© 2006 American Thoracic Society doi: 10.1164/rccm.2512004
Preventing Ventilator-associated PneumoniaTiptoeing through a MinefieldLahey Clinic Medical Center, Burlington, Massachusetts
Tufts University School of Medicine Boston, Massachusetts For more than 50 years, mechanical ventilation has been a minefield, fraught with hazards for patients. Between 9 and 27% of intubated patients acquire ventilator-associated pneumonia (VAP), with a median incidence of approximately five episodes per 1,000 ventilator days (1–3). Crude mortality rates vary from 20 to 60%, and many survivors have lengthy hospital stays, significant morbidity, and health care costs ranging from $12,000 to $40,000 per patient (1, 3, 4). These poor outcomes underscore the need for better prevention strategies. VAP pathogenesis is a dynamic process, involving a wide spectrum of pathogens and complex interactions with host defenses (1, 3, 4). Bacteria causing VAP usually originate in the oropharynx. The endotracheal tube increases the risk of VAP 6- to 20-fold, facilitating bacterial access to the lung and providing a nidus for the growth of biofilm-encased bacteria (1, 3–5). Poor patient outcomes are associated with late-onset disease (> 5 d) and infections caused by multidrug-resistant bacteria, such as Pseudomonas aeruginosa, Acinetobacter species, or methicillin-resistant Staphylococcus aureus (4). Investigators have attempted to prevent VAP by reducing oropharyngeal colonization with head elevation, continuous aspiration of subglottic secretions, or selective decontamination of the digestive tract (SDD), using combinations of topical antimicrobials, with or without systemic antibiotics (2, 4, 6, 7). Although more than 50 randomized clinical trials and 10 meta-analyses of SDD demonstrate significantly reduced rates of VAP, the impact on mortality is inconsistent, and there are concerns about engendering antimicrobial resistance (7). Topical antiseptics, such as chlorhexidine (CHX), provide an attractive alternative, but initial success in cardiac surgery patients could not be confirmed (8, 9). In this issue (pp. 1348–1355), Koeman and coworkers provide important data from a multicenter, double-blind, randomized clinical trial of VAP outcomes for subjects treated with 2% CHX paste (n = 127), 2% CHX + 2% colistin (COL) paste (n = 128), or placebo (n = 127) (10). COL was added to augment the relatively weak activity of CHX against gram-negative bacilli. The daily risk of VAP was reduced 65% in the CHX group (p = 0.01) and 55% in the CHX-COL group (p < 0.03) compared with placebo, yet no differences were noted in duration of mechanical ventilation, intensive care unit stay, or survival. Nonetheless, this is an impressive result for an inexpensive, nontoxic modality and warrants further attention. The study of Koeman and colleagues raises several important concerns (10). The use of "sequential analysis" is an intriguing concept and offers promise of more efficient study design, but the small numbers may have limited power and increase the possibility of an erroneous conclusion. For example, there appear to be significantly more males and patients with infections in the placebo group, which questions the effectiveness of randomization. Second, it is difficult to reconcile significant reductions in VAP risk with an absence of effect on ventilator days, length of stay, or mortality. Indeed, absolute mortality data are not provided, nor is there a Kaplan-Meier plot of the incidence of VAP in each group. Why wasn't CHX ultimately more effective and why did some patients fail prophylaxis? Data are limited on how best to apply CHX paste and its pharmacokinetics, in vitro efficacy, impact on biofilm formation, or possible bacterial resistance, as reported for other topical agents (11, 12). Furthermore, it is important to understand how the use of CHX and CHX-COL will complement other recommended prevention strategies and health care improvement projects for VAP (3, 4, 6, 7). Compared with clinical diagnosis, quantitative diagnosis of VAP improves specificity (4). In this study, VAP rates appeared high, perhaps reflecting the inclusion of Candida species and other commensals that may represent colonization rather than VAP. In one randomized trial, quantitative culture data obtained by bronchoscopy with bronchoalveolar lavage (> 104 bacteria/ml) or protected specimen brush (> 103 bacteria/ml) resulted in fewer diagnoses of VAP, significantly lower 14-day mortality, and fewer antibiotic days than in patients managed clinically (13). Nonbronchoscopic bronchoalveolar lavage offers a convenient bedside alternative that allows expeditious initiation of empiric antibiotic therapy (4). In the future, quantitative methods for VAP diagnosis, like those for urinary tract infection, may also provide a better standard measure for comparing rates among hospitals. Liam Donaldson, chairman of the World Alliance for Patient Safety, recently reported that the risk of death from a medical error is 1 in 300 compared with 1 in 10 million for airline travel (14). There is growing interest in applying the principles of industrial safety to prevention of health care–associated infections, but the response has been notably slow (15, 16). The Institute for Healthcare Improvement's "100,000 Lives Campaign" (www.IHI.org) has helped translate guidelines from the bench to the bedside, successfully enlisting nearly 3,000 hospitals to establish safety programs that include a "VAP prevention bundle," recommending elevation of the head of the bed 30° to prevent aspiration, sedation vacations for earlier extubation, and prophylaxis against both stress bleeding and deep venous thrombosis. Some participating hospitals are now reporting zero episodes of VAP over sustained periods of time (D. Berwick, National Forum on Quality Improvement in Health Care, Orlando, FL, December 13, 2005; available at www.IHI.org). Confirmation of these dramatic results in peer-reviewed journals is eagerly anticipated. Prevention of VAP is a multidisciplinary team effort in which nurses, respiratory therapists, physicians, and administrators each play a vital role. These teams can take a further quantum leap by collaborating with infection control and quality improvement staff, who add expertise, personnel, and administrative and logistical support to facilitate best practice. Recent experience suggests that "zero tolerance" is becoming an achievable goal. Regulatory and payor agencies, such as the Joint Commission for Accreditation of Healthcare Organizations and the Center for Medicaid Services, have adopted aggressive benchmarks allied with "pay for performance" incentives. Our remaining task is to clear the minefields, exploring the benefits of quantitative diagnosis, VAP bundles, and topical antiseptics while applying the lessons we have learned in the past. FOOTNOTES Conflict of Interest Statement: D.E.C. is part of the Bard multicenter study of the randomized clinical trial evaluating a silver-coated endotracheal tube ($100,000) to prevent pneumonia. He has received honoraria for speaking at symposia, meetings, and local conferences from Pfizer ($8,000), Merck ($5,000), Elan ($6,000), Cubist ($5,000), and Wyeth ($1000). He is a member of the data-safety monitoring board for Johnson and Johnson ($2,500). R.A.D. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript REFERENCES
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