Chapter 72: Clinical Controversies: Ventilator-Associated Pneumonia: Does It Exist?

In the United States, ventilator-associated pneumonia (VAP) is the most commonly diagnosed hospital-acquired infection in intensive care units (ICUs), affecting upward of 20% of ventilated patients with varyingly estimated attributable mortality ranging from 10% to 55%.¹ Acquisition of VAP is responsible for prolonged ICU and hospital length of stay (LOS), increased hospital costs, and increased utilization of antibiotics. In a post hoc retrospective-matched cohort analysis of microbiologically confirmed cases of VAP in the North American Silver-Coated Endotracheal Tube study, the authors calculate median total charges for patients with VAP were almost $200,000 compared to under $100,000 for patients without VAP. This was accounted for by the patients requiring intubation up to 5 days longer and as a consequence, significantly prolonging their ICU and hospital stays by 11 and 13 days, respectively.² A subsequent large, retrospective study comparing 2144 patients who had VAP as determined by International Classification of Diseases, Ninth Revision code to a matched cohort of patients without VAP showed similar findings. The patients with VAP had longer mean durations of mechanical ventilation (21.8 vs 10.3 days), prolonged ICU and hospital LOS (20.5 vs 11.6 and 32.6 vs 19.5, respectively), and an increase in hospital costs of almost $40,000.³ The high attributable mortality and costs associated with VAP have garnered much attention from national patient safety organizations as well as state and federal health agencies, mandating compliance with preventive measures and reporting metrics.

However, to begin any discussion about VAP, one must first consider by which criteria VAP is defined. Until recently, there was significant discrepancy between medical professional society’s definition of VAP and the Centers for Disease Control (CDC)/National Healthcare Safety Network’s reportable surveillance definition (Table 72–1). Crucial differences in timing of the onset of pneumonia in a mechanically ventilated patient and whether microbiologic criteria were necessary for diagnosis left these competing criteria at odds. As clinical and reporting definitions of VAP diverged, our ability to reliably estimate rates, costs, and impact of VAP diminished. This is demonstrated in a study by Klompas, where 3 infection control personnel (following the CDC surveillance definition) and 1 physician (used clinical judgment), independently reviewed 50 cases and were only able to agree on a diagnosis of VAP in 3 patients while the range of cases identified varied from 7 to 20 depending on the reviewer.⁴ In response to widespread confusion and concern over the discrepancy leading to misleading VAP rates and unclear VAP-associated mortality, the CDC altered its definition to include solely objective data for diagnosis and limited the diagnosis to onset after a minimum of 48 hours of ventilation with stable ventilator settings. This led to an entirely new classification of reportable ventilator-associated events (VAEs): ventilator-associated condition (VAC), infection-related ventilator-associated complication (iVAC), and finally possible VAP and probable VAP.⁵ Some would argue, however, that these new diagnoses, VAE, VAC, iVAC, and their criteria have yet to be fully vetted for sensitivity, specificity, preventability, and significant impact on patient outcomes. Therein lies the controversy surrounding VAP, our community of health care providers lacks a unified view of what the real clinical problem is and whether that fairly compares to what regulatory bodies feel should be preventable and thus a marker of ICU quality.

As previously stated, the lack of uniformly accepted diagnostic criteria for VAP has led to variability in publically reported rates, difficulty in determining accurate causes, epidemiology, prevention measures, and effective treatment. The Infectious Disease Society of America (IDSA) and American Thoracic Society (ATS) define VAP as pneumonia that develops more than 48 to 72 hours after initiation of ventilation via an endotracheal tube (EET) or tracheostomy tube.^6,7 Pneumonia is suggested by a new or progressive infiltrate on chest X-ray associated with signs or symptoms of infection (fever, leukocytosis, and purulent sputum) and worsening oxygenation. Chest X-ray findings are integral to the clinical diagnosis, wrought as they are with subjectivity, and difficulties in interpretation in the ICU setting due to the presence of overlying lines and tubes, as well as frequently abnormal baseline radiographs in patients admitted for respiratory failure due to pneumonia and acute respiratory distress syndrome. This constellation of clinical criteria possesses high sensitivity but low specificity. The addition of a lower respiratory tract specimen is recommended as it can improve diagnostic accuracy and guide antimicrobial use. This microbiologic approach, however, is also contentious with regards to how the specimen should be collected (protected specimen brush, bronchoscopically, tracheal aspirate, or mini-bronchoalveolar lavage) and how it should be analyzed (quantitatively or qualitatively). Regardless of the microbiology, the principle of VAP diagnosis according to these professional guidelines focuses on clinical criteria and initiation of empiric antimicrobial therapy pending clinical improvement. The original CDC surveillance definition for VAP also began with chest radiograph interpretation, this time specifying serial X-rays, distinguishing findings on whether the patient had an abnormal X-ray at baseline. After meeting radiographic criteria, innumerable combinations from an extensive menu of signs and symptoms of infection (including subjective assessments of character and quantity of sputum, findings on auscultation, and respiratory symptoms such as dyspnea and cough), worsening gas exchange, and laboratory data could arrive one at a diagnosis of VAP on clinical grounds alone or by virtue of positive culture results.⁸ The wide array of diagnostic possibilities may have been intended to provide the infection preventionist (someone trained in the field of infection control) with a menu of all the possible observed phenomena that could occur as a result of VAP; however, in practice, this was burdensome, impractical, and easily manipulated.

Since at least 1987, it has been recognized that the presence of an ETT predisposes patients to the development of pneumonia.⁹ In the constant battle between host defense mechanisms and microbial virulence factors, the presence of the ETT and ventilatory circuit present a worthy adversary. Bypassing anatomic barriers such as the glottis with an ETT, impairing cough reflexes with sedatives and hampering mucociliary function by desiccation of secretions from continuous air flow, undermines the body’s ability to prevent aspiration of organisms into the normally sterile lower respiratory tract and lung parenchyma. Risk of infection is compounded by eventual biofilm formation on the ETT and colonization of the upper airway with gram-negative organisms and frequently resistant hospital-acquired flora. Additionally, independent risk factors for VAP have been indentified and include nonmodifiable host factors (age > 60 years, underlying pulmonary disease and severity of illness) as well as modifiable risk factors inherent to bedside management of the patient (histamine-2 receptor antagonist use, sedation, duration of mechanical ventilation, maintenance of the ventilatory circuit, head of bed (HOB) position, and presence of a nasogastric tube).¹⁰

As earlier mentioned, in efforts to simplify VAP surveillance and reporting, the CDC revamped its surveillance definition to include a compilation of VAEs in January 2013.⁵ This shift in surveillance stemmed from the dispute and complexity of defining VAP, nonpneumonic complications associated with the ventilator (eg, ventilator-associated tracheobronchitis) and a desire to develop objective-surveillance criteria for uniformity and ease in reporting. VAEs as listed earlier include VAC (minimum sustained increases in positive end expiratory pressure (PEEP) or FiO₂ after a 2-days period of ventilator stability), iVAC (VAC plus signs of infection and initiation of a new antimicrobial agent that is continued for at least 4 days), possible VAP (iVAC plus symptoms of lower respiratory tract infection or positive cultures from respiratory specimen), and probable VAP (iVAC plus symptoms of lower respiratory tract infection and positive culture results from respiratory specimen).⁵ This new surveillance approach depicts VAEs as a spectrum of disease (Figure 72–1). However, Muscedere et al showed that agreement between VAC, iVAC, and VAP was low with positive predictive values of VAC and iVAC for VAP of only 28% and 40%, respectively.¹¹

A large retrospective multicenter study examining VACs, as evidenced by threshold increases in ventilatory support (> 2 days of sustained increase in PEEP of 2.5 cm H₂O or FiO₂ > 15 points) after a 48-hour period of stability, found a statistically significant association between VAC and duration of mechanical ventilation (median 13 vs 6 days, P < 0.001), ICU LOS (median 16.3 vs 8.0 days, P < 0.001), and hospital LOS (median 21 vs 16.0 days, P < 0.001) as well as hospital mortality (38% + VAC, 23% – VAC, P = 0.001) when compared to matched patients without VAC.¹² The authors appropriately cite the concern that it may be difficult to distinguish a VAC from a patent who requires increasing ventilatory support for respiratory failure from a disease that progresses despite intubation. This concern is mirrored by Muscedere’s study which showed higher Sequential Organ Failure Assessment (SOFA) scores in patients who subsequently developed VAC and iVAC compared to those who did not.¹¹ A subsequent small retrospective study by Lewis et al evaluating risk factors for VAEs, identified use of mandatory ventilator modes, positive net daily fluid balance, and benzodiazepine use prior to intubation as independent risk factors for VAC (mode of ventilation and fluid balance) and IVAC (benzodiazepine use).¹³ Not surprisingly, there was no impact of the individual ventilator bundle components on VAC or IVAC cases when compared to controls. So, while VAEs are more readily identifiable by objective criteria that can be easily extracted from the medical record, until more, large, prospective studies can be performed the clinical entity of VAEs as preventable, VACs remains debatable.

There are innumerable reports in the medical literature touting the achievement of “zero VAP” rates with implementation of the “VAP bundle.” Except, these publications vary in how they define VAP and no such VAP bundle actually exists. The ventilator bundle was introduced by the Institutes for Healthcare Improvement in 2005 as a means to improve clinical outcomes in mechanically ventilated patients.¹⁴ The elements of the ventilator bundle are well known and now routinely referred to as the VAP bundle despite measures such as deep venous thrombosis and stress ulcer prophylaxes that have no direct benefit to preventing VAP and in the latter case, may even increase risk of pneumonia and other complications such as Clostridium difficile infection in critically ill patients.¹⁵ Other bundle elements, including daily sedation “vacation” to limit duration of mechanical ventilation and HOB elevation target well-established independent risk factors for VAP as mentioned earlier but can be difficult to achieve in real practice. Nonetheless, health care quality agencies and state governments require compliance with these ventilator or VAP bundle elements to achieve zero VAP rates. Although all ICUs would aim to provide the best evidence-based care to achieve optimal outcomes for their patients, zero VAP is an unrealistic benchmark. There are nonmodifiable patient and disease-related risk factors that are outside of a care provider’s control. By proposing this benchmark, patient safety forums are misleading the public into believing that a patient’s course on a ventilator should be brief and uncomplicated, and if not achieved, may speciously reflect poor care and lack of bundle compliance. Furthermore, hospitals may be persuaded to use the subjectivity of some of the surveillance definitions to their advantage in order to report potentially lower VAP rates.

As with other hospital-acquired infections, the surveillance definition is not meant to be used clinically and differs out of the necessity to apply the surveillance definition across all hospitals, regardless of resources available, and ideally allows for minimal subjective interpretation to minimize case finding bias and allow for fair comparisons among hospitals. The CDCs replacement of VAP with publically reportable VAEs such as VAC and iVAC will undoubtedly shift focus away from the controversial and subjective VAP and toward establishing VAC and iVAC as the real threat to mechanically ventilated patients. And as with any novel initiative to improve patient safety and outcomes, new and potentially costly ideas for prevention will be brought to light and added to our ventilator bundle. As critical-care practitioners continue to strive to provide the best available evidence-based care for their patients, whether current clinical practice and professional guidelines will reflect this shift remains to be seen.