What are the key principles of preventing ventilator-associated pneumonia?

Ventilator-associated pneumonia (VAP) is caused by aspiration of pathogens from the aerodigestive tract into the lungs. Prevention of VAP therefore depends upon mitigating the risk of aspiration with pathogenic organisms. The key principles of prevention can be divided into the following categories:

Limit the development, selection, and spread of pathogenic organisms in the intensive care unit

Antibiotic stewardship can limit the development and selection of difficult to treat organisms. Rigorous hand hygiene, adherence to contact precautions, adequate staffing, and environmental cleaning can limit the spread of pathogens from patient-to-patient via healthcare workers and equipment.

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Minimize exposure to the ventilator

The biggest risk factor for developing VAP is intubation and prolonged mechanical ventilation since the endotracheal tube acts as a locus for bacterial colonization of the airway and inhibits the body’s natural mechanisms for clearing pulmonary secretions.

If it is possible to manage a patient with non-invasive positive pressure ventilation instead of intubation than their risk of VAP is lower. This has to be counterbalanced to some extent by the risk of aspiration in a patient without definitive airway control so non-invasive positive pressure should be reserved for patients with a reasonable gag reflex and level of consciousness.

If a patient must be intubated then sedation management protocols have repeatedly been shown to shorten patients’ duration of mechanical ventilation. Key components of an effective sedation management protocol include: daily interruption of sedation, daily assessment of readiness to extubate, and protocol driven decreases in sedative doses.

Mechanically prevent aspiration

Continuous elevation of the head of the bed at 30 to 45 degrees recruits gravity to help prevent regurgitation of gastric contents from the stomach into the lungs. This is especially important in patients on enteral tube feeds where the risk of gastric regurgitation is particularly high.

Oral secretions that pool above the lower cuff of the endotracheal tube are another potential reservoir for infection that can precipitate pneumonia if they leak around the endotracheal tube cuff and into the lungs.

Maintaining cuff pressure above 20cm H2O and specialized endotracheal tubes equipped with a suction port above the cuff for continuous aspiration of subglottic secretions may reduce the volume of fluid seeping into the lungs across the cuff. Minimizing gastric over-distension reduces the likelihood of gross aspiration from the stomach.

Reduce colonization of the aerodigestive tract

Regular oral care with chlorhexidine can decrease the reservoir of pathogens in the mouth that might enter the lungs if the patient aspirates around the cuff of the endotracheal tube.

Lowering the acidity of the digestive tract may favor colonization and infection hence minimizing use of proton pump inhibitors and other acid suppressants may decrease the risk of VAP. These agents should be reserved only for patients at high risk for gastrointestinal bleeding. Nasotracheal intubation increases the risk of sinusitis, which in turn can precipitate VAP, hence orotracheal intubation is preferable.

Prevent inoculation of the patient from the ventilator circuit

The ventilator circuit is another potential reservoir of pathogens that can trigger VAP. Manipulation of the circuit is a risk factor for backwashing condensate in the circuit into a patient’s lungs; therefore avoid unnecessary manipulation of the ventilator circuit.

Condensate levels can be controlled through the use of a heat and moisture exchanger and regularly scheduled drainage of accumulated condensate. Inline suctioning through a closed circuit with a multi-use catheter reduces the risk of extrinsic contamination. A new ventilator circuit should be used for each patient but the ventilator circuit should only be changed if visibly soiled.

Current practice favors combining some or all of these measures into a prevention bundle in order to maximize prevention, simplify implementation, and take advantage of possible synergies between prevention measures.

The optimal components of a prevention bundle have not been well defined but at a minimum should probably include daily interruption of sedation, daily assessment of readiness to extubate, elevation of the head of the bed, and regular oral care with chlorhexidine. Staff education regarding the importance of VAP prevention and the advantages of a bundle approach facilitates staff ownership and adherence.

What are the key conclusions for available clinical trials and meta-analyses that inform control of ventilator-associated pneumonia?

Many trials of prevention measures have reported decreases in VAP rates but few have shown an impact on patients’ lengths of stay or mortality.

The following measures decrease patients’ ventilator days and/or mortality: daily interruption of sedation and daily assessment of readiness to extubate, ventilator weaning protocols, and digestive decontamination with oral and parenteral antibiotics.

Despite its impact on mortality, digestive decontamination is not routinely practiced in North America due to fears of promoting antibiotic resistant flora. Digestive decontamination is more commonly practiced in Europe.

Based on trial data available to date, the following measures decrease VAP rates but do not impact patients’ lengths of stay or mortality: regular oral care with chlorhexidine, elevation of the head of the bed, continuous aspiration of subglottic secretions, and silver coated endotracheal tubes.

What are the consequences of ignoring key concepts related to control of ventilator-associated pneumonia?

Very high rates of adherence to all components of prevention bundles appear necessary to realize bundles’ full potential.

Some studies report that adherence rates of 95-100% were necessary before they started to see dramatic decreases in their VAP rates.

Failure to maximally lower VAP rates has deleterious consequences for patients and for hospitals. VAP is associated with increased length of stay, increased hospital mortality, and increased antibiotic usage (which in turn drives risk of Clostridium difficile-associated disease, antibiotic resistant flora, and cost).

In addition, VAP prevention is an emerging national patient safety goal promoted by The Joint Commission. The Centers for Medicare and Medicaid Services are reportedly considering making VAP a non-reimbursable condition. Failure to maximally lower VAP rates is liable to not only hurt patients but also to damage a hospital’s reputation, accreditation, and/or compensation.

What other information supports the key conclusions of studies of ventilator-associated pneumonia e.g., case-control studies and case series?

Many institutions have reported remarkable decreases in their VAP rates with the implementation of VAP prevention bundles.

VAP series from the 1980s reported VAP rates of 25% or more whereas series published in the past few years reported rates of 5% or less.

Likewise, the national median VAP rate reported by the CDC has decreased from 9.3 and 4.9 VAPs per 1000-ventilator-days in 2004 (surgical and medical units respectively) to 5.3 and 2.5 VAPs per 1000-ventilator days in 2008. A number of institutions have also reported sustained periods with no VAPs.

Summary of current controversies.

  • The definition of VAP is subjective, labor intensive, and of limited accuracy.
  • There is no consensus on how to operationalize the surveillance definition.
  • Endotracheal tubes designed for continuous aspiration of subglottic secretions are associated with decreased VAP rates and antibiotic usage in some studies but not all. No study has yet shown an impact on patients’ outcomes.
  • Silver coated endotracheal tubes reduce VAP rates but have not yet been shown to impact patient’s outcomes
  • Digestive decontamination with enteral and parenteral antibiotics decreases bacteremia and mortality rates but may cultivate antibiotic resistant flora.
  • The optimal components of a VAP prevention bundle have not been defined.
  • The optimal approach to bundle implementation and monitoring has not been defined.

What is the role of and impact of ventilator-associated pneumonia or infections and the need for control relative to infections at other sites or other specific pathogens?

VAP is often cited as the most morbid of healthcare-acquired infections. The crude mortality of VAP is between 30-50%. Calculating the attributable mortality is elusive since the population at risk tends to have severe baseline disease but current estimates using sophisticated statistical models suggest an attributable mortality of about 10%.

Overview of important clinical trials, meta-analyses, case control studies, case series, and individual case reports related to infection control and ventilator-associated pneumonia.

Elevation of the head of the bed

Drakulovic et al. 1999 randomized 86 patients supine (0 degrees) versus semi-recumbent (45 degrees) positioning. They observed a VAP rate of 34% in the supine group versus 8% in the semi-recumbent group (P=.003). There appeared to be a strong interaction between enteral feeding and supine position: 88% of supine patients with enteral feeds developed VAP.

Van Nieuwenhoven et al. 2006 randomized 221 patients to semi-recumbent (45 degrees) versus supine (10 degrees) positioning. They found no difference in the VAP rates between these two groups. The study included continuous measurement of patients’ actual head of bed position. The average elevation in the semi-recumbent group was only 22.6 degrees versus 16.1 degrees in the supine group.

This study bespeaks the practical difficulty in maintaining head of bed elevation for prolonged periods.

Continuous aspiration of subglottic secretions

Bouza et al. 2008 randomized 714 patients to an endotracheal tube with continuous aspiration of subglottic secretions versus a conventional endotracheal tube. They found no difference in VAP rates but a 28% decrease in daily defined doses of antibiotics in the group assigned to continuous aspiration of subglottic secretions (P<.001).

There was no difference between groups in the duration of mechanical ventilation, length of ICU or hospital stay, or mortality in the intention-to-treat analysis.

Dezfulian et al. 2005 conducted a meta-analysis of trials assessing subglottic secretion drainage for preventing VAP. Five studies enrolling 896 patients were included. Subglottic secretion drainage decreased the rate of VAP by 49%.

There was no difference in duration of mechanical ventilation and ICU length of stay in the intention-to-treat analysis but when the authors excluded one study and limited the analysis to patients ventilated greater than 72 hours they found that secretion drainage delayed the onset of pneumonia by 6.8 days, shortened duration of mechanical ventilation by 2 days, and shortened ICU length of stay by 3 days.

Silver coated endotracheal tubes

Kollef et al. 2008 randomized 2003 patients to silver coated endotracheal tubes versus conventional endotracheal tubes. The authors stipulated a microbiological definition for VAP that required patients to have positive quantitative cultures of BAL.

There was no difference in the rate of clinically diagnosed VAP between the two groups but a 36% lower rate of microbiologically defined VAP in the silver-coated endotracheal tube group.

Notably, the authors’ definition of positive cultures included organisms such as Candida spp., Enterococcus spp., and “normal flora” hence the observed decrease in microbiologically-defined VAP was at least partially attributable to decreased colonization of the endotracheal tube rather than a decrease in invasive pneumonias.

There was no difference in patients’ duration of mechanical ventilation, ICU length of stay, or mortality.

Oral care with chlorhexidine

Chan et al. 2007 published a meta-analysis of trials assessing oral care with antibiotics or antiseptics to lower VAP rates.

There was no impact on VAP rates amongst the studies that used antibiotic decontamination. They assessed seven trials with 2144 patients that evaluated oral antiseptics (six trials of chlorhexidine, one of povidone-iodine). Oral antiseptics lowered the VAP rate by 44% (95% confidence interval, 19-61%). There was no impact on patients’ duration of mechanical ventilation, ICU length of stay, or mortality.

Digestive decontamination

De Smet et al. 2009 compared selective digestive decontamination, selective oropharyngeal decontamination, and standard care in a cluster randomized trial in 13 Dutch intensive care units. The study enrolled 5939 patients.

Selective digestive decontamination consisted of 4 days of intravenous cefotaxime and topical application of tobramycin, colistin, and amphotericin B to the oropharynx and stomach. Selective oropharyngeal decontamination consisted of the identical regimen but without intravenous cefotaxime.

The primary outcome of interest was 28-day mortality. There was no difference in mortality between the three study arms but the authors noted a failure of randomization whereby the average APACHE II score of patients in the standard care arm was significantly lower than patients in the two digestive decontamination arms.

In accordance with published standards for cluster randomized trials, the authors therefore performed a logistic regression to adjust for available covariates including APACHE II scores. In the adjusted analysis, both selective digestive decontamination and selective oropharyngeal decontamination were associated with lower mortality rates (hazard ratio 0.83 and 0.86 respectively).

Silvestri et al. 2007 conducted a meta-analysis of digestive tract decontamination. They included 51 randomized controlled trials assessing 8065 patients. They found a significant reduction in bloodstream infections (OR 0.73, 95% confidence interval 0.59-0.90) and mortality (OR 0.80, 95% confidence interval 0.69-0.94).

Daily sedative interruptions

Kress et al. 2000 evaluated the impact of daily sedative interruptions in mechanically ventilated patients. They randomized 128 patients to daily interruption of sedatives until wakefulness versus standard care (sedative management at physician’s discretion).

Patients randomized to sedative interruptions were ventilated for 2.4 fewer days (P=.004) and remained in the ICU for 3.5 fewer days (P=.02) compared to the standard care group. There was no difference between groups in complications such as self-extubations.

A retrospective analysis of the patients in this trial noted a lower albeit statistically non-significant VAP rate in the intervention arm (Schweickert et al. 2004).

Daily spontaneous breathing trials and sedative interruptions

Girard et al. 2008 assessed the additive benefit of daily sedative interruptions above a baseline regimen of daily spontaneous breathing trials. They randomized 336 patients to daily sedative interruption followed by a spontaneous breathing trial versus usual care with a spontaneous breathing trial.

Patients in the intervention arm were ventilated for 3.1 fewer days (P=.02) and discharged from hospital 4.3 days sooner (P=.04) compared to the control arm. More patients in the intervention arm self-extubated but there was no difference in re-intubation rates.

Controversies in detail.

The definition of VAP is subjective, labor intensive, and of limited accuracy.

The CDC’s National Healthcare Safety Network publishes a surveillance definition for VAP that has become the defacto standard for operational VAP surveillance and for many research studies.

The definition requires patients to fulfill radiographic, systemic, and pulmonary signs. Positive microbiology is optional. Radiographic signs include new or progressive infiltrates and consolidation. Systemic signs include fever, abnormal white blood cell count, and delirium. Pulmonary signs include rales, crackles, changes in the quality or quantity of pulmonary secretions, and worsening oxygenation.

Case series assessing the accuracy of these signs relative to histology, however, have repeatedly reported poor sensitivity and specificity. The complexity of operationalizing the VAP adds insult to injury since it requires painstaking analysis by a clinically sophisticated observer yet the inherently subjective nature of most of the criteria mean that different reasonable observers will come to different reasonable conclusions.

In essence, the definition requires surveyors to invest a great deal of time and effort to generate rates of questionable validity that are of limited suitability for comparisons across time and between institutions.

Some observers fear that high profile movements to lower VAP rates are subconsciously driving surveyors to interpret signs strictly and thereby artificially lower VAP rates.

Some advocate requiring positive sputum or BAL cultures (qualitative or quantitative) in order to add objectivity to the definition but in practice this adds little accuracy to surveillance due to high propensity for both false positive and false negative cultures.

There is no consensus on how to operationalize the surveillance definition.

The CDC recommends applying the surveillance definition through prospective daily bedside assessments. In practice, though, institutions have operationalized the CDC definition in very different ways. Many conduct surveillance retrospectively. This invites a risk of missing signs that might have been poorly documented.

Some institutions use chest radiographs as an initial screening instrument with further review only of patients with new or progressive infiltrates. Radiographic review is variously performed by institutional radiologists, intensivists, and infection preventionists. The latter sometimes review reports and sometimes review the actual chest images.

Other institutions screen patients on the basis of microbiology reports: only patients with positive sputum or BAL cultures are reviewed further for the presence or absence of VAP. Per the CDC definition, however, it is possible for a patient to have VAP without a positive sputum or BAL culture so this technique inherently misses cases.

Yet other institutions screen patients on the basis of changes in ventilator settings.

Continuous aspiration of subglottic secretions.

Endotracheal tubes equipped with a suction port above the tracheal cuff permit regular drainage of secretions that pool above the tracheal cuff and may therefore decrease the probability of secretions seeping around the cuff and inoculating the lungs.

These specialized endotracheal tubes have been evaluated in at least eight studies. Four of the six English language studies reported lower VAP rates with endotracheal tubes equipped with subglottic secretion ports. None of the reports demonstrated a decrease in ventilator days, ICU days, hospital days, or mortality.

Notably, the reports that did show an impact on VAP rates all limited enrollment to patients expected to require ventilation for at least 1 day (1 study) or 3 days (2 studies) whereas the reports that found no impact on VAP rates included all patients regardless of expected duration of mechanical ventilation.

This implies that aspiration of subglottic secretions may lower VAP rates in patients with longer ventilator stays. Operationally, however, it is very difficult to predict in advance who these patients are likely to be. It is therefore unclear whether or how to deploy these tubes rationally.

The Compendium of Strategies to prevent VAP jointly published by the Society of Healthcare Epidemiologists of America and the Infectious Disease Society of America recommends continuous aspiration of subglottic secretions as a second line measure for hospitals that have difficulty controlling VAP rates using first-line measures alone.

Silver coated endotracheal tubes.

A single, large, multicenter randomized controlled trial reported that silver coated endotracheal tubes are associated with 36% lower VAP rates compared to conventional endotracheal tubes. A follow-up cost-effectiveness evaluation suggested that silver coated tubes are cost effective.

Clinicians have not yet embraced this technology, though, because despite enrolling over 2000 patients and documenting a substantive decrease in VAP rates, there was no observed impact on patients’ ventilator days, lengths of stay, or mortality.

Digestive decontamination.

European clinicians have long embraced digestive decontamination with oral and parenteral antibiotics as a strategy to decrease the frequency of nosocomial infections including VAP and bloodstream infections. Many studies and meta-analyses have been published affirming that this strategy does decrease bacteremia, VAP, and even mortality rates.

Despite this evidence, North American clinicians have been slow to adopt this strategy. They fear that broad use of broad-spectrum agents will exacerbate high baseline rates of antibiotic resistant flora. Their concerns have been borne out in some studies of the microbial ecology in units using this strategy although not all. Interestingly, some studies even suggest that routine digestive decontamination with antibiotics lowers overall antimicrobial consumption.

The optimal components of a VAP prevention bundle have not been defined.

There is marked variability in the VAP prevention bundle components adopted by various institutions. The most famous bundle is that advocated by the Institute for Healthcare Improvement Prevention under the auspices of their 5 Million Lives Campaign.

This bundle includes elevation of the head of the bed, daily sedative interruption and assessment of readiness to extubate, peptic ulcer disease prophylaxis, deep venous thrombosis prophylaxis, and daily oral care with chlorhexidine.

Some hospitals, however, specifically exclude stress ulcer prophylaxis from their bundle since it seems to facilitate VAP and argue that venous thrombosis prophylaxis has nothing to do with VAP. Other hospitals include additional measures in their bundles such as one or more of staff education, hand hygiene, avoiding gastric over-distension, aspiration of subglottic secretions, lung protective ventilation, and ventilator weaning protocols in their protocols.

There are currently no prospective, controlled trials of VAP prevention bundles hence the evidence supporting one bundle versus another is sparse.

Bundle implementation and monitoring is variable.

Hospitals not only differ in which measures to include in VAP prevention bundles, they also differ in how to define and measure adherence to bundle components.

There is no consensus, for example, on the frequency of oral care with chlorhexidine, how it should be applied to the mouth, and what constitutes a valid contraindication. Likewise, there is no consensus on how to measure adherence with head of the bed elevation (should it be measured once daily, multiple times per day, or continuously) and who should do the measurements (the nurse caring for the patient or a more objective external observer).

Appropriate contraindications for foregoing daily sedative interruptions and daily assessment of readiness to extubate are also open to interpretation. Depending on how hospitals choose to define these measures and assess adherence, it is possible for similar apparent rates of adherence to conceal very different clinical practices at the bedside.

What national and international guidelines exist related to ventilator-associated pneumonia?

The CDC and the Healthcare Infection Control Practices Advisory Committee published “Guidelines for Preventing Healthcare Associated Pneumonia” in 2003. This document is comprehensive but slightly dated.

The American Thoracic Society and the Infectious Diseases Society of America jointly published guidelines for the diagnosis and prevention of VAP in 2005. This document includes a rich summary of the epidemiology, pathophysiology, diagnostic methods and dilemmas, and treatment recommendations.

More recently, the Society of Healthcare Epidemiologists of America, the Infectious Diseases Society of America, the CDC, and the Association of Professionals in Infection Control jointly published a “Compendium of Strategies for Prevention of Ventilator-Associated Pneumonia” that concisely summarizes key practices recommended to prevent VAP.

This document has been broadly endorsed by many additional professional societies and implementation-focused organizations including The Joint Commission, the American Hospital Association, the National Quality Forum, and the Institute for Healthcare Improvement.

Three European Societies (European Respiratory Society, European Society of Clinical Microbiology and Infectious Diseases, and the European Society of Intensive Care Medicine) have published a European perspective on defining, treating, and preventing hospital-acquired pneumonia.

What other consensus group statements exist and what do key leaders advise?

Rello and colleagues published a European care bundle for the prevention of VAP that formally weighted prevention recommendations using a technique called “multi-criteria decision analysis.”

Marin Kollef, a leading VAP researcher, published a seminal review on “Prevention of Hospital-Associated Pneumonia and Ventilator-Associated Pneumonia” in 2004.


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