It Is Time to Care About Ventilator-Associated Tracheobronchitis* Jennifer A. Muszynski, MD Division of Pediatric Critical Care Medicine Department of Pediatrics Nationwide Children’s Hospital Columbus, OH; and Center for Clinical and Translational Research The Research Institute at Nationwide Children’s Hospital Columbus, OH Sarah Steward, MD Division of Pediatric Critical Care Medicine Department of Pediatrics Nationwide Children’s Hospital Columbus, OH Richard J. Brilli, MD, FAAP, MCCM Division of Pediatric Critical Care Medicine Department of Pediatrics; and Hospital Administration Nationwide Children’s Hospital Columbus, OH
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entilator-associated pneumonia (VAP) is associated with increased morbidity and mortality in children and is a common target for quality improvement (1, 2). Unfortunately, Centers for Disease Control (CDC) criteria used to diagnose pediatric VAP suffer from poor inter-rater reliability and may underestimate the true prevalence of infection (3, 4). Although VAP is infrequently diagnosed, nosocomial lower airway infections are often identified and treated. In fact, nosocomial lower airway infections are among the most common indications for antibiotic use in the PICU (5, 6). Some PICU respiratory infections that do not meet CDC criteria for VAP may be captured by CDC criteria for ventilator-associated tracheobronchitis (VAT) (7). The clinical significance of VAT in children is unclear. It is also unclear whether VAT represents a distinct infection or rather early pneumonia not meeting VAP criteria. Recent studies demonstrate reduced VAP rates after successful implementation of VAP prevention bundles (1, 8). These reduced rates should theoretically result in improved clinical outcomes and decreased antibiotic use in the PICU. However, this may not
*See also p. 565. Key Words: infection–related ventilator–associated complications; nosocomial infection; pediatric intensive care unit; ventilator–associated pneumonia; ventilator–associated tracheobronchitis Dr. Muszynski’s institution received grant support from the National Institutes of Health and the National Institute of Child Health and Development. The remaining authors have disclosed that they do not have any potential conflicts of interest. Copyright © 2015 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies DOI: 10.1097/PCC.0000000000000417
Pediatric Critical Care Medicine
be the case if VAT increases while VAP decreases, as reported by Wheeler et al (9) in this issue of Pediatric Critical Care Medicine. During the course of a quality improvement initiative targeting VAP reduction, the authors noted an increase in VAT cases and undertook a case-control study to evaluate outcomes related to VAT development in the PICU. In this single-center study, VAT was associated with longer durations of mechanical ventilation, increased PICU and hospital costs, and a trend toward increased mortality compared with matched controls. Upon initial review, we were struck by the remarkable cost per VAT event ($230,000), especially in the context of a study published in 2008 (2005– 2006 cost data) using similar methods, wherein VAP costs were $50,000 per event (10). These reviewers have assumed that VAP is a more severe PICU respiratory infection compared with VAT, and therefore, VAP costs would be predictably higher than VAT costs. Examination of at least two issues may clarify some of the differences. First, the length of stay (LOS) for the VAT cohort described by Wheeler et al (9) was nearly twice as long as the VAP cohort described by Brilli et al (10). Second, healthcare cost inflation over 10 years is also a substantial contributor. Using Bureau of Labor Statistics to calculate compounded healthcare inflation costs, we estimate at least a 50% increase in costs over the decade 2005–2015 (11). Using the LOS differences and impact of healthcare cost inflation, we estimate the costs per VAP event in today’s dollars at closer to $150,000–$180,000. While VAT costs are still higher, they are more in line with VAP costs, using the aforementioned adjustments. We commend the authors for including VAT surveillance in the course of their quality improvement initiative targeting VAP and for examining its distinct impact on patient outcomes. We believe the case-control study design is a good approach, although some limitations associated with that study design point to the difficulties encountered when trying to ascribe outcomes related to nosocomial infection. Namely, when factors such as duration of mechanical ventilation are both risk factors for infection development and outcome measures, it can be difficult to attribute outcomes to the infection itself as opposed to the underlying severity of illness. Furthermore, it can be very difficult to match cases to controls in a heterogeneous PICU population. Thus, the fact that the authors were unable to match all of their cases is not surprising. In addition, among the matched cohort, there is wide variation in hospital lengths of stay for both cases and controls, and despite statistically similar ICU lengths of stay for VAT and matched controls, the median hospital length of stay difference was quite large (54 d for VAT patients vs 33.5 d for controls; p = 0.23). The only statistically significant difference between the VAT patients and controls was ventilator days (17 d, VAT vs 10 d, controls; p = 0.01). Because we are unsure why VAT would independently influence hospital stay after ICU discharge, we speculate that there may have been other underlying differences between groups not www.pccmjournal.org
593
Copyright © 2014 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies. Unauthorized reproduction of this article is prohibited
Editorials
accounted for in the matching criteria. The authors could have tried to account for cohort differences with additional measures of illness severity; however, this would likely have resulted in even fewer matched cases and a potentially underpowered study. Alternatively, others have used propensity scoring as a method to match cohorts (12). Propensity score matching often allows for larger numbers of matched patients; however, the use of administrative databases for matching groups engenders its own set of challenges (13). The reviewers suggest that this alternative approach might be useful in future studies. Despite the challenges inherent in any retrospective study design, this is now the second study to demonstrate associations between VAT and increased resource utilization in the PICU. For example, we found that children in whom VAT developed had significantly fewer ventilator-free and ICU-free days compared with mechanically ventilated children in whom VAT or VAP did not develop (4.9 vs 22 and 0.5 vs 19, respectively) (14). These findings remained significant in multivariable analyses accounting for patient demographics, baseline diagnoses, and severity of illness (Pediatric Risk of Mortality III score). In our report and the study by Wheeler et al (9), cases of VAT were not associated with progression to VAP, suggesting that VAT alone has important and distinct clinical significance. The significant contribution of ventilator-associated infections to antibiotic use in the PICU, coupled with mounting evidence of VAT’s distinct impact on clinical outcomes, points to a need to include all ventilator-associated respiratory tract infections in surveillance programs and quality improvement initiatives. However, a major challenge exists due to the lack of a gold standard to diagnose ventilator-associated infection. Although strict criteria for VAP may miss clinically relevant infections, current criteria for VAT have the potential to overdiagnose infection. Recently, Willson et al (15) demonstrated that culture alone, even with purulence, may represent colonization as opposed to true infection. Many of the other current CDC criteria for VAT are either subjective (e.g., change in secretions) or infrequently observed in sedated, mechanically ventilated children (e.g., cough or apnea). In the future, biomarker-based approaches utilizing procalcitonin and/or C-reactive protein may potentially identify true infection with enhanced clarity. Unfortunately, the utility of inflammatory biomarkers to accurately diagnose nosocomial respiratory infection, particularly in children, is not yet established. The recently adopted CDC criteria for infection-related ventilator–associated complications or possible ventilator-associated pneumonia include more objective elements and may be of benefit—though these criteria have not yet been applied to or validated in pediatric patients (16). It remains unclear whether these criteria will improve nosocomial respiratory infection diagnostic accuracy in critically ill children. In summary, Wheeler et al (9) have contributed important new information about the clinical and financial impact of VAT
594
www.pccmjournal.org
on critically ill children. We believe that it is time to care about and implement VAT prevention strategies in our PICUs; however, future studies are needed to develop and validate accurate diagnostic algorithms that encompass all ventilator-associated infections in children. This work is vital because only by recognizing and measuring the true prevalence of nosocomial lower airway tract infections can we move toward zero harm in the PICU.
REFERENCES
1. Bigham MT, Amato R, Bondurrant P, et al: Ventilator-associated pneumonia in the pediatric intensive care unit: Characterizing the problem and implementing a sustainable solution. J Pediatr 2009; 154:582–587.e2 2. Gupta S, Boville BM, Blanton R, et al: A multicentered prospective analysis of diagnosis, risk factors, and outcomes associated with pediatric ventilator-associated pneumonia. Pediatr Crit Care Med 2015; 16:e65-e73 3. Stevens JP, Kachniarz B, Wright SB, et al: When policy gets it right: Variability in U.S. hospitals’ diagnosis of ventilator-associated pneumonia. Crit Care Med 2014; 42:497–503 4. Thomas BW, Maxwell RA, Dart BW, et al: Errors in administrativereported ventilator-associated pneumonia rates: Are never events really so? Am Surg 2011; 77:998–1002 5. Blinova E, Lau E, Bitnun A, et al: Point prevalence survey of antimicrobial utilization in the cardiac and pediatric critical care unit. Pediatr Crit Care Med 2013; 14:e280–e288 6. Carcillo JA, Dean JM, Holubkov R, et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Collaborative Pediatric Critical Care Research Network (CPCCRN): The randomized comparative pediatric critical illness stress-induced immune suppression (CRISIS) prevention trial. Pediatr Crit Care Med 2012; 13:165–173 7. Horan TC, Andrus M, Dudeck MA: CDC/NHSN surveillance definition of health care-associated infection and criteria for specific types of infections in the acute care setting. Am J Infect Control 2008; 36:309–332 8. Esteban E, Ferrer R, Urrea M, et al: The impact of a quality improvement intervention to reduce nosocomial infections in a PICU. Pediatr Crit Care Med 2013; 14:525–532 9. Wheeler DS, Whitt JD, Lake M, et al: A Case-Control Study on the Impact of Ventilator-Associated Tracheobronchitis in the PICU. Pediatr Crit Care Med 2015; 16:565–571 10. Brilli RJ, Sparling KW, Lake MR, et al: The business case for preventing ventilator-associated pneumonia in pediatric intensive care unit patients. Jt Comm J Qual Patient Saf 2008; 34:629–638 11. Bureau of Labor Statistics Data. Available at: http://data.bls.gov/ timeseries/CUUR0000SAM?output_view=pct_12mths. Accessed February 4, 2015 12. Goudie A, Dynan L, Brady PW, et al: Attributable cost and length of stay for central line-associated bloodstream infections. Pediatrics 2014; 133:e1525–e1532 13. Schneeweiss S, Rassen JA, Glynn RJ, et al: High-dimensional propensity score adjustment in studies of treatment effects using health care claims data. Epidemiology 2009; 20:512–522 14. Muszynski JA, Sartori J, Steele L, et al: Multidisciplinary quality improvement initiative to reduce ventilator-associated tracheobronchitis in the PICU. Pediatr Crit Care Med 2013; 14:533–538 15. Willson DF, Conaway M, Kelly R, et al: The lack of specificity of tracheal aspirates in the diagnosis of pulmonary infection in intubated children. Pediatr Crit Care Med 2014; 15:299–305 16. Ventilator associated pneumonia (VAP) events. 2015. Available at: http://www.cdc.gov/nhsn/PDFs/pscManual/10-VAE_FINAL.pdf. Accessed January 23, 2015
July 2015 • Volume 16 • Number 6
Copyright © 2014 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies. Unauthorized reproduction of this article is prohibited
V
entilator-associated pneumonia (VAP) is associated with increased morbidity and mortality in children and is a common target for quality improvement (1, 2). Unfortunately, Centers for Disease Control (CDC) criteria used to diagnose pediatric VAP suffer from poor inter-rater reliability and may underestimate the true prevalence of infection (3, 4). Although VAP is infrequently diagnosed, nosocomial lower airway infections are often identified and treated. In fact, nosocomial lower airway infections are among the most common indications for antibiotic use in the PICU (5, 6). Some PICU respiratory infections that do not meet CDC criteria for VAP may be captured by CDC criteria for ventilator-associated tracheobronchitis (VAT) (7). The clinical significance of VAT in children is unclear. It is also unclear whether VAT represents a distinct infection or rather early pneumonia not meeting VAP criteria. Recent studies demonstrate reduced VAP rates after successful implementation of VAP prevention bundles (1, 8). These reduced rates should theoretically result in improved clinical outcomes and decreased antibiotic use in the PICU. However, this may not
*See also p. 565. Key Words: infection–related ventilator–associated complications; nosocomial infection; pediatric intensive care unit; ventilator–associated pneumonia; ventilator–associated tracheobronchitis Dr. Muszynski’s institution received grant support from the National Institutes of Health and the National Institute of Child Health and Development. The remaining authors have disclosed that they do not have any potential conflicts of interest. Copyright © 2015 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies DOI: 10.1097/PCC.0000000000000417
Pediatric Critical Care Medicine
be the case if VAT increases while VAP decreases, as reported by Wheeler et al (9) in this issue of Pediatric Critical Care Medicine. During the course of a quality improvement initiative targeting VAP reduction, the authors noted an increase in VAT cases and undertook a case-control study to evaluate outcomes related to VAT development in the PICU. In this single-center study, VAT was associated with longer durations of mechanical ventilation, increased PICU and hospital costs, and a trend toward increased mortality compared with matched controls. Upon initial review, we were struck by the remarkable cost per VAT event ($230,000), especially in the context of a study published in 2008 (2005– 2006 cost data) using similar methods, wherein VAP costs were $50,000 per event (10). These reviewers have assumed that VAP is a more severe PICU respiratory infection compared with VAT, and therefore, VAP costs would be predictably higher than VAT costs. Examination of at least two issues may clarify some of the differences. First, the length of stay (LOS) for the VAT cohort described by Wheeler et al (9) was nearly twice as long as the VAP cohort described by Brilli et al (10). Second, healthcare cost inflation over 10 years is also a substantial contributor. Using Bureau of Labor Statistics to calculate compounded healthcare inflation costs, we estimate at least a 50% increase in costs over the decade 2005–2015 (11). Using the LOS differences and impact of healthcare cost inflation, we estimate the costs per VAP event in today’s dollars at closer to $150,000–$180,000. While VAT costs are still higher, they are more in line with VAP costs, using the aforementioned adjustments. We commend the authors for including VAT surveillance in the course of their quality improvement initiative targeting VAP and for examining its distinct impact on patient outcomes. We believe the case-control study design is a good approach, although some limitations associated with that study design point to the difficulties encountered when trying to ascribe outcomes related to nosocomial infection. Namely, when factors such as duration of mechanical ventilation are both risk factors for infection development and outcome measures, it can be difficult to attribute outcomes to the infection itself as opposed to the underlying severity of illness. Furthermore, it can be very difficult to match cases to controls in a heterogeneous PICU population. Thus, the fact that the authors were unable to match all of their cases is not surprising. In addition, among the matched cohort, there is wide variation in hospital lengths of stay for both cases and controls, and despite statistically similar ICU lengths of stay for VAT and matched controls, the median hospital length of stay difference was quite large (54 d for VAT patients vs 33.5 d for controls; p = 0.23). The only statistically significant difference between the VAT patients and controls was ventilator days (17 d, VAT vs 10 d, controls; p = 0.01). Because we are unsure why VAT would independently influence hospital stay after ICU discharge, we speculate that there may have been other underlying differences between groups not www.pccmjournal.org
593
Copyright © 2014 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies. Unauthorized reproduction of this article is prohibited
Editorials
accounted for in the matching criteria. The authors could have tried to account for cohort differences with additional measures of illness severity; however, this would likely have resulted in even fewer matched cases and a potentially underpowered study. Alternatively, others have used propensity scoring as a method to match cohorts (12). Propensity score matching often allows for larger numbers of matched patients; however, the use of administrative databases for matching groups engenders its own set of challenges (13). The reviewers suggest that this alternative approach might be useful in future studies. Despite the challenges inherent in any retrospective study design, this is now the second study to demonstrate associations between VAT and increased resource utilization in the PICU. For example, we found that children in whom VAT developed had significantly fewer ventilator-free and ICU-free days compared with mechanically ventilated children in whom VAT or VAP did not develop (4.9 vs 22 and 0.5 vs 19, respectively) (14). These findings remained significant in multivariable analyses accounting for patient demographics, baseline diagnoses, and severity of illness (Pediatric Risk of Mortality III score). In our report and the study by Wheeler et al (9), cases of VAT were not associated with progression to VAP, suggesting that VAT alone has important and distinct clinical significance. The significant contribution of ventilator-associated infections to antibiotic use in the PICU, coupled with mounting evidence of VAT’s distinct impact on clinical outcomes, points to a need to include all ventilator-associated respiratory tract infections in surveillance programs and quality improvement initiatives. However, a major challenge exists due to the lack of a gold standard to diagnose ventilator-associated infection. Although strict criteria for VAP may miss clinically relevant infections, current criteria for VAT have the potential to overdiagnose infection. Recently, Willson et al (15) demonstrated that culture alone, even with purulence, may represent colonization as opposed to true infection. Many of the other current CDC criteria for VAT are either subjective (e.g., change in secretions) or infrequently observed in sedated, mechanically ventilated children (e.g., cough or apnea). In the future, biomarker-based approaches utilizing procalcitonin and/or C-reactive protein may potentially identify true infection with enhanced clarity. Unfortunately, the utility of inflammatory biomarkers to accurately diagnose nosocomial respiratory infection, particularly in children, is not yet established. The recently adopted CDC criteria for infection-related ventilator–associated complications or possible ventilator-associated pneumonia include more objective elements and may be of benefit—though these criteria have not yet been applied to or validated in pediatric patients (16). It remains unclear whether these criteria will improve nosocomial respiratory infection diagnostic accuracy in critically ill children. In summary, Wheeler et al (9) have contributed important new information about the clinical and financial impact of VAT
594
www.pccmjournal.org
on critically ill children. We believe that it is time to care about and implement VAT prevention strategies in our PICUs; however, future studies are needed to develop and validate accurate diagnostic algorithms that encompass all ventilator-associated infections in children. This work is vital because only by recognizing and measuring the true prevalence of nosocomial lower airway tract infections can we move toward zero harm in the PICU.
REFERENCES
1. Bigham MT, Amato R, Bondurrant P, et al: Ventilator-associated pneumonia in the pediatric intensive care unit: Characterizing the problem and implementing a sustainable solution. J Pediatr 2009; 154:582–587.e2 2. Gupta S, Boville BM, Blanton R, et al: A multicentered prospective analysis of diagnosis, risk factors, and outcomes associated with pediatric ventilator-associated pneumonia. Pediatr Crit Care Med 2015; 16:e65-e73 3. Stevens JP, Kachniarz B, Wright SB, et al: When policy gets it right: Variability in U.S. hospitals’ diagnosis of ventilator-associated pneumonia. Crit Care Med 2014; 42:497–503 4. Thomas BW, Maxwell RA, Dart BW, et al: Errors in administrativereported ventilator-associated pneumonia rates: Are never events really so? Am Surg 2011; 77:998–1002 5. Blinova E, Lau E, Bitnun A, et al: Point prevalence survey of antimicrobial utilization in the cardiac and pediatric critical care unit. Pediatr Crit Care Med 2013; 14:e280–e288 6. Carcillo JA, Dean JM, Holubkov R, et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Collaborative Pediatric Critical Care Research Network (CPCCRN): The randomized comparative pediatric critical illness stress-induced immune suppression (CRISIS) prevention trial. Pediatr Crit Care Med 2012; 13:165–173 7. Horan TC, Andrus M, Dudeck MA: CDC/NHSN surveillance definition of health care-associated infection and criteria for specific types of infections in the acute care setting. Am J Infect Control 2008; 36:309–332 8. Esteban E, Ferrer R, Urrea M, et al: The impact of a quality improvement intervention to reduce nosocomial infections in a PICU. Pediatr Crit Care Med 2013; 14:525–532 9. Wheeler DS, Whitt JD, Lake M, et al: A Case-Control Study on the Impact of Ventilator-Associated Tracheobronchitis in the PICU. Pediatr Crit Care Med 2015; 16:565–571 10. Brilli RJ, Sparling KW, Lake MR, et al: The business case for preventing ventilator-associated pneumonia in pediatric intensive care unit patients. Jt Comm J Qual Patient Saf 2008; 34:629–638 11. Bureau of Labor Statistics Data. Available at: http://data.bls.gov/ timeseries/CUUR0000SAM?output_view=pct_12mths. Accessed February 4, 2015 12. Goudie A, Dynan L, Brady PW, et al: Attributable cost and length of stay for central line-associated bloodstream infections. Pediatrics 2014; 133:e1525–e1532 13. Schneeweiss S, Rassen JA, Glynn RJ, et al: High-dimensional propensity score adjustment in studies of treatment effects using health care claims data. Epidemiology 2009; 20:512–522 14. Muszynski JA, Sartori J, Steele L, et al: Multidisciplinary quality improvement initiative to reduce ventilator-associated tracheobronchitis in the PICU. Pediatr Crit Care Med 2013; 14:533–538 15. Willson DF, Conaway M, Kelly R, et al: The lack of specificity of tracheal aspirates in the diagnosis of pulmonary infection in intubated children. Pediatr Crit Care Med 2014; 15:299–305 16. Ventilator associated pneumonia (VAP) events. 2015. Available at: http://www.cdc.gov/nhsn/PDFs/pscManual/10-VAE_FINAL.pdf. Accessed January 23, 2015
July 2015 • Volume 16 • Number 6
Copyright © 2014 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies. Unauthorized reproduction of this article is prohibited
