented by health care providers.

  The use of oral antiseptics significantly reduces the incidence and the relative risk (RR=0.56) of VAP, suggesting that this measure is efficient in its prevention.61 Due to its very broad spectrum of action, which covers microorganisms such as Pseudomonas aeruginosa, Acinetobacter spp., and methicillin-resistant Staphylococcus aureus,62 some of the most common pathogens implicated in VAP, chlorhexidine (CHX) is the most studied antiseptic, and its efficacy in the prevention of VAP has been proven.63,64 In fact, the most recent guidelines recommend oral decontamination with CHX as a preventive measure of VAP.25–27,30,37 However, no guidelines recommend a posology for this preventive measure. Studies used concentrations of 0.12%, 0.2% and 2% of CHX administered 2, 3 or 4 times daily.62 A more recent study suggests the use of 15ml of an oral solution of 0.12% of CHX twice a day until 24h after extubation.65

  The Canadian guideline is the only one that, besides recommending the use of CHX as an oral antiseptic, also recommends that the use of iodopovidone should be considered in patients with severe head injury, based on a single study performed in this patient population.37

• b)

  Antibiotic prophylaxis: Selective oropharyngeal decontamination (SOD) and selective digestive decontamination (SDD)

  SOD consists of enteral administration of antimicrobial agents, while in SDD the parenteral route is also used. These decontaminations are selective because the aim is to prevent the oropharyngeal and gastric colonization by aerobic Gram-negative bacilli, S. aureus and fungi species like Candida, without affecting the commensal flora.65 Antimicrobial regimens studied do not vary very much. They consist essentially in the administration four times a day of antibiotics that act only in the gastrointestinal tract, i.e. which are not absorbed (e.g., colistin, polymyxin E, tobramycin and/or amphotericin B), and antibiotics administered intravenously (e.g. cefotaxime or ciprofloxacin) in the case of SDD.54,62

  de Smet et al. have conducted the largest study concerning SOD and SDD to date, they confirmed a 2.9% decrease in the mortality rate with SOD, and a 3.5% decrease with SDD. Both decontamination procedures reduced the duration of MV, ICU and hospital length of stay, daily doses of antimicrobials and the incidence of ICU-acquired bacteremia caused by S. aureus, P. aeruginosa and Enterobacteriaceae. Moreover, isolation of Gram-negative bacteria decreased considerably in patients who were treated with SOD and SDD. Authors defend the administration of DSO because it does not include widespread systemic prophylaxis with cephalosporins, and so avoids the increase of antibiotic resistance in ICU.66 However, this study has a characteristic that has prevented the generalized recommendation of SOD and SDD: antibiotic resistance recorded in the studied ICU (Holland) is considered low (<5%) when compared to the rates of antibiotic resistance in other countries such as the USA.54,65 Studies in different locations, with different rates of antibiotic resistance, are needed in order to obtain a better and more widespread perception of the long-term effect of these measures.

  A later study, carried out in the same ICU, evaluated the impact of SOD and SDD on antibiotic resistance in Gram-negative bacteria, concluding that although SOD and SDD reduced mortality, both measures were associated with a gradual increase in antibiotic resistance, primarily to ceftazidime.67 Thus, American guidelines and other more recent ones do not recommend routine use of prophylactic antibiotics and SDD, due to concerns about the rising problem of antibiotic resistance.5,30,37

• c)

  Probiotics

  Probiotics are viable microorganisms present in sufficient number so that they can have a beneficial effect on the health of the host, which is achieved by colonization and changes of the microflora in a compartment of the host (e.g. oral cavity, gut), where they remain temporarily, favoring the growth of bacterial species beneficial to the organism, and decreasing the presence of potential pathogens.68,69

  A meta-analysis including five studies that analyzed the effect of probiotics in ventilated patients, concluded that its implementation reduced the incidence of VAP, ICU length of stay and colonization of the respiratory tract by P. aeruginosa; however, no differences were observed in mortality rates and MV duration.70 Two other studies that were not included in the mentioned analysis also proved the efficacy (reduction of VAP incidence and antibiotics use) and safety of probiotics administration in the prevention of VAP.69,71 It is a fact that probiotics administration has been shown to be promising in preventing VAP, possibly representing an alternative to antibiotic prophylaxis, due to the increasing problem of resistance. However, to date, no guidelines recommend their use. More studies are needed, with more representative patient populations, in order to extrapolate the results.

Besides all specific measures to prevent VAP, guidelines also recommend one of the most basic and common preventive measures of nosocomial infections: hygiene and disinfection of the hospital environment, healthcare professionals and medical devices.5,26–30 Regarding the latter, disinfection of the respiratory equipment, removal of the condensate with the ventilator circuit closed during the procedure, and use of sterile water when rinsing the reusable devices are recommended.

Adherence to hand hygiene programs is considered one of the most important preventive measures of healthcare-associated infections,72 and also has the advantage of being cheap. The CDC Guideline for Hand Hygiene in Health-Care Settings analyzed data from observational studies concluding that the percentage of health professionals who implement the recommended procedures for hand hygiene is highly variable, with an overall average of 40%.73 In order to reduce poor adherence, training of health professionals and assessment of their performance, distribution of information leaflets and lectures are suggested.74

Some guidelines emphasize the importance of VAP education and training programs for health professionals who are directly involved in providing health care to patients under MV,5,26–30 since it is associated with proven efficacy in reducing the incidence of VAP by 50%.79 A questionnaire carried out with 1200 USA nurses revealed that only 82% adhere to hand-washing practices, 77% use gloves, 52% raise the head of the bed to 30–45° during the entire day and 36% aspirate the subglotic secretions; it also revealed that nurses who used a protocol of oral hygiene were associated with a greater knowledge of the disease and a higher compliance with good service practices to reduce the risk of VAP.80 There are reasons for non-compliance with guidelines by health professionals, such as disagreement with the results of the studies, patient discomfort, fear of adverse effects, lack of resources and the associated costs with preventive measures.29

The authors declare that no experiments were performed on humans or animals for this study.

The authors declare that no patient data appear in this article.

The authors declare that no patient data appear in this article.