Prevention of Ventilator-Associated Pneumonia

By Saadia R. Akhtar MD, MSc

Ventilator-associated pneumonia (VAP) is nosocomial pneumonia occurring in a mechanically ventilated patient > 48 hours after intubation. It is categorized as early-onset (defined by most experts as 48-96 hours after intubation) and late-onset (> 2-96 hours after intubation): these differ with respect to responsible bacterial agents as well as outcomes. With an estimated incidence of 8-28% of intensive care unit (ICU) patients, or 13-35 cases per 1000 ventilator-days, VAP is common.1,2

The pathogenesis of VAP involves 2 key steps. The first is bacterial colonization of the aerodigestive tract due to disruption of normal host defenses. The second is aspiration of colonizing organisms from the aerodigestive tract into the lower respiratory tract3. Thus, anything that promotes bacterial colonization or aspiration may increase risk of VAP. There is a 1-3% increase in risk with each ventilator day. Nasal intubation, nasogastric tubes, re-intubation, frequent ventilator circuit changes, sedation and paralysis, and feeding patients in the supine position all amplify the risk. Specific patient populations appear to be more likely to develop VAP: patients undergoing cardiothoracic surgery or major abdominal surgery and those with head trauma, burn injuries or underlying COPD are some examples. Prior antibiotic use may offer some protection against early-onset VAP but seems to increase risk of late-onset VAP.1-3

How best to make the diagnosis of VAP remains controversial. Traditional clinical criteria (new or progressive radiographic infiltrates, leukocytosis, fever, new purulent sputum production) or the clinical pulmonary infection score are usually utilized with or without airway sampling.1,4 Recent data demonstrate that addition of lower airway sampling significantly reduces inappropriate antibiotic use but does not impact overall survival.5 Based on this, some experts recommend lower airway sampling as standard practice. Others suggest that diagnostic strategies without lower airway sampling may produce similar results if consistently combined with a protocol to limit antibiotic use.6 Further studies are under way to try to resolve these issues.

The impact of VAP on patient outcomes is great. Attributable mortality is estimated to be 10-30% and is highest for late-onset VAP. In addition, VAP is associated with prolonged duration of mechanical ventilation and ICU and hospital stays as well as higher costs ($40,000 per patient).1,2 VAP prevention programs have been shown to improve outcomes and reduce costs. Thus it is recommended that all ICUs have a defined VAP prevention program in place to monitor incidence and outcomes and update practice by implementing preventive strategies supported by clinical evidence and national guidelines.3,7

General Preventive Strategies

Hand-hygiene is one of the most essential and clearly effective methods of preventing nosocomial infections, including VAP. Use of alcohol-based (> 60%) disinfectants is the recommended method for hand-hygiene as it is more efficient and appears to improve compliance compared to usual hand-washing.8 However, compliance remains unacceptably low at < 40-45% in most reports. Thus programs to monitor and improve adherence to hand-hygiene should be an essential part of every ICU.9

Increasing the use of non-invasive ventilation in appropriate circumstances (such as for acute respiratory failure in awake, alert COPD or CHF patients) will prevent VAP.10 For patients who must be intubated, use of orotracheal (rather than nasotracheal) intubation and measures to avoid re-intubations will reduce VAP risk. The latter include minimizing unplanned extubation by securing endotracheal tubes and utilizing proper restraints and sedation levels, using non-invasive ventilation in appropriate circumstances and continuing to develop our understanding of how to predict successful extubation.1,3

Respiratory Care Issues

Multiple, controlled trials have demonstrated that frequent (daily or every 48 hours) ventilator changes do not reduce and may increase risk of VAP compared to less frequent (every 7-14 days or as needed).11 Current recommendations are to change circuits only as needed. There is no clear data on the impact on VAP risk of the type of humidification system, in-line nebulizers vs metered-dose inhalers for bronchodilator delivery, closed vs open suction devices or routine chest physiotherapy.7,12

Patient Positioning

Studies using radioactively labeled gastric contents have demonstrated that reflux and aspiration of gastric contents are highest in the upine position and can be reduced in a semi-recumbent position. Multiple epidemiological studies have identified supine body position as a risk factor for VAP. Most recently, a randomized prospective trial of supine (0°) vs semi-recumbent (45°) position in 86 intubated, mechanically ventilated medical-respiratory ICU patients revealed a significant difference in VAP incidence (23% vs 5% for microbiologically confirmed pneumonia). The study was ended at the interim analysis due to this marked difference. The odds ratio of VAP for supine position was 6.8 (95% CI, 1.7-26.7). The effect was even greater for those patients receiving enteral nutrition in the supine position.13 Further prospective studies of semi-recumbent positioning are under way. Although 1 small single-center trial should not usually change practice, I suggest considering this intervention in every ICU because it is a simple, safe and cost-free strategy that may make a big impact.

Feeding

Gastric feeding in the supine position and gastric over-distention are associated with a greater likelihood of reflux, aspiration and VAP. Thus feeding in a semi-recumbent position and careful advancement of feeds with monitoring of residuals and use of pro-motility agents as needed may normalize VAP risk.3,13 Though it has been proposed that small-bowel feedings may reduce VAP risk, this has not been confirmed in randomized prospective trials.14 Until such information is available, I suggest that gastric feeding in the semi-recumbent position be employed. Only when this cannot be instituted successfully should small-bowel feedings be considered.

Continuous Aspiration of Subglottic Secretions

Decreasing pooling of secretions (contaminated with bacteria) above the ETT cuff may reduce aspiration of these secretions into the lower airways and, in turn, prevent VAP. Specially designed ETTs allow continuous aspiration of subglottic secretions (CASS). Valles et al applied CASS in a randomized controlled trial in 190 medical-surgical ICU patients. They found a significant reduction in VAP (RR 1.98; 95% CI, 1.03-3.82 in control patients), particularly due to H. influenza and gram-positive organisms. The onset of VAP was also delayed by an average of about 6 days in patients receiving CASS.15 Kollef et al randomized 343 cardiothoracic surgery patients to CASS or usual care. Though they observed less VAP in patients receiving CASS, this difference did not reach statistical significance. They did note, as Valles et al did, a delay in VAP onset as well as reduced Gram-positive and H. influenza infections in patients receiving CASS.16 Thus CASS may reduce and/or delay onset of VAP. Because of the latter, CASS may have its greatest role in patients with anticipated short-term intubation. At this time, although CASS is not universally recommended, it should be strongly considered and evaluated by each ICU for incorporation into its VAP prevention program.7

Choice of Stress Gastritis Prophylaxis

Because gastric alkalinization is associated with gastric bacterial colonization, it has been postulated that stress gastritis prophylaxis with H2-blockers or proton-pump inhibitors may increase risk of VAP. Though smaller studies have shown a protective effect of sucralfate when compared to H2-blockers, a recent large multicenter clinical trial demonstrated no significant difference. Twelve hundred medical and surgical ICU patients requiring > 48 hours of intubation were randomized to receive either sucralfate or ranitidine. There was no significant difference in incidence of VAP (defined either clinically or with microbiological-confirmation) in either arm. There was also no difference in ICU length of stay or ICU mortality. There was, however, reduced GI bleeding with ranitidine (RR, 0.44; 95% CI, 0.21-0.92).17 Thus, I suggest that mechanically ventilated ICU patients requiring stress gastritis prophylaxis should receive H2-blockers.

Selective Digestive Decontamination

Selective digestive decontamination (SDD) aims to limit or eliminate bacterial colonization of the oropharynx and GI tract of critically ill patients: a variety of regimens have been proposed including topical antimicrobials administered orally, intravenous (IV) antibiotics alone or a combination of topical and IV agents. The most commonly used topical pastes contain an aminoglycoside, polymyxin B and an antifungal agent. The usual IV antibiotic is a third-generation cephalosporin. Multiple clinical trials evaluating SDD over the past 2 decades were summarized in 2 recent meta-analyses which were critically appraised by Kollef in a recent commentary.18 The key findings are: 1) the reduction in VAP and any mortality benefit reported with use of SDD are found principally in postoperative and trauma populations; 2) only the regimen combining topical and IV antimicrobials is effective; 3) there is considerable evidence of colonization with Gram-positive organisms, Acinetobacter and other resistant organisms in patients treated with SDD. Thus, SDD is not recommended for universal use. However, in select surgical ICUs and with close monitoring and surveillance for impact on institutional microbiology, SDD may be an important strategy for VAP prevention.

Kinetic Bed Therapy

There is some evidence to suggest the benefit of kinetic bed therapy in reducing VAP incidence in immobilized critically ill patients and stroke patients. The largest controlled study to date was done by Gentilello et al19 in 60 ICU patients who were immobilized due to head injury or requirement for traction. They found a significant reduction in the combined end point of atelectasis and pneumonia with use of kinetic bed therapy but now for either alone. There are no larger studies and no controlled studies in other patient populations. No US or international critical care guidelines recommend this as a general measure: however, it is a part of the Canadian Critical Care Trials Group VAP Prevention guidelines.

Other

There is no defined role for IV prophylactic antibiotics or immune globulin for VAP prevention in the general critically ill population at this time.3

There is limited data on the efficacy of chlorhexidine oral rinse for reducing VAP risk in cardiothoracic surgery patients. Houston et al compared a 0.12% chlorhexidine rinse with Listerine in 561 patients undergoing cardiothoracic surgery. Though there was no difference in VAP overall, in retrospect, patients intubated for > 24 hours and with positive sputum cultures had significant reduction in VAP rates (58%).20 Further study is warranted to confirm the benefit of chlorhexidine oral rinse and define appropriate patient populations for use. It is not recommended for use at this time.

In vitro and animal investigations demonstrate that silver-coated ETTs prevent Pseudomonas colonization.21 Clinical utility is yet to be defined.

Conclusion

Available evidence supports the routine use of a number of specific measures to prevent VAP (see Table, below). Every ICU should have a VAP surveillance and prevention strategy in place. Careful monitoring and frequent updates are necessary for such a strategy to be effective. At a minimum, every ICU should encourage compliance with hand-hygiene. In addition, use of non-invasive ventilation when appropriate, orotracheal instead of nasotracheal intubation, orogastric instead of nasogastric tubes and change of ventilator circuits only as needed are all practices that should be in place universally. Semi-recumbent (45°) positioning should be strongly considered while further data are pending: it should at least be employed for all patients receiving gastric feedings. Finally, application of CASS and SDD should be individualized: in select ICU populations, these interventions are safe and important means of reducing VAP incidence.

References

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2. Heyland DK, et al. The Attributable Morbidity and Mortality of Ventilator-Associated Pneumonia in the Critically Ill Patient. Am J Respir Crit Care Med. 1999:159:1249-1256.

3. Kollef MH. The Prevention of Ventilator-Associated Pneumonia. New Engl J Med. 1999:340: 627-634.

4. Fabregas N, et al. Clinical Diagnosis of Ventilator-Associated Pneumonia Revisited: Comparative Validation Using Immediate Post-Mortem Lung Biopsies. Thorax. 1999:54:867-873.

5. Fagon JY, et al. Invasive and Non-Invasive Strategies for Management of Suspected Ventilator-Associated Pneumonia. A Randomized Trial. Ann Intern Med. 2000:132:621-630.

6. Singh N, et al. Short Course Empiric Antibiotic Therapy for Patients with Pulmonary Infiltrates in the Intensive Care Unit. A Proposed Solution for Indiscriminate Antibiotic Prescription. Am J Respir Crit Care Med. 2000:162:505-511.

7. Tablan OC, et al. Guidelines for Preventing Health-care-Associated Pneumonia, 2003: Recommendations of the CDC and the Healthcare Infection Control Practices Advisory Committee. MMWR. 2004;53:1-36

8. Harbarth S, et al. Interventional Study to Evaluate the Impact of an Alcohol-Based Hand Gel in Improving Hand Hygiene Compliance. Pediatr Infect Dis J. 2002;21:489-495.

9. Boyce JM,et al. HICPAC/SHEA/APIC/IDSA Hand-Hygiene Task Force. Guideline for Hand Hygiene in Healthcare Settings. MMWR. 2002; 51:1-45.

10. Liesching T, et al. Acute Applications of Non-invasive Positive Pressure Ventilation. Chest. 2003;124:699-713.

11. Hess D, et al. Weekly Ventilator Circuit Changes: A Strategy to Reduce Costs without Affecting Pneumonia Rates. Anesthesiology. 1995;82:903-911.

12. Hess DR, et al. Care of the Ventilator Circuit and Its Relation to Ventilator-Associated Pneumonia. Respir Care. 2003;48:869-879.

13. Drakulovic MB, et al. Supine Body Position as a Risk Factor for Nosocomial Pneumonia in Mechanically Ventilated Patients: A Randomized Trial. Lancet. 1999;354:1851-1858.

14. Kearns PJ, et al. The Incidence of Ventilator-Associated Pneumonia and Success in Nutrient Delivery with Gastric Versus Small Intestinal Feeding: A Randomized Clinical Trial. Crit Care Med. 2000;28:1742-1746.

15. Valles J, et al. Continuous Aspiration of Subglottic Secretions in Prevention of Ventilator-Associated Pneumonia. Ann Intern Med. 1995;122:179-186.

16. Kollef MH, et al. A Randomized Clinical Trial of Continuous Subglottic Aspiration of Subglottic Secretions in Cardiac Surgery Patients. Chest. 1999;116:1339-1346.

17. Cook D, et al. A Comparison of Sucralfate and Ranitidine for the Prevention of Upper Gastrointestinal Bleeding in Patients Requiring Mechanical Ventilation. N Engl J Med. 1998;338:791-797.

18. Kollef MH. Selective Digestive Decontamination Should Not Be Routinely Employed. Chest. 2003; 123(5 Suppl):464S-468S.

19. Gentilello L, et al. Effect of a Rotating Bed on the Incidence of Pulmonary Complications in Critically Ill Patients. Crit Care Med. 1988;16:783-786.

20. Houston S, et al. Effectiveness of 0.12% Chlorhexidine Gluconate Oral Rinse in Reducing Prevalence of Nosocomial Pneumonia in Patients Undergoing Heart Surgery. Am J Crit Care. 2002;11:567-570

21. Hartmann M, et al. Reduction of the Bacterial Load By the Silver-Coated Endotracheal Tube (SCET), a Laboratory Investigation.Technol Health Care. 1999;7:359-370.

Dr. Akhtar is in the section of pulmonary and critical care medicine, Yale University School of Medicine, New Haven, CT.