Chapter 17. Prevention of Ventilator-Associated Pneumonia

Harold R Collard, M.D.
University of Colorado Health Sciences Center

Sanjay Saint, M.D., M.P.H.
University of Michigan School of Medicine

Introduction

Ventilator-associated pneumonia (VAP) is a leading cause of morbidity and mortality in the intensive care unit (ICU). The incidence of VAP varies greatly, ranging from 6 to 52% of intubated patients depending on patient risk factors. The cumulative incidence is approximately 1-3% per day of intubation. Overall, VAP is associated with an attributable mortality of up to 30%. Attributable mortality approaches 50% when VAP is caused by the more virulent organisms that typify late-onset VAP (occurring 4 or more days into mechanical ventilation). The cost per episode of VAP is substantial, although specific data are lacking. The average cost per episode of nosocomial pneumonia is estimated at $3000 to $6000, and the additional length of stay for patients who develop VAP is estimated at 13 days.

VAP is typically categorized as either early-onset VAP (occurring in the first 3-4 days of mechanical ventilation) or late-onset VAP. This distinction is important microbiologically. Early-onset VAP is commonly caused by antibiotic-sensitive community-acquired organisms (e.g., Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus). Late-onset VAP is commonly caused by antibiotic-resistant nosocomial organisms (e.g., Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus, Acinetobacter species, and Enterobacter species). Most episodes of ventilator-associated pneumonia (VAP) are thought to develop from the aspiration of oropharyngeal secretions containing potentially pathogenic organisms. Aspiration of gastric secretions may also contribute, though likely to a lesser degree. Tracheal intubation interrupts the body's anatomic and physiologic defenses against aspiration, making mechanical ventilation a major risk factor for VAP.

This chapter reviews 4 practices that carry the potential to reduce the incidence of VAP in patients receiving mechanical ventilation. They are: variation in patient positioning, continuous aspiration of subglottic secretions, selective digestive tract decontamination, and the use of sucralfate.

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Subchapter 17.1. Patient Positioning: Semi-recumbent Positioning and Continuous Oscillation

Background

Aspiration of gastric secretions likely contributes to the development of VAP. Semi-recumbent positioning of mechanically ventilated patients may help reduce the incidence of gastroesophogeal reflux and lead to a decreased incidence of VAP. Immobility in critically ill patients leads to atelectasis and decreased clearance of bronchopulmonary secretions. Both of these sequelae may lead to increased risk of VAP. Continuous rotation and movement of critically ill patients (termed continuous oscillation) may thus help prevent such changes.

Semi-recumbent positioning

Practice Description

Semi-recumbent positioning is generally defined as elevation of the head of the bed to 45 degrees. This is generally achieved in a hospital bed with patients' feet remaining parallel to the floor (i.e., the entire bed is not tilted) but this is not explicitly described in the published trials. Semi-recumbency is generally continued for the duration of mechanical ventilation.

Opportunities for Impact

Outside of select medical centers that have studied this practice, semi-recumbent positioning has not been widely adopted as the standard of care. Thus, such an intervention would have enormous opportunity for impact should it prove beneficial.

Study Designs

There have been three trials of semi-recumbent patient positioning and its effect on the incidence of VAP. Two of these studies measured aspiration events using nuclear medicine techniques, the other was a randomized trial with the primary outcome being VAP. In the one randomized trial, 86 patients were randomized at the time of intubation to semi-recumbent body position (45 degrees) or supine body position (0 degrees). All patients received the same general critical care (e.g., sterile endotracheal suctioning, stress ulcer prophylaxis with sucralfate if tolerating oral medications, no ventilator tubing changes, no selective digestive tract decontamination).

Study Outcomes

In the one randomized clinical trial, VAP was clinically defined as a new and persistent infiltrate on chest radiography, plus two of the following: temperature of >38.3C, leukocyte count >12,000/mm³ or <4000/mm³, purulent tracheal secretions. Microbiologic confirmation required the above criteria be met and the isolation of pathogenic bacteria from an endotracheal aspirate or bronchoscopic procedure. Mortality was reported at time of discharge from the ICU. Both studies of the frequency of aspiration measured radioisotope counts (counts per minute) of endotracheal aspirates at various time points before during and after semi-recumbent positioning.

Evidence for Effectiveness of the Practice

Only one randomized clinical trial of semi-recumbent patient positioning in mechanically ventilated patients has been published to date (see Table17.1.1). Semi-recumbent positioning was associated with a statistically significant reduction in both clinically and microbiologically-diagnosed VAP. There was no significant difference in mortality. These findings corroborate earlier studies that demonstrated decreased frequency of gastroesophogeal reflux with semi-recumbent positioning, and an independent association of supine positioning with the development of VAP.

Potential for Harm

No adverse effects were observed in patients randomized to semi-recumbent positioning. However, patients were excluded if they had any of the following conditions: recent abdominal or neurologic surgery (<7 days), shock refractory to vasoactive therapy, and previous recent endotracheal intubation (<30 days).

Costs and Implementation

The cost of semi-recumbent positioning is negligible and implementation is simple but will require healthcare provider education.

Continuous oscillation

Practice Description

Continuous oscillation utilizes mechanical beds that employ either rotating platforms or alternating inflation/deflation of mattress compartments to turn patients from side to side. These beds achieve 40 to 60 degrees of tilt and can cycle every 5-30 minutes as programmed. In general, in published trials, continuous oscillation was started within 24 hours of admission to the ICU and continued until discharge.

Opportunities for Impact

Continuous oscillation is infrequently applied to critically ill patients. Thus, this intervention would have significant opportunity for impact should it prove beneficial.

Study Designs

A meta-analysis of six randomized controlled trials evaluated the effect of continuous oscillation on clinical outcomes, including pneumonia, in critically ill patients. The vast majority of patients were mechanically ventilated but the absolute percentage is not reported in most trials. Five of the six trials included were limited to surgical and/or neurologic patients. A subsequent randomized controlled trial included 103 medical and surgical patients. In most cases, continuous oscillation was compared to standard critical care practice of rolling patients every two hours.

Study Outcomes

The definition of VAP varied among trials but was generally clinical and required a new infiltrate on chest radiography, fever, and leukocytosis. Microbiologic confirmation was not consistently obtained. Mortality was recorded at time of ICU discharge.

Evidence for Effectiveness of the Practice

The role of continuous oscillation in the prevention of VAP is unclear (see Table 17.1.1). A meta-analysis of six randomized controlled trials on this subject found a statistically significant reduction in the risk of pneumonia. Five of these studies were limited to surgical and/or neurologic patients. The sixth study, which included primarily medical patients, failed to find any significant effect. A subsequent randomized controlled trial of medical and surgical patients also failed to find any benefit.

Potential for Harm

There were no significant risks of continuous oscillation in any of the randomized trials. Inadvertent disconnection of intravenous lines, increased ventricular ectopy, and patient intolerance were reported, but not quantified. Conscious patients tolerated the procedure poorly.

Costs and Implementation

The incremental cost of specialized beds capable of continuous oscillation has been estimated at approximately $100 per day. A significant reduction in VAP incidence and length of stay could result in cost savings.

Comment

Both semi-recumbent positioning and continuous oscillation are relatively low-cost, low-risk interventions. The one randomized trial to date of semi-recumbent positioning shows it to be an effective method of reducing VAP. While it has not proven to provide a mortality benefit, semi-recumbent positioning is a safe and straightforward intervention whose effectiveness should be confirmed by additional randomized clinical trials. Continuous oscillation is less clearly beneficial, although it may be effective in certain subgroups of patients (e.g., surgical, neurologic). It also deserves continued study.

Table 17.1.1. Patient positioning*

Study Design		Study Design, Outcomes	Pneumonia or Aspiration	Mortality
Continuous oscillation	Randomized controlled trial of semi-recumbent patient positioning in 86 mechanically ventilated patients. Primary outcome was VAP. (Drakulovic, 1999)	Level 1, Level 1	RR 0.24 (p=0.003)	RR 0.64 (p=0.289)
	Two-period crossover trial of semi-recumbent patient positioning in 15 mechanically ventilated patients. Primary outcome was pulmonary aspiration. (Orozco-Levi, 1995)	Level 3, Level 2	RR 0.65 (p<0.01)	-
	Randomized two-period crossover trial of semi-recumbent patient positioning in 15 mechanically ventilated patients. Primary outcome was pulmonary aspiration. (Torres, 1992)	Level 3, Level 2	RR 0.23 (p=0.036)	-
Semi-recumbent positioning	Randomized controlled trial of continuous oscillation in 103 critically ill medical and surgical patients (90% mechanically ventilated). Primary outcomes included pneumonia. (Traver, 1995)	Level 1, Level 1	RR 0.62 (p=0.21)	RR 0.85 (p>0.05)
	Meta-analysis of 6 randomized controlled trials of continuous oscillation in critically ill surgical or stroke patients (majority mechanically ventilated). (Choi, 1992)	Level 1A, Level 1	RR 0.50 (p=0.002)	No significant difference (data not reported)
	Randomized controlled trial of continuous oscillation in 86 critically ill medical patients (majority mechanically ventilated). Primary outcomes included pneumonia. (Summer, 1989)	Level 1, Level 1	RR 0.57 (p=0.40)	RR 0.93 (p>0.05)

* RR indicates relative risk; VAP, ventilator-associated pneumonia.

References

1. Craven DE, Steger KA. Nosocomial pneumonia in mechanically ventilated adult patients: epidemiology and prevention in 1996. Semin Respir Infect 1996;11:32-53.

2. Thompson R. Prevention of nosocomial pneumonia. Med Clin North Am 1994;78:1185-1198.

3. Drakulovic MB, Torres A, Bauer TT, Nicolas JM, Nogue S, Ferrer M. Supine body position as a risk factor for nosocomial pneumonia in mechanically ventilated patients: a randomised trial. Lancet 1999;354:1851-1858.

4. Orozco-Levi M, Torres A, Ferrer M, Piera C, el-Ebiary M, de la Bellacasa JP, et al. Semirecumbent position protects from pulmonary aspiration but not completely from gastroesophageal reflux in mechanically ventilated patients. Am J Respir Crit Care Med 1995;152:1387-1390.

5. Torres A, Serra-Batlles J, Ros E, Piera C, Puig de la Bellacasa J, Cobos A, et al. Pulmonary aspiration of gastric contents in patients receiving mechanical ventilation: the effect of body position. Ann Intern Med 1992;116:540-543.

6. Kollef MH. Ventilator-associated pneumonia. A multivariate analysis. JAMA 1993;270:1965-1970.

7. Choi SC, Nelson LD. Kinetic Therapy in Critically Ill Patients: Combined Results Based on Meta-Analysis. J Crit Care 1992;7:57-62.

8. Traver GA, Tyler ML, Hudson LD, Sherrill DL, Quan SF. Continuous oscillation: outcome in critically ill patients. J Crit Care 1995;10:97-103.

9. Summer WR, Curry P, Haponik EF, Nelson S, Elston R. Continuous Mechanical Turning of Intensive Care Unit Patients Shortens Length of Stay in Some Diagnostic-Related Groups. J Crit Care 1989;4:45-53.

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Subchapter 17.2. Continuous Aspiration of Subglottic Secretions

Background

Ventilator-associated pneumonia (VAP) frequently develops from the aspiration of oropharyngeal secretions containing potentially pathogenic organisms. Tracheal intubation interrupts the body's anatomic and physiologic defenses against aspiration, making mechanical ventilation a major risk factor for VAP. The accumulation of contaminated oropharyngeal secretions above the endotracheal tube cuff may contribute to the risk of aspiration. Removal of these pooled secretions through suctioning of the subglottic region, termed continuous aspiration of subglottic secretions (CASS), may reduce the risk of developing VAP.

Practice Description

Continuous aspiration of subglottic secretions requires intubation with specially designed endotracheal tubes (see Figure 17.2.1). These endotracheal tubes contain a separate dorsal lumen that opens into the subglottic region, allowing for aspiration of any pooled secretions. The amount of secretions is monitored (usually daily) and the patency of the suction lumen is tested frequently (every few hours). In studies of the impact of this practice, aspiration has been applied from time of intubation to time of extubation. One of the studies tested manual aspiration performed hourly instead of continuous mechanical aspiration.

Opportunities for Impact

Continuous aspiration of subglottic secretions is an uncommon practice. The opportunities for impact are therefore significant should this practice prove beneficial in lowering rates of VAP.

Study Designs

There have been three randomized controlled trials of CASS to date. (Table 17.2.1) Two have included both medical and surgical patients requiring mechanical ventilation for greater than 72 hours and one included only post-cardiac surgery patients. All three studies randomized patients to CASS or standard care. Attempts were made to control for additional, potentially effective preventive strategies such as patient positioning, frequency of ventilator circuit changes, type of stress ulcer prophylaxis used, and administration of antibiotics.

Study Outcomes

All trials reported development of VAP and mortality at the time of extubation, ICU or hospital discharge. VAP was generally defined as a new radiographic infiltrate plus two of the following: fever, leukocytosis/leukopenia, or purulent tracheal aspirate. Microbiologic confirmation was not consistently obtained. Time to development of VAP was also reported. Mortality was reported at time of discharge from the hospital.

Evidence for Effectiveness of the Practice

One of the three trials found a statistically significant decrease in the incidence of VAP with CASS when compared to standard treatment, while a second study showed a strong trend (See Table 17.2.1). All three trials reported a statistically significant delay in the time to development of VAP, ranging from 48 hours to 8 days. Two trials found a decreased incidence of VAP caused by Staphylococcus aureus and Hemophilus influenzae, but no change was observed in the incidence of VAP caused by Pseudomonas aeruginosa or Enterobacteriaceae. No difference in mortality was observed in any of the trials.

Potential for Harm

There is minimal potential for harm to patients from the application of CASS and no adverse patient events were reported in over 150 patients.

Costs and Implementation

The cost and cost-effectiveness of CASS have not been examined. The direct costs appear minimal. Hi-Lo Evac tubes cost approximately 25% more than standard endotracheal tubes, putting the estimated cost of each unit at less than $1. The cost-savings per episode of VAP prevented could therefore be substantial. Implementation would largely be a matter of making the specialized endotracheal tubes available and providing staff training. The mechanical suctioning apparatus would require frequent monitoring by nursing or respiratory therapy to insure adequate function.

Comment

Continuous aspiration of subglottic secretions is a promising strategy for the prevention of VAP. Two randomized controlled trials have suggested a decrease in the rate of VAP in patients requiring prolonged (>3 days) mechanical ventilation (only one trial was statistically significant). The third trial showed no difference, but the patient population in this trial included many short-term intubations (mean duration of 36 hours) and was restricted to patients undergoing cardiac surgery. Larger randomized controlled trials are needed to address the impact of CASS more definitively.

Another interesting observation is the delay in the development of VAP and the decreased incidence of Staphylococcus aureus and Hemophilus influenzae. This suggests that CASS may provide most of its benefit by preventing early VAP caused by community-acquired organisms, and its use could therefore be targeted to those patients requiring mechanical ventilation for intermediate periods of time (i.e., those at greatest risk for early VAP).

Figure 17.2.1. Diagram of continuous aspiration of subglottic secretions (copied with permission)

Table 17.2.1. Randomized trials of continuous aspiration of subglottic secretions*

Study Description	Study Outcomes	Relative Risk of Pneumonia (95% CI)	Relative Risk of Mortality (95% CI)
Kollef, 1999: 343 patients undergoing cardiac surgery and requiring mechanical ventilation	Level 1	0.61 (0.27-1.40)	0.86 (0.30-2.42)
Valles, 1995: 153 patients requiring prolonged mechanical ventilation	Level 1	0.47 (0.21-1.06)	1.09 (0.72-1.63)
Mahul, 1992: 145 patients requiring mechanical ventilation for more than 3 days	Level 1	0.46 (0.23-0.93)	1.14 (0.62-2.07)

* CI indicates confidence interval.

References

1. Craven DE, Steger KA. Nosocomial pneumonia in mechanically ventilated adult patients: epidemiology and prevention in 1996. Semin Respir Infect 1996;11:32-53.

2. Mahul P, Auboyer C, Jospe R, Ros A, Guerin C, el Khouri Z, et al. Prevention of nosocomial pneumonia in intubated patients: respective role of mechanical subglottic secretions drainage and stress ulcer prophylaxis. Intensive Care Med 1992;18:20-25.

3. Valles J, Artigas A, Rello J, Bonsoms N, Fontanals D, Blanch L, et al. Continuous aspiration of subglottic secretions in preventing ventilator-associated pneumonia. Ann Intern Med 1995;122:179-186.

4. Kollef MH, Skubas NJ, Sundt TM. A randomized clinical trial of continuous aspiration of subglottic secretions in cardiac surgery patients. Chest 1999;116:1339-1346.

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