American Journal of Respiratory and Critical Care Medicine

For every action, there is an equal and opposite reaction.

—Sir Isaac Newton, Philosophiæ Naturalis Principia Mathematica

The above quotation, commonly used as a simplistic summary of Sir Isaac Newton’s work, actually offers profound insights into the relationship between a body and the forces acting on it, and explains as much of life and medicine as it does classical mechanics. One of the best examples in critical care medicine is the effort of the Department of Health and Human Services, Center for Medicare and Medicaid Services, Centers for Disease Control and Prevention (CDC), and The Joint Commission to decrease hospital-acquired infections, particularly ventilator-associated pneumonia (VAP), through public reporting of comparative rates and pay-for-performance. The reaction to these punitive efforts was to “game” the system by recategorizing patients with all the traditional criteria for VAP as purulent ventilator-associated tracheobronchitis or “sepsis” or to just avoid use of the word “pneumonia” in any progress note. Diagnosis and correct classification by infection control practitioners were limited by the notoriously subjective interpretations of chest radiographs, as well as other issues (1, 2).

With lack of consensus after decades of research focused specifically on VAP diagnosis (3), the CDC sought to revise the definitions used for VAP surveillance (2). They chose to overtly unlink their VAP surveillance definition from clinical management of patients and “focus its efforts on enhancing the reliability and usability of the VAP surveillance definitions” (2). The result is the new list of acronyms—ventilator-associated event (VAE), ventilator-associated complication (VAC), and infectious VAC (IVAC). IVACs with a positive respiratory tract Gram stain and/or culture would be defined as probable or possible VAP. Only VAC and IVAC are intended as possible candidates for future use in public reporting, hospital comparisons, and pay-for-performance, fully recognizing that VAC and IVAC can result from many complications other than VAP (2).

In this issue of the Journal, Klouwenberg and colleagues (pp. 947–955) add further evidence to the vagaries of the new VAP surveillance paradigm (4). They examined the correlation of VAE categories in a prospective study of VAP using well-defined criteria. With either a conservative or a more specific quantitative culture-based diagnosis of VAP, VAC criteria were only 33 to 44% sensitive and IVAC only 18 to 25%. More than half of VAPs were therefore not detected by either VAC or IVAC criteria. The reason most patients with VAP did not meet VAC criteria was insignificant increases in ventilator settings around the time of VAP diagnosis. So the central hypothesis of the VAE criteria—that VAP and other potentially preventable complications of mechanical ventilation can consistently be detected by worsening gas exchange—is clearly not true (2, 5). Because this VAE algorithm is a flow-down model, if a patient does not meet VAC criteria, they cannot meet the possible or probable VAP criteria. This finding calls into question the reliability of IVACs to assist in antibiotic stewardship projects, a hoped-for side benefit of new definition (6). To now concentrate all quality-improvement efforts on VAEs will clearly miss cases of VAP, the original goal of the CDC redefinition (2).

Just as classic mechanics ran into problems explaining bodies in motion, particularly above the speed of light, stability is an important issue with the VAE surveillance model. One of my early mentors strongly emphasized that stability in a ventilated patient is bad. The reason some patients with VAP may not meet the VAC criteria is that VAP delays improvement in gas exchange, rather than worsening it. Conversely, stability for 48 hours on low FiO2/positive end-expiratory pressure (PEEP) settings is an indication for spontaneous breathing trials, which may “destabilize” gas exchange, potentially requiring a subsequent increase in PEEP or FiO2. The more aggressive the attempts to extubate, the more likely will be the need to change FiO2 or PEEP for failures. Klouwenberg and colleagues analyzed a failed intermittent weaning trial as a VAE and demonstrated a significant increase in the total numbers of VACs with greater than 50% discordance in patients identified from their original definition (4). Although their method of analysis is flawed by artificially assigning a room air value to these episodes, the effect of weaning trials on VAEs needs further exploration to avoid a possible negative effect of VAE surveillance on efforts for early extubation. Earlier extubation is clearly the most effective intervention to avoid VAP and other ventilator-specific complications (7, 8).

The finding that PEEP increases caused the majority of VACs in the study of Klouwenberg and colleagues is surprising (4). Although possibly representing the intermittent weaning issue, the more likely explanation is that the usual approach to ventilation in the authors’ institutions is a higher PEEP/lower FiO2 strategy. This raises issues of variability in ventilator management strategies that will impact comparability of VACs between institutions (9). Institutions that do not decrease FiO2 aggressively after reaching 0.40 will have a much greater margin before deterioration in gas exchange can be detected compared with those who aggressively titrate FiO2. A correction factor for the ratio of arterial saturation to FiO2 may be needed to avoid gaming this criterion.

One of the great hopes of the new VAE surveillance protocols is that monitoring can be done electronically with resultant decrease in infection control practitioner time (2, 5, 10). The electronic minute-to-minute monitoring of ventilator settings used in the study of Klouwenberg and colleagues demonstrates potential problems with this as well (4). They correlated a variety of algorithms for their minute-to-minute data with prospectively defined VAP. Their primary analysis was incorrect in that it used the lowest recorded FiO2/PEEP for any duration of time. The official CDC definition for “minimal daily PEEP or FiO2 used for surveillance is the lowest setting during a calendar day that is maintained for at least 1 hour” (11). So the author’s “sustained settings rule” is actually the correct analysis for the current VAC algorithm, but the results are essentially the same as their primary analysis (although the individual patients identified may differ). That may not be true for centers with different ventilatory strategies (9).

So has the VAE surveillance algorithm delivered on any of the proposed benefits (2)? Clearly, with properly programmed electronic surveillance, the VAE algorithms will decrease infection control practitioner time commitment. Reliability for between-hospital comparisons is questionable, whereas intrahospital comparisons may be valid (9). However, the actual clinical entity being compared is unclear, and therefore its use for quality improvement is questionable. The study of Klouwenberg and colleagues confirms others’ findings that VAEs poorly correlate with VAP (4, 9). A VAC “bundle” to address all the multiple potential causes, including variability resulting from the original disorder leading to mechanical ventilation, will be difficult to design. So with VAE surveillance, we do not know what we are detecting or what to do about it, but we can detect it faster and easier.

If VAE surveillance is subsequently linked to public reporting or pay-for-performance, the Newtonian-predicted reaction will be manipulation of ventilatory strategy to minimize VAEs without resultant clinical benefit. The missing factor of this equation is better diagnostics. Once these are available, we can enter the quantum mechanics era of VAP prevention.

1. Klompas M. Interobserver variability in ventilator-associated pneumonia surveillance. Am J Infect Control 2010;38:237239.
2. Magill SS, Klompas M, Balk R, Burns SM, Deutschman CS, Diekema D, Fridkin S, Greene L, Guh A, Gutterman D, et al. Developing a new, national approach to surveillance for ventilator-associated events. Crit Care Med 2013;41:24672475.
3. American Thoracic Society; Infectious Diseases Society of America. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med 2005;171:388416.
4. Klouwenberg PMCK, van Mourik MSM, Ong DSY, Horn J, Schultz MJ, Cremer OL, Bonten MJM. Electronic implementation of a novel surveillance paradigm for ventilator-associated events: feasibility and validation. Am J Respir Crit Care Med 2014;189:947955.
5. Klompas M, Kleinman K, Platt R. Development of an algorithm for surveillance of ventilator-associated pneumonia with electronic data and comparison of algorithm results with clinician diagnoses. Infect Control Hosp Epidemiol 2008;29:3137.
6. Klompas M. Complications of mechanical ventilation—the CDC’s new surveillance paradigm. N Engl J Med 2013;368:14721475.
7. Ely EW, Baker AM, Dunagan DP, Burke HL, Smith AC, Kelly PT, Johnson MM, Browder RW, Bowton DL, Haponik EF. Effect on the duration of mechanical ventilation of identifying patients capable of breathing spontaneously. N Engl J Med 1996;335:18641869.
8. Girard TD, Kress JP, Fuchs BD, Thomason JW, Schweickert WD, Pun BT, Taichman DB, Dunn JG, Pohlman AS, Kinniry PA, et al. Efficacy and safety of a paired sedation and ventilator weaning protocol for mechanically ventilated patients in intensive care (Awakening and Breathing Controlled trial): a randomised controlled trial. Lancet 2008;371:126134.
9. Muscedere J, Sinuff T, Heyland DK, Dodek PM, Keenan SP, Wood G, Jiang X, Day AG, Laporta D, Klompas M; Canadian Critical Care Trials Group. The clinical impact and preventability of ventilator-associated conditions in critically ill patients who are mechanically ventilated. Chest 2013;144:14531460.
10. Klompas M, Kleinman K, Khan Y, Evans RS, Lloyd JF, Stevenson K, Samore M, Platt R; CDC Prevention Epicenters Program. Rapid and reproducible surveillance for ventilator-associated pneumonia. Clin Infect Dis 2012;54:370377.
11. Centers for Disease Control and Prevention CfDCa. Ventilator-associated event (VAE) [accessed 2014 Mar 5]. Available from: http://www.cdc.gov/nhsn/PDFs/pscManual/10-VAE_FINAL.pdf

Author disclosures are available with the text of this article at www.atsjournals.org.

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American Journal of Respiratory and Critical Care Medicine
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